Filariasis research annual report 1952
Item Type monograph
Publisher East Africa High Commission
Download date 26/09/2021 08:03:59
Link to Item http://hdl.handle.net/1834/35518 EAST AFRICA HIGH COMMISSION
FILARIASIS RESEARCH ANNUAL REPO T 1952
.: . ~ , '. 1953 PRINTED BY THE HIGH COMM:lSSION PRINTER, NAIROBI FILARIASIS RESEARCH UNIT ANNUAL REPORT No.4, 1952 SECTION I-GENERAL lntrodnctor:y Note Due to the long waiting period before publication of articles in medical and scientific journals, the earlier Annual Reports of this Department have been detailed in presentation. As a result, such Reports could only be made available to a small proportion of interested workers. Accordingly in this publication a return is made to the more usual method of presentation, a summary being given of work done, with detailed sectional reports submitted for publication in scientific journals.
Aims Prior to World War II it was thought that, with the exception of the South Pacific area, the filarial infections of the torrid zones were of secoudary import ance, and that no effective remedies were available. The experience of the Allies at war was such, however,' that by 1947 the pendulum of medical thought had swung to the other extrem~, to the view that the filarial infections are of primary importance. Also, as the result of much research, there had become available preparations claimed to be effective against the filarial infections. This change of view was responsible for tbe establishment of the Filariasis Research Unit, created in 1949 as a High Commission Service to investigate the problems of filariasis in East Africa. There are three such iufections found in this area, namely, filariasis bancrofti, onchocerciasis and .acanthocheilonemiasis; we have not studied this last-named infection in any detail, as this work had been undertaken by the Liverpool School of Tropical Medicine. Work was planned from three aspects- first: to establish the relative importance of the filarial infections by determining the incidence and by establishing the effect on the infected individual; second; to investigate methods of control, aimed at the vector, or at the reservoir., or at both; third: to investigate methods of treatment.
Accommodation The Research project has its headquarters at Mwanza on Lake Victoria. The European housing is complete and the laboratory is now almost ready for occupation.
Staff Director: Lt.-Col. W. Laurie, DB.O., M.D., T.D.D., LM.S. (Retd,). Physicians: P. Jordan, M.B., B.S., D.T.M. & H. One vacancy. Helminthologist: One yacancy. Entomologist: A. Smitll, B.Se., Ph.D. Lahoratory Technicians: R. Rhodes-Jones, W. Edwards, R. C. Young. Photographer: Vacant. Librarian: Vacant. 2
SECTION 1-BANCROFTIAN FILARIASIS IN EAST AFRICA (1) Southern Highlands Pro In this Pro'vince particular Introductory cerciasis being present as wen previously been reported as a The two important late manifestations of bancroftian filariasis are hydro Province. In this search tbe spec coele and elephantiasis. The incidence of such late manifestations varies con administration was utilized as ou siderably from area to area, e.g. elephantiasis is common in the South Pac.ific, whereas hydrocoele is uncommon. Another complication, hitherto recognized only (a) Location and geography in the South Pacific area, is "mumu", defiued as "an acute recurrent condition The Province is bounded t< associated with lymphangitis of an extremity, with funiculitis and epididymo by the Central and Western ] establi~hed orchitis or both". This is a sensitisation phenomenon and is withiu boundary) and in the soutb it a few weeks in the majority of individuals exp'Osed to infection. It was this Lake Nyasa. condition which produced 25 per ceut casualties in the American South Pacific Force in World War 11. The Provinc;e is roughly tl angle bein~ formed by the nort Any disease which is capable of affectiug large nnmbers of the population Highlands extending from Iring and which early produces attacks of crippling fever, etc. must be regarded as a area at the northern tip of Lak serious medical and economic problem. This general consideration is reinforced and finally the low-lying area in the case of bancroftian filariasis by the fact tbat elephantiasis is a common The central part of the triangle late manifestation. of tsetse-infested bushland to th River in the east. If this were the picture 01' East African filariasis bancrCF/ti there could be no two opinions as to its seriousness. But as has been pointed out in ewier reports, we consider tllat tbe South Pacific disease is quite different from (b) Climate that found in East Africa. Here mumu is very rare, if it occurs at all; and hydro The climatic conditions e) coele is a much COITunoner late complication than is elephantiasis. graphical features outlined abc a year and in parts receive as north of Lake Nyasa has the g Field Surveys this gradually decreases towards The first essential in investigating the importance of filariasis is to establish 40 inches. The central area reo accurately the inCIdence of such infections through the whole of East Africa; this towards the east. the methods of work have been describ::d in detail in our 1951 Report. Here it need only be said ithat the work is difficult and that progress is slow, largely due Temperatures again rougr to the cutting down of the field staff and to bad communications, which allow temperature of less than 50·P. of work being carried out only for about eight months per annum. The Tanga in most places of 75°F. to 80 nyika Survey is almost complete, and survey work has begun in' Kenya. temperatures. The are This 1952 Report gives details of findings in the Southern and Southern Highlands The vegetation consists mai Provinces. Other results are not yet ready for pnblication. The work throughout has been the responsibility of Dr. P. Jordan of this Department. (c) Results Bancroftian filariasis.-Th It is hoped later to publish fuller details showing the close association of the clinical findings are shown bancroftian filariasis with high temperatures and high humidity. ~. '. !. 3 ,SIS IN EAST AFRICA (1) Southern Highlands Province In this Pro'vince particular attention was paid to the possibility of oncho cerciasis being present as wen as other filarial infections; onchocercias,is had previously been reported as a rare occurrence in two isolated areas in this lancroftian filariasis are hydro' Province. In this search the specific reaction of onchocerciasis patients to hetrazan late manifestations varies con admin.istration was utilized as one diagnostic method. common in the South Pacific, ication, hitherto recognized only (a) Location and geography , "an acute reCllrrent condition vith funiculitis and epididymo The Province is bounded to the east by the Southern Province, to the north ~enon and is establi~hed within by the Central and Western Provinces (the latter also forming the western DoSed to infection. It was this boundary) and in the south it borders on Northern Rhodesia, Nyasaland and Lake Nyasa. in the American South Pacific The Province is roughly triangular in shape, the southern apex of the tri rge numbers of the population aUgle being, formed by the northern end of Lake Nyasa, the eastern side by the rer, etc. must be regarded as a Highlands extending from Iringa to the lake and the west side by the low-lying lera] consideration is reinforced area at the northern tip of Lake Nyasa, the Poroto Mountains south of Mbeya, that elephantiasis is a common and finally the low-lying area round Lake Rukwa together with the lake itself. The central part of the triangle is mainly undeveloped, consi~ting of large areas of tsetse-infested bushland to the west and the low-lying valley of the great Ruaha ltiasis bancrofti there could be River in the east. las been pointed out in earlier isease is quite different from (b) Climate e, if it occurs at all; and hydro The climatic conditions experienced in the area are governed by the geo ,n is elephantiasis. graphical features outlined above. The Highlands average 50 to 60 in, of rain a year and in parts receive as much as 80 in. or more. The area immediately north of Lake Nyasa has the greatest rainfall in the Territory, with over 100 in., this..gradually decreases towards the Lake Rukwa area, which averages only 30 to :ance of filariasis is to establish 40 inches. The central area receives 30 to 40 in. in the west but rather less than Igh the whole of East Africa; this towards the east. ' IiI in our 1951 Report. Here it Jat progress is slow, largely due Temperatures again roughly foHow the contours, there being a mJnlmum i communications, which allow temperature of less than 50°F. round most of the high ground, with a maximum nonths per annum, The Tanga in most places of 75°F. to 80 OF., though the higher areas have still lower 'k has begun in' Kenya. temperatures.. The area', at the northern end of Lake Nyasa has a minimum tem perature of between 65°F. to 70°F. The maximum temperature ranges are from of the following Tanganyika 75 oF. to 80°F. over most of the high ground, with slightly lower temperature ranges in some places, The lower areas round Lake Nyasa and Rnkwa and most of the central area have a maximum temperature of over 80°F. The population of the Province varies with the geographical features-the Highlands supporting a moderately dense population, while the area north of Lake Nyasa is one of the most densely populated areas in the Territory, As mentioned above, most of the central area is uninhabited. outhern and Southern Highlands The vegetation consists mainly of varying combinations of grass and woodland. ,blication. The work throughout this Department. (c) Results Bancroftian filariasis.-The results of the blood examinations together with howiug the close association of the clinical findings are shown in Table No. 1. d high humidity, .. 4 Onchocerciasis.-Five hun ,~ '" '":::l :::l presence of nodules on their "o C C g fast flowing streams provided a .~ .; ~ "0 ""0 were found. ~ c: .5 ] "6 C: C: c . c c . i P cd cc ~ I 2:.~'~s .b.g .b.g ~.2 .Du .Du Three hundred and thirty! ~~ "'$ .Dc .Dc 0._ p.5 0._ hetrazan per kg, body weight, I P:: .:i:; &:: their skin 2 to 8 hours after the > --:::----j-_.. _---- 0: pruritus associated by Laurie ( ::: ~~ I .§§ . i3'" patients. ;;: ..J~(C 8~~X 0: .~~ w ..... ~ ~~E I :::=~.-= ~~·Er-.~ ~ :<:;;: I z,,,,Z -,.. " .-' "1:-:,"" 5 On.cnocerciasis.-Five hundred and eighty-six males were examined for the presence of nodules on their trunk, chest, neck and arms in the areas where fast flowing streams provided a potential place for Simulium breeding. No nodules were found. Three hundred and thirty of the above were also given approximately 3 mgms. hetra.zan per kg. body weight, but although some complained of irritation of their skin 2 to 8 hours after the drug, none experienced the immediate and intense pruritus associated by Laurie (1951) with the giving of hetrazan to onchocerciasis patients. Peters (personal communication) working at Njombe has performed. skin snips on six blind persons, none of whom showed nodules, with a negative result in each case. (d) Discussion. -0"-000 Bancro/tian filariasis. -It WIll be seen that WIth two exceptions bancroftian \f filariasis does not occur in the Southern Highlands Province of Tanganyika. Of the area in which it has been found, that at the northern end of Lake Nyasa was known previously, being reported by Hawking (1940) and fully described by Trant (1949). The present survey, however, has helped to' localize it, since Hawking (194D) reported an incidence of (?) 10 per cent as far north as Tukuyu, whereas our findings show that at Masoko, about half way between the lake and Tukuyu, filariasis does not exist, and the finding of two blood infections at K~ira 16 'miles north of Tukuyu is probably due to non-indigenous infections being encountered. It is considered likely that the Lake ;Nyasa focus is limited to a radius of about 16 miles from the lake, where the foothills of the Poroto Mountains are encountered It was unfortunate that at Lusungo, on the lake shore, the population were unco-operative and no random sample was obtained for the determination of incidence of clinical conditions. Thi:;:, area of filarial infection localized, as it is likely to be, to a small area round the head of Lake Nyasa is suitably situated for attempts at eradication by either wide-spread hetrazan administration, extensive use of insecticides or a combination of both. QlrlOlrlV< oor-ooQOOO ~6IAd.6 r---r-r-oo~ The second endemic focus appears not to have been described in Hawking's review of filariasis in Tanganyika (1940). It will be seen that the 1llarial rate in adult males at Kimande in Iringa district is 24 per cent. This village is situated in the valley of the great Ruaha River, near an extensive swamp area and about 40 miles north-north-west of Iringa. The extent of this focus is not known at present but will be investigated in further surveys. At Rujewa (Mbeya district) a filarial incidence of 4 per cent was found. This village is at the south-west extremity of the great Ruaha Valley, and the finding of filariasis here suggests that the infection extends down the valley from Kimande, 6 The high hydrocoele and elephantiasis rates found at Lugarawa in Njombe (2) Filariasis in the Southeli district c.re somewhat o-f a surprise. Although the persons were questioned as to The survey described he; previous residence elsewhere, they maintained that they had only lived in July, and was completed in No, Lugarawa. This may indicate a focns of some other infection causing hydrocoele. In this respect it is of interest to note also that a case of elephantiasis was seen METHODS 1S well. The Province is divided of these was visited, and a vilh villages were selected at rand· The finding of two cases of infection with A. perstans at Kibau probably was impossible to select a viI represents infection in non-indigenous Africans who may have come from the munity of about 1,000 person: heavily infected A. persIans area in the neighbouring Province. very few and far between in numbers of bloods obtained in In any case this low incidence is unlikely to be of any importance. The administrative authori visit and to help to allay thl (e) Onchocerciasis strange European, "out for blo Although some hundreds of persons were examined, no evidence of nodule backward community. When p formation was found. the people to come at night, a blood specimens were taken to The necessity for taking the b Pup ; ~ 7 found at Lugarawa in Njombe (2) Filariasis in the Southern Province of Tanganyika Territory . persons were questioned as to The survey described here was started during the months of June and that ~hey had only lived in July, and was completed in November, 1952. er infection causing hydrocoele. METHODS t case of elephantiasis was seen The Province is divided administratively into a number of districts. Each of these was visited, and a village in each geographical region was surveyed. The villages were selected at random by the local authorities, but in some cases it A. perstans at Kibau probably was impossible to select a village having sufficient numbers of people. A com who may have come from the munity of about 1,000 persons is considered ideal, but viHages of this size are ring Province. very few and far between in this sparsely popuLated province-hence the low numbers of bloods obtained in some places. be of any importance. The administrative authorities were asked to assist with propaganda for our visit and to help to allay the fears and snspicions that the appearance of a strange European, "out for blood", at night, inevitably produces amongst such a ~amined, no evidence of nodule backward community. When possible, a film show was put on in order to entice the people to come at night, a drop of blood being the price of admission. Night blood specimens were taken to determine the incidence of W. ban.emjti infection. The necessity for taking the bloods during the hours of darkness prevented our 'ornbe and Lugarawa in Njombe getting the same co-operation from the Africans as ;would have been 'en identified by McMahon as given us if we had been able to work by day, since oUr ns of the Poroto Mountains in type of work is naturally under suspicion of being some fprm of witchcraft, ached to rocks in fast flowing only volunteers could be examined and bled. Such a method, leaves much to be desired statistically, but under the circumstances little more could be done unless considerable time was to be devoted to each village. It must also be borne in mind that the prese.nce of lion and other wild beasts presented very real :iasis in an area where S. ntevei dangers to those travelling at night, and the very scattered arrangement of many 940) may be accounted for by vinages did not make the task of attracting people easier. 