REGIONAL OFFICE FOR THE WESTERN PACIFIC of the World Health Orsanization Manila

REPORT ON THE SECOND

REGIONAL SEMINAR ON VENEREAL DISEASE CONTROL

MANILA. PHILIPPINES, 3 - 12 DECEMBER 1968 ., REGIONAL OFfiCE fOR THE WESTERN PACIFIC OF THE WORLD HEALTH ORGANIZATION MANILA

~PORl' ON rrHE SECOND REGIONAL SEMlNAR ON VENEREAL DISEASE CONTROL

- Manila. Philippines 3 to 12 Decemher, 1968 WPRO 0144

SECOND RlOOIONAL SEMINAR ON VENEREAL DISEASE CONTBOL

Sponsored by the

WORLD HEALTH ORGANIZATION RIDIONAL OFFICE FOR THE WESTERN PACIFIC

Manila, Philippines

3 to 12 December 1968

FINAL REPORT

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by the

REGIONAL OFFICE FOR THE WESTERN PACIFIC of the World Health Organization Manila, Philippines August 1969 CONTENTS

PREFACE ~ 1. INTRODUCTION: THE CHANGING ENVIRONMENT •••••••••••••••••••••••• 1

2. NATURE AND ~ OF THE PBOBLEM ...... 2 3. DIAGNOSIS OF VENEREAL DISEASES ...... •..••...... •• 6 4.. TREA'D-mNT OF VENEREAL DlSEAS:e:f> ...... 11

5.. VENEREAL DISEASE CONTROL ...... 17

6. BEHAVIOURAL PA'1"1'ERNS, HEALTH ElXJCATION AND ATTITUDES ...... 33

7 .. roruRE (J(]IJ!I.()OK ...... 35 8. SUMMARY AND RECOMMENDATIONS ...... •...... •.... 35

9.. RE:P'ERmlCES ...... 4:5

ANNEX I LIST OF ~UIPMENT AND SUPPLIFS FOR VDRL TEST (see 3 .. 1.2" .. ( 6) ) ...... 66

ANNEX II LIST OF EQUIPMENT AND SUPPLIFS FOR FTA TEST (see 3.1.2(c)) ...... 67

ANNEX III SUGGESTED FORM FOR USE BY CLINICS/DOCTORS WHEN SENDING SERUM SPECIMENS TO A LABORATORY FOR EXAMIN­ ATION FOR SYPHILIS (OR OTHER TREPONEMATOSES), AND SUGGESTED REPORTING FORM FROM THE LABORATORY (see 3.1.2(c» ...... 68

ANNEX N NOTE ON PRESERVATION AND TRANSPORT OF SERA IN LIQUID NITROGEN AT 15<)0C TO 1960C (see 3.1. 2( e) ) ...... 70

ANNEX V SUGGESTED SCHEOOLES FOR THE TREATMENT OF SYPHILIS (see 4.1.1) ...... 17

ANNEX VI SUGGESTED SCHEOOLES FOR THE TREATMENT OF GONORRHOEA IN AREAS OF HIGH RESISTANCE (see 4.2. 4) ...... 78 tI ANNEX VII SUGGESTED TREATMENT OF SOME lMPORT.AN.r SEXUALLY TRANSMITTED DISEASES OTHER THAN SYPHILIS AND GONORRHOEA (see 4.3) • • • . • • ...... • .. . • • ...... 81 r

.. I - 2 - ..

ANNEX VIII FORM OF CONrACT SLIP USED IN THE UNITED KINGOOM (see 5.3.1(b» ...... 80 ,.

ANNEX IX MECHANISM OF BUILD-UP OF RESISTANCE OF THE GONOCOCCUS TO ANTIBIO'rICS IN THE WESTERN PACIFIC RF.(}ION • • • • • • • • • • . • • . . • • • • • • • . • • • • • . • • • • • • • • • • • . • • • 87

ANNEX X INTERNATIONAL ASPECTS OF VENEREAL DISEASE AND TREPONEMATOSES CONTROL ••..••...•••.•....•..•..••.. 90

TABLE I TRENDS IN THE PREY' ALENCE OF EARLY SYPHILIS IN REPORTING CLINICS OF SOME COUNTRIES OF THE WESTERN PACIFIC REGION OF WHO 1960-19b7 (see 2.1.2) ...... "...... 50

TABLE II SEROPOSrrIV'ITY FOR SYPHILIS IN PROSTITUTES 19b7 . (see 2.2.2) ...... "...... 51

TABLE III SEPOSrrIV'ITY FOR SYPHILIS IN MIXED GROUPS (see 2.2.2) ...... 52

TABLE IV' RESULTS OF SERUM TESTING BY REAGIN TESTS ON EXPECTANT MOTHERS IN SOME COUNTRIES OF THE WESTERN PACIFIC REGION OF WHO (see 2.2.2) •••••.••• 5}

TABLE V REAGIN SERUM TEST RESULTS IN KOREA COMPAREID WITH THOSE OF REITER PROTEIN COMPLEMENT-FIXATION REACTION (see 2.2.2) • • • • • • • • • • • • • • • • . • • • • . • • • • • . • • 54

TABLE VI TRENDS IN THE PREY' ALENCE OF GONORRHOEA IN REPORTING CLINICS OF SOME COUNTRIBS OF THE WESTERN PACIFIC REGION OF WHO (see 2.}.1) ••••••••••••••••• 55

TABLE VII ANTIBIO'rICS USED IN THE TBEATMENr OF GONORRHOEA (see 4.2.1) ...... , ...... 56

TABLE VIII SENSrrlVrrIES OF 4, MIXED STRAINS OF GONOCOCCI FROM THAILAND, HONG KONG, TAIWAN AND VIET-NAM EXAMINE:D 1967-1968 AT THE WHO NEISSERIA CENTRE COPENHAGEN (see 4.2.2.6) •••.•••••.•.••••••. 57

TABLE IX SERUM LEVELS IN UNITS/ML FOLLOWING 5 MmA UNITS OF BENZYL PENIClLLIN WITH AND WITHOUT 1.0 GM PROBENECID (PROBENECID GIVEN HALF AN HOUR BEFORE INJOOTION, see 4.2.4) •••••••••••.•••..•••••.•.•.•• 58

TABLE X GONORRHoEA IN PROSTITUTES - 19b7 (see 5. b. 2 ) • • • • • • 59 - 3 - ~ ~ FIG I PENICILLm SENSITIVITIES OF MIXED AND UN- .,. SELECTED STRAINS OF GO~OCCI IN THE FAR EAST AND m LONDON26, 2 , 71 (see 4.2.2 b) 61

FIG II SERUM LEVELS FOLLOWING 2.4 MOOA UNITS OF PROCAINE PENICILLIN m EIGHT SUBJEC~8, 75 (see 4.2.3) ...... 62 FIGS IIa &I IIIb SERUM LEVELS OF PENICILLIN (u/mJ.) AFTER 2-8 HOORS FOLLOWING 5 MOOA UNITS OF BEN.zn. PENICILLm WITH AND WITHOUT PROBENECID HALF AN HOUR BEFORE mrECTION (see 4.2.3) ...... 63 FIG IV BUILD-UP OF RESISTANCE OF THE GONOCOCCUS TO ANTIBIOTICS (see Annex IX) ...... 64

.. Pm'ACE

The Second WHO Regional Seminar on Venereal Disease Control took place at the WHO Regia1al Office, Manila, PhilippineS, fran 3 to 12 December 1968. It was opened by Dr. F.J. Dy, Regional Director, who, in welcaaing participants, pointed out that the First Seminar which had been held in Tokyo in 1958, had provided an inventory of information concerning the ex­ tent of the problems of the venereal diseases and the services to deal with them in countries of the Region. A decade had now elapsed and because of the many striking cbaDges which had since occurred, it was time~ that a second Seminar be convened to appraise developments.

'!'he meetinf.was attended by 19 participants from 15 countries*, four WHO consultants ,eight local obaervers***, and four members of the WHO secretariat**** • 'l'here was simultaneous translation into English and French of the discussions throughout the Seminar.

Dr. G.V. Balbin (Philippines) was elected Chairman; Dr. Dang-Van CUong (Viet-Bam) Vice Chairman; Coronel R. Guiraud (New Caledonia) French Rapporteur; and Dr. F. Jepson (New Zealand) English Rapporteur. Professor E. Aujaleu served as Director of the Seminar and Dr. R.R. Willcox (Uni:ted Kingdan) as Overall Rapporteur.

TIlis report has taken into account the Country Reports of partiCipants, both written and verbal, the dai~ notes made by the English and French rapporteurs, the papers presented at the meeting, the background material prOY'ided to the Seminar and 1n:formation obtained in different countries during the pl"e-Seminar viSits of the WHO consultants.

*Dr. I.P. Wilson (Australia); Dr. A. Tarutia (Papua and New Guinea); Dr. Kuang-Yu-Fan (China-Taiwan); Dr. Shun-An Chang (China-Taipei City); lobe. M.C. Duprat (French Polynesia); Dr. N. Sanerive (Fiji); Dr. Wong Kwok-on (Hong Kong); Dr. M. Ashizawa (Japan); Dr. Bak. Chin Chung (Korea); Coronel Robert Guiraud (New Caledonia); Dr. F.L. Jepson (New Zealand); Dr. G.V. Balbin, Dr. P.A. Santos (Philippines); Dr. Koh Kim Yam (Singapore); Dr. T. Ishoda (Trust Territory o:f the Pacific Islands); Dr. Dang-Van-CUong, Dr. Huynh-Duc-Tinh and Dr. Ngu;yen-Duc-BaDh (Viet-Ifam) and Dr. L.F. Tautasi (Western Samoa).

**:Professor E. Aujaleu (France); Dr. H. Ita. Nielsen (Denmark); Dr. T.V. Tiglao (Philippines) and Dr. R.R. Willcox (United Kingdom).

***Dr. D.Q. Geaga; Dr. L. Ibarra; Dr. S. Santos; Dr. A. Zalamaa; Dr. L. Arabit; Dr. I. de Jesus; and Dr. L. Vira;y (Philippines) and A.E. teager (UNICEF Representative, Manila).

.. ****Dr. T. Guthe, Chief vm Section, WHO, Geneva; Dr. C.H. Yen (Opera­ tional Officer) and Dr. B. Vel.1m1rOY'ic, Regional. Advisers on COlllDl1lnicable Diseases, Western PaCific Region, and Dr. T. Oyama of WHO Communicable Disease Advisory Team, WPR • • 1. INTROOOCTICN

THE CHANGmG ENVDlCNMENT

The Western Pacific Region of WHO is vast, stretching from .the Arctic to the Antarctic and inclUding a number of countries on the land mass of Asia, a sUbcontinent in the Southl and a myriad of scattered large,. smaller and even minute islands and atolls in the China Sea and Pacific Ocean. Within the Region in spite of war and military mobilization, politioal readjustments and alignments, a considerable economic advanoe­ ment - the early fruits of which are already olearly visible • i8 occurring. Although there is still poverty in many areas expanding building programmes and higher living standards both bear witness to this situation.

Since the 1958 Sem1nar66 there has been an acceleration in oommunica­ tion between countries by the introduction of the jet aircraft, trade has expanded and the shipping lanes are today filled with faster and bigger vessels. More Asians than before are visiting Europe and the Western Hemisphere while, in reverse, cultural, business and tourist traffic are inoreasing year by year. There have also been widespread civil and military migrations from one country to another both within and from outside the Region. Venereal disease problems arising in one country are thus no longer confined to that area28.

All of this has been acoompanied by increasing urbaniz ation and industrialization both in previous~ developed and in developing areas, J' while riSing birth rates, some of which have been slowed down by familY planning programmes, have and are increasing populations to a marked extent. Although, in the deserted areas of some countries, the population may still be sparse, in others they are of increasing~ high densi~ leading to overcrowding or requiring upward building and reclamation of land from the sea.

With the inevitable homogenization of the world's ideas and cultures, the ancient and solid traditions of oriental society are being altered at an accelerating pace, particularly amongst the young. Meanwhile there is the paradox that in spite of parallel advances in the field of medicine, the venereal diseases are increasing not decreasing in importance, in some places as an indirect result of effective medical action22 (e.g., less fear of venereal disease with modem effective treatmentsJ less immUnity to reinfection with syphilis now that effective treatments are available; more susceptibles to syphilis now that yaws has been reduced in prevalence).

These multiple epidemiological and social factors in the changing environment, particularly those related to military mobilization - which .. has always been accompanied by an intensified incidence of venereal disease through increased promiscuity - have placed further demands on the venereal disease control facil1ties. which in general have not been matched by a comparable effort by health administrations. In many areas an adequate service to meet the new problems involved has in consequence not yet been provided. - 2 -

2. NATURE AND EX.TEm' OF THE PROBLEM

2.1 Diffioulties in assessment

Differences in requirements of notification and efficiency of reporting oontinue to exist throughout the region, making even an approximate estimation of the total numbers of oases or the trends involved extremely diffioult. Clinic returns, agart fran excluding the oonsiderable . numbers treated by the military 7. give an inaocurate pioture, as existing facilities are not oOlllll8nsurate with the demand. Private physioians, who oontinue to treat the vast bulk of infeotions treated by dootorslO, ,1. seldom report their oases even when legally required to do 5071 l.3, ,2 and an unlmown and probably muoh greater number are treated by pharmaoists and by the patients themselves8•

The Seminar noted with approval that spot surveys, the use of whioh was reported by Japan at the 1958 Seminar66 - whioh reoommended that their applioation be extended - have since been employed in other parts of the region, e.g., Korea, in addition to Japan.

2.2 SyphiliS

2.2.1 Primary and seoondary syphilis 1 As in other regions where the disease has increased sinoe the deoline following World War II17, 19, syphilis remains a problem in the Western Paoifio Region. The numbers of oases of primary and seoondary syphilis have reportedly deolined in reoent years in some smaller areas suoh as Frenoh Polynesia, New Caledonia, Papua and New Guinea. the Trust Territory of the Pacific Islands and Western Samoa. but also in the Philippines and to a slight extent in Singapore. On the other hand, in Fiji (albeit from small numbers), in parts of Australia, New Zealand, Vietnam, western Malaysia, and also in Japan - where the reporting system has changed - there has been a notioeable rise in reported cases (see Table I) while in Hong Ko~ a spectacular increase has been followed by an equally sharp fall'. In other areas too, including Korea, Taipei, Taiwan, where increasing seropositivity rates have been noted2, the data indioate the disease still to be of publio health signifioanoe.

2.2.2 Latent Syphilis

The figures for total syphilis are usually many times those for primary and seoondary oases, as much of the syphilis reported in the Region is "serologioal", the majority of oases being found by screening in the mi ! and other progranmes: primary ohanores and exotic secondary lesions are said to be relatively unoommon, possibly also due in part to frequent self-treatment with antibiotics or similar treatment given by general practitioners and pharmaoists. - 3 - •

The higbest rates of sero-positivity have been found in prostitutes, entertainers and similar occupational groups (ranging fran 3.2 - 16.6 per cent. in the Philippines, 'raipei City, Korea, 'ra!wan, Japan and Vlet-Nam ('l!abl.e II», whil.e similar high rates have been found in prisoners (e.g., 5.1 - 10.8 per cent. in Singapore).

In many countries of the Region the focus of public health attention in venereal disease control has been and is still on prostitutes as the principal carriers 01' disease. Neverthel.ess, there is evidence of an overspill of syphilis into the general population, even when al.lawance has been made for the percentage of sero-positivity- due to false-positive results.

For exam.pl.e sero-positivity- findings of 2.6 - 3.5 per cent. have been reported in students fran Singapore and Korea (0.2 per cent. in Japan), whil.e pre-marltal tests involving ver:l J..arse numbers in Japan have shown. 1.1 per cent. to be positive7 ('rabl.e III).

In the mil1tar:1 in New Caledonia, Korea and 'raiwan, between 0.6 and 5.4 per cent. have been sero-active, whil.e hospital inmates in Viet-Nam .. and mixed groups in Japan have reached 6.7 - 8.0 per cent. of sero-positivity-• In one large series of blood. donors exam1 ned in Korea the high figure of 21.1 per cent. was found8 •

In maternal and child health programmes ('l!abl.e IV), sero-positivity­ ." findings between 1.0 - 6.9 per cent. have been recorded in expectant mothers in Japan, New Caledonia, 'l!aiwan, Viet-Nam, 'l!aipei City and KoreaJ. or approxi­ mate4t 9 - 60 times those experienced in SaDe Western countriesl~. In Korea the rates are increasingf>7. Iot1ch lower figures (0.08 - 0.3 per cent.) have, however, been found in the Philippines, Singapore and Hong Kong.

Neverthel.ess, the Seminar emphasized that in the absence of specific tests it is not possibl.e to know the exact meaning in terms of treponema] disease of these results Which, when based on reagin tests alone are like4t to be overstated. Using the not ver:l satisfactor:l Reiter protein c~l.ement­ fixation test as an arbiter in Korea, for exam.ple, sero-positivity-rates would be reduced by a factor of from two to five8, 69 ('l!abl.e V), while in Viet-Ham, where a sero-positivity rate of 6.4 per cent. was obtained with the VDRL test, only 1.8 per cent. of positive results were forthcoming in ll78 patients tested also with the more satisfactor:l F'rA_l.OC)l.5.

