Itd*Nr woRLDHEALTH oRGANrzArroN vBc/90.1 V,FIk$l'lHil,V/ MAUgO.1 N\FSfglz ORGAMSATTONMONDTALE DE LA SANTE

-t \ ENGLISHONLY Distr.:LIMITED

VECTORBIONOMICS IN THE EPIDEMIOLOGYAND CONTROL OF MALARIA

PARTII

THEWHO EUROPEAN REGION I AND THEWHO EASTERN MEDITERRANEAN REGION

VOLUMEII APPLIEDFIELD STUDIES

SEGTIONI: AN OVERVIEWOF THE RECENT MALARIA SITUATION ANDCURRENT PROBLEMS

SEGTIONII: VECTORDISTRIBUTION

PREPAREDBY A.R. ZAHAR DISTR.: LIMITED WORLD HEALTH ORGANIZATION DISTR.: LIMITEE

ORGANISATIONMONDIALE DE LA SANTE vBc/90.1 @ MAL/90.1

ENGLISHONLY

VECTORBIONOMICS

IN

THE EPIDEMIOLOGY AND CONTROL OF MALARIA

PART II

THE I,IHOEUROPEAN REGION

&

TIIE WIIOEASTERN MEDITERMNEAN REGION

VOLUME1I: APPLIED FIELD STIIDIES*

SECTION I: AN OVERVIEWOF THE MALARIA SITUATION AND CURRENTPROBLEMS SECTIONII: VECTORDISTRIBUTION

PREPARED BY A.R. ZAHAR

FORMERWI1O ENTOMOLOGIST

*Literature search ceased at end December 1988.

This document is not issued to the generalpublic, and Ce documentn'est pas destin6 i Otredistribu6 au grandpublic all rights are reservedby the World Health drganization et tous les droits y affdrentssont rdservdspar l'Organisation (WHO). The document may not be reviewed,abstracted, mondiale de la Santd (OMS). ll ne peut etre commentd, quoted, reproduced or translated, in part or in whole, rdsumd,citd, reproduitou traduit,partiellement ou en totalitd, without the prior permission written of WHO. No part sansune autorisationpr6alable dcrite de l'OMS.Aucune partie of this document may stored be in a retrieval system or ne doit Otrechargde dans un systdmede recherchedocumen- transmitted in any form - or by any means electronic, taire ou diffus6esous quelque forme ou par quelquemoyen mechanicalor - other without the prior written permission que ce soit - dlectronique, m6canique,ou - of WHO. autre sans une autorisationprdalable dcrite de l'OMS. The viewsexpressed in documentsby namedauthors are solely Les opinions exprimies dans les documentspar the responsibility des auteurs of thoseauthors. citis nommdmentn'engagent que lesditsauteurs. vBc/90.1 MAL/90.r Page 2

VOLUMEII: APPLIED FIELD STUDIES

MAIN CONTENTS (this issue) Page

I'OREWORD

INTRODUCTION

DETAILED TABLE OF CONTENTS

SECTIONI : AN OVERVIEWOF TUE RECENTMALARIA SITUATION AND CI'RRENTPR.OBLE},IS

1. THE EUROPEANREGION 8

2. THE MEDITEFRA].IEANREGION 65

2.L THE }IE|DITERRANEANBASIN 65

2.2 ASIA hIESTOF INDIA 66

CONCLUSIONS 69

SECTIONII : VECTORDISTRIBUTION 7L

CONCLUSIONS 74

SELECTEDREFERENCES: SECTIONS I & II 81 vBc/90. 1 l,rAll 90. r Page 3

FOREWOFO

The present series, PARTII of Vector Blononics in the Epidemiology and Control of l,lalaria covers a very wide geographlcal area conprising two of Ehe WHORegions: The European and the Eastern Mediterranean. VOLIJMEI of this series which has already been issued, dealt wlth Vector Laboratory Studies.

This is to introduce VOLUI'IEII, Applied Fie1d Studies consistlng of this and two subsequent documents. In a speclal section, the recent infornation on inported nalaria and its inplication in continental Europe and non-European countries of the Mediterranean Basin, is presented. Actions taken Eo overcome the problen and preven! the consequences of inported malaria, including those taken by WHOto assist countries have been reviewed.

Fron field studies in different countries of the geographlcal area under review, a wide spectrum of aspects of veclor bionooics has been conpiled and gaps in knowledge have been outlined. Likewise, epideniological studies and control experiences as well as infornation on the oalaria situation i.n countries of the two Regions have been anply sunmarized. Thus, epidenlologists and entonologists, particularly those assigned at a central or di.strict level of the Prinary Health Care system in countries undertaking antlnalaria activities, can find background knowledge from their own or neighbouring countries 1n the two Regions. This will assist them in planning or reorientating malaria control at perlpheral and dlstrict J.evel, avoiding duplicatlon of studies or repeating unsuccesaful attenpts. The background will also assist central planners and consultants to pursue the tasks assigned to then without spending nuch time on tracing prevlous infornatlon.

The whole series represents a valuable material for training courses in rnalaria epideniology and control to be conducted at national or international level.

Dr J.A. Najera Director of the Division of gontrol of Tropical Di.seases (CTD) vBc/90.1 MAL/90.1 Page 4

INTRODUCTION

V0LUMEI of the present series has been devoted to "VECTORLASORATORY STUDIES' (Document VBC/88.5 - MAP/88.2). VOLU!fiiII has been designed to conpile "APPLIED FIELD STUDIES". Despite the fact that the present series deal Itith the geographical area covered by the WHOEuropean Region and the WHOEastern Mediterranean Region conbi.ned, it has been found more appropriate to dlvide this area into: the European Region and the Mediterranean Region irrespective of the WHORegional boundaries. Also for the purpose of the present series, E.helatter Region has been further divided into two sub-regions: The llediterranean Basin and Asia West of India as shown in Fig. I and explained in detail in the text.

The present documenEis the first issue of VOL. II conprising tlto sectlons.

- SECTIONI: dealing with tne status of nalaria eradicatlon ia the European Region' the situation of lnported malarla and associated probleas including induced and accldental oalari.a. Since the early 1970ts, reports of nalaria cases associated with international airports in Europe (for brevity terrued "airport nalaria") have been i.ncreasing and all point to infectlon belng effected by exotic mosguito vectors carried by aircraft coning from malaria enderoic areas. These records are retabulated and updated. Also, action taken by countries involved and by WHOas substantiated from meetings aud conferences dealing with the problen of lnported nalarla and protectlon of internatlonal travellers is reviewed. In this section too, synopses of the nalaria sltuatj.on aud current problens were given for countries of the llediterranean Basin and Asla west of Indla. llore details on the malaria situation in these two sub-regions wlll be shown in subsequent issues of VOL. II: as shown below.

- SECTIONII: This section deals with vector distribution in the whole geographical area of the WHOEuropean and the WHOt'tediterranean Regions. The range of distribution of each species is lllustrated on a series of oaps, supplenented with notes showing the areas where a species ls acting as an active vector. More details lrlll be given on the local spatial distribution of potential and active vectors iu the forthconing lssues of VOL. II: SECTIONSIII(A) The Medlterranean Basin, (in press), and III(B) Asia I'Iest of Inclia, (in preparatlon).

A few errors have so far been found in VOLUMEI, for whlch a corrlgendun is shown in this docunent as ANNEX1.

Acknowledgements of the cooperatlon of all persons and institutions ltho contributed to the preparation of this and subsequent documents, are shown in SECTIONIII(A): Document vBc/90.2 - r"tAL/90.2.

As from 8 January 1990, the Division of Vector Biology and Control (VBC), the Malaria Action Programne (MAP) and the Parasltic Diseases Progranne (PDP) have been disestablished, and a new set up: Division of Control of Tropical Diseases (CTD) has been establlshed. As the present and subsequent docunents llere near finalization towards Ehe end of 1989, lt has been decided to retain in the text the nanes of the old units, but the nanes of the units of the new Division will appear in the Acknowledgetrents in SECIION III(A) (in press). v8c/ 90. I MAL/90.1 Page'5

VOLIJMEII APPLIED FIELD STTJDIES

DETAILED TAELE OF CONTENTS

Page

SECTION l: AN OVERVIEWOF THX RECENTMALARIA SITUATION AND CURRENTPROBLEMS

1. The European Region 6

1.1 Status of nalaria eradication and control d

1.2 Inported malaria 1n Europe and associated problens 10

1.2.1 Authorst views l0 (i) The extent of the problero of inported roalaria 10 (il) Induced and accidencal nalaria 35 a. Transfusion malaria 35 b. Accidental malaria 39 (iii) I"talari.a associated with airports .+z L.2.2 Action by WIiO )z

2. The Medlterranean Regton 65

2.1 The llediterranean basin 65

2.2 AsLa west of India 66

CONCLUSIONS:SECTION I 69

SECTIONII: VECTORDISTRIBUTION 7L

1. Species distribution 7L

2. Vector distribution 7L

2.1 l"tajor vectors 7L

2.1.1 The An. roaculipennis cooplex 7L 2.L.2 eW.Picts- IL 2.1.3arl.ser8entii_ 72 2-1.4qt-rt'".o"""i". lz 2.L.5 An:-fiuf iams 72 2.L.6 An. pulcherri.nus IL 2.L.7 An. stephensi 72 2.1.8 An. cullcifacies IJ 73 2.L.9 @onplex

2.2 Secondary and suspected vectors 73

2.2.L An. claviger 73 2.2.2 An. hyrcanus s.1. 74 2.2.3 An. d'thali 74 z.2.4li5ffitor 74

CONCLUSIONS:SECTION II 74

SELECTEDREFERENCES: SECTIONS I & II 81

A}INEX I 90 vBc/90.1 )|ALl90.1 Page 6

:

z f, tt

J z 6 cD s5 at z

ta u.t = i=ffiffi at) € -2z o z ut z E E ut F o UJ = ur

qi

ll- vBc/90.I r'rAL/90.r Page 7

FIG.2 EPIDEMIOLOGICALASSESSMENT OF THESTATUS OF MALARIA,1985

a/,191 C Areasin which malariahas disappeared, been eradicated or neverexisted @ Areaswith limitedrisk @ Areaswhere malaria transmission occurs vBc/90.1 MAL/90.1 Page 8

SECTION I: AN OVERVIEWOF THE MALARIA SITUATION AND CURRENTPROBLEI'IS

Infornation conpiled here is derived fron WHOsources. Authorst views are also incorporated. In the present conpilation, the WHORegional boundari.es are not strictly adhered !o, because is now with WHO/AFRO,l'lorocco with WHO/EIIRO,and Israel with WHO/EUR0. Thus, the area under revlew is arbitrarily dlvided into: The European Region coroprising conti.nental Europe, and the Mediterranean Reglon coropri.sing the Mediterranean Basln and the zone of Asia west of India which extends fron the eastern shores of the Medlterranean to the east up to and including Pakistan (see Fig. 1). The epideniological assessment of the malaria status in the area under review in 1985 is napped in Fig. 2r

1. The European Region

L.1 Status of roaLaria eradication and control: Malaria eradication has been achieved in the European Region except in the Asian part of Turkey. Of a cotal population of 820 nillion in t.his region as estimated in 1985, 383 nillion llve in originally malarious areas (a country or terrltory is considered malari.ous when indigenous cases were sti1l rePorted after 1953). Table 1 shows the countries on the WHOOfficial Register of areas where malaria eradicatlon has been achieved, and Table 2 provides a supplementary list of nalaria-free areas where nalaria never exlsted or has been eliminated before 1953 without specific malaria eradi,cation measures.

An excellent well-documented book was prepared by Bruce-Chwatt & Zulueta (1980) on behalf of the WHORegional Office for Europe to give the history of oalaria in the continent and to commemoratethe centenary of the discovery of oalaria parasites by Alphonse Laveran in 1880. In a brief introduction the book presented the theories of the origins of nalaria ln Europe since the last glacial period, followed by a historical account of developmeut of knowledge on ualaria and its vectors since anclent Greek and Ronan times. The book further dealt wlth the history of nalaria and its disappearance in 24 continental countries includlng European Turkey and trro llediterranean islands (Malta and Cyprus), either through ecological changes and socioeconomrni.cfactors or under speciflc antimalaria neasures. Data of inported rnalaria and the risk of reintroduction of the disease into nalaria-free areas have been shorrn. For country by country J.nformation, the book should be consulted. In concluding chapters, the role of the international organizations in the eradj.cation of nalarla fron Europe and the future prospects have been well described.

It Ls worth notlng that despite eradication of malaria in the large part of continental Europe by the 1970ts, malaria transmission persisted or was renewed in certain countries. Fron data conmunicated to WHOby health authorities 20 indigenous cases were reported from Greece, and 2 fron Corsica, France ia L972 (Zulueta, 1973, and Postiglione, L974). ISee more recent infornation under f.2.f(i) below] The cases from Corsica Itere reported at the end of an episode of nalaria transmi.ssion that resulted from inported cases anong North African inoigrants (see details below).

Table 1.2 wHo Oftr.i.1 R.gi"r"r of t

country or area Date of registration

Hungary l'lar. L964 Spain Sept.1964 Bulgaria July 1965 Cyprus oct.1967 Poland Oct. 1967 Romania Oct.19b7 ItaIy Nov. 1970 Netherlands Nov. 1970 Portugal Nov. 1973 Yugoslavia Nov. 1973 l. Extracted from Wld hlth statist. quart. 40 (1987), p. L44, with the adjacent areas of the Afrotropical Region and West Indla added. 2. Froo Wld hlth statis. quart. 40 (1987), p. 161. vBc/90..l MAL/90.1 page 9

Table 2.1 SuppLernentary list of malaria-free areas in the European Region

Country or territory Date of notification

Belglun Feb. 1963 Denmark Flnland Iceland Ireland Malta Monaco Norway San Marlno Sweden Switzerland Unlted Klngdom Czechoslovakia Apr. 1963 Gibraltar July 1963 'l M-., OA? Austria LEj LreJ Federal Republlc of Gernany Feb.1964

As the USSRhas not been shown on the Offlcial WIIOReglster (Table l) despite the great advances made ln the study of the epidemlology and control of malarla, an atlenpt is made here to assemble some informatlon on the malarLa sltuation from certaln publicatlons written ln Engllsh. Due to the language problen, the wealth of Russian literature on ualaria and its controL could not be explored. Bruce-Chwatt (1982) explalned that although an official certlflcatlon of malarla eradlcatlon has not been sought fron WIIO, the virtual eradlcatlon of nalarla was declared ln 1960, cltlng Serglev (1968). Zulueta (1973) and Postlgllone (L974) who reviewed the data of rnalarla reported to WHOby countrles of Europe Lt L972, polnted out that the areas under the consolldation phase were located in the Republlcs of Azerbaijan, Georgla, Tajikistan, Kazakhstan and Uzbeklstan of which only the flrst two could be consldered as part of continental Europe, but no inforretion on the roalaria sltuation in the USSRwas recelved slnce the first semester of L970.

Froro lnforoatLon coromunlcated to WttOby USSR (WHO, L977 ' tltclf-Eplaen. nec.. ) there were 2155 cases of rnalarla lnported into the USSRfron 64 countries during L963-L973. Nearly all these cases \rere recorded ln areas of the USSRwhlch were consldered receptive to malarla | 63.4"/" of these cases were detected in areas where cllnatic conditions favour the annual transmlssion of malaria, and the remainlng cases ltere recorded in areas where transmission rJas occaslonal. However, it was enphaslzed that 79.5% vere located in torfils where the re-establlshnent of local transmission was unllkely and the renaining 20.52 of. cases nere seen ln sub-urban and rural areas. Reference was made to experioents showing that local malaria vectors were refractory to exollc P. falciparun strains but susceptible to P. vivax. In the area of annual receptivity to malarla, there were 24 cases of p. ffiFcaused by local transolsslon in 10 locallties where autochthonous oalaria had ileeileradtcated long ago. As a result of pronpt antimalarla measures, transmlsslon was lnterrupted in eight foci ln the first year and in the reoaining two ln the second year.

Measures to counteract the problern of inportation of malaria in the USSRwere outllned. A11 Sovlet cltlzens leavlng the country for roalaria endemlc areas are bri.efed on how to protect theuselves from nalarla includlng the use of cheuoprophylaxis, house screening, the use of repellents etc. Organized groups such as ship crews, geologists etc. receive regular prophylaxls. A11 persons entering Ehe USSRfrom malarlous countries such as students, are routinely examlned for nalarla and other parasltlc diseases. A11 lndlvlduals returnlng fron tropical countries are instructed to inforn their general practitioners of their nedical history and any travel or residence abroad. As soon as imported or induced malaria cases are detected, notiflcatlon is nade by telephone to the responsible Sanltary Epideulology Statlon, and by cabLe to the Mlnistry of llealth of the respective Republlc. Ttre extent of preventlve measures to be undertaken 1s deterulned by the epideniologlst of the station. In areas of hlgh malarlogenlc potential (high receptivity coupled with hlgh vulnerabtllty), case detectlon and vector control measures

f . 48, No. 9' 2 March 1973, p. 106. vBcl 90 . I MAL/90.1 Page l0 are carried out on a regular basis. Training and refresher courses for nedical and laboratory personnel in nalaria pathology and laboratory diagnosis and treatmen! are regularly organized parli.cularly for staff working in vulnerable areas. Post-graduate training in nedical parasitology includlng malarlology and nedical entoxoology, as well as in troPical nedicine, is organized for nedical personnel nho are to be sent abroad to work.

Detailed data communicated to WHOon lhe malaria situation in the USSRin 1981 (WHO, 1983 - Wkly Epidem. Rec.) were as follows.' (population in nillions)

(a) Total population 267.7 0 (b) Population in areas originally malarious 253.32 (c) Population in areas clained to be free from malaria 252.86 (d) Population in areas where transnission is clained to be interrupted 0.46 (e) Nunber of nalaria cases detected in areas of (c) and (d) (f) PopuJ.ation and number of cases in areas under attack phase of an eradicati.on or a control programme (g) Total number of cases reported (inported cases only) 304

I'lore recent infornation cornrnunicated by the USSRto }JHO[l'1r J. llernpel, Epideniological l'lethodology and Evaluation (EllE), l,lAPl showed the following data for 1986: Nunber of inported cases: 537 of which 516 were detected in areas of the malntenance phase, and 2l in nonaalarlous areas. In addition, one introduced case and five induced cases were detected. Parasite species: P. fal.ciparuo 43.4"/. P. vi.vax 4L.2"4 P. .".1e LL 7"1 P. nalariae 0.67" ffid--ffitlons L.5"4 Undeternined L.LZ

Views of Soviet authors on imported nalaria in the USSRand recornmendedmeasures to prevent t.he reintroduction of oalaria are shown under L.z.I below.

1.2 Inported nalaria in Europe and associated probleus

Since the early 1970fs when the last foci of nalaria transmission in concj.nental Europe were coulng to an end, several authors published articles dealing wich the extent of the problen of lnported oalaria and the related infections of induced and accidental malarla as well as infections raised by inported anophelines. Someof these publications are selectively sumarized as showrr below. In addition, action taken by WHOto asslst the efforts nade by countries of Europe to overcome the problenn of ioported nalaria is also reviersed.

L.Z.L Authors t vi.ews

L.z.L (1) The extent of the problen of inported nalaria

It ls more appropriate to give first the views of certain authors who dealt with the problen of i.nported nalaria in continental Europe in general.

Bruce-Chwatt (1970) presented the probleo of inported nalaria as a growing world Ehreat. With the increase in international travel, the chances for inPortation of the infection into areas free or freed of nalaria ln various parts of the world are increasing. The data of lnported malaria hithert.o reported in France, Germany, Great Brltain, the USSRand USA were revlewed. The problen of induced oalaria due to blood transfusion nas also discussed. Regarding Britain, Bruce-ChwaEt, Southgate & Draper (L974) reviewed the records of inported rnalarla during L960-L972 and found that the country had the second highest number of inported cases among the European countries. During L970-I972; there was a substantial increase in inported cases, but this oay have been due to iaproved notification. The average Dortality among 323 P. falciparun cases during those three years was 6.52. Attacks of P. vivax may occur several months after the travellerts return fron a malarious country. vBc/90.1 MAL/90.1 Page.lJ-

Zulueta (1973) sunrnarized the data of the nalaria situation In continental Europe received by WHOat the end of 1972. The total number of positive cases during that year was 1285, and their classificati.on reported to WHowas as follolts:

Irnported 1240 Indigenous 22 (2O froro Greece, 2 from Corsica, France) Relapses 4 Induced 19 lntroduced U

As can be seen fron the above, the inported cases constituted the najority of the reported cases (96.51!). The inportation of malaria into Europe has been increasing with t.he continued increase in air travel as well as the recruitment of labour from outside Europe, coinciding with the resurgence of malaria in recent years in many tropical areas. Zulueta considered Ehat the rlsk of reintroduction of malaria in northern Europe, despite the presence of An. atroparvus as a potential vector, is nil unless the ecological and socioeconooic condit.ions are drastically changed. ln contrast, the risk of reintroduction of the disease in southern Europe is a real one, as it could result from novement of the population including nigran! workers. The soall outbreak of nalaria that occurred in Corslca during L97I-L972 which rras attributed to the presence of infected persons among inroigrant workers fron North Africa (see deEails below), polnts to the high prooability of reinlroduction of malaria into the Dlediterranean countries of Europe. Nevertheless, the recePtivity of southern Europe ls not well understood, but it oust be dependent on such factors as vector density, the degree of vector/nran contact, and vector longevity under the prevailing ecological conditions. Zulueta further examined the records of inported cases ln Europe recei.ved by WHOfor the period L967-L972. The nuuber of inported cases reported by Portugal was nearl)' half the total number of iDported cases reported from Europe. This was due to the return of nilitary personnel and other groups from Portuguese overseas terrltories who either presented relapses or first infectlons after their arrival ln Portugal. These represented true inported cases. However, the reports from Portugal lncluded these and another group defined as "comnunicated from overseas terrltories but found negative in Portugal", and these do not fa1l within the definltion of irnported cases. For example Ln 1972, the number of true imported cases was 584 plus 4400 conrnunicated froo overseas terrltorles but found negative i.n Portugal. Despi.te the fact that a total of 2447 true inported cases was recorded in Portugal during L967-L9721 ao introduced indlgenous cases were found in the country. 0f the above total of inported cases, t.here vere 434 P. falciparuu of tropi.cal orlgin. In this connection, Zulueta recalled the work of Shute (1940) in the [JK, who showed that the English strain of An. atroparvus nas not susceptible to P. falciparun of tropical origi.n but could be infected with Italian P. falciparun. Thus, the refracloriness of loca1 anophelines to tropical strains of P. falclparun may have prevented the reintroduction of this infection in areas of southern Europe, where vector densities and nan/vector contact would have been otherwise sufficient for resumption of ualaria transmission.

Zulueta further remarked that with the high number of inported P. falctparun recorded in Europe during L967-L972 (1709 of 57O4cases) deaths should be expected, and in fact 62 deaths lrere reported to IIHOduring that period. A delay in establishing the correct diagnosis explains the occurrence of most of these fatal cases. So far, there have been no records of P. fglglpgr$o resistance to chloroquine in Europe, but the risk of introduction of such strains from South East Asia and tropical. America is increasing, for which clinici,ans and public health administrators should be alerted.

In his revlew of the malaria situation in Europe, Postiglione (1974) also presented records of inported nalari.a cases reported to the WHORegional Office, EURO, by countries of conEinental Europe for the period L967-L972. He considered that these records were generally underestimales for the following reasons:

(a) sone benign cases become spontaneously cured without belng diagnosed; (b) certain fatal cases also escape diagnosisl (c) certain cases escape detection; (d) in certaln countries, the diagnostlc facilities were insufficient; (e) certain countries did not send their reports regularly. vBc/ 90. 1 :YAL/90.1 Page 12

Of a total of 5685 cases reported it 1972, 5640 were lnporred, 4 relapses, 19 induced and 22 indigenous (20 in Greelceand 2 in Corsica, France). The most frequently observed parasite species was P. viva>i, followed by P. falciparun, but P. nalariae and P. ovale were quite restricted. In 1972, P. falciparun constituted one third of tne positive cases. As the infection withr P. n@E-long-rived, it poses a particular problen for blood transfusion. P. ovale :.s proE"ury aifficuit to identiiy, and a certain nunber of sases were shown as "unclassj.fied" because no conplementary examinati.on was carried out. The data also showed that thel level of inported cases remained approxlmately identical excePt in L}Kand Portugal. 1[he latter country showed a very rnarked increase in irnported cases fron 1969. As explained above by Zulueta (L973), Postiglione pointed out that Portugal added to the inported cases those cases which were communicated froo overseas cerritories but found negative wheo checked in Portugal, although these do not correspond strictly to WHOdefinition of inported cases. As mentioned above, these cases amounted to 4400 in L972. Like Zulueta (:1973), Postigli.one considered the risk of reintroduction of roalaria inlo southern Europe to be high as a result of moveroent of lhe hunan populati.on, glving also the outbreak of Corsica as an example.

To conclude, Postiglione suggested the following Deasures to deal with the problen of irnported nalaria in Europe:

- At a national level: The type of action depends on the existence of receptive and vulnerable zones ln the counfry concerned. It is essential to ensure the detection, diagnosi.s, notification and treatment of inported cases, without being hindered by large nunbers of travellers. These actlvitles should be entrusted to the nedical and sanitary staff who should receive the appropriate training for applying correctly the diagnostic and treatment procedures. For diagnosis, it is necessary to collect information on the Past and Present history of siuspected cases, and record the tlne spent in malarious areas. It is necessary also to repeat the parasitological examination of the blood (particularly when the first sanple is negative) and to identify the species of the rnalarla parasite. Regarding treatoent, it ls lnportant to utillze the antinalarial drugs appropriate to the parasite srpecies for obtaining radical cure which should be confirned by parasltological examination, and for ascertaining the non-lnfectivity of the person to nosquitos. It is also equalJ.y inportant to apply rapidly and correctly the treatment of serious conplications of P. falciparun infections whlch can be fatal particularly in children, if not pronptly dearlt witil In this respect too, 1t is necessary to have available antinalarial drug preparatlons of rapid action and to have facilities for intensive care. Moreover, ttre receptive countries should organize surveillance Particularly for the groups at high rlsk, and conduct epideniological and entooological studies. For this, it is necessary to naintain a small group of trained and well-equipped antinalaria personnel. Health education for lnforming the public particularly the j.nternational lravellers is an essential neasure which requires excellent coordinaEion with conpanies of sea and air travel, ninistries concerned for disseminating infornation on: oalarious zones in the world, preventive measures (chenoprophylaxis), the diagnosis and treatment of malarla, and on lhe necesslty for consultlng rapidly a physici.an in case of an lllness that could resemble nalaria synptoms. Finally, countries concerned in Europe should conduct periodic evaluation for reassesslng the receptlvity and vulnerability of different zones and for assessing the effect of the nethods adopted. - At an international level: The principal measures to be underEaken by international agencies should be the collection and dissenlnation of information, establishnent of standard terninol.ogy, promoting research, establishing standards for international nethodology, coordination of efforts for preventing the resumption of nalaria transmissi.on, organizing neetings for exchanginB experiences, and assisting counlries i.n conducting training courses.

In the light of their experimental study that demonstrated the refractoriness of the Italian An. atroparvus and An. labranchlae to P. falciparun from Easc and West Afrlca, Zulueta, lbnsdale & Coluzzi (1975) [see also Ransdale & Coluzzi (1975) in VOLIMEI, under 2.8.2 (ii)' pp. 158-1611 discussed the relevance of the findings !o the na.Laria situatj.on in Continental Europe, where 3L.5"/. of the inported cases recorded during L967-I974, were P. falclparun fron tropical countries. tlistorically, the refractoriness of An. atroparvus nust have prevented the spread of P. falciparun in Europe for a considerable tine in the Past. Only after a long process of selection, the exotic strains of the parasite brought to Europe fron Afrlca or southwesE Asia oay have become adapted to transmisslon by the rtrost widespread vector. vBc/90.1 MAL/90.1 Page I 3

In his review of the probleu of malarla ln the world, Bruce-Chwatt (1979) pointed to the presence of a large reservoir of endeuic nalarla ln most tropical countrles. Consequently there is increaslng concern about malaria being one of the tropical diseases now frequently reported from Europe, USA and other areas of the temperate zone. The constantly increasing internatlonal travel at moderate cost has 1ed to massive iroportation of communicable diseases into countries where these lnfections Itere absent or gradually disappeared with public health developments. About 3000 cases of ualaria were lnported lnto Europe in 1977 and more ln 1978.

Bruce-Chwatt (1982) devoted a whole review for the world-wlde problen of iroported malaria wlth special enphasis on Europe, cltlng many relevant references. New informatlon on air travel in the world showed that the total number of passengers on scheduled fllghts exceeded 800 nlllion in 1980, and wlth the addition of unscheduled (charter) fllghts, the number was probably over 900 nilllon. 0f this total number, about one-quarter were tourlsts, and thls group of travellers is exposed to the rlsk of conlracting tropical dlseases. Slgnlficant lncreases 1n alr travel to Asia, Far East, I'llddle East, Afrlca and Latin Amerlca would polnt to the future epldeniological probleos. Although air travel is the most important route of population movement, the role of land transport is not negllgible and roore dlfficult to control. In Europe alone, the number of nlgrant workers froro varlous countrles nas about 12 nllllon durlng the l970rs.

Bruce-Chwatt tabulated the yearly data of lmported qases received by WHOfrom varlous countries of contlnental Europe coverlng the perlod 1971-1980. The problem of nalarla loported from varlous endemlc areas ln the world lnto Europe has become more serious slnce L97O. The data showed that the total number of inported cases steadlly increased from 2868 in 1975 to 4531 ln 1978 and 4041 ln 1979 whlle ln 1980 lt was 3170, but the data for that year were only preliolnary. For the whole of Europe, the number of deaths due to malarla during L97L-L979 vas 246. The overall nean fatallty rate is difflcult to calculate. In thls calculatlon only cases of P. falclparum should be used as denoninator, as P. vlvax and other specles rarely cause deaEfiI1iiiiffiiately, rellable statlstlcs of P. Fiparun cases are not recorded in all European countries. Regardlng Brltaln, the lnformatl.on presenled by Bruce-Chwatt, Southgate & Draper (I974) was updated by Bruce-ChwaEt (1982). The data of 1973-1980 showed a further rise in the number of irnported cases reachLng a peak in 1979, but for the flrst tine during the decade, there rras a decllne ln 1980. Over the whole decade, 87.9"/" of the lnported cases in the IJK were P. falclparuo origLnatlng in Afrlca, whlle 5.97. of the cases came from other parts of the world. With regard to P. vlvax, 737. of the cases came from Asia, but most of P. nalariae andP.ova1eor1g1nated-EEca.Bruce-Chwattfound1td1ff1cu1ttopresent_a-- meanlngful picture of the clrcumstances of fatal cases of P. falclparun recorded in UK, since the avaLlable lnfornatlon of the lllness is often scanty and unreliable. During 1974-f980 the total nuober of fatal cases due to P. falciparun nas 38 out of 1966 lnfectlons of thls specles: 30 Brltlsh, flve born-G-EffiiliZ-n subcontinent, three foreign vlsitors, and two of unknown origln. There nere tno deaths of elderly, Indian-born patlents due to P. vivax wlth ensulng conpllcatlons. Ten inported cases of congenital malaria were recoiffiEEing the period under review and these represent a new phenomenon ln the UK. Regardlng the tlne-lnterval betrreen the return of travellers to the UK and the onset of malarla s)mptorns, the data of 1395 selected inported cases during L970-L974 were analyzed. Thls shosed that 927"of P. falciparuo patients presented their ftrst cllnical atrack less than one oonth after reEIilG!:6-TUe UK, while only 82 of the patients had their flrst attack wlthin 2-6 nonths. tllth P. vlvax and P. ovale lnfections, 43Z of the patlents presented the flrst syuptoms wlthln onElnolffi afteiffiiag, 38:l withln 2-5 nonths, 23% vl-t}l.ln slx uonths to one year, and 4Z after oore than one year. With P. malariae infections, 76"1of the patienEs presented the first synptotrs within 2-6 uonthi-affiEir return, but 23"Awlthin 12-L8 months. Cases of post-operative malaria not arlsing fron blood transfuslon, though belng rare, may belong to this group of delayed attacks, and such recurrences of an old lnfectlon was reported by other workers. Such delayed attacks particularly in lnfections wlth P. vivax rnay contribute to errors ln the diagnosls and treaEment. A delayed attack of p.G-Tnfections may occur after a year or more ln stralns characterlzed by a long incG161-perlod, which are commonin the temperate zone of the world, but they also occur 1n some troplcal areas. The data of lmported malarla ln other countrles of Europe (vlz: France, Belgium, Federal Republic of Germany, Swltzerland, Poland, and USSR) as well as USA and Australia were discussed and relevant publlcations cited. Finally Bruce-Chwatt underlined the inportance of surveillance of imported oalarla. He explalned the risk of reoewed transmission by local vBc/90.1 MAL/90.r Page 14 vectors as being the product of two epldenlologlcal factors: the receptlvity and vulnerabillty of an area. Receptivity reflects the transolsslon potential by the local vector durlng the warn and ralny season, nhen transmlssion ls llkely to occur. Vulnerability expresses the amount of the plasnodlal parasite brought into a defined area, elther as human carrlers, or rather exceptlonally, as lnfected Anopheles. In order to assess the two factors and to protect the human population, the mai.n task of health authoritles is to organlze epldenlologlcal surveillance. The flrst-degree preventlon would be to undertake oeasures against inportatlon of carrlers of plasuodia or infected vectors. Ideal1y, this type of prevention would necessltate screening and/or treatment of all persons comlng from malarious areas and also the follow-up of thelr health, but practlcally this is lnposslble, although some countries such as Maurltlus has applied thls Deasure with sone success. The second-degree preventlon would be to concentrate on measures against re-establishment of malarla transmission, and this is nore applicable in practlce. Bruce-Chwatt further stressed the irnportance of alertlng the oedical and other professlonal staff. Equally important is the provislon of dlagnostic facllltles and the availablllty of an epidemlological surveillance service wlthln the general natlonal health organlzatlon which should be able to carry out speedlly and efflciently other more specific tasks whenever necessary. One of the best ways of preventing the inportation of malaria by tourlsts and other travellers is the provlslon of adequate lndivldual prophylaxls by approprlate antixoalarial drugs. Thls has now become less reliable because of the lncreasing lncldence of stralns of plasuodla, especially P. falclparun, reslstant to antlfolic cornpounds (proguanil and pyrinethanine), to 4-aninoqulnollnes (chloroqulne and arnodLaquine) and even to some nener drug combinatlons of antlfolates and sulphones or sulphonanides. It ls extreoely irnportant that lnforuatlon on malarla rlsk for travellers such as the one publlshed perlodlcally by I{ltO should be widely dlstrlbuted not only to the nedlcal and allied professions but also to the travel agencies and general publlc.