'e the altitude limit originally When our visit was being publicized by the administration, no mention was hocerciasis. The temperature at macie of hydrocoeles. The people were told that eJephanti.asis was being investi ~ of development of the larval gated and that this disease is spread by a mosquito wlUch introduces a small worm into the skin and that later the person may develop the disease. A suitable story was told in the simplest terms of the nature of the disease, and the aims and objects of our work were described, nevertheless, in spite of much hard work of this accessible only with difficulty nature, it is unlikely that the people understood what was happening. The chief 'e been found at Njornbe itself who told his people we were inoculating them against the disease prodnced evei and S. damnosum. have a more people than would have come with hours of persuasion! possible, therefore, that small Bloods were taken from as many people as possible after 8 p'.m. Bloods ly be found in the hills rou.nd {rom two persons were taken on each numbered slide, the number, sex and approximate age of all persons being noted. Legs were examined for elephantiasis, and scrota for evidence of filarial disease. Since no mention had previously been made of the scrotal inspection (which is usnally carried aLIt amid uproarious is supported by the work of laughter), it is considered that the results are not unduly biased in spite of the lusage" forms of Mj. volvulus non-random sample. HydrocoeJes are not generally associated with elephantiasis direct flight muscles and thus by the people. u this it is suggested that the range o{ the vector. The bloods were dried overnight, stained with hrematoxylin and eosin within the next few days and examined for microfilarire of W. banaojti and A. perstans in the laboratory by trained African laboratory assistants working under the lroughout the Province, and it direct supervision of the writer. Each slide was examined by twO' such Africans been found lit is of no very independently and the two results compared. If the results differed greatly, the g Simulium is probably more slide was examined by the writer, who also examined 10 per cent of all the negativecS. The number of microfilarire Were counted. 8 Since the sample of population varied in the' villages-in some cases adult The inhabitants of this P males only; in other males and females, but no children; in yet others many recently they travelled little. chiLdren-and since it is recognized that the micro·filarial rate varies with sex groundnuts, and the addition~ and age, the microfilarial rate of a village is defined as the incidence of micro to travel much more than was I filarire of W. bancrofti found in the blood of adult males (over the age of 16). Since only one blood specimen was taken from each individual at a time several RESULTS hours before the microfilarial peak, it is considered that many cases of micro The accompanying table filarremia were missed. The microfilarial rates as given in the table are there microfilarial incidence of W. , fore almost certain to be below the true rates of the villages concerned. and adult females are given, microfilarial rates are calcuh: The number of microfilarire counted in the blood sample gives some idea filariasis-the clinical rates ar of the microfilarial density per thick drop of blood (approximately 30 cmm.). for A. perstans infection. Since the bloods are taken over a period of time when the microfilarial counts are rising, such a method is considered to give a reasonably accurate indication The "filarial raie" JepreS I of the density of microfilarire. microfilarremia or clinical fila! Climatic data are also giv' LOCATION The Southern Province borders on Portuguese East Africa to the south; to DISCUSSION the east it is bounded by the Indian Ocean, and to the west by Lake Nyasa. To Hawking (1940) producel the north-west lies the Central Province of the Territory. of filariasis in the territory. other investigators, and in all Topographically the area consists of a coastal plain with a rising hinterland of bancroftial filariasis was intersected by a number of rivers. Heights vary from sea level in the east to slides-thus no accurate estirn: 9,000 ft. in the west.' be made. The area with a cs.: both for W. bancrofti and A. CLIMATE the great variation of inciden that a high incidence is found The Indian Ocean, with the north-east and south-west monsoons on the one decreases, except in the rive hand, and the mountains in the west on the other hand, determine the climatic (Kilamarondo). Generally Spl condition~ in the Province. The r.astern half of the area has an average of 30 to mean vapour pressure, a low( 40 in. of rain a year, the western half a little more than this, with the extreme west averaging b.etween 50 and 60 inches. Throughout the Province, the rain The highest incidence wa: falls mainly bet~een November and March. The maximum temperature in the (in adult males) of over 70 p eastern half of the area is over 85 e F., whereas in the west it is slightly lower than that in a highly endemic filar this (SO°P, to S5°F.) apart from the mountainous region where the temperature lation are infected. In this vilJ is lower still. ' correct when it is remembered before the generally accepted In the cool s'eason, the narrow coastal belts have an average of over 70°F., would almost certainly be fOl while over the rest of the eastern half of the Province the temperature is between infection was found to be Vel 65°P. and 70°F. In the west the temperature is lower, except for the shore of Lake Nyasa (65 e F. to 70 e p.) and the mountains (55°F. to 60° F.). High rates were also reel dence was found. Although t The isopleths run north-south. At the coast the mean annual vapour pressure 2,000 ft. escarpment, where c is in the region of 26 millibars and it diminishes steadily further inland to abollt of the district. 18 rnillibars half way across the Province. This is the recording for the rest of the Province, willi some slight reduction in the high ground. Mikindani district covers the River Ruvuma. The high VEGETATION coast, 54 per cent a shOlt dis A coco-nut belt on the coast gives way to woodlands and wooded grasslands ln Newala and Nasasi di further inland. The area on the whole is dry and waterless except during the at the'coast. These districts 1 rains, as drainage is facilitated by porous soils. peratures than places nearer t POPULATION lower. This Province is one of the least populated in the territory, principally In Tunduru district it is ~ owing to large tracts of waterless country and the tsetse fly. The coastal belt and reached. No bancroftial disea the Rumuva River area in the south are well populated. and very little at Npelembe, 50 ;.. :~l ';' ,.. " 9 ae villages-in some cases adult The inhabitants of this Province belong to many different tribes, and until 10 children; in yet others many recently they travelled little. The development of the area, particularly for llcrofilarial rate varies with sex groundnuts, and the additional transport facilities available, enable the Africans fined as the incidence of micro to travel much more than was possible previously. dult males (over the age of 16). each individual at a time several RESULTS ered that many cases ':If micro The accompanying table summarizes the results of the village surveys. The IS given in the table are there microfilarial incidence of W. bancrofti and A. perslans for children, adult males . the villages concerned. and adult females are given, together with the clinical rates. The bancroftial microfilarial rates are calcUlated for the number of persons free of clinicat , blood sample gives some idea filariasis-the clinical rates are determined for adults examined as are the rates load (approximately 30 cmm.). for A. perstans infection. Je when the microfilarial counts a reasonably accurate indication The "filarial rate" represents the number of adults-male or female-with microfilanemia or clinical filariasis in the population examined. Climatic data are also given for each village. :se East Africa to the south; to DISCUSSION to the west by Lake Nyasa. To Hawking (1940) produced a map of Tanganyika showing the distribution Territory. of filariasis in the territory. His paper was based principally on the work of other investigators, and in all reports from the Southern Province the occurrence 11 plain with a rising hinterland of bancroftial filariasis was demonstrated by the examination of day blood from sea level in the east to slides-thus no accurate estimate of the incidence of the bancroftial disease could be made. The area with a calculated incidence of 5 per cent' or more is shown both for W. bancrofti and A. perstans infection. The present tepDrt demonstrates the great variation of incidence throughout the endemic filarial area. It is seen that a high incidence is found at the coast and for some way inland but gradually outh-west monsoons on the one decreases, except in the river valleys where a high incidence is still found er hand, determine the climatic (Kilamarondo). Generally speaking, the fall in incidence follows the fall in le area has an average of 30 to mean vapour pressure, a lower mean annual vapour pressure occurring inland. are than this, with the extreme )ughout the Province, the rain • The highest incidence was observed in the Kilwa district, where filarial rates ~ maximum temperature in the (in adult males) of over 70 per cent were found. O'Connor (1932) considered the west it is slightly lower than that in a highly endemic filarial area probably 100 per cent of the adult popu IS region where the temperature lation are infected. In this village it is easy to imagine that this hypothesis is correct when it is remembered that the bloods were taken at 8 p.m.-four hours have an average of over 70 o P., before the generally accepted peak period, at which time more positive cases 'ince the temperature is between would almost certainly be found. In thi;> area also the incidence of A. persl(111S lower, except for the shore of infection was found to be very high. (55°P. to 60 o P.). High rates were also recorded in Lindi district, but at Rondo a lower inci dence was found. Although this. place is near the coast it is on the top of a Ie mean annual vapDur pressure 2,000 ft. escarpment, where colder conditions are experienced than in the rest steadily further inland to about a f the district. is the recording for the rest of high ground. Mikindani district covers a smail coastal area and includes the estuary of the River Ruvuma. The high rates found in this district-63 per cent on the coast, 54 per cent a short distance up the river-are what one would expect. 10dlands and wooded grasslands od waterless except during the In Newala and Nasasi districts the rates are shown to be lower than those at the coast. These districts have much higher ground and slightly lower tem peratures than places nearer the sea; the mean vapour pressure also tends to be [ower. :d in the territory, principally In Tunduru district it is seen that the edge of the bancroftial area has been tsetse fly. The coastal belt and reached. No bancroftial disease was found at Mbesa, near the Ruvuma River, tted. and very little at Npelembe, 50 miles north-west of Tunduru. Iv Songea district appears to be almost free of bancroftial disease-this is not The survey described surprising, since much of the area is On high ground. At Lituhi on Lake Nyasa a A. perSians is more widesprea, rate of only 3 per cent was found. It was expected that in this area a higher indicated. rate would be found, and it is interesting to note here that at the northern end of tbe lake very high rates have been recorded (Hawking (1940), Jordan (1953)). As mentioned above, J The two places are on the lake and thus at the same altitude, and temperature elephantiasis when considerin; recordings' are very similar, but at Lusungu the rainfall amounts to over 100 in. the table that in this part of per year, whereas at Lituhi about half this figure is recorded. It is thought that portance, and hydrocoeles ar this difference is probably sufficient to account to a large extent for the different that in some places over 30 filarial rates noted, since the high rainfall at Lllsung,o will result in a much to be affected. This differencl increased seasonal mosquito population, and the seasonal vapor pressure will festations is interesting, since be high, thus facilitating transmission of the disease. Other places in Songea much higher elephantiasis ra were free of the disease. confirms Brygoo's (1951) vie~ The results from Ruponda district are not as complete as elsewhere since t'estations varies locally, in Sj the investigating research o·fticer was unable to carry out clinical examinations further demonstrated when owing to, illness. Bloods were, however, taken by the African laboratory assistants, investigated. In all, seven ca: and the results of these are shown in the table. It will be seen that in this Likiwage in Kilwa district. district high microfilarial rates were found. The results obtained during this survey are consistent with our view that a An analysis of the sex l high incidence is found when a high temperature is combined with a high relative that only eight occurred in m whereas the remaining 11 we) humidity. The endemic area of A. persIans infection is very much smaller than the When the villages are gr W. bancrofli area" bjjt very high rates were found in some villages-villages also males and the clinical rates d having high bancroftial rates-viz. Nanjirinji, Likiwage in Kilwa districr, and is a very much bigher incide Ruponda, Liwale and Kilamarondo in Rupondo district. It must, however, be the highest rates:-- noted that the disease does occur in other areas free of bancroftial infection. A number of infection were found in infants. The ages of Africans are invariably unknown to the indi\;iduals themselves, and all ages have, therefore, Villages Total to be estimated. In adults fairly large errors may be made, but in infants it is with adult mal considered that one can, estimate age to within a few months. When ages of the mf. rates examine. infants below wete noted, the tendency was always to increase the age slightly. Bearing this in mind, t.he following are the youngest infants found infected, together with their village of origin:- 0-19% 130 Infection ---- Village Age I 20--39% .. I 1,136 I 1-----·- 40 % and higher ! 632 Namasakata 9 months (approx.) I A. persIans. It will be shown in a fu Kilamarondo 12 months (approx.) , A. perSians. filarial rates the microfilarial that the incidence of clinic~i 18 months (approx.) .. i A. persians; W. bancrojii. the microfilarial density in I Departmental Report for 195C 18 months (approx.) .. I A. persIans. i I The youngest patient oc Likiwage \8 months (approx.) .. I A. persIans; W. bancrojii. who had bilateral disease of 1 elephantiasis occurring in chi 8 months (approx.) Nanjirinji A. perstans; W. bancrojti. children was seen. 9 months (approx.) .. A. perstans. A rough estimate is mal 12 months (approx.) .. A. perSians. bancroftian filariasis througbc of people are infected and if, ..._------. ~------,---'-~-~ a cause of much ill health, it . It will be observed that infection with A. perstans appears to affect infants filariasis must be regarded as more frequently than does W. bancrofti infection. '. '" ." 