2.2.3 Late sYJ)hilis

Although few5, 9, 15 or no more cases12 may be seen in the venereal diseases clinics, patients with cardiovascular and various forms of neuro­ syphilis are still being encountered in general hospitala throughout the ... 4 -

Regioo67. As is the general experience in otbel' regions, the relative~ small numbers of mown cases bave recentl,y increased2, 7, 8, 61 or remained staticlO in some areas, and appear to have declined in others6, 13.

2.2.4 Congenital syphilis

Although congenital syphilis is stated to be declining and to repre­ sent no significant problem in a number of countries of the Region (e.g., New Caledcaia, New Zealand, Trust Terri tory of the Pacific Islands, Western Samoa and the Philippines) considerable number of cases especially in relat100 to those of pr1111817' andseconciary syphilis, have been reported from. others {e.g., Japan, where in 1967 there were 1025 cases, lOb of which were \mder the age of 4 years; 'laiwan - 573 cases; Taipei City - llB cases; Hong Kong - 61 cases (16 under.one year) and Korea, where 12 sucll cases were found in a one-~ spot survey» add appreciable numbers, in relation to population Size, have also been encountered in FiJ i and Singapore. This situation is not surprising in view of the mown sero-positivity findings in expectant mothers. The real numbers are Ukel,y to be IID1ch greater as cases tend to be concealed, being scattered between venereological, obstetriC, paediatric, dermatological, pathological and other departments67. Physicians in these departments, and also private practitioners, should be obUged to report their cases.

The Seminar concluded that syphilis remained an important public health problem in the Region, the more so as the WBO-assisted yaws campaigns which have· been conducted in many countries had created a new generatiQn of sus­ ceptibles to venereal syphilis now that the immunity resulting from~revious 1n1'ectiOIUl with yaws had largel,y been removed by mass treatment17, •

2.3 Gonorrhoea

2.3.1 Prevalence

The continuing increase .1n the number of' cases of gonorrhoea, which is being experienced in many countries of the world17, 19, 66 is occurring no less in the Western Pacific Region of WHO, wJrre this disease - which is reaching epidemic proportions in SaDe areas1 - represents by far the greatest venereal disease problem.

Substantial increases have been reported from. Australia, Fiji, Hong Kong, Korea, Hew Zealand, Philippines, Taiwan, including 'laipei City, Trust Terri~ tory of the Pacific Islands, Viet-Nam and Western Samoa ('lable VI). A lesser increase has been noted in Singapore, wh1le there haS been a decrease in the smaller Pacific Islands of French Pol,ynesia and New Caledonia and also in Japan - where it is suggested that this could have arisen f'rom. reduced reporting due to proportionatel,y more cases receiving treatment from. private ! pllysicians7. Many cases are being treated by pharmacists, in SaDe areas also by herbalists14, and there is widespread self-treatment.

r - 5 - •

The current highest recorded annual rates for gonorrhoea have been . reported from Sweden - name~ ~7 per 100 000 of the population19 - where it has been suggested that this high figure is but a reflection of the good reporting in that country. If such a rate were applied to the approx1mate~ 240 million people in the Western Pacific Region of WHO it would sUS6est that near~ a million cases IIIB¥ be occurring ann~ in this area'l.

Extreme~ high rates of gonorrhoea are occurring in military popula­ tions (an attack rate in one month equivalent to 700 per lOOO per annum was found in one unit ot U.S. troops while in a unit of a national ~ (Korea) a spot survey showed 2.8 per cent. to be infected on one particular da;y67). In spite of longstanding attempts at control ot prostitutes in SaDe countries by means ot the regular medical examination and treatment of large numberso7 substantial 1n:f'ection rates, often exceeding thirty per cent.3, 7,. 15, have been encountered particular~ in Taiwan, Hong Kong, Korea, Japan, the Philippines, Singapore and Viet-Nam.

2.3.2 Complications

Although cases of urethral stricture are occasion~ encountered in the surgical departments ot general hospitals67, as in other regions19, the prevalence of canplications of gonorrhoea (epididym1tiS, salpingitis, barthOlinitiS, etc.) is apparent~ low - presumab~ due to the general use of antibiotics - and the tigures are split up between a number departments • ."' ot Nevertheless, cases of vulvo-vaginitis and of ophthalmia neonatorum are being encountered in ma.ny countries, particular~ Hong Kong and Singapore where 191 and ll3 cases of ophthalmia, respective~, were reported in 1967, and also in Fiji with 19 cases in theSalJle year. As gonococcal ophthalmia· is not notitiable in ma.ny countries, it is like~ to be more prevalent than the figurtt indicate. Moreover, its prophylaxis is by no means univers~ practiced J.

2.4 Other venereal diseases

Lymphogranuloma venereum and chanQI'oid continue to be recorded in areas in which data are collated5, 6, tl, 9, 13, 15. Some 478 cases of chancroid were encountered in Singapore in 1967 - 36 of which were in AaJDen13 while 86 cases ot what is n~ regarded as a rare venereal disease - viz., granulaaa 1ngu1nal.e or Donovanosis - were discovered within a tew months during a special survey in Papua and New Guinea, in which area the disease has been made than us~ prevalent tor ma.ny years.

As in other regions19 the most important sexu.alJ.y transmitted disease, other than gonorrhoea and syphiliS, is non-gonococcal urethritis cases ot which, not being reportable in most countries, are included with those of - 6 -

gonorrboea. Botb conditions are large~ treated by private physicians, pharmacists and the patients tbemselves.

In Korea, New Caledonia and Viet-Nam the numbers of reported cases of non-gonococcal urethritis exceed tbose of gonorrhoea. In Hong Kong, the Philippines, Singapore, Taiwan and Western Samoa they are less.

A1tbough there are no firm data to present, the stated eJqlerience of gynaecologists and clinicians in New Zealand, Western Samoa and elsewhere67, and recorded eJqlerience in other areas, would s~est that trichomoniasis is widespread p~icular4r among prostitute s67 • Condylomata aCuminata66, pediculosis pubis , mollusC\Ull contagiosum66 and otber conditions are also encountered.

The Seminar discussed the merits of considering all of these diseases, together with syphilis and gonorrhoea, as sexual.ly transmitted diseases irrespective of wbether they were reportable or not, and also tbe use of alternative names for 'venereal diseases clinics', e.g., 'social hygiene clinicS' as is employed in some parts of the Region6, 13.

DIAGNOSIS OF VENEREAL DISEASE

3.1 Sypbilis

3.1.1 Darkfield examination

The diagnosis of syphilis is normally confirmed by darkf1eld and by serological examinations. Darkfield diagnosis is difficult wben applica­ tion of antibiotics or disinfectants to sores has been made15, 61 and impossible if antibiotics have been taken systemic~. The 1958 Seminar noted that darkfield tests were not being performed sufficient~ in the Western Pacific Region, being available in some countries in the larger bospi tala and central clinics only, while in others no attempt was being made to separate syphilis from chancroid by tbis means, and it recommended that sucb tests should be made on all genital sores whenever posSible66• It was reported to the present Seminar that, although the darkfield was stated to be available by II of 13 countries furnishing country reports 32 , in the one country which provided more detailed information concerning individual clinics - namely, the Philippines - no darkfield was available in 16 of 20 clinics12• A new development since the 1958 Seminar as an alternative to the darkfield50 is immune-fluorescent staining, which is used on dry speCimens, but there were no reports of its use in the Region. - 7 - •

,.l.2 Serum tests (a) Laboratory services

The laboratory services in a number of areas are inadequate8, l4-. The stafts are ill-trained and small, equipment is ol.d2 and there is sometimes a scarcity of reagentso7. Serum tests bad had to be dis­ continued tor some months owing to a shortage of antigen in one busy clinic visited by participants. In Papua and lfew Guinea, sera tor syphil.is testing have to be sent to Sydney or Mel.bourne, Austral.ia, and in Western Samoa to New Zealand.

The 1.958 Seminar emphasized the need tor the centralization of laboratory services66 as performance was better if larger numbers of sera were tested in a few centres than if a few tests were made in 1IIBllY. Today, such central.1zation is even more necessary with the growing shortage of trained technicians. When autOlllS.ted techniques now available are introduced into routine use in the future, even further centralization may be desirable trom an economic viewpoint.

The 1.958 Seminar al.so emphasized the need for a central. sero­ l.ogical. laboratory to be established in each country to ensure the necessary standardization of reagents and methods employed in the provincial. and satellite l.aboratories, for which purpose international. standard reference preparations of cardiolipin and lecithin, and of freeze-dried sera reactive both to cardiol.ipin and treponema1 antigens, is obtainable from WHQ22, 2" 55. The present Seminar considered that these recommendations of a decade ago were stil.l apt.

(b) Tests· with lipoidal. antigens

Of tests employing lipoidal. antige~, the VrBL2, 3, 6, 8, l.5, Kabn4-, 1.0, Kl.ine9, LaughlenlO, the Wassermann or its modifications5, 7, 9 (e.g., Kolmer9 and Ogata7) and the RPR card test8, l.4-, 70 are amongst those in use· in the ~gionb7.

The Seminar considered that for· screening purposes a te~t based on cardiolipin antigen was· essential and that VDRL was tbe most suit­ able. WHO has prepared a list ot6~quipment and supplies required tor laboratories performing this test' (Annex I) •

.It was noted that the RPR card test2} on finger prick bl.ood has been found of vaJ.ue in areas where venipuncture is abhorredl.5, 70 and has an educative and case-hol.ding ef:fect on syphilitic patients, who can be shown ·:lJr!mediately how their blood differs from normal. Also tbe test can be done on a mobile basis. Its results are being read in Viet-NaIll by midwivesl.5. Moreover, the apparently much higher cost of the antigen and card for this test compared with that of VDBL antigen is considerably offset when the costs of syringes for venipuncture, gl.assware and transport of sera to the l.ocal. l.aboratory, inherent in • the performance of the latter test are taken into consideration • - 8 -

(0) Tests with treponemal antigens

The Reiter protein complement-fixation test6• 8, 10. <5, 69 and fluore.cent treponemal antibody (FTA) teChniqUes23 , 35, 36, 39, 48 have. been employed only to a small extent outside Japan. Some 1178 ser~have been tested by means of the F'l'A-lOO in Viet-Ham. The TPI test has been soarcely used in the region and only in one laOoratory in Japan67 . The treponemal haemagglutination (TPHA) test23 has been studied in a few laboratories also in Japan67, but before the value of this test oan be ascertained in relation to established treponema! tests (e.g., FTA and TPI) a properly controlled inter-laboratory assay, suoh as WHO has organized with the TPI and other tests involving treponemal antigens22, '5f, is needed<5.

Developments in fluorescent techniques were oonsidered, particularly in relation to the Fl'A 200 and the newer FTA-ABS<5, 40, 49 test, the latter apparently being the more sensitive, but the newer FTA inhibition test, now under investigation, might prove to be more satisfactory than either23.

Fluorescent techniques are much Simpler than the TPI test and can be satisfactori~ iirformed on mailed specimens of~ied blood on absorbent rondelles , 42, 62 even from the tropics (see Annex II). This test uses dead treponemes and there is no danger to laboratory personnel as there is with the TPI test56, which, however, remains the on~ t~ specifio serum test of treponemaldisease.

The TPI test should not be used in the initial diagnosis of the early infeotion61 and neither the TPI nor the FTA test is suitable for surveillance following treatment, fer which purpose tests with cardiolipin antigens are tho~e of oooice23• Also no known test can distinguish between sero-positivity due to syphilis from that due to yaws<5 and this causes difficulties in a number of countries of the Region4, 16, 67. More consultations are required between serologists and clinicians as to the interpretation of results in individual cases23 and some suggested forms for encouraging such liaison are to be found in Annex nr. The 1958 Seminar stressed the need for treponemal antigen tests involving acourate assessment of the incidence of treponematoses. The use of lipoidal antigens gives some false reactions but at the time of the first Seminar, the adoption of treponemal tests was Dot pressed for, since the laborai.o~·ies performing cardiolipin tests 66 were not yet firmly established • l

Much of the syphilis in the Region is II serologioal", baa8d on results of qualitative cardiolipin antigen testing alone. The diagnostio meaning of such testing is uncertain and studies are needed to define their relationsb1p to treponema! antigens test - 9 - • results. In Viet-Ham, tm" example, it. vas I5bmm t.bat. the 118. ot the Fl'A-1OO test m1ght reveal 71.~ false"'posit1vity to the VDRL tests15. The present Seminar cons1dered that· the time had now come when ... oountries should, by means of the Fl'A and TPI tests, try to determine the true 1noldence of treponema! d1sease in the Region.

(d) M1n1mal reqw.rements

The Seminar stated the m1n1mal requ1rements for the diagnosiS of syphilis in the Region to be (a) in the olinio: the darld'ield.; (b) at the local laboratory level: the qualitative VDRL with the quantitative VDRL23 being used in reactive cases; (c) at the level of the provincial laboratory: the quantitative VDRL plus a complement-fixation test involving cardiolipin antigen2J and the Fl'A test when resources beoome available; and (d) at the level of the central reference laboratory: the quantitative VDRL, cardiolioin complement-fixation tests, the Fl'A-ABS test2J and the TPI testg}, '46.

(e) WHO Reference Laboratory

The 1958 Seminar recolIIDended establishing an Internatigga!­ Serological Laboratory in the Western Pacifio Region of WHO to assist and co-ordinate the central laboratories in the performance of the more sophisticated tests, to collaborate in regional assays of sero-reactivity and test perfonnance. to undertake inter-country studies of serological problems, and also to act as a training centre for serologists and technicians in the countries of the Region. SUch a centre would f'urthennore be helpful in the· surveillanoe of other treponema! disease, notably yaws in the Western Pac1f'1.c Region.

The present Seminar re-affirllled this recoDlllendation as a matter for iDmed1ate consideration. It also discussed methods whereby in the ~antime serological surveys could. be conducted in collaboration with the WHO Serological Laboratory at Copenhagen55, for whioh purpose the WHO method and eqw.pment for the inert preservation ~ long-distance transport of sera in l1q\Ud n1trogen at - 2OO·C22, vould be aae£u1 (Annex IV) ..

3.2 Gonorrhoea

3.2.1 Methods in use

The 1958 Seminar noted that the methods and standards of diagnosis of gonorrhoea varied oonsiderably throughout the Region. Methylene blue - and not Gram-staining - was st1ll employed in sane areas (although Neisseria cannot be accurately identified in this way25) and cultures were by no means widely used. In view of the practice in some areas of examining cervical or solely vaginal smears the necessity '!11S stressed of obtaining .. specimens from the urethra as well as the c~rv1x06. The 1968 Seminar - 10 -

again observed the many methods and standards of diagnosis. that methylene blue was still being employed2, 3, 7. 16, 67, that although. the gonococcus was be~ cultured in a tew laboratories in a number of countrie&', 4, 5. • 8. 15. this was on a limited scale and seldOm as a routine, even in the female67. Moreover, smears from females continued to be takm only from the cervix or only from the vagina in a number of centres 7.

The present Seminar disapproved the diagnosis of gonorrhoea by clinical examination only, by urine examination only, by the use of methylene blue smears in the female. by the examination of specimens taken solely from one site in the female, by the numbers of leucocytes seen in either sex - all of which methods are still being practiced in various parts of the Region6'7.

3.2.2 Methods recOIIIIIended

The Seminar affinned that in males the Gram-smear should be routinely used (although in areas where this was not at present possible a methylene blue smear was better than no smear at all) and in the female Gram-stained smears were essential on specimens taken from both urethra and cervix.

The deSirability of making urethral and cervical cultures in the female was stressed and by their use the percentage of positive findings would be sUbstantially increased. Until these methods of diagnosis are in foroe, known female oontacts of males with gonorrhoea should be treated on epidemiological grounds. When oultural diagnosis in the female has been widely established it oould then be extended also to the male, thus revealing cases of gonorrhoea amongst the cases at present diagnosed as non-gonocoocal urethritis.

Recent developments in selective media containing antibiotics and in trans;gort _l}Iedia were disoussed, as was 1IIrnuno-fluoresoent staining25, :;'0, b4 whioh is at present in limited use in a few oentres32•

When performed on direot smears the fluorescent method is reportedly of less value in the male but in both sexes will give better results than Gram-stained smears if delayed direot tests are done on the oultured organism38 •

3.3 Other oonditions

Chancroid requires to be separated from syphilis by darkfield. More specialized techniques are required for the diagnosiS of lymphogranuloma venereum (e.g., the Frei test which is employed in some areas6) and of granuloma inguinale. In cases of non-gonoooooal urethritis the gonocoocus should first be exoluded and trichomonads looked for in persistent cases. Giemsa-st~ ~or inclusion bodies is being undertaken in some cases in Hong Kong' 7. . - II - •

A new incentive to find and cure trichomoniasis since the J958 Seminar has become available in the form of an administered drug, metronidazole. Trichomonads can be found by light or dark:f'ield micros~opy of wet Spec~DS and the yield can be approximately doubled by culture2 , but the culture of the gonococcus should have the higher priority.