Having shown the views of certaln authors on the problem of luported ualaria in contlnental Europe ln general, the extent of the problem ln several countrles as described by varLous authors ls glven below startlng froo the east and rnoving to the nes!.

In the USSR, Chagin et al. (1975) lndlcated that durlng 11 years (f963-1973) 2155 nalaria imported cases froro 64 countrles were notified. Analysis of data of L927 cases showed that 976 were P. vivax, 762 P. falclparun of whom 543 were forelgn students, 56 P. nalarlae, 115 P. ovale, and 18 nLxed lnfectlon (falclparuu and vivax). As a result of these lnported cases, malarla transmlsslon nas re-establlshed and 23 lndigenous cases vtere recorded ln 10 locallties, where oalarla had been absent for oany years. The systeo of ualarla prophylaxls ln the USSRls effective, but further perfection ls needed. Great attentlon must be paid to the educatlon of oedlcal personnel on malaria peculiarities.

Da5hkova et al. (f978) analyzed the data of 294 cases of malaria (L22 in Soviet residents and L72 ln forelgn resldents) lnported lnto Moscow durlng L974-L976 fron 45 countries. P. falciparum constltuted 60.82 of these imported cases. This species came mainly frorn ffiEE[G-and were oostly found ln indigenous resldents. Anong the persons vlsitlng the USSRfor the flrst tLme, 72.9% vere parasite carrlers. Patients with acute manlfestations of thls lnfection pre.sent practically oo danger as possible sources for lnfectlng nosqultos, but those who prove to be ganetocyte carrlers are epidemlologically inportant in the southern parts of the country where An. sacharovi and An. subalPinus occur. P. vivax nalaria (L7.2"1 of the cases) nas detected oostly in Soviet .citizens lnfectedTai-nly in South Asia. This parasite is the oost dangerous for infecting local vectors and renenal of nalaria transmisslon.

Duhanina et al. (197g)l suggested that to deal wlth problems arising fron imported malaria ln the USSR, it is necessary to lnprove and ratlonaLLze prophylactic measures, and to intensify scientific Lnvestigatlons as follows:

(a) to study the malarlogenlc potentlals ln areas of agrlcultural and lndustrial development as well as those of land reclamatlon; (b) to study the ecology of oalaria vectors; (c) to conpile the accumulated experLeoce of preventlng nalarla and its norbidity among the Sovlet citizens durlng their stay abroad;

1. The surumarles of thie paper and the papers of Kouznetsov & Neulmln (f984) and Soprunov (1984) have been made through the kind cooperatlon of Dr R.L. Kouznetsov, ffilO l.talariologist, MAP/PAT, WtlO, Geneva, by translatlng parts of the original text,. vBc/90.1 MAL/90.1 Page. 15.

(d) to apply serological oethods for detectlng nalarla infecElons among those who return to the USSR; (e) to determlne the susceptlbility of local vectors to inported nalaria paraslte stralns. (f) to contlnue testlng the susceptlblllty of local vectors to lnsecticidesl (g) to develop criterla for assessing the natural and socloeconomlc factors that would determine the posslblllty of resumption of malarla transmissi.on; (h) to develop neEhods for deternining the prognosis of malarlogenlc potentials; (1) to develop and introduce various combinaclons of antixnalaria measures lncluding the integrated approach for vector control.

Kouznetsov & Neuinin (1984) revlewed the problem of inported nalaria in the USSR. Most P. falciparun funported cases come from Afrlca, while P. vivax cases originate in Asla. Durint-EE past tno years a conslderable increase ti-E!6fed cases golng to rural areas in the USSRwas observed. In the 1960tsr 7.57" of the total lnported cases were recorded 1n rural areas, and in 1982 this percentage increased t.o 297. The epideniologlcal consequences of the iroportatlon of malarla into rural areas has been a great lnerease ln the lntroduced cases, prlnclpally P. vivax. I{hite there was only one case of lntroduced P. vlvax during L974-L979, there were 32 lntroduced cases detected during 1980-f982. Transmission nas effected by the local members of the An. naculipennis complex.

Soprunov (1984) pointed to the large increase ln introduced cases ln Daghlstan ASSR and Tajikistan, all of whlch were P- vlvax. In Tajikistan the number of lntroduced cases lncreased to as many as 3-fo1d ana-Zl6ETa the total number of indigenous cases in 1981 and 1982 respectlvely. 0f the urgent tasks to deal with the problen of lntroduced malaria ls the need for development of an all-Union speclal progra'ne for the prevention and control of oalarla ln order to undertake the following:

(a) to draw a unlforn oap of malarla foc1, and to develop nodels of epideniological Patterns ln foci of dlfferent types whlch should asslst ln the prognosls of oalarla;

(b) to develop differentlal measures for control of vectors and malarla parasltes;

(c) to study anthropogenic changes of landscapes and the changes ln the malarla sltuation especially in the southern republLcs where intenslve work on lrrlgation and land reclamation is taking placel

(d) for terrltories where there ls a risk of nalarla transmlssion: to develop a uniform system for nonltorlng the changes in vector density and susceptlbllity to insectlctdes as well as the response to various control oeasures;

(e) to provide lnstructlons for the use of dlfferent insecticidesl (f) to provide radical treatment for ualarla cases; (g) to lnitlate dlfferent types of research; (h) to seek international cooperatlon for studylng the rnalari.a situation abroad.

It should be recalled that Dlskova & Rasnicyn (1982) sunnarlzed and reviewed the studies carried out in the USSRon the susceptibllity of members of the An. rnaculipennis cooplex to dlfferent funported stralns of human malarla parasites. An. atroparvus, An. messeae and An. sacharovi were highly suseeptlble to strains ofE..ffiEi troplcal arrrcalG anaEitT[GEGa. The first two anophellne species weFefracrory ro tropical strains of P. falclparun fron Afrlca and Asla. An. subalpinus could be infected [email protected]. Results of experlnents with tropical P. falclparun in An. sacharovi nere contradictory, because ln oost experlnents lnfectlon falled to develop, while in- flve experiments sporozoltes nere seen Ln the sallvary glands. Isee Vo1. I, under 2.8.2 (ii), pp. 160-161].

In ltungary, Vdrnat 6 Banhegyl (1986) polnted out that autochthonous malaria has not been encountered since 1960, and that the number of llungarians worklng ln roalaria endemic areas abroad has been lncreaslng gradually stnce the 1960rs, but the numbers have suddenly lncreased in recent years. It L962, compulsory chenoprophylaxis was introduced concurrently wlth an inforrnation prograltne for all persons assigned to foreign servlce and coupulsory screenlng exaolnation upon thelr return to llungary. The lnfornatlon programe conslsts of: vBc/90. 1 MAL/90.1 Page 16

- provldlng the travellers wlth lnfornatlon on the epideniological sltuation in the country of destlnalion stresslng the lmportance and possible ways of protectlon against uosqulto bltes.

- supplying the travellers with chernoprophylactic drugs. Chloroquine is provided for travellers going to non-chloroquine P. falclparum resistant endemic areas. The recornrnendeddose for adults is two tablets weekly, contalning 300 ng chloroquine base. In cases of long-term servlce ln areas with high chloroqulne resistance (R II, R III), the adult traveller is glven one tablet of pyrlnethamlne. Travellers to nulti-resistant regLons are provided wlth two separate drugs, to be taken on tno separate days of the week. Taking the drugs must be started two weeks before travelling ln order to detect any possible side-effects, in whlch case alternative drugs are provided. Chenoprophylaxls Dust continue for four weeks after returning hone. As part of oalaria surveillance conpulsory screening examLnation conslsts of :

(a) an lntervLew to obtaln detalls of taklng the chenoprophylactlcs (regularlty, posslble intolerance), prevlous illness accompanied by fever, malaria hlstory and antimalarlal drugs taken for treatnent, and the results of parasltologlcal examina|ions;

(b) physical exaolnatlon to exclude hepato-splenomegaly.

Parasltologlcal exauinatlon of blood ls conpulsory 1n Hungaryl lt is carrled out wlthin two days of returning home. The speclflc IgG type antitest oethod wlth Falciparun Spot Test lras introduced in 1982 to obtain retrospectlve data on P. falciparun lnfectlon. Stnce1981tn.v1trodrug8ens1tiv1tytestforP.fa1c1parurn1nfffiEen Lntroduced.

About 20 000 travellers have been provtded wlth chernoprophylactlc drugs ln Hungary since L962. Data of L2 780 travellers who spent at least one year in malaria endenlc areas were analyzed. The prevalence of malarla infectlon among 12 300 who took the drugs regularly was L.21(, whlle the rate anong the remalnlng 480 who dtd not take the drugs was L2%, L.e., the rlsk of contractlng oalaria Lnfection was 10 times greater in the case of people not taking the antlnalarlals. For travellers to chloroqulne-resistant regions, the comblned dosage of chloroqulne and pyrinethanine has been recotnrnendedsince 1981, but data collected so far has not been sufftcient to draw a flnal concluslon. There has been nir serlous side effects. Individuals provlded wlth chloroqulne chemoprophylaxis have had regular ophthalnologlcal exauination; ln 20 years no chloroqulne-lnduced retinopathy has been observed. As the people screened had taken chloroqulne for no longer than four or flve years, the total doses of that drug has not exceeded 100 g. In vitro chloroquine-reslstance tests made on five cases of P. falciparum detected in the course of threeyearsshowednoch1oroquineres1stance.rtna@ffi?isstressedthatma1aria infection can occur even wtth the most thorough chenoprophylaxis. For this reason travellers are provided wlth therapeutic doses of combined antlfolic compounds (Fansidar), and they are advlsed to take tt (6 tablets in 3 days) when they have fever, ln the absence of physlclans.

In Romanla, Teodorescu (1953) discussed the rlsk of reintroductlon of malarLa in the llght of her experimental infection studles with An. atroparvus uslng strains of nalaria parasltes orlginatlng fron dlfferent geographicafA?iilffJG:6-tlffE I, under 2.8.2 (i1), pp. 150-1611. In tloldavia under the maintenaoce phase, An. atroparvus is very receptive to P. vivax origlnating frou Asla and West Indla, and to-ffiEllffi'tropical Africa. fearfnfrInind also the lack of lnnunlty tn the human pop-ffiffin, the resumption of natural malaria transmission is hlghly likely, especially when the detection of irnported cases and gaoetocyte carrters stationed in thls zone during the rrarm season 1s delayed. The fallure to lnfect An. atroparvus wlth foreign P. malarlae does not exclude this posslblllty also, bearlng in nind that this vector was rarely experloentally lnfected with a local strain of this paraslte. The experinents showing the refractorlness of -An. atroparvus to Afrlcan P. falclparun conform wlth the flndlngs of other European lnvestigators.

In Bulgarla, Petrov (L977> reported that durlng L966-L975 L32 cases of inported nalarla were registered conprisLng Bulgarlan citizens and forelgners from Afrlca and Asia. Of L27 cases, there were 68 cases (53.5%) wlth P. vi.vax, 48 (37.82) cith P. falclparun, 10 (7.92) with P. ovale, and I (0.82) wlth P. nalarLae. Asynptooatlc carrlers nere prevalent among foreLgners, while Bulgarlan persons suffered fron the acute vBc/ 90. 1 llAll90. r Page 17 disease. Anong Bulgarian citizens 502 livecl in tropical countries uP to one month' and of these there were trro who spent only one day. A complex of Deasures are being applied to protect Bulgarian travellers leaving for tropical countries, and to Prevent the spread of malaria from iroported cases. Despite favourable clinatic conditions and the presence of a high density of potential vectors, no introduced cases have been detected.

In Greece, Belios (f976) present.ed the history of nalaria and lts control and the reorientatlon of its progranme towards eradlcation sEarting fron 1957. lle lndicated that by 1964 the nalaria prograume of Greece had achieved its goa1s, but. the application of the WHOcriteria for eradication was expected to be applied it L976. Violaki, Avramidls & Trichopoulou (1976) reported the results of a study of 2L5 malaria inported cases detected during 1963-1975. Of these, 130 cases were recorded durlng L97I-L975. The parasite speci.es were: P. tit.* (45.671), P. falciParun (35.57") and P. nalariae (I8.12). The age-group 2f-30 years constituted 32.L2 of the cases. The geographical distribution of the cases showed that seamenwere most affected (46.9"1). ltosE of the inported cases originated froo the African Continent. Although Greece is susceptible to the reintroduction of malaria due to its receptivity by the presence of anopheline vectors, the probabillty of the reappearance of the disease is low because the efficient malarj.a survelllance netrdork of the public health service is able to detect early and treat the ualaria cases enterlng the country.

Fron the book of Bruce-Chwatt & Zulueta (1980) 1t was reaU.zed that nost of the cases reported in 1973 in Greece orlglnated fron llacedonia and Lesbos. A sero-epideniological survey was carried out in Septenber 1973 in Henathia, a nomos (prefecture) of I'lacedonia, using indirect fluorescent antibody test (IFA test), by Bruce-Chwatt et al. (1975). A total of 4605 blood samples were collected representlng about 20% of the population of Henathia,andtestedagainstP.vivaxand3:-{.@'.Asdiscussedbytheseauthors, the apparent absence of oalaria antibodies detectable by the IFA test Ln 2965 serutl samples fron the population of Hematia under 20 years of age, born since the coxnmencement of intensive malaria control followed by survelllance activlties, justifies the conclusi.on that there has been very llttle or no nalaria transnisslon in the area in recent years. This conclusion, though plausible, is not absolute; flrst, because the sarnple was limited in size, although it covered about 357"of the relevant age-group of the population studied, and secondly, because lt ls possible that some of the antibodies resufting fron recent infections may already have been lost. Bruce-Chwatt & Zulueta (loc.cit.) indicated that epideniologlcal investigations suggested that most of the cases previously reported fron Henathia were elther relapses or not of local origin. Drug adninistraeion ltas applied to a group of gypsies residing in some areas of Henathia and there r.tere no new cases reported during L973-1974. Bruce-Chwatt & Zulueta believed that the nomos of llenathia represented the last focus of indigenous malaria and that its elininacion has 1ed to the eradication of malaria 1n Greece.

From a report of a LIHOnission to Greece (S. Goriup, unpublished report to WHO,1978) the number of nalaria cases detected during L975-L977 ltas as follows:

Year Total cases Classification of cases Indigenous Relapses IoPorted Int roduced

L975 34 2 0 27 5 L976 4L 5 2 32 4 L977 48 0 J 39 6

The species distribution was: P. vivax 4L.57"; P. falclparuo 32.5%; P. malariae L6.31!; undeteroined 9.77. l4ost of the lnported cases were found in Athens, Piraeus, East and t{est Attikis. The inported cases were detected among sea and air personnel, workers, students and tourlsts orlginating or having stayed for certain periods in Africa, Asia and the Middle East. The five indigenous cases detected in 1975 and 1976 were all located in four villages in.the nomos of Evros in Thrace, very close to the Turkish border. No more positive cases were found in this nomos during 1977. Wlth the exception of Evros, indigenous cases of malaria have not been observed in Greece slnce 1973r when the last cases were detected In Hemathla nomos. It was reconrnended that in areas of hi-gh recept.ivity especlally ln Evros, where malariogenic potential has increased considerably through the proximity of the Turkish foci, vigilance should be strengthened and vBc/ 90. 1 r,lAll90.1 Page 18 supplenented where appropriate by active case detection through xoonthly house visits, at least durlng the favourable season of anophelines.

In Coluzzi- (1979) - lta1y, & l'lonzali dren attentlon ro the increaslng risk of relntroduction of naLaria with the increase of inported cases. The annual mean number of inported cases was 33 during I966-L970, and 51 durlng L}TI-I975. In 1975 and 1976, rhe Eotal nunber of inported cases was 103 and 140 respectively. About 8O7"of the cas;s orlginated in Africa with the najority being P. falciparun infection, although the Proportion of P. vivax tended to increase in 1976 and 1977. Inported nalaria poses two major problens:@ the delay in diagnosis of P. falciparum infection causes deaths of Ehose untreated cases; secondly, the delay in adequately treatlng the inported cases increases the risk of resumption of malaria transmlssion i.n receptive areas. However, the risk is very low with regard to transnission of P. falciparuo because of the poor recePtivityofanophe1inesinIta1ytothistnte-on,uuttnisisnotvalidforP.vivax.

CoLuzzL (1980) indicated that entonologlcal investigations carried out recently 1n Italy demonst.rated that in certain areas Anopheles vecEors of nalaria particularly An. sacharovi and An. labranchiae disappeared or became very rare. This has not resulteo from anti-vector measures but fron environmental changes. However, Anopheles populations are stilL Present in alL areas not affected wlth great environmental changes. Thus, hi.gh densities of An. labranchlae have been reported from sooe sectors in Lazio of Viterbo province and Toscana in Grosseto provi.nce, as well as in Calabria, Sicily, and Sardinia. The author reiterated that Ehe risk of transoission arises fron the detay of diagnosis of inporEed cases or in giving the appropriate treatnent. Poor recepttvlty of An. labranchiae to exotic P. falciparun reduces the risk of transmission of this G?ection, lrnTitce j.rnportedFEiEfr6it on the whole receptlvity is low due to the fact that the Anopheles population has showed narked deviation froo endophlly and anthropophily coupled with reductlon in longevity.

Entonological surveys carried out by Betti.nl et a1. (1978) in San Donato locallty and surroundings in central Italy, provided evidence that the newly i.ntroduced rice cultivatlon has greatly increased the density of An. labranchiae populations from unknown pre-existi.ng breeding foci [see more details in SECTIONIII(A) under (i) 1.2 in document VBC/90.2 -I4AL/9O.2). The situation was viewed wlth concern as resunption of nalaria transroj.sslon appeared to be a possible event ln view of the following factors:

(a) the very high density of the potential local vector and the extension of rice fields;

(b) the proxlnity of the breeding places to human settlemenLs; the town of Albinia with 1500 inhabitants as well as camping sites having a capacity of 10 000 visitors are situated at about 2 kn fron the to$rr;

(c) the high rate of exchange of the sunmer canping populationsl

(d) the constant increase of microscopically confirned inported cases; and

(e) the absence of acquired innunity to malarla of the local population under 30 years of age.

Referring to the experinents of Zulueta, Ransdale & Coluzzi (L975) and lknsdale & CoJ-uzzi (1975) [see VOL. I as noted above] in which the P. falciparun strain fron Kenya could not lnfect the Italian An. labranchiae, Bettini et aI. suggested that nore experinentsshou1dbecarried_o]ffi6-esusceptibi1ityofAn.1abranchiaetostrains of P. falciparun from other tropical regions, or with P. vivax. Exanples of relntroduction of P. vivax roalari.a in Corsica and European USSRwere given, citing Zulueta, Ransdale 6'-ffi7i G975), and in Sardinia arlsing from an inported case, citing CoLrtzzi (1965). Careful nonitoring of condltlons of man-made breeding places such as rice cultivatlon in liarenma region, central. Italy was recommended.

Oddo & Piccardo (1982) reviewed the hlstory of the campaign against malaria in Italy since 1947 untll eradlcation was achieved and certified in 1970. With nalaria continuing to be endemic in large areas of the world, inported ualaria represents a permanent menace for relntroduction of the disease into malaria-free areas. Of 895 itrported cases recorded vBc/90.L ltAL190.1 Page.19

in Italy durlng L974-L979, 76"Avere lnfected tn troplcal Afrtca, 16Z ln the llIddle East, 67. tn Central and South America, and 2Z in the Indlan subconcinent. Of these infectionst 642 were P. falciparun, 342 P. vivax and L.4Z P. malarlae and 0.42 P. ovale. Of the lnported cases, 54"/"uere tourists who went' to malaria endemic areas, 352 were persons undertaklng diverse actlvlcies (working, commerce, professloual aclivlties etc.), 81 were air pilots and oariti.me navlgators, and 3Z diplonats, students, nisslonarles etc. The study of the distributlon of the lnported cases by reglou in Italy deoonstrated thar high vul.nerablllty occurred in reglons which are less receptlve (toms) and vice versa. However, the notified cases of luport.d malarla r"p..i"ot only the trp iTTTffieberg", because many cases are not dlagnosed or not reported to health authorlties. Tlro loportant factors are influencing the lnportatlon of oalaria ln Italy:

(a) a large proportion of Italian travellers especially tourists are not inforned of the risk of contraction of infectlon in endenic areas, and have not been given sufficient informatlon on prophylactic meaaures.

(b) The diagnosis of a large proportion of lnported cases ls delayed.

The actions taken by the Mlnistry of Health are:

- inprovement of inforEatlon to travellers by oaklng nider distrlbution of translated WHOpublicatlons concerning international travellers, also uaklng use of tourlst agencles;

- better infornatlon to rnedlcal offlcers and healch authorltles at alrports and seaporEs;

- givlng lnstructlons to regional health authorltles to Donltor the densitles of potenti.al. vectors, and if necessary to carry out aotl-vector measures;

- organizing training and refresher training couraes for health workers concerned.

Oddo, Onori & Goriup (I987)f revlewed the problems of ualari.a in the world wlth special reference to iuportatlon of malaria in ltaly, for which new data were provided. During 1C years (L974-L984) there were 1644 ioported cases, and aoong these there vete 27 deaths (L.72). The dlstrlbutlon of the lnported cases lras slmilar to prevlous years with the northern part of the country being uore vulnerable, bu! Iess receptlve. The parasite specles rrere: 652 P. falclparun, 302 P. vlvax and @!g, 4.97. P. malariae, and 0.12 oixed infectlon of P. falciparuo * P. vlvax. The type of people involved in inportation of nalarla has a new element, the lmlgrants and refugees constituting an appreclable proportion as shown in the followlng.'

- Itallan expatrlates, 34"1; It,alian and foreign tourists, 3L.7Zi - Religious persons, 5.52; Air and maritime personnel, 5.52; - Immigrants, l8Z; Refugees, 5.3"4 .

The dlstribution of the origin of the 1644 inported cases was:

76.2i( fron tropical Africa. L8.3"1 fron Asia. 4.5"1 from Central and South Amerlca.

Somecountries from which the inported cases originated, reporled chloroquine reslstance in P. falciparun. For this reason four centres were eslablished to carry out in vlvo and in vitro tests respectively 1n: Rone, !{11ano, Torino and Pavia. The preventj.ve oeasures remain the same as reported above. Sone data were given on induced malari.a and infection aoong drug addlcts [see under 1.2.1(ii) of this SECTIONbelow].

In @, several authors reported on imported roalaria; only selected paPers are presented here. Sautet & Ouilici (197f) reported on the malaria situation in Corsica. The nalaria eradicatlon campaign which was launched durlng L948-L952 mainlained its gains

1. Sunnarles of thls paper and the papers of Coluzzi & llonzall (1979), Coluzzi (1980)' Oddo & Piccardo (1982), and Oddo' Onorl & Goriup (1987) were made through the klod cooperatioo of Dr F. Oddo' former I{HO}lalariologlst, }'lAP, Geneva, by translating Parts of the text of these papers. vBc/90.1 MAL/90.1 Page 20 as evldenced by the disappearance of autochthonous [= indigenous] cases of malaria uP to 1955. Thls favourable situatlon allowed, ln part, the exploltation of littoral plains' prevlously known to be malarlous, and also led to a substantial increase in tourlsm to the seashore which had been abandoned in the past due to mal-arLa. Ilowever, this situation did not last, for a new element appeared as a consequence of cultivatlon of tire vast coastal plalns. Repatrlates froo North Africa having faced the shortage of the local manpowert resorted to enployment of North Afrlcan workers who often came froo the poorest Parts of the Maghreb which are endeuic for malarla, thus constltutlng a danger of relntrocution of malaria !n Corslca. Durlng L965-L967 five cases were detected in the north of Corsi.ca; the epiderolological lnvestl-gation hltherto carried out revealed the presence of P. vivax infection a6ong North African workers. Antinalaria measures were applied inneaia@@Ctt house spraylng and chemoprophylaxls) which led to ellnlnatlon of this snall focus, and the years 1968 and 1969 passed wlthout any incident. This experlence showed tile rePercussions tha! arose from reorientatlon of control measures after malaria eradicatlon rJas achieved: the antilarval neasures were largely dtrected to the control of Aedes and Culex, being the source of mosquito nuisance to tourists, while the control of the AnoPheles vector of nalarla [An. labranchlae] lost lts exclusive character. In 1970, revival and extension of thls focus-GEffif-wlth the followlng cases reported (with a certaln number contracting the infection ln the northern focus): 20, of whon four were Europeans who cane for vacation; 11 detected among North Africans, of whom nine were found in the same northern area, and two froo other reglons, lndlcatlng the high nobtlity of the labourers. Measures were applied towards the end of 1970, and reinforced in 1971 in order to elininate this focus, thus preventlng the re-establlshrnent of oalarla endenlcity. Attention of the medical practltloners was drawr to the present experience wlth nalaria cases which have so far been P. vlvax, constitutlng a risk 1f not diagnosed in tirne. Practitloners lrere also renLnffihe standLng regulations necessitatlng compulsory notificatlon of malarla lndlgenous cases, as thls would lead to the discovery of the affected zones.

Ambroise-Ttrooas, Quillcl & Ranque (1972) reported the results of a sero-epiderniologlcal lnvestlgatlon of nalarla carried out ln Corslca durlng February-March 1971 before the onset of the transmlssion season. A total of L275 persons were examined: 1054 Corslcans and 221 North Afrlcan workers. As far as posslble, the sample represented the trro sexes and different age-groups: less than 2 yearsr 2-5,6-14 and 15* years. Fron each person, trro thick smears were taken for direct microscopical examlnation, and two blood samples for the indlrect innunofluorescent test (IFA test). It was not possible to carry out spleen examlnation at the same tlne. A11 the slldes examlned microscopically rrere negative, but there erere 81 inmunofLuorescent posltlve reactlons using Plasoodiun cynonol-gi bastlanelll antigen. Of these, 68 showed very weak reactlon (1/20), while the renaining 13 gave a very strong reaction. It was surprislng to observe that reactions rrere less frequent and less intense among the North African workers than in the Corsicans. It was realized that the l{orth Afrlcan I -lgrants upon their arrival in Corslca were submitted ln an almost systematlc mElnner Eo malaria treatoent by amodlaqulne. Thls treatment obviously resulted ln appreclably reducing the fluorescent antibody titre ln thl,s group. The authors considered, however, that the IFA test is undoubtedly an lmportant tool ln regions such as Corsica where people are well aware of nalaria symptons. As soon as they get fever episodes which they thenselves recognize as due to nalaria, they resort to taklng antiroalarlal drugs. Enquiry by the authors during the present investigatton showed that this phenomenonis qulte widespread. This explained the negative results of the mieroscoplcal examination. On the contrary' this trealnent only causes a reduction in the fluorescent antibody titre, but does not lead to complete disappearance of the reactlon. In conclusion, the results of the present investigation pernltted anticipatlng the spread of malarla in the southern area of Bastia and i.n the central part of the eastern plain, but the southern part of the island remained malarla-free. The records tabulated by the authors for the whole island showed that lndigenous cases continued to be detected tn 1971 ln additlon to imPorted cases: 10 and 9 resp-ctlvely. The authors noted that the reappearance of malaria ln Corsica creaEed diverse reacti-ons ln the nedlcal press of Britaln. Ihey were, in fact, pointing to a report by Brltt & Itutchlnson (1971) who diagnosed P. vivax infection Lrt a 24-year old Brlttsh citlzen after his return froo a summer holidayFsouthern Europe, including 12 days ln Corslca rrhere he stayed at a camp site by the sea and slept soroe nlghts ln the open at St. Florent, experiencing numerous lnsect bites. Although the exact place aE which the infection was contracted in southern Europe could not be ascertalned, it was thought that St. Florent, Corsica was the nost likely place. Attention was drawn to the need for increasing arrareness of the possibility of oalaria among people returning to vBc/ 90 . I MAL/90.1 Page 21'

Britain fron southwest Europe. Bruce-Chwatt (1971) cornmentedon the above communicationr pointing out that reliable infornation fron WHoindicated that autochthonous malaria in souLhern Europe no longer exist.s. However, this does not exclude the possibility of sporadic cases of malarla being inported from elsewhere into areas where the disease has been eradicated. Such cases nay infect local anophelines which may transmit the disease to some vlsitors. Actention was drarn to P. falciparuo infection which nay develop rapidly with serlous complications. For this reason, Ehe possibility of nalaria in any febrile patient who had returned from any tropical or subtropical area should always be kept in mind.

Brunpt' Petithory & Giaconini (1978) pointed out that mal.aria observed in France is often mortal. In 1973 alone, there were 186 malaria cases with eight deaths as declared by 13 out of 28 regional hospltals including those of Paris. These records are oost incoropletel nalaria norbidlty and mortality rates are, J.n fact, nuch higher than those reported. Extrapolating fron these figures and taking into account that. only the nore severe cases are hospitalized, lt can be deduced that a figure of about 2000 nalaria cases Per year (with 20 deaths) is a reasonable estimate, witlr 2/3 of it being P. falciparun cases. It is a regrettable sltuation because the effective ueans of prevention are avallable, the nost inportant of which is chenoprophylaxis. Although the tern inported malaria is well defined, a clearer definitlon is required for the terxos of autochthonous and introduced nalaria. According to modern terminology, the tenu autochthonous should be reserved for cases of peroanently endemic foci. Therefore, this tern does not apply nolr, because autochthonous malaria has di.sappeared fron conti.nental I'rance since the first decade of the century and more recently from Corsica. It folLows that autochthonous malaria should not be confused with introduced nalaria which is observed only frou time to t1tre. The anophelines are always present in France which could become infect.ed by feeding on ga&etocyte carrlers aDong travellers and lnnigrants, bu! the local potential vectors are not adapted to the tropical stralns of P. falclparrrm. From a study of 226 inported cases in 1975, about half were seen in Septeober ind October. This period corresponds to the return of French people and also the Afrlcans who nent on holldays. The latter group rePresents students and inrnigrant workers who usually pass their holidays in their original countrles. They have lost their lnmunity to nalaria after residi.ng in France for some years, hence they becone very susceptible to malaria infection. llore susceptibte also are their children who were born j.n France and go to Africa with their parents without any Precautions. An investlgation showed that their prophylaxis nas insufficient durlng their stay in Africa or was lnterrupted for tlro Donths after their return to France. For prevention of importation of malaria, it ls necessary to disseninate the relevant infornation to travellers, tourists and the Africans going to their homeland. In thls respect, assistance should be sought fron hollday clubs, tourist offices and air conpanies. It is also inportan! to lnforo physicians; it is regretted that parasitology is beconlng reduced during nedical studies. For this reason the authors assisted in Post8raduate studies by distributing abou! 6000 slides containing blood parasites Eo physicians' biologists and technicians since 1943. On the other hand, the legislation of obligatory declararion of autochthonous cases of malari.a needs to be nodified and aneli.orated. As nentioned above, the obligatory notification under the decree of. 29 January 1960 does not solve the problem since prinary autochthonous cases of oalaria -sensu stricto has disappeared from France a long tlne ago. The facultative declaratio., by laboratories as reguired by the circular of 25 September L972 is ineffective as can be reflected from its name. To conclude, the authors underlined the need for obligatory notification of all nalaria cases whether autochthonous, lntroduced, induced or accidental, as a basis for epidenlological follow-up. This represents an iuportant step in the rlght direct.ion for solving the problen of imported malarla, since the other measures have not so far been sufficiently effective.

Bastln & Charnot (1980) studled 100 inported cases of nalaria hospitalizeci at Claude-Bernard Hospital, Paris, France. These were 73 men and 27 wonen aged 20-50 years. Of these, 77 vere French, 21 fron tropical Africa, 1 Canbodian and 1 Vietnamese. Of the French natlonals, 33 travelled to a malaria endemic area for professional reasons and 38 for tourlsm, but six cases were undelernined. 0f the Afrj.cans, 16 spent thelr holidays ln their country of origin. Chenoprophylaxis was absent in 66 cases, discontinued on return to France in 21 cases, correctly administered ln 1l cases, and undeternined in the remaining cases. The Africans lose their lmunlty to malaria, as they lived in France for a long time. The najority originated froo areas of the lrlest African savanna and their holidays are taken in sunner, colnciding with the net season which is a peri.od of intense vBc/90. 1 !,rALl90.1 Page 22

nalarla lransmission in their country of origln. Wlth regard to paraslte specles of these imported cases, 83 were P. falciparum, l0 P. ovale, and 7 P. vivax, while P. nalarlae was totally absent. The perffil-.fTffie-5-etweei@ure fron-a inlc area-ai?l-fe-- appearance of the flrst fever was determined for the 100 cases exaoined as follows: less than one month for 77 cases of P. falciparum, 1 case of each of P. ovaLe and P. vivax; 1-2 oonths for 6 cases of p. tatctpliGTlEFof P. vivax, and 3 .ry roonths for 8 cases of P. ovale, and 3 cases of P. vLvax. Difficulties and limltations of drug prophylaxis were 6ffi[,notably chloroqu-ne reslstance ln P. falciparurn strains exlstlng ln South East Asia and Latin Amerlca, whlch ls extendlng-;;G;i--1 Africa as well as resistance to antlfolic coupounds (pyrlnetharoine and proguanll). Suggestions were nade for the types and dosages of drugs to be taken by travellers to endemlc areas for chemoprophylaxis. The possibllity of reintroductlon of malaria lnto France froo inported cases infecting potentlal loca1 vectors such as An. nacullpennls and An. claviger in the Par1sareawasdiscussed.Ther1skwasconsiderE-:E6-@woriffiaseof Afrlcan P. falclparuo, based on the experloental evldence provlded by ZuJ-ueta, Ramsdale & Coluzzi (1975). On the contrary, the rlsk ls high in the case of l4edlterranean stralns of P. vlvax, bearing in olnd the epLsode of Corslca ln 1970.