11 bancroftial disease-this is not The survey described indicates that infection with W. banerafli and md. At Lituhi on Lake Nyasa a A. persians is more widespread in the Southern Province than previous reports had ~cted that in this area a higher indicated. e here that at the northem end Hawking (1940), Jordan (1953)). As mentioned above, most workers tend to stress the importance of same altitude, and temperature elephantiasis when considering the effects of the disease, but it will be seen from :ainfall amounts to over 100 in. the table that in this part of Africa elephantiasis is not of any very great im e is recorded. It is thought that portance, and hydrocoeLes are likely to be much more troublesome-it is seen I a large extent for the different that in some places over 30 per cent of the adult male population were found ~usllngo will result in a much to be affected. This difference between the incidence of these two clinical mani e seasonal vapor pressure will festations is interesting, since with similar microfilarial rates in the Pacific very isease. Other places in Songea much higher elephantiasis rates have been found (Buxton, J928), but it further confinns Brygoo's (1951) view that the occurrence of the different clinical mani as complete as elsewhere since festations varies locally, in sp~te of similar microfilarial incidences. This fact is carry out clinical examinations further demonstrated when the incidence of elephantiasis of the scrotum is he African laboratory assistants, investigated. In all, seven cases were seen, and six were in the same village .e. It will be seen that in this Likiwage in Kilwa district. ;onsistent with our view that a An analysis of the sex distrihution of the 19 cases of elephantiasis shows :s combined with a high relative that only eight occurred in males, of whom 1,790 were, examined, (0.4 per cent), whereas the remaining 1l were found in 1,359 females (0.8 per cent). is very much smaller than the When the villages are grouped according to the microfilarial rates of adult I in some villages-villages also males and the clinical rates determined for each group, it is ~pparent that mere jkiwage in Kilwa district, and is a very much higher incidence of clinical manifestations in the group having I district. It must, however, be the highest rates;- ;ee of bancroftial infection. nts. The ages of Africans are I, and all ages have, therefore, Villages Total No. Per Cent No. I be made, but in iufants it is with adult males of cases of incidence of of cases of few months. When ages of the mf. rates examined hydrocoele hydrocoele elephantiasis .ys to increase the age slightly. , ungest infants found infected, ---I 0-19% 130 9 7 I Infection 20-39% 1,136 106 9 40% and higher 632 204 32 6 -..-1 A. persians. ---- It will be shown in a further paper that in the villages with higher micro A. persians. filarial rates the microfilarial densities are also high. It thus seems not unlikely that the incidence of clinical manifestations is dependent, in part at least, on A. persians; W. banerO/li. the microfilarial density in the area, as was put forward by Laurie in the Departmental Report for 1950. A. persians. The youngest patient observed with elephantiasis was a boy of 14 years A. persians; W. banera/ti. who had bilateral disease of his legs. Jordan (1952) reported four other cases of elephantiasis occurring in children below this age. No case of hydrocoele in A. perstans; W. bancrojii. children was seen. A. perstans. A rough estimate is made below of the number of adults infected with A. persians. bancroftian filariasis throughout the Province. It shows that very large numbers of people are infected and if, as some beheve, the late effects of filariasis are r.l'tans appears to affect infants a cause of much ill health, it is obvious that in parts of this province bancroftian filariasis must be regarded as a disease of major importance. TABLE n.-FILARIASIS IN THE SOUTHERN PROVINCe, TANGANYIKA TERRITORY. Non-clinieal Cases Clinical Rates 'II Ban· [Non-clinical Bloods ,. Temperature -'1---croftian I .positive ~ Incid~nce '. , , Males Femat6s' MJ. perstans \ M/ Filafial: !-'''', Alti RalQ- i ~ bancroftl 1n blood' --.------Rates I ~ l District Village tude fall i__ ,'__ 1------I Ele- I Ele------~ p~a':l- -- feet ins. r ,8 .: Adults Hydrocoelet I phan------', Adults M M' I'" "" Chll- 1------· . hasls , tmsls I ~ I CM- ---- ~ of'l ;F' 5. dren 'I Males IFemalesj--,-o-----r-- o-- 11• -';x I dren Males Females .I ~ I :5' ----1---, Nos., % Nos.! % "'~,S ------__ 1 . .--I--~~-~.%+vel\ %+ve! %+~,!~enseen_l-.!een .~!~ I~_+ve%+ve %+ve Kilwa I Nanjidnj; '500 30--40 I >85 65-70 24 100 9 I' 55.1 40 t- 46 37 2 (1)* 0 73! 40 I 12 41 'I 32 Likiwage 750 30-40 >85 65-70 24 2,000 9 63 40 I 77 38 0 1 77' 41 24 44 39 Kilwa 0 30-40 >85 >70 26 3.000 I 18 73 none Inot random sample 73 0 6 scen Lindi Mcllinga 0 30--40 > 85 > 75 26 3,000 I 19 45 25 23 21 1 3 54 26 0 0 0 Rondo 2,000' 40-50 >85 65-70 26 500 0 18 0'1 1 3 0 0, 21 0 0 0 0 Mtama 400' 30--40 > 85 65-70' 25 2,OlJO 15 46 25 18 20 3 (2)* 1 '58 26 0 I 0 0 Mikindani Ndumbwe 0 30-40 >85 >75 27 1,400 31 44 42 18 35 0 2 63 144 0 0 0 Kilayo ,100 30--40 >85 65-70 27 1,000 19 40 35 13 22 0 5 54 38 0 0 0 Newala ., Namikuda ., 750 30--40 >85' 65-70 25 1,200 small 22 111 72 13 0 1 35 1{ 0 0 0 Nos. Newala 2,000 30--40 >85 65-70 25 2,000 0 15 3 6 4 0 0 I 18 3 0 0 0 N Kitanga:ri 1,750 30-40 >85 65-70 25 1,500 6 26 20 II 7 I 0 O· 31 20 0 0 0 Masasi Chydia 2,000 30-40 >85 65-70 24 1,000 9 13 \10 3 I 9 I I 0 24 10 0 0 0 Lulindi ., [,500 30-40 > 85 65-70 24 1,000 I 22 10 5 6' 1 0 28 10 0 3 3 Tunduru Namasakata 2,000 40-50 80-85 60-65 18 400 I 0 18 0 3 8 I 0 0 24 0 6 33 23 Mbesa .. 1,500 40-50 80-85 65-70. 18 1,000 0 0 0 0, 0 0 0 0 0 0 3 [4 Nampungu,. 2,500 40-50 80-85 60-65 18 700 small 17: sma,1l 2 I 9 I 0 0 23 I 10 6 19 10 Nos. '1 No" I I Mpelembe .. 3,500 40-50 80-85 60-65 18 300 0 0 0 I 5, 0 0 5 I 0 4 20 4 Songea " Lusewa .. 2,500 40-50 80-85 60-65 18 500 0, 0 I 0 0 0: 0 0 0 I 0 6 37 15 Myangayanga 4,200 40-50 75-80 55-60 16 700 O! 0 0, 0 I 0 0 0 0 i 0 0 0 0 Lituhi 1,500 50-60 80-85 65·-70 17 1,200 0 0] 0 i 2 'I 3 '0 0 3 I 0 0 0 0 Ruponda Ruponda 1,200 30-·40 >85 65-70 24 1,000 'small 22 small 112 8 I () - 1 28 - 33 44 , Nos, Nos. J Liwale 2,000 30--40 >85 65-70 20 2,000 I 5 35 13 not reported 35 13 21 50 20 Kilamarondo, 1,200 30--40 >85 65-70120 11,000 I 10 49 38 I not reported 49 38 Hi 62 I 51 ·Cases of elepbantiasis of the legs with hydrocoele, tHydrocoele cases include all cases of genital filarial disease, i,e" hydrocoele and elephantiasis of scrolllm, SOUTHERN PROVINCE RESULTS:- W. bitncrofri: rates are for persons not showing elephaut.iasis or hydrocoele, Clinieal rates: represent incidence of hydrocoele or elephantiasis (percentage for e(ephantiasis nol given since it would be so small in most cases), Filarial rates: represent total rate of filariasis-mierofilaraemia, hydwcoele and eLephanliasis. A. persIans rates: based on total numbers examined, i.e" clinical and non-clinical cases, All figures to the nearest whole number. No cases of onchocerciasis seen but in t.he mountains there are streams in certain of which there is breeding of Simuliidae. ~ ~ '?'~. I>' ::tJ '0 ...... ~;4l ~UJ PJ _. p.1 0 a 8 Z 3 ~ p;-0 ~, 'D ~o> 0>- ~ g-~~>~~ -0 s _. ::r ::r (IJ i=t ~::s~g~~gs(p .; 00 ...... LI\ ~ I>' 0 d o d (1)<=,'0::::;'-"" '-' ~ p ...,::\...... U) ...... @ '" ... ", .... ::r::r ...... ~ (1) _ ~ "'::r N c: ::J ~ d ?> -. (rJ("D~~~~~r:n -'-O~o::r::r ... (1) ~ it ::i' Pi I>' . 1 ~;:o '" ?> tiQ. OQ (JQ ...... zo ("D en 0 ,...., ;'; (I> .... {JOo~ :=tOQ c: o.~'''''''''d '< '<0 ...] II';' :::: 0 s:::: CD (Jl 0 _. 0 f;f os. ;;:;. 0 ::J ~ ~ ~ '" (1) () ~§;ot<1 \0 '" .... g \0 3 v;.;j. _ v) ; S' ::r n ,~(1)~.~~ ...... _. rJ) v-. ::r _. (I'l t...J, o $, '&~ q" ,..." 0 P ~ ;:; c (1) o .l---'-S:::: (JJ (f) l" ...... ' .... ", o ~ , ...... ·0 ~o r-+p:lp;!~P'O"~ ~ ~ v:;. () S ...... C C 0. ~ a S <: ~ >-3 q ~ ~ o. 1>''O'<;;l 3;> ...... ~ (J) fA ~.~ ...... ';:::t ~< 0 o l" 0 "'0 0". o' 0 ~ GO ;:l,o ...... (1) ?>,...,t1> I>' 0 CJ ....., ..... (1) '"(1) ::r ~ .... n 9::r~00,<: ~ &'~ 8..~ 0.. 0. N' ~ 0 '" 3 0''< ;J:~ ~ f!l.3p .....g .., ::J P '" ..... C/) o .., g.::r"" 0 goo -e: (JQ... 0 '<:_. '" 0 ;::r("D ~~~~ ~~ ~~ ~ ~O·~~ §,~ 8. ft" : _. CD 0 ...... -O~- Ii ~ d>--j""" q" po. (JQ5";><0.. d ::::. c:: 0 '" C> "'"'0 l" d e; n (I>.go ..... OQ ~ .., 0 (JQ::r ~ <1 ~.~ a ~. '. t ..... ", 15 al cases, compared with 14 out (b) Filarial cases: lp. Although it is realized there 1/8,000. Twenty-three positive out of twenty-nine. , is considered that the majority 1/12,000. Two positive out of two. ) filariasis and that the figure of 1/16,000. One positive out of seventeen. cates that a large proportion of bably filariaL (Further sup,port Cases excluded from 2 (a) as in 1 (a). ~e work.) This is in ket'ping with 1/12,000. Four positive out of five. persons in an endemic area are 1/ 16,000. Three positive out of five. ing Ear elephantiasis, hydrocoele tion of filarial incidence in a (3) L. carinli. (a) Filaria-free cases; serious attention be given to 1/12,000. Seven positive out of twelve. likely to confuse the issue. 1/16,000. Five positive out of twenty-two. 19 the original criteria, i.e. blood Cases excluded as in 1 (a). tiasis for the "apparently filaria- 1/12,000. Two positive out of five. I /16,000. Two positive out of twelve. t' evidence of thickening oE the in the "apparently filarial-free" (b) Filarial cases: ~d as filarial cases; the results of 1/12,000. One positive out of two. 1/16,000. Three positive out of seventeen. Cases excluded as in 1 (a). 'ease in size of bleb at 10-minute 1/12,000. Three positive out of five. 1/16,000. Three positive out of five. TABULATED RESULTS Filaria Free I-three. 1/8,000 I...... ,_1_/1_2_?_00__1__1_/1_6_,0_00__ J. was a control reaction, or those D. immitis 23-14 positive \ 5-1 positive 12-2 positive !isis or adenitis or evidence of D. medinensis I 23-18 positive II 5-1 positive 12-2 positive lHowi ng results are obtained;- L. carinii I - 5-2 positive 12-2 positive e. Filarial Cases .y-nine. 1/8,000 1/12,000 1/16,000 1------I------1. D. immitis ...... 29-14 2-1 17- 5 :roup above- (Cases excluded from filaria free group) .. 5-3 6-2 D. medinensis 29-23 2-2 17-1 (Cases excluded from filaria free group) .. 5-4 5-3 L. carinii 2-1 17-3 (Cases excluded from filaria free eact. group) .. 5-3 5-3 Filarial cases From the above limited numbers, D. medinensis antigen appears the best in 1/12,000 dilution, but much larger numbers are required. 16 (2) Elephantiasis in East Afriea hydrocoele i1 In the text above and In the earlier reports attention is drawn to the lack of tiasis, the incidence of the f( knowledge of the disease processes in the filarial infections. This is particularly higher than the incidence of true of elephantiasis. The list of possible causative agents suggested by previous the importance of bancroft workers include:- As an example, figures are gi The worm itself living or dead. INCIDENCE OF LATE The microfilarire. Accumulation of ova. Hypertrophy of the reticulo-endothelial system. It is the writer's opinion that in the beginning the process is a sensitization AGE GROUP IN phenomenon, a local reaction to the presence of the, adult worm. Later the local YEARS Iv -- changes reach a non-specific phase. This view is supported by recent satisfactory No. pathological investigations, e.g., Rifkin and Thompson (1945) suggest three stages of tissue change, namely, an early acute allergic stage followed by a sub-acute stage of gra11ulation tissue overgrowth in the areas round the adult parasite, and 0-9 2 finally a stage of chronic non-specific tissue overgrowth. 10-19 1 20-29 2 A paragraph from the 1951 Report may be repeated here:- 30--39 12 40-49 "This consideration of elephantiasis is important for two reasons: 8 50-59 15 firstly, if the view be correct that elephantiasis is due to an irreversible local 60 and over 10 tissue change " then the affected individual can expect little help from - drugs and secondly, if the view be correct that the cause of the tissue ..;,,~ " '. '.' " ; " 17 in East Africa hydrocoele is much commoner and more crippling than elephan tttention is drawn to the lack of tiasis, the incidence of the former being ten times that of the latter and 250 times 11 infections. This is particularly higher than the incidence of non-specific hydrocoele in Britain. We consider that ive agents suggested by previous the importance of bancroftian hydrocoele has been seriously under-estimated. As an example, figures are given below from a survey On Ukara Island. INCIDENCE OF LATE MANlFESTATJONS OF BAlliCROFTIAN FILARIASIS _. --, PHYSICAL DEFECTS system. - Elephantiasis Legs Hydrocoele ing the process is a sensitization AGE G ROUP IN , y EARS the adult worm. Later the local Male Female ~--- No. supported by recent satisfactory % No. I % No. % npson (1945) suggest three stages I : stage followed by a sub-acute , as round the aduJt parasite, and 0-9 ·. ·. 2 - ~ -- 1 - ergrowth. 10-19 ·.·. I - 2 1 12 2 20-29 ·. · . 2 1 14 4 27 13 ~ repeated here;- 30-39 · . · . 12 5 14 5 , 36 15 40-49 8 5 24 29 17 is important for two reasons; · . ·. 10 50-59 · . . 15 11 12 9 18 I 13 sis is due to an irreversible local · I 60 and over · . 10 8 6 10 28 I 24 lUal can expect little help from 1--- it the cause of the tissue changes TOTAL · . 50 3 72' 4 151 I 8 reatment may actually be harm- =~;::;:=:=:;;;::;=~=~;;;;:;;;;;;:;;==~ Investigations are at present being carried out on hydrocoele fluids in an attempt to differentiate filarial and non-filarial hydrocoeles. To date the only indings differ from those of the significant difference found is that of microfilarire in certain of the hydrocoele lsis is not a common complica fluids. obably the most heavily affected :is in the whole population does (4)· FUarial Lymphadenopathy that elephantiasis is found as a Although much has been written on filarial lymphadenopathy in the Pacific, ; are intense, i.e. where not only little is known on this subject in East Africa. This problem has recently been the population but also where studied by Jordan of this department. ria counts: the microfilanemia d from the South Pacific where The present investigation indicates that. lymphatic enlargement is not as lifference are; in East Africa pronounced in this area as in the Far East. The cases seen have been divided ~gs or the male genitalia (80 per into fom groups:- :presenting not more than 1 per (i) A control group showing no microfilarremia and absence of hydrocoele let in East Africa is much earlier and elephantiasis. 'Port) and Jordan (1951 Annual (ii) Persons with microfilarremia, but no hydrocoe1e or elephantiasis. :hildren under eight years of age. lfection becomes established very (iii) Persons with microfilara:mia and hydrocoe1e or elephantiasis. ·filanemia in two cbildren a few (iv) Persons with hydrocoele and elephantiasis but no microfilarremia. In any patient with lymphatic enlargement for which no obvious cause could be found has, for the purposes of the present investigation, been regarded as filarial in origin. Bitateral and unilateral cases have not been differentiated, and rotum, lymph scrotum, and un no allowance has been made for size--all glands considered by the observer to complications always begin as be pathological have been recorded. the consideration of prevention. The results are analysed in the following table, which shows that in the infected rican bancroftiasis shows itself groups there is little increase in the incidence of lymphadenopathy over the con :riasis malayi and wuchereriasis trol series apart from a higher incidence of enlargement of the femoral and is not found and in the pacifica inguinal glands in patients with established hydrocoele or elephantiasis; this ltion than elephantiasis, whereas incidence is higher in the group with negative bloods than in those showing microfilaria:: in their blood. 18 DISTRIBlITION OF WORKING ---_.•------Total PALPABLE GLANDS No. ------Days Lost per Year Seen Femoral rng. Epitro. Axill. Neck --~ -- I 0- 30 .. 2 Negative blood no evidence of I 31- 60 .. 1 filarial disease-control · . 58 20 15 25 2 I 61- 90 .. I Microfilaraemia only .... 60 20 15 14 2 , 2 91-120 .. Microfilaraemia with hydrocoele . 121 onwards or elephantiasis .. · . 36 18 9 17 1 1 Negative blood with hydrocoele or E elephantiasis .. .. ·. 83 49 32 23 0 2 From the above tables it KEy: Ing.=Ingninal. Epitro. = Epitrochlear. Axill.