4. ~ OF VENEREAL DISEASE

4.1 Syphilis

4.1.1 Penicillin

Penicillin remains the drug of choice for the treatment of syphilis both in the early and late infection20, 52, 61 and cure rates exceeding 90 per cent. are obtained in the primary and secondary stages when many of the apparent relapses may even then be re-infections. The treatment results are as good as can be reasonably expected from any therapeutic drug. Mass treatment with penicillin has been given (e'f" in Morocco) when sero-positivity rates reach or exceed 12 per cent.5 •

A serum level of penicillin exceeding 0.03 units per mil has to be maintained for 8 to 17 days20 depending on the stage of the disease. This level may be achieved either by the use of daily injections of aqueous procaine penicillin or by single, double or multiple injections of reposi­ tory preparations such as procaine penicillin G in oil with al.um1nium stea­ rate (PAM) or benzathine penicillin (DBED)52 , 61. The Seminar recCXIIIIend.ed I I that repOSitory penicillins be used because of their ep1demiological. and practical. advantages. For itemized therapy schedules, see Annex V.

Even in the later stages of the disease, when - in contrast to results in the early infection - sero-positivity to reagin tests will usually per­ sist for long periods following treatment20, 61, penicillin is preferred to other treponemicidal. antibiotics or to treatment with arsenic and bismuth for reasons of effectiveness, lack of toxicity and econo~. Steroid drugs combined with antibiotics are being used in selected cases by some physicians in the Region5, 52, as are mercury cyanide5 as pre-treatmentO, 67 or con­ solidation with bismutb9. However, it appears that whatever the drug used in late syphilis attenuated, often virtually avirulent ("dormant") treponemes may sometimes persist in the l3m.Ph glands and certain other sites; the full significance of this is not yet clear20.

4.1~2 Other antibiotics

For syphUitic patients likely to be al.lergic to penicillin, erythro­ mycin by mouth has been the first al.ternative choice20, 61 al.though it has been less well eval118.ted than penicillin and its results are less good •

• - 1.2 -

'l!he tetracyclines (tetracycline, chlortetracycline, o~tracycline, demet~lcblortetracycl1ne) by mouth give somewhat better results than erytbrcla!\Y'cin and are preferred by many for male and non-pregnant f'emale patients, but if' given to expectant mothers may result in discoloratiCD of' the teeth of the ch1ld20. Chloramphenicol is contra-indicated because of its baemopoietic side effects2a•

Cephalorid1ne20, 52 by da1l¥ injection is currentl¥ under investiga­ tion. Itacan usuall¥ be given to penicillin-sensitive subjects without reactIon2 •

4.2 Treatment 01' gonorrhoea

4.2.1 Drugs in use

'!'be treatment schedules in use in the Western Pacific Region are very varied. PenIcillin is the cheapest antibiotic, and, in different dosages of different preparations, is that most generall¥ given in the public cliniCS, ~uall¥ as procaine penicillin alone, or fortified with benzyl penicillin. Probenecid with penicillin is now in increasing use by the U.S. Armed Forces but not in the civilian clinics. There is also wide­ spread use of chlorampbenico167. Other more expensive drugs, including tetracyclines, erythr~cin, spir~cin5, ampicillin, kan8ll\Ycin and pyostacin5 are beiIlg prescribed by private practitioners and by some public clinics1.2, 67 and ampicillin and kanalI\Y'cin particular~.have been shown to be effective67. letacycline, anew tetracycline comPound, is being evaluated in Viet-Name PeniCillin, combined with sulphonam1des and local treatment, is being used in New Caledonia. The Seminar noted that the sulpbonamide drugs could be r. more effective in gonorrhoea by the simultaneous use of tr1methoprtm2 , 52 and that combined preparations are now cOlllllerciall¥ available. A list 01' antibiotics active against gonorrhoea is found in 'rable vn. 4.2.2 Resistance of the gonococcus to antibiotics

(a) Clinical evidence The problem of the development of strains of gonococci less II sensitive to penicillin was already regarded as "disturbing" at the l.958 Seminar when higher dosages of penicillin had become necessary as success rates to treatment had fall.en to 70 per cent. in some areas28, 52, 67. This situation has worsened considerabl¥ during the past decade. Although in some isolated areas (e.g., Western Samoa) small doses of penicillin are apparE!ntl¥ still

..- -13-

sufficient, and the antibiotic is still apparently effective in conventional doses in civilian practice in others, it has been necessary in some areas further to increase the dose by single injection of procaine penicillin to between 2.4 and 4.8 mega units. .b.veu so, amongst the United States Armed Forces - and their prostitute consorts" where the problem is apparently greatest - up to 30 per cent. of failures are currently being noted28, 67. In some areas the high ~ailure rates can, however, be explained by the low dose used 7.

(b) Laboratory evidence

Laboratory data26, 28 concerning the penicillin sensitivity of mixed and problem strains of gonococci examined earlier from Ceylon and the P~ippines and more recently from Hong Kong, Taiwan and South Viet-Ham at the WHO International Gonococcus Centre at Copenhagen have shown not only evidence of increasing resistance in Asia but that some highly resistant organisms requiring an MIC equivalent of up to 5.6 units/ml. are being encountered, 7'}/fJ of these strains with an MIC equivalent of 1.0 Wlit or more compared with 35.6 per cent. in mixed strains in Austral1a72•

On the other hanel, unselected strains examined locally in Taiwan28, 71 have shown less resistance, only 11.1 per cent. being resistant to 0.5 units of penicillin per ml. or more, compared with 9 .. 1 per cent. for mixed strains28, and 0.5 per cent. for unselected strains in London28 and 14.9 per cent. in Moscow59 (which figure had risen from 0.9 per cent. in two years59) - Figure I. Differences in techniques of testing and of reporting make ~~t !~arisons difficult and there is a need for stafidard- hatton' •

In addition to a lowered sensitivity to penicillin, a widespread complete resistance to streptomycin and a lessened sensitivity to tetracycline and to spiramycin have also developed. Of the Far Eastern problem strains examined at Copenhagen, 90 per oent. showed a lessened sensitivity to penicillin, of which ar per cent. were resistant to streptomycin, 82 per cent. were less sensitive to tetracyoline and ar per cent. to spiramycin26, 28 - Table VIII. Moreover, there are signs that a lessened sensitivity to chloramphenicol, er,ythromycin and kanamycin is developing.

(c) Need for fUrther information II Apart from the data quoted there have been only limited measurements of the sensitivity of the gonococcus to antibiotics, I e.g., in VietMNam (where 10 of 14 strams tested were markedly • less sensitive to penicillin), Hong KOng and Japan67 but using disc methods. Data available suggest that a higher degree of - 14 -

resistance is found amongst se~ct~ problem strains than amongst unselected or "street" strains' , 71, 72.

Further infonnat1an is required on the sensitivity of the gonococcus to antibiotics-in different parts of the Region, particUlarly of the precise situation at the present time, as a baseline from which to assess the trends. Three reference strains of gonococci of known sensitivity are availabl~ on_request from the WHO Neisseria Laboratory at Copenhagen22, 00, {)4 by the use of which local laboratories can control their f1ndings59.

I I 4.2.3 Basis of therapy i i The serum level oftha antibiotic mst obviously be in excess of the min~ inhibitory concentration of the antibiotio required for the organism , but the decisive factor is the concentration at the 1 ! infection site (which may be tnfluenced ~ other factors including protein binding of the antibiotia in the serum and tissues and alosed focus of infection).

Unlike syphilis, for which prolonged serum levels are necessary - most conveniently achieved with repository penicillins - gonorrhoea requires a high serum leval over a relatively short period of time, the first eight. to twelve hours being the vital period •. This has in the past enabled the widespread use of single injection procE!>iures with aqueous proaaine penicillin. As treatment results are usually less satisfactory in females, whatever the therapy it has been customary to repeat their treatment on the following day28, 52,

Long-acting penicillins no longer have a place in the treatment of gonorrhoea because the serum level achieved is insufficient but also because the ensuing long "tail" of penicill1naemia at a low level may convert the pati~t into a biological medium for the culture of less sensitive strains2 • Treatment shOUld be with high doses of shorter-aating penicillins given over a relatively Short period of time. II

The Seminar considered the serum levels obtained following single injections of 1.2.- 2.4 mega units of aqueous proaaine penicillin noting that very considerable variations are found between the maximum and m1n1llUm levels in different patients given the same dose (Figure II) and that repeating the same dose in the same patient28, 75. may not reproduce the same level. 1 The average penicillin serum levels obtained with 2.4 mega units of procaine penicillin are sufficient to reach the l1mits of resistanae recently reported from London28, Austral1a72 and those found in the largely unselected strains in Taiwan7l, but would be unable to overaome the degrees of resistance encountered in the mixed and largely problem strains from Viet-Nam, Taiwan and Hong Kong26, 28 (Figure II). - 15 -

Both the maximum and minimum serum. levels of procaine and aqueous penicillin can be raised by the simultaneous use of the kidney blocking agent probenecid28, as can those of ampicillin, but not of other anti­ biotics. By- giving only one dose of probenecid, serum. levels following a single dose of 5 mega units of benZll penicillin can be made adequate to overcome strains of high resistance~(6 (Figure IIIi Table IX).

4.2.4 Choice of schedule In view of the 30 per cent. failure rate reported in males given single injections of 4.8 mega units of aqueous procaine penicillin inesome parts of the Region67, it is evident that the limit is being reached2 of what can be given in a single dose of this preparation, especial.ly' in rela­ tion to the weight and therefore the injectable tissue of some especially female-patients15 • The alternatives are (1) to continue to use penicillin, which remains the cheapest antibiotic, in two or three daily injections in high dosage - which is practicable only in hospi~lized patients; (2) to delay the ex­ cretion of penicillin by the simultaneous use of probenecid, which can • both heighten and prolong the high peak levels of penicillin following a single injection (Figure UI; Table IX); or (:~) to use a more expensive antibiotic, such as injectable kanamycin or multiple doses of orally administered ampicillin or tetracycline, all of which have in controlled 28 s trials been shown to be effective in the Region , 67 (see Table VII). Chloramphenicol is also effective, relatively cheap and readily available, but its widespread use in gonorrhoea is not recommended on grounds of toxicity. Some schedules for use in areas of high resistance are given in Annex VI, but, whichever is chosen to meet the situation, Health Administra­ tions must be prepared to meet higher drug costs for the treatment of gonorrhoea28•

As it is quite impracticable to perform antibiotic serum. levels or under­ take sensitivity testing on individual cases, the most convenient method of determining the implications of pre~il1ng antibiotic resistance, which varies in degree in different areas ,is by careful evaluation of the results of therapy of males with gonorrhoea, who should be regarded as the best available indicators of the situation. Few such evaluations are being I I made in the Region at present67. The schedule chosen in the male should be I I shown to aChieve approximately 95 per cent. of success in properly controlled I I studies. No less intensive treatment should be given - but on two successive days - to their female counterparts.

Although lower dosages may be sufficient in areas of less resistance, the working rule should be to give too much rather than too little over a relatively short rather than a long period of time. There is sane evidence from Europe that by increasing the dose of penicillin for gonorrhoea the problem of reSistance ~ dim1nish26, 28. - 16 -

4.3 other venereal diseases

The treatment of other sexually transmitted diseases particularly of non-gonococcal urethritis which is the most important6, 8: 9, 12, 13, 15,,16 is outlined in Annex VII. , 4.4 Penicillin side-reactions

At the first Seminar in 1958 considerable attention was paid to allergic reactions to penicillin, particularly fatal anaphy!gxts, and a working group was set up to consider methods of their preventionv • \-THO surveys had indicated that the frequency of deaths was in the order of I in 70 000 patients treated and. it was stated that the seriousness of such reactions should not be over­ emphasized, particularly since deaths could be prevented by resuscitation remedies very readily on hand.

The fear of fatal anaphylaxis is still present in the Region2, 8, although individual doctors own to haVing encountered either none~ or only one or two cases, in relation to large amounts of penicillin usedv7. Moreover, WHO surveys have shown no further increase in incidence73, At the private physician level such misapprehension is aggravated by fears of poesible ad­ verse publicity or even legal action should such a reaction occur67. Methods of prevention in use in the Region include the taking of a history of previous penicillin administration and subsequent reactionj the use of pre-testing by skin test, which is widespread, while ophthalmic tests and tggtipg With oral tablets are also employed, particularly in parts of Japan ,D"(; keeping the patient in the clinic for 15 minutes following an injection (e.g., in Hong Kong67) J and having available an emergency kit containing the requisite drugs, particularly epinephrine, and the ~eans of administering them for prompt treatment should the occasion arise6 , 73,

Although some progress has been made in the immunological field towards a test which might accurately determine penicillin sensitiVity in advance20, 53, the present methods of skin and. other testing, including those employing penicillinoyl polylysine, give both false-positive and false-negative results and. acutely sensitive pereone might even have a serious reaction from the testing procedure itself52, 61, "(), II The 1958 Seminar agreed that providing phySiCians, before administering or ordering the use of peniCillin, determined whether their patients had had a previous history of severe allergy or of penicillin sensitivity (in Which case an alternative antibiotic would be used), and. arranged for an emergency kit to be readily available, ~asonable steps had been taken to prevent the occurrence of such reactions6 . This was endorsed by the 1968 Seminar, which also noted that the provision of emergency kits had increased the acceptance of penicillin in Taipei3. • - 17 -

.. 5. VENEREAL DISEASE OONTKlL 5.1 Notification 5.1.1 wYPes of notification TheSem1nar recognized three main types of notificationl7: (1) numerical. non-nominative notification of patients for statistical purposes, as is generally, but not universally, performed ~ venereal disease clinics; (2) nominal notification of patients .. which was originally designed large:Qr for case-holding purposes when t1"eatments vere longer and less e:f'f'ective than 1xlday; and (,) nomal noWieation of contacts for the purpoae of contact­ tracing.

The laws and practices of notification of venereal diseases vary considerably throughout the Western Pacific Region. In some (e.g., French Po~sia, New caledonia) notification 'is compulsory and so Ss treatment, while in others (e.g., Taiwan) these diseases are not legally reportable but numer1 cal retUX'tlS are made frQlll the clinics. In some cOWltries (e. g. , French Polynesia, New Zealand, Western Samoa) the lavs require every person who bas reason to believe he is suffering from venereal d.isease either to attend a private doctor for treatment or to be detained in hospital until he bas been treated67• In tvo territories (in one state in Australia, and ~ in New Zealand) notification is by name and the doctor is paid a fee for each patient notified.

Many patients seek private treatment because of fears of notification should they attend the public clinics, where false names are not infrequentlY given because of such fears. Few private practitioners notify' their casesl T even where notification is compulsory, atter warning ~ letter as in Fiji. In general, mare cases are reported. if no names are required to be given.

Since the introduction of rapid treatments vith peniCillin, nominal notification for case-holding purposes is no longer so important and its retention may make doctors hostile to the very word "notification", to the detriment of their performance of the other' tvo more important and more acceptable methods of notification.

5.1.2 Non-nominative notification or reporting for statistical purposes

Non-nominative notification or repartingof diagnosed cases to health administration for statistical purposes is us~ performed by venereal diseases clinics even if no legislation exists • There is much less co-operation from health centres67 and even less from general practitioners, also when officially required to do s04. Such "notificatIon" can ecial:Lly be achieved anonymously in a collective fashion on a quarterly, monthly or weekly basiS or in relation to individual cases ~ hospital doctors and practitioners. No breach of confidence is involved as no names are revealed . • - 18 -

As both syphilis and. gonorrhoea have been shown to be many times more f'requent in the Western Pacific Region than indicated by the returns f'rom the venereal disease clinics;l, there is need for all practicing doctors_ to record all cases of venereal disease they treat and report these to their health administration so that a more meaningful picture of disease trends can be obtained. This reporting should. be undertaken also in several sectors of the public health programme, notably in maternal and child health, occupational health and rural health services, in addition to private practice. Health administrations in countries in the Western Pacific Region should organize reporting systems to th1s effect, without delay. " 5.1.3 Notification of contacts

Notification of contacts by name is required for the purpose of contact­ tracing and treatment, especially of source contacts, if they are unable or unlikely to be secured by persuasion. Information regarding contacts should be regarded as a privileged communication between doctors, be it between the private physician and the clinic doctor or between the private physician and the health officer. The public health nurse27 or other contact ilWestigator, who traces the contacts and persuades them to undergo treatment, is acting on the behalf of the contacts. It is essential.. however, for the establishment of the necessary confidence of both patients and private physicians, that only medical agencies should be involved.

The Seminar considered that there was need for better education of doctors concerning the meaning, methods and. purposes of non-nominative reporting of diagnosed cases to health administratiOns for statistical purposes and of confidential notification of contacts.