- Dehoont et al. (1980) pointed out that untll recently ft{arch 1980 see below], it has been dlfflcult to estlmate the annual incldence of cllnical cases of lnported nalaria because medlcal practitloners declared only cases considered as prinary autochthonous lnfections. Consequently, notlflcatlons conveyed to natlonal and lnternatlonal health authorlties have not permitted the evaluation of the true frequency of inported malarla cases. In view of thls deflclency, an lnvestlgatlon nas carried out in soue hospltals in large towns to estltnate the nuuber of lmported oalarla cases, and to study their epidenlologlcal characterietics. Fron the whole of metropolitan France, 45 loported cases were offlcial-ly reported to WtlOdurlng L973-L975, while a retrospective study revealed 64 cases ln hospitals of a slngle city, Marsellle. 0n the whole, enquiry at all hospitals showed an lncrease ln the annual Lncldence of the inported cases, but dld not reflect a valld estimate of the real frequency. Recently, the Mlnlstry of ltealth and Social Security requested the departmental dlrectorates of Health and Social Affalrs to enqulre fron ttre speclallzed services of unlverslties and the princlpal hospitals about the number of malaria cases thaE have been conflrmed parasltologically. This retrospective enqulry revealed that 535 lmported nalaria cases nere recorded ln a single year, 1978. This figure gave a better representatlon of the sltuatlon than the results of an enquiry dlrected to 500 prlvate general practltloners lrorklng ln the Provence-C6te drAzur and in Corsica. From 319 repltes, 1t could be establlshed that in 1978, at least 40 inported cases were diagnosed parasltologlcally by the private medLcal secEor, and that hospitallzation was not requlred except for flve cases. To estLmate the number of lnported cases the followlng fornula rras utllized: ax = by, where: x = the nunber of inported cases seen ln hospltals y = the number of Lnported cases seen outside hospltals. a = the percenEage of cases conflrmed before hospltallzation b = the percentage of cases transferred to hospitals among those detected outsLde.

Through enqulry at hospltals, it ls fairly easy to deteruLne (a) and (x).

In Marsellle the results obtalned fron hospital enquirles and those derived fron the theoretical calculatlons were falrly identlcal; they showed that about 3/5 ot the inported cases were dlagnosed outside hospltal-s. Extrapolatlon fron these results on Detropolitan France, taking into account the population and the number of physicians ln private practlce, lt was estimated that there rrere Dore than 2000 cases of imported roalaria [ln 1978?]. In naklng this estinate, only cllnical cases which were parasitologically confirned were taken into account, as the nlcroscoplcal examlnatlon ltas not always dernandedby the treatlng physician. Moreover, sorne patients decided to take antlmalarlal drugs before rnedtcal consultatlon. I{hen estlmating the number of lnported cases, lt is also necessary to bear in nlnd that a large number of persons are asymptomatlc carriers. Whlle lnported oalarla has become a real problem, it was surprlslng to obtain the following answers fron general practitioners who were asked to give vlews on the variation ln the annual lncldence of lnported cases during the past five years:46.L7. had no opinion, 34.27" affirned the stablllty of the incidence, 17.22 pointed to its diminution, and only 2.57" tndLcated that the incldence increased. In concluslon, it ls necessary to oake the notlficaElon of inported nalarla obllgatory and that efforts be nade by national vBc/90. 1 MAL/90.1 Page 23 and lnternatlonal authorltles to lnforn the uedlcal corps about the recrudescence of the lnported lnfection.

Genrillni er al. (1981) indicated that durlng L970-L979, 433 nalaria cases were diagnosed at the Pltl6-Salp6trldre hospltal group ln Parls. The annual figure showed a sEeady increase, rlsing fron 7 in 1970 to 93 in 1974. The parasite sPecies were:

P. falclparum 66.72 P. ovale L3.97" P. vlvax 14 7" F]-niGTLa e 5.2% ilEGiEi bastianelli (1 case)

There were mlxed lnfectlons as follows: P. falciparum * P. nalarLae (7 cases), P. falciparun * P. ovale (3 cases), P. falcipiffi-:FElffiax CrcGsand P. nalarl?e * p.;tale-(iEse). Ttre uonthly breakdown of the cases showed the occurrence of a regular lETFrou August-October. The increase cotncldes wlth the return to France of nany surnrner holidaynakers froo malarla endeolc areas where lntensive malaria transmlsslon takes place durlng the rainy season ln most of troplcal Afrtca and Asia. NeverEheless, there has been an increase ln the number of cases observed throughout the year, and this was explained by the lncrease in intercontinental business travel and uinter holldays and the frequently observed l-ong lncubatlon perlod of specles other than P. falciParum.

Of the 443 patients diagnosed, 192 were observed by the authors and thelr nedlcal reports analyzed as summarized in the following:

- Natiooallry: French cltizens 6O.97"; persons fron troptcal Africa 33.4%; North Afrlcans 12; Asians L.6%; Latln Aoericans 2.L71; Europeans excluding France 12. Most of the people froro troplcal Afrlca were from French-speaking countries, and 802 of them were lmmlgrants, workers and students who stayed in France for perlods varying from two to 16 years, while the remalnLng 207"were lLvlng ln Africa before thelr stay in France.

- Origin of the infectlon: The rnajorlty of the cases (83.32) originated in troPical Afrlca, particularly in the French-speaklng countrles of West and Central Afrlca, vlrtually assoclated wlth the important econoulc and cultural exchanges between France and these countrles. From Asia 8.92 of the cases wlth most of the infection contracted ln Indo-China and Thailand. Only 3.77. of. the cases orlglnated ln Latln Amerlca. Three cases (L.5%) orlginated Ln France: the flrst lras an lnfant sufferlng from congentlal malaria [the origln of lnfection of the mother not shown]; the second adult probably infected near Orly Airport by an exotic Anopheles carrled by an alrcraft from a nalaria endemi.c area (citlng Gentilini et al. 198); anA the third case was a laboratory technlclan who was - accldentally lnfected by P. cynotoolgl bastianellii (clting Druilhe et al.' 1980) see under L.2.L (li)a, below.

- Age and sex: Young adults (20-29 years) constituted 55.57" of the French Patients coopared wtth 4l-.97" of I -igrants of the same age.

- Incubatlon perlod: It was dlfflcult to establ-ish with accuracy the lncubatlon perlod because of the large variatlon 1n the duratlon of stay in endernlc areas. The authors considered the time that elapsed between the departure from the endemlc area and the flrst appearance of clinical syuptons as representlng the ninimun lncubatlon Perlod. In the case of P. falciparun, this perlod was less than 15 days in 83.27" of the cases, and over two rnonthsffi]Jffi, wi-th the rnaxiuurn belng eight months. With P. ovale' the onseE of symptons nas observed in a perlod of less than tlto months ln 21.2% of the cases, durlng the thlrd or fourth oonth tn 42.4%, and after a longer perlod ln 36.4%, with the oaxluum belng 15 nonths. Wtth P. vlygx, the first syuPEomsappeared before two months in 587"of the cises, durlng tire ttrFi-iFourth nonth ln 10.5%, and after a longer period 1n 3L.57". Of nine cases of P. malarlae, five presented the flrst syltrPEomswithin one montht and the remalning four during the thlrd and tenth oonth.

- Conditions of cheooprophylaxls: Almost all cases of P. falciparun infection were due to lack or lncomplete chenoprophylaxls. llowever, ln three cases infectlon occurred despite taklng thelr cheooprophyLaxis correctly. The stralns of this lnfectlon origlnated fron South East Asla or the Aroazonreglon of Brazll and were probably resistant to vBc/90.1 t'AL/90.1 Page 24

chloroqulne. A large proportion of patients wlth P. ovale and P. vlvax lnfections had followed their chenoprophylaxls correctly. TaktngFnto account-ElGn-gth of the lncubatlon period and the posslblllty of relapses, i.t can be inferred that although the perlod of two months norually reconrmendedfor contlnuing chemoprophylaxis after return can prevent attacks of P. falclparun in almost all cases, lt cannot give protectlon fron the more delayed attacks of the other specles of Plasoodia. The authors further discussed thelr flndings in relatlon to those previously reported by other authors in France and elsewhere in Europe wlth respect to the dlstrlbutLon of paraslte specles of imported nalarla, the origl,n of patients and the lncubatlon period. Wlth regard to incidence in France, it was pointed out that the declaration of lmported nalarla became obllgatory only ln March 1980, hence the prevlous evaluatlon of the annual nunber of lmported cases was fortuitous. Reference ltas made to Bruopt, P6tithory & Giacomini (1978) who estimated that the annual nuober of imported cases was 2000 wlth 20 deaths. It ls posslble that the current lncidence ln France ls rouch hlgher. In the group of cases observed by the authors there were no fatal cases, even though 11 patlents had cerebral nalarla. Rapid diagnosis and treatoent are essentlal for preventlng deaths. In concluslon, the authors polnted out that the recent increase tn funported nalaria ln Europe calls for establlshing an lmporved information service for physlclans, who, ln general, are not fanlllar with this disease. Slnilarly, an efflclent informatlon servlce is needed for travellers to naintaln drug prophylaxis correctly and to avold lnterruptlng lt prenaturely. Airllnes can provlde the necessary lnforrnation to travellers golng to nalaria endemlc areas, in the forn of booklets, infornatlon sheets placed ln the aircraft aod lnfornatlon broadcasts on loudspeakers or through lndividual earphones.

Gentillnl & Ilanls (1981) surnmarlzed the records of autochthonous or introduced malaria whlch were reported by various workers ln the European territory of France durlng 1969-1978. The tern autochthonous nas Eeant to cover cases consldered to have been lnfected by local or imported anophellnes, thus lt excludes cases of lmported, induced and congenltal oalarla. The authors grouped the reported autochdrcnous cases into three types:

Type I : Introduced, as exempllfied by the rnalarla outbreak ln Corsica durlng L970-L97L where P. vlvax transmlssion was effected by the local vector, An. labranchiae under favourable crioatic condltions, and the orlglnal infectlon was arrffi-:E6-ffih Afrlcan i nigrants (see above).

Type II: Undetermlned, the mode of transolsslon of whlch remalns inexplicable. These were seven cases (5 P. falciparun and 2 P. vivax). Ilalf of these cases nere recorded in the north of France where the cLirnate varles from less favourable to oulle suitable for oalaria transmisslon. These cases were:

P. falclparun

- 2 cases (a nale and a fenale) detected in BreLagne in August L969. [The two cases were detertnined later as alrport mal-aria - see below. ]

- a case of a fenale aged 27 years detected ln Sologne in August L977, reported by Chavanne et al. (1979).

- a case of a nale aged 70 years detected in Paris in Decernber1978, reported by Guillausseau et al. (1980).

- a case of a male aged 23 years detected ln Yvellnes (Plaisir) in Septenber 1978, reported by Cassaigne, Brualre & L6ger (f980).

P. vlvax

- a case of a oale aged 82 years detected in Val de Marne (Saint-ltand6), ln August 1977, reported by Sallou et al. (1978).

- a case of a fenale child aged 6 years detected ln October 1978 in Nornandy (Elbeuf), reported by Morln et al. (1980).

Genttlini & Danis (loc.cit.) explained that wlth the exception of the case of P. falclparun detected In the Parls reglon ln December, all other cases as shonn above vBc/90.1 MAL/90 . 1 Page 25 were observed in suumer or autumn, a perlod durlng which An. maculipennts cornplex and An. clavlger are usually present. Theoretically, Lhese specles are suscePtible to P. vivax ffi-n, wh1le their capaclty to transmlt i. falclpirun ls doubted, partlculaffEE- stralns of this paraslte originating ln tropical Afilca and frequently encountered aaong imlgrants in France. In this connectlon reference was made to experinents showlng the refractoriness of European An. oaculipennis complex to exotlc P. falciParun, carrled out by Shute (f940), Zulueta, Ramsdale & Coluzzl (1975) and Rarnsdale& ColuzzL (L975). Moreover, temperature condltions requlred for conpl,etlon of sporogony ln P. falciparun (19-:Oo C in 10-30 days) are rarely met ln the nortrhern and central regions of France. Ilowever, the source of infection of these anophelln,es with P. falclParun could noE be establlshed wlth certainty (see further infornation below).

Type III: "Alrport" malaria, exaoples were given of lncidents of malarla transmi.tted by exotic anophellnes transported by aircraft.

Recently, B6gu6 et a1. (1984) descrlbed a case of a 7-year old child who was subroitted to surglcal lntervention (for d6colleoent biaurlculalre) on 26 March 1983 and had a febrile episode on 11 Aprll 1983. ltlcroscoplc exam:lnatlon of a blood smear revealed the presence of P. nalarlae. Ihe fever subsided after chloroqulne treatment. The node of transmission ln thls case nas puzzLlng ln that the chlld has never had any blood transfusion since birth. Moreover, nelther he nor his parents left I'letropolitan France. They l1ve in the Parls reglon, but not near any internatlonal alrport. Accidential infectlon through lnfected needles was entirely exc.Luded. The only posslblllty was that the chlld contracted the infectlon during his surnme:rvacation ln Alsne departnent in France when the temperature nas above 18o C for a fortnight whlch is the period necessary for sporogonic development in a local potential vector. The effect of the flrst parasite invaslon must have passed unnoticed, but the surglcal interventlon in March 1983 must have reactivated the Lnfection. As there was no evldence to support thls hypothesls, the authors were lncllned to consLder this case undetermlned following type II of Gentillni & Danls.

Gentlllni & Danis though lncluded among the five cases of P. falclparun classifled under Type II, two cases detected in August 1969 in Brlttany (Bretagne), north of Frnace, 15 days after their arrlval fron Paris, suggested that their infection may have been of type III. In fact, Doby & Gulguen (1981) who sere rllrectly responsi.ble for the parasltological dlagnosls of the tno cases objected to thelr classlflcatlon under Type II, and gave a full account of thelr hlstory as well as detalls of epldeuiological and entomologlcal lnvestigaEi.ons. The tlro cases were ln fact a couple who were living and travelllng togetber in Brl.ttany. Fifteen days after their arrival ln Brlttany they suffered from fever and the tnan dled after four dayri. P. faLclparun infection was ldentlfied on post-mortem. The woman whose blood e:

- the presence of infective cases ln the area oiE Brittany where the couple resided: investigatlon on the spot excluded thls posslbllity;

- the exlstence of specles of anophellnes that blte nan: entomological searches revealed the presence of An. claviger which is esserrtially anthropophllic but nainly bltes nan outdoors. An. atroparvus was found in the coastal area. This species is essentially zoophllic but sffiFroan;

- the degree of receptivlty of the European anopbelines: the experimental evidence demonstratlng the refractoriness of An. atroparvus to exotic P. falciParum strains was cited (as shown above);

- the oeteorological condltions in Brlttany dur:tng the period preceding the arrival of the couple which may have permitted the sporogony of P. fal-icparum to be coopleEed in a local anophellne: checklng the available local meteorological data showed thls is not absolutely inpossible, but seems to be hlghly iuprolrable;

- the posslbillty of contracting the infection jLn Parls in the days precedlng the arrival in Brtttanyi having been unable to confirm any of the three above-mentloned posslbllities with absolute certainty, the authors llound it more plausible to consider that the two patlents were lnfected tn the Parl,s arr:a before departure to Brittany. Thls vBc/90.1 MAL/90.1 Page 26

assumptlon was supported by the fact that they must have shared the saoe house sltuated a few hundred meters fron Le Bourget airport where probably an lnfecled vector from a tropical area nas brought by a passenger or cargo airplane. Therefore, the two cases should be considered examples of airport malarla infections.

The risk of resurnption of nalarla transmlsslon in France was discussed by Rodhain & Charnot (1982). Mter reviewlng the cases of malaria that had been recorded in the past, reference was oade to cases that have been detected in recent years as follows:

- 11 cases (10 P. falctparun and 1 P. vlvax) rrere observed durlng L969-L978 ln persons havlng contact with lnternattonal airports in Parls, including the two cases ln Brittany (shown above).

- five cases (3 P. falclparun and 2 P. vlvax) were reported between August 1973 and October 1978 (citing several authors as has already been shown by Gentilini & Danis, 1981). These cases could not be explained by their associatlon wlth lnternatlonal airports. From their hisEory, four of these cases were recently hospltallzed and the fifth was a nurse ln a hospital. It was dlfflcult to draw a firn conclusion on whether an unrecognlzed carrier could lnfect a 1ocal susceptlble Anopheles which lransmltted the infection wlthln the hospltal. However, the rare occurrence of such cases contrasts wtth the large number of inported cases reported annually ln France (1500-2000) lncluding an appreciabJ.e number of gametocyte carriers. The potentLal vectors that can be responsible for malaria transmlssion are three species of the An. nacullpennls coroplex:

_ An. atroparvus, prevlously recognized as a princlpal vector. It is wldely dlstrlbutedE coastal areas breedlng ln brackish rraters particularly in northern Eurooe (e.9., northern France and the Netherlands).

- An. oesseae ls usually zoophilic but lras connected with epldemics at times.

- An. labranchiae breeds ln swampswlth vegetation ln the lrestern part of the MediterraneanTaffi@ Italy, Siclly, Sardlnla, Corslca and Tunlsla).

I'Iith regard to receptlvity of these specles to rnalarla infectlon, reference was also made to the experi.mental evldence that demoustrated the refactorlness of the European members of the ao. rac"ffp"""f". complex to the tropical stralns of P. falcipar*., although [email protected],P.v1vax-EffiTfr1caor Turkey where lts vectors belong to the An.-Gdli-ennts con!ffi-n be consldered a Potential source for re-establishing P. vLvax transoisslon ln rrestern Europe as was the case In Corslca. This would necessltate organizlng careful survelllance of oalarla, notably in the Mldl, France. The factors necessary for creating a focus of malaria transmisslon were outllned as follows:

(a) the presence of a sufflclent anophellne density having adequate contact with man;

(b) lntroductlon of a sufflcient number of gametocyte carriers during the favourable season;

(c) conpatlbility between the paraslte lntroduced and the loca1 potential vector - as mentloned above the stralns of P. vivax fron the Mediterranean basin are quite conpatlble;

(d) the presence of favourable clioatlc condltions, particuLarly temperature suitable for P. vivax (not less than 17o C);

(e) lnadequate or absence of a survelllance system.

To conclude, the authors constder lt hlghly inprobable that arrival in France of ganetocyte carriers from troplcal regions would lead to resumptlon of roalarla transmission. Ilowever, foci can be established only in the case of massive introductton of P. vlvax of Medlterranean ortgln as lt was observed in Roussillon in 1939-1943 wlth the arrTEf-Frnore than 200 000 Spanlsh people. Ibis type of foci, however, ls unstable nalarla whlch is relatlvely easy to eradicate. vBc/90. 1 MAL/90.1 Page.27.

Some cases of congenltal nalaria were reported jln France as related to funported infectlon. Vernes et al. (1973) descrlbed the cllniLcal aspects and blood plcture of a female infant born on 17 Novetnbet L977 and was hosp:ltallzed on 7 Deeember L977 as she was sufferlng from fever. Examination of a thick blood smear durlng the fever eplsode revealed the presence of asexual and sexual forms typtcal of P. vivax. She was l.-edlately tieated with chloroqulne and was succeselfully curffiiG roother of this snall infant was a Canbodian refugee who arrived in France>ot 22 September L977. Her pregnancy was norual but she was sufferlng fron severe anaeol;r. The birth was normal, but on the following day she suffered from an attack of fever wlth rlgors; examlnation of her blood revealed the presence of P. vivax. The congenital characteristlcs of the malaria infection ln the lnfant a-na rts occurrence in wi.nter in northern France, nakes the assumptlon of post-natal transmisslon by a local Anopheles ioprobable. The authors indicated, however, that cases of congenital nalarla in France are qulte rare.

Excler (1930) reported on a case of congenltal nralaria ln an infant who suffered froro lnterolttent fever for 28 days slnce his blrth on 5 June L974 at the hospi.tal in Lyon anc was referred to roedlcal examlnatlon on 2 July 1979. The results of all cllnical and laboratory lnvestLgatlons includlng serological tests were described. Microscoplcal examinatlon of a blood snear taken from the infant on 3 July 1979 revealed the presence of asexual stages of P. vlvax but an IFA test nas negatlve. The lnfant nas successfully treated by the app-@E dosage of chloroqulne. IIls uother, a Cambodlan refugee, aged 25 years, llved in France for a year prevlously duriLng whlch she became pregnant. Durlng her pregnancy she suffered from frequent eplsodes oi: fever partlcularly during the last three months, but none of these eplsodes presented j-tself durlng her prenatal examlnatlon, and no blood examloatlon for malarla parasttes was made. She dellvered nornally, but ln the week that followed she suffered from bouts of fever. Mlcroscoplcal examination of her blood and a serologlcal test by IFA rrere negative. She was given antloalarla and antlhelulnth treatments, the latter was lndlcated by the hlgh eoslnophllla. To explaln the infectlon ln the lnfant, three hypotheses were discussed. The first rras that the lnfecElon resulted from an lnfectlve blte by AnophelLes, but thi.s was excluded on account of absence of autochthonous oalarla cases ln the hospltal in Lyon durlng June 1979. The second nas neo-natal lnfectlon passed by the notherts parasltlzed blood to the lnfant through cutaneous excoriatlon, but the delivery was normal wlthout using forceps. Even if thls happened, the infant should have had hls flrst fever after 2-3 weeks, whlch was not the case. The thlrd posslblllty lras a congenltal malari.a and thls was supported by the fact that the mother had eplsodes of fever parttcularly during the last three months of pregnancy, the iurnedlate appearanee of fever in the lnfant upon blrth, and hls advanced cllnical plcture (enlarged ltver and spleen plus anaemla). It ls regretted that nelther the placenta nor the cord were examined. It ls clear that the uother had been lnfected in Canbodia wlth P. vlvax. The lmmunological status of the mother and her child was discussed.

The recent situatlon of iuported nalarla ln Frarrce was clted ln the WHO(1987 &U Epiden. Rec.) fron the "Bulletln 6pid6niologlque hebdonadalre, (BEII), Dlrectlon g6n6ra1e de la Sant6, No. 23/1987". In 1985, 49 laboratories attached to universlty and reglonal hospltals agreed to take part in prospective data collection on malaria as from the nonth of June. The results showed that durlng the first six months 47 laboratorles notlfied 631 cases of nalarla dlagnosed nicroseoplcally, to the llatlonal Reference Centre for Inported Diseases (response rate 90%). The species most frecluently encountered was P. falclParuu (76"/" ot the cases), whlch lras aEtributable to the f€lct that a high proportion of Patients (792) were lnfected in Afrlca where P. falclparrln pr:edoolnates. In six cases, lnfectlon occurred in Metropolltan France. Four patlents nere infected through blood lransfusion (2 with P. falctparun and 2 ldth P. nalariae) and ttrere were two indlgenous cases: one was a P. malartae:l.n:Fect:lon contracteilln Languedoc-Roussllon and one a P. falciPaluq rnffi-n co-ntracted close to llarsellle airport. Comparlson of datalffiffi those recorded ln L986 is shown below.

Jeannel et al. (BEII, 1988) presented an account of the oost recent records of inported rnelarla Ln France. As from 1985, the preparation oll lndividual cards for each patient presenting a ualarla fever nas putsued tn 1985 and l-987. It was through the collaboratlon of 46 laboratorles belonglng to university and reglonal hospltals that 1025 cases of malarla lrere reported ln 1986, for which detailed derta were given as sunmarized in the followlng: vBc/90.1 !,IAt/90.1 Page 28

- Specles and country of origin of lnfectlon: P. falclparun rras the most frequent lnfectlon encountered (832). P. vivax, P. ovale aid-Tlt,ffiEe (not associated wlth P. falclparun) constitured 8%,-8%d-lz. E...Gs res!@ 0f P. falclparurn cases 912 originated ln troplcal Afrlca. A total of 34 cases contracted the infection in Asia, of which only elght were P. falclparuo. SlollarLy 34 cases contracted the infectlon in Latln Aoerica, of which 23 were froro French Gulana. In Metropolltan France, there were four cases attributed to blood transfuslon (1 P. falciparum, 1 P. malariae, I P. vivax and I P. ovale).

- Dlstrlbution of patlents by nationallty, age and sex: 59%of the cases were Europeans (439 French of 523 Europeans) and 382 Africans. The mean age was 28.4 years; the patlents ln the age-group 20-39 years represented 53z. of the cases and of less than 20 years of age represented 257"of the cases, but the age dlstrlbutlon varled accordlng Eo the geographlcal orlgln of the patlents. There were more males than fenales (682 among Europeans ar:.d627" among non-Europeans).

- Cherooprophylaxis: There vere 275 persons (34%) who followed the chenoprophylaxis correctly. About half of the European patlents properly admlnistered the prophylactlc drugs, brtt 237" took nothlng. Anong non-Europeats, 6LZ took no prophylactic drug, whlle 13% apparently followed complete chenoprophylactlc reglmen. 0f the 275 patlents who took a cooplete course of chenoprophylaxls, 222 exhtbited a secondary P. fal-clparun infectlon. Of these, 151 were reported as drug-resistant (91 proved by ln vitro test, and 60 consldered suspected).

- Interval between return to France and the dlagnosls of P. falclparum: Inforuatlon was avallable for 539 cases. It was lese than one uonth tn 76ffi-ese gases and two months ln 892 of the renalning cases. In 20 cases, the attack was delayed for more than six months.

- Pernlcious oalaria: Of 847 cases of P. falciparun, 50 exhlblted pernlcious manlfestations, of whou 41 were Europeans. Drug resistance was proved or suspected ln 19 cases (2 Afrlcans and 17 Europeans).

- Drug resistance: In vltro tests conflrrned the presence of chloroquine reslstance ln 107 patlents (12.67" of SZ6ffilciparum cases). The orlgln of the lnfections was: Centra1Afr1ca(76cases),m;J6cases),SouthAfr1ca(6cases),EastAfr1ca(6 cases), French Guiana (3 cases), and undetermined orlgln (3 cases). Drug resistance was suspec8ed ln 114 cases (L3.57. of P. falciparum cases) on the basis of clinical and therapeutic crlterla

- Distributlon of cases in France: P. falciparum was the species frequently encountered in all regions or departments, but the natlonallty of the persons was not the same. Of all reported malaria cases, 6L% vete dlagnosed in the Parls region, nostly Africans, whi.le 247"of the cases were recorded 1n all other reglons.

- Comparlson between the results of 1985 and 1986: Although the results of 1985 covered only six months, cooparlson of the results of the two years polnts to the followin$: P. falciparun constltuted the naJorlty of inported cases in 1985 and more so in 1986; the origin of infection has been essentlally African. The nunber of Africans exceeded that of the Europeans (52"1 Afrlcans vs 447"Europeans) ln 1985, but the reverse lras seen ln 1986 (38% Afrlcans vs 59% Europeans). Chernoprophylaxis was absent or ineomplete ln the najorlty of cases (78% tn 1985 and 667. La 1986) particularly among non-Europeans. This partly explalns the appearance of a large number of persons with oalarla attacks. An increase in proven and suspected cases of chloroguine reslstance IJas an ioportant development ln the tno years. Ot 482 P. falclParuo cases reported ln 1985' 2.7% ptesented proven chloroquine reslstanee, 5.52 suspected. Of 846 P. falciParun cases reported in 1986, the percentages of proven and suspected resistance ltere respectively L2.6% and 13.57", i.e., the lncldence of chloroqulne resistance proved by in vitro test lncreased nore than 4-fold.

In concluslon, the extentlon of the area of chloroqulne-resistant P. falciparun in Afrlca ls a major concern. The pernlclous manifestatlons of P. falclparun infection is also worrylng, as these nay lead to death. In 1986 as ln 1985, the proportion of cases that exhlblted pernlcious DanlfestatLons was 6% of all P. falclParun cases. This ls vBc/90.1 MAL/90. r Page.29 probably an underestimate, since laborat,ories do not always have access to the clinical findings. This is why an lnvestlgation on deaths due to malaria has been ordered by the dlrectorate general of health.

In Britain, llorgan (1987) explained that the lfalaria Reference Laboratory (]A.R.L.) is the main surveillance centre for nalaria cases in the country. It uonitors countries where there is a malaria risk and the spread of chloroquine resistauce, and advises on nalaria prophylaxis to be glven accordingly. The latroratory also acEs as reference centre for blood fl1ns suspected of having malaria. The latroratory receives lts noti.fications froo three main sources: the first source is the M.R.L. standard forn conpleted by the doctor treating the patlent; the second is the blood slide which would be accompanled by a standard forn; and the third are coples of the Offlce of Populatlon Censuses and Surveys (0.P.C.S.) Notlfiable Disease forn sent by the HealtLr Authority where the case is diagnosed. "Foreign visitors ill wlth nalaria in Bri.taln" category was first used by the M.R.L. in 1975, and is now the second largest group arfter "iomigrants vlsiting counlry of origin". These foreign vlsltors are import,ant becausie thelr proportlon ou! of the total nunber of cases is increaslng, and also they have a hrigher proportlon of P. falciparun, the potentially fatal lnfectlon. The author reviewedl the data of 1985 notlfication to the I'{.R.L. and studied in detail those reported as foreig;n visltors. In 1985, there vere 22L2 notificatlons of which 427 (L9.32) were classlfied aer foreign visitors ill whlle visiting Britai.n. Of these foreign visi.tors, 47.52 lrere reported as having P. falciparun, and one third of the cases (143) were 1n the 20-29 age-group. Classifying the cases of the vlsitors by country of blrth showed that 30.52 (L30 c.ases) were born in Nigerla, of whom 112 had P. falciparun nalaria. Thls represented 53.212of P. falclparun cases anrong visitors and 16.37 of all cases of P. falclparun reporrted. About 29.3"A (125 cases) of the vlsitors were born in Indla, of whon 110 had P. vivax malaria and this represented 6O.4i( of P. vivax cases among visitors and 8.22 of illlFLvax cases reported. occupation rdas given tor I72 foreign visitors, these included 66ElFs wtrose occupatlon was stated as students, of whom 43 were fron Nigeria. Three hundre,d and one forelgn visitors were recorded as not having taken autlnalarial drugs, 53 did take nalaria prophylaxis, but infornation was lacking for 73 cases. The i.nterval between arrlval ln Britaln and the date of onset of the illness was studied ln relation to the type of ualaria, the age and the country of birth of the forelgn visltors. Analysis of these data showed rhat 66i( of P. falclParun cases were presented withln one Donth of arrival, whereas 37.47. P. vivax cases came within thls perlod. This was probably due to the more acute and severe nature of P. falclparuo compared wlth the relatlvely oore chronlc and relapslng P. vivax. It was also observed that LIZ of th.e 427 foreign vlsltors nere slck before arrival. In his dlscusslon, the author suggested that foreign vlsitors comlng from malaria endenic areas who are reported as havlng nalaria, would probably fall lnto three categorles:

(a) Those who by virtue of livlng in Brltain for a substantial length of !ime, lose some of their inrnunity to Dalaria and becone reinfected while visiting their native country, e.g. r students studylng in Britain.

(b) Those persons who are seml-iromune to malaria, but suffer a recrudescence of their chronic parasitaeoia while in Brltain.

(c) Those persons who for unknown factors suffer from a disruption in the host-parasite equilibriun which results ln a malaria attack. This would expiain the large ProPortion of foreign visltors (68.67" ot 427) with the onset of rnalaria symptomswithin one week of arrlval in Britain.

Phillips-Howard et al. (1988) analyzed the data of nalaria recorded in Britain during L977-L986, as suomarized in the following:

- Incidence: Over the past decade, l8 374 nalaria cases were reported to the Malaria Reference Laboratory, of whi.ch 27i( uere P. falci,paruur lnfections. After falling in the early I980rs, the nunber of cases progressively incre,ased reaching 2 2L2 in 1985 and 2309 in 1986. In 1978-1979, the number of cases reached a. peak coinciding with the advent of new inmi.grants eDtering tsritaln, whereas recent data suggest that the groups who are lnportlng malaria are already resldent in Eritain and travel for short vlsits to malaria endemic areas. A parallel lncrease in the number of P. falciparun cases has been observed ln recent years reachlng 738 ln 1986 conpared wlth 25EE'197mlth regard to P. vivax, an average of about 1200 cases are reported each yea!, constitutlng 652 of aLL vBc/90. I MAL/90.1 Page 30

lnfectlons. P. ovglg cases are few, having lncreased frou 1Z to 37 of all cases (nainly fron Nigeria)FfrIfe-p. malariae cases have been conslstently less than I% of all cases. - Malaria acqulred in AfrLca and south Asla: Over 802 of P. falclparun infectlons were contracted In Afrlca south of the Sahara. The nr:mber of casEs ortgl.natlng fron Anglophone l{est Afrlca remalned steady betrreen L977 and 1982 but doubled by 1986 consituting 607" of P. falclparun cases from Afrlca. There has been a 6-fold lncrease ln the number of cases froro Southern Afrlca, a 3- fold tncrease ln the number of cases from East Afrlca and a 2-fold lncrease 1n those orlginatlng ln Central Afrlca and other parts of West Afrlca. IGnya is the main country ln East Afrlca where non-lrmune Brltish resldents who go for hollday or buslness, contract Dalarla, and have shown the hlghest nortallty. Over the last decade 104 cases of P. vlvax were recorded Ln travellers from Nlgerla' some of which were conflrned by ttre UaEETeference Laboratory. The orlgin of the lnfection is not yet clearly understood. Also froro Nigeria, 86 cases of P. ovale were reported durlng the perlod under revlew, half of these were in the last two yE,i- Malarla cases froo South Asia constltuted over half of all lnported cases into Brltain each year; 847. of. all P. vLvax cases are lmported fron South Asia, ualnly in settled iunigrants who travellffillGit frlends and relatlves. During L979-L9-84, rhe incidence of P. vivax from India declined, but rates for P. f"lgipglg. Lncreased 2O-fold. During ttre-ilE6-FErlod, the rates of both P. falclparui-?6?ffiilax increased l0-fold 1n trave11ersreturn1ngfronPakis..'.@l*'raE!ffii.SouthAsl.aarest1111ow compared to those fron troplcal AfrLca, but thls trend follows the epldeolologlcal pattern ln South Asia, lndicatlng a relatLve Lncrease in P. falclparun lnfectlon. The spread of chloroquine-reslstant P. falclparum through Asta ffiiffi. - Population groups and reason for travel: The pattern of lmported ualarla ln dlfferent populatlon groups in Brltaln has changed over the past decade. Tn L977, cases were distrlbuted equally between forelgn and Brltish resldents. During the early 1980's there ltasr proPortlonately, a hlgher incldence tn Brltlsh resldents. The lncidence ln varlous groups rras presented as folLows:

Brltlsh resldents: The lncldence of nalarla ln Brltlsh residents has doubled since L977. The largest increase is aoong settled iomlgrants who travelled to vi.sit frlends and relatlves. P. vivax Lnfection ls predoolnant Lu residents of South Asian orlgln. The number of naGE- cases in Brltlsh resl.dents travelllng for other reasona has remalned under 500/year, constituting about a guarter of all cases, mogt of then are tourlsts and business travellers. The incldence ln other groups such as Brltish resldents who live overseas, schoolchlldren vlsitlog parents abroad, civlllan a1r and sea crens, and uilltary personnel have lncreased 3-fold to about 100 cases/year.