= Axillary. completely crippled a high I As regards the relia.biJity of the control series it has to be remembered Histories taken from several that in an endemic area it is likely that many more people are infected in that in the recurrent cripplinl the population than is indicated by the microfilarial rate and the hydrocoele. pains in the legs and pains in elephantiasis rate. O'Connor (1932) considers that probably 100 per cent of of classification, details are persons in a hyperendemic area are likely to be infected. If tnis is true, then it histories. means that it is virtually impossible to get a true control series in an endemic area. (In the observer's opinion the same objections apply to the use of controls CLASSmCATION 0 for skin testing select~d from an endemic filarial area.) This criticism of tne control group may account for the similarity of fintlings Degree of Pain- between this group a.nd the micro-filarremia gronp. The greater increase in lymphadenopathy in the next two groups is comistent with the view generally held that these later manifestations are due to ohstruction caused by the adult Nil Pain originally but no recurrei filaria; enlarged inguinal lymph glands are considered by Manson-Bahr (1951) to Slight recurrent pain, not cript be one of tne signs of the tertiary stage of filarial infection. But it is also of Pain when present affects work interest to note 1}ere the low incidence of epitrochlear glandular enlargement even in the late s'tages of the disease; Manson-Bahr (1951) also lists enlarged epitrochlear glands as a sign of the tertiary stage of the disease. Buxton (I928) (Similar investigations Ci) showed a positive correlation between epitrochlear glandular enlargement and give a figure of about 70 pc elephantiasis. The attacks of pain admi It would appear therefore that this sign at any rate is not common in ably, from one to two days c filarial disease in those parts of Tanganyika which have been surveyed to date. prevent work at any time. Th (5) The Economic Aspects of BlmcroHian Filarias~s work in the year (compared v The importance of filariasis paCifica lies in the "mumu" of the early stages analysis was made to investi€ of infection and the elephantiasis found commonly as a late complication. There With microfilarremia but no Sl1 is nO mumu seen in East Africa: the economic importance of the disease lies The above findings are a, in the crippling effects of genital filariasis and of elephantiasis. This problem was discussed in the 1951 Report, "rom which tvlO tables are given below. &'1ALYSIS OF WORlONG DAYS LOST (1) Introduction Annua1-1------Since individuals showin venienced by the parasite, thl No. of I No. or Average I Annual have any effect either on the I No. case:s I cases ~~ cases days lost Average DISEASE of missing doing, missing by those days lost coele or on the recurrent cr: cases some I no work I work missing by total important cause of loss of \\ wcrk I work. cases seen evidence of efficiency in pre tiasis, a possibility which has Hydrocoele I 168 661 I 39 63 25 of recent years. In this com Elephantiasis 102 63 II 1 , ,63 i 63 38 "Whereas in most protozo. Mixed cases 34 19 2 I 56 I 97 , 55 I I I _____·r_.· ~~~ ,. '. t" .; " , . ", ~ 19 DISTRJBUTION OF WORKING DAYS LOST BY PERSONS WITH CLINICAL FILARIASIS CONDITIONS PALPABLE GLANDS -'-~~I------Days Lost per Year Hydrocoele Elephantiasis Mixed - JIng. IEpitN. IA,m. Nock I I % % I % 0- 30 · . ·.·. 29 44 23 37·1 5 26,3 31- 60 ·. · . · . 14 21'2 15 24·2 5 I 26·3 15 I 25 2 I 61- 90 · . ·.·. 10 15 ·1 13 21·0 3 15-8 15 I 14 2 2 91-120 · . ·. ·. 6 9'1 6 8·0 2 10·6 121 onwards , . ·. 7 10·6 6 9·7 4 21·0 9 17 66 100 , 63 100 19 100 32 23 o 2 From the above tables it is seen that although relatively few individuals are lear. Axill. = Axillary. completely crippled a high proportion of individuals lose much working time. ~ries it has to be remembered Histories taken from several hundred patients (hydrocoele or elephantiasis) show i more people are infected in that in the recurrent crippling attacks the patient suffers from fever, groin pain, laria! rate and the hydrocoele pains in the legs and pains in the scrotum. Using the degree of pain as a method l1at probably 100 per cent of of classification, details are given below of a few of such hydrocoele case infected. If this is tme, then it histories. Ie control series in an endemic lUS apply to the use of controls CLASSmCATION OF RECURRENT ATTACKS OF FEVER, ETC. I area.) mt for the similarity of findings Degree of Pain-Scrotum or Groin Hydrocoele roup. The greateT increase in .sistent with the view generally No. % bstruction caused by the adult Nil 21 36 10 ered by Manson-BahT (1951) to Pain originally but no recurrence 17 Slight recurrent pain, not crippling 6 11 ':ial infection. But it is also of Pain when present affects working capacity 21 36 'ochlear glandular enlargement ahr (1951) also lists enlarged ------_.,------'----, ; of the disease. Buxton (1928) (Similar investigations carried out with patients suffering from elephantiasis ear glaudular enlargement and give a figure of about 70 per cent showing interference with working capacity.) The attacks of pain admitted by the 21 patients in group I V varied consider t any rate is not common in ably, from one to two days off work per month to a degree of pain sufficient to ~h have been surveyed to date. prevent work at any time. The average time lost per person amounted to 47 days ,is work in the year (compared with 63 days as reported in last year's summary). An he "mumu" of the early stages analysis was made to investigate whether the occurrence of pain was associated [y as a late complication. There With microfilanemia but no such relationship could be established. importauce of the disease lies The above findings are again considered below in regard to treatment. elephantiasis. This problem was )les are given below. Treatment ,YS LOST (1) Introduction Since individuals showing only microfilara:mia appear not to be incon Annual venienced by the parasite, the only problem in treatment is whether drugs used Average Annual have anyeffed either on the physical changes present in elephantiasis and hydro '~ cases days lost Average nissing by those days lost coele or on the recurr~nt cTippling attaeks of pain, etc., which are the most work missing by total important cause of loss of \vorking time. Drugs should also be considered for work cases seen evidence of efficiency in preventing the onset of hydrocoele and of elephan tiasis, a possibility which has received little mention in the voluminous literature 39 63 25 of recent years. In this connexion we again quote Temkin (1945), who sayS-, .63 63 38 "Whereas in most protozoan and helminthic infections the object of the 56 97 55 -----~_._------20 therepeutic attack is well defined, this is not the case in filariasis ... it is not MICROFILARlJE LEVELS IN BI certain that a drug which will kill the filarire will also cure the disease ... dead AF" parasites may in themselves be responsible for some of the manifestations of filariasis". The only other workers who have kept this in mind are Culbertson Tot et at. (1946) and Oliver-Gonzales et al. (1949). ' '. Total ! Total Mic Dose Drug IPatients --. (mgms. per kg.) In all discussions on drugs for the treatment of bancroftian filariasis the Before questions to be considered are:- ---,. ------1. Is the drug microfilaricidal? This is only of importance as a measure of Under 50 18 1,234 assessing the effect of the drug on the adult worm, at least on the adult 51-70mgms... 29 3,523 female worm. Over 70 mgms. 63 4,783 2. Has the drug any effect on the physical changes of elephantiasis and of *Excll hydrocoele? 3. Has the drug any effect on the disabling recurrent fever, etc., associated Tlle results quoted in th with the latc manifestations? workers elsewhere. One poiU' 4. Has the drug any effect iu preventing the onset of elephantiasis or of count obtained immediately, hydrocoele in individuals harbouring W. bancrofti, i.e. any effect on again even many months aft( symptom-free bancroHiasis? so treated may be in a hyper depression of the microfilari (2) Hetrazan female worm has been killed This substance 1-diethyl carbamyl 4-methyl piperazine is marketed as the dihydrogen citrate salt. Harned et al. (1948) give details of the pharmacology. HETRAZAN MiD PUBLIC HEAL This preparation is replarkably safe and is a strikingly effective microfilaricidal In the absence of any I agent even in the smallest of doses. It is an expensive drug and little is knoyvn of indication of the chemother its action on the bancroftian parasite. Previous departmental reports discuss remarkable effect of hetrazan certain results in detail, and the l11aterial which follows is an extension of suc~ prove of value as one metho reports. difficult completely to rendel the microfilarremia be of a hi EFFECTS ON SYMPTOM-FREE BANCROFTIASIS filarial count in any patient <: In the present state of ignorance the only way of assessing the value of over a period of time. One i a drug in preventip.g elephantiasis and hydrocoele is to administer the drug to certainty what is the level of large numbers of patients with symptom-free bancroftiasis and to follow the . infective to the iusect vector. histories of such patients over a period of years. This has been done in two of the at one time the "safe" level worst areas in Tanganyika, namely Kyela and Ukara. In both experiments we Hewitt (1949) stated that the chose symptom-free individuals with heavy microfilanemia and aimed at adminis 10 mfs. per 60 mm'. This is tering a total does' of salt of not less than 70 mgms. per kg. body weight. than it has received. Work on Kyela Campaig;;,--Dne hundred and twenty-five individuals were treated halted because of technical d during August, 1950. (Both sexes, all adults with the exception of eight children.) show that in blood meals t, To date (January, 1953), no individual has developed hydrocoele or elephantiasis. unit volume of blood may be whom the mosquito had fed. Ukara Campaign.--Dne hundred and thirty-one individuals were treated is that the microfilaria: are r during October, 1951. (Both sexes, all adults with the exception of 12 children.) but exist il1 clumps. Another To date (January, 1953), no individual has developed hydrocoele or elephantiasis. insect's proboscis may strike Over the years a random untreated group of 256 sympton-free individnals of from a pool formed through both sexes should show an incidence of about 20 cases of elephantiasis and first-mentioned type of feedi about 20 cases of hydrocoele. It is still too early to see whether we have succeeded mlcrofilarire. With this in mil in preventing the onset of hydrocoele or elephantiasis in the individuals treated eradication 0:£ filariasis based by us. the affected individuals' micr( EFFECT ON MICROFILAR..EMIA HETRAZAN AND EUPHANTIAS] Reports from aU affected parts of the world are unanimous in their agree In the last tlu'ee years ment that hetrazan is strikingly and immediately microfilaricidal When adminis patients with elephantiasis of tered to individuals showing bancroftian mkrofilara:mia. This has also been seven females with elephanlia our experience: a typical table ill given below. were adulti. More than 100 ;.' ,; ., ~. 21 se in filariasis •.. it is not MICROFILARIIE LEVELS IN BLOOD OF INDIVIDUALS ON UKARA FIFTEEN MONTHS 10 cure the disease ... dead AFIER HETRAZAN TREATMENT ne of the manifestations of ------,------,------this in mind are Culbertson Total of No. of Mf. Counts p. 60 mm3 in Pal. . Total Total Microfil Reduc Pat. not made Mf.-free Dose Drug Patients tion made I (mgrns. per kg.) Me Under I Over of bancroftian filariasis the Before After Neg. 10 mf. 10-30 30-100 100 ----~--I----I---·--1----1----1 % importance as a measure of Under 50 .. 18" 1,234 40 97 11 5 2 . worm, at least on the adult 51-70mgms... 29 3,523 20 99·4 18 11 Over 70 mgms. 63 4,783 45 99 53 9 ------'------1ges of elephantiasis and of ·Excluding one exceptionally high value. :urrent fever, etc., associated The results quoted in the above table are in keeping with those quoted by workers elsewhere. One point worthy o·f note is that the low or zero, microfilaria onset of elephantiasis or of count obtained immediately after administration of hetrazan is not found to rise bancrojli, i.e. any effect on again even many months after treatment has been given, although the individual so treated may be in a hyper-endemic area of filariasis. This seemingly permanent depression of the microfilarial count indicates that at the very least the adult female worm has been killed or sterilized. . erazine is marketed as the retails of the phannacology. HETRAZAN AND PUBLIC HEALTH ~gly effective microfilaricidal In the absence of any proof that microfilaricidal activity may serve as an e drug and little is kno~n of indication of the chemotherapeutic value of a drug, the ir11portance of this :lepartmental reports discuss remarkable effect of hetrazan on microfilarremia lies in the possibility that it may )WS is an extension of sucjJ. Prove of value. as one method of eradicating filariasis. Although it is sometimes difficult completely to render an infected person microfilaria-free, especially if tme microfilarremia be of a high degree, it is easy markedly· to depress the micro filarial count in any patient even with doses as low as one to two tablets weekly of assessing the value of over a period of time. One important drawback is that no one knows with any s to administer the drug to certainty what is the level of microfilanemia below which the human host is non :roftiasis and to follow the infective to the insect vector. Work on this subject has been vr::ry unsatisfactory: has been done in two of the at one time the "safe" level suggested was 30 mfs. per 60 mm" but recently ra. In both experiments we Hewitt (1949) stated that the "safe" level is much below this, probably below a~mia and aimed at adrninis- 10 mfs. per 60 mm". This is a basic experiment requiring much more attention per kg. body weight. than it has received. Work on the subject in this department has been temporarily ve individuals were treated halted because of technical difficulties, but already our results (see 1951 Report) exception of eight children.) show that in blood meals taken up by mosquitoes the microfilaria count per hydrocoele or elephantiasis. unit volume of blood may be mnch higher than the level found in the host upon whom the mosquito had fed. One suggestion put forward to explain our results oe indivitiuals were treated is that the microfilarire are not distributed evenly through the peripheral blood e exception of 12 children.) but exist in, clumps. Another possibility is that chance may play a part, e.g., the hydrocoele or elephantiasis. insect's proboscis may strike' a venule, it may enter a capillary, or it may suck , sympton-free individuals of from a pool fanned through leakage from vessels damaged in passing. Only the cases of elephantiasis and first-mentioned type of feeding is likely to permit of the ready taking-up of ~ whether we have succeeded microfilarire. With this in mind it is inadvisable at present to plan campaigns of is in the individuals treated eradication of filariasis based on the assumption that it is necessary only to lower the affected individuals' microfilarial blood levels below 10 per 60 mm". HETRAZAN AND ELEPHANTlASIS ~ unanimous in their agree In the last three years we have been able to treat adequately over 200 icrofilaricidal when adrninis patients with elephantiasis of the legs; one patient with elephantiasis arms; and rremia. This has also been seven females with elephantiasis breasts. The sexes were almost equal; almost all were adult!:. More than 100 patients have been followed-up for over two years 22 and nearly 50. for over one year. Measurements show that there has been no significant change in the sizes of the affected limbs. This does not mean that Later results are:- hetrazan is of no value in the treatment of elephantiasis. In the text above it has (a) Hetrazan and filarial. been shown that the real disabling factor in elephantiasis is not the physical simple increase in scrotal siz change alone but the recurrent attacks of fever and pains in the Xegs in whom, before treatment, t and groins. In our 1951 Annual Report we mentioned that elephantiasis had been satisfactorily treate patients treated with hetrazan had volnnteered the information that since treat than 70 mgms. hetrazan per ment they had not suffered from such recunent disabling attacks. The importance of this was not stressed at that time, as we wished for fuller proof. Our latest Results of 17 observed survey of results of treatment shows without doubt that this is a true claim, in Cured that at least half of the paients treated have been relieved of all symptoms. The patients themselves speak enthusiastically of the results of treatment in spite Worse of the unchanged condition of the elephantid legs. It is therefore our opinion that hetrazan I'S of value when a.dministered to individuals suffering from bancroftian Reduction in size 01 elephantiasis. No change Note.-Since writing the above a patient has reported to us with what seems Note.