5.2 Organization

5.2.1 General observations

The venereal disease control programme should include measures tending to: (a) improve the general level of health (e.g., personal hygiene, health and. sex education); (b) provide specific protection (e.g., prevention of congenital syphilis and ophthalJnia neonatorum); ( c) assure early diagnosis and. treatment of patients and contacts; (d) lim!t sequelae (e. g., prevention by treatment of progression of established disease; rehabilitation of patients); (e) provide a diagnostic and treatment service including drugs without costs to patients or contacts. It should also have the means of evaluating its own effectivenese17•

With the exception of a few countries in the Region, where venereal disease control services are fairly well estaglished, many countrigs have ~ 67 a poorly organized service or none at al.132, 7. In most areas2, , 12, 14, 2, at present, the budget is too small2, 8, 12, 14 and the staffs too few. - 19 - •

5.2.2 At the national level

The Seminar considered that at the national level of organization, there should be a strong central unit, both medical and technica.l, to un~.r- . take planning, distribution of funds, collection and collation of statistics. from doctors, clinics and laboratories, and to assume responsibility.for international aspects17. The unit should be under a specialist or closely advised by one and there is a strong case for this person to be engaged for some of his time in a venereal disease clinic involved in the day-to-day handling of clinical and epidemiological problems, research and evaluation and in undergraduate and post-graduate training (as in Singapore and Hong Kong) • Experienced specialists in venereal diseases are few, and persons selected for such a post may have to be sent abroad for additiQQal post-graduate training, for which purpose the WHO Fellowship programme22 1118¥ be helpful.

The central unit should have an AdviSOry Committee composed of persons interested in all aspects of venereal disease control (e.g., a gynaecologist, obstetrician, paediatrician, psychiatrist, epidemiologist, health education­ alist, statistician and members of the nursing and social services, etc.) so that the venereal disease programme 1118¥ be properly co-ordinated with the other public health programmes17.

At the top executive level, there should be at least one specialized centre (in large developed cities several will be required), preferably ~ attached to a large teaching institution, where standards of diagnosis and treatment sui ta.ble for local conditions can be set, undergraduate and poe t­ graduate training can take place and research can be undertaken and fostered. The staff of such a centre should include a public health nurse27 and contact with private pbysicians31 should be developed and maintained.

Likewise, at the top level, there should be a strong central laboratory to serve as a reference centre and to supervise the peripheral laboratories16, 66 so as to assure unifOrmity in the use of methods, reagents and performance. This llIS¥ be best organized as a syphilis serology department or unit of the main general public health laboratory.

5.2.3 At the level of district or province

At the provincial level, venereal disease control should be under the authority of the health officer in charge of the health services of the region17 who should prepare regional venereal disease programmes, integrate them with those of other services, co-ordinate health education and foster collaboration with th~ general practitioner3l.

In the larger cities specialized centres, with an experienced doctor in charge and a public health nurse27, will be required. In the smaller towns and rural ~as, venereal disease clinics under the local public health service 1118¥ also be necessary, particularly in special areas such as ports and those adJacent to military camps. In many rural areas, however, which generally have a much lower incidence of venereal disease than in the cities, the service should be less specialized and more fully integrated into the broader - 20 -

programmel1. It should be pose1ble for contact-tracing to be handled adequately by the staff of the central social service who would not be engaged solely in venereal disease workl1. Likewise, serology', etc. sh<:W1ld be perfomed in multi-purpose laboratories although there is, at the same time, a need also for s~9iallzed laboratories, which shou1d, as far as possible, be'centralizedOO.

5.2.4 Integration with other services

No venereal disease programme can be effectively performed without co-ordination'mid "an 'integrated effort with other health services at all'l.evelal 7. No . specialty subject should be treated in isolation and the money for venereal disease programmes has to have equal priority among other subjects.

Such integration is of considerable value in undergraduate and post­ graduate teaching, in central and peripheral administration, in case-finding - for which multi-purpose screening is more economical than screening far a single condition - and in SOllIe research projects. It is obligatory in rural areas with a low prevalence of venereal disease not justifying a specialized structure. Nevertheless, it is essential that the central foundations at the administrative. clinical and laboratory levels are strong and those in charge have sut1'1c1ent time and budget to supervise, maintain and evaluate their programmesl1• Integration might, otherwise, result in apparent disappearance of the problem..

5.2.5 Role of the public health nurse

The Seminar stressed the preventive importance of the public health nurse or social worker, ~rticularly in case-finding and tracing civilian defaulters fran treatment21• The nurse should co-ordinate her efforts with the military where required and should also engage in social wel:f'are in the wider senae, in health education and in the training of personne121• Her ability in obtaining the confidence of patients by personal relationship may frequently result in "cluster testing", as these persons, althOUgh not asked to do so, often bring in their friends and associates far examination.

At the larger centres, the public health nurse may be seconded to the clinic fran the central health administration, and her most significant activity would be that ot case-finding. In the smaller rural areas, she wou1d be attached to the public health department and be employed tor more of her time on other social wel:f'are and public health activities. In either scene, she would be a very important link between those administering venereal disease programmes and the private physician3l. However, in the rural areas, owing to her multi-purpose activities in a small carmunity, the public health nurse is usually very well known. Shou1d an extensive outbreak ot venereal disease occur (as happened in New Zealand), it may be ai~ntageous to call in an unknown contact-interviewer from outside the area • , - 21- •

5.2.6 Venereal diseases clinics .a A good deal of social stigma regard1ng venereal disease persists in some countries of the Regionl ,lO,12 but has not developed in some others (e .13., some Pac11"1c islands14 ). There are advantages in venereal disease clinics being attached to seneral hospitals, particularly in regard to easier anonymity, the lack of 'Which is an obstacl.e to the use of the clinics by some. The venereal disease service is combined w:lth that of other activities in ma~ areas (e.g., with dermatology and leprosy in Hong Kong and Singapore).

The clinicS should be so sited as to be easily accessible and should be open at hours convenient to patients. In rural districts mobile motorized clinics operate in some parts of the Region (e.s., Hong Kong, Singapore) while 10 the outlying islands of others (e.s., the Pac1tic Islands and also in HODg Kong) the personnel travel by boat.

Confidentiality' should be maintained and the patients should be handled kindJ.y and w:lth dignity. The aim is to make the venereal disease service free for both diagnosis and treatment17" as is already the case in mal\Y of the countries of the Regionl , 2, 3, 4, 10, 12, 13, but tree treatment is not yet available in ell areas, even in countries where tree services are obtainable in the larger citieslO• Free diagnosis may be offered without tree treatment (e.g., in Japan). In many areas, even when tree treatment is theoretically possible, the clinics may have no drugs to suppJ.yl4 (especially the more expensive antibiotics) and the patients have to purchase these themselves. The Seminar expressed the opinion that in all circumstances obligatory treatment should always be free.

5.3. case-finding

5.3.1 IndiVidual contact-tracing

This 1s a most 1mportant method of venereal d1sease prevent1on2l, "the spearhead at attack"lO. It is aimed at secur1ng not onJ.y the source ot infection but also secondary contacts to whain the d1sease may later have been passed by the patient since infection. For its success speed is essential and it is thus more diff1cult to undertake in mobile populationsl • In parts of the ~~1on no systematic contect~tncing is being attempted at the present time .(.

(a) By patient interview and hane Visit1ng ! !

IndiVidual contect~tracing is achieved by patient interview and by II subsequent outs1de Visiting. It has been shown usualJ.y to be more eff1ciently II pertCXL'llled by a trained person other than the doctor (e.g., the public health DUrse27). The patient is persuaded to give the D8IIle at the contact 1t Imown or particulars such as nickname, physical characteristics and site of - 22 - assignation, so that the contact may then be visited and brought in for examination and treatment. Source contacts are not told the name of the informi,ngmale patient. Information concerning additional secondary con­ tacts, not given to the doctor, is frequently forthcoming during the more prolonged interview which is possible with the public health nurse. .

The Seminar considered that private pnysicians should use this service where available. (b) B[ contact slip

The tracing of secondary contacts (e.g., wives, fiancees and friends subsequently exposed to the male infection acquired elsewhere), which requires considerable delicacy16, can often be achieved by persuasion of the patient without home vil'lit, and the use here of the anonymous contact slip is helpful. When completed, this bears the name of the clinic, the patient's number, the date, and a standardized code diagnosis (see Annex VIII), and is then given by the doctor or the public health nurse to the patient for delivery to the contact. The contact can then take it to any clinic or private doctQr cognizant of the code (who should then return it to the person who issued it). This facilitates the first attendance of contacts, who are relieved of embarrassing explanations.

( c) International aspects

Apart from the local and national importance of individual contact­ tracing, the Seminar emphasized its international aspects22, particularly in the Western Pacific Region of WHO where there is much travel between countries.

One of the functions of the central administration should be to act as a clearing house of international contact information obtained. Hong Kong and Singapore already have established mechanisms for international referra127. In Hong Kong the documentation of prostitutes operating in bars is sufficiently complete for a fairly simple description of the girl and the name of the bar in which she was' operating (if remembered) to be sufficient for her to be traced where she nominated as a source by someone who had left the country. Some physicians prefer such communications to be II between the doctors of the clinics in the countries concerned, particularly when they are acquainted with each other. It is certainly a more speedy procedure.

5.3.2 Cluster testing This technique, whereby the social and not necessarily the sexual contacts of patients with venereal disease I are persuaded to attend for 2l examination, has been shown to be of value in some Western countrles • - 23 -

It may be regarded either as ~on-applicable or as already in force with • the collective examination of prostitutes which is being undertaken in IIIB.Dy' parts of the Bagion.

5.3.3 Collective case-finding (a) TYPes of survey Surveys by means of serum testing are more often applied to syphilis than to gonorrhoea. There is at present no quick end accurate diagnostic method suitable as a survey technique for gonorrhoea21, although ~earch is in progress towards finding a serological test for this purpose • Nevertheless, one dey spot surveys, in which all physicians are required to be treated on a particular day, can be used for both conditions1, 8.

Other types of survey include mass surveys of a large segment of the population, selective surveys end multi-purpose surveys21.

Selective surveys are usually made of sexually active age-groups of selected populations, where the yields are expected to be high or the information is required for particular purposes. For gonorrhoea, this method is used in the routine testing in gynaecological clinics, of all women with a vaginal discharge but the highest yields are found when applied to delinquent girls end prostitutes. For syphilis, selective screening is

.p frequent4r made of prostitutes, prisoners, military personnel, seamen, hospital in-patients, blood donors, end by pre-marital end entenatal testing.

MUlti-purpose surveyS are those in which tests for venereal diseases are combined with those for other diseases in a co-operative programme. Examples are the testing for gonorrhoea in family planning or cencer screen­ ing progr8lllllles, - although the yields may be be below average where most of the patients are married end for syphilis combined with API) end Rhesus blood group end haemoglobin testing in lCH programmes, the last ll8IIIed being an example. of a multi-purpose selective survey.

All such case-finding is carried out large4r outside the venereal disease service I e.g., in obstetric end gynaecological centres (pre-marital end post-natal examinatioas), child welfare clinics, end to a lesser degree by occupational health services, the priSon medical service end those responsible for seamen, military personnel and hospital patients17, 21.

The method has first place in pre-natal blOod-testing for syphilis, for which tests using lipoidal entigens are best suited23. By this means not on4r is the disease found end treated in the mother (end in family members by contact-tracing) but also it cen be prevented in the child or cured while still in uterO. Even when sero-positivity rates are low this method should be continued •

• • - 24 -

(b) Use of surveys in the Western Pacific Region

One-day spot surveys for syphilis and gonorrhoea have been conducted amongst certain personnel in Korea and in Japan66 • Mass Surveys have been widely used in the rural ~eas in the WHO-assisted yaws campaigns in a number of Asian countries but few have been directly concerned with venereal syphiliso1•

Concerning selective surveys many countries of the Western Pacific Region now require routine pre-natal serum testing for syphilis, which procedure is 1ntg~te~ into the maternal and child health programmes2, 3, , "(, , 9, 12, 1" 15, 21. However, although such tests are generally conducted on patients having pre-natal examination in clinics and beal.th centres, the coverage in relation to the total number of births is less than thirty per cent. in a number of areas1, 13 and less than ten per cent. in sane8, although very high percentages of seropositivity, ranging between 1.1 and 6.9 ~r cent. are encountered in the mothers in a number of countries2, 3, 1, 8, 9, 15 (Table IV). The more complete implementation of this technique is therefore regarded as a first priority. Free pre­ marital tests are now reaching 15 per cent. of those concerned in Japan. .. Numerous other selective surveys for syphilis have been made, usually, but not always, of high risk groups in many countries of the Region (Table III) including bar girls2, 3, food-handlers2, 12, hostesses and en§ertainers8, 12, prostitutes1, 16, prisoners13, vagr.ants1, military persQnne12, 8, • hospital inmates15, employees1, students3, 1, 8 and blood donorstl (Table III), particularly in Taiwan, Taipei, Hong Kong, Japan, Korea, New Caledonia, Singapore and in the Philippines and on a wide and varied scale in Viet-Nam (Table III). CuriOUSly, outside Viet-Nam, few data have been presented concerning the most high risk group of all patients treated for gonorrhoea and other venereal diseases. In the Region it is by no means universal practice for this productive group to be sero--tested for syphilis routinely in the venereal disease clinic61. - Selective surveys for gonorrhoea are routinely made on prostitutes in a number of these countries, including Taipei City, Japan, KOrea, the Philippines and Viet-Nam, wh~le the maternity and child health programme in ~~~ Philippines has included smear testing for gonorrhoea in sane areas, Where a 2.0 per cent. yield has been obtained. There is an urgent need for surveys by cultures on cases of ophthalmia neonatorum and vulvo--vsginitis, which are not uncommon in the Region61. 5.3.4 Problem groups (a) Young persons Although venereal disease in teenagers was not considered a problem in sane countries (e.g., Hong Kong, where the traditional Chinese strong family ties persists), it was stated to exist as in other world areas30, and to be increasing in many countries of the Region including Korea, New Zealand, Singapore, the Trust Territory of the Pacific Islands and Viet-Nam. In New Zealand, although only 2.8 per cent. of infections of - 25 -

gonorrhoea in males have been encountered in persons under 20 years of age, the figure is no less tban59 per. cent. in females. Of 2076 cases of venereal • disease encountered in 1967 in Saigon, Viet-Nam, approximately one-half' was in persons aged 14-20 years 15 • A sD.all proportion seek treatment voluntarily because of symptomslO• In one country of the Region SOllIe female university students were stated to be prostituting tbemselves to ~ for their tuition fees when they had spent their allowances67.

Factors considered as contributing to this situation include earlier physical maturation30; industrialization and urbanization8 which encourage young persons to COllIe from the rural areas to the larger towns and cities4 , 5, 15 where, removed from parental control, the sexes may live in close proximity under crowded coodi tions32; lack of gainful. employment which leads young girls to turn to prostitution27; a revolt against the previous authoritarian ideas of parents and teachers30; and the generally more permissive attitudes of Society towards sex17, 19. ,

Alcoholism amongst the young was stated to be associated with venereal disease in Western Samoa and illegitimacy rates are riSing in some countries (e.g., New Zealand), but this carries little stigma in some of the PaCific is lands ll.

Health education, applied early, would appear to be the most appropriate method to deal with this situation, but it has difficulties in application as children grow older unless it is provided by those in sympathy with the • younger generation and is realistically adjusted to their attitudes. More­ over, in some pal"ts of the world very high venereal disease rates have been reported in students in spite of their being the best educated group30.

(b) Homosexuals

In recent years homosexuals have become an important factor in the transmission of infectious syphilis in IlI&Il¥ Western Countries30, where in some clinics, the bulk of early infections are now found in this group. Overt homosexuality is as yet not sign1:ficant in the spread of venereal diseases in Western Pacific countries (e.g., Hong Kong and New Zealand). It was considered to be increasing in Korea. Moreover, rectal infections have been noted in the Philippines amongst the so-called Billy Boys12, and transvestite male prostitutes were stated to be openly soliciting foreigners in Si!l6apore where some 80 homosexuals are on the venereal disease registerl }.

( c) Migrant workers and internal ethnic groups

Immigrant and migrant groups generally have. higher venereal disease rates than in the same age-groups of the home population30, ~~ and this is the case also in the Western Pacific Region (e.g., among GreekS in Australia). Language difficulties sometimes necessitate special measures in their case-management and health education. In some countries a screening test for syphilis is required before permanent immigration.

~ In certain areas an internal ethnic minority may show the higher rates of infection32, e.g., the aborigines in Australia, Fijians in Fiji and Maoris in New Zealand. ·26.

5.4 Maritime aSpects of venereal disease control

The world's total shipping tonnage is increasing30 and higher venerea disease rates are being encountered in seamen than in other ~t1ent groups30 , Seafarers, .Wo are particularly exposed to venereal disease2 , are constgte~t exporters and importers of disease, particularly syphilisl , 3, 10, 13, , 7, 53.