"Autochthonous casea": The authors used thls tertr to cover cases classlfLed as congenital, transfuslon, and "airport malarla", totalllng 24 cases. Durlng the past decade, congenltal malaria was reported 1n 14 bables, of whoo trro nere lnfected with P. falcLparun of African orl.gin, and elght wlth P. vlvax of Aslan orlgln. Of 10 cases of malaria recorded ln patients who had not travelled to Dalarious areas, six were assoclated with hosPltal treatoent. 0f these, four recelved blood products and were found infected with P. falg.lparuu. lhe authors further referred to tno cases of P. falclparurn reported nearG-t-ffia1rportin1983andwerec1ass1f1edas..a1rportna1arI1@the lnfectton was caused by inported lnfectlve mosqultos. Reference was also nade to two other cases of P. falclparun diagnosed in two women returnlng to Britaln fron Italy; their outgoing plane GfirigGGd froro Ethiopla, and an lnfected "conmuter" nosquito was assumed to have caused the lnfectlon. - see also under L.2.L (lii.) below.

Foreign residents: There has been a 5-fold lncrease ln the number of malaria cases reported ln foreign vlsitors arrLvLng Ln Brltain reachlng 287" of. all cases ln 1985. Fewer cases of luported malarla are seen ln new lmrnlgrants, probably reflecElng the reduced rate of nlgratlon to Britain froo South Asla.

- Deaths fron P. falclparum: During L977-L986, there were 67 deaths assoclated rdlth P. falciparum. The fatality rate ln P. falclparum lnfectlon decllned from 2.77 to 0.52 ln I9B6;TiFEffis'should not be taken toEiE?FiAiecllnlng trend because ln 1982, the death rate vas 2.67". 0f 63 cases for whlch natlonallty nas recorded, 54% vete white Brlttsh non-lnmune persons, nine were of Aslan orlgln and four were of Afrtcan descent. Of the total number of cases, 56 travelled to Afrlca, five to India, and slx did not state vBc/ 90. 1 MAL/90.1 Page 31 the country vlslted. Informatlon on conpllance wlth prophylaxls ln travellers who have dled has not always been conplete. Of the 67 patlerrts who died, 16 were rePorted to have taken pyrLnethanine alone, although the Ross Institute, for several years, has not reco'n-ended thls drug for prophylaxis. It is of concern that of nlne deaths reported in 1985 and 1986, three rrere travelLers who had been p:cescrlbed Pyrlnethamlne.

- Use of prophylaxls by travellers: The use of prophylaxls is poorly documented ln the report forms of nalarla cases. In 1986, no informallon was glven tn 397"of cases. Of the remalnlng 1521, 7O%of patLents had taken no ciremoprophylaxls. 0f the 457 patients who had taken cheooprophylaxls, 8Z gave no detalls of the drug used, 8Z took chloroquinet 4% used proguanil, 3Z took proguanll and chloroquinr:, atd 8% had taken other drugs including pyrinethanlne, Fansidar, l'laloprim, or anodlaqulne. Lack of lnfornation on drug regiuens, compliance, or drug use ln the denominato:r travelllng populatlon has Prevented measureoent of drug efficacy. Moreover, drug senslElvlty tests on parasites have not routlnely been cariled out.' Thtts, lt is not known whether the rePorted drug fallures truly reflect resistance to the prophylactic or non'-compliance.

- Attack rates ln different categorles of travellers: Travel data fron the Office of Populatlon Censuses and Surveys, and the Internatlornal Passenger Survey (conpiled by the Deparrmenr of Enployoent 1979-1986) were revlewed to provlde denoninators of the population gronpl who travelled to malarlous areas. Because data on the duration of the vLslts are not adequate, attack rates were calcula!,ed per 100 000 vlslts overseas. The calculated rates are preliminary fl.gures. The calculated attack rates suggest that ment young adults and chlldren are at greater risk of na.larla than nomen and older people. Rates are highest ln imlgrants who have settled in Brltaln but vlslt relatives in malarlous areas: 315 and 331 per 100 000 for Afrlca and Asla respectlvely; 120 and 39 ln tourlsts ln the same two reglons; and 228 and 38 In business travellers to those reglons.

In their discusslon, the authors polnted to the increase in the number of lnported P. falclparun cases over the past decade as being associated wlth increased Eravel, more pafari..a fn vfsitors fron overseas, especially fron Nlgeria, and tncreased transmission of P. falcl,parun ln South As1a. Ihe rlsing lncldence of P, falciParum infecElons in East and C=itraffi; can be related to the spread of chloroquine resLstance. The increase ln P. falclparun cases froo South Asla nay also in part be due to drug resistance. To aeterofie ttre efflcacy of dlfferent prophylactic reglnens and changlng PatEern of drug reslstance, accurate reportlng of the chenoprophylaxl.s taken by the patLents is needed. Malarla reports should speclfy the name, dose and duratlon of the antlnalarlal drug and the conpllance of the patlent lrlth the reglnen. The authors further underlined that the use of pyrlmethanine by non-lmrnune has been consl.dered uusatlsfactory for some years. Although a knowledge of drug use in the general travelllng populatlon i.s required to establlsh the true assoclatlng rlsk, the avallable data suggest that pyrimethamine taken alone is lnadequate. Calculatlng attaek rates helps to deflne the groups of travellers at highest rlsk of contractlng ualarla. llore detailed studles are required co define the travellers at hlghest rlsk, and to deteroine the efflcacy of the prophylactic drugs in use. Chitdren under age 15 had the highest attack rate (176 per 100 000 travellers) ' more than double the rate in the age-group 35- 54 years. Susceptiblllty to infection may be due to the absence of prophylaxls, poor compliance, or the use of drugs of 1ow efficacy. In concluslon, malarla continues to iopose a threat to international travel. Doctors need to be vigllant ln dLagnoslng and treating the nalarla Patlents. Reporting nalaria cases to the Malarla Reference Laboratory and suspected adverse reactions of anEloalarial drugs to the Conmlttee on Safety of Medicines ls essential to balance the risks and benefits of prophylactic drugs.

In the Netherlands, lletsteyn & Geus (f985) carried out an investlgation on chloroquine res1stancecffiParun1nlortedcases.Dur1ng'January1979-January1983,atota1of 461 lnportea nl]ffi-serwere registered ln the Nletherlands, 136 of which were diagnosed Ln Amsterdam and 89 of these were infected with P. fal-clParum. In 4J- patients (53% of 77 patients), decreased sensitlvity to chloroqulne courld be confiroed. Signs and synptoms in th""" patients dlffered fron thl classlcal picture. The place of orlgin of the 41 cases nas as folfows: Tanzanla: 14; IGnya: 9; several co,untrles in East Africa: 2; Surinao: 3; Indonesla: 2; and South America: 1. Reslstance to sulfadoxlne-pyrimethamine (Fansidar) was establlshed Ln slx Patlents. Parasitaemia was found twlce during dapsone-pyrlmethaslne (l{aloprln) prophylaxls. lhus, full protectton can no longer be lnsured. Resort rras made, therefore, to a comblnatilon of proguantlr 100 mg Per dayr and vBc/90. I MAL/90.1 Page 32 chloroquine, 300 ng base per week. Thls conblnatlon ltas suggested for prophylaxis ln areas with P. falclparum chloroqulne-resistant stralns, but has not been tested extenslvelyfiTase o? fallure, cases should be treated wlth sulfadoxlne-pyrinethamine ln a slngle dose of 3 tablets, lf-possible to be combined wlth qulnlne, 600 og t.i.d. for 3-4 days. To conclude, the authors consldered that close observatlons of patlents wlth chloroqulne-resLstant P. falciparun are of value ln relation to the sltuation lu malaria endeoic areas. A low faaE-oF-;esfstance wlll ernerge flrst ln the non-lrnnune traveller or expatrlate, while the lndlgenous populatlon w111 continue to be protecEed by the acqulred partlal lmunlty. An lncrease ln the level of reslstance w111 also flrst be observed ln nOn-lnmune pefsons.

In Spaln, the receptlvlty to nalarla \ras assessed by entoroologlcal surveys carrled out durlng Ig73; 1978 and 1979 uslng searches for adult mosqultos supplenented by larval searches as reported by Blazquez & Zulueta (f980). The surveys revealed that An. labranchiae has disappeared from its foroer area of distrlbutlon in the southeastern i;rt-ofthecountry.Th1swasthoughttohavebeenduetornod1fiedagr1cu1turalpractiees and the widespread use of residual- pestlcldes ln agrlculture. 0n the other hand, An. atroparvus was stlll found ln most parts of lts previous dlstrlbutlon ln the country - see SECTIONIII(A), under (i), 1.5 Ln docunent VBC/90.2 - MAJ'/90-2.

BLazqtez (f982) revlewed the receptlvlty to malarla ln Spaln. Based on thls paper and on an Engllsh sunm:rry ln the Revleu of Applled Entouology, Serles B (1983, 7L (7) Abst. No. 1942)rr nrlarla eradlcatl.on nas achleved ln Spaln in the early 1960rs. Slnce 1973 surveys have been carrled out ln several areas of the country to monltor the populatlong of poEentlal vectors, and their susceptlblllty to lnsectlcldes. Referrtng to the disappearance of An. labranchl.ae as shown above, An. atroparvus rernains a unlque Potential vector. Only lnported malarla cases have been reported ln Spaln. An. at,roparvus has become almost excluslvely zoophlllc. Moreover, it ls unlikely that it can transmlt P. falciparun strains fron troplcal Afrlca as waa ehowr experimentally (cltlng Zulueta, Ramsdale & Coluzzl, 1975).

Fernandez Maruto, Lorenzo & Blazquez (f982) revlewed the nalaria sltuation in Spain. Based on thls paper and on an English susmary in the same lssue of the Review of Applled Entonology (Abst. No. 1941)rr nalarla eradlcatlon in Spaln was offlcLally declared ln L964. Between 1975 and 1980, there lras an anuual lncrease ln the nuuber of lnported cases. In 1981, there were fewer cases than ln 1980. Thls reductlon was explained as belng due to the lnforoatlon transnltted to travellers by the Spanlsh health servl.ces on the reconmended chemoprophylaxis. The orlgln of luported cases was shown to be troplcal Afrlca, Asla and Amerlca. Partlcular reference was made to Equatorial Guinea as belng the orlgln ot 8O.2% of the total nuober of imported cases froo Afrlca and 65.8% of the total cases recorded ln 1980. Regardlng the frequency of the paraslte specles, while the proportion of P. falctparun showed a declLne fron 582 of the total lnported infectLons in 1979 to 37% It 1981, the proporrion of P. vlvax increased frou 34.87" ln 1979 to 57.8% ln 1981. The lnported cases were detecteaETdlrovlnces and thls indicates that vlgilance covers the totallty of the country as part of the work of the provinclal health servlces. Under the vlgllance scheme, all inported cases are reported lomedlately by health lnstltutlons (dlspensarles and hospltals) to the provlncial dlrectorate of health. When cases are confirmed, a parasitological lnvestlgation and an epldenlologlcal enqulry are undertaken. The declaratlon of malaria cases is obllgatory in Spaln. Studies carried out on the receptlvlty of the prevlous endeulc zones to nalarla showed that A+jltIrc has regained the same level of denslty as that whlch exlsted before malarla was eradicated. Susceptlbillty tests showed that this species ls resistant to DDT and dleldrin, probably reslstant to oalathlon and hlghly reslstant to carbamates lncludlng propoxur. [Laboratory studles reported ln 1982-1983 confinned the presence of a broad sPectrun of reslstance to DDT, dleldrln, organophosphate and carbanates as well as Pernethrln in a straln of - An. atroparvus that orlglnated frorn the CadLz area, Spaln see VOL. I, under 2.6.1r pp. 9f+Tf-

Alvar et al. (1985) cormunl.cated a brlef report recordlng the flrst case of inported chloroqulne-resistant P. falclparuu detected in Spatn. A 48-year old nale returned to Spaln on 18 Aprtl 1984 after havlng llved tn l.[alawl for 20 years Ln Kasungu ln the

l. Perutssion to use this abstract froo the Revlew of Applled Entonology - Serles B, was granted by C.A.B. Internatlonal. vBc/90.1 MAL/90.1 Page 33

Lilongwe region, an actlve zone for nalaria transulsslon. Durlng the prevlous 12 monlhs, he took pyrirnethanlne on hls own as malaria prophylaxls. Itls clinlcal picture and chloroquine treatxoent given to hin following the onlret of nalarla syuptoms on 8 April were descrlbed. He was hospitalized in Spain on 28 AprijL when chloroquine resistance was suspected. His clinlcal conditlon and response to further treatment were described., A blood sanple revealed the presence of an extraordlnerry parasltaemia showlng 1.5 x 10o parasite/ I blood. In vltro (nacro) chloroqulne re$lstance test of P. falclparuu fo11ow1ngtheWHOstii?a-ratechn1quewasperformed.Thetestindtca@nceof chloroquine resisEance at RII level.

In Portugal, Bruce-Chwatt & Zulueta (L977) revlelwed the early history of malaria and steDs undertaken for its control untll eradicatlon was achieved and offlcially certified by Wt{Oln Noveruber I973. Previously the prograrnrneof actlve case det,ectlon whlch st.arted ln 1964 was discontinued in 1965, since the number of new cases detected was 146 and most of theu were already reported by passive case detection. Besldes which, the cost of actlve case detection was very high. Slnce then the rnalarla eradlcatlon prograume was ln the oaLntenance phase, which was consldered by the national health authoritles as the stage of vigilance. Durlng this stage (L966-L973), attention was focused on the detectlon and treatoent of lnported cases wlth lntensLve control of ftonlgrants and coordlnation of surveillance with overseas services" The antlmalaria servlces whlch were established in 1938 were reorganized in 1945 under the name "ServLgos de ltlgieoe Rural e Defesa Antl-Sezonatica" (SIIRDAS). Thls organlzatlorr had a certaln degree of technical and admlnistrative autonomy. The antlnalarla canpaign earried out by this organizatlon ltas the foundation upon whlch malaria eradlcation ln Por:tugal progressed. The SI{RDAShad a central dlrectorate ln Lisbon and ten peripheral units. Ihese untts represented a network covering the whole country. They carrl.ed out blood examinatlons of persons presentlng febrlle synptons, or carrled out such examlnatLons art the request of nedlcal practltloners. Mditlonally, they oade epideniologlcal enqulrles ln relation to each confirmed case, treated and followed up the patients, and lnspected groups of seasonal workers and overseas I rlgrants. The units also applled resldual house spraying, wherever a focus of ualarla transmisslon occurred. Inforoatl.on on loported nalarla carne fron the Dlrectorate General of llealth whlch recelved frorn the nllitary authorities and clvillan offlcial organizations a llst of persons that returrred from overseas wlth their addresses. These erere contacted by the approprtate zone invltlng then to report dlrectly or through thelr doctors to the nearest SIIRDASunlt for examlnatlon. Most people responded to the lnvitatlon, and records of iroportedl malaria cases were based on the results of blood examlnation. Any positive case nasi treafed accordlngJ.y. The other soulce of lnformatlon on inported cases nere the rnedlcal practitloners, as nalaria has been a notlfiable dlsease ln Portugal slnce 1938. llhe notlficatlons used to be forwarded to the Dlrector General of Health Services and were subsequently transnltted to SIIR.DAS. The efficiency of surveillance activity carrled out by this organization can be lllustrated by the fact that durlng L97O-L972 over 1.10 000 persons ltere examined, and 1536 imported nalarla cases were dlagnosed and treated. SLnce L972 the adninistrative organization of SIiR-DASunderwent sone changes relaterd to replanning of all nedical and soclal servlces, based on a netnork of health centrers which, ln turn, were foreseen to be related to the network of all exlsting hospltals. Lntegratlon of SIIRDASand other slnilar units lnto the health centres nas proceeding.

In their conclusious, Bruce-Chwatt & Zulueta (J-oc.clt.) ernphaslzed that slnce 1973, in spite of a large number of imported cases followlng the tndependence of former Portuguese overseas terrltories, there has been no evldence of LocaL transmission, although one case detected tn 1975 at BeJa night have been contracted locally. It was fortunate that about 8O7"of. the people returnlng settled down ln urban areas where condltions for local transmlsslon of malarla dld not exist. The nuuber o,f potential malaria carrLers ln former nllltary personnel who were returnlng to civlllan llfe and settling down in rural areas rural areas was relatlvely snall. This alone reduced the posslblllty of introductlon of malarla into rural areas where the vector is abundanrt. With the satlsfactory coverage of the country by health units and the easy avallability of treatment as well as a suPPortlng health educatlon system, any naJor degree of nalaria. transoisslon was nost unlikely. From past studLes, there is a wealth of evidence that malarla transmlssion ln Portugal by An. atroparvus'much depended on high vector densities related to rice fields. Thls vect,or ls gene-eIly zoophillc, but under special condltions of hlgh density eoupled with poor housing and low sEandards of llving, malarla transuission can occur. Recent entomologlcal observations have confirned a strlklng reductlon ln vector denslty. This conblned with a vBc/ 90.1 rl}J-/ 90.1 Page 34 posslble lack of receptlvlty of the local An. atroparvus to troPical P. falcl,parYn (cltlng Shute, 1940 and Zulueta, Rarosdale & Coluzzl T975fnay e:

Cambournac (1978) also revlewed the development of the antloalarla canpaign 1n contlnental Portugal untll eradlcatlon was achieved and certlfied. He also explained the survelllance scheme applled to detect ioported cases of malarla arnong clvllians and ni.litary personnel returnlng from overseas territories. After blood examination for malaria parasltes and taking lnto account the place of orlgln, the person was classLfled and reglstered in the unit of the Servlces of Rural Hyglene and Protectlon agalnst Malarla (SIIRDAS)as:

(a) unllkely carrler (no recent lndicatlon of a febrlle dlsease); (a) probable carrier; (c) very probable carrler.

Based on thls classiflcatlon, actlon was taken as follows: persoos of group (a) were not vlsited unless they thenselves requested; those of group (b) were vlslted at an lnterval of 1-2 months durlng the flrst year and ln March-Aprll of the following year; those of group (c) were vlslted nonthly untll they are shifted to one of the above Sroups dependlng on the results of follow-up observatlons. Mllitary personnel were examined upon their arrlval ln Portugal, or durLng the return trlp when they travelled by sea. Startlng fron 1974 and as a consequence of the exodus of personnel froo the new lndependent countrles whlch were foruerly Portuguese terrltorles, speclal actlon was adoPted. Personnel of the Servlces of Rural Hyglene and Protection agaLnst Malarla ltent to exaoine and treat the returning persons Ln thelr place of residence whlch ltas provlded by the authorlttes concerned (Comlssarlat for Displaced Persons or ReEurnees). Patlents were treated locally or if necessary Ln speclal sectlons ln hospltals ln vartous Parts of the country. The systen rras carried out efflciently and proved to be highly satlsfactory. IE included not only nalarla but also other tropical dlseases. Addltlonally, uaLarla has been a notlflable dlsease ln Portugal, and prlvate doctors all over the country have been greatly cooperatlng. Some cases of lntroduced malarla ltere detectedr the last case of whtch was reported from the south coastal reglon ln Aljustrel area ln 1975. It was a case of a chtld wlth P. falctparum lnfectlon who was radlcally treated in tlue, and an epidenlological ffi;tidffi; was carried out followed by applicatlon of resldual spraying ln houses and anirnal shelters. No more cases were detected later desplte a very active search Ln the area. Froo the tabulated data, cases observed by the SHRDASln 1975- 1976 were:

P. vivax P. falciParun P. malarlae P. ovale undetermlned

L975 7L3 119 11 28 11 L976 393 58 1 5 2

Anong arued forces there were 669 cases of P. vlvax and 229 cases of P. falclParuu derecred tn 1975. The possibility of introducttoi-ffialarla ln PortugalffiGFed. Reference was oade to the experlmental evldence lndlcating the refractoriness of An. atroparvus to the tropical P. falciparurn stralns. Carobournacalso added that Alnelda noquffi(c1t1ngperiona1cotrounraffi.n)prov1deds1rn11arevidenceus1ng An. atroparvus fron Aguas de Moura, Portugal. At field level, the present density of In. atroparvus 1s much lower than that which preval].ed ln the former nalarlous areas' possififlue to the presence of Ganbusia in rlce flelds and as a result of appllcatlon of agricultural pesticides and herblcJdes. In some areas of the south' however, An. atroparvus exhlblted a certain degree of resistance to DDT and the cyclodlene group of Lnsecticldes. Arnongother factors that nay nilitate against the lntroductlon of malaria ls that the trlghest proportlon of fuoported cases usually reside Ln urban areas where the rlsk of malarla transmlsslon ls very low. Cambournac, however, thought that lE would be safer to eonslder that the recepttvlty to malarla contlnues to exist desplte some adverse vBc/ 90. 1 llAL/90.1 Page'35'

factors. With regard to vulnerability, the number of inported cases ldas expected to decrease, but it would be prudent to conslder that vrrlnerability will continue to be high i-n f uture.

Antunes et al. (f987) in a brief connunicati.on reviewed the recent records of inported cases in Portuga.i-. They recalLed that in 1974, there were 903 ioported cases among thousands of civilian and nilitary personnel returning hone following the independence of former Portuguese overseas territories. Neverthelesli there nas no evidence of an epidenic surge of autochthonous malaria, apart from a single case in Aljustral in the southern part of the country (see above). Fron t.he tabulated data of inported cases recorded during L977-1985, there were 137 cases In L977 representing less than a quarter of those recorded in 1974. Thereafter the nunber of inported cases gradually decreased reaching 19 in 1982, but appreciably increased reaching 57 in 1985. Detal,ls were given of 65 inported cases diagnosed and treated in the Departnent of Infectious and Parasitic Diseases of Santa Mari.a hospital, Lisbon, f.ros L977 up to Septenber 19{}6. Of these cases, 61 came from different countries of tropical Africa, and one from India which was due to blood transfusion, and one P. falclparun caused by accident-al infection. P. falciparun and P. vivax constituted $LZ of the inported cases. Severe and conplicated malaria Iras seen G se\ten palients, one of whorndied, even though tre:rted with quinine as chloroquine resistance was suspected. Another patient developed serious renal failure that required dialysis. The authors considered that Dalaria, whether inported or caused by blood transfusion, or due to accidental infecti.on has agai.n become a serious problen in Portugal, as is the case in other countries of Europel (citing several authors).

1.2.1 (11) Induced and accidental nalaria

The Terninology of l'lalaria (WHO, 1963) defined the tertr induced malaria as.' "Malaria infection properly attributed to the effect of a blood transfusion or other forn of parenteral inoculation, but not to normal transmission by the mosqulto. The course of infection nay be different fron that observed in the normal case. Induced malaria may occur accidentally or may be produced deliberately for therapeuti.c or experfunentaL PurPoses." For convenience, the available infornation on induced nalaria is conplled here under two main subheadings: Eransfusion-induced roalar:ia (or sinply transfusion nalaria), and accidentally-lnduced malarla (or si.nply accidental oalaria). Deliberately-induced malaria for therapeutic or research purposes is not dealt with here.

a. Transfusion nalaria

In a comprehensi.ve and well-documented review of blood lransfusi.on and tropical diseases, Bruce-Chwatt (1972) lncorporated a section on oalaria, a surlmary of which follows. During the 1940's the use of stored blood gradually replaced the old technique of direct blood transfusion when there eras no barrier: between the circulatlon of the donor and that of the recipient. The incidence of transfusion malaria decreased as more attention was given to the selection of donors. However, with the increasing use of blood transfusion in nedicine and surgery, transfusion induced infection increased. This becane evident when the problen of detection of imported, introduced and induced malaria came within the framework of survelllance actlvities of malaria eradication programmes coordinated by WHoin 1956. The fact that the incidence of transfusion malaria has been increasing in several countries reflects not only the better diagnostic nethods and iuproved reportlng, but also the rising trend of malarla inported inEo some countries frou nany troPical nalaria endemic areas ln the world. Apart fron the data provlded by survej,llance activities of the [prevlous] rnalaria erardlcation progranmes under consolidation or maintenance phases, the reliability and accuracy of information from other countries on transfusion malaria have not J.oproved, and oost of the available data are gleaned fron publlcations or occasionaf reports. There is no doubt that nany cases have not been recorded and there is a concensus amongst several authors that f,ransfusion malaria is grossly under-reported, si.nce any such epi,sode nay inply sone negligence on behalf of the institution concerned. The blood transfusion centre represents only the first link in the long chain of events subsequent to a blood transfusion, and a nunber of observations renain confined to hospital files.

From the available infornation, Bruce-Chwatt tabulated data of induced nalaria that occurred ln 49 counlries during 1950-1970, including paraslte identification and the respective references. These data showed that 1247 c.ases of induced nalaria recorded vBc/90.1 MAL/90.1 Page 36 during the above perlod was uuch hlgher than the nuober of 350 cases rePorted durlng the flrst 50 years of thls century. Thls was due to the greater use of blood transfusLon and to the fuoprovedmethods of case detectlon and dlagnosls. The najorlty of the cases (642) were ldentlfled as P. rnalariae. Thls was explalned by the change to the technique of blood transfuslon uffiffii- blood, and to better selection of blood donors. At the same tltre thls also enphaslzes the growlng concern about long-tern infectlons with P. malarlae. In flve countrles of southern Europe, lnfections (especially P. naLariae) ilelffiUlood transfuslon as recorded ln the 2}-year perlod under revlew were: Bulgarla (14 cases), Greece (84 cases), Ita1y (60 cases), Romanla (148 cases), and Yugoslavta (54). The fact that quartan malaria may rerneln a latent lnfection for nany years explains the hlgh nunber of cases of transfusLon malaria in these countries. It was estlmated that in the Macedonlan part of Yugoslavia lrlth a populatlon of 1.5 mlllion, there were about 550 synptomless carrlers of P. malarlae. In the USSR, uuch attention has been glven to transfus1onmalar1a.Drrr1ng@47casesofinducedna1ar1ar'ererePorted:42had been glven blood and five received plasma. Transmisslon of malarla by plasna was probably due to the contaoinatlon of syrlnges. P. oalariae nas identlfled ln 39 cases,,P. vlvSx in seven cases and there nas one case of P.FalClpbrun. Aoong P. malarlae lnfectlons, there vere 22 cases due to the practlce of lntramuscular blood lnjection for preventlon of measles ln chlldren. In a special survey made ln the USSRauong blood donors, repeated and prolonged mlcroscoplcal blood exaolnatlons revealed only two asymPtouatic carriers of P. ualariae. In Spaln, where a snall number of lnduced nalarla cases had been rePorted in th" p""t, the year 1971 wlntessed an unusual outbreak of 43 cases of P. vivax subsequent to whole blood transfusLon, and 11 cases of the same specles followlnE@s-naphoresls. It was thought that ln the latter teehnlque, the reclplents were not glven thelr own blood cells but those of other donors. Most of these caaes orlgtnated from a blood bank ln Barcelona which used workers frou North and Central Afrlca as donors.

Bruce-Chwatt further poloted out that the incubatlon perlod of blood lnduced lnfection ls qulte different fron that of mosqulto transoltted nalarla, as no tlssue stages ln the llver are lnvolved. Ttrus, the pre-patent and pre-synptonatlc (= incubatlon) perlods depend to a large extent on the nunber of parasltes introduced, the uethod of lnoculatlont and on the susceptlbillty of the reclplent. Much Lnfornatlon on thls subJect has been gathered by those who have been undertaklng malarla therapy and several publlcations were revlewed. In thls connection, lrany authors polnted to delays and errors that occur in the dlagnosls and treatment of malarla. Thus, the attentLon of the nedlcal profession Dust be drawn to the possiblllty of ualarla as a complicatlon of blood transfusLon. In the case of any unexplained fever ln a patlent who recelved a blood transfusioo uP to three months prevlously, the posslblllty of malaria must be cousidered, and microscopical exanlnation of the blood, and lf necessary serologlcal tests carrled out.

For prevention of lnduced malaria, three posslblJ.ltles were considered and various experiences reviewed:

- Excluston of suspected donors: Thls may be based on the ellmlnatlon of anyone who has ever had malaria. Few people nould know with certainty lf they have had malaria, as the lllness may have been in the foru of slnple transient pyrexia, partlcularly lf the person nas on a chenotherapeutic reglnen. Regulattons governlng the accePtance of donors of whole blood anong counErles were revlewed. In nany countrles the regulatlons prescribe the acceptance, as donors for whole blood transfusion of persons vbo have had ualarla less than three years or less than flve years before preseutlng for blood donation. It ls difflcult to obtaln fulJ.y rellable lnfornatlon from the prospectlve donors in a system of co erciallzed donation. Thls ls self-evldent and need not be emphaslzed. When the long-lastlng and often asFoptooatlc lnfectlon of P. nalariae is considered, no rellance can be placed on the past hlstory of the most sincere aad truthful donor. This rlsk w111 have to be accepted ln some parts of the world, but the use of lmunologlcal screening would contrlbute to solvlog this problen.

- Detectlon of malaria lnfectton: Detectlon of -"larla ln a suspected donor oay Prove very dlfftcult. l'llcroscoplc exaolnatlon of a blood smear is of llttle value for detectlon of asynptomatlc parasltaeula which ls usually very scanty. Several nethods of lndlrect dlagnosis of ualarla by the appllcatlon of l@unologlcal techaiques have beea developed. In a revlew of the IFA test, Sulzer & Wllson (L972> conflrned ttre value of thls test in l0 cases of transfuslon nalaria, and indlcated that an antlbody tltre of L:256 or hlgher is suggestl.ve of a current ualarla lnfectlon if there has been no specific treatEent during vBc/90.1 MAL/90.1 Page. 37 the previous six rnonths. Reference nas also rnade to an l'nrnunologlcal Lnvestlgatlon carried out ln France by Anbrolse-T'homas, Garin & Kien Truong (1971) coverlng nore than 1000 donors who had llved ln malarlous areas overseas. Using P. cynouolgi Ibastianellii- asanant1genforIFAtests,theseauthorsfoundthat1n58.zzjfjG1EI6a-"onors who, on thelr return to France, rJere not exposed to the infectlon for less than flve years, the test rras negatlve and these persons could be used as blood donors. On the other hand, tt 28.27 of the persons previously exposed to n:larla and llvlng in France for over flve years, the IFA was stll1 positive. Therefore, the use of their blood would be unsafe because of the possiblllty of transfusl-on oalarla. Thus, thls study dellonstrated thaE the roughly suggested 5-year llntt as a "safe perlod" for preventl.on of transfuslon oalarla roay be overoptlmlstlc. The value of the IFA test for detectLon of asynPtonatic carriers of malarla was endorsed by Bruce-Chwatt et aL. (L972) ln thelr Lnvestigatlon of blood donors ln the lIK. It should be remembered, however, that a Posltlve test slgoifles only previous lnfectlon and cannot be consldered a crlterlon of the actual Presence of nalarla parasltes.

- Treatment of donors or reclplents: Several authors stressed the practical difficultles and the unrellablllcy of pre-nedicatloo of susPecEed donors. On the other hand, treatoent of reclplents of suspected blood has been found more relLable and easler in practlce. Several authors agree that a dose of 600 ng of chloroqulne (base) glven to a reclplent of lnfected blood 24 hours before transfuslon Protects fron induced nalaria. It nay be prudent no! to rely on a slngle dose of chloroqulne but to continue Eo glve the reclplent suppresslve chloroqulne aE 300 ng base once a lteek for at least a month. As lt is unlikely that true relapses would occur after a blood transfuslon of P. vivax and P. oalariae, radical treatoent with prluagul.ne ls not needed. Treatment of the reclplent seets toTa the best solutlon appllcable to sltuatlons where there are unusual rlsks of transfuslon malarla, but the poeslblllty of chloroqulne-reslstant P. f"@. stralns should be kept ln ulnd.

Bruee-Chwatt (1974) presented a uore conclse revlew of transfusloo malarl.a nearly along the same ll.nes shown above.

Frou a recent experlence in France, Ranque, FaugEre & Scoffler (1930)1 presented the problen of malarta lnfectlon due to blood transfusl.on ln relation to lnported aalarla. Transfusion oalarla ls becomlng au lmport,ant problen ln France, belng connected ltlth Mrlcan lnr*lgratlon, professlonal and tourlsttc travel to rnalaria endemlc areas. Besides which, the lncreaslng deoand for blood transfuslon coupled wlth the utlllzation of large quantltles of blood ln oaJor surgl.cal lnterventlons has lncreased the rlsk of transmisslon of oalarla lnfectlon over the past 20 years. Betneen 1960 and 1980, there were 82 cases of transfuslon malarla wtth P. falclparum belng predomlnant through the close relatlonship of France wlth troplcal AtriE-Gl[G thls problen, some approaches were dlscussed. To exclude all subjects who spent some tl.me ln malarla endenlc areas would result, Ln elinination of a large number of bLood donors. To conslder a perlod of five years that must elapse after the last clLnical oanlfestaElon of tralarla ls not acceptbale because of occult lnfections. Llnltlng this excluslon to trto years would pernlt the elLnlnation of only P. falciparuo. To examLne the blood of healthy carriers is extremely difficult and uncerffif,E.EEst solution is to resort to innunologlcal tests. IFA test ln partlcular ls mos! sultable, but its results have to be interpreted ln the light of the following lnformation:

- duration of stay ln endeulc areas; - the perlod that elapsed between the cessatlon of the chemoprophylaxls and the date of the serologlcal test.

Such inforoatlon nas used in interpreting t,he results of IFA tests uade on 257L sera provided by blood transfuslon centres ln Marsellle and Nlce. The geographlcal orlgln of l-nfectlon of the donors rrere: tropLcal Afrlca nhere the rlsk of lnfectlon is hlghr and North Afrlca where oalaria eudernlclty Is low, frorn whlch a large number of donors orlginate. The donors presentlng antibodies are those who generally resided for a long tlue ln nalarla endemlc areas or those who made frequent vlsits. Two thlrds of the donors whose serological tests were poslElve dld not declare any prevlous clinical symptolls. f-me sunoary of thls paper has beeo Eade through the cooperatlou of Dr R. Le Berre, WHO Entooologlst, TDR, WIIO, Geneva, bY translatLng parts of the text. vBc/90.1 MAL/90.1 Page 38

When a level of. L/2O was adopted as an lndicator of posltivlty of healthy carrlers by the IFA test, the number of Plasnodiun carrlers was overestirnated. On the contrary, the negat1v1tyofsuchatesffindofaper1odoffourmonthsafterthereturnfrouan endemic zone, or tno months after the cessaElon of cheooprophylaxls as in France (a period which 1s sufficlent to constltute the antibodies when nalaria Lnfectlon exlsts in the blood) would pernlt the utillzatlon of the donor wlth absolute securlty. Thus, a large proportion of donors can be recuperated as it happened tn the present serles when 86.9% of the donors could be retal.ned. On the basls of th1s, the following schemes were proposed by the authors:

- Donors frequently visit naLarla endeuic areas: to be excluded. - Qther donors should be excluded for four oonths after thelr ret.urn to France, subsequently they can be retained if the IFA test is negative.