-In more than to be a cured elephantiasis o:f one leg. The individual, an African male aged 30, (Every cure occurred in was admitted on 18th November, 1950, with a complaint of elephantiasis left sized hydrocoeles.) Four leg of four years' duration this being associated with recunent attacks of pain anCe of the crippling aUae and fever. Examination showed the left lo,wer limb to be larger than the right, the enlargement being limited mainly to the foot and ankle, an early degree As a striking example of of elephantiasis with no skin changes, typically the kind of patient we suggested report received from an Afr whom we sent hetrazan for (1951 Report, p. 39) m,~ght bet;lefit from hetrazan administration. The patient was given a total of 90 tablets each 50 mgms. of banocide in three days, a total do~age "1 beg to report on IT of 75 mgms. per kg. body weight. I took the first med On 20th February, 1953, the patient returned claiming he had been cured; after one hour I vomitel measurement showed 110 difference between the right and the left leg, and the I felt like vomiting till latl patient was wearing shoes of nonrial size. He also stated that all attacks of pain day 1 took the second pa and fever had ceased after the treatment. Our record shows that this "cure" hour and felt the same take the medicine at bedti had been reported iin a f~llow-up observation (1951) by one of the medical staff, like vomiting every now who had decided to give a longer period of observation before making public with the exception of one the findings. After six days treatlT HETRAZAN AND GE!,!ITAL FILARIASIS and the ~.crotum has rett By reason of its bulk alone genital filariasis even of moderate degree is area of one square inch usually much more crippling than is even moderately advanced elephantiasis of medicine and finished it al the legs: also, as shown above, genital filariasis is more common than elephan treatment but the said a tiasis. In areas where bancroftian filariasis is hyper-endemic genital filariais may be found in one of every four male adults over middle age. Altho,ugh the treat (b) Genital {ilariasis.-Thi ment of genital filariasis is a pressing problem, remarkably little attention has ago. Physical findings followi been paid to such conditions. Hydrocoeles, lymph scrotum, and elephantiasis Improved or cured scrotum do not only cripple the patient because of the tissue changes. As with Worse elephantiasis, the really crippling factor is that of recurrent attacks of fever and pains: such attacks correspond exactly to those seen in elephantiasis. In the No change study of the value of any drug therefore two questions have to be answered: Note.-As with eleph firstly, does the drug in any way affect the physical changes present, and secondly, skin changes have develop does the drug in any way affect the recurrent attacks of fever, etc. In our 1951 sion of such skin changt Report we claimed to have cured two simple hydrocoeles (total seven patients) reported disappearance of by the administration of hetrazan. This was an important advance, the signifi cance of which is not likely to be appreciated except in areas where bancIoftian It is considered that in e hydrocoele i& a senoul> problem. prove of value in the control cure a significant proportion ,. ", " ." 23 ; show that there has been no lbs. This does not mean that Later results are:- mtiasis. In the text above it has lephantiasis is not the physical (a) Hetrazan and filarial hydrocoele (where there are no changes other thap fever and pains in the leas simple increase in scrotal size).-It has been possible to trace 54 such patients mentioned that elephanti~sis in whom, before treatment, the skin changes were slight or absent, 17 of whom le information that since treat had been satisfactorily treated at least one year previously (treatment not less sabling attacks. The importance than 70 mgms. hetrazan per kg. body weight). led for fuller proof. Our latest Results of 17 observed tht that this is a true claim, in 1 relieved of all symptoms. The Cured 8 ) results of treatment in spite Worse It is therefore our opinion that 'uals suffering from bancroflian Reduction in size of hydrocoe1e No change 7 reported to us with what seems dual, an African male aged 30, Note.-In more than 50 per cent of patients complete cure was recorded. complaint of elephantiasis left (Every cure occurred in individuals originally showing small Qr moderately with recurrent attacks of pain sized hydrocoeles.) Four of the remaining nine patients reported disappear ance of the crippling attacks of pain and fever. nb to be larger than the right, ot and ankle, an early degree As a striking example of the efficacy of hetrazan we give in full below a Ie kind of patient we suggested report received from an African patient so.me 800 miles away from here, to ldministration. The patient was whom we sent hetrazan for the treatment of his condition:- ide in three days, a total dosage "I beg to report on my illness as follows:- I took the first medicine with water as directed before breakfast, but claiming he had been cured; after one hour I vomited and felt weak, sleepy and had a headache, and 'ight and the left leg, and the I felt like vomiting till late evening, when I regained.my usual strength. Next I stated that all attacks of pain day I took the second package after breakfact but vomited again after one record shows that this "cure" hour and felt the same sym.ptoms as outlined above. Then I decided to 1) by one of the medical staff, take the medicine at bedtime, which I did, but with great difficulty. as I felt ervation before making public like vomiting every now and then, but otherwise' it was quite'aU right with the exception of one night only, when I vomited after three hours. After six days treatment I found that all the swelling has disappeared and the scrotum has returned to its usual size with the exception of an '> even of moderate degree is area of one square inch where the fat still exists. I continued with the ltely advanced elephantiasis of medicine and finished it all. It is now about 15 days since I have finished the i more common than elephan treatment but the said area of one square inch is still there." 'r-endemic genital filariais may liddle age. Although the treat (b) Genital {ilariasis.-Thirteen such patients were treated over 12 months 'emarkably little attention has ago. Physical findings following treatment are:- )h scrotum, and elephantiasis Improved or cured Nil )f the tissue changes. As with recurrent attacks of fever and Worse Nil seen in elephantiasis. In the No change 13 testions have to be answered: changes present, and secondly, Note.-As with elephantiasis limbs, it would seem that once well-marked cks of fever, etc. In our 1951 skin changes have developed, the giving of hetrazan does not lead to regres sion of such skin changes, but here also at least one half of the patients :lrocoeles (total seven patients) reported disappearance of the disabling attacks of pain and fever. mportant advance, the signifi :pt in areas where bancroftian It is considered that in elephantiasis and in genital filariasis hetrazan may prove of value in the control of secondary disabling features. Further, it may cure a significant proportiou of individuals suffering from simple hydrocoele. 24 The tabulated data shows (3) Protostib toxic level there was no guall INTRODUCTORY or sterilized. In fact the hea~ This is the trade name (May & Baker) of N-methyl glucamine antimoniate body weight, only lowered tt in which pentavelent Sb forms 27 per cent of the total. The substance is whereas much lower total dc marketed in ampoules of 30 per cent strength for use intravenously or intra [n one individual, not includ( mnscularly. Excretion is via the kidneys and is rapid. 2,200 per 60 mm:! fell after tre It is generally presumed that the effectiveness of heavy metal preparations is due to the heavy metal, in this case antimony, and reports on such substaru:es PROTOSTIB AND ELEPHANTIASI usually express the dose in terms of the metal itself, as is done below. Of the 56 elephantiasis I This is not the whole answer: the factor which determines the safety of the months ago it has been possil preparation and the total amount requiIed is the salt itself, not the heavy metal total amounts of the drug. content alone, e.g. in the treatment of kala azar it may be necessary to give to adults tctal doses as high as 72 grm. of the salt, i.e. 20 grm. of antimony, a dosage Results greatly in excess of what is tolerated or what would be necessary with certain Y No change in size of afj other Sb preparations. . complete abolition In previous reports we have pointed out the disadvantages of protostib: pains, etc. heavy doses are required of this expensive preparation: it is not without danger, e.g. we quoted four patients of 164 developing exfoliative dermatitis: the sub No change in size of stance must be given by injection; patients agree that the injections are painful: recurrent attacks of and here also we do not know enough about the disease to know whether it is a good thing to kill the adult worm, which protostib undoubtedly seems to do in N a change in size of a a proportion of patieots receiving sufficient treatment. improved or worse Because of the above disadvantages we do not recommend this drug for field It will be seen that pro work, although, as will be seen below, it has proved beneficial in certain of our affected patients; but such I patients. by the use of hetrazan. EFFECT ON SYMPTOM-f'REE BANCROFTIASIS Our large-scale field experiment was carried out with the same objects in PROTOSTIB AND GENITAL FlU view as the experiments with hetrazan, i.e. to establish whether or oot adminis (a) Sirnple hydrocoele.-: tration of protostib to symptom-free individuals showing micr01ilarrernia will mcnths ago. affect the incidence of late complications. Of the 130 patients treated 18 months ago we have traced 110. So far no single individual has developed late compli cations either hydrocoele or elephantiasis. Observation contioues. Results EFFECT ON MICROFlLARA::MIA Cured, i.e. clisappearanc symptoms and sigm We have already stated in previous reports that the effect of protostib on the microfilarial level in no way resembles that of hetrazan: there is no direct Improved, i.e. reduction microfilaricidal effect; the fall in the microfilarial blood level is slow and in number of attack undoubtedly related to the effect of the heavy metal on the adult female wornl. Given sufficient time, however, protostib does by this effect produce a marked No change .. and sustained fall in the microfilarial blood levels. This is shown below. M1CROFILARlAL LEVELS IN BLOOD OF PATIENTS EIGHTEEN MONTHS AFTER The individuals showinl TREATMENT WITH PROTOSTlB originally had been large, oj ---~:~-:~--- I Total I No. of I MI'. counts' per 60 -:l~ NOle.-Protostib, /il<. Dose D~ug Tota~ microtilariae Reduc- I patients patients not made mr. free small or moderately size mgms. "b. patten,s -- tlOn I made 1---1 ---1---1 1--- drug hetrazan is to be p, per kg. mr. under Over Before I After I free lOmfs. I 10--30 31-100 100 ~-i--I % ~------i-- ('b) Lymph scrotum or el Under 200 'I Q I observed for more than 12 mgms. Sb 15 1,107 232 79 II 4 6 2 3 the condition of the skin or 200-240 mgms. I I I Sb. .. 68 5,421 I 448 92 I 29 25 9 5 stated most positively that l Over 240 rngrns. I I Sb. 47 3,925 i 387 91 I 23 15 5 3 of the recurrent pain, ----- ~ .., 25 The tabulated data shows that even with total doses dangerously near to the toxic level there was no guarantee that the adult female wom1 would be killed or sterilized. In fact the heaviest total dosage given. of 274 mgrns. SbY per kg. 'l'-methyl glucamine antimoniate body weight, only lowered the initial microfilanemia to 50 per cent of its value, Df the total. The substance is whereas much lower total doses often rendered the individuals microfilaria-free. for use intravenously or intra rn one individual, not included above, the initial high microfilari blood level of rapid. 2,200 per 60 mm3 fell after treatment only to 350 microfi[arire per 60 mm3 blood. :ss of heavy metal preparations and reports on such substaru::es PROTOSTIB AND ELEPHANTIASIS elf, as is done below. Of the 56 elephantiasis patients treated by us with protostib more than 12 ich determines the safety of the months ago it has been possible to trace 40 of whom 39 had received satisfactory salt itself, not the heavy metal total amounts< of the drug. it may be necessary to give to ~. 20 grm. of antimony, a dosage Results vould be necessary with certain No change in size of affected limbs: much improvement or . complete abolition of recmrent attacks of fever, leg he disadvantages of protostib: pains, etc. 28 'ation: it is not without danger, exfoliative delmatitis: the su b- No change in size of affected limbs: some lessening of that the injections are painful: recurrent attacks of fever, leg pains, etc. .. 6 e disease to know whether it is ;tib undoubtedly seems to do in No change in size of affected limbs: recurrent attacks not nent. improved or worse 5 ,t recommend this drug for field ved beneficial in certain of our It will be seen that protostib in sufficient dosage does bring relief to the affected patients: but such relief can be o'btained more safely and more easily by the use of betrazan. out with the same objects in PROTOSTIB AND GENITAL FILARIASIS ablish whether or not adminis s showing microfilarremia wi!! (a).Simple hydrocoele.-Seventeen patients, treated with Protostib over 12 130 patients treated 18 months months ago. lual has developed late compti ,ation continues. Results Cured, i.e. disappearance of hydrocoele and of all related 1t the effect of protostib on the symptoms and signs 9 . hetrazan: there is no direct rial blood level is slow and Improved, i.e. reduction in size of hydrocoele with reduction ~tal on the adult female worm. in number of attacks of recurrent fever 2 . this effect produce a marked ,Is, This is shown below. No change .. 6 ; EIGHTEEN MONrHS AFTER lsnB The individuals s.howing no change were those in whom the hydrocoeles I originally had been large, of a diameter of 30 em. or more. I f i Mf. counts per 60 lllmJ in Note.-PrO'to'Stib, like hetrazan, can cure a certain proportion of simple 1.8 i patients not made mf. free small or moderately sized filarial hydrocoeles but here again the ,~impler safer it~K ~o8r drug hetrazan is to be preferred. _I \10-30 ,I 31-100 [ ! I (b) Lymph scrotum or elephantiasis scrotum.-Five treated patients have been i observed for more than 12 months: in no case was there any improvement in 6 2 3 i I the condition of the skin or the size of the tumour, but two of the five patients 25 I 9 5 I' stated most positively that they felt greatly improved, with no crippling attacks l5 5 3 of the recurrent pain. 26 (4) Neostibosan and SoIustibosan EFFECT OF SOLU These preparations are produced by Messrs Bayer & Co., who have kindly kept us supplied with material free of charge. I Tol Total Dose I Total I micTOfi mgms. Sb5 patients N £OSTIBOSAN per kg --- The makers state that neostibosan is diethylamine p-aminophenylstibonate Before with the antimony pentavalent and representing 42 per cent of the total. The undeT~Omgms.II--->--- compound is sold as powder in ampoules. It may be injected intramuscularly or I intravenously. The solution is prepared with distilled water: it must be freshLy Sb5 .. 