The shipping routes of the Far East include a number 01' ports in the Western Pacific Region of WHO. Venereal disease may thus be readily transferred fran one oriental country to another3 and seamen have been incriminated 8S introducing resistant strains of gonococci into new areas of other countries in this lIBYl.

The SeJDinar noted that facilities for the treatment of venereal disease in seafarers are sanetimee situated far fran the port areas and that treatment is not alllBYs tree67 as it should be in countries that are II Signatories of the Brussels Agreement of 1922 - revised in 1960 by the World Health AssembJ.y22 - although such treatment i3 commonlY but not alllBYs paid for by the shipping canpanies concerned67. It was also observed that the World Directory of Venereal Disease Treatment Centres at Ports and the International Treatment Eooklet (Carnet Individual) were not always available in major ports in the Region67. Attention was drawn to • the desirability of wider adherence by goveraments to this agreement.

5.5 Military aSpects of venereal disease control

,j The necessity for increased co-operation between the military and civilians concerned with venereal. disease problems was strongly stressed at the 1958 Seminar and this was equally strongly re-emphasized in 1968.

Extensive military mobilization of bQth home and overseas forces continues in some countries of the Regiontl, 15, This has intensified civilian prostitutionsl activities not o~ around the camps8, 12, 15 but also at rest and recreational (R and R) Centres to which foreign troops arg being sent in considerable. numbers in maQ;y parts of the Region3, , 13. This double problem has resulted not only in much gonorrhoea fran repeated exposures6r, in spite of health education and other control meaaures applied to the. troops 74, but also in a more marked deterioration of the sensitivity of the gonococcus to antibiotiCS, and therefore of treatment results, than is being noted in other world areas28.

Although military-civilian co-operation was stated to be grOwing in some countries (e.g., Australia), a closer liaison is required between the civilian and military authorities in many areas2l to arrange effective treatment schedules for military cases in order to reduce feed-back Of infection into the promiscuous female poo168, and to ensure that source contacts are quickly and accurately- identified and given treatment camnensurate with that known to be ei'tective in the male.

Such co-operation should be developed locally on personal level. between the military and civilian doctors and public health nurses and contact-tracers involved, and on a central level between those holding general.responsibility for the respective programmes,'in addition to diSCUSSions by local and national £ommittees concerned with Social matters in military-civilian relationsh1psl:l, 15. - 27-

5.6 Prostitution and venereal disease • 5.6.1 Extent at the problem Pros'titution as such has gf;nerally been made 1llegal but it has in fact increased in some areas15,67. In countries in Which brothels have been closed there has been a scattering of infections7, 30, and the . re-introduction of controlled prostitution is being debated in some countriesl , 4. Prostitution is likelY to persist as long as there is a demand for it, as in the Far East where such demand has been considerably increased by the presence at military forces27. All types at prostitution exist in the Region. Clandestine prostitutes (harlots8), operatipg from private dwellings or as street walkers, who are d1fficult to trace14; and Who are therefore examined medically only when ... nominated as contacts, are universal. Collective prostitutes l1v1ng in brothels in designated districts, the owners of Which may be formed into a mutual association, and the girl inmates subject to re~ medical examina­ tions, are still to be found in some areas, e.g., Korea' 7. While in many countries2, 3, 6, 7, 8, 12, 13, 15 large numbers (sometimes referred"to as part-time prostitutes) work also as bar-girls, hostesses and dancers, often being described as "entertainers" and who combine the promotion at the sale at alcohol with prostitution. Being more or less tied to a place at entertainment situated in a fairly conspicuous place near to their potential clients these girls are more easy to i~ent1fy and are officially • or unofficially registered in many countries and subject to regular medical examinations (e.g., in Hong Kong, Korea, Philippines). A further large part-time group have more settled employment, as massage and bath attendants, meal.companions in restaurants, and as guides, cashiers or waitresses on the regular staff at clubs, coffee and tea houses and restaurants. These are usually subject to less f're!uent examinations (e.g., six-monthly in Korea) being grouped with food-handlers, barbers, etc. and ue not generally termed prostitutes. In sane other countries, e.g., Japan, only girls arrested for prostitution are examined.

660S~itution is. thus closely linked to the sale of alcohol and vice versa , 7 and reqwes a modest hourly charge. "Beat" hotels are common­ place in many areas 7. In Korea, it is estimated that there are about 22 000 registered prostitutes, over 30 000 harlots and about 80 000 entertainers. In Hong Kong some 2000 girls work in some 140 bars. Prostitutes are the principal vectors at venereal disease in most countries at the Western Pacific Region and 80-90 per cent. or more of infections in males may be contracted from this group6, 13, 30, 66, 67. In some Pacific Islands, however, prostitution has not yet become organized .. and free love in both senses still prevails, but to a lesser degree than f'ormerly5. In others the amateur "good-time girl" or "fellBl1e facile" is assuming a more important role, as is the case in many Western Countries30. - 28 -

5.6.2 Venereal disease in prostitutes

Very high rates ot infect~on are being encountered in prostitutes2, 6, 13, 15, 30, 66, 67. Seropositivity tor syphil1s 1.a . demonstrable in ,.2-16.7 per cent. in the Philippines, ~aipei City, KOrea, ~aiwan, Japan and Viet-Bam (~able II), while gonorrhoea bas been tound in 29.8-33.4 per cent. of prostitutes in Japan, ~aipei City and Viet-NaIll (~able X), but these tigures may reter to single or an unspecified number of repeated examiIlations and, in addition, may be under or over-stated in relation to the accuracy of the methods ot diagnosis used.

5.6.3 Medical examination of prostitutes

As the bulk of venereal disease arises fran prostitutes it bas been logical to direct control activities towards this group27, 67.

In the vicinity of army ca~s (e.g., in KOrea, Philippines, Viet-Nam), and sane rest and recreational (R and R) areas used by foreign troops. (e.g., Hong KOng, ~ipei City), known prostitutes have been registered for medical reasons 'When they were working in bars or clubs, or named as a contact and found to be infected. ~ey are then subjected to periodic medical examination tor gonorrhoea, usually made once12 or twice8 veekly or every two weeks3, while serum tests for syphilis are performed usually (but not always) quarterly or sometimes at six-monthly intervals8• ~ose • found to be infected are in small groups caupulsorf1,y adm.1ttedto hoepita18~ 12. In sane areas (e.g., Taiwan, Viet-Nam) the girls are given regular prophylactic treatment, generally with repository penicillin, but in other areas it is given spasmodically12, 13. In other countries (e.g., Japan, where 3794 prostitutes 'Were examinlloC;l in 19677) they are only brought in for examination after arrest for solicitIng and prior to conviction. It found infected they are then compulsorily admitted to hospital until considered cured7, 8. In the examination of prostitutes culturing ot gonococci are used in very tew countries3, 6. Even their cultlJl"es are not always ~l.oyed for routinely but confined to nawed contacts6 • In some areas specimens are taken sOle~ from the cerviJeO j only methylene blue stained smears are e~1Q,Yed7, even though Gram-staining ~y be used on routine clinic patients7, albai1> on a sol.itary specimen. In one area gonorrhoea has been diagnosed according to the number of pus cells seen in the cervical smear and even urine specimens have been used in this way. In spite of these inadequate measures, epidemiological treatment is by no means always given to temales named as contacts and who show a negative test. Moreover, in at least one aree no serum tests tor syphilis bave been done tor long periods owing to a shortage of antigen.

Many prostitutes are examined and treated privately either by the same private practitioner as performs the routine examinatiOns or by a private physician e~loyed by the club or restaurant concerned or chosen by an association of bar-lII8ll8gers. Fifty per cent. of prostitutes in Viet-Nam were stated to obtain usually inadequate doses of antibiotics each week in this w~. Also, in an often successful attempt to defeat the consequences of regular examination, ~ prgetitutes indulge in self-treatment with a wide range of antibiotics , 5, • There is evidence in Japan of the consider­ able use of vaginal tablets containing antibiotics66, and a spermocidal substance. ~y are used as a preventive against both pregnancy and genital infection and are also active against trichomoniasis and thrush by inclusion of m,ycostatin and carbarzin. - 29 -

Because of widespread mobility of the prostitute population between • cities and camps, and the probabl3r much larger untraced and medical~ unsupervised clandestine prostitutes than those under regular examination6, 8, .14, these methods have shown on~ limited success, as judged by very high attack rates amongst their clientele, although slight differences in venereal disease prevalence have been noted amongst prostitutes in brothels and like establish­ ments and those operating indiv1duaiiy6. As at present performed, these examinations give a false sense of security to the prostitutes, their clients and also to the civilian and military health authorities.

Moreover, the use of long-acting penicillins for preventive reasons2, 12, 13, of schedules of treatment not necessarily commensurate with those shown to be necessary to remove the same organism fran the male, and the obvious incentives for otten inadequate self-treatment by prostitutes when canpulsory admission to hospital is threatened, has resulted in the whole operation providing a breeding ground for the more resistant organisms to antibiotics which are now emerging. A possible mechanism for the build-up of resistance is suggested in Annex IX.

5.6.4 Attempts to evolve more effective medical management of prostitutes

In an attempt to introduce more effective methods for the medical management of prostitutes, including the improvements in diagnostic methods urgent~ required in some areas - see 3.2.2, two proposals for pilot studies were agreed by the Seminar.

\, (a) Co-ordination of effective treatment in both male and female, and mass treatment

Instead of the present rather inco-ordinated individual case treatment it was proposed that selective mass treatment be attempted in a study area. '.rhe first steps would be (1) to determine the gonolThoea rate in troops in the area which bad been derived from.known, registered bar - and club­ girls, and (2) to utilize an effective treatment schedule which would give approximately 95 per cent. success based on high doses of benr.yl or procaine penicillin G with probenecid and which WOuld give sufficient~ high blood­ duration levels to exceed the tolerance of the most resistant circulating. strains of N. gonolThoea; an alternative in penicillin sensitive persons would be the use of tetracyclines, erythromycin or ampicillin by mouth, or KanamyCin by injection. Such therapeutic studies are already being conducted by the U. S. Navy67.

Once established as effective, one of these two treatments should be given Simultaneously to all prostitutes attached to "on limits" bars and .. establishments. Some assistance by the military with antibiotic supplies would be necessary. While the operation goes forward the troops should be COnfined to camp for 3-5 days, this would cut out most of the "feedback" infections to the infectious female poo127, 68 originating fran males with as yet undeclared relapses or by those incubating the disease, since it would allow time for their infective status to becane apparent. .. 30-

Subsequently routine periodical. examinations of the girl.s for gonorrhoea should be suspended tor some time. This wouJ.d reduce the 1ncent1ve for sel.f treatment, al.though the periodical. serum testing for syphUis should be retained. Attempts could then be made at vigorous contact-traciDS in connection with any further infected mal.es, and the femal.e consorts so found should be examined and treated, whether' or not gonorrhoea was diagnosed and followed up if' it was. They shoul.d not be hosp1tal.1zed canpul.sorily but encouraged to briDS in nat1onal. 1n addition to international. mal.e consorts, so that those may al.so obtain treatment. All new girl.s admitted to the bars, eilo.,. shonl.d be given s1milar pre-emp1.oyment treatment. The indicator of progress would be the gonorrhoea attack rate in the armedf'orces personnel. infected by known girl.s in the bars and cl.ubs concerned, canpared with that previously found. It shoul.d be noted that neither this method nor other methods now in existence can control. the infection in clandestine unknown prostitutes. The subsequently observed trend in the attack rate would determine when it would be justified to repeat the procedure.

The study obviously requires cl.ose co-operation between and interest of m1l.itary and civil.ian doctors at the l.ocal. and central. l.evel.s, of bar managers and of contact-tracing personnel.. The out cane of the project depends on the canpil.ation of accurate data by' the mil.1tary authorities~ The procedure woul.d presumably provide a more ef'f'ective approach than the present individual. one. The attempt to put it into operation wouJ.d itsel:f increase the l.1aison between the c1vil. and mil.1tary physicians.

(b) Use of l.ocal. propb;yl.actic vaginal. tabl.ets

The Seminar al.so agreed that an extensive trial. should be undertaken to determine the ,prapbylactlc effectiveness of _vagiilal.~ tabl.ets in W9J/IeIl!, on which prel.1m1nary resul.ts were reported to the l.958 Seminar :from Japan66 the use of which is still continuing in sane areas67. "

A regul.arly examined prostitute population shoul.d be sel.ected in an area in which cul.tures as well as Gram-stained urethral and cervical. smears are being used for diagnosis. ,After a.base-l.1ne assessment period of 2-3 months the girl.s would be instructed by suitabl.e heal.th educational. procedures to util.1ze vaginal. tabl.ets (containiDS penicill.1n, a spermocidal. substance (hyamine) an anti-trichanoniasis ,(carbarzin) and anti-m,on1l.ial. canponent ' (mycostatin) ) ,before each inteil!'COUl"Se. 'This trial. period of J.;.2 months wOU.l.d be foll.owed by a further period of assessment of 2-3 months without the use of tablets.

Throughout, the existing diagnostic methods and other procedures woul.d not be al.tered. The women would continue to be routinely e~ned by urethral. and cervical. smears and by cul.tures every two weeks. At each visit the estimated number of intercourses per girl. since the previous examination, their degree of co-operation, and the 1'1Dd1ngs of the emm1.nations etc. woul.d be recorded in the study forms establ.1shed. The ,outcome of the study woul.d be measured by canparison of the gonorrhoea rates (and syphil.is seroposit1vity) before, during and after the trial.. .. ' 31 ..

5.6.5 Rehabilitation of prostitutes • Several ~ountries of the Region have programmes for the rehabilitation of prostitutes67 (e.g., Korea, Japan, SineJlPore and Viet-Ham). All have stressed the difficulties in rehabilitating prostitutes, but the Seminar considered that the effort was worth while, particularly for young girls who had been engaged in prostitution for only a short t1Jne27. Many- of these girls are procured and made indebted to their procurers. Repressive legislation against procuring shoul.d be rigidly enforced. The young prostitute should be regarded as a juvenile delinquent and handled separately from established prostitutes27. , 5.7 The private 'physician and venereal disease control 5.7.1 Scope of private physician

J:t1s generally believed that the private physiCian handles between 80 and 90 per cent. of ve~al disease cases treated by doctors in the Western Pacific Region3l, 67. In addition to attending to an extensive practice, obviously devoted also to many- other diseases( he 1s expected to function in venereology in the fC!Ulowing fields: (a) diagnOSis; (b) therapeutics; (c) epidemiology (providing statistics, undertaking case-finding by sero-testing of obstetric patients( processing contact.­ traCing and giving epidemiolog1cal treatment); Cd} health education, .. and ee) the evaluation of treatment results, even though he may have had little undergraduate and even less post-graduate training in these subjects31. His overall perf'ormance can hardly be expected to be adequate, particularly in the reporting or notification of cases3, 4, 7, 17, 32 and in epidemiological contact-tracing31, 32.

5.7.2 SuggestiOns for improvement (a) Need for more education More undergraduate and post-graduate instruction is required in regard to basic elements, practical venereal disease control methods and the overall problems in the area. At present the time spent on undergraduate training in venereology in Asia is v~ry variable ranging fran 61.2 hours in India to 5 hours in Thailand30, 63, as documented by the study undertaken by the International Union against venereal diseases and Treponematoses. All students shoul.d work actively for sane time in a venereal disease clinic, even if geographically it is situated away fran the university premises. The students should learn public health techniques of venereal disease control, particularly case~finding and contact-tracing. Questions on the subject should be included in examination papers3l.

Post~graduate instruction should also take place in the clinic (e.g., in Singapore, post-graduate physicians study for the Diploma of ! Public Health). Seminars, week-end courses and lectures should be given to medical professional groups (as has been done in the past in Manila). -32-

(b) Closer contact between the private_ physician and venereal disease service

Closer contact should be established between the private physician, the venereb1.ogtst'and.thelll!d.ieal-off1cerin charge-of venereaL-;d1aeases or for the local or central health administration. The same applies to the laboratory2;, the public health· nurse27 and the social worker;l. Diagnostic and therapeutic information and advice should be freely offered to the practitioner, on wan his health administration depends to continue to treat cases in private practice11. He should be encouraged to use the public health n\'~se for contact-tracing purposes (1J8rticularly of source contacts), as he has no facilities for outside visiting himself17. Contact slips should be used. These give good results in_ secondary- cases, (See 5.;.1 (6) - Annex VIII). Such slips have so far been mainl.y used by clinics. It would be useful to introduce these to selected private physicians for organized use in the Western Pacific Region 'Within, and possibly between countries. By such means the value of the numerical notification of cases for statistical purposes, 'Will became evident in the estabUshing of incidence trends. The naninal notification of contacts would remain a privileged ccmnunication between doctors mutually engaged in preventive medicine. •

5.7.; Greater identification of the private physician with the ;programme

The private doctor actively involved in the treatment of venereal disease shoUld be given a greater sense of participation in and identifica­ tion 'With the overall public health programme and made conscious of his importance 'Within it;l.