Ilowever, there is no absolute security with all preventlve measures lncludlng the latter schene, because of the posslblllty of error in lnformation ProvLded by the donor.

Recently, Saleun et al. (1987) polnted to the lncreaslng lncldence of transfusion malaria in France. Recalllng the data collected by Saleun et al. (1981), the number of reported cases of transfuslon malarla increased frou 24 In 1960-1969 to 79 1n 1970-1979. It must be adnltted that Ehe number of cases reported is undoubtedly inferlor to the actual number of cases. The sane reasons for the lncrease shown above were also given by the authors. Moreover, the developnent of rnethods of transfuslon uslng concentraled erythrocytes increases the chances of infectlon wlth nalaria parasites. Citing also the data of Saleun et a1. (1981), P. falclparum has been responslble for increasing proportlons of transfuslon malarla constitutirg L5.47" of all cases detected ln 1950-1964, 45.5"1 ln 1965-1969, 79% ln 1970-1974 reachlng 847"tn L974-L979. P. vlvax did not exceed 47"ta Lg75-Lg7g, and P. malarLae decreased fron 45.57. Ln fgOS-fSOgE-:I5:9% in L970-L974 and8Z1n1975-1979.ffiasneverbeennentioned1nanyinvest1gation.Perhaps thls paraslte oay be na@ other vlrulent plasnodial parasltes such as P. falciparun particularly where both occur in association ln troplcal Afrlca. P. falciparun is known by lts grave conseguences for the patlent, and for thls reason, th-ffiffitematlcally Eested the blood of the donors for the nalarla antibodies starting fron 1981. The roethod of IFA assay as applled by Deroff et al. (1982) was descrlbed. The antigen used is cornmercially produced by Blo-M6rleux Instltute under the name "Falclparuro Spot I.F.", and ls prepared fron P. falciparum in vltro culture. The dllutlon of 1/20 was adopted as the lnferior llnit of posltlvlty. Drrlng the perlod 1981-1985, 158 788 blood units were sampled. After Lnterrogatlot, L747 subJects were consldered donors at rlsk representlng L.L% of the total sanple. Of these 107 were posltlve in IFA tests, representlng 6.L2% ot the donors at rLsk, but only 0.6%o of the total blood unlts sanpled. Statistically, there lras no signlflcant dlfference between the frequency of seropositive subjects aoong those who spent less than four nonths after their return to Franee and those who spent between four months and tno years. On the other hand, this period of stay in France before testing does not give any ldea on the duratlon of the pre-serology phase, since lnforuatlon on the exact perlod of resldence in the nalaria endemlc area is lacking. Ilowever, Lt seems that testlng donors after a perlod of four months after the return to France ls sufflclent for avolding transoission of malarla through blood transfusion. The geographical orlgln of 1285 donors lras Eraced. 0f these, 8.45% orlglnated fron tropical Afrlca, 7.537" from North Africa, Djibouti and the Mlddle East, 5.947" frorn South America, 2.44"1 fron the Indlan subcontinent and Far East. The htgh proportlon of seropositive donors frox0 troplcal Africa is related to the frequent exchange between France and this region whlch contains hlgh rlsk malaria endemLc areas. Of the seroposi.tive donors from North Afrlca, seven caue from Morocco and two from southern Algerla, but the exact destlnatlon should be verifled as they may have passed through other countrles. The 1ow proportion of seropositlve donors fron South Asla ean be attrlbuted to the lioited emlgratlon and tourlstlc Journeys from counlries of that region to France. In conclusion, the authors pointed out that the screenLng procedures of the donors largely depend on the rnedlcal hlstory. Although the results are satlsfactory, they could be loproved by using specific monoclonal antibodies.

In Swltzerland, malarla lnfection not dlrectly related to blood transfus-ion has recently been recorded. As com-unlcated by Zuber & Ilolzer (1986), two patients ltith renal lnsufficiency who had never reslded in a molarla endeol.c area were operated for kidney transplant in December 1984. The donor rtas an African aged 27 years who died fron cerebral haemorrhage, but otherwise was in a healthy condition. Ilis blood film was vBc/90. 1 MAL/90.1 Page 39 negatl.ve. Nine and 15 days after the interventlon, the two patlents respectlvely developed lnternittent fever and P. vlvax was ldentifled ln thelr blood flfuos. The two patlents responded well to 3-day ElFroqutne treatment.

In Ronanla, Panaltescu & Fillottl (1980) lndlcated that after the lnterruption of oalarla transoisslon ln 1951, the number of P. nalarlae cases recorded durlng 1963-1978 was156,ofwh1ch132wereduetob1oodtranffi24veterelapses.The epldeniologlcal lnvestlgatlons of these cases showed that most transfuslonal cases were dlstrlbuted over the forner malarla endeolc terrltorles of Ronanla, and that their detection was due to the efficlent dlagnostlc systeD ln the country.

Recently, Prof. Iti{sslg of Bern, SwLtzerland (1987) organlzed an lnternatlonal foruo to obtain vlews on the followlng question: "Which are the approprlate nodlflcatlons of exlstlng regulations deslgned to prevent the transmisslon of nalarla by blood transfuslon, in vlew of the increaslng frequency of travel to endemlc areas?" Prof. lliisslg as editor presented the views of five leadlng authorltles, whlch can be read ln detall ln the origlnal publlcation, or brlefly in two abstracts by Prof. L.J. Bruce-Chwatt ln the Tropical Dlsease BulleEln respectlvely Nos. 997 and 998, VOL. 85(4), 1988. At the end of these abstracts, Prof. Bruce-Chwatt renarked: "This exchange of vLews provlded several useful points for a wlder lnternatlonal meeting on the subject of transfuslon malarla. It showed the llnited consensus of oplnlon on the detalls of screening procedures although a couplete agreement on the lmportance of the subject. It ls hoped that the forthcoming International Congress on Blood Transfuslon due to meet ln July 1988 tn London w111 devote some tine to thls probleo. "

b. Accldentel nalarla

There are several reports of accLdental lnfections transnltted through contamlnated needles aoong hospltal staff or drug addlcts, and ln a few cases through contamLnation of wounds when handllng lnfected b1ood. Included here also are tlto cases of accldentally acqul.red lnfectLon through handllng lnfected mosquLto colonLes, although such a mode of transmisslon does not fall under the category of accldentally-lnduced oalarLa.

In France, PastlcLer et al. (L974) described a case of an asslstant nurse aged 27 years at Senlls hospital whose lnfectlon was mlcroscoplcally dlagnosed as P. August 1973. She also suffered frou typhold at the same tlme. The posslble her mal-arla lnfectLon were consldered as follows:

- Possible source: through an lnfected nosqulto ln Spaln where she spent one month durlng the prevLous year, or in Landes in France where she spent four days before showlng fever. - Definite source: as a result of accldental needle prick (10 days before her illness) when she was drawing blood r{lth a syrlnge from a wonan hospitalized sufferlng from malaria whose infectlon was identtfled as P. vivax but the blood sllde ltas not preserved. This patlent left the hospltal afteilB-lilurs and froo a brlef enquiry, lt appeared that she llved Ln Africa for three years and resided ln New Caledonla for a long tlme. The authors favoured this latter node of lnfectlon since the period of 10 days that elapsed between the contact wtth the infected blood and the appearance of malarla sympEoms would not be sufflclent lf transnlssion was caused by the bite of an infected mosqulto. [But the author dld not explaln how the asslstant nurse conEracted P. falciparuro malarlar while the Lnfectlon of the hospi.tallzed patlent was P. vivax. Could lt be that the patient had P. falciparun lnfectlon as rtell but ltas noE recognLzed,?l

Petlthory & Lebeau (L977> descrlbed a case of a student aged 25 years worklng ln the rnedlcal blology departoent of the Ceutre Hospitaller of Gonesse, France who was hospltallzed in November 1974 and his lllness nas attrJ.buted to mlcroscoplcally conflrmed P. falciparun infectlon. Ills history showed several prolonged perlods of soujourn in Algerla, Madagascar and Sonalla, but this was excluded as lt occurred 10 years prevlously and he had adulnlstered the chenoprophylaxls correct.ly. Ills infectlon on the C6te drAzur where he went for a short holiday three uonths before his lllness ltas also excluded since no autochthonous malaria cases have been reported fron that reglon. Llkewise lnfectioo ln t.he Parls region was ruled out as it was too cold at that tloe of the year. No blood transfusl.on was involved. The oaly probable explanatlon rtas that he acqulred the lsfectlon ln the laboratory whlle haodllng a blood sample highly lnfected wlth P. falciparum through skin excorlations, although such a rnode of lnfectlon is extremely rare. vBc/90.1 rrAL/90. 1 Page 40

Bastin et a1.(1979) descrlbed a case of a 20-year old Vietnamese young m:n who came directJ-y to France fron Saigon on 5 April 1976. Following an intravenous injectlon of heroin, he suffered fron fever for which he was treated wlth arnpicilline for septicemla with no response. He was adnitted to Claude Bernard hospital, Paris, where a blood examLnation revealed the presenee of P. falciparun infectlon. He was treated initlally with chloroquine' but with no response. As chloroquine resLstance was suspected, he was given quinine perfusion (L g/2a h). The fever subsided and his blood became negative except for the presence of ganetocytes. Therefore, he was given 3 tablets of joint sulfadoxine-pyrlnethamine, after whlch the blood became totally negatJ-ve, but IFA test wlth P. falciParun antigen was positive at a titre of 1/600. Based on lnformat1on obtained from the patlent, the source of lnfection lras suspected to be one of three young Vietnauese inmigrants during the previous 3-4 months. IE was possible to examine the blood of one of then by IFA lest for P. falciparun and found posltive at a tltre of 1/800. The authors recalled that accidental malarla transmlssion has been known for a long tine' citing Brunpt (1949) who revlewed the literature hitherto avallab1e on this mode of transnlssion. The authors, therefore, reminded that malarla should be suspecled when a drug addict using intravenous injection suffers from fever, hence mlcroscopic examination of his blood must be sought in the flrst place. On the ot.her hand, the epideniological consequences of the present observation should await the appearance of new cases.

In Switzerland, Zuber & Holzer (1985) reported a case of accldental nalaria in a Swiss nurse aged 27 years who had never resided 1n a troptcal country. On 25 June 1985, she accidentally pricked her finger nith the needle of a syrlnge whlle taking a blood sample from a PatLent who was hospltallzed for undertermlned fever. This patlent returned to Swltzerland after residing ln Kenya wlthout taking any cherooprophylactlc drug. Two weeks later, the nurse went for a holiday ln Israel where ualaria does not exist. Two days after her arrival there she developed febrlle episodes accompanied by dlarrhoea for which she ltas hospitalized and treated wlth antiblotlcs. Subsequently she was flown to Switzerland where she was hospltalized. E:

Two cases not accidentally lnduced, but accldentally transmitted through bites of laboratory reared lnfected mosquitos were reported ln France by Drulhle et al. (1980). They were two laboratory assistants: a 28-year-old female and a 30-year-old nale in charge of naintalning laboratory colonles of An. freeborni infected with a strain of P. cynonolgi bastianellll kept in a Rhesus no@). They presenred themselves with fEvEi-End nalalse to the Laboratoir;lGnrrafte Taraslrologle er Consultation des l.laladies Troplcales et Parasltaires, Parls ln May L977 and May L979 resPectlvely. The first patient was glven antibiotic and chloroquLne lreatment by her Private doctor before any laboratory examinatlon. Thls treatment vras stopped after three daysl subsequently, a blood snear examlned a week later lras negative bu! IFA test was positlve at 1/1300 and 1/1800 with P-lalciparrn anrlgen. The patient responded well to full chloroqulne treatnent. e tnict--6Gi?G fron the second patient was positive but the parasite was very rare (one infected r.b.c. per 20 000); the parasite was identtfied as P. cynonolgi bastlanellii after prolonged examination. Two healthy Rhesus monkeys were lnoculated intravenously with heparinized blood collected fron ttre second patient on adulsslon. The blood of the two nonkeys rras parasitized on tire 17th and 24th day of inoculation, and P. cynonolgl bastianellii was clearly identlfied. Serological investigat1onbyffioe1ectroPhoresisusingdifferentantigenss rendered useful lnforrnation. Ihe tno assistants recalled that durlng their normal work with the laboratory lnfected colonies, they were frequently bitten by nosquitos.

Bruce-Chwatt (f982) in his review of lnported nalaria, tabulated the data recorded ln the IIK during 1970-1980. 0f 11 032 cases there was only one case described as accidental malaria. He explalned that this was a case of P. vivax wirlch occurred in 1980 ln a nurse, who pricked her finger witn a contanainated neffiF-en giving an injection to a patlent wtth confirmed infection.

In West Germany (Federal Republic of Germany), Bdrsch et al. (1932) described the cllnical synptoos of a 39-year-old nurse who took a venous blood sample from a malaria patient ln August 1982. The patient was a 39-year-old male Paklstani whose infection was microscoplcally confirrned P. vivax. Ile recovered after treatment with chloroquine and vBc/90.1 l,rAL/90.1 Page 41 prinaqulne. In September L982, a blood smear fron the nurse revealed the preseoce of P. vi.vax, whlch was corroborated by a hlgh antibody titre (1:320) in IFA test. The nurse dld not give any hlstory of long-disEance travel. She had not had any blood transfuslon in the previ.ous 17 years, no! had she been living near an lnternational aLrport. She was not conscious of a needleprick, though she remembered having several- srnall scratches on her flngertlps (caused by peeling potatoes) while handling the blood sauple without wearlng gloves. Since other modes of infectlon have been excluded, the authors considered that parenteral transmlsslon of P. vivax was undoubtedly the cause of this case. This would suggest that even minor in]ffiould be a realistic, though rare, threaE to the nedical staff.

In lta1y, Orlando et al. (1982) described an outbreak of P. falciparun nalaria among drug addicts which occurred ln Milan durlng February-July 1981. The flrst case was a 32-year-o1d Italian male who was adnltted to ltilan hospital suffering fron fever of unknown orlgin. His symptomswere fever, chills, anaenia and hypotenslon, simulatlng sepsls,b*tL-E.@'wasidentif1ed1nhlsblood41daysafterilisadnl.ssion.llewas treated with chloroquine at an initial dose of 600 ng followed by 300 ng six hours 1ater, then by 300 og daily. On the 5th day of treatment the patient was still febrile, and ring forms could be found in a thln flln of hls blood. Ile was, therefore, lreated with quinine sulphate at a dosage of 600 mg every eight hours. However, parasltaenia persisted until the 9th day, but later he was dlscharged ln good health and had no relapses subsequently. firis could be a case of chloroquine resistance. Eleven other heroln users affected by P. falclparuo lnfectLons were later observed ln the hospital; all caoe fron the same area of the clty. The tLne lapse between the onset of thelr synptoms and diagnosis was shorter than ln the flrst patlent due to the anareness of the cllnlcians. Cllnical synptons of these patiento at the tloe of adroisslon lrere generally fevers and chills, and two of the patlents were conatose. Al1 cases were due to P. falciparun infection, and were glven quinine treatment as chloroqulne reslstance ras-iiffia.-ooe patient died and a post-mortem examlnatlon revealed congestlon of the cerebral and vlsceral capillaries with parasltized red blood cells and asperglllosls of the lungs. One patlent ltas readmltEed after one month for recrudescence. The flrst source of thls outbreak remalned unknown. None of the patlents travelled to nalaria endenic areas. Probably an asymptomatic carrier coming froo a ualarlous area inltlated this outbreak by sharing his lntravenous equipment with other drug addlcts. The lncubation period of these infectlons could not be establlshed because of the dlfflculty ln deterninlng the tirne of the infective lnjection. Up to this episode, malaria infectlon among heroin users has not been reported in Italy and this ls why physlcians did not consLder thls posslbillty ln the dlfferential diagnosis of fevers arong heroln addicts. Public health xoeasures to prevent the spread of malaria infectlon lnvolved lnforning heroin usera through perlpheral centres for addlct asslstance. No more cases were seen after July 1981.1

In Spain, GorzaLez Garcia et al. (f986) reported on an outbreak of P. vivax melaria atrong heroln users whlch occurred in Madrid in the spring of 1984. Thi€ i-;-ffi first outbreak of lnduced nalarla among lreroln users ln Spaln, and the first one caused by L vlvax ln Europe. Five whlte nale drug addLcts, 17 to 18 years o1d, who had never vislted malaria endemic areas, nere adnitted to hospltal because of nalaise and fever. The history of drug addlctlon began six months before. The diagnosis of oalaria was microscoplcally confirned in thick and thln blood fllns. The flve drug addlcts came from the same area of Madrid and shared contaminated injection equipnent nith a commonfriend who had often travelled to Equatorlal Guinea and was affected by nalaria, and Ehis r,tas the source of the outbreak. A seventh young man dlagnosed as having malaria, refused to be adnitted to the irospltal for further study. Four of the patients were diagnosed mieroscopically ln thick and thin blood flLns as P. vlvax with low parasitaenia ranging from 1 to 3% red blood ce1ls. The fifth patlent Gffisrfled as "seropositive contact" because he had a febrile syndrome and posltive IFA (1:160), but no parasites were detected ln his blood fllns. Chloroquine treatment nas given at a dosage of 1500 mg over three days. Parasitological blood examlnation became negative ooe to two days after comencing treatment. No recrudescence of malarla was observed durlng a mean follow-up perlod of six months. No prinaquine treatment nas necessary, since in induced malaria there ls no exocrythrocytlc cycle as the parasites llve and nultiply in the red blood cells. Unt,il the present outbreakr nalaria has not been reported 1n Spain anong lntravenous drug abusers and this ls the reason why physicians had not been aware of the possibillty of

1. An offlclal publication connunicated to WHOby ltalian authorities showed that the total nalaria cases in drug addicts was 23 ln 1981 - see Table 4(b). vBc/90. 1 MAL/90.1 Page 42

malaria in the dlfferential diagnosis of fever in drug addlcts who have never travelled to malaria endemic areas.

The nunber of malarla cases among drug addicts has recently decreased, but the reasons are not known. This nay have been due to the efforts of the centres of addicts assistance as in ltaly. In USAwhere an epldemic of malarla (P. falciparun) broke out in the 1930's and persisted for about 10 years. As lndicated by Dover (1971) no further cases nere seen follorving the detection of qulnine as a conrnondiluent or adulterant of confiscated heroin. Thls factor does not seen to have been investlgated in Europe.

1.2.1 (ili) Malaria ssociated with al,rports

Since 1977 several reports have been published in France and elsewhere in Europe describing malaria cases anong people working in or living near lnternatlonal airports. For sinplicity these were termed "airport malaria". A11 reports polnt to the possibility of transmisslon being caused by lnfected anopheline vectors escaping fron alrplanes coming froro troplcal countries. Sorneauthors when reviewlng airport malaria, sumnarlzed the available lnforoatlon in tabular form, e.9., Cassaigne, Brualre & L6ger (1980), Gentilini & Danls (f981), Holvoet, Michielsen & Vandepltte (1983), and Smlth & Carrer (1984). More detalled and up-to-date inforrnrtion on airport malaria is sunrrnarlzed here in Table 3. Few cases thought to have been contracted through bites of what has been termed "commut.er mosquito" in flights orlglnating fronmalaria endemic areas, are also included. In this tabler inforuatlon ls arranged chronologically accordlng to date of publications.

Some entooologlcal investigatLons have been carrled out in conjunctlon lrlth airport ualaria. In France, Pesson et al. (1980) presented a sunoary of the results of entomological surveys carried out for recording the local potential anopheline vector whlch may transuit malarla ln and around lnternational. airports ln the Paris area, and L6ger et al. (1981) reported these results ln more detall. Durlng L976-L979, 13 cases of malaria associated wlth airports were recorded: 5 among the temporary or permanent staff of Rolssy-Charles de Gaulle, 4 llvlng at about 4 km fron thls airport, and 4 at a longer dlstance from alrports. 0f the 13 cases, 11 were recorded in sunmer and autumn seasoos, one in February, and one in Decenber. The entomological surveys nere started in August 1978, by lnspecting the water collectlons that could serve as larval breeding places for uosqultos. In addltlon to ground inspection, a helicopter lras used once during Ehe dry period and once ln the ltet perlod of the sumrner. The searches covered the Orly and Roissy alrports and the surrounding comunltles. At Orly, nine potential breeding places were inspected regularly and all nere negatlve for Anopheles larvae. At Rolssy, aoong 45 potential water collectlons located by ground and helicopter lnspection, 25 were surveyed regularly during the summerof 1979. Besides breeding places of Cx. pipiens s.1. and Culiseta annulata,-places four places harboured larvae of An. claviger and An. roaculjll?ennis s.1. These breedlng nere basins for retention of affiage waters. Eii[.lune-septeober 1979' inspectlon of two breedlng places close to the alrport indicated that they can suPPort at least three generations of Anopheles species. Surveys of five localities around the airport lrere all negatlve for Anopheles. Search for adults by hand capture in translt and passenger ha1ls revealed only a lluited number of douestic insects. In luggage tunnels, many insects comlng from outside were collected, but the only nosqui-to encountered was Culiseta annulata.

L6ger et al. (loc.clt.) and L6ger, Timbal & Pesson (1980) reported the results of an investlgatlon on survlval of Anopheles in air flights carried out to elucidate the possibility of transporting exotic roalaria vectors from endemic zones. The investi.gation conprlsed transportlng nosqultos in cablns and luggage stores which are pressurized on Iong distance flights. On a flight of Boeing747 operating between Rio de Janelro and Parls, caged mosqultos were placed in the pressurlzed cabln, 1nslde baggage and in luggage stores in dry and hunid atmosphere. Under such usual conditions of transportation of passengers and luggage, mosquitos survi.ved the journey until safe arrival. In addltion, an experinent lras oade by conflning caged mosquitos (An. stephensl and An. naculipennis s.1.) in pressurlzed containers at varying temperatures (fron -80oC to 25oC). Mosquito cages rrere protected from the dry lce which was used for producing low tenperatures. The containers nere plaeed on a fllght sinulating Paris-Dakar using two types of planes: Boeing 747 flyLrtg at a oaximun altitude of L2 000 n, and Focker at a maxloum altltude of 4000 o. Ttle two Anopheles specles well supported the action of the pressure, whlle the tenperature was the onLy factor influencing their survival. The vBc/90. 1 MAL/90.1 Page 43 survtval rate nas 1002 at 25oC, L07. at OoC, and 07" at -10oC, whether oosquitos were placed under controlled or unconlrolled pressures. Fron this lt was lnferred that the survlval of some uosqultos outside the cabln of the alrcraft ls qulte posslble but such a condition was consldered rare. (See new observations belos on survLval of lnsects in wheel bays of an alrcraft.) Searches for mosquttos 1n containers transPorted by airplanes coming fron illfferent countries of troplcal Afrlca and the Far East were all negatlve.

In llght of all the above results, the authors discussed the posslble modes of transmlssion of airport nalarla. In favour of the hypothesls of transmisslon by loca1 anophellnes are the following findlngs:

- Nearly all the malarla cases rrere associated wlth Rolssy-Charles de Gaulle Alrport, except one case recorded in L974 near Orly Alrport. The present entomological lnvestigatlon gave contrary results betlreen the two airports, in that Anopheles nosgultos were found breedlng only ln the Roissy area.

- Most of the alrport cases were observed durlng the sunnner of exceptlonally irot years.

Against thls hypothesls is the fact that 10 of the alrport cases were P. falclParum, a species whlch has dlsappeared fron Europe where the local anophelines have been found lncapable of supportlng the development of strains of thls paraslte of Afrlcan orlgln, although they are more adapted to exotlc P. vlvax. Eowever, the authors felt that the susceptlbiltty of the local anophelines to exotlc P. falllparun st1ll await flro conclusions, ln vlew of the experlments nade ln the USSRindlcatlng the susceptlblllty of certaln specles of the An. rnacullpennls complex to some African strains of P. falclparun, clting Da5kova (L977) and Dzhavadov et al. (1978)r. The authors also renlnded that ln the roalarla outbreak that occurred in the valley of BlEvre ln 1940, there were trro cases of P. falciparun. For some reason, no experlmental iufectlon could be carried out ln France lnvolvlng alrport nalarla. However, negaElve results would be ooly of relattve value slnce the exact geographlcal orlgin of the stralns that caused alrport malarla remains unknowa.

Belng unable to draw firm conclusions favourlng one of the tlro hypothetical nodes of transmlsslon of the alrport cases: by local anophellnes or luported infective vectors, the authors reconmended certaln protectlve measures to be linlted, for the ttne belng, to the area of Rolssy-Charles de Gaulle Alrport as it ls proved to be the nost exposed to such lnfections.

These measures are:

- replaclng dieldrln wlth nalathion as resldual spraylng because of resistance of_the An. nacuiipennis complex to dleldrln. Malathlon ls to be applled at a dosage of 2g/mz twice annually (May and July). Ihe spraylng should cover passenger and luggage halls as well as J-uggage transferring tunnels (see information on the effect of thls spraylng below);

- larvlcldlng of breedlng places around the airport ltlth temephos at 1 ppn in tlto rounds (at the beglnning of each of May and July), and to contlnue appllcation of Baclllus thurlngiensls-serotype H-14;

- renindlng air companies to adhere to internatlonal regulatlons of WHOfor dlsinsecting alrcraft ;

- health education for the staff of alrports to lnforrn them about the risk of contractlng nalarla;

- alertlng nedlcal practioners to the possiblllty of accldental and airport assoclated malaria.

-n-Tater revlew by Da3kova & Rasnlcyn (1982), experlnental infectlon studies involvlng troplcal stralns of P. falclpaluq ln An. sacharovl and An. subalplnus were reviewed - see under 1.2.1 (i) aloF."-a [email protected] (i1). "rso vBc/90. 1 r,rAL/90.1 Page 44

In the UK' Curtis & Whlte (1984) reviewed the reports of malarla associated wlth alrports ln Europe and the trro cases recorded ln Rusper and llorsham in Sussex, England durlng 1983, as well as reports of searches rnadeln alrcraft lncluding those arrlving in Gatwick Airport for detecting nosqultos. Ihey further discussed the possibtlity of transmisslon by local potentlal anopheline vectors ln Sussex from an lnported P. falclParum case. To find a sultable P. falciparun gametocyte carrler in Sussex was consldered unllkely, but thls posslbility exists at Gatwick Airport. However, the chances of a local anophellne to travel 10-15 kn to the hones of the tno pat,lents would be no greater than those of an lnfected troplcal vector carried by an alrcraft from an endenlc area. It was more plauslble to assuDe that the infected mosqulto was transported passively fron the airport by a vehicle (as explalned iu Table 3). A few days after the dlagnosis of the two cases ln August 1983, Curtls & Whlte vlsited the homes of the two patlents in Sussex and could collect larvae of An. clavlger and An. plunbeus. Based on literature review, it was polnted out that ttre qffii-iFrtretnililIot tttese two species are susceptible to tropical P. falciparun does not seem to have been deflnitely settled, and has been confused ln publlcatlons by several misquotatlons of various publlcations. It was suggested that nlth the availabillty of P. falclparun gameEocytes cultured in vitro, the questlon of the susceptlblllty of the two anophellne specles should be clarifled. Of other Brltish anophellnes, An. atroparvus used to be the vector of malaria ln England. It was found susceptlble to European strains of P. falciparun but refractory to Afrlcan or Asian P. falciparurn citing Shute (1940) and t6ffiiETork of Zulueta, Ransdale & Coluzzi (r9ffia narsa"le & ColuzzL (L975) uslng strains of this parasite occurring ln Nlgerla and Kenya. Reference was also nade to experlnents of Da5kova (L977>, Dzhavadov et al. (1978) and Da3kova & Rasnicyn (1982). While An. atroparvus was refractory to Afrlcan P. falclparun sone posltive results \Jere obtained with An. subalplnus and An. sacharovl (as shown above). Curtls & Whlte thought that as the1EsT-6-E65Eisof@complexoccur1nsouthernandeisternParts of Europe, thelr susceptlblfity to african e. faf"ip"r would be irrelevant for a dlscussion of potentlal vectors in northwestern Europe.

In thelr concluslons, CurtLs & Wtrite underllned the following: - Two cases of P, lqlclparum trausmisslon in Sussex that were recorded during July-August 1983 reliffiffirrst cases of n,larla transuisslon in Britain since 1953. fhe only record of P. falclparun transmission ln Britaln was tn 1920.

- Two addltional cases of P. felciparum were dlagnosed ln two resident Brltish women rtho travelled independently on the saue Ethioplan Alrllne fllght froo London Heathrow Alrport to Rome on the evenlng of 11 June 1983. It seems almost certaln that both women must have been infected through an Lnterrupted bloodoeal by an Afrlcan vector on board the alrcraft which origlnated in Ethiopia.

- The British nosqulto specles: An. claviger and An. pluubeus were found near the homes of both patlents 1n Sussex, but it seerns very unllkely that these mosquLtos could have been lnfected fron P. falclparun gametocyte carriers.

- Perhaps all Brltlsh anophellne specles are refractory to troplcal P. falciparun sErains as dlstlnct froo the presenEly extlnct European stralns of thls parasite.

- As proposed earlier, the two Sussex cases most probably were bltten by a single tnfected mosqulto loported on an alrcraft and transported by a car to Sussex. Its survi.val would have been aided by the hlgh anbient temperature during the suurmerof 1983.

- Ot 67 aircraft searched upon arrlval at Gatwlck Airport, 12 harboured culicines of African origln. The only anophellne rnosquito was An. claviger apparently of Brltish orlgin. Soue of the alrcraft lrtth J.lve mosquLtos had been sprayed wlth insecticide aerosols.

- Laboratory tests roade ln a sealed room showed no evldence of resistance to aerosols ln the progeny of culiclne mosquitos collected allve ln the aircraft.

- Caged mosqultos (nales) delLberately placed on comerclal fllghts showed 1002 nortality when the alrcraft lras sprayed wlth 57% or nore of the recormended aerosol dose, but inconplete mortality resulted when less than half of the recomended dose was applled. vBc/90.1 MAL/90.1 Page.45.

- To prevent the transport of lnfective malarla vectors and posslble spread of non-lndlgenous specles to nen areas, Lt ls necessary that alrcraft from malarla endemLc regions are treated with an adequate dosage of insectlcl,de.

- Under current internatlonal health regulatlons all Lnterlor parts of the alrcraft need to be sprayed wlth the full dose reconmended by WIiO.

- The substitutlon of aerosols by resldual spraying of aircraft by low toxlclty insecticides would nerlt further study. [Actually this has now been included in the new recommendatlons of I{HOfor dislnsection of alrcraft - see below under L.2.2).

Curtls & White also referred to the recomendatlons of L6ger et al. (1981) who stressed the need for applylng resldual spraylng ln baggage tunnels and halls in Charles de Gaulle Airport. Since thls measure was adopted in 1981, no cases of alrport malarla have been recorded in Parls (citlng personal communication from N. L6ger to W. Peters).

Snith & Carter (1984) rrrote a chapter on the lnternational transportatlon of mosquitos and lts inpl-lcatlon ln public health. The chapter includes: a revlew of reports of nosqulto-borne dlseases transmltted by the lntroductlon and establishnent of exotic specles of rnosqultos; records of oal-arla cases assoclated wlth European lnternati.onal alrports arlsing from lnported lnfectlve vectors, from publtshed lnforoatlon up to 1982; factors affectlng and contrlbutlng to the establlshnent of mosqulto vectors and the lntroduction of uosqulto-borne dlseases Lnto neer areas; requlrenents for inprovlng control and survelllance 1n internatlonal transportation of mosqultos of public health i.nPortance; and preventlve and control measures. In an appendix, records of mosqultos detected in lnternational shlps or alrcraft are lIsted. For details of these aspects, the orlginal chapter should be consulted. It 18 sufficlent here to suomarlze the appropriat.e preventive and control measures as claselfled by the authors into grro categorles:

(a) Survelllance wlthln receptive areas: Survelllance ln a receptive country lnvolves maintenance of effectlve detectlon mechanlsn and control measures. The WtlOExpert Cornnittees have repeatedly emphaslzed the need for malntenance of effective antimosquito measures wlthln and around internatlonal alrports and ports. These measures should lnclude:

- Approprlate sanLtary englneerlng principles should be observed in the design and rnaintenance of internatlonal alrports to mlnlul.ze vector breedlng and prevent vector entry lnto alrport buildings.

- Maintalnlng regular entomologlcal surveys, and applicatLon of larvicides to breedLng places. It nay be necessary to treat buildlngs within and around airports aod porfs wlth resLdual and ultralow volume (IILV) lnsecticide formulations. Vectors should be susceptlble Eo insecticldes used.

Survelllance procedures should also include detection of exotlc vectors in international alrcraft and ships. This aspect needs nore precise study than at present, with tire aln of deternlning the sources of lnfestatlon of aircraft and ships because the risk of infestation is much greater on sorDeroutes than on others. When the vulnerable routes are identifled, lt nay be posslble to redirect the actlvity of detectLon and control of exotic vectors to only those lnternatlonal alrcraft travelling regularly on these routes. Ttre nethod of dislnsectlng passenger cabins lnroediately after disenbarkatlon as practlsed ln the US, awaits wide trial. Other nethods for aircraft disinsectlon that are acceptable to crew and passengers await developroent.

(b) Internatlonal cooperation to control the mosquito vectors at source: Governments having internatlonal alrports in areas infested wlth mosquito vectors should be encouraged to:

- make ln-depth vector studies in and around thelr internatlonal airports and ports, and assess the inpllcatlons of the flndings fron an lnternatlonal standPoint;

- describe the current vector control operatlons, and indicate the degree of contlo1 achlevedl vBc/90.1 MAL/90.1 Page46

TABLE 3. MALARIA ASSOCIATEDT.TITH AIRPORTS q'B E= i 3 I ii.. .i?.r .E q t i 1'd>.! ! tn 6 6uc . .H .2" Ej E I .gb .3 tc'l 'dr8d 3.i ! 6t-- p'id!!".:tia issftE 'i-a !i €:! U!FE i!ei; .;8 35'*H 'iE'dtE F:*E!'1 qEigrlrri lE si: !Enl&5 'dt33. E; r; ieH; .:$Ae -'!g€g -Hti+E;*.:E.E'i es oo uro!r -B!9t rE'r* ;q;: ;; ;,x i:g* ilgiX ltl*l iSri;E :sEai:;$ !u'rEuF .;sia gl.gE6u .9u&'6 as iE =io)* E3!q t: IT^.f, a 1".:t A t F5n 3- . *; I [I: lst H *3'9" ocHE.ii r HIc* 'F! r*ai'sc H F{a'

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r r r H NN \o rF@ o\ 4 uO @@ @ r tsOrr o.d o\ o\ ch o\ oro Fl I cro UO o .9 I = (!|r 0o o0 0. o0 A o0 c o OoJ F, 4, .n a (n € FT >1 qqqq 6d a }rt lr !Llrotr F{ >,o >o h c rl .r{ 6 €q= tU @C.tCAo oa oru\oEFOoqJ F(!ottoolr NC) r l. N o lr {5 6 U lr .l!Oqrl|dO ! E.EUO -9 -O .1.0J -d .o .o o o -t U o o (!3 o.d O. o o c, o =.4 ou o o o 5.d o 0, i F i o q H 3 g i aq i Ei i E C)q (!(!q(!0.!q d.nq 6 = | = | 60 >l Ef=roztlElo

to n tu E'O dl OE I u !- ' q, QJ!d q, .r (!Gl ErH o q) o >>rD st(J1(! 0 0 o\ ol t E! q, h 6 F, I aJloq) \o dltrq otr lr !v @ .lo F tr q) OOa ! >r^ Q^ oc 6l ur, E^ .d@ (! (!@ (!@ rg qr ol'o ! o I Or o 0J^ or or ! or or 0, >oum TilO o.?| dclr g dd!@ o ..{lo aE o e .i o\ oor lro\ O.l r! O 'r ot t! OF o, O- A- O O.lol (,v tOAv E.d A- 5 (tll! tr E J4 Ov Flv

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- lndlcate the constralnts that hanper the m"lnt,enance of vector control operatlons ln and around airports and portsl

- consult with other countrles concerned, and wlth WllO, as to how these constraints, includlng those related to technical, personnel and financlal problems, may be reduced;

- publlsh the results.