2 I 217 prepared and must not be heated. The makers recommend that treatment begin I with small doses and state that using kala azar treatment as a basis the total 30-60 mgms. Sb. 5 4 I 295 dosage for an adult (of about 100 lb.) is 3.0 g. of the salt, i.e. 1.26 grm. of Oyer 60 mgms. 3 1 263 antimony. This total dosage can be given as an intensive course daily over eight days, or intermittently every two to three days up to the required total. No conclusions can be 1 Contraindications include ascites, nepluitis, pneumonia and jaundice. EFFEcr OF SOLUSTlBOSAN ON A point already made in the text above is that, although the dosages are Satisfactory data for a 10 expressed in terms of SbY , the compound containing the Sb Y is of importance and not merely the dose of the heavy metal itself, e.g. the total dosage of available only from 14 patil neostibosan recommended by the makers as sufficient for the treatment of kala measurement of the leg enh SUbjective improvement with azar is only 3 g. (J .26 g. of SbV ), whereas the corresponding total dosage of V patients reported that such at protostib is 72 grm. of salt (20 g. of Sb ). Excretion is mainly via the kidneys at first rapid, then slow. This slowing-up of excretion and the firm linkage of Sbv On the question of the ( in the compound may account for the activity of the substance. are insufficient to permit of a A mass therapy campaign with neostibosan was begun on Ukara Island but (5) Arsenamide had to be temporarily, abandoned, As a result, very few patients have been observed for a sufficiently long period to allow of our reporting on the use of this INTRODUCTORY drug in bancroftian filariasis. Introduced first by Otto, formula:- SOLUSTIBOSAN AS (S.CHCOOH Solustibosan is'the diethYl-amino-ethanol salt of sodium antimony gluconate: here also, the Sb is pentavalent; with the newer preparation (solustibosan con centrated) antimony forms 37 per cent of the total. The drug is marketed as a sterile aqueous solution of which .1 m!. contains approximately 370 mgms. of salt, The drug must be given JOO mgms. Sb Y • The drug may be given intravenously or intramuscularly. It is by the bowel and the kidneys rapidly excreted via the kidneys, 80 per cent being excreted on the first day. cent trivalent arsenic in amJ Although this compound is said to be very similar in its chemical structure to dosage recommended is 0.2 1 protostib, the total doses of soIustibosan recommended as necessary for the cure fifteen days. Latterly one of of kala azar, when measured by the total antimony administered, are only one half the time, in seven days. sixth of the dose recommended for protostib, i.e. the makers recoounend total doses of solustibosan up to 13.3 grm. (not 5 grm. as reported in our 1950 The material used by us Filariasis Report p. 44). Probably due to its rapid excretion, the substance is Messrs. Lilly and Messrs At relatively safe and daily doses as high as 110 mgms. of substance per kg. (not 90 preparations in certain respe. mgms. as stated in our 1950 Report) are well tolerated by rabbits. microfilaria;, and reports oc Certain workers consider th: The doses recoounended by the makers for the treatment of kala azar: trivalent and pentavalent an Average daily dose for adults=O.l mls. per kg. body weight for ten consecutive bility to a satisfactory propc days. For a 50 kg. adult this \vould represent a total of 50 mls. of substance. who> have much experience c Another preparation is solustibosan oleosum, in which 1 ml. of the sub From our animal expcrimcn 5 be used in the field, and, as .stance contains 200 mgms. of solustibosan and 54 mgms. Sb • So far we have not used this preparation. hospitalized during the full c numbers treated. Recentty OI Treatment of patients has begun with solnstibosan but only a few individuals developed jaundice a few da~ have been observed for a sufficiently long post-treatment period. Brief details been due to infective hepati· are given below, likely cause. ~' 27 EFFECT OF SOLUSTIBOSAN "conc." ON MICROFILARiEMIA 'ayer & CO., who have kindly ~'A· __• ___•• ------Total No of Mr. counts p. 60 mm3 in patients Total Dose I Total Il1Icrofilanae I RedUC- Ipatients ' not made mf.-free mgms. Sbs patients Hon made ------Under Over per kg. mf 10-30 31-100 lmine p-aminophenylstibonate -1-Before After I 1 neg. 10 ruC 100 --,-----1 2 per cent of the total. The I be injected intramuscularly or Und<;;r30mgms. I I %Q I Sb' . 2 217 201 Nos. .ed water: it must be freshly I insig- omrnend that treatment begin I nificant reatment as a basis the total 30-60 mglrls. I Sb.s 4 295 II 96 2 2 f the salt, i.e. 1.26 grm. of Over 60 mgms. 3 263 7 98 2 1 intensive course daily over I ays up to the required total. 'nia and jaundice. No conclusions can be reached on the small numbers shown above. EFFECT OF SQLUSTIBOSAN ON ELEPHANTIASIS .1, although the dosages are lng the SbY is of importance Satisfactory data for a long enough post-treatment period of observation are Of, e.g. the total dosage of available only from 14 patients: no patient showed any improvement in the ent for the treatment of kala measurement of the leg enlargement but 6 of the 14 patients reported much orresponding total dosage of subjective improvement with no recurrence of periodic attacks of pain and four 1 is mainly via the kidneys at patients reported that such attacks were much less frequent and severe. and the firm linkage of Sb Y On the question of the effect of solustibosan on filarial hydrocoele the data he substance. are insufficient to permit of analysis. This work continues. begun on Ukara Island but (5) Arsenamide ;ery few patients have been Jr reporting on the use of this INTRODUCTORY Introduced first by Otto and Maren, this organic arseFlical preparation has the formula :- AS (S.CHCOOH)2 CH.NH2 . sodium antimony g1uconate: ./--> II )reparation (solustibosan con ",-_ a I. The drug is marketed as a -roximately 370 mgms. of salt, The drug must be given intravenously and is excreted fairly rapidly equally usly or intramuscularly. It is by the bowel and the kidneys. It is. marketed as the sodium salt containing 18 per 19 excreted on the first day. cent trivalent arsenic in ampoules of 1 or 2 per cent buffered solution. The r in its chemical structure to dosage recommended is 0.2 mgms. of arsenic daily per kg. of body weight for ded as necessary for tbe cure fifteen days. Latterly one of our workers has given the same total dosage in 1 administered, are only one half the time, in seven days, by giving injections twice daily. the makers recommend total m. as reported in our 1950 The material used by us in our tests was kindly supplied free of charge by d excretion, the substance is lvlessrs. Lilly and Messrs Abbott. This heavy metal differs from the antimonial . of substance per kg. (not 90 preparations in certain respects: the As is trivalent; reports state it acts on the ited by rabbits. microfilarire, and reports on the question of its toxicity are very conflicting. Certain workers consider that in filariasis it is practcally impossible both with the treatment of kala azar: trivalent and pentavalent arsenical preparations to reconcile effect and tolera iy weight for ten consecutive bility to a satisfactory proportion: on the other hand Otto and his co-workers, otal of 50 mls. of substance. who have much experience of arsenamide, consider it to be relatively non-toxic. in which 1 m!. of the sub From our animal experiments we are not satisfied that arsenamide may safely 5 be used in the field, and, as a result, all patients treated by us have had to be .gms. Sb • So far we have not hospitalized during the full course: this has imposed a serious limitation on the numbers treated. Recently one patient treated with a full course of arsenamide ;an but only a few indtviduals developed jaundice a few days after the course finished. Although this may have 'eatment period. Brief details been due to infective hepatitis, arsenical posioning cannot be excluded as the likely cause. 28 In two years it has been possible to treat satisfactorily only 36 patients. Transrnissioll Of the 36 patients, 13 have been under observation over a period of time suffi ciently long to permit of conclusions being drawn. Brief details are given below. One of the aims laid do eliminating filariasis from ari EFFECT ON MrCROFILARtEMIA methods of control present tl In the six patients for whom records exist the drug did appear to have a or to remove the vector. In direct effect on the level of: microfilaria; in the blood. This effect was not nearly sterilizing or so lowering the so marked as is found with hetrazan: by the end of a fifteen-day course the him non-infective to the vecto] findings in the six patients were~ As yet the factor preventing 3 knows what is the microfila Total microfilaria; levels before treatrnent=461 per 60 mm . become infected to any signiJ Total microfilaria; levels at end of course = 46. more fully in the future. This effect is also shown on Mr. perstans: one of the six patients had a double infection i.e. W. bancrofti and D. perstans and the Mf. persIans level fell The other method of can as fast as the Mf, bancrofti level. possible by tbe introduction 0 Twelve months after treatment the findings in detail were-- ing of such a method is not control must be maintained experiment, we have maintaiu, L~-I 5 function of which is to obt ______. p";",, No, [ 3 I 4 1___1 6 methods of vector control. l j 3 flight range of vectors, and, Before treatment I' 210 mfs. p. 60 mm 1 25 I 10 'I' 28 I[ 38 1 ISO should be little risk of re-inv After treatment ('; II I I 8 . 1 ' ! I I The year's work consist. In patient No.5, a female who had the double infection, no Mf. perstans Island. were found in the blood. Dissection Results EFFECr ON ELEPHA.."ITIASIS Two of the elephantiasis patients treated have been observed for over a year. Most adult mosquitoes t In neither patient has there been any lessening of the size of the elephantoid the north coast, and Nyamanl legs, and neither patient reports any of the subjective improvement which has cent and at Nyamanga 24.8 pe been so' marJced' with certain of the other preparations discussed above. filariasis. Individuals of II following is a summary for EFFECT ON GENITAL FILARIASIS Five such patients have been observed [or periods longer than one year. In four of the five (patients the cOildition was advanced, with elephantoid changes of the scrotal skin. The remaining patient showed a smali hydrocoele only. One Number Species dissected of the four elephantoid scrota showed also lymph scrotum with Mf. banerofti in tbe escaping fluid. Immediately after treatment the Mf. bancrofti disappeared from tbe lymph scrotum fluid. Results of treatment have been:- -_._---,~ (i) Patient with the early bydrocoele considers himself cured: there is now no evidence of hydrocoele and no recurrent attacks of pain and fever. A. gambiae 3,187 A. junestus 1,128 (ii) Of the four patients with advanced genital filariasis one is very pleased: A. pharoensis 93 he feels much better and claims that his scrotal swelling has decreased T. ajricanus 1,106 in size. (This is supported by measurements before and after treatment.) T. ud/armis 1,080 The other three report no change and complain that the treatment has C. antermatus 34 had no e'ffect on tbe recurrent attacks of fever and of pain: one patient reported that these attacks had become worse and more frequent, the last one causing him to be confined to bed for two weeks. Biting Incidences Until we are satisfied that arsenamide is of value and safe for use in the Catches, made seasonaUJ field it wil1 not be possible to carry out extended field trials such as reported that A.. gambia! and A. [lines above for other d,rngs. night, with very smail numbe well. Catches made concurrei Summary.-The number of patients treated is as yet too small to express any C. annulioris and C. antenn definite views, but it would seem that arsenamide is not capable of doing anything from 7 p.m. to 3 a.m. and are' which cannot be done more easily and more safely by other drugs. j: ,. '. ;- 29 satisfactorily only 36 patients. Transmission on over a period of time suffi Brief details are given below. One of the aims laid down is tbat we study methods of controlling or eliminatiag filariasis from areas where this is thought necessary. Two obvious methods of control present themselves, namely to render the host non-infective rre drug did appear to' have a or to remove the vector. In the text above we have discussed the question of lad. This effect was not nearly sterilizing or so lowering the microfilaria: count in the host's blood as to make ld of a fifteen-day course the him non-infective to the vector. Retrazan has been suggested as the drug of choice. As yet the factor preventing large-scale control on such Jines is that no one I per 60 mm·. knows what is the microfilaria: blood level below which the vector does not become infected to any significant degree. It is hoped to investigate this matter 6. more fully in the futme. one of the six patients had a and the Mf. perstans level fell The other method of control, that of eUminating the vector, has been made possible by the introduction of the newer insecticides. The planning and the cost in detail were---- ing of such a method is not easy particularly when it is remembered that vector control must be maintained for about ten years. As a preliminary to such an experiment, we have maintained on Ukara Island a field entomological team, the 3 I 4 I 5 I 6 function of which is to obtain the basic data necessary in the planning of -----I---i--- methods of vector contra!' Ukara Island has been chosen because it is ont of flight range of vectors, and, in the event of vector control being attempted, there 10 28 II 38 150 8 1 should be little risk of re-invasion by mosquitoes. The year's work consisted largely of field studies on m?squitoes of Ukara ble infection, no Mf. perstans Island. Dissection Results been observed for over a year. Most adult mosquitoes have been collected from two vilJages-Bubanja on )f the size of the elephantoid the north coast, and Nyamanga near the centre of the island. At Bubania 25.9 per ective improvement which has cent and at Nyamanga 24.8 per cent of the inhabitants are infected with bancroftial I'ations discussed above. filariasis. Individuals of 11 species of mosquitoes have been dissected. The following is a summary for species found with filarial "worms:- riods longer tban one year. In Iced, with elephantoid cbang,es Number % with Number %with a small hydrocoele only. One Number with develop- with infective Species dissected develop- mental infective forms h scrotum with Mj. bancrojti menta! forms forms the Mf. bancrofti disappeared forms nt have been:------himself cured: there is now no ittacks of pain and fever. A. gambiae 3,187 52 1·7 15 004 A.lunes{us 1,128 35 3'1 11 1·0 filariasis one is very pleased: A. pharoensis 93 12 12·9 0 0 scrotal swelling has decreased T. a.fi"icanus 1,106 8 0·7 0 0 lts before and after treatment.) T. uni;formis 1,080 6 0·6 0 0 rnplain that the treatment has C. antennatus 34 1 3·0 0 0 of fever and of pain: one ---_. orne worse and more frequent, o bed for two weeks. Biting Incidences value and safe for use in the Catches, made seasonally, of mosquitoes biting a man in a cone but show :l field trials such as reported that A. gambhe and A. funestus are the most numerous species biting indoors at night, with very small numbers of T. atri'canus. T. uniformis and C. annulioris as well. Catches made concurrently outdoors show that T. ajricanus, T. uniformh. as yet too small to express any C. annulioris and C. antennatus are largely outdoor biters. Collections extend not capable of doing anything from 7 p.m. to 3 a.m. and are made on alteruate nights until three such collections { by other drugs. 