A system is being tried in same areas where there are few or no public cUnics (e.g., Japan, Korea, Philippines) whereby sane private physicians are "approved" by health administrations07. But those "approved" should not include doctors examining prostitutes etc. onl.y but also those managing male cases. To secure such "approval" the doctors should demonstrate a certain standard and experience. A short part-time training course might with advantage be made a criter10n of entry-. Once approved a cert1t1cate might be issued to that effect and free penicillin provided against systematic numerical reporting of casea on standard forms, use of contact slips and contact-tracing machinery-, etc.

Such approved pract1tioners should be encouraged from time to time to attend professional and social group meetings. Fran such beginnings a professional section or society may came to be establisbed (as for example 1n the Philippines). This is of great ultimate value in raising professional standards effectiveness of performance, -sense of social responsibility and prestige;i • -" -

6. • 6.1 Behavioural as]ileots

Sexuall,y transmitted infections are usuall,y "behavioural diseases"18. There is general acceptance that changes in behavioural patterns have been occurr1ng111 19, with greater pemis81veness in sexual matters. The rising incidence of venereal inteitions thus points to the desirability ot social approach to their contro~' •

In the Region some ancient sexual customs and beliefs persist. For example, pol,ygamy, although no longer lega~, is encountered in sane areas as is the once widespread bellef that gonorrhoea can be eliminated by intercourse. Present-day attitudes are very variable. While amongst scme people in sane aXleas there is apparentl,y innate conservatism, reticence or sbyness concerning sex matters21 12, 16 in others s~~ ~Ue and practices as well as venereal diseases are treated lightl,yl, 4. Factors such as declining religious and famil,y influences, beliet in the virtue of pre-marital chastity, removal of the tears ot pregnancy by contraceptive • pills and intra-uterine devicesl and of the venereal diseases themselves now that quick and effective treatments are available have further reduced l118ay inhibitions to prOlll1scu1ty2, 3, 8, 11, 19, 22, 30. At the same time incentives to promiscuity have been stimulated by higher l1ving • standards17, 19, 21, 30, IIlOre travel, the availability of alcohol as a facilitator and notabl,y the emphasis on sex in mass media', 4, B, 16, 32. M!ay have emphasized that the young have different attitudes from their parents and that this change is now accelerating in sane areas ot the Region. .

The Seminar considered that more studies are required concerning behavioural patterns and community attitudes related to h1storiaal, cuUural, psychological and other factors in rapidl,y developing societies so that the present methods of health education can be more effectivel,y applied and gew methods may be deve~oped better suited to ~ocal social environment1 •

6.2 Leve~ of health education

Health education in the venereal disease tield in the Region varies greatl,y17. The point has been made that health education should not be blamed for its failures in venereal disease control when, in spite of much lip service, it has scarcel,y been tried18•

6.2.1 Primary health education or prevention of risk This approach aims at preventing the problem before it arises e.g., education of the young with a view to reducing praniscuous..proPensities, and therefore acquisition and spread of venereal diseaseslH• - 34 -

Such health education must be applied early, as many children in the Region leave school at 14. In some areas (e.g., Western Samoa). Regular talks to schoolchildren are given. It is anticipated that sex education will be introduced into Australian secondary schools by 1970. As a whole .. there are, however, canparatively few schools where sex (or venereal disease) education is systematically undertaken3, 4, 6, 8, 14 although in some instances it may be integrated with other subjects, such as home economics, biology and health education12• A lack of suitable teachers is a major obstacle32 and the first step is to educate the teacher18, 30, as is being done in Western Samoa. Thus activities of parents, teachers, youth group and recreational leaders, education authorities, etc" have to be closely integratedll, 27. Promi,scuity has often been shown to have its .roots in the first few years of l11'e, when the parent-child relationship somewhere went adrift, often from a broken home30. Approaches emphaSizing the importance of the family as a unit are therefore necessary in the social prevention 01' venereal diseasesl • In New Zealand parents are being included in family life education in secondary schools. other examples of primary health education include marriage guidance and the instruction 01' the young concerning the desirability of avoiding promiscuity, and being discriminate in sexual matters. Entertainers, hostesses, dancing girls, etc. in the Western Pacific Region were usually highly promiscuous prostitutes.

6.2.2 Secondary health education or early treatment Action here should be focused on those whose norms have been established and who are unlikely to change their habits whatever health education is provided30, i.e., habitually promiscuous persons, including prostitutes2 and "repeaters". These form a considerable bulk of those with venereal diseases, notably gonorrhoea18• Secondary health education includes advice concernigg behavioural discriminetion30j methods 01' prophylaxis by mechanical16, 53, chemica 19 , 16, and other means53j rendering potential patients more aware of the early signs of disease, the importance of early treatment and the available facilitieslBj and the dangers of self-treatment with antibiotics. Special attention should be paid to migrantsl , 30, 33, certain indigenous ethnic groupsl, 4, 10, the military74, seafarers16, 21, 30, prostitutes2, 6, 13, 15, 30, 66, 67 and other high risk semi-captive groups, and to those persons who often control them. For example, co-operation with brothel owners and bar managers2, 3, 12, may be useful in dealing with prostitutes. 6.2.3 Tertiary health education or prevention of recurrence , This rehabilitation approach should be applied to selected groups most . likely to benefit. Included here is attempted rehabilitation of prostitutes6, 7, 13, 15, 26, 61 (See 5.6.5), and the possibility of psychiatric treatment of homosexua1s5, 30 and of disturbed promiscuous persona18• The success of tertiary health education by present methods is . ' usually very limited ccmpared to the effort expended. Behavioural treatment, like medical treatment, is more successful when applied early18. -'5-

6., Media of health education The media of health education, applied by the doctor, public health nurse,· bealthvisltor, health educatlaoal1st, or other agencies 1ncl~e tbe.. d1rect spokenvord by 1Dformal talkII or. lectures, the recorded vord through tape. or gramophone record, provided direct~ or by radiO, the visual lIOrdby Ulustrated or non-illustrated posters, pamphlets, ne:ws­ papers, magazines, :tlip charts2 and by means of exhibitionsl " films Ql! tel.ev1s1002, ,. Many of these media are employed in the Western PacifiC Region although television, for which prosr&mmes are in preparation15, has yet to be wide~ exploited, aDd its JJ.m1tation should be realized. 0W1ns to language d11'f1culUes amongst migrants and different indigenous cultural ~s in many countries, it is otten necessary for propaganda to be made in several languagesl ,.

7. Ft1rURE Ot1l'IOOK

The 1968 SemiDllr noted that many recaomendations made at the 1958 Seminar were still applicable, that in the decade between these two Seminars the venereal diseases, partiCularly gonorrhoea had becane increasing~ important and that little progress had been achieved in their control in the Western Pacific Region in the WHO. The medical and • pubUc health efforts which had been made had been outbalanced by human ecological influences and rapid changes in the pbysical and social environments. It is l1ke~1 therefore, that the venereal diseases will remain national and international health problems in. the Region until or unless effective vaccines against them can be developed through intensified research19, 22, 611.. This method should not d:l.scourage efforts to intensify" control activities. The techni~l review of the probl.emaconcerned provided by the Semiou in its report clearly indicates that such efforts are needed in the c1rc~tances which prevail :l.n the Region.

Migration, travel, tour:l.sm, caumerce and trade have great~ :l.ncreased in the Western Pacif:l.c Region since the First Regional Venereal Disease Contral Seminar tn Toqo :l.n1958. Extensive urbanization, industrialization and econClllic development have taken place. MiUtary mobilization in· many countries has added f'urther to this rapidly changing eZlVironm.¢Ijt. These factors have facilitated spread of Venereal disease within aDd between countries in the Region. IncreaSing demands have under the circumstances • been placed on venereal disease cont.rol fac:l.Uties, demands which have not been matched by the ef:torts of health adm:l.n1strations. Most of the recommendations made at the Venereal Disease Control SemiDllr ten years ago rema:l.n valid and are not reiterated in the present text. -36- ...

8.1 Trends

A study of trends in the Region indicates that the frequency of syphilis has increased. in sane countries, has remained stationary 1n others, and in sane has shown a downward trend. Gonorrhoea has shown a cons1derable increase throughout the Region and has in some countries reached near ep1demic proportions in some parts of the populat1on. Chancroid, lymphogranuloma venereum and granuloma inguinale appear to be of limited importance, whilst non-gonococcal urethritis is in sane areas encountered more frequentl;y.

There is eVidence of an important and widening consumption of antibiotics in the Reg1on, often for undefined prevent1ve purposes by use of repeated small dosages. Th1s is llkel;y to have contributed to increase the res1stance of N. gonorrhoea to several antibiotics, but may also have had a certain preventive effect on the spread of T. pallidum. 8.2 Notif1cation, etc.

Both syphilis and gonorrhoea have been shown to be many times more , , frequent than has been brought out by available statistics, and systematic notification of cases from all sources should be obligatory. Disease trends could thus be based on data originating in several parts of the public health programme, notably in maternal and child health, occupational health and rural health services, in addition to private doctors and of course from venereal disease clinics. Surveys and studies of the prevalence of syphilis and gonorrhoea in different population groups should also be encouraged. By these means stimulus can be provided for this group of diseases to be ap­ praised realistically for priority and apportionment of funds in the integ­ rated public health programme. The Seminar therefore recommends:

that WHO encourage as a first step, regular reporting of each diagnosed and treated case of syphilis by all doctors in private practice or in medical institutions to their health administration for inclusion in annual reports (identified as early infectious syphilis, congenital syphilis, latent syphilis and late syphilis) and that after 3-5 years of experience this reporting system - as a second step - be expanded to include gonorrhoea.

8.3 Syphilis

More uniformity in serological methods and tests in use in t.he ftegion is desirable. A few adequately equipped laboratories with large capacity and trained staff are preferable to many small laboratory units, and would result in greater comparability in testing methods and procedures. Minimal requirements for diagnosis of syphilis were considered by .. the Seminar to be: darkf'ield examination in clinics; qualitative VDRL screening and quantitative titration or reactive specimens at the local laboratory level; both these tests and a cardiolipin complement fixation test at the provincial laboratory level and these three tests and a treponemal antigen test (FTA/ABS or TPI) at the national reference laboratory level. - 37-

Seroreaetivity rates in different population groups varied in the countries of the Region, but much ·serological syphilis· appears to be • diagnosed on the basis of qualitative cardiolipin antigen testing alone (pregnant women, blood donors, hostesses, entertainers, prostitutes, etc.). Properly' organized studies to define the true relationship betwen cardiolipin test seroectivity, treponemal. antigen test results and actual. syphilitic disease are needed.

The need for a WHO Regional Reference Centre in the Western Pacific (al.so recommended at the ~ok;yo Seminar in l.958) was re-empbasized. National centres .. existing or to be established - could collaborate with this Reference Centre in regional assays of seroreactivity and test performance, and inter-country studies of serolog1cal. problems could be undertaken in the Region. ~e Centre would furthermore be helpful in the surveil.lance of other treponemal diseases in the Region, notably ya~.

The Seminar recommended:

(a) that greater uniformity in reagents and serological methods be sought by quantitative cardiolipin antigen testing of • specimens reactive in qual.1tative screening: the use of treponemal. antigen testing be introduced in national laboratories; the establ.1shment of a Regional. WHO Reference Centre be pranoted in an existing laboratory in the Region , to advance further serological work; (b) that a study be undertaken to define "serological syphil.is" diagnosed in mass testing of population groups in several countries of the Region. In such studies the WHO International Serol.ogical. Reference Centre, Copenhagen, is prepared to co-operate with national. workers in different countries.

~atment results in earJ.y syph1l.1s, congenital syphl1is, latent and late syphilis are good, approaching what can reasonably be expected fran a therapeutic drug. An appraisal of therapy outcane and acceptable treat­ ment schedules in different stages of syphilis with Benzathine, penicillin G, PAM and aqueous peniCillin, with difterent blood-duration-level capaCities, are given in detail. in the report and al.ternat1ve drugs are suggested for use in cases of penic1l.l.in allergy.

8.4 Gonorrhoea

Gram staining ot: smears t:or the intracellular diplococcus is ot: greater value in the diagnosis ot: gonorrhoea than methyl.ene bl.ue staining, etc. notably in the female, in which sex specimens from both urethra and cervix are necessary. In addition more extensive facilities are needed for culturing • and biochemica.l ident1:fica.tion of the gonococcus.

It bas oeen estao.11sI1ed \;bat macy strains of N. gonorrhoea circulating in the Western Pacific Region show increased resistance to penicil.l.in and to sane other antibiotics. This observation is of practical importance since high treatment failure rates in certain civilian and military populations are observed and since penicil.l.in remains the cheapest and most widely used of 1,. I

-38- - ~I the antibiotics empJ.oyed against gonococcal in1'ections. Further inf'OlW.tion on patterns of resistance is needed to establish a more complete regioDlll picture and as a baseline for possible future regressioa at resistance under altered treatment practices. Substantial increase of dosage of penicillin with probenecid added would assure high aDd suff1clentl¥ proJ.onsed gonococco­ cidal blood and tissue levels which are necessary to reduce the high faUure rates. Orientation at individual therapy in this direction is needed in the Western PacUic Region. Health administrations should be alerted to this situation and increased drug costs muat be foreseen.

It is recommended:

(a) that substantiall¥ increased penicillin dosage schedules be used in ..les and females in the ccnmt;r1es of the Region in the future .. based on short-act1Dg rather than long.. acting penicillins and in association with probenecid, (See 4.2.4.lIind Annex VI).

(b) that the study of antibiotic sensitivity of Circulating strains of N. gonorrhoea in the Western Pacific Region be pursued by the WJl() International Gonococcus Centre, Copenhagen, in co-operation with clinicians and laboratory workers in the various countries so as to provide a more complete picture of changing sensitivity patterns.

8.5 Other venereal diseases Susgested treatment at important sexually transmitted diseases other than syphilis and gonorrhoea are given in Annex VII.

8.6 Praniscuous female gr01.WS and venereal disease

In several countries in the Region a large portion of venereal disease (notabl¥ gonorrhoea) arises fran prostitutes. Many are registered .. Periodically examined and treated.. particularl¥ in the vicinity of military camps and in rest and relief (R and R) areas of lIhich there are a number in the Region, . but t~ dose of pen1cil11n g1ven to proSt1tutes 1s not al~ CCllllllel'llSurate with that required for the male. Other prantscuous groups are apparentl¥ examined and treated outside this scheme by private practitiooers. There is also considerable self-medication.

The limitation of the information ~ the extent of gonorrhoea in these groups 1s recognized. It is evident .. however, that the infection rates are high. Moreover, a high incidence of disease perSists in the Civilian, and particularl¥ military.. male consorts of these waoen in spite of. periodic medical examioations and prophylactic penicillin treatment of the WQIIen often in small doses, repeated over a long period of time. Although this prophylactic procedure is of some epidemiological importance, a false sense of security is engendered in the female, the ale partner and the public in general, as lieU as in the doctor and the health 'departments concerned. '!'be Pl'ocedure tends also to enhance the development of antibiotic resistance of N. gonorrhoea. • -39-

Certain antibiotic vag1na1 tablets in an effervescent base have been demonstrated to have preventive effect against N. gonorrhoea and vaginal flora, but no large-scale study in female risk groups has so far been undertaken. Based on the above considerations, an approach may be attempted in pilot projects to eliminate the self-perpetuating female reservoir of gonorrhoea in high prevalence groups. It is recommended: (a) that a first study be based on simultaneous mass treatment of a defined female group in a selected ares, using high dosages of aqueous penici111n with probenecid - on other drugs shown to be effective in their infective male consorts - and USing the infection rate from this group among observed .ma1e partners as the indicator of possible pr~ess. (b) that a second study concern the systematic use of prophylactic vaginal tablets in exposure (containing penic1111n or another gonococcida1 drug) in a defined female group already followed regularly by Gram smears and cultures for N. gonorrhoea. The changes in the positivity rates of smears and cultures may be indicators of the possible preventive effect of the tablets • • 8.7 Organization, Administration and co-ordination of venereal disease control To direct organization, administration and co-ordination of venereal disease control activities in the public health programme, a responsible officer or unit is needed in the health administration. The functions of this person should not only comprise cOlleetlOD and collation of data from doctors, clinics and laboratories, but should also include practical york with clinical, epidemiological, laboratory and related problems in a national venereal disease control centre. The programme should concern measures tending to (a) improve general level of health (e.g., personal hygiene, pre-nuptial examinations, health and sex education) (b) provide specific protection (e.g., individual and mass prophylaxiS, prevention of congenital syphilis and ophthalmia neonatorum) (c) assure early free diagnosis, drugs and treatment of patients and contacts (d) limit sequelae (e.g., preven.. tion by treatment of progression of established disease, rehabilitation of patients). In the general health service both urban and rural health centres should be prepared to detect and treat venereal disease. The maternal and chil.d health centres and hospitals should also be an integral element of venereal disease activities. The venereal disease control service should • stimulate and co-ordinate these activities as well as the social services needed for contact-finding, an essential activity where greater efforts are required in developing countries if spread of venereal disease is to be prevented~ Such epidemiological efforts can only succeed by assuring confidentiality and dignity in the handling of infected patients and contacts. .. 40 -

It is recaomeoded:

Ca) that a more integrated approach be taken in the organization, administration and co-ordination of venereal disease control, aiming at a 1I'1der utilization of all urban and rural health services in case-finding, treatment and control of infected persons in addition to the 'WOrk in venereal disease centres.