The role of WIiOwas deflned as follows:

- to encourage tralnlng of personnel for internatlonal vecEor control; - to stiDulate research and development to lEprove technlques for lnternational vector control, and to develop insectlclde formulatlons for aircraft dlsinsectlon; - to advlse Member States on methods of assessment of vector lnfestatlons and vector control in internatlonal sltuatlons; - to encourage MeroberStates to fulfll thelr obllgations under the Internatlonal Itealth Regulatlons regardlng the naintenance of ports and airports free fron mosquito veccors; - to advlse the Internatlonal Clvll Avlatlon 0rganlzatlon (ICAO) and Internatlonal Alr Transport AssociatLon (IATA) of the need of contLnul.ng alrcraft dlslnsectlon on vulnerable routes.

It ls interestlng to note that Russell (1987) conflned samples of insects: mosqultos (Cx. qulnquefasciatus), houseflles (Musca douestlca), and flour beetles (Tribolluo confusun) in cages and plaeed these wlthln the wheeL bays of a Boelng 7478 aircraft. These lnsects survlved travel on the followlng nornal conmercial routes: Sydney-Melbourne; Melbourne-Slngapore; Singapore-Bangkok; Bangkok-Slngapore; and Slngapore-llelbourne. Survlval of alL three species was high, averaglng 847" for mosqultoes and higher for flies (932) and beetles ( 992>. Although external teoperatures nere -42o C to 54o C for alrcraft crulslng at 10 700 - 11 900 m, olnlouu temperatures wlthln wheel bays ranged fron +8o C to *25o C. Aeroeol dlsinsectlon of rrheel bays lonedlately before departure would assist 1n preventing transport of nrny insect specles, depending on lnsectide formulatlon, unless an autouatlc dlslnsection device can be lncorporated into the wheel bays.

L.2.2 Actlon by l.{tlO

Durlng the past decade, several oeetings nere organlzed by or wlth the partlclpation of the WHOReglonal Offlce for Europe to deal with probleus of prevention of reintroductl.on of malarl.a or to coordlnate the antlmalarla activities. Only the recorn'rendations related to problems of irnportatton of oalaria ln areas where the dlsease has been eradicated in the European Reglon are sumrarized here.

In Septenber 1978, a WIIOl{orking Group met in Izmlr, Turkey (WIIO, l-979a) to dlscuss problems of receptlvlty to malarla and other parasitic diseases. It was concluded that lnported ualaria ls increaslng ln most European countries, wlth infected travellers arrlvlng from Afrlca, Asla and elsewhere. Importatlou of ualaria into highly receptlve areas constitutes a serlous hazard. The procedures by whlch the risk of reintroduction of nalarta can be assessed ln terms of ualarlogenic potential of an area LTasannexed. 0f the specific recommendatlons related to malarla, reference ls uade to:

(a) The dlstrtbutlon, abundance a'Dd vectorLal capaclty of potentlal nalarla vectors should be further examlned Ln foroerly malarlous counlrles, with particular reference to their susceptlblllty to exotLc Plasuodiun strains.

(b) Susceptlblllty of nalarla vectors to lnsectlcldes should be regularly nonitored in case there ls a renewal of nalarla transmission.

(c) Fleld studles should be lutenslfled to assess the risk of introductlon and spread of known malarla vectors fron nelghbourlng or dlstant areas, lrlth speclal attentlon to the viclnlty of Lnternational airports aad such major routea as the Trans-Saharan road.

(d) In vlew of the threat posed by the spread of chloroqulne-resistant strains of P. falclparun, every effort should be made to apply the avaiLiable technlgues to determine vBc/90.1 MAL/90.r Page.53 the sensltivlty Level of the parasite to chloroquine and other drugs lthen cases of P. falclparun lnfectlon are detected.

(e) As a general prlnclple surveillance in countries with medlurn or hlgh roalariogenlc potentlal must be intensifled ln order to detect and ellnlnate any focal transmission arJ"sing fron lntroduced oalaria cases, or from relapses among lndigenous infections.

(f) It is essential to strengthen reference institutlons in endenic and high-risk countries in order to carry out nonltorlng and research activtties. Reglonal and natlonal laboratories should be establlshed or reinforced. Such laboraEorles should be lnvolved ln the development and evaluatlon of control strategles ln endenic areas, and be able to assist in the tralnlng of personnel.

(g) WHOshould pursue through its channels lncluding lts research and trainlng programme in troplcal and parasltlc diseases, the research for new antlmalarlal drugs, vaccines, and asslst ln thelr evaluatlon through a network of collaboratlng centres and field projects. there is a partlcularly urgent need for a radical curative agent for P. vivax lnfecrlon that can safely be used in lndivlduals wlth GCPDdeflciency' whlch I"fFET-r" nany lndividuals ln the Region.

(h) WHOshould ensure contlnulng productlon and dlssemlnatlon of inforrnatlon required for health educatlon and tralnlng on the control of vector-borne dlseases.

In October L979, a coordlnatlon meetlng on the preventlon of reintroductlon of nalarla ln countrles of the west Medlterranean vras convened ln Erlce, Italy Jointly by the I{HO Regional Office for Europe and the Itallan Government (I{HO, 1979b). The meeting was attended by partlclpants froo Algerla, Morocco and Tunisla, as well as France, Italy, Portugal and Spaln. The neetlng revtewed the malarla situatlon ln the participating countrles and the probleo of lnportatlon of rnlaria lnto contlnental Europe. Furtherr the Deetlng discussed the rlsks of reintroductlon of nalarla Ln relation to the roalarlogenlc potential and the need for epideniologlcal surveillance Ln relatlon to the degree of rlsks of relntroductloan of the dlsease.

Of the series of recomendatlons rnade by the Deetlng, reference is nade Eo the following:

(1) In vlew of the nalarla sltuatlon ln the world, the epldenlologlcal situatLon should be perlodically evaluated Ln order to make the necessary adjustments 1n the survelllance systeo as would be necessary to prevent the reintroductlon of nalarla.

(2) As experlence over the last decade has shown that reintroductlon of oalaria can be attributed to lack of an appropriate systen of vigilance, surveillance activities proportlonate to the risk of lntroduction or recrudescence of the dlsease, should be established or reorganized according to the rnalarlogenic potential in each area of the countries concerned. The survelllance sysEetr should be based on a regularly updated epidenlological strattflcatlon of varlous Parts of the country.

(3) In view of the real and lrmedlate danger of lmportatlon of malarla, notification of all types of ualarla caaes (indigenous, introduced, imported, induced, etc.) should be made compulsory ln countries where thls has not so far been done.

(4) In vlew of the practical difflculties of loposing conpulsory screening of lngernational travellers for malarla, more lnformatlon should be disserninated on the areas where there ls a rlsk of malarla infectlon, and clear, precise and sirnple instructions should be lssued on malarla chemoprophylaxis and other oeasures of lndivldual protectlon. For this, closer collaboratlon should be establlshed wlth travel agencles and companies operatlng ln malarlous areas etc., to provide more acEive suPPort by naking information avallable to thelr cllents and staff. There is also a need for appropriate coordLnalion to be establlshed between health servlces and lmlgratlon agenclesr partlcularly ln countrie6 where there are large scale populatlon oovements to and from malarla endemlc areas lnvolvlng pllgriosr rePatrl'ates, refugees, etc.

(5) In vlew of the real danger of importation of infected anophelines by aLr froru countrles where oalarLa ls endenlc, lt was recontmendedthat the International Health vBc/90.1 r'{ALl90.1 Page 54

Regulatlons concerolng dlsinsectlon of ports, alrports and aircraft carrylng passengers or goods should be strlctly applled. In the case of the trans-saharan highway, it is essential to set up as soon as posslble at the polnt where the hlghway enters Algerla, a dislnsectlon statlon for treating vehicles coming from areas of Afrlca south of the Sahara. There ls also a need for an entornological monitorlng systeo to cover all water points and lrrlgatlon sites 1n the vlclnlty of the hlghway ln order to detect any establlshnent of a troplcal anophellne specles as rapidly as posslble, and to take the necessary measures.

(6) As the denslty of vector populatlons tends to increase when spraying operatlons are dlscontlnued, recoouendatlons were made for countries concerned as follows.. to maintain a tean of technical staff and the necessary speclallzed lnfrastructure to take rapld and lomedlate actlon in case of malarla epLderolcs; to nonitor the level of suscePtlbllity to lnsectlcldes used and to deternlne the alternaEive Lnsecticldes to be applled when necessary; co apply other ueasures to llnit the density of vector populatlons and prevent any expanslon of the area of thelr dlstrlbutlon (blological control, source reductlon, etc.); to establlsh cooperatlon between the }tlnlstry of Health and mlnlstries and authorltles responsible for nater-resources projects (reservolrs, constructlon or extenslon of lrrigatlon systems, expansion of rlce cultivatlon, etc.) for uonltoring the maintenance of tire schemes, as well as the correct use of water resources so as to avold the formation of pockets of water that nlght favour the spread of anophellnes.

(7) In vlew of the increasing shortage of speclallzed staff (malarlologlsts, entonologlsts' sanltary engLneers, technlcians, etc.), ffiO should encourage and support the organlzatlon of perlodlc and regular courses ln oalarlology and control nethods. For thls r theoretlcal and practlcal traLnlng could benefit frou the resources avallable in the particlpatlng countrtes. Fleld tralnlng could be conducted 1n countrles where control operatlons are underway.

(8) Mto should cooPerate with Lnterested countrles for promotlng basic and applied research ln nalarlology and methods of control particularly the following aspects:

(a) evaluatlon of the effect of blologtcal control of larvae on the denslty of adult anopheline populatlons;

(b) selectlon of the most cost-effectlve methods of ultra-1ow-vo1u.me lnsectlcide appllcatlon and assessment of their effictency;

(c) conductlng long1tudlnal studies on posslble varlatLons ln the conposlttonr. behavi.our and vector potentlal of local anophellne populations;

(d) conductlng studles on breedlng preferences of dlfferent vector specles of the Itestern Mediterranean (lncluding the Sahara region). Such studles should lead to a uore ratlonal plannlng of source reductton measures based largely on the cooperation of the comunitles;

(e) conducting studies aloing at further clarlfylng the question of the potential of the exotic stralns of P. falclparuro and transmitting then to human hosts;

(f) carrying out objective evaluatlon of the beneflts accrued fron oalaria eradlcatlon or the reduction of its tncldence in each of the particlpating countries, wlth the establishment of norms and crlteria to assess:

- the lmpact of malarla control on socioeconomlc development. - tire lnpact of socloeconoulc developoent on endemlc nalarla.

(9) In vlew of the steady increase of the resistance of P. falclparun stralns to chloroqulne, and taking into account the prophylactlc and therapeutic problems facing the lnternatlonal and natlonal travellers of the partlclpating countries, it was recom'nended:

(a) that each country should deslgnat,e a national reference centre to establlsh in vltro culture of Pr_ Jglglpgrgrr and rnake a systematic study of sensitlvlty tests to tEE Fn-lnoqulnollnes-ln stralns of thls speeies that nay be ietected in patients lrlth suspected signs of reslstance; vBc/90. 1 MAL/90.1 Page 55

(b) ttrat ffi10 should organlze further trainlng courses on sensitivity tests;

(c) that all conflrrned cases of P. falciparun resistance to the 4-anlnoquinolines should be reported to WHOas rapidly as posslble.

(10) Slnce the ellminatlon or sharp reduction of endenic malaria 1n the ParticiPating countrles has led to a reduced interest among the population as a whole and the nedical profession in particular, the teachlng of parasitology and troplcal nedlcine should either be reintroduced or made conpulsory ln facul-ties of nedlclne and blology and in schools of paramedlcal and auxlliary personnel.

(11) In view of the rlsks assoclated with the use of residual insectieides (environuental pollution and the selection of lnsecticide reslstance), it. ltas recomrnended that health authoritles should acquire the necessary legislalive Powers to exereise effective and balanced control in the field.

(12) For successful lnplementalion of the above recoomendatlons and for exchange of information among partlclpatlng countries, especially those of Maghreb, further coordination meetings were recornnended. Also, a seminar on information and coordinaEion eras suggested comprislng North Afrlcan countrles and the adjacent nelghbouring countries of tropical Africa, under the sponsorshlp of ffilO Reglonal Offices' AFRO' EMROand EIIRO.

In March 1980, the WHOReglonal Office for Europe and United Nations Development Programme, ln collaboratlon wlth the Government of Bulgarla, organized a oeetlng in Sofia for the purpose of establlshlng coordlnatlon of antlnalaria actlvltles among countrles of south easE Europe (WIIO, 1980a). The neeting was convened wtthln the frarnework of an lntercountry project set up by WIiOand IINDPin 1978, ln order to oeet the challenge of malarla resurgence, partleularly ln vtew of the vulnerabillty and receptlvlty to the dlsease ln several countries. ParticLpants fron countries particlPatlng in the projects were lnvlted namely: Bulgaria, Greece, Turkey and Yugoslavla, as well as Syria froo the WtlOEast Mediterranean Reglon. The neetlng revlewed the oalaria situation in the partlclpating countries and the existlng organization and facilities. The meeting also discussed the amount, type and periodicity of lnformatlon to be exchanged, and the possiblllty of exchanglng expertise and resources in cases of emergency. The proposed actlvltles of the I{HO/UNDPproJect and Lts coordination rrere also discussed. A suronary of the recomendatlons follows:

General

(1) to adjust the nature and intenslty of vtgllance activities to the axoountof risk of malarla transmission, and to revierd the activities perlodlcally in the light of environmental and social changesl

(2) in llaison with other insecticlde users, particularly crop Protectlosn services, to rationallze the appllcatlon of lnsecticides for publ-ic health, in order to delay the evolution of insecticide resistance;

(3) to prepare lnventory facilitles for research and training in each country' on the basis of whlch mutual exchanges of personnel and teachlng materials can be madel

(4) to establish a standard epldenlological infonnation system using an agreed forxoat;

(5) to encourage lnmunologlcal screening of groups of people coning from nalarious countrles;

(6) to organlze coordinatlon meetlngs once a year in each country in turn to review the oalarla situation, update the plan of work of the project, and discuss the related natlonal activlties;

(7) whenever necesaary, speciflc border problems and activltles of significance to sooe countries shouLd be consldered at bllateral/trilateral meetlngs, while recognizing that the naln thrust of the project should be towards eradication of nalaria in the affected areas and preventlon of reintroductlon of transmlssion in vulnerable areas. wc/90.1 MAL/90.1 Page 56

For countries nhere malarla transmlsston exlsts

(8) to strengthen cooperatlon wlth netghbouring Mlddle East countries, partlcularly lraq and Syrla, which face malarla control probJ-ens simllar to those in Turkey, and wlth other countries of south east Europe not represented ln the neetlng regarding:

- exchange of technlcal lnfornetlon and expertlse as requlred; - conductlng antinalarla activltles partlcularly ln border areas;

(9) to glve special attentlon to progresslve transfer of responslblllty for malarla control to the general publlc health service as soon as the developoent of the prfuoary health care network peroits.

For countries where malaria no longer exlsts

(10) every country should have at least one malarla vlgllance uoit to perform and supervise operatlons at country level partlcularly in:

(a) impleroentlng approprlate antlmalaria measures; (b) preparlng regulatlons and Lnstructlons concernlng lnportatlon of rn"larla lncludlng:

- oeasures alned at Preventlng lnfectlon of cltizens travelllng to malaria endemlc areas (chenoprophylaxis, health educatlon); - Beasures alned at early detectlon of nalaria 1n lnternatlonal passengers conlng from enderolc areas as they arrLve at the border of the country (inforuatlon, leaflets, referral for nedlcal exaulnatlon and taking blood sanples when lndlcated, survelllanee, etc.)1

(c) conducttng regular entomologlcal actlvlties ln selected localitles on the basls of the procedures outllned by ffitO.

Several topLcs were suggested in the report of the neeting for undertaklng basic and applled research coverlng: malaria parasites and the human host; parasltes ln the mosquit.o host; vector blology; lnsecttcldes; and vector control and its evaluatlon.

In October 1980, a conference was held ln Cagllarl, Ltaly on the occaslon of the celebratlon of the thlrtieth annLversary of nalaria eradlcatlon Ln Sardlnla, in collaboration wlth the WIIORegtonal Office for Europe, the Government of ltaly and the Regional Government of Sardlnia (WttO, 1980b). The conference nas attended by partlcipants from several countrles of continental Europe as well as Algeria, l4orocco and Turkey. In deflnlng the purpose of the conference, lt was polnted out that desplte the efforts of the ffiIO Malaria Actlon Programme, nalaria persisted at an endemic level 1n many tropical and sub-troplcal countrles, glving rise at tlmes to epidenic outbreaks. The lncreaslng Lnterchange of populations betrteen malaria-free (or freed) areas and those whlch are stlll malarlous, i.s responslble for the conttnuous increase ln Lhe number of oalarla cases lnported i.nto continental Europe causlng serious concern, for the patients tlremselves, for the nedlcal professlon and for health authoritles, because of the possible resurgence of malaria ln focal outbreaks in the receptive areas particularly those sltuated ln the Mediterranean basln. The conference provided an opportunity to discuss and agree on joint actlon that would support the WHOMalarLa Action Prograune.

The conference reviewed the malarla slutatlon ln the world with special reference to the global problens and future prospects and dlscussed the bastc and applied research needed for solving technlcal problens and for clarifylng epideroiological sltuatlons as well as testing tools and approaches for oore effective oalarla control. The conference also reviewed t.he malaria situatlon ln the WHOEuropean Region and dlscussed the problens of contlnued focal nalaria transmlssion in Algeriar and Moroccor, and the exploslve epldeolc that broke out ln Turkey during the past three years. Enphasis was laid on the probleu of fuaported and lnduced malarla ln contlnental Europe and the assoclated risk of ffiTgffi;e Morocco hitherto ln the Wtlo European Reglon, now in the I.IHo Afrlcan Region and the WIiOEastern Medlterranean Reglon respectlvely. vBc/90.1 !,tAL/90.1 Page 57. relntroductlon of malaria transulsslon. Tralning needs and the faclllties exlstlng ln Europe were dlscussed. Several reco'nrnendatlons were made for actlon to be taken at an international level- to provlde technical and flnanclal asslstance to the Malaria Action Programme. Speclflc recommendatlons were made for supporting research and trainlng actlvltles 1n malarLous countries of the !lI{O European Regi.on as suosarized in the following:

(1) Support should be glven for increasing the research and tralnlng to be established as jotnt actlvltles between instltutlons in maLarlous and nalarla-free counlrles.

(2) International tralnlng courses should be organlzed ln an lnstltute ln Ita1y, wlth the posslbllity of practical field training ln a demonstratlon area 1n Turkey.

(3) There 1s a need to organize and develop research in thls demonstration and trainlng area to be used by Turkey and nelghbourlng countrles for developlng nalarla control strategies based on the concept of prlnary health care, to be applled in areas of long transoj,ssion season assoclated with lrrigation and vector multl-reslstance to lnsecticl-des. M{0, ln close llaison with European and other countrles concerned, should explore the ways and means to speed up the developnent of thls facl.llty, whlch could serve countrles of south Europe, Mlddle East and North Afrlca.

Speciflc recornmendatlons were also made for countrles where rnrlaria is no longer endeolc ln the European and other Reglons, as sunmartzed, in the following:

(1) Countries should oalntain and, Lf necessary, lncrease thelr expertlse in the fle1d of malarla, in order to adjust thelr vigllance actlvltles to the degree of malarla risk, and that they should strengthen thelr technical cooperatlon wlth countrles that sttll have malarla as a probleo.

(2) There is a need to ensure that notiflcatlon of all cases of ualarla, whether lndlgenous, luported, Lntroduced or lnduced ls carried out by all health lnstltutlons.

(3) A national oalaria reference centre should be establlshed by each country.

(4) Necessary and pertlnent lnformatlon about malaria rLsk should be provided to all travel agencles and travellers.

(5) There ls a need to increase the awareness of the posslblllty of malaria outbreaks, so that countries should have the necessary human and technical resources for rapld deployoent, and to prepare a plan for concerted actlon involvlng the early release of funds, llfting of relevant customs barrlers and restrlctlons on purchase of oaterlal and equipnent not avallable locally.

(6) The receptivlty of varlous lnportant Anopheles species to human plasnodla of troplcal ortgln should be investigated fully and speedily.

In October 1986, a Deetlng of a WltOWorking Group on malarla risk for lravellers vtas held at the Hungarian Tropical ltealth Instltute in Budapest, Peoplers Republic of llungary (WHO, 1987). fhe worklng group was forrned of partlclpants frorn Austria, Ilungary, Sweden, Switzerland, the United l(lngdom, the USSRand Yugoslavia. WtlOwas represented by Dr J.A. Najera, Director of the Malari.a Action Prograome. A study was carrled out by Professor D. Bradley (United Klngdon) and Professor F. V6rnai (Hungary) involving collection and analysis of information from various countrles ln Europe to find out the risks eocountered by dlfferent groups of travellers. This provided ample basic material for dlscusslon and fornulatlng the recomendations. Tabulated data of lnported cases reported to I"[IO by natlonal health authoritles coverlng the perlod 1974-1985 were preseoted and discussed ln the meetlng.

The Working Group examlned the problern of inported nalarla 1n contlnental Europe and made several observations of whlch reference is nade to:

(a) Examination of data reported by health authorltles to llllO indlcates that the number of fuaported cases has been lncreaslng steadlly over the past 12 years, frou 2385 cases reported tn 1974 to 5634 cases in 1985. Ithis flgure of 1985 reas revised later to vBc/90. 1 MAL/90.1 Page 58

- 62L5 see Table 4(a) belowl. Thls rlse corresponds to the lncrease ln the number of travellers to areas of endenLc malaria, and to the overall increase 1n nalarl-a transmlsslon ln some parts of the world. Wtth few exceptlons, the llnear increase shows a constant trend. However, anlaysis of data by country shows great varl.ation from country to country and fron year to year. Thls was attrlbuted to a number of objectlve factors such as the number of travellers, the motlve for travel, endemlc area vislted and the length of exposure to infectlon, preventive measures undertaken, etc. However, subjective valrables related to recording and reporting of the lnported cases must also be consldered. Despite the fact that nalarla is a notlfiable dlsease ln most countrles of Europe, lt is believed that the number of malaria cases is, in fact, conslderably greater than rePorted. In support of this belief, it lras polnted out that most countries of Europe have well establlshed nechanlsms for dealing wlth lmported nalarla, such as speclallzed hospltals or lnstlLutes of tropical diseases or reference centres for diagnosls. These lnstltutlons are also responslble for collectlng and analyzlng epideulologlcal Lnforoatlon, but 1n oany lnstances there is no way of studyl.ng ihe actual coverage attained by these diagnostlc and treatment faclllties. Reported nrrmberof deaths lndlcate a case fatallty rate of 0.5 - 17" fot ualaria lnfectlon as a whole, and specific fatallty rates for P. falciparuro ln some countrles have been as hlgh as 7%. These fatallty rates are lncompatlble wlth the quallty of rnedlcal care generally avallab1e 1n Europe, and should be taken as an indicatlon of inadequate appllcation of knowledge and managenent of resources for diagnosis and treatment. These are probably sone of ihe reasons why the extent of the problen of Lnported nalarla has not been fu1ly recognlzed at a natlonal level.

(b) The epldenlological characterlstlcs of loported malarla (e.g., the relatlve proportlons of varlous paraslte specles, areas of the world froro which the infectlon originates' and the meln soclal, ethnlc or occupatlonal groups predoulnantly affected), apPear to remaln constant for a given country. These characterlstlcs reflect the tradltional pattern of travel and trade llnks of the country concerned. Ilowever, there is some evldence thatr as a result of the growth of travel and noblllty of labour a6ong European populations, the rtsk of acqulrlng roalarla nay have spread well beyond the traditlonally exposed population groups.

(c) The lnstructlons given to prevent malarla among non-lnmune travellers visltlng malarla endenic areas oay have created the lnpresslon that the drugs used for chenoprophylaxls Prevent the infection ln all sltuatlons, and t.hat these drugs are sufflclently safe to be recomended without reservattons. For this reason ualarla chenoprophylaxLs has recently become the only measure applied by tnternatlonal travellers. Ilowever, studles publlshed Ln the past fen years on the efflcacy and safety of prophylactlc drugs lndicate that these are nelther as effectlve nor as safe as they are belleved to be. Furtheroore, a wlde range of advlce is being offered by dlfferent servlces ln an attennPt to strlke an appropriate balance between drug safety, efficacy and avallablllty. Thls is further conplicated by the fact that inforuation on adverse reactlons to antlnalarlal drugs ls lnconplete, and ln certain instances, apparently contradlctory. Infornatlon about compliance wlth the preventive advice is available fron lttrlted studies in a few countrles. The need to balance the risk of exposure to infectLon agalnst the rlsk of adverse drug reactlons ca1ls for oore accurate targeting of advlce in relation to speclflc areas and populatlons. Efforts to inprove compliance with ttre preventi.ve advlce may becone more relrardlng when focused on hlgh-risk situatlons.

(d) In some countries, the lnctdence of inported malaria ls apparently higher among i qrigrant populatlons than among non-immune European travell-ers. The nost plausible explanatlon for thls is that iroroigrants lose thelr innunlty to nalarla as they reside i.n Europe, and consequently they easily becone lnfected when they return to ualaria endemlc areas in thelr native countries.

(e) Reslstance of P. falciparun to chloroquine has been confirned in nore than 40 counErles, and ln 1985 it extended its dlstrlbutlon in troplcal Africa as it was reported for the flrst time from Caueroon, Congo, Senegal and South Africa. Reslstance to Fansidar now exists ln 11 countrles (lncludlng Kenya and Tanzania). Resistance to quinlne was reported from three countries ln Asla, and reslstance to nefloqutne was observed Ln E[e Phlllppines, Ihalland and Tanzanla. Although the increase in the total number of imported malaria cases ln Europe has not so far been greatly affected by P. faLciparun reslstance toant1a1ar1a1s,theconstantPresenceofsuchres1stanceposesffiforthe approprlate treatment of rnalarla cases. vBc/90.1 MAL/90.1 Page 59.

(f) There are only a few epldeniological studies on lnported nalarla ln Europe and the way 1n whlch it ls 'nanaged. In addltlon, these studles are the result of lndivldual initiatives and lack appropriate coordlnation. Health servlces do not yet. appear to be ready for using the epidenlological lnfornatlon to lmprove thelr managenent of the problen.

Observations nade on mrnagement of malaria showed that lnforrmtlon provLded by natlonal health servlces in Europe lndicate that there are conslderable variation 1n the data collected on lnported malarla. Hence, lt is alnost inposslble to compare between countrles when it cones to detalls regardlng the actual compared with the theoretical risk of infection, or wlrh regard to the incidence per nuuber of travellers. Nevertheless, there is a certain consistency ln that nost countrLes record data on parasite specles and origin of infectlon. On the other hand, there are countrles in whlch tnore than one agency compiles reports, and others ln whlch reports froo perlpheral laboraEorLes do not match reports based on indlvldual notificatlon of cases. Studles have shourr, however, that if sone addltlonal efforts were made at national level to coordlnate the actlvitles of all health establishments lncludlng prlvate physlcians, and to cooperate with other countrles, the problem of funported nalarla could be deflned more realistically and managed more effectlvely.

The results of enqulries recelved fron 1l countrles in Europe lndicated that desplte many gaps, the lnformatlon provided could serve as a good basls for comparison. However, some lmportant data on cllnical and epldeulological events were lacklng such as reasons for travel, length of exposure, and the degree of coupllance wlth the recommended chernoprophylaxls and/or personal protectlon measures, nor have data been collected on the hlstory of malaria fevers among travellers temporarlly reslding in areas with endenlc malarla. There would be a great advantage lf European countrles adopted a comrnonand uniform approach for recordlng data on imported malarla. For thls, the working group proposed a quesEionnalre for further conslderatlon and consultation by national authorltles responsible for oalarla control through WtlO.

The Worklng Group further examlned the inforuatlon provLded by certaln countrles on chenoprophylaxls recort ended to travellers vlsitlng areas of chloroqulne-susceptlble and chloroqulne-resistant P. falciparun. The slde effects of varlous antinalarial drugs were also examlned on the basls of many papers publlshed ln the past two or Ehree years, and speclfic reconnnendatLons were rnede ln thls respect (see below). On prevention of man-nosqulto contact, frorn lrrltten inEervlews nade ln Slrltzerland with 10 000 travellers, 587" of. the SwLss tourlsts clalned to uae such measures. There nere no data avallable frou other counErles. Booklets have been publlshed on life in tropical counErles giving details of protectlve measures agalnst nalarla and other tropical diseases, and some countries (e.9., Bulgaria) such booklets are provlded free of charge. However, it is not known to lthat extent these instructlons were followed. Natlonal health services when advislng travellers about malarla endemlc areas, sbouLd attach equal imporEance to the methods of personal protection such as screening of windows and the use of bed-nets or repellents.

The llorklng Group further pointed to the research for evaluatlng t.he risk of malaria. Research on the epldenlology of furported malarla has been confined to conpilation of data on reporEed cases. It ls only recently that certaln aspects have been studled ln Hungary, Swltzerland and the IlK. Toplcs of studles that have been completed or i.n progress were shown as follows:

- retrospectLve analyses of rlsk in relation to chemoprophylaxis (Ilungary and Swltzerland); - cohort studies of package tour travel-lers (Switzerland); - assessoent of coopllance with advlce glven (ttre Uf); - studies of compliance among alr travellers (Switzerland and the ItK); - rlsk analysls for ethnic ninorlty groups (the UK); - arrlving traveller populatlon studles (the IIK); - assessrDent of rlsk Ln overland travellers to Asia (the IIK).

The l{orklng Group added that further research is needed to define the high risk groups in order to reduce the extent and consequences of lmported malarla. Research must also be carried out to assess the actual versus the theoretlcal risk of infection for different categorles of travellers (buslnessoen, tourists, short-term personnel, dlplonats, etc.) to vBc/90.1 tlAL/ 90 .1 Page 50

deternine the Dost effectlve and safe prophylactlc regiuens, to define the best advlce to be glven for each subgroup, and to flnd out the best nay to convey advice so as to achi.eve tlaximum compliance. Models of studles already lnltiated could be used by countrles other than those mentloned above.

On the basis of aspects discussed, the l{orklng Group presented a series of reconrmendations as quoted below:

"1. National health servlces in Europe are urged to adopt a systematlc and responslble attitude to the oanageoent of inported nalaria. While lt ls clear that all the countries of Europe have the necessary expertise to dlagnose and treat malaria, there is an obvious need to develop nechanisms to ensure better utillzation of thls expertlse. In fact, the management of ltrported nalarla should be an lntegral part of the management of imported diseases ln general. To achieve this, national health services should use existing facilltles to nalntaln interest in and focus attentLon on dlagnosis and treatoent, case reporting, prophylactic advlce and health education of travellers, together with the organlzatlon of approprlate health measures. Medlcal assoclattons and, ln partlcular, their sections for preventlve mediclne can nake a considerable contrlbution to carrylng out this task by organlzlng special Eeetings or seminars.

2. In view of the need for comparable and complete reportlng on lmported malarla as a basls for rational management of the problem, steps should be taken to adopt a cornrnon approach to the epideniology of malarla. To achieve this, the World llealth Organization in conjunction wlth Member States could jointly convene a meeting to be attended by rePresentatives from each country of Europe and alned at achlevlng comparable reporting. Prlor to this roeeting, a small worklng group could be organlzed to develop proposals.

3. In vlew of differences in the lntenslty and seasonal patterns of malaria transnission in varlous parts of the ltorld, as well as the different patterns and duratlon of exposure of non-immune people to malarlal lnfectlon, further studtes should be made of the actual malarla risk for various groups (buslnessuen, tourlsts, temporary resldents ln endeoic areasr lrnrn{ga3nts froD endemic areas residlng ln Europe).

4. The cholce of chenoprophylactics for regular use should be based on an evaluatlon of the rlsk of adverse reactions fron the drug(s) used as against the rlsk of infection. Safety and efficacy should be appropriately balanced. It should be recognized that, in oany lnstances, complete protection wll1 not be achleved by chenoprophylaxls.

5. Prevlous efforts to prevent infectlon of travellers by cherooprophylaxis have not been very successful. Glven the evolutlon of the nalarla problen in endemic countrles and the reduced effectlveness of chenoprophylactlc agents, greater enphasls Eust be placed on pronoting personal protection agal.nst mosquito bites, lncluding the use of bed-nets, screened accormodation, appropriate clothing and behaviour and repellents, as nelL as on I ediate recourse to appropriate diagnosis and treatment in the event of fever or to a full course of treatroent Lf such facilities do not exist. Travellers should be provided wlth approprtate drugs for treatment and should be made aware of the need t'o alert their doctors to the fact that they have been in a malarlous country if they fall il-1 after their return.

6. Since the continued incldence of malaria Ls due in part to imported infected mosqultos, prefltght dlslnsection of aircraft is lmportant. MemberStates should insist on thls being done on a regular basis.

7. In order to prevent induced ualaria secondary to inported paraslte carri.ers appropriate screening of blood donors must be carrled out when the donor has travelled abroad.