30 are made in each village. The average number of mosquitoes collected indoors per The distribution of mosq~ night between 7 p.m. and 3 a.m. is interpreted as a rough estimate of the number Collections of mosqu which bite a sleeping person at night. At Bubanja, A. gambia? bites are of the order of 200 per night at the end of the long rains (March-May) and three per 1. Mosquitoes rest a night at the end of the long dry season (June-September). A. funestus bites at found higher thaI the rate of 30 per night at the end of the long rains, 50 per night in July, and 11 huts at Busan one per night at the end of the long dry season. The incidence of biting of C. annulioris weT A. gambia: and A. funestus is lower at NY'amanga than Bubanja. the aid of alai beyond the react fumes from the An occasional T. airicanus, T. uniformis, and C. antennarus is taken in the top of the hut collections at Nyamanga but at Bubanja the biting incidences of these species are high. Local abundance of these species can be accounted for by their exten 2. A. gambia: and A. sive breeding in a bay in the coast nearby. dark half of a j cattle half. In a The T{eniorhynchus species do not show extreme peaks of biting, although at female A. gambifJ the end of the long rains T. uniformis bites at the rate of 65 per nigbt outdoors, cattle sections c( compared with 10 per night at the end of the dry season, T. africanus appears collected simultan to be more even in its seasonal biting incidence, and bites at the rate of 20 per tions, 337 A. gam night at the end of the long dry season. As these Ta:niorhynchus species are mainly sections compared outdoor biters, their habits have been investigated to find the times when, and sections. the places Where, they come into contact with man and animals. The Wakara sit outside theil' huts, often grouped round a small fire, before they have their 3. There is an indicati, evening meal indoors at about 9 p.m. At this time they are exposed to t4e bites for resting in man of T a:niorhynchus species and C. antennarus. People are also brought into con tions the ratio of tact with Ta:niorhYl1chus, and are bitten, when they visit latrines. The latrines is 13 per cent COl are often situate-d amongst rocks and closely pruned trees which occur together. A. gambia? restin! In some villages, such as Bubanja, and Busangu, trees are pollarded 6 in. to of collections in 3 ft. off the ground and a Clump of pollards forms a latrine. At Bubanja, A. gambia! was f, T. africanus, T. uniformis and C. antenna/us rest in crevices in rocks, among cent in man's sec the leaves of plants near rocks, and among the leaves of pollarded trees. In the shade of the pOllards and the rocks people are bitten day and night, although the latrines are used mainly at night. Factors affecting biting ael 1. A hut fire. It is tIl Host preferences. fire is always sma sticks are kept bu Mr. Weitz of the Lister Institute of Preventative Medicine in England very at 7 p.m. The fin kmdly undertook the analysis of a large number of blood smears. Precipitin tests smoulder for two on mosquitoes resting on the walls of huts show that 91 per cent of A. gambia:, bait" in a hut wil 85 per cent of A. funestus, 36.8 per cent of T a?niorhynchus airicanus, 26.1 per huts, fires and be cent of Ta?niorhynchus uniformis and 13.9 per cent C. annulioris had fe-d on fe~ analysis, Which sh man. Whereas Culicines resting in 'huts had largely on domestic or wild animals activities of A. gao A. gambia? and A. funestus collected from the walls of huts had fed mainly on man. The precipitin test results confirm dissection findings that on Ukara island Culicines can be excluded as vectors of bancroftian filariasis, and strongly supports 2. Attractiveness of c bo~ that infective forms of fiJari~ in A. gambia? and A. funestus, taken resting in huts, showed that a are derived from man. It is also concluded that, although a low percentage of as a man of 38 yel A. gambia: and A. funes/us are infective there is a very high probability that the bution of childrel infective forms will be transmitted to people and not to domestic or wild animals. six and sixteen hi A. phwa:nsis is normally scarce on the island, but follOWing failure of the short the bites of A. gao rains in November, there was a slight increase in numbers at Bubanja, although none were found at Nyamanga. A. phara:nsis has been recorded as highly anthro Outdoor resting places pophilic by other workers, so there is a possibility that this species may be a T. africanus, T. unifo. minor vector on Ukara. It occurs in such small numbers, however, that even j'f doors, can be collected eaJ infective forms do exist, this species is of little importance (lS a vector on Ukara. have been made of blood ,. ~ .-" ' .. " 31 toes collected indoors per The distribution of mosquitoes resting in huts h estimate of the number Collections of mosquitoes resting on the walls of huts show:- gambice bites are of the -arch-May) and three per 1. Mosquitoes rest at the base of the. wans of a cone hut and are rarely found higher than 7 ft. above the ground. Collections were made from ler). A. funeSlus bites at 11 huts at Busangu on the. east coast. Ninety-three A. gambia: and six jO per night in July, and C. annulioris were taken by coHectors standing on the floor, and with e incidence of biting of the aid of a ladder simultaneous searching revealed no- mosquitoes Bubanja. beyond the reach of a collector on the floor. It is thought that the fumes from the fires, or their sticky resinous deposit on the walls at antenna/us is taken in the top of the hut, repel the mosquitoes. cidences of these species unted for hy their exten- 2. A. gambia: and A. funestus are found resting in greater numbers in the dark half of a hut which comprises man's section than the lighter cattle half. In a series of collections from 20 huts at Nyamanga 276 aks of biting, although at female A. gambia: and 46 A. funestus were collected from the walls of of 65 per night outdoors, cattle sections compared with 433 A. gambia! and 91 A. fUl1'estus ,on, T. ajricanus appears coHected simultaneously in man's section. In another series of collec ites at the rate of 20 per tions, 337 A. gambia! and 90 A. funestus were collected resting in cattle ynchus species are mainly sections compared with 777 A. gambia! and 256 A. funest·us from man's find the times when, and sections. nd animals. The Wakara ~, before they have their 3. There is an indication that female A. funestus shows a stronger preference . are exposed to the bites for resting in man's half than female A. gambia:. In one s:eries of collec re also brought into con tions the ratio of A. funestus to A. gambia: resting in the cattle section iisit latrines. The latrines is 13 per cent compared with 21 per cent ratio of A. funestus to ees which occur together. A. gambir:e resting in man's half. This is supported by another series s are pollarded 6 in. to of collections in which a ratio of 25 per ~nt female A. funestus to ; a latrine. At Bub·anja, A. gambir:e was found resting in cattle sections compared with 35 per revices in rocks, among cent in man's sections. of pollarded trees. In the y and night, although the Factor~ affecting biting activities in a hut 1. A hut fire. It is the custom of the Wakara to cook in their huts. The fire is always small, because firewood is scarce, and only three or four sticks are kept burning. Fires are lit at noon and for an evening meal !fedicine in England very at 7 p.m. The fire may be built up before the people go to bed and )0. smears. Precipitin tests smoulder for two or thrce hours. Mosquitoes were collected off "human 1 per cent of A. gambia:, bait" in a hut with a fire and a hut without one. All combinations of nclms africanus, 26.1 per huts, fires and hoys were employed to give data for proper statistical 7. annulior'is had fed on analysis, which showed that fires had no significant effect on the biting domestic or wild animals activities of A. gambia! and A. funestus. , huts had fed mainly on ngs that on Ukara island 2. Attractiveness of child and adutt. An experiment at the end of May isis, and strongly supports - showed that a boy aged teu years was equally attractive to A. gam.bia! I'tus, taken resting in huts, as a man of 38 years. Observations on type of bed covering and on distri lugh a low percentage of bution of children in beds showed that children between the ages of high probability that the six and sixteen have tittle bed clothing and are thus most exposed to domestic or wild animals. the bites of A. gambia: and A. funestus. )wing failure of the short bers at Bubanja, although 'ecorded as highly anthro Outdoor resting places ,at this species may be a T. africanus, T. uniformis and C. antennafus, which largely bite man out ers, however, that even if doors, can be collected easily from their natural outdoor resting places. Smears lee as a vector on Ukara. have been made of blood fed individuals of these species resting outdoors and 32 analysis will give ns some indication of their host preference. C. univittatus and SECTION 3-0J C. annulioris are commonly fonnd resting in crevices in river banks and along Introductory the sides of gullies madc by erosion at the centre of the island. Nearly every specimen in these places is nnfed but occasional individuals of C. univittatus Our aims and intentions taken from a hand-made pit at Nyamanga are freshly gorged. Collections from introduction to this report, the pit in July indicated that Anopheles ru[ipes and Anopheles longipalpis are onchocerciasis, to investigate common outdoors in July although they are rarely found indoors. A. gambire. Field Surveys A. funestus and A. rhodesien.sis have been taken from the hand made pit and The first stage is to carr from caves towards the centre of the island. Collections made at intervals of fashion as that used to establi an hour over 24 hours from the walls of a cave show that A. gambia, A. funeslus to date is:- and other species leave the cave afteT dusk and that individuals of the sam13 species enter the cave at dawn and that a small number of them are gorged with Tangankiya.-Isolated Ci blood. suffering from onchocerciasis, to certain parts of the Sourr Breeding placey reported above, it was not pc the Southern Highlands Pro It is mentioned in the 1951 Report that little breeding occurs in coastal is possible that two to three waters, and that there is a high seasonal peak after the long rains. A larval survey so limited in extent, and til in May and June shows that extensive cultivation of rice in river valleys is unlikely that onchocerciasis v the main factor in producing the high seasonal incidence of A. gambire and in Tangany'ika; in any event A. funestus. Rice is planted principally in the river basins in March and by means the methOds now in use in K of a well-regulated system of irrigation the Wakara flood wide' areas of land. have begun The livers rise in the high centre of the island and spread over wide beds in Kenya.-We shall require to do little mOT< the coastal region. The bulk;. of the rice is grown on the west side of the tion available shows that the island. A coarse grass called rubimbili is widely grown as cattle fodder..This with five foci all found in g,rass is planted in the sandy beds of rivers, in small fields and pits dug in the Victoria. One of the areas is ( sandy beaches. The pits and fields contain water and in some areas such as the the number of people at ris north-west coast they are the main breeding places of A. funestus in the locality. The breeding places of other mosquitoes have been noted and these and other Kenya, the disease is a seriOI are now almost completed, details will be published in due course. Ueanda,-As we havc TIl Snails have been collected 'from various parts of the island to find the host latest information (already r' or hosts of Schistosoma species. the east there is a large focus in the centre of the country, the White Nile, there is a la size, extending along practica, and forming a line related to Throughout thc affected breeding habits of which rene Symptoms and Signs (1) Introductory Economically and clinical problem than is bancroftiasis, late manifestations suffer an individual infected is a sick may mean practically the whc importance, but. the skin chan and even in the early stages ti ness a common eud-result in The essential difference ; lies in the agent responsible fl the elephantiasis and genital fi adult worm (living or dead we changes are all due to the I ~ .~ '" .... ," 33 preference. C. univittattts and SECTION 3-0NCHOCERCIASIS IN EAST AFRICA ices in river banks and along Introductory 'e of the island. Nearly every Our aims and intentions in regard to onchocerciasis are as quoted in the I individuals of C. univittatus introduction to this report, i.e. to establish how common and how serious is eshly gorged. Collections from onchocerciasis, to investigate methods of control, and to investigate treatment. I1d Anopheles longipalpis are :ly found indoors, A. gambite, Field Surveys from the hand made pit and The first stage is to carry out a survey of the three territories in the same llections made at intervals of fashion as that used to establish the picture of W. bdncrofli iufection. Information JW that A. gambi~, A. funestus to date is:-- that individuals of the same Tangankiya.-lsolated cases have been reported in the past of individuals llllber of them are gorged with suffering from onchocerciasis. Such cases are very few in number and are limited to certain parts of the Southern Highlands Province: in a survey of that area reported above, it was not possible to demonstrate any case of .onchocerciasis in the Southern llighlands Province, although suitable vectors were identified. It tie breeding occurs in coastal is possible that two to three isolated foci of infection do exist, but they must be the long rains. A larval survey so limited in extent, and the number of individuals at risk so few, that it is ou of rice in river valleys is unlikely that onchocerciasis will ever be anythiug other than a minor problem iucidence of A. gambite and in Tanganyika; in any event it will be easily possible to control the vector by basius in March and by means the methods now in use in Kenya. .ara flood wide areas of land. Kenya.-We have begun survey work in Kenya but iLis expected that we and spread over wide beds in shall require to do little more than confirm the exact work of others. Informa lin on the west side of the tion available shows that the disease is limited to the Nyanza Province of Kenya, grown as cattle fodder. This with five foci all found in an area bounding the north-<;ast corner of Lake maH fields and pits dug in the Victoria. One of the areas is continuous with affected areas in Uganda. Although and in some areas such as the the number of people at risk is a relatively small proportion of the total in I of A. funestus in the locality. Kenya, the disease is a serious problem: fortunately adequate control measures :en noted and these and other are now almost completed. Uganda.-As we have not yet started work in Uganda, we give below the of the island to find the host latest information (already reported. 1951) contributed by Bamley (1952). In th~ east there is a large focus extending from the Mount Elgon area in Kenya: in the centre of the country, extendiug from Jinja a coufiiderable distance along the White Nile, there is a large focus: there are many scattered foci, small in size, extending along practically the whole of the western boundary of Uganda and forming a line related to the Great Lakes, Lake Albert and Lake Edward. Throughout the affected areas in Uga.nda the vector is 5'. damnosum, the breeding habits of which render it more easily controlled than S. neavei. Symptoms and Signs (1) Introductory Economically and clinically onchoceriasis is proportionately a more serious problem than is bancroftiasis. In the latter infection only the relatively few with late manifestations snffer any inconvenience, whereas in onchocerciasis every individual infected is a sick person requiring treatment. In certain areas this may mean practically the whole population of the area. The nodules are of no importance, but the skin changes are crippling (leading to suicide in rare cases) and even in the early stages the eye lesions interfere with efficiency, with blind ness a wmmon end-result in the late stages. The essential difference between .onchocerciasis and bancroftian infection lies in the agent responsible for the production of the changes: in bancroftiasis the elephantiasis and genital filariasis are caused in one way or another by the adult worm (living or dead we do not know), hut in onchocerciasis the important changes are all due to the microfilaria:, the positive phototropism of which 34 accounts for its presence in C()untless numbers in the skin and in the eyes: the microfilari~ skin becomes sensitized to dead and the presence of the larval forms (1) !ntroductory in the eyes leads to the local tissue reactions which produce interference with The fact that elimination function. Undoubtedly the nodules found in the skin are caused by presence of not relieve the clinician of hi! the adult worm but these are of no clinical importance. Other changes reported do more harm than good: tl include onchocercal elephantiasis and hydrocoele, but we have never seen such may be very trying for the lesions, which must be ra re in East Africa. nothing will make good any c The more important diagnostic aids are dealt with in detail below: these has made progress so slow: e include skin biopsy, reactions to antigens, nodule biopsy, skin changes and eye the control of an ophthalmol changes. produce drug schedules safe the investigation of every drug (2) Skill Biopsy particularly the skiu lesions a This method is laborious and time-consuming and only positive results are filaria;? What effect has the of value: due to the irregular scatter of the microfilaria; over the body, even obviously infected individuals may show negative skin snips. In spite of this we (2) HetraZ!lD USe skin snipping as one method of diagnosis. The snips are always taken from EFFECT ON SKIN CHANGBS the right shoulder to aJlow of standardization of results. The harmful agent is th< unlike bancroftiasis, the mie (3) Reactions to Antigens factor, and it is only to be So far this has proved as unsatisfactory in onchocerciasis as in bancroftiasis: skin changes and pruritis un skin tests and serological tests with antigens are not as yet of any practical value. This means that for the first low to