(b) that surveys suited to local conditions in the different countries of the Region be introduced on the widest possible scale .. particular~ ante-natal serum testing in the co­ operating MCH part of the programme - -and also that smear. aod culture surveys for N. gonorrhoea.be undertaken rout1ne~ in risk groups to appraise the nature, extent and spread of these infections - as 'liell as for case-finding purposes.

8.8 The private physician and venereal disease control

The private phySician may treat 80-9~ of gonorrhoea in many developing countries. He is expected to be responsible for diagnOSiS, treatment, epidem1olosY, health education, evaluation of results, etc. But a recent study of teaching of venereology and venereal disease control in medical schools throughout the world (Internat10nal Union against Venereal Diseases and Treponematoses) shows that his bas1c training for this task is often l1m1ted. Furthermore, l1ttle possibility is furnished for post-graduate • education. Venereal disease instructional courses for practicing doctors should therefore be arranged periodica~. A greater sense of participation in and identification with venereal disease control activities would thus be provided, and he should be encouraged also to use the contact-tracing service. Sane incentives, e.g., official approval of practitioners active 1n venereal d1sease control might be g1ven by the public health authorities.

It is recaomended that:

(a) teaching of venereoJ.osy aod venereal disease control be strengthened in medical schools, since a large proportion of venereal d1sease, notab~ gonorrhoea, is treated by medical practitioners, and possibilities be provided for periodic post-graduate orientation courses in elementary laboratory work, therapy, epidemiology and other aspects of venereal disease control.

(b) consideration be given by health .authorities to providing some recognition or approval of practitioners active in venereal disease control, possib~ by establishing a system of acknowledgment in Which the pract1tioner 1s accepted as part of the programme. - 41 -

8.9 International. aspects

The spread of venereal disease between countries bas been facilitated by developments in the Region in recent years. Direct exchange of contact information between doctors at clinics and in health services is desirable.

International. aspects of venereal disease and treponematoses control concerning technical policies, standardization of methods, techniques and reagents, research, ass istance to governu:ents I training and education, etc., including aspects concerning the implementation of the Brussels Agreements relating to seafarers were considered by the Seminar in the context of the World Health Organization's programme in venereal diseases and treponematoses and are contained in Annex X.

8.10 Third WHO sponsored venereal disease seminar in the Western PacifiC Region

At the conclusion of the Seminar it was agreed that the Seminar had adequately served the functions intended and it was recommended that:

A further venereal disease control seminar be sponsored by WHO in the Region in due course when the many changes and complete developments affecting venereal disease problems could again be reviewed • •

II II

i I • .. .:; - 42 - .,

• • 1 9. REFERENCES

9.1 Count:.:l Re;eorts Country

1. AUSTRALIA Country Report Dr. Ina P. Wilson 2. THE REPOBLIC OF Country Report on Venereal Dr. Kuang-yu Fan CHINA (TAIWAN) Disease Control (Taiwan)

3. THEREPOBLIC OF Country Report on Venereal Dr. Shun-An Chang CHINA (TAIWAN) Disease Control (Taipei City)

4. FRENCH POLYNESIA Expose Relatif Aux Maladies Mme. Marie Claude Veneriennes et Aux Duprat ProbU!mes Qu'elles Posent

5. FUI Country Report on Venereal Dr. Noki Sanerive Disease in Fij i 6. HONG KONG Report on Venereal Diseases Dr. Wong Kwok-on in Hong Kong

7. JAPAN Country Report Dr. Masami Ashizawa

8. KOREA Country Report on Venereal Dr. Nak. Chin Chung Diseases Control in Korea 9. NEW CALEOONIA Rapport sur la Lutte Anti- Col. Robert Guiraud venerienne en Nouvelle- Ca1.8donie 10. NEW ZEALAND Country Report on Venereal Dr. F.L. Jepson Diseases Control in New Zealand

11. PAPUA 8. NEW' GUIIiEA Country Report (Verbal) Dr. A. Tarutia 12. PHILIPPINES Country Report Dr. Pablo A. Santos Dr. G. Balbin

13. SINGAPORE Country Report on Venereal Dr. Koh Kim Yam Diseases in Singapore 14. TRUST TERRI'roRY Country Report Dr. Tregar !shods OF THE PACIFIC ... ISLANDS 15. VIET-NAM Rapport Prepare Pour le Dr. Huynh-Duc-Tinh Seminaire due 3 decembre Dr. Dang-Van-Cuong l,968 a. Manille sur la Dr. Nguyen-Duc-Hanh Lutte Anti-Venerienne 16. WESTERN SA}.()A Country Report Dr. L.F. Tautasi - 43 -

Papers presented at the Seminar

17. Professor E. Aujaleu The Organization and. Administration of Venereal Disease Control Services

18. Dr. John Burton Bel;lavioural Diagnosis am Educational Treatment (Presented by Dr. Same notes on the control Tiglao) of Venereal Diseases

19. Dr. T. Guthe & The Nature and. Extent of O. Ids~e Venereal Diseases: World Trend.

20. Dr. T. Gutbe & Antibiotic Treatment of WFB/vm/8l . O. lde~ Syphilis WHo/Vrtr/57.341

21. Dr. T. Guthe & Some Epidemiological WFB/vm/77 • O. Ids~ Aspects of' Venereal Im!/V'fJr/68.235 Diseases

22. Dr. T. Guthe & Some International Aspects O. Ids~ of Venereal Disease and Treponematoses Control

23. Dr. H. Aa. Nielsen Serological Diagnosis WFB/vm/73 of' Syphilis and Other INT/V'fJr/fB.240 Treponema! Diseases for Individual and Mass Use 24. Dr. H. Aa. Nielsen Laboratory Diagnosis of WPR/VJ:Jr/74 Trichomoniasis Im!/vm/fB.24l 25. Dr. A. Reyn Laboratory DiagnOSis of WPR/vm/80 (Presented by Dr. Gonococcal Infections H. Aa. Nielsen) Supplement to Bull.Wld. Im!/Vm/68.239 Hlth.~. 2,g, IiJi9-4'b9, 1965 26. Dr. A. Reyn Antibiotic Sensitivity WFB/vm/82 (Presented by of' Gonococcal strains INT/vm/68.237 Dr. H. Aa. Nielsen) isolated in the East Asian Region 27· Miss catherine Walsh The Role of the Public WFB/vrJr/69 Health Nurse in an Epidemic of' Venereal Diseases - 44 - •

28. Dr. R.R. Willcox Problems in the Treat- wm.jvm/TL ment of Gonorrhoea in South-East Asia and the Western Pacific (~o ~onger versicm: WHD/Vm/bB.353) 29. Dr. R.R. Willcox Suggested Treatment of WPR/Vm/72 some Important Sexual.ly Transmitted Diseases Other than Syphi~is and Gonorrhoea

~. Dr. R.R. Willcox Environmenta~, Sociu and WPRjvm/70 Psycho~ogica~ Factors in the Spread of Venerea~ Disease

3~. Dr. R.R. Wi~~cox Private physician and Venerea~ Disease Contro~

32. Dr. C.H. Yen and Venereal Diseases in the T. Oyama Pacific Region of WHO

9.3 Background Materiu provided for participants

33. British Co-operative Importaticm of syphi~is WHO/vm/33l.65 CUnicu Group Study into Gt. Britain. A British Co-operative Clinicu Group Study

34. Brown, W.J. Proceedings of the Wor~d Forum on Syphilis and Other Treponematoses (Washington, D.C., September 1962)

35. Brown, W.J., WHO evaluation of f~uor­ Harris, A. and escent treponema! antibody Price, E.V. technique (~ in sero~ogy of syphilis: pilot study (Study I)

30. Brown, W.J., WHO eva~uation of f~uor­ Harris, A. and escent treponema! antibody Price, E.V. technique (FTA:200 in sero~ogy of syphilis: pilot study (Study II) (p~us summary docUll¥!nt) .. 37. Chacko, C.W. Cross-immunologicu re­ actions between syphi~is and yaws. A pre~iminary report .. - 45 -

38. Danielson, Dan Demonstration of N. gone WHO/VDr/RES/GON/4 with the aid of fluores­ cent antibodies. Part n. A comparison between the fluorescent antibody tech­ nique and conventional methods of detecting N. son. in men and women-

39. Eng. J., A comparative study of Nielsen, H.Aa. and fluorescent treponemal Wereide, K. antibody (FTA) and Tre onema 1dum. immob- ilization '!'PI testing in 50 untreated syphlli tic patients

40. Fribourg-Blanc, A. DiagnostiC s~rologique WHO/VDT/RES/7l.65 and Niel, G. Paris de 1& syphilis par l' immuno-fluorescence. Adsorption des anticorps non­ s~cif'ique par le T. Reiter ultrasonne

41. Guthe, T. Transport of frozen sera • and dried bl.ood by improved methods 42. Guthe, T. Fluoreaeent trellonemal WHO/VDr/RES/36 Vaisman, A. and antibody testing of dried Halwalin, A. blood eluent compared with FTA, TPI and lipoidal antigen reaction in serum

43. Guthe, T. Resultats de FTAlOO WHO jvJJr/BES/ 66.105 Vaisman, A. and effectues simultanement avec Halwal1n, A. les ~mes echantillons de sang preleve sur rondelles de papier Cancon No. 435 et sur rondelles de papier. Schleicher Sa Schuell No. 740-E

44. Guthe, T. La technique des anti corps WHOjvDT/BES/57 Vaisman, A., and fluorescent pratiquee sur Halwalin, A. sang desseche et elua II. Etude de la conservation et du transport des echantillons a. des te.ratures eJ.evees 45. Hardy, Jr. Paul, H. Tbe use of a bacterial WHO/VDT/RES/53 lee, Young, C. and culture filtrate as in aid Nell, E. Ellen to the isolation and growth of anserobic spirocbaetes - 46 - •

46. Uederstedt, B., and Quantitative Treponema WHOjvJ1I!/PBS/5O Skog, E. fallidum immobilization TPI) . test in earl,y syphil.is·

47. Kir&l,y, K. Quantitative fluorescent WHOjvJ1I!/PBS/&o treponemal antibody (FTA) studies with balanities "Problem" sera

48. Kiral,y, K., Jobbagy, The value ·of fluorescent WHOjvJ1I!/BEB/5b A. and Mecher, T. treponemal antibody test- ing (FTA.;5Q) in the verif- ication of "problem sera" characteristics conjugated immune sera

49. Kir8.l,y, K., JobbSgy, Group'anttb'odies·in fluores- . WHOjvJ1I!/REB/66.JD8 A. and Kovats, L. cent treponemal antibody (FTA) test .. 50. Kellogg, Jr., The identification of T. WHO/VDT/REB/GON/7 Douglas, S., and pa111dum and N. Gonorrhoea WHO/VDT/RES/65 Deacon, W.E. by a new rapid immuno- fluorescent staining procedure ....

51.• Kupka, K., Indices for decision WHOtm/REB/bb .lll Orusco, M., and .' mak1D.g in syphilis control Kodlin, D.

52. Luger, A. (Editor) Current· Problems in S. Karger, Basel Dermat~logy; Antibiotic pp 187 Treatment of Venereal Diseases'. : .

53. Magnusson, B., and International teamwork. WHOjvDT/319 Otterland, A. to combat'venereal disease in young seafarers

54. Medina, Rafael Reactions produced in pinta, WHOjvJ1I!/RES/ 6 3 yaws or syphilis patients, in inoculation with Treponema pertenue Castellani 1905. Its possible application to the test of cure of these treponematoses ..

55. Nielsen, H. Aage Annual Report of the WHO WHOjvDT/REB/67.65 Serological Reference Centre for Treponematoses, Copenhagen for the year • 1963 - 47 -

~ 56. Nielsen, H. Aage LabQJ:'atary infection in man WHO/VI11!/P.m/70.65 by the Treponema pallid.um (Nichols) 57. Nielsen, H. Aage COmparative study of the WHo/vrlr/RES/49 TPI test and. other trep- onemal tests 58. Ovcinnikov, N.M. Further study of' gonoc- WHo/VI11!/RES/OON/ occal sensitivity to 66.1~ penicillin

59. Ovcinnikav I N.M. , The sensitivity of' gonoc_ WHO/VrJr/PES/OON LurIe, S.S. and occi to penicillin 66.11 Saharava, N.J. 60. Reyn, A., and International reference WHo/VI11!/RES/OON/ Bentzon, M.W. strains of' N. gonorrboea ~.65 for use in ~eterm1natlon of susceptibility to penicillin • 61. United. states Public SyphiliS, a synopsis U.S. Gavt. Printing Healtb Service Office, Washington. PUb. Blth. Sel'Vice • Publication No. lbbO 1967 pp l~' 62. Vaisman, A. Hamelin, Fluorescent treponemal WHO /VI11!/PES/~ A., Guthe, T., and antibody testing of dried Descombes, A. blOod. eluent compared wi. th FTA, !PI and lipoidal antigen reactivity in serum.

6,. Webster, B. The teaching of venereal WlJD/Ym/330.65 diseases in medical school WlJD/EWC/135.65 throughout the vorld. 64. WHO Meeting on Neisseria WH0I'm.j//E;{GON/B Research First Report WHO/BD Men 1.65 65. WHO List of equipment and· WHO/VrJr/3lf3 supplies required. for a VDBL laboratory

66. WHO Report on the First WHO WlJD/WmJ/July 1959 ! VD .Control Seminar of the Western Pacific Region, Tokyo, Japan, 17-29 March, 1958

~ - 48 - •

67. WHO Pre_sem1lD .. rvilllits~to Cambodia I Hong Kongl Korea Japan, Singapore and Taiwan by E. Aujaleu, T. Guthe, H.A.a Nielsen and Dr. R.R. Willcox (1968) unpublished reports to WHO

68. Willcoxl R.R. The essence of gonorr­ WHo/Vrlr/?/29.65 hoea control plus Add. 1,21 3, 4,5.65

9.4 other References

69. Kim Joo Deuk &, Lew Joon (1963) Dept. of Microbiology, Yonsei University Medical College, Seoul, Korea

70. Kim Joo Deukl Kim Hyon Joo &, Kim Kyung OK (1968) Dept. of Microbiology, Yonsei University • Medical College, Seoul, Korea

71. Ho Ting Jao &, Chang Shueh-Shen

72· Smith D.D., &, ~vey (1967) Mea. J. Australia, !, 849-850 J.M: 73· Ids~e, O. Guthe, T., (1968) Bull. WId. Hlth Drg. , 38, 159-188 74. u.s. Army Regulation "Medical Service: Prevention and Control of Venereal Diseases", No. 40';15, 29th Aprll,.i..l:968

75· Lucas, J. B. (1968) Personal communication to R. R. Willcox

76. Schmidt H. &, Roholt K. ( 1965) Ugesker. laeg., 127/14/ 8/4, 478-482 11· Holmes. K.K., Johnson, (1967), J. Amer. Med. Ass., 202, 461-466 D.W., ,. Floyed, T.M.