8. I{hile appreclatlng the need for flexiblllty in providing advice on partlcular drugs or drug conblnations, the Working Group cannot recommendnefloquine (Larlan) as a long-term prophylactlc on.the basis of inforrnatlon currently avallable. Regarding Fansidar, the I{orklng Group relterates the view that this drug glves good protection in nany cases of chloroquJ.ne-reslstant P. falciparum malarLa. llowever, its admlnistration is absolutely contralndicated for people who have prevlously ^nifested sulfonamide lntolerance. Data on Fansidar safety among travellers at large are somewhat conEradictory. An incidence of vBc/90.1 I,!AL/90.1 Page 61

Stevens-Johnson syndrome of the order of 1 per 10 000 tests, with fatal adverse cutaneous reactions in 1 per 20 000 tests, as observed in the Unlted States of Anerica and elsewhere, contrasts with an apparent high degree of safety in Swiss travellers. According to some investi.gators, the concurrent administration of chloroquine might have contributed to the frequency of adverse reactions, and the use of Fansidar in conjunction with chloroquine appears to be ill advised. lhe fact. should not be ignored, however, that ln nuoerous instances Fansidar alone has provoked the same types of adverse reaction. For thls reason the rlsks involved in the use of Fansidar alone require further study. Meanwhile, the adnisnistration of this drug as a prophylactLc should conforu to the spirit of recommendation 5 above.

9. Recognizing that research on the epideniology of inported ualaria needs to be broadened, the Working Group recomends that stronger support should be given to such research by countries'national health services and by WHO. Large-scale studies of relative risk, prophylacti.c efficacy and compliance with advice given need to be increased in number and in the variety of approaches adopted, in order to obtain valid data under different conditions, and especlally atrong neglected categories of populations and travellers to whomit is not easy to gain access. Activities described in section 41 of this report should be taken as an integral part of this recornrnendation."

Recently, WHOhas updated its reconrmendationson the dislnsection of aircraft. These cover general description of aerosol dispensers, WHOprocedures for testlng of aerosol dlscharge and biological performance, the foruulation of the standard reference, aerosol and alternative aerosol foroulations; disinsecting procedures: before take-off, "blocks artay", dislnsecting on the ground upon arrival, and resldual treatment of aircraft. For details of these recomrnendationsthe WIIO(1985Wkly Epiden. Rec.) should be consulted.

The latest records of luported malarla in continental Europe lrere conpiled from data cornrnunicated to WHoby health authorities during 1980-1986 as shown in Table 4({2. The WHOWorklng Group that net ln Budapest in 1986 has already cornmentedon the data of iuported cases i.n Europe up to 1985 (see above). It is clear that there has been a marked increase in the number of cases startlng froo 1985, reaching 6883 ln 1986, i.e., more than 2000 cases higher than ln 1984. This has been due to a beEter reporting systen in France and probably so ln the Federal Republlc of Germany (FRC). The highest nuober of iroported cases 1n 1986 Itas reported fron the United Kingdon (UK) (2306 cases), followed by FRG (1099 cases) and France (102f). The hlghest death rate nas observed ln Spaln (2.2%) and ln PortugaL (2.L%), and the lowest death rate in the UK (0.L7"1) and USSR(0.1S2). Derails of other malari.a infectlons that are related to inported cases or imported anopheline vectors has been cooplled in Table 4(b)2. The total nunber of these infections rhat have been reported during seven years is 179. About half of these (90) were lnduced cases trost Probabi-y due to blood Eransfuslon. These were followed by cases of drug addicts (L8.47">, relapses (10.12), airport malaria (7.8"1), congenital oalaria (7.8%), while only very small numbers of introduced, cryptlc and undeterolned cases were recorded, each constituti.^8 L.I7" of the total cases. Of 165 cases for which parasite identificatlon was provided,6S%were p. ..:ari*., L7.4% P. vlvax, 132 -TGEE-expeP. falciparun and 1.4%P. ovale. Of 78 ca s es o f i nduc edGElffl5t . t Z werdTlGlar ia e . c t ed ri6il-EEE-tong lastlng infection of P. malarlae constit"ti"g?f"rge proportlon of transfusional nalaria Isee Bruce-Chwatt, 197t]I;if6;:1.-J.1(ii-a) abovel. Congenital nalaria invarlably appeared ln the UK each year, maklng a total of 11 cases in seveo years, of which eight were P. vivax and the renainLng cases were P. falciparum. Ihis is nearly similar to the ffnaf.rgs of Philips-tloward et al . (198S-t who i;dfc.ated that P. vivax infections ln babies were of Asian origin, while P. falciparun lnfections were of Afrfcin origin [see 1.2.1(i) above]. Malaria infectlons arong dr"g;edicts were exclusively reported fron Italy - and Spaln with two najor episodes ln 1981 and 1984 respectively Isee under 1.2.1(ii-b) abovel. As shown 1n an official publlcation of the Italian llinistry of Health that nas comunlcated to WlO, there were more cases of rnalaria recorded in Italy in 1981 lhan those reported by Orlando et aL. (1982). Thereafter, there were only a few cases in 1982 and 1983, probably due to health education of heroin users at peripheral centres for addict asslstance. During 1980-1986, malarla cases associated with alrports were reported only

1. This refers to the types of research actlvities which have already been initiated by llungary, Swltzerland and the UK as outlined above. 2. Coopiled by Mr J. Henpel of the Epldenlologlcal Methodology aod Evaluarlon Unit (EME), MAP, WHO,Geneva. vBc/90. 1 MAL/90.1 Page 62

from six countries, vi-z: Belgiun, France, Ita1y, the Netherlands, Spain and the tIK (see also Table 3). In Belgiurn, after the two cases recorded in 1982, airport malaria cases continued to be detected with one case reported in 1983 and five cases in 1986. ln Francer no cases of alrport malaria have been reported recently except a single record from Marsellle Airport ln 1985. It has been explained that since the application of resldual spraying 1n Charles de Gaulle Airport no further alrport cases have been detecEed in the Parls area [see Ehe last paragraph under 1.2.1(iii) above]. The report of the t\ro Britlsh citizens who acquired the infection in 1983 from a coumuter vector on board a fllght comtng fron Ethiopia, remains as a single record of this exceptional mode of transmission.

Nowadays, the new trend is to protect tourlstst health froo infectlons and parasitic diseases as a whole, including nalaria. For this purpose, trro meetings were held during the first quarter of 1988. The first was an inter-regional meeting held jointly at Rlnlni, Italy durlng 8-11 February 1988 by the Societd ltaliana di Medicina de1 Turismo (SIMT), WHO,and the l.Iorld Tourlsm Organizatlon (WTO). As shown ln the WHO(1988a Wkly Eplden. Rec.), the ai.n of the neeting was to dlscuss the prevention and control of lnfectlons among tourists in the Mediterranean area. Although the more serious infectlous diseases (typhoid fever, malaria, schlstosoniasls, louse-borne typhus, anthrax) have been ellnlnated or brought under control, a lorr endenlclty of these dlseases st111 exists ln certain parts of the Medlterranean area. The nost frequent lnfections to whlch tourists are exPosed include: dlarrhoeas, other gastrointestinal lnfections and lntoxlcations, acut.e respLratory infectlons, sexually transmltted diseases, zoonoses and some parasitic diseases. There have been many instances of hesltatlon to dlssenlnate the results of disease survelllance for fear of dlscouraging lourists. The tnterchange of disease surveillance informatlon betrteen the Mediterranean countries and those fron whlch the tourlsts come has often been slow or absent. Therefore, there ls a need to re-examl.ne the problen of disease survelllance from the standpoint of contemporary tourism and increaslng international travel. The neeting stressed that the protection and promotion of the health of tourlsts requlres the conblned efforts of several disciplines and professions such as medlclne, envlronuental health, and other health sciences, clvil englneering, transportr hotel catering and tourist lndustries as well as governmental and non-governmental agencies. The xoeetlng further proposed that "tourist health" be recognlzed as a speciaLLzed branch of publlc health and that the three organizing agencies (SIMOT' WIIOand I{T0) should conslder holding an expert consultatlon in order to define this disclpline and to plan educatlon and training in various participaEing flelds/sectors, advise on organization of servlces and coordination of roultisectoral contrlbutlons at different levels. The report of this meetLng is being prepared.

The second meeting was in the foru of a conference held in Ziirich, Switzerland during 5 April 1988 on International Travel Medicine, under the sponsorship of the Swiss Federal Offlce of Public llealth, the British Publlc Itealth Service, the US Centers for Disease Control, I{TO, WHO,and the London School of ltygiene and Tropical Medicine. As shown in the WI|O(1988b l{kly Epidem. Rec.), the aim of the conference was to improve the prolection of the travellei$G.ffiive and more unifonn recommendatlons by all concerned, with particular emphasls on epi.demiological and preventive respects. Particlpants froo 40 countrles and terrltories including those of the European Reglon as well as representatlves of all six WtlORegions attended this Conference. During plenary sesslons, presentattons were made and discussions took place on general epideoiology including travel statlstics, the inpact of internatlonal travel on developlng countries and health risks associated wlth such travel: oalaria, vaccines and vaccine-preventable diseases, diarrhoea, sexually transoitted diseases and AIDS, specific health problems, health information and communieation and certain individual health risks to which the traveller oay be subjected. In addition to the subjects dlscussed at the plenary sessions and further enlarged upon at other sessions, attention was also glven to the health risks, health protectlon and oedical care abroad, to a review of the parasitic and other diseases found in returnlng travellers, and to health advice to travellers and in-fllght environmental problens. Round-table dlscussions were held on a number of subjects lncludlng malaria cheootherapy and self-therapy, irnmunization for travellers, AIDS and the preventlon of dlarrhoea among travellers. At each of these discussion sessions, recornrnendations were formulated whlch w111 appear in the forroal published- proceedings of the Conference, entitled "Internatl.onal Travel Medicine" (in preparation)r.

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2. The Medlterranean Reglon

As mentloned earlier, lt has been found convenient not to follow the boundarles of the WHORegions, because Algeria is now wlth WHO/AFRO(prevlously with WEO/EURO),I'lorocco ls now wlrh WtlO/EltRO(prevlously wirh WHO/EIJRO)and Israel ls now with WHO/EURO(previously with WHO/EMRO). Therefore, the deslgnated llediterranean Region has been arbitrarlly divlded into two sub-reglons as shown in Fig l: The Mediterranean Basin coverlng the l,lediterranean countrles of Europe and countries of Africa north of the Sahara (Algeriat !1orocco, Tunisia, Libya and Egypt) as well as Jordan, Israel, Lebanon and Syria, and the zone of Asla west of India extending fron the eastern part of the Mediterranean to the [email protected]}1ed1terranean Region nith the exceptlon of Israel. The recent oalaria 61tuatlon in these geographieal areas has been conpiled fron infornatlon shown in the Wld hlth statlst. quart. (WEO 1985,1986 & 1987) for the years 1983, 1984 and 1985 respectively as follows: of [For rnore details - see Subsectlon (11) EPIDEhIOLOGYAND CONlts'OLOF ]IALARIA in each SECTIONIII(A) (in press), and SECTIONIII(B) (ln preparatlon) to be issued laterl.

2.1 The Medlterranean Basin (Flg. 1)

The status of nalarla eradlcation and current problens in the Mediterranean countrles of Europe have been dealt wtth under 1.1 and 1.2 above. Only Turkey and the renalnlng countries of the Medlterranean Basin are dealt wlth here.

havlng almost In $!g, endemlc malarla has perslsted 1n certalo areas. After disappeared in 1968, the number of cases started to bulld up gradually until an epidenic broke our ln 1976 and 1977 when 37 000 and 115 000 cases ldere recorded respectively. The most affected areas were: Adana; Igel (Chukurova); and llatay (Aolkova). Eoergency measurea brought the sltuatlon under control to some extent. The number of cases after decreaslng to 29 000 lu 1979, rose agaln to 34 000, 55 000, and 62 000 In 1980, 1981 and 1982 respectively. In 1983, the annual lncldence reached 67 000. In both 1982 and 1983, over 502 of the cases sere reported from Chukurova plaln, and malarla focl continued to persist in certaln area6 (Antalya, Edlrne, Izmlr, Konya, Nigde, Yozgatr while foci expauded ln some others (Aydin, Manlsa). Iu 1984, the sltuatlon luproved, as the number of cases decreased to 55 000. The iuprovement was thought to be due to changing the insectlcide used for restdual house spraylng as malathlon waa replaced by piriniphosaethyl. The reductlon in the nuober of cases occurred not so mucb in Chukurova ptain Lut natnty ln eastern Anatolia where the number of cases decreased fron 20 900 ln 1983 to 12 500 ln 1984. The prevlously known focl continued to Persist, but with fewer cases.

The total population of countrles of Africa north of the Sahara reached 103 oillion in 1985. About Z-gnfftfon li.ve in originally ualarious areas. In L983' ualaria transulssion was much reduced and continued to be confined to soall foci. The number of cases rePorted decreased fron 561 in 1982, to 453 in 1983, but this trend was reversed as 666 were recorded in 1984, and 921 ln 1985.

In Morocco, Iocal P. vivax transmisslon increased 1n northern Provinces; the total number of cases reportm-E84 was 318 conpared with 62 and 75 in 1982 and 1983 respecglvely. In 1985, the number of cases sharply increased to 7L3. l'lalaria cases Itere detected in 21 provinces as in 1984, but the number of sectors and locallties with positive cases increased frorn 63 to 79 and from 85 to 150 respectively. The data of 1984 showed that passlve case detectlon, 1.e., health posts and hospitals, dlscovered 53%of all cases, while 43"1were found by epldenlological survey around detected casest suggesting that survelllance lras at times deflclent. In 1985' indigenous cases were r"infy reported from five provlnces: Chefchaouet (46iO, Benl l'1e11a1(L97")' Tetouan (L2"4), Nador (72) and 41 Hoceioa (72). Renedlal measures were appli'ed.

In Algeria, report6 of 1982 shorred that the 26 northern provinces (W11ayat) were free of tndtgenous nalarla for the first tlme slnce the 6tart of the malarla eradication progranme ln 1969. All these provlnces ltere expected to eDter the malntenaoce phase fron 1984 onwards. The snall focus in Adrar province (health sector of ) perslsted in 1983 wlth 12 new caaes detected: 3 P. vlvax and 9 P. malariae. In 1984' the northern provloces continued to be free of indigenous ualarla. In the focus of Adrar provincet oaly three indigenous cases were recorded. Addltlonally, there were tlto locally vBc/90.1 LAL|90.L Page 66

tontracted P. vivax cases in In-Salah, but the epideniologlcal lnvestlgaEion did not reveal any other cases. ln the Sahara provinces, there vete 27 cases detected, and all tere inported ones originatlng nostly fron l,tali. In 1985, only four isolated cases were letected: one indigenous P. vlvax in , one relapse case of P. vivax each in Juargla (Djanet sector) provinces, and one relapse case of p. n"ffiiln (Douera sector)."i?-EE? In addition, there were 40 cases detected but all, as in 1984, rere inported frour neighbouring counEries south of the Sahara.

In Tunisla and !l!g all cases detected in 1983 and 1984 vere inported. In 1985, both :ountrlffireportea 6if,rnported cases, but Tunisia also recorded three cases of induced aalaria.

Cyprus, Jordan, Israel and Lebanon remalned free of indigenous malaria. The surveillance schenes in mos! of these countries (excluding Lebanon where activities are linlted) successfully prevented the re-establlshment of nalarla transmission despite the very large number of i.mported cases recorded.

In ngypt, there were 198 cases reported in 1983 compared with 423 cases in 1982. An i.ncrease of incidence eas reported fron lbfr-El-Sheikh governorate ln the central nort,hern part of the NiIe DeJ.ta, and in Fayoun governorate transnission continued to persist. ln 1984 and 1985, a very low incidence of rnalaria con8inued to be reported fron the whole country, with P. falciparun transuission remaining confi.ned to Fayoum governorale.

In Syria the number of nalaria cases steadlly decreased fron 2 200 i.n 1982 to 1300 in 1983, 840 in 1984, and 435 ln 1985 (all were P. vivax wlth the exceptlon of three loported infectlons). The record of 1985 was the lowest lncidence recorded slnce 1975. The improveoent in the epidenlologlcal sltuation has been attributed to the good spraying coverage and the use of pernethrln in areas where inhabltants refused malathion spraying. In July 1984, a focus developed io the Ghoute agricult,ural area near Damascus. A mass ulood survey yieldeo further caae6 in August and SepteDber; the total nunber of cases ln chls focus was 157. The caaes of 1985 were distributed as follows: 132 in the foci of ltalklya (north-eastern border) on the Tigrls river; 75 Lt Idleb; 41 in Lattakia; I29 near Damascus; 50 in Deraa. Renedial, measures were applied.

2.2 Asia west of India (Flg. 1)

The total populatlon ln this area was estimated in 1985 to be 222 mj-LJ-lon, of which 186 llve in orlginally oalarlous areas, while 15 nilllon people llve ln areas which have been freed from malarla, and 35 nllllon live ln areas with llnlted rlsk. About four nilllon people are not protected by epeciflc antlnalarla measures.

Bahraln, Kuwalt and Qatar continue to be free of indlgenous malaria.

Of other countrles ln this aree, Iraq, Iran, Onan, Pakistan, Saudi Arabia and the United Arab Enirates (UAE) have natlonwlde antinalaria activitles. The ancimalari.a actlvltles ln Afghaniatan, Yemen and Democratic Yemen do not cover all the population living ln originally nalarious areas. It should be re-enphasized,that southlrest Saudi Arabia, Yemen and Democratic Yemen have been dealt with in PART Ir [see also PREFACEof VOL. I of the present series] because thelr anophellne fauna partly belongs to the Afrotropical l(eglon. Slnce these chree countries form an integral part of the Arabian Peni.nsula regarded as a meetlng place of the Palearctic, Oriental and Afrotropical fauna, it is useful to cover then by an updated overvielr of the malaria sltuation from the available infornation comnunlcated to WHOin 1984-1985. In the overview of the malaria sltuation given below, countries are arranged according to their geographical Iocation starting fron the west and moving eastwardly.

ln @g, the nuuber of malaria cases steadily increased frorn 2400 1n 1983 to 3300 in 1984, and to 4800 in 19E5. l{alaria transmlssion continued in 1985 in four provinces in che Northern Region (Ninawa, Dehok, Sulainanyia aud Erbil)r especially in the old foci. In the other three reglons (Central, Central Euphrates, Southern) as well as in Al.-Tanin province in the Notthern Reglon, interruptlon of transmisslon ltas generally naintained. Nearly aLL 327 cases detected in these areas were imported.

1. Docuuent vBC/85.3 - MAP/85.3, pp. 2LL-24O. vBc/90. 1 MAL/90.1 Page 67.

In Saudl Arabia, the number of nalarla cases decreased frorn 18 000 in 1983 to 11 000 fn 198a1-5Fi.rrcrea-sed to 16 OOOln 1985. The Eastern and Northern provlnces and the A.slr plateau in the south, are consldered free from nalarla transolsslon. Also the I'{estern province is free from malaria transmission except for small resldual foci in the Hljaz of nountaln range. Ilowever, Dalaria ts stlll endemlc ln the foothlll and lowland areas the Tlhana Region (southwesE coastal plaln along the Red Sea), and about 75"4 of. the cases detected in 1985 orlglnated frou this area. Weekly larviciding wlth tenephos applied on a large scale could not prevent the occurrence of a ualaria outbreak ln the Glzan area durtng the rainy season. More than 10 000 cases nere recorded during January-April 1985, and remedial measures had to be applled to control the sltuatlon.

In Yenen, baseline dara collected fron the Tlhaua Reglon ln 1984-1985 indicated that nalarla-IT[ypoendeuic and unstable with focal distrlbution. Relatlvely high parasite rates and vector densities were observed during the cooler period of the year (Noverober-February). So far, sone 90 000 inhabitants are protected by residual house spraying and about 5000 by larvicldlng operations. Perlpheral malaria detection Posts have been established in oost of the health cenEres ln the Tlhana Region, and two ln the foothlll reglon and in the reglon of interuedlate altitude. These Posts provlde dlagnostlc servlces and treatment of cases and serve to oonltor the oalaria situation ln these regions.

In Democratic Yeoen, 1984 nas an exceptionally dry year and consequently the number of oalarla cases was Gp-aratlvely lou. Due to shortage of financial resources and trained manporrer, malarta control operatlons contlnued to be applled ln llnited areas of econooic lgportance and high ualarla endemlclty. Aoong the slx governorates, AJ. l'lahara has no antioalarlal activltles, and in Shabwa, the actlvltles are very llnlted. Malaria risk is uinlnal ln the narrow coastal belt, and is practlcally absent ln Aden clty, but prevalent ln the lnterior. In Socotora island nhere very high ualarla endeolclty prevalls, no antlnalarla Eeasures have been undertaken up to 1985. In areas under oPeratlonsr the actlvlties include residual house spraylng, larvlclding, source reduction on a limiEed scale, and disseglnatlon of local larvtvorous flsh (Aphanius dlsPar) lnto natural perennlal breedlng sites. Case detectLon is llnlted to Lahj, Ablyan and lladranut governorates, but reportlng by hospltals and health centres is deficient and many cases are diagnosed on cllnical grounds only.

hlgh prlority. The steady In the E, the antinalarla prograone contlnued to receive decllne fn ttre nuober of nalarla cases has continued. In 1984r there were 3500 cases compared wlth 23 000 ln 1978. Many of the cases were iaported as assoclated with the unrestrlcted lnflux of labourers from South Asian countries. Ilowever, with the declining job opportunLtles due to the saturatlon of the constructlon sectorr fewer people fron malarlous counlries have been entering the Enirates, and consequently the nuober of imported cases has started to decllne. Malarla survelllance is carried out through the network of prloary health care (PllC) centres. In 1985, 2600 cases ltere recorded, more than 75i( of whlch were iroported. Three quarters of the population are living in areas where oalarla risk has been practically eliminated. Local transmlssion occurs only in the northeastern part of the country. More than 951^of the population are procected through vector control by larvicidlng wtth tenephos.

In Oman, nalarla is constdered highly unstable in the foothill regions, unstable in the desErt-areas, and stable in the coastal areas. The nunber of oalaria cases decreased froo 35 000 in 1983 ro 23 0OO1n 1984, and likewise the slide positivity rate fell froro 2OZ to 9"A. The ouch reduced rainfall certalnly contrlbuted to this reduction, but there was also an added effect of an improvement in the imPleuentatlon of antimelaria activities wtth a larger proportion of the populatlon protected. Slnce 1981 all areas of the Capital Region have been protected by antllarval measures and nany of the cases detected seemed to have contracted the lnfectlon outside urban areas. Resldual house spraying carried out in several regions, generally, appears to have had little iupact on the malaria situation. On the other hand, larvlclding seems to have been effectlve in reducing oalaria prevalence in Batlnah, Sur-es-Salaan, and Sharkyla regions. Surveys based on adequate sample s_ize qases. few carried o.ri ir, 1983 and 1984 1n Dhofar Region did not reveal any oalaria A cases detected among outpatlents of health facillties aPPear to have been infected outside thls reglon. fn f985, .""" detectlon actlvlties (excluding surveys) dlscovered 14 000 cases.' The decrease ln the nuober of cases fron the 1984 level was observed in a1l areas includlng the coastal reglon where enhanced control operations are thought to be the naln contrlbuiing factor. Other factors have been the wldespread drought and lmprovements in housing and general socloecononic standard of the PoPulatlon. vBc/90. 1 MAL/90.1 Page 58

In lran, the nunber of ualarla cases decreased frorn 43 000 detected in 1983 to 31 000 recorded in 1984' of whlch 26 000 originated fron the attack phase areas compared with 42 OOOIn 1983. rn 1985, the number of cases furrher declined Eo 26 000 of which 21 000 were from the attack phase areas. Thls rnarked reduction was attributed to climatic condltlons and the tinely appllcation of spraying operatlons. In the areas where transmission is considered lnterrupted (consolidatlon phase areas wlth a population of 22 nlllion) the number of cases lncreased sllghtly fron 4100 ln 1983 to 4400 ln 1984, lncluding 2900 inported from Afghanlstan. The detection of several foci ln these areas demonstrates the risk arising fron the high number of irnported cases especially since these cases occur rnalnly in areas of dlfficult accessibility coupled wlth uncontrolled populatlon trovement. In 1985, the nuober of cases ln the consolidatlon phase areas further increased to 5600, including soroe4300 ioported fron Afghanistan. The increase in the nunber of inported cases led to Ehe occurrence of rnany new foci in these areas.

In Afghanistan, the number of malarla cases rose further to 119 000 (provlslonal) in 1983 conpared wlth 34 000 1n 1979. Despite dlfflcultles, antlnalaria actlvltles contlnued although on a much reduced scale. A great nalaria epldenlc broke out 1n 1983 in Jalalabad, Talogan, Laghnan and Kunar unlts. Linited mass drug prophylaxis lras carried out ln 1983 ln Khost, Jalalabad, Faryab, Faizabad, Khanabad and Pulkhumrl units (total populatlon 94 000). Only 33 perlpheral laboratorles functlon in 1983 out of 150 planned. In 1984, the nuober of malarla cases contlnued to rlse reaching 156 0OO (provlsional). Whereas in L979' 2.67" of the blood slldes collected were found posltive, ln 1984 this rate vas 282. The number of P. falciparun tnfectlons, although very low, rose from 272 In L983 to 391 ln 1984. Most of these seen to have orlglnated from border areas wlth Paklstan and Iran. The large epidenic that broke out in 1983 continued ln Jalalabad, Laghman and Talaguan. In 1985, the nalarla sttuation continued to deterlorate as the provisional nuober of cases reached 228 OO0, and the proportlon of positive blood slldes lncreased to 332. Itigh nalaria lncldence ltas reported from the followlng oalaria servlce units: Kunduz, Imarnsahlb, Taloquan, Falzabad, Laghman, Kunar, Jalalabad, and Ghazlbad. Desplte prevalllng condltLons, all antlmalarl.a actlvitles continued in 1985, although on a very much reduced sca1e.

In Pakistan, although the number of nalarla cases was lower ln 1983 than in 1982, epldenlologlcal lndtces showed no funprovement over the sLtuatlon in 1983. The number of bLood slides collecEed from fever cases dropped frou 3.3 olllion to 2.6 million, most of these coolng from actLve case detectlon. The contrlbutlon of the general health services to case detectlon was-rolnLnal, desplte the integratlon of malaria control wlthln Lhese services in PunJab and Slnd provlnces, where 8OX of. the population at risk live. The relatlve prevalence of P. falciparun lnfectlons increased fron l3Z ln 1981 to 3ZZ in 1983. The prevalence of thls parasite was 337 La Punjab and Slnd provinces , L6% in North-West Frontier province and 497"ln Baluchistan province (after belng 2O"ALn 1982). Monitorlng of the response of P. falciparun to chloroquine revealed signs of low-grade resistance ln at least three dGtricts;-"njab province.. Sheikhupura, Balhawalnayar and Jhang. In 1984, the number of nalaria cases reported rose to 74 000 fron 52 000 in 1982, which further lllustrates the general rlsing trend of lncidence in recent years. In fact, the proportlon of posltlve blood slides rose froo 0.45"1 in 1979 to Q.59i(, L.37", L.7"/" atd 27"Ln subsequent years reachlng 2.3% tn L984. Integratlon of malaria actlvlties to various degrees withln other health services was extended to each provlnce. However, cooPeratlon and coordlnation of the emerging PIIC system stlll reualns to be developed. In 1985' the number of nalaria caaes recorded from January-November nas 61 O0O, indicating that the rising trend has been halted. An improveuent in the particlpation of general health services in malaria survelllance has been noted particularly in the North-West Frontler and Baluchistan provlnces. However, the relatlve prevalence of P. falciparurp lnfections lncreased further, reaching 537(in Sind and 52i6 tn Baluchlstan. StraLns of P. falciparun resistant to chloroquine have already been detected in slx dlstricts in PunJab. Signs of lncreasing tolerance to chloroquine have also appeared in the North-Ilest Frontler Province. vBc/90.r lrAL/90.r Page 69 coNcLUSIoNS (SECTIoNr)

Great concern has been expressed by oany authors and in reglonal conferences about the substantial. increase of imported malaria in cont.inental Europe where malaria has been eradicated or dlsappeared. This increase has been cfosely associated with the increase i.n ai.r travel and novement of nigrant workers. The wldespread P. falciparuo drug resistance in Asla and its increasing distribution in troplcal Africa adds greater dinension to the problen. There is a consensus of opinion that measures against inportation of malari.a should prlnarily be directed to lntensifying health educatlon for travellers to malaria endenic areas for not only coroplylng wlth chenoprophyJ.axls but also to undertake personal Protectlon Deasures against mosquiLo bites. The collaboration of Eravel companies and Eourist agencies operating betlreen Europe and endemic areas should be fully exploited.

There are lndications Ehat the incidence of Eransfuslon malaria is grossly underestimated. As mi.croscopical diagnosls of infection j.n the blood of donors has proved dlfficult, use of serologica.L nethods (e.9., IFA test,) and the crlterla for accepting a donor have been recornmended. 0f other problens assoclated lrith lnported nalaria are the accidentally-induced infections. Two outbreaks of malarla auong drug addicts occurred in Italy and Spain 1n 1981 and 19E4 respectLvely, but later only a few cases were reported, the reason for such a decrease ls not understood. This may have been due to the efforts of the centres for addicts asslstance as in Italy. However, in USA where an epldenic of P. falclparun nalaria broke out anong drug addicts 1o the 1930fs and perslsted for nearly l9-years, no further cases ltere seen followlng the detectlon of qulnlne as a comnon dlluent or adulterant of confiscated heroln, (Dover 1971). This-does not seem to have been investigated Ln Europe. Other accldentally-lnduced malarla has been invarlably recorded aDong hospltal staff due to laxity ln taking the necessary precautions when drawlng blood sanples from patlents.

Followlng reports from France and Switzerland durlng the 1970's pointlng to inpllcat.ion of lnternatlonal alrports lu malarla transuiseion by lnported infective anophellne vectorg, attention has been directed to thle uode of transnission which previously had not been recognized. Thus, reports of "alrport malaria" subsequently followed in France, the Netherlands, Belgium, the UK and Spain. Of a total of 25 airport cases recorded during the period 1970-1986, 23 were P. falclparun, one P. vivax and one P. malarlae. The exact geographical orlg1n of P. falclparun canno! be deternined with certainty, but an African origin has often been assuqed when Ehe alrport concerned ls known to recelve planes fron tropical Africa. Coutraction of the infection from an infected vector on board an airplane originatlng fron a troplcal country as in Ehe case of the two British cltizens (see Table 3) should direct the atteDtion Eo this node of transmisslon that lDay occur fairly frequently but pass unrecognized. To counteract the inportatlon of lnfected vectors, disinsectlon of alrcraft according to l./HOinstructions has been re-emphaslzed, and as an additiooal Deasure residual spraying luggage tunnels and halls has been recomnended in France.

Some cases of P. falciparun ualarla whlch did not fit in any of the above mentloned categorles have renained inexpiicable or undetermlned (Gentllini & Danis, 1981). Local transmisslon by a potentlal vector of the An. macullpennls complex has been discounted on the basis of the avallable experiuental evidence polntlng to the refractoriness of An. atroparvus and An. labranchlae to exotlc stralns of P. falciparutr. Sooe views have suggested that the susceptlbllity of members of the an: r"*lipen"is- and other important speci'estoP.fa1c1Parulstrainsfroud1fferentregi6iffiG1nvestigated(Bettini et a1., L978 and tlHO, 1980b). This is supported by the fact that experiments in the USSR demonstrated the susceptlbility of An. subalpinus to Afrlcan stralns of P. falciparum, while An. sacharovi gave contradictory results-(OaSkova & Rasnicyn, 1982). lt woula also beusefu1tfthe8uscePt1bilityofAn.clav18ers.1.toexoticstrai'nsof3@'is re-investlgated (Curtis & White, 1984).

Inproving surveillance and re-enphasizing the importance of notification of nalarla cases ln contlnental Europe have been stressed. As nalaria has been forgotten for a long tiDe ln Europe, alerting the nedical profession to the need for microscoplcal blood exaulnatlon in febrlle cases has been repeatedly enphaslzed. Attention has also been drawn to the need for more elaborate parasitology teaching ln undergraduate nedical studies, and for organizing courses ln ualarlology for uedlcal officers and biologists. vBc/90. I r"tAll90.1 Page 70

In order to assist countries of Europe ln reportlng comparable lnforoatLon on lmported nalarla and related lnfectlonsr WHOis trylng to develop a standardized and homogenous foru of reporting in consultatlon wlth health authorities concerned (I{HO, 1987).

An overvlew of the malarla sltuation and nalarla control has been presented covering countries of the North African lledlterranean basin and those of the Eastern Mediterranean zone up to and lncluding Paklstan. Steady lmprovement of the malaria situatlon has been observed in Turkey since the epldenic of L976-L977. In the North African countries nalaria transmlsslon has been interrupted or has persisted ln snall focl. Varlable degrees of progress have been recorded ln other countries wlth natlonwide antimalaria activities. The norst situatlon has been observed in Afghanlstan aa can be exPected under the prevalling adverse conditlons. l,lalaria ls still endeoic i.n southwest Saudl Arabia despite large-scale malaria control operatlons, and ln Yemen and Southern Yemen where lirnited resources and tralned nanpower allowed ouly suall-scale antimalaria activitles. Surveillance and/or vector control actlvitles are applled ln countries originally free or freed of nalaria lransmlsslon namely Bahrain, Cyprus, Israel, Jordan, Kuwait and Qatar where inported cases contlnue to be recorded. vBc/90.1 !'ALl90.r Page 71

SECTIONII: VECTORDISTRIBUTION l. Species distribution

The distribution ranges of important anopheline species occurring in the geographical area under review are presented on a series of naps. Figs. 3(a &^b)a show the dlstributlon of nembers of the An. naculipennis couplex. Flg. llz illustrates the dlstrlbution of the two membersof the An. claviger group. Figs. 4-10r present the dlstribution of seven oEher species.

2. Vector dlstrtbutlon

It is well known that the abillty of a species to transmit malaria may vary throughout its distribution range. Therefore, it ls necessary to outline briefly here the areas where a species bas been known to be a vector with special euphasis on its vector status at the presen! tine, but more details will be given later in SECTIONSIII(A) & (B). lhowledge on vector status conpiled here ls partly taken fron Zahar (L974) supplenented with sone general information frou Service (1986) and more specific infornation from other rel.evant references.