prevent damage to the (4) N (}du~es Thereafter, when almost all 0 If nodule'S be exCised, it is easy to demonstrate in them the presence of the to increase the dosage, in the adult worms, but such is not a practicable procedure in field work and ~ not the adult worms. For the Ii; essential. The site and character of the nodules are almost diagnostic in them along, the liues used in the selves and can be tak;en as valuable confirmatory evidence in doubtful cases. to it (reactions may be con histaminics). In our original ( (5) Skin Changes day, our doses being in sorr In well-established cases, when taken in conjuncti{)n with the history of (1949). This was done delibe intense generalized itching day and night, the skin changes should suggest the only permissible because the I diagnosis. The \Vhole affected skin area is thickened, dry, rough, shiny and Such C()urses should never be inflamed and shows linear scratch marks. The pruritis precedes the skin changes, one mgm. per kg. body weil some of which may be due to the trauma of continuous scratching. skin reaction becomes minilm That the skili reactions are a sensitization phenomenon related to the death drug per kg. body weight thn in situ {)f micro-filaria; is well shown by the administration of hetrazan. As in drug per kg. body weight. Thi bancroftiasis this drug is markedly microfilaricidal and the administration of even one week. one tablet to a patient wilh onchocerciasis results in an almost immediate marked exacerbation of the pruritis with the whole of the skin inflamed and with the Hetrazan is remarkably n face showing peau d' orange. This is a valuable diagnostic aid. kills or sterilizes the female that it does not do so and t (6) E)'e Le~iolIs within a year. Even if this I Microfilarite volvulus are commonly found in the eyes of patients with value: the importance of tl: onchocerciasis, this being one indication of the positive phototropism of the larval courses or of giving routine forms, which in turn is a result of the day-biting habits of the vector. Photophobia weekly, as a suppressant. is the earliest symptom, with blindness the end-result. The incidence of eye lesions The Kisii area of Kenya varies from area to area: Bowie (1950) talking of the Belgian Congo mentions or not hetrazan in adequate "caravans" of hlind men and women. In Kenya the incidence of eye C()mpIica to do with W. bancroft!: the tions is probably less than was suggested by the original surveys, which probably work designed to eradicate S. included blindness due to other causes. The exciting agent in the production ot fore now be given without i eye changes is the presence of dead microfilarire. In this work on onchocerciasis explain certain of the failure we have been fortunate in being allowed to co-opt Dr. Roy McKelvie by kind details were given of the rcsu permission of the Director of Medical Services, Kenya. Dr. McKelvie is ao series of hospital patients. A, ophthalmologist with much experience of the eye changes in onchocerciasis. For before the eradication experir our 1951 Report he contributed an authoritative summary of the problem. to follow them up'. A much h - ,<:'';~'. ~ ... 35 I skin and in the eyes: the Treatment )resence of the larval fonns (1) Introdudory produce interference with The fact that elimination of the vector of onchocerciasis is practicable does are caused by presence of not relieve the clinician of his legacy of sick people. But careless treatment may Ice. Other changes reported do more harm than good: the intense skin reaction to over-enthusiastic dosage t we have never seen such may be very trying for the patient, although it does finally settle down; but nothing will make good any damage done to the eyes. It is tbis possibility which lith in detail below: these has made progress so slow: each patient must be hospitalized and must be under )psy, skin changes and eye the control of an ophthalmologist: only by such measures will it be possible to produce drug schedules safe for field use. Problems which must be answered in the investigation of every drug are; has the drug any effect on the changes present, particularly the skin lesions and eye lesions? What effect has the drug on micro 1d only posItIve results are filarire? What effect has the drug on the adult worm? 'lalire over the body, even i1 snips. In spite of this we (2) lHetrazan :lips are always taken from EFFECT ON SKIN CHANGES Its. The harmful agent is the dead microfilaria: consequently in onchocerciasis, unlike bancroftiasis, the microfilaricidal activity of a drug is the important factor, and it is only to be expected that an effective drug will exacerbate the erciasis as in bancroftiasis: skin changes and pruritis until the great mass of microfilarire has been killed. ; yet of any practical value. This means that for the first two to three days of treatment dosage must be low to prevent damage to the eyes or even death of the patient (Rodhain, 1949). Thereafter, when aJmOSI all of the microfilarire havc been killed, ~t is safe greatly n them the presence of the to increase the dosage, in the hope of completing the cure by killing or sterilizing e in field work and is not the adult worms. For the first few days the pattern of treatmeut shOUld be almost diagnostic in them along the lines used in the administcrIng at scrum to au iudIvidual sensitive dence in doubtful cases. to it (reactions may be controlled to some extent by administration of anti histaminics). In our original experiments we used heavy doses even on the first day, our doses being in some cases 50 time higher thau those used by Burch LCtion with the history 01 (949). This was doue deliberately, to investigate certain eye' changes, and was :hange-s should suggest the only pelmissible becausc the patients were under the care of ·an ophthalmologist. ;d, dry, rough, shiny and Such courses should never be used m field work. The type of course suggested is precedes the skin changes, one m~m: per kg. body. ~eight of hetrazan citrate ~hree times daily until the uous scratching. skm reactIon becomes mlTIlmal, then an lllcrease of th{s dosage to about 5 mgm. menan related to the death drug per kg. body weight three times daily, with a total dose' of about 70 mgm. ;tration of hetrazan. As iu drug per kg. body weight. This means that the course of treatment will last about the administration of even one week. I almost immediate marked .kin inflamed and with the Hetrazan is remarkably microfilaricidal, but what is not known is whether it )stic aid. kills or sterilizes the female adult worm. Much of the published work suggests that it does not do so and that the skin becomes reinfested with microfilarire within a year. Even if this be tIlle it does not mean that hetrazan is of no the eyes of patients with value: the importance of the condition fully justifies the giving of repeated : phototropism of the larval courses or of giving routine prophylactic treatment, even as low as two tablets of the vector. Photophobia weekly, as a suppressant. 'he incidence of eye lesions The Kisii area of Kenya provides a suitable testing ground to settle whether e Belgian Congo mentions or not hetrazan in adequate dosage can sterilize the female worm as it seems incidence of eye complica to do with W. banero-iti: the Kenya medical authorities have almost completed Lal surveys, which probably work designed to eradicate S. neavei. Treatment of infected individuals can there :rg,ent in the production of fore now be given without the complicating factor of re-infection which may his work on onchocerciasis explain certain of the failures reported in the literature. In our 1951 Report )r. Roy McKelvie by kind details were given of the results obtained by the administration of hetrazan to a :nya. Dr. McKelvie is an series of hospital patients, As these patients were later re-exposed to infection nges in onchocerciasis. For before the eradication experiments began it has not beeu thought worth while Lmary of the problem, to foHow them. up. A much larger series of patients is now being treated. 36 EFFECT ON EYE CHANGES EFFEcr ON EYE CHANGES Hetrazan may harm the eyes of patients given this drug for the treatment of onchocerciasis. On the other hand it may do good, e.g. Boase (1952), an East The preliminary report ab African ophthalmologist, reports that a patient admitted blind to hospital with is not strongly microfilaricidal : severe bilateral optic neuritis recovered normal sight after treatment with hetrazan. ment with protostib. In the eyes. With McKelvie we gave in our 1951 Report our findings in 16 patients treated reaction such as seen with hetr with hetrazan: in no case did the hetrazan cause other than temporary upset; the photophobia and "crawling a re-examination of the patients several weeks after treatment showed that the relieved by the time the series drug had done no obviolls harm to the eyes and had at least temporarily cleared that their sight had improved, the skin of microfilaria;. These patients have not been observed further to date. namely blurring of vision as present at the end of the cour (3) Protostib The value or otherwise of INTRODUCTORY depend on its effect on the adu than the lack of marked mic] Details of this drug have been given in section II of this Report. will be an advantage. The efte· The three immediate problems presenting themselves are: what effect has ~tudied by excision of nodules, protostib on the eye and skin changes, on the microfilaria;, and on the adult worm? Further, if the drug is of benefit, what is a safe schedule of treatment? (4) Solustibosao So far we have been able to treat only 22 patients (17 males and 5 females), all adults except three chIidren under eleven years of age. With two exceptions all fNTRODUCTORY patients showed microfilaria; in the skin clippings and seven showed nodules: The .preparation used as : ~,hat in view of the fact we were testing a new drng all patients chosen for section 2. The problems to be ! treatment had no physical changes in the eyes except three individuals ~ith effect has the drug on the ph minimal nummular corneal opacities. Eight others showed photophobia only, adult worm? This study has be and seven repO'l'ted "things moving in the eyes". 19 received suflicient quantities the patients were adults, eight n The total dosage we aimed to give was that found effective in certain ban. showed microfilaria; in the skin croftian lesions, Le. a total of over 240 mgms. Sbv per kg. body weight, this initial eye lesions are described t total being sp'read over ten days, with first amounts small because of dange1 of reactions. EFFECT ON SKIN CHANGES In this study we describe 0 EFFECT ON SKIN CHANGES giving of the drug. Only genera The time that, has elapsed since the treating of the patients is too short to too small to permit of detailed 'Jllow of our assessing what eftect treatment has had on the skin thickening, etc. This note refers to the skin changes during treatment to cut reactions to a With this drug, as with prot minimum. Doses given in the first two to three days were low. The numbers as those following hetrazan. OnI treated (22 in all) are too small to permit of a detailed analysis by groups but mation of the skin was absent our reports give some indication that a certain pattern of reaction was common second day and continued for I to almost all the patients. not so severe as with hetrazan, ment. Every patient showed itc Important points are- that every patient complained 0 (a) even with initial doses as high as 12 mgms. Sbv per kg. body weight, the the course of treatment. skin did not react in the violent fashion so typical of that following hetrazan administration: the itching, if it appeared, was not intense, From the results with thl and (Edema and inflammation of the skin were absent or minimal: suggests that solustibosan is mOl hetrazan. Reactions did not bef (b) when itching did appear as the result of treatment, this itching was found tinued practically throughout th to be present for several days during treatment; From the point of view of tt (c) three of the 22 patients showed no reaction throughout treatment. patient's view-point it is a disad an individual as the African I The picture shown suggests that there is no mass death of microfilaria; such get steadily worse with treatmer as occurs with hetrazan treatment, i.e. it suggests that the protostib is not actively refuse to finish the treatment. microfilaricidal. Tbe effect of treatment on the adult worm will only be ascer· tained by a long post-treatment observation period. It is not possible as yet tc on the adult worm. ~. '. ,~~ t. -., ., 37 EFFECT ON EVE CHANGES lis drug for the treatment of , e.g. Boase (1952), an East The preliminary report above on the skin changes suggests that protostib litted blind to hospital with is not strongly microfilaricidal; this is supported by the eye 'changes during treat fter treatment with hetrazan. ment with protostib. In the eyes, as in the skin, there was no immediate wild local ldings in 16 patients treated reaction such as seen with hetrazan treatment. Of the 22 patients five stated that )ther than temporary 11pset; the photophobia and "crawling in the eyes" present before treatment had been treatment showed that tbe relieved by the time the series of injections had finished: two patients reported I at least temporarily cleared that their sight had improved, and only one patient showed an adverse reaction, en observed further to date. namely blurring of vision as though "looking through smoke": this was still present at the end of the course of treatment. The value or ·otherwise of peotostib for the treatment of onchocerciasis will depend on its effect on the adult worms. If the drug proves to be an adulticide than the lack of marked microfilaricidal effect will not be a disadvantage: it of this Report. will be an advantage. The effect of protostib on the adults can only be directly selves are; what effect has studied by excision of nodules, work which we have not begun as yet. :rofilari~, and on the adult safe schedule of treatment? (4) SoIustibosan 17 males and 5 females), all INTRODUCTORY 1ge. With two exceptions all I lnd seven showed nodules: The preparation used as solustibosan "conc." is described in the text in rug aU patients chosen for section 2. The problems to be studied here have already been outlined, i.e. what cept three individuals with effect has the drug on the physical changes, on the microfilar,l I 39 REFERENCES ::it were more BARNLEY. G. R. (1952) Personal communication. blind in one Vol. Pag, ..~ ophobia with maining nine BOASE, A. J. (1952) East African Med. Jou,.. 29 316 ,ugh all had BOWIE, 1. H. (1950) Edinburgh Med. Jour. 57 561 BRYGOO, P. R. (1951) Sowh Pacific Conference on Filariasis and It is that the Elephantiasis at activity of )ef of micro BuRCH. T. A. (949) Bioi. San. Panamericana 28 233 nt of damage BUXTON, P. A. (1928) Research Memoir No. 2 ot the London tibosan to be School of Tropical Medicine & Hygiene. CuLBERTSON, J. T., ROSE, H. M.. HERNANDEZ-MORALES, F., nistration of OLIVER-GONZALEZ, l. and PIUTI, C. K. (I946) The owed photo Puerto Rico Journal of Public Health & Medicine 22 139 e had photo I small num FAIRLEY, N. H. (1931) Trans. Roy. Soc. Trap. Med. Hyg. .. 24 635 ents showing HARNED, B. K., CuNNINGHAM. R. W., HALLIDAY, S.. VESSEY, R. E., "crawling"}, YoDA, N. N .. CLARK, M. C. and SOBBAROW, Y. (1948) eye lesions. Annals of New York Academy Science 50 141 increasing in injection and HAWKING, F. (940) Ann. Trap. Met!. ParasiloJ 34 211 sensation of HEW1Tf, R. (1949) Nature 164 11)5 JUt treatment tion ("smoke JORDAN, P. (1951) Annual Report. Filariasis ReSei:HCh UniL 207 (] 952) Trans. Roy. Soc. Trap. Med. Hyg. .. 46 f . or counting (1953) (In Press) « ~r l the first in LAURIE, W. (950) Digest Report. Filariasis Research Unit. ied, with one (1951) Annual Report. Filariasis Research Unit. >atients com~ So eyes, while LEBlED, B. (1952) quoted from Trap. Dis. Bull. 49 789 Observation MANSON-BAHR, P. E. C. (1951) quoted in Trap. Dis. Bull. (In Press) O'CONNOR, E W. (932) Trans. Roy. Soc. Trap. Med. Hyg. 26 18 iscussion on OLIVER-GONZALEZ, J., SANTIAGO-STEVENSON, D., and MALDONALDO, '01. We have J. E, (949) Jour. A mer. Med. Ass. 139 308 'eli advanced RrFKlN. H., and THOMPSON, K. R. (1945) Arch. Path. 40 220 Jlern for the RODHAIN (1949) Ann. Soc. Beige de Med. Trap. 29 177 TEMKIN, O. (1945) National Research lnstitute, Office of Medical Information, Washington. C::1 ~ l • ,. ). 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