2.1 }(ajor vectors

2.1.1 The An. naculipennis complex, Flgs. 3(a & b): An. oaculipennls s.s. aad [email protected]. extends lts distribution to northern lran where 1t acts a6 a vector (llotabar, Iabibzadeh & l4anouchehri, L974). An. aEroparvus and An. labranchiae are also regarded as Potential vectors in Europe. However, the ouEbreak of P. vivax ualarLa that occurred in Corslca, France in 1970-1971 should serve as a reolnaeffie possibility of reintroductlon of nalaria by An. labranchLae fron P. vlvax inported cases [see SECTIONI under France ln f.2.f(1) above]. WlEh regard to P. falciparum, experiuental evldence has so far shown that An. atroparvus and An. labranchiae are refractory Eo inported exotic strains of this parasite (see CONCLUSIONSof SBCTIONI, above). An. labranchiae is still regarded as the rnaln vector in North Africa (Algeria, llorocco and Tunlsia). It was recorded fron Trlpolitania in Llbya whtch seeDs to be Lts easternmost llnlt of distrlbution in North Africa (t4acdona1d, L982).

An. sacharovi, Flg. 3(b) ls a potentlal vector in southeastern Europe, but an important acllve vector in Turkey, Syria, Irag (northern regiou), and Iran (northwestern, centra1andsouthwesternareas).InIsrae1'@forner1yoneoftheoa1n vectors, disappeared fron 1960 to 1969, but subseguenEly reappeared and increased ln numbers in recent years. To preven! the reintroduclion of nalaria fron inported cases, and ln view of the reappearance of An. sacharovi, and the persistence of the former vectors:An.sergentii,@.P1ssand4L-s1avigg,continuedsurveillancehasbeen reconmended (Pener & Kitron,1985a). An. sacharovi and An. superpictus have been regarded as the najor vectors in Lebanon before the elluination of malaria transmission, (Granlccla 1953), but no recent inforuatlon on the present sltuation coul.d be traced.

I. Reproduced (with nodification) by perolssion of Dr V.N. Stegniy, and Dr W.W.M. Steiner (ed.) froro Fig. I in the article of Stegniy (1982). In: Recent Developnent ln the Genetics of Insect Disease Vectors. 2. Reproduced (with enlargement and some additions) by permission of Prof . I'1. Coluzzi, and Service des Publlcatlons de 1'ORSTOII, from the article of Coluzzi, Sacci {! Feliciangefi (1965) ln Cah. ORSTOII.s6r. Ent. n6d. Parasitol. 3. Reproduced fron a VBC document (I.JUO,1989a).' "Geographical dlstrlbution of arthropod-borne diseases and their principat vecEors." ChaPter l. l"ra.l.aria, prepared by Dr G.ts. Uhite. (The nap of An. sergentii has been reproduced here with nodification). /BCl90.r tALl90.L Page72

2.L.2 An. superplctus, Fig. 4: In the wide area of its dlstriburlon, ln. superpictus has been regarded as a vector in Turkey, Iraq, Syrla north of Saudl lrabiar lran, and in certain parts of Afghanistan and Pakistan. An. superpictus and {n. sergentii are found in association i.n Israel and Jordan where they are considered lotent.ial vectors and kept under vlgilance and control because of the threat of relntroduction of nalarla transmission as a result of an lnflux of lmported cases in both :ountries. Ao. is a potentlal vector in Cyprus as it has perslsted after nalaria has EG-Graafcatea"rtgp.S_ fron the island. In Lebanon, superpictus together with sacharovl had been regarded as [raJor vectors before nalarla transmisslon nas elininated as Ilentioned above.

2.1.3 An. sergentii, Fig. 5: ln the area of its dlstribution, An. sergentil acts as an inportant vector of malaria in the oases and the western desert and Faiyun province in Egypt, west and southwest Saudi Arabi.a, Yemen and Southern Yenen. Fornerly, lt had been regarded as an important vecEor ln Israel, Jordan and Llbya but now it stands as a Potential vector. It was the responsible vector in three southern governorates in Tunisia (Gafsa, GabEs and l'16d6nine). It disappeared as a result of aerlal spraying of insectlcides but reappeared later (tlernsdorfer, unpubllshed report to WHo, L973). lt exlsts ln snall foci in the southern oases of Algeria and Morocco. It extends lts existence to Canary Islands ln the Atlantic Ocean, but lt has never been recorded ln the northern Medlterranean area, with the exception of a slngle record frou Bulgarla, the - locality of whlch remalns unkaown (Senevet & Andarelll, 1956) [eee more details in SECTIONIII(A) under (t), 2 ln document VBC/90.2 -l'lAL/90.21. More recently, ir was newly recorded by DrAlessandro & Sacci (f967) who dlscovered the preaence of a populatlon of this species during an entomologlcal survey carried out ln conjunctlon wl.th an epldenlologlcal investigatton of tlro cases of ualaria regarded as indigenous in the lsland of Pantellerla, Slelly, Italy. The norphology of the larval speclmens exanlued sllghtly dlffered fron the typlcal An. sergentii.

2.L.4An.pharoens1s,F1g.6:A1thoughw1de1yd1str1buted,49:-P@-actsas an luPortant vector of malarla only 1n Egypt. Genetic and cytogenetlc studles showed that the form of An. pharoensis exlstlag in Egypt can be dlstlnguished fron other forns that occur in tropical Africa by the presence of an inverslon on the X-chrooosome, and it ls qore closely associated wlthman (see VOL. I, under 1.5, pp 6L-62).

2.L.5 An. fluviatllls, Fig. 7: Thls species has a wlde dlstribution range. In the Preaent geographical area, lt has been considered aa a vector 1n Iran and Pakistan. In Iran, it occuples the southern slopes and foothllls of the Zagros mountalns and is associated rrith An. superpictus and 4g:_g!g@!.. Both An. fluvlatilis and An. superpi.ctus Irere responslble for nai.ntaluing malarla transmlsslon j.n those areas in Iran despite house spraying, due to their exophlllc behaviour. In Pakistan, & fluviatllis is found ln the foothlll regions of the mountainous tracts i.n Ehe north. Although it is known to be a vector in the neighbouring countries of Iran and India, its role Ln malarLa transmission 1n Paklstan needs further study. llalaria was reported to be hypoendenic ln the area occupied by An. fluviatills 1n Paklstan.

2.L.6 An. pulcherrlmus, Flg. 8; It is also wldely distributed, but was only considered a vector of inportance only in Iraq and Afghanlstan. In Iraq, it was incrinlnated on epldenlological grounds as it was the only specles present durlng a nalaria outbreak in Kerbala provi.nce ln 1969. In Afghanistan, 1t was incriminated through the findlng of sporozolte-posltlve specimens in Kunduz area ln the north ln 1969 (Badawy, unpublished report to WHO,1970), and it has been regarded as the naln vector responslble for nalaria transuisslon after the cooplete disappearance of the former principal vector, An. superpictus for more than 15 years followlng the lnitial DDT nouse spraying.

2.L.7 An. stephensi, Flg. 9: It is an loportant vector over mueh of its d1stribut1onr5fl,especiat1yinandaroundurbanareas.Severalstudiessug8estedthat the tlto foros: An stephensi and its varlety An. stephensi mysorensis should be consldered as populattoo vlif3frffi vol.. r, under l.@ record of An. stephensl came frou outside the normal range of lts distrlbutlon (Gad, L967), as lt Idas reported fron Shoukeir locality area Ras Gharib south of the'Gulf of Suez, Egypt. As cited by Zahar (L974>, Dr P.F. l,lattlngly of the Brltish lluseum (Natural History) London, foundthatthenateria1resemb1ed@corradetti'butcons1dereditan aberrant forn of 4".--gg92!"""L. tfr'ere was no evldence of nalaria transmission Ln thls area whlch was pui under lntenslve oil larviclding. Ga

Recently, a mosqulto survey was conducted durlng 1981-1983 by Gad et al. (1987) i'n the Red Sea go1rlrnorate i.n Egypt (ttre Egyptian western coast of the Red Sea). Larvae of the species described by Gad (L967) as stephenst were collected frou the tyPe locality and from a siollar area 14 kro further norttr. llorphological studies showed that this specles is slnilar to Anopheles salbaii Maffl & Coluzzl. Biologleal, ecologi.cal and norphological find1ngsinalcffiquitospeclesisnot.stephensi,andnaybeanewspec1es. The authors lndlcated that studles deslgnatlng this new species w111 be publlshed later, and will provislonally be referred to as AnoPheles ainshansi.

[Ir nay be argued that the orlglnal stephensl was eradicat,ed under the effect of lntenslve larvicidLng operatlons hltherto instituted 1n the type locallty. Subsequently, no materlal could be obtalned frou thls focus for crossing experftnents with known stralns of srephensi to conflrm the ldentlty of this nosquito as suggested by Zahar (L974). It folfows that the new taxon now dlscovered ln the type locallty may have exlsted as an assoclating species, but for unknown reasons escaped the ldentlflcatlon and persisted ln the area defylng the actlon of larvlcldlng; a polnt whlch is very dlfficult to Prove or deny. When the full descrlptlon of the nelt taxon is published, the sltuatlon nay be clarified I .

2.1.8 An. cullclfacles complex, Fig. 10: An. cultcifacles s.1. is nuch more widely distributea an over oost ofTts range. Four oeobers of the An. culiclfactes complex: A, f, C ana O trave recently been identlfied cytogenetically (see vot. ffi|fl . In the present geographlcal area only species A and B have, so far, been identlfied ln Pakistan and species A in UAE and Onan. Unlike An. stePhensi, An. cullclfacles s.l. extends its exlstence to southnest Arabia namely in Yemenand Soutirern yenen-Jut not in southwest Saudt Arabla. In Yeoen and Southern Yemen, the - subspecles An. cullcifacies adenensls also exlsts (see PART I, docuoent VBC/85.3 MAP/85.3,p1ess.1.isan1nportan!vectoroverouchofits range.

2.I.9 The An. ganblae complex: The dlstribution of membersof the An. ganblae cooplex has been shown in PART I (docuuent vBC/84.6 - t4AP/84.3,PP. 69-75). It ls sufficlent to mention here that of oembers of this cooplex only An. arablensis occurs in soutlurest Saudi Arabia, Yenen and Southern Yenen where it acts as a najor vector of rcalaria particularly in the coastal plalns.

2.2 Secondary and suspected vectors

2.2.L An. claviger grouP, Flg. 11: In Europe, An. claviger s.1. had been regarded as a non-vecEor or at most a vector of olnor lmportance. In Turkey, it has also been consldered a vector of oinor importance and has llttle lnfluence on recePtivity to ryllli. in areas where transnlsslon has been lnterruPted (Postlglione, Tabanli & Raosdale, L972). In contrast, An. claviger s.1. has been regarded as an important vector in certain areas of rhe Ufadle EafiGfifccia (1956) polnted to the role of tui. claviger s.L. as a vector over a wlder area namely: Cyprus, Paiestlne, Lebanon, MesopotdlElEFJAzerbaidjan)and

ffiFb1ishedbeforeZu1uetaetal.(1968)po1ntedoutthat1nFaoMam1aha locallty, south of lraq, the breedlng places of An. stePhensi often have a very hlgh saltnlty'(equal to or hlgher than sea-water; see nore detailJ 1n VOL. I, under L.4-2' p. 49). uBc/90.1 lALl90.L Page 74

routhern ltaly. CoLuzzL, SaccE & Feliclangefi (1964) ldentified An. clavlger s.s. fron Larval sarnples collected in Palestlne, and lndlcated that lt ls most probably responslble for nalaria transmisslon ln certai.n areas of the Mlddle East due to the presence of tavourable envlronoental conditions which do not exist elsewhere. An. claviger s.l. was assoclated with an outbreak of P. vlvax malaria in Aleppo, Syrla rnl6TffiO, where no cther anophellne species exlste?ai?i-Zsporozoite-posltive specluens were detected out of 20 fenales dissected (lluir & Kellany, f975).

2.2.2 An. hyrcanus s.l.: The geographical- dlstributlon and the taxononic status has been re*rieiffil6l-i, under L.r. rn Turkey, An. sacharovl and An. hyrcanus s.l. occur in the Chukurova plain which occuples rnuch of the provlnces of Adana and Igel on the Medlterranean coaat. While An. sacharovi is the major vector of nalarla, the possible involvement of An. hyrcanus s.1. in nalaria outbreaks in this area could not be excluded (Post1g11one,Ti-b.''li&R"'sdale,1973).IntheKunduzarea'northernAfghanistan, An. hyrcanus s.1. was found with salivary gland infection ln 1969 (Badawy, unpublished report to WHo, 1970), and it is believed that it plays a role in oalarla transmissi.on early ln the season (!,tay-June), after whlch perlod An. pulcherrimus takes over to the end of the season (July-October).

2.2.3 An. dfthali: It ls a very abundant specles, widespread in eeni-arid reglons from the Atlantic coas! of North Afrlca to Baluchlstan and northrrestern Pakistan. South of the Sahara, lt is the dominant specles ln uany areas bordering the Red Sea and the Gulf of Aden, and it extends fron the Sudan coast through Ethiopla, southern Arabia doltn to Just north of Mogadishu (Glllies & De Meilloa, L96E). Unconfirmed observatlons were reported fron Soualla where one sporozolte-polsttve speclmen was detected out of 14 - females dissected (Rlshlkesh, 196l) [see PARTI, docunent VBC/85.3 - MAP/85.3, p. 89]. It was only in lran that sporozolte-positive speclnens of An. drthall were repeatedly detected durlng L965-L967 ln areas where oalarla transnlssG--was perslstlng. An. d'thalt !ta6r therefore, consldered a secondary vector in southern Iran (Manouchehrl, Ghlassediu & Shahgudlan, L972).

2.2.4 An. nultlcolor: A north Afrlcan specles which extends lts dlstrlbutlon eastetards to Pakistan. In Afrlca, lt extends up the Nile as far as the Sudan and also occurs on the Red Sea coast around Port Sudan (Gt1l1es & De llelllon, 1968). Although Klrkpatrick (1925) coneidered An. rnultlcolor a vector on epldeotologlcal grounds, thls species has never been shown t6ffifra-tural vector of ualaria in ugypt (Balawani & Shawarby, 1957). This eeeus to hol.d true despite the fact that lt ha6 been successfully infected experimentally ia Egypt. (see VOL. I, under 2.8.f). In Llbya, it was suspected to be a vector on epldentologlcal grounds (Goodwin & Paltrinlerl, 1959 and others) since it was found alone or associated with An. sergentli in southern oases where malari.a transuisslon persisted durlng the 1960ts. In Iran, a slngle fenale of An. nulEicoloE was detected during 1955 with ooly a gut lnfection, and the species has been regarded as a suspecled vector (Eshghy, L977).

CoNCLUSIONS(SECTTON rr)

The present geographical area which covers Europe and the l"lediterranean Region is rich in anopheline vector fauna. Of the subgenus Anopheles, uembers of the An. maculipennis complexarew1despreadinEuropeaodactasPotentialma]'ar1avectors'but49:@ acts as an important vector in Turkey and the !1lddle East, erhile An. uacullpennis is a 1oca1izedvectorinIran.otherspeciesofthesubgenusAnophe1es'49@'and An. hyrcanus are local.lzed secondary vectors in the lliddle East. The subgenus Cellia is represent,ed by An. culicifacies, An. drthali, 1!=g!!g complex, An. fluviatilis, 1$ multlcolor, An. pharoensis, 1[-pg}g$g!ry, 1!g,-g!1i_, An. stePhensi, and Arr.suPerP1ctus.Arr.cu1ic1factesand@i.arew1de1yd1str1butedintheea6tern part of the present geographical area and act as lmportant Ealarla vectora over most of thelr distrlbutlon ranges. An. sergentii ls an funportant vector in the oases of North Afrlca and Egypt. An. arablensls is the najor vector of malarla in Southweslern Arabian Penlnsula. ttre i.nc?Iiifi?Effif-ln. t'thall as a secondary vector waa coufirned only in Iran, while An. multicolor stlll remalns a suspected vector on epldeniological grounds.

ltlore details are glven on the vectorial status and local spatlal distrlbution of major, secondary and suspected vectors ln SECTIONIII(A): Document VBC/90.2 - I'1AL/9O.2and SECTIONIII(B); Docunent VBC/90.3 - MAt/90.3, to be issued later. gBc/,90.1 MAr/90.1 '75 Page

Fig.3 (a) Distribution of members of theAnopheles moculipennis complex

@ otroporvus e messeoe s labranchioe (IDbeklemishevi @ martinius @ maculipennis o subalpinus

Fig.3 (b) Detailed distribution of four membersof the Anopheles maculipennis complex

@ sacharovi @ otroporvus s 'mortiniuslobronchiae @ vBc/90.1 MAL/90.1 Page 76

(,l il !-:''-) el L^' .dl b'l +l :l 6l 3l HI ol :l OI €l

r! ol

(al3l Elsl .elu'l 9l

u

t{ ! vt a

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i.

q) r ./*r .1 i >... .; q) i _{Y

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Fig. 7. Distributiou of An. fluvlatilis

Fig. 8. Dlstrlbution of An. pulcherriuus

pulcherrimus ':.-' -J '' r' vBc/90.1 MAL/90.1 Page 79

Flg. 9. Distribution of An. stephensi

stephensi

Fig. 10. Distribution of An. culiclfacies

culicifacies ^t = I v-j

.-^f-.r it-! ttlllfilllltllfitttttrrr,i.. vBc/ 90.1 !{AL/ 90. 1 Page96

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ct q)

ct

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SELECTEDREFERENCES

VOLIJMEII: APPLIED FIELD STUDIES

SECTION I: AN OVERVIEWOF TIIE MALARIA SITUATION AND MALARIA CONTROLPROBLEMS

The references are arranged alphabetically under each oaln subject heading following the same sequence as in the text. References of L.2.1 (1) are arranged bY countrY in alphabetical order - those dealing with more than one country are placed first under GENERAL. References clted by authors are narked in the margin with c, and those not seen f.r ttre original are narked with an asterisk.

L. The European Reglon

1.1 Status of malarla eradication and control

Belios, G.D. (1976) - see under GRIECEbelow.

Bruce-Chwatr, L.J. & Zulueta, J. De (f980) Ttre Rise and Fall of Malaria in EuroPe. Oxford Unlverslty Press, London.

c Bruce-Ch\tatt, L.J. et al. (f975) - see under GREECEbelow.

Vlolakl, M., Avranldls, D. & Trichopoulou (1976) - see under GREECEbelow.

World Itealth Organlzatlon (1977) Imported Malarla.'Union of Soviet Socialist Republlc. Wkly Epldeu. Rec. 52 (No. 10): 95-97.

World Health Organlzatlon (1983) Synopsis of the World Malaria Sltuation in 1981. Wkly Epldeu. Rec. I (llo. 26):L97'L98.

1.2 Iuported malaria in contlnental EuroPe

1.2.1 Authorst vlews

GENERAL

Bruce-Chwatt, L.J. (1970) Inported malarla - a growlng world problen. Trans. R. Soc. Trop. Med. Ilyg. 652204'2O9.

Bruce-Chwatt, L.J. (L979) Man agai.nst malaria: conquest or defeat. Trans. R. Soc. Trop. t"ted.t{yg. 73:605-6f7.

Bruce-Chwatt, L.J. (f982) Inported nalarla: An unlnvited guest. Brit. Med. BulI. 38:174-185.

Postlgllone, M. (1974) Le plaludisne en Europe. In: Maladies lrans.issibles WHO/EURO, No. 3 Copenhagen.

Zuluet'a, J. De (1973) Malaria eradlcation in Europe: The achi.evernents and the dlfficulties ahead. J. TroP. Med. Hyg. 76:279-282-

BRTTATN (ltK)

Bruce-Chwatt, L.J. (f982) - see under L.z.L GENERALabove.

Bruce-Chwatt, L.J., Southgate, D.A. & Draper, C.C. (L974) Malarta in the United Klngdou. Br. !led. J. 2'.7O7'7L1.

Morgan, D. (1987) Malarla in forelgn vlsltors to Britaln. J. Trop. Med. Hyg. 90:3L9-323.

Philips-Iloward' P.A. et al. (1988) Malaria in Britain: L977-L986. Br. Med. J. .6/-.ar.<_t/,o vBc/ 90. 1 MAv90.1 Page 82

BI'LCARIA

Petrov' P. (L977) The probleu of lmportatlon of malaria into the Peoplers Republic of Bulgarla. Med. Parazlt, Moskva. !6268-7O. FRANCE

Anbroise-Thomas, P., Qull1cl, M. & Ranque, P. (L972) R6apparltlon du paludlsne in Corse. Int6r6t du d6pistage s6ro-6pld6niologique. 8u11. Soc. Path. Exoot. 65:533-542.

Bastln, R. & Charraot, G. (1980) Epid6nlologle du paludlsrne en France, et prophylaxie de cette parasitose. Nouvelle Press M6d. 9: 1003-1006.

B6gu6, P. et al. (1984) Paludisne autochtone i Plasnodluu nalariae chez un enfant. Presse M6d. 13:502.

8rltt, R.P. & llutchlnson, R.M. (1971) Case of Plasraodiuu falclparun contracted ln Southern Europe. Brit. Med. J. 2:206.

Bruce-Chwatt, L.J. (1971) Malarla in Southern Europe. Br. t'ied. J. 2:528.

BrunPt, L., Petlthory, J.C. & Glacordnl, T. (L978) Actualltd du paludLsme en France.

Cassaigne, R., Brualre, M. & L6ger, N. (1980) Paludlsne autochtone. Cent ans aprds Laveran: le paludisne i Paris. I. Les vlctLnes. Cah. ORSTOM.s6r. Ent. n6d. et Parasltol. L8 :L7 7-L79.

Chavanne, D. et af. (1979) Paludlsne autochtone. Nouvelle Presse M6d. 8:1352.

Delmont, J. et a1. (1980) Essai dr6valuatlon de la fr6quence du paludtsne importd en France. Cah. ORSTOM,s6r. Ent. n6d et Parasltol. 18:181-182.

Doby, J.U. E Gul.guen,C. (1981) - see under 1.2.1(11i).

Erccler, J.L. (f980) Paludlsoe cong6nltal i Plasnodiun vlvax. Cah. ORSTOM,s6r. Enr. n6d. et Parasltol. 18:182-184.

Gentllinl, M. & Danls, U. (1981) La paludlsme autochtone. M6d et Mal. Infect. LLz356-362.

Gentilini, l'1. et al. (1978) - see under L.2.1 (lil) below.

Genttllnl, M. et al. (1981) Inported malarla in a hospttal in Paris. Trans. R. Soc. Trop. Med& Hyg. 75:455-460,

Guillausseau, P.J. et al. (1980) Paludisne autochtoned Plasnodlun falciparun. Une nouvelle observation parlsienne. Nouvelle Presse M6e;T756=Z5Z-

Jeannel, D. et af. (1988) Le paludlsne drlmportation en France ln 1986. Bulletin 6pid6niologlque hebdonadalre, BEH No. 8/1988:29-31. Dlrectlon g6n6ra1e de la Sant6, France.

Morln, C. et af. (1980) Paludisne autochtone chez 1'enfant. Nouvelle Presse M6d. 9:L24L-L24L.

Rodhaln, F. & Charnot, G. (1982) Evaluatlon des risques de reprJ.se de transmisslon du paludisme en France. t16d. et Mal. Infect. L2:23L-235.

Sallou, P. (1978) - see also under 1.2.1(lli).

Sautet, J. & Qulllcl, M. (1971) A propos de quelques cas du paludLsoe autochtone contract6s en Flance pendant 1'€t6. Presse M6d. 792524. vBc/ 90 ' 1 MAL/90.1 Page F3

- Vernes, A. et al. (1978) Paludisne cong6nlEal i Plasnodiurn vlvax Un cas. Nouvelle Presse M6d. 7:1960.

World Health Organizatlon (1987) Malarla: France Wkly EPi4en- Rec. 52 No. 38z286-287](aaseaonBEHNo.23/1987,D1rec@i--Sant6,France).

GREECE

Bellos, G.D. (1975) From ualarla control to eradicatlon: Probleus, solutions. Archeta Ugleines, AthEnes. 27: 54-72.

Bruce-Chwatt, L.J. et al. (1975) Sero-epideniological survelllance of disappearlng nalaria ln Greece. J. Trop. Med. Hyg. 78:.194-2OO'

Volakl, M. Avramidls, D. & Trichopoulor(1976) Au sujet des cas de paludlsme inport6s en Grdce pendant la p6rlode de 1963 a f975. Archela Ugieines, Athdnes- 26:31-41.

HUNGARY

V{rnal, F.- & Bdnhegyl, D. (1986) Experlences wlth malarla prophylaxis. Ann. TroP. Med. ParasLt. 802279-283.

ITAIY

Bettlnl, S. et al. (1978) Rlce culture and Anopheles llabranchlae ln Central ltaly. tttroeographed document l[ro/MAL/7 8.897 - lftto/VBc/7 8.686.

c Coluzzl, A. (1965) Datl recentl sulla malarla Ln ltalla e prolerd connessl mantenlmento dei risultatl ragglurtl. Rlv. Malar. 442L53-L78.

Coluzzl, A. (1980) Eradlcazlone della ualarLa ln Italla e posslblllta dt rlPresa della transmlsslone. Glor. Mal. Infett. Parasslt. 32: 477i478- [With Engllsh suuoary].

CoLuzzL, A. & I-lonzall , C. (1979) Acuuento dl cast de malarla i.nportatl 1n ltalla. Parassitologla 2Lz64-65.

ln Oddo,'Iralla. F. & Plccardo, V. (1982) Lractuale sltuazlone epideuiologlca della ualaria Gior. Mal. infeti. Parassit. 34:1077-1081. [Wlth Engllsh sunmary].

oddo, F., onorl, E. & Gorlup, s. (1987) La ualaria oggl tn ltalla e nel oondo: problerol antichi e nuovl. [Malarla today In Italy and the world. 01d and new probleusl. pp. 347-388. In: Aspettl stortci e Sociali del1e Infezloni Malarlche in Sicllia e in ltalia. Atti del II seotnario di studi (Palermo ' 27-29 November 1986i. Centro Iraliano dl Storia Sanitarla e Ospltaliene, Slcllla' 1987.

NETIIERLANDS

Wetsteyn, J.C.F.U. & Ilegeus, A. (1985) Chloroqulne-resistant falciparum malarla lnported ln the Netherlands. Bull. Wld Hlth Org. 63:101-108.

PORTUGAL

Antunes, F. et al. (1987) Malaria ln Portugal. 81:56L-562.

Bruce-Chwatt, L.J. & Zulueta, J. de (L977> Malarla eradlcation in Portugal. Trans. R. Soc. TroP. lled. HYg. 7L:232-24O-

Caubournac, F.J.C. (1978) Serlous threat of relntroduction of endemic malarla ln Portugal. Revista Portuguesa de Doengas Infecclosas. 1:387-400.

SPAIN

Alvar, J. et al. (1985) Chloroguine-resistant falciparun rnelarla funported into Spaln fron Malawi. Trans. R. Soc. Trop. Med. Ityg. 79:4L9. vBc/ 90. 1 MAL/90.1 Page 84

Blazquez, J. (L982) Receptindad al paludlsao en Espafra. Rev. San. 1{1g. P6b. 56:683-691.

Blazquez, J. & Zulueta, J. de (f980) Ttre disappearance of Anophel-es labranchiae fron Spain. ParassLtologia 22:L6L-L63.

Fernandez Maruto, J., Lorenzo, A. & Blazquez, J. (1982) Situacl6n actual del paludlsno en Espafia. Rev. SSlqr-It19. !6b. 56:673-681.

USSR

Chagln, K.P. et al. (1975) Ihe probleo of ualarla lnportation to the USSRfron abroad. Medskaya Parazlt. 44: [In Russian wLth Engllsh sunnary]

Dashkova, N.G. et al. (1978) Characteristics of malaria imPortation fron abroad to Moscow (L974-L976) Medskaya Parazit. 47:105-109. IIn Russian]

Duhanlna, N.N. et al. (1979) Present problems of prevention of malaria ln USSR. Medskaya Parazlt. 48:3-10. IIn Russian with English sunnary].

Kuznetsov, R.L. & Neulmln, N.I. (1984) Present malaria situatlon Ln the world and the problens of nalarla irnported lnto the USSR. t'ledskaya Parazlt. No. 4:3-8. IIn Russlan wlth Engllsh sumroarY].

* c Serglev, P.G. (ed.) (1968) F{alarla. In Protozoan diseases. helminthiasesr arthroPods of medlcal lmportance and venomous anlmals.s. Vol.Vol . IX of I'lanual on nicrobiology, clinicaf aspects and epldenlology of lnfectlous diseases. ] Mediclna, l{oscow.

Soprunov, F.F. (f984) Urgent tasks ln the organlzatlon of the prevention of nalarla. Zurnal Mikrobtologll, Epideulologl . No. 7:45-50. [In Russian

1.2.1 (11) Induced ualarla

c Aobrolse-Thomas, P., Garln, J.P. & I(len Truong, T. (197f) Int6r6t de lrlnmunofluorescence dans le d6plstage et lr6tude 6pld6nlologique des paludlsmes hunalns. BuIl. l{1d Hlth Org. 442699'706.

Bastin, R. et al. (1979) Transmisslon Par la seryngue de paludisne i Plasoodlun falciparum chez un hdroinonane. Nouvelle Presse M6d. 8:699-700.

Biirsch, G. et al. (1982) llalaria transmission from Patient to nurse. Lancet (ti):1212-

Bruce-Chwatt, L.J. (L972> Blood traosfusion and tropleal disease. TroP. Dis. Bull. 69t825'862.

Bruce-Ctrwatt, L.J. (1974) Transfuslon oalarla. 8u11. W1d ltlth 0rg. 5O2337-346.

Bruce-Chwatt, L.J. (1982) - see under 1.2.1 CENERALabove

c Bruce-Chwatt, L.J. et al. (1972) Sero-epidenlologlcal studles on populatlon groups prevlously exposed to oalarla. Lancet (1):5f2-514.

i la * c Brumpt,-pathologle L.C. (1949) Paludlsne autochtone ou paludisne accidentel. Contribution par la serlngue. Bull . l,!6o. Soc. l{6d. tt6p. Paris 65:392-397.

c Deroff, P. et al. (1982) Ddpistage des donneurs de sang suscePtlbles de transolttre P. 25:3- -falciparum. Rev. Fr. Transfus. Iomunohematol.

Dover, A.S. (1971) Quinlne as drug adulterant and malaria transElsslon. J. An. Med. Ass. 21.8:1830-1831.

Druilhe, P. et a1. (1980) Deux cas dfinfectlon humalne accidentelle par Plasuodluu cynonolgi bastlanellll. Etude clinlque et s6rologlque. Ann. Soc. belge M6d. troP. 50:349-354. vBc/90 .1 I'IAL/ 90. l Page g5 .

GodzaLez Garcl.a, J.J. et af (1985) An outbreak of Plasoodlun vtvax ualarla auong heroln users ln Spaln. Trans. R. Soc. Trop. Med. Ilyg. 80:549-552.

Hxsslg, A. (1987) (Edltor) Whlch are the approprlate uodlflcatlons of existlng regulatlons deslgned to prevent the traneolgston of ualarla by blood transfuslont ln vlew of the lncreaslng frequeocy of travel to endemlc areas? !ryggttnl"_' 52:138-148.

Orlando, G. et al. (1982) An outbreak of Plasnodlun f"f"lfgg* ualarla amoog drug-addlcts. Revta. rb6r. Parastc. ffi

Panaltescu, D. & Fllottl, P. (1980) Aspects 6pld6olologlques de 1'lnfection i P. ualarlae dans la phase drentretlen de lt6radlcatlon du paludlsue en Rouoanle GonnGG-rron non pr6sent6e). Cah. ORSTOM,s6r. Ent. u6d. et Parasltol. 18:185-186.

Past.lcier, A. (1974) Paludlsue autochtone. ProblEues dlagnostiques. Bu1l. Soc. Path. Exot.67:57-64.

Petlthory, J. & Lebeau, G. (L977> Contaulnatloo probable de laboratolre Par Plasuodluo falclparuu. Bull. Soc. Path. Exot. 7Oz37L-375.

Ranque, J., Faug6re, B. & Scoffler, J. (f980) Le paludlsue post-transfuslonuel en France. Epld6uologle et prophylaxte. Cah, ORSTOII.s6r. Ent. o6d. et Parasitol. 18: 184-185.

Saleun, J.-P. et al. (198f) Paludlsoe transfuslounel en Frauce de 1950 a 1979. Nouv. Pres. Med. 10:981-984.

Saleun, J.-P. et.al. (1987) Paludlsoe Poat-transfuslonnel. Donn6es statlstlques partlellee. Approche prophylactlque par le d6plstage des donueurs de sang i rlsque. Ann. Parasltol. HuE. Coup. 6229-L5.

c Sulzer, A. & tfllson, l.t. (1972) fire lndlrect fluorescent aotlbody Eest for the detectloa of occult ualarla la blood donors. 8u11. Wld Hlth 0rg. 452375-379.

World ltealth Orgaulzatlon (1963) Terulnology of Malarla and of Malarla Eradlcatlon. Report of a draftlng Coultt

Zuber, C. & Eolzer, B. (1986) PaludlsDe-transmlgslon lnhabltuelle. Bulletln des Bundesuates fUr Gesundhettswesen No. 4:18.

1.2.1 (111) Malarla assoclated wlrh alrports

Bentata-Pessayre, l.[. et al. (1978) Paludlsue autochtone et fole palustre. A propos drune observatlon. Bull. Soc. Path. Exot. 7L:4L7-423.

Boletfn Mlcroblol6gico Seolnal (1985) Inforuacl6o del BMS:Nota lnforuatlva sobre un caso atlclpo de paludlsno. BMS4/85:l- (Centro Natlonal de Mlcrobiologla, Vlrologla e Lomunologla Sanctarlas).

Cassalgne, R., Bruaire, M. & L6ger, N. (1980) - see under L.z.L (i) - FRANCE.

Chauvagnat, S.C., Masslp, P. & Aroengaad, M. (f979) Actuallc6 du paludlsoe aut.ochtone i Plaeoodluo falclparuo: i propos d'une observatlon. R6v. M6d. Toulouse 15:369.

Cololgnler, ll. et al. (1978) Paludlsue concract6 en France. Nouvelle Presse M6d. 7:1855.

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Al.lNEX 1

CORRIGENDTJMTO VOL.

Page

1l Place the reference of Eruce-Chwattr L.J., Garrett-Jones, C. & Weitz, B. (1966) after the reference of Bruce-Chwatt' L.J. & Gockel, C.W. (1960)

L6 Authors and copywrlght should read Authors and copyrlsht.

r8 Llst of nanea under VBC: Dr G. Quelenec should read Dr G. Qu6lennec.

151 3rd paragraph, 2nd l1ne: TadJlh ehould read TadJlk.

203 Last l1ae: Parassltologlca should read@.@..

2L4 2nd line; The reference of Zulueta, J. de et al. (f951 should be placed at the end of the reference llst of 2.6.3 An. stephensl ln p. 216.