78. Lomho1t, G., &, Berg, O. (1966), Brit. J. Vener. DiS., ~ 1-7

79· Wren, B.G., (1967) Mea. J. Austral. b 847-849

80. Maddocks, I. (1967) Papua and New Guinea Med. J. !Q., 49-54 (see Abe. Hvg. 1968, No. 2437 )

" - 49 -

~

TABLE I TRENm IN THE 'REV' ALENCE OF EARLY SYPHILIS IN REPORTING CLINICS OF SOME COUNTRIES OF '!'HE WES'J!ERN PACIFIC REGION OF WHO 196O-l967 (see 2.1.2)

TABLE II SEROPOSl'l'IVl'l'Y FOR SYPHILIS IN PROSTl'l'UTES - 1967 (see 2.2.2)

TABLE III SEROPOSl'l'IVlTY FOR SYPHILIS IN MIXED GIOJPS (see 2.2.2)

TABLE JY RESULTS OF SEllJM TESTING BY REAGIN 1'ES'l'S ON ~1'ANT I>IlTHERS IN SOME eotmTRIES OF '!'HE WESTERN PACIFIC REGION OF wm (see 2.2.2)

TABLE V REAGIN SmJM 1'ES1' RESULTS IN KOREA COMPARED • Wl'l'H 'l'HOSE OF RElTER PBO'1!Il:lll COHPI.ailMUt-PIXA!mR HEAC'l'ION (see 2.2.2)

1'.ABLE VI 'l'RENIx:I IN THE PRE.VALEllCE OF GONORRHOEA IN REPORT- ING CLINICS OF SOME COUNTRIES OF THE WES1'ERH • PAClFIC REGION OF WHO (see 2.3.1)

TABLE VII AN'rmI01'ICS USED IN THE 1'READIENT OF GOR>RRHOEA (see 4.2.1)

TABLE VIII SENSl'l'IVl'l'IES OF 43 MIXED STRAINS OF GOr«>COCCI FR>M 1'HAILAND, HONG KONG, 'l'AIWAN AND VlE'r-NAM EXAMINIl:D 1967-1968 AT THE WHO NEISSERIA CENTRE COPENHAGEN (see 4.2.2.6)

TABLE IX SEmIM LEVELS IN UNITS/ML FOLLOWING 5 MEGA UNl'l'S OF BEl'rZXL PENICILLIN WITH AND Wl'l'JI)V1' 1.0 GM PROBENECID (PROBEItECID GIVEN HALF AN HOUR BEFORE INJECTION, see 4.2.4)

TABLE X GOR>RRHOEA IN PROSTrroTES - 1967 (see 5.6.2) •

TABLE I • TRENOO IN THE PREVALENCE OF EARLY SYPHILIS IN REPORTING CLINICS OF SOME COUNTRIES OF THE WE8TERN PACIFIC REGION OF WHO 1960 - 1967

Country Type of Syphilis 1960 1967 Per cent. increase

Fiji (4) 81 and 82 2 10 500.0 New Zealand (10) 81 and 82 56 144 157.1

Viet-Nam (15) Sl and S2 14 25 64.5 • Japan (7) Sl and 82 910 1249 57.5 Australia (1)* Unspecified 794 958 18.1 8ingapore (15) Sl and 82 222 192 minus 15.5 New Caledonia (9) Sl and 82 9 7 minus 22.2 Hong Kong (6) Sl and S2 66 25 minus 62.5

Nil returns were reported in both years from the Philippines (9), Trust Territory of Pacific Islands (ll) and Western Samoa (12).

*Data available for 6 states on~.

• ! - 51 •

TABLE II

SEROPOSTIIVITY FOR SYPHILIS IN PROSTTIUTES 1967

Country Type of Number Per cent. prostitute Te~t examined Positive positive

Viet-Nam (15) Arrested Unstated 1 524 254 16.7 prostitutes

Japan (7) Suspected Ogata WR 2 858 588 15.7 prostitutes

! Taiwan (2) Bar girls ) restaurant girls ) unstated 9 060 925 10.2 foodhandlers ) • Korea (8) Entertainers VDRL 59 509 5 148 8.8

Taipei Cityr Bar girls unstated 826 68 8.2

Philippines (12) Hostesses & unstated 4 090 5.17 Waitresses

,. -52- •

TABIE In • SEROPOSITIVITY FOR SYPHILIS IN MIXED GROUPS

No Per Number Country Year Test . reac- cent. Group examined t1ve reactive

Students Kflrea (8) 1967 VDRL 200 7 5.5 Students Singapore (5) 1967 Unstated 114 2.6 (Male) Students and Japan (7) 1967 Ogata WR 51 682 0.2 schoolchildren • Pre-marital Japan (7) 1967 OgataWR 172 555 1.1

Employees Ie) students ) Japan (7) 1967 Ogata WR 478 8.0 (mixed) ) Hospital Viet-Nam (15) 1967 VDRL 11 855 6.7 inmates

Military Taiwan (2) 1967 VDRL 12 730 685 5.4

MilitaIY Korea (8) 1964 VDRL & RPCFl' 1 580 44 2.8

Military New Caledonia (9) 1"966 . Kline & Kolmer 172 0.6

Bl "d donors Korea (8) 1965 VDRL 5200 1100 21.2

Vagrants Japan (7) 1967 Ogata WR 6 953 6 603 9.5

Prisoners Singapore (15) 1967 Unspecified 448 5.7 Venereal ) .. disease ) Viet-Nam (15) 1967 VDRL 5 555 20.7 patients )

~ - 5~ -

!M.BLE IV

RESUIll'S OF SERUM TEarING BY REAGIN TESTS ON EXPECTANT M:>!rHImS m SOME COUNTRIES OF THE WE9l'ERN PACIFIC REGION OF WHO

Country Per cfllt. Year Test Tested Positive posit1ve

Korea (8) 1966 VDRL 330 23 6.9

Taipei City (3) 1967 VDRL and Kahn 1 555 6.6 Viet-Nam (15) 1967 VDRL 11 060 6.4 Taiwan (2) 1967 VDRL 17610 542 3·0 ~ New Caledonia (9) 1967 Xlizte & Kolmer 988 1.5 Japan (7) 1967 Ogata WR 609 607 1.1 • Hong Kong (6) 1967 VDRL & RPCF'l' 55 012 189 0.3 Singapore (13) 1967 Unspecified 12983 0.3

Philippines (12) 1966 Unspecified IS 586 0.08 TAllIE V . .. BEAGIN SERUM 'fE8.r BESUIll'S IN KO~ COMPABED WITH 'l'llQSE OF REl'l'ER PlI>TEIN COMPIEMBNT.,.FlXATION JfEA.CTIONS69

·VDRL Kolmer BPCF No. No. No. Tested Pos- 1- Pos- 1- Tested Poe- ~ iUve it1ve It1ve

ProstItutes for 910 1511- 16.9 190 20.9 209 4, 4.7 foreigners Prostitutes for 168 18 10.7 27 16.1 27 9 5.4 local persons Leprosy patients 188 46 24.5 5J.. 27·1 58 2, 12.2 .:: . '. ":.:.: "Normal sports- 337 25 7.4 ·,1 ; 9.2 34 5 1·5 men" .. - • 55 •

TAl3IE VI

TRENOO m THE PREVAmNCE OF GQNOBRHOFA IN REPORl'ING CLINICS OF SOME COUNTRIES OF THE WESTERN PACIFIC REGION OF WHO

country 1967 Per cent. increase

Western Samoa (16) 35 244 597·1 Phil.ippines (12) 1190 4397 268.7 Fiji (4) 380 962 152.6

! New Zealand (10) 992 2305 142.4 Viet-Nam (15) 992 2066 108.;

Austral.ia (1)* 4948 7112 55·9 • Trust Territory Pacific IaJ ands (14) 342 488 42·7 Hong Kong (6) 6506 7344 12.9

Singapore (13) 2529 2617 3·5 Japan (7) 7050 6049 minus li..2 New caledonia {9' 140 loB minus 22.9

*Data fran 6 states only

.. -56- •

TABLE VII • ANTIBIOrICS USED IN THE TREAT!4ENT OF GONORRHOEA

INJECTABLE PREPARATIONS

Crystalline penicillin G, aqueous procaine penicillin, mixtures of crystalline and procaine penicillin! repository penicillins - as benzath1nel and benethamine penicillin or mixtures containing theml , ampicillin and the cephalosporins synnematin B and Cephaloridine. Penicillinase-resistant penicillins are ineffective.

Injectable tetrac,yclines including ro11tetrac,ycline, chloromYcetin succinate2, kan~cin, speetinoJqycin5 and streptonvcin5•

ORALLY ADMINISTERED PREPARATIONS

Pheno:x;ymetbyl penicillin (V), phenethicillin, ampicillin, • panamecillin4.

Chlortetrac,ycline, o~tetrac,ycline, tetrac,ycline hydrochloride and phosphate complex, demetbylchlortetrac,ycline, limecycline, methac,ycline, clomoc,ycline, d~qycline, mixed tetrac,yclines.

Chloramphenicol2 and its analogue thiamphenicol, erythronvcin, oleandoJqycin, spiranvcin, pristinonrrcin, hetacillin, rifampicin5•

Sulphonamides with trimethoprim.

1. Not recommended as likelr to foster developing resistance.

2. Not recommended on grounds of toxicity.

5. Not recommended be,cause of resistance.

4. Not reported upon.

5. Not currentlr commerciallr available.

Serum levels with all penicillin preparations can • be enhanced and prolonged by the use of probenecid. TABLEVIII

SENSITIVITIES OF 4, MIXEDSTBAINS CF GONOCOCCIFROM THAIIAND, HOC:=':~AH AID VIET·HAM - !."XAlaNED 1967·l.968 AT WIlD IEISSERIA CJ!llIt.tRE,

Antibiotic Method Definition Sensitive Moderately Less Resist- '" less sen- of resistance Sensitive Sensitive ant sltive or or lessened resistant sensitivity

Penicillin Plate IC50 0.088 4 90.7 dilution u/ml. (0.05' '9 method mcg/ml.) or 1ess-J.ess sensitive StreptODtfcin ditto IC50 25 mcg/ ml. or more 7 - ~ 79·1 Spiramycin ditto IC50 0.95 meg/ 9 ~ 79.1 ml. or more In Tetracycline ditto IC50 1.1, mcg/ ml. or more 11 ,2 74.4

Erytbro!lwcin Disc 10 mcg (+++ .. method sensitive ++ = moderately sensitive, + .. less sensitive 0= resistant) 9 1 2'·3 KanaD\YCin ditto 50 "'" 4 '9 Chloramphenicol ditto 50 mcg rttO)ditto) 32 "11 Sulpbatbiazole ditto 238mcg ditto) 40 3 NalidiXic acid ditto 50 meg ditto) 43

me 1s apprax..tmc.te~·dOuble the IC50

.., ... -, .. • •• - 58 - •

TABLE IX • SERUM LEVElS IN UNITS/HI. FOLLOWING 5 t1EGA UNITS OF BENZYL PENICILLIN WITH AND WITHOUT 1.0 GM (PROBENECID GIVEN HALF AN HOUR BEFORE INJECTION)76

Time after Number of injection observations Maximum Minimum Average

HALF HOUR Without probenecid 17 140 21 74.4 With probenecid 27 245 20 95.7 ONE HOUR '\oJithout probenecid 9 127 47 75.4 With probenecid II 180 47 104.8 TWO HOURS • Without probenecid 9 91 17 49.9 With probenecid 11 155 45 94.2 FOUR HOURS 'l-lithout probenecid 17 61 2.0 15.1 With probenecid 28 92 10 42.8 EIGHT HOURS Without probenecid 8 8.8 0.05 1.8 With probenecid 10 22 0.6 5.5 TWENTY-FOUR HOURS Without probenecid 8 0.12 nil* 0.02 \Vith probenecid 10 0.10 nil* 0.02

*readings of 0.02\1. ! ml. or less taken Cas zero TABLE X GONORRHOEA IN PROSTITUTES - 1967

country Group Total Positive Per cent. examined poe.tive

Viet-Nam (15) Arrested 1524 33.4 prostitutes

Taipei City (3) Bar girls 957 311 31·5 Japan (7) Arrested. 3794 1129 29·8 prostitutes, call girls, hostesses •

Tot a 1 6275

• ..

FIGURES .. FIG I PENICILLIN SENSI'l'IVITIES OF MIXED AND UN­ SEIEm'ED STRAIIffl OF GONOCOCCI IN THE FAR EAST ANn IN LONDoN26, 28, 71 (see 4.2.2 b) .

FIG II SERUM lEVEIB FOLLOWING 2.4 MmA UNI'l'S OF PRO- CAINE PENICI~ IN. EIGHT SUBJ,EC'l'S2:l, 75 (see 4.2.,) FIGS IIa & lITh SERUM !EYErs OF PENICILLIN (u/mlJ AFTER 2-8 HOURS FOLWtlING 5 MroA UNITS OF BENZYL PENICILLIN WITH AND WITHOU'l' PROBENECID HALF AN HOUR BEFORE INJECTION (see 4.2.,)

FIG IV BUIID-UP OF RESISTANCE OF THE GONOCOCCUS TO ANTIBIOTICS (see Annex IX)

.. -oi-

1.",-, -'-. J.'.,.j. L. f'ENTeT~.:.Tr, . -;,:~~ r7I~J-r;IF~: O!-"' >{IXE~'.i ,,'.:';~: ~r;~3EJ E.·:n'}:D :..~frRAINS OF • C.. ;\~'~;rCCGcJ It{ THY F'AR E,~Sj ,;'1ND LCrrrC.t-1 28

......

nnites/ml

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~~.• n fI.3 J.• 0 8.::1 e.}~ 11.1 22.2 O.12S or.:! o 100

----,----~----.-~------~------:~. S 1.0 -:. {I 9.6 0.t-J 35.6 .'1 i '- ..... 44.2 • o 1.00

..... __".- ___.~. __'__.~ .. __ .H ___" __ ~ ____'_ .". ______..- __ .. ' __• ______, ______

~ i~ -+ ... \..1 11.8 5.,} 25.6 r: .- j~ •• ; ,6.5 2.C 58.::' 11'"~\ "4.4 100 -62-

_.. ' .. •

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" I,.:);;r=- ~,:'r'~ .~ :"':~.('r' \C'j-~-;hrl' d '[K'I;/"t: ~ ,lrr2~ I l!lJ~':- ;';,~;~

y;w:::!Hra ~ t \,\i n~)Cl.'il~r!1~ :1"111 . m~Ce'-IHrandn Pl

.. •• .. I. • ".,L F;E;:Ji,!.': ,il ~:j(~;'.~f\f-:. 111"

j~l~\r .. - .. ------.---~- "~n' .. --'-.~,-:-'-,..-'-,_._-... ,._-- . SUJ(UM'-- -'--',--. LLVI:;!.3 \..if t t,i,i"':lw":;'" t U/'MC) AFTU£ 2 t.o 8 Si:;hUJo\i2Vr~l...S ,..;F' } t.NICli..LIN (U/I'.L) HTdi. ;; Tv 8 HUUiJ. .HUUl1.S""~i4·J;;;!_N·'; :> ""i:J:;;;'JNiT.. ,,1' B-,,-tU.Y~liNICILLIH l"OLWWING 5 jofuGA UNlT~;uF Bl!.liZYL ["N1.(;lLL1N wlTHUuTT l 1\ . "J rr:~.:; i \ : ~M ')14f H~'~';--: ~. \..;" ho' ,I" h- ,u' }J( ;.'('j., I' 'J" T 0 "M ,. B'L

CLNCI!:N'l1tATlON DE I EN.'IClllINl: DANS .k. SERUM (UNITES/: C(;fIc~NTH.A'fUN 1,,;'; ;. t,.;qC::u ..d,~ ;",~NS U. J.i:.rtUI1 (UNiTi!.5/ PC l ML) ENl'Rt, 2 A B HLU.u,S Ai'l1.t;S AV;'llt:I.3THATION Dj<;, I ,'1(\ ML) ¥-NTP~2 A 8 lil:.li'iSv AtllLS iI1JNINl::iT,(J\nON Db 5 MEGA DE I UNITE Bi.NZILPENICILLlNE SANS ADMINISl'aA1'lup i"ihCJ..-VNlT.c,:; vi:, Bi:,],,;L.J'.t.NICi ....l..iNI!: AV~C,J..'J/JtU::iTi:iATJ.O i f DE 1 G l)i', i-Hl)B;:.Nl!:Cim~UNE DEMI-mJJ,JCAVANT .,I I ,_ I D]:; 1 (), v1 trtlJBtJ~CliJhLiNL Ul:.r-ti-hlJJ£\t. AV"l>;T 6 1 ",~ L'INJECTION7 , " 7L. r t-. '. ,\..' INJ.c.CT lUN v \ I

.~,~~,;;:.tl-~7~?\ ~\\"'~,i IX) \ ,:r c-mICFN1RI-\110N ~':"'-":"'U~/\Ah:,,/.n;:f."': \ "-41r.\.,'nL':~:~/:..()..,!.1_/t' -:;L­ <. ;"": ;(/.. '~:I'-<'}1,' ~ E ~';c~!":ft 10!/t.J 1 /!(; ;;;\~~n~\ i\; 'r,:' ~,l::'f;i1\J; .11 i'?I_;/~ ~.'),',~;,,:,;,,,ie tl(l~, . \ l;\(,\: ""'w.\" ~ , , , \ \ \ I , ~ I \ ill: '\ .~ i '~,'i" \ , '\ ~. r \ ! \ \ I " ~: I \ \ I " \ 7(\r \. I:~ ,j \ i ~ \, ~ ! ' & N! ' \ ':i. c', r \.. \ i, " \ -., '-., , "\. ,. \ \ 7' '" :4 " \ , I , I \ t,, , \. \

""'~ ~'--~.. '" "L' \---..- '.'. /' ! C . ~ '~., ;) .. - I ! ~~ ! ..... '+- -, "'~...... ,......

Q , ___ ,- ____ .L. _____ . __ =.:-:':=_~-:'::''-'':'::~''':~'::::.:L...,._--'--__..,_._., __ ,_,..._. ___ ,_ ... :~~-:.. ______J •.1 'L _ .. --- ....._- + ~----- ~ 8 ~ 1:1 B\.!\.hG:>AFT uU INJ i!.CTlI.iN filA!.;:'; Antit INJl:.CT lVN i.::JlIIbre d' lleures apr!!s .l.' injection Nombre diheures apr~sl'injection ...

..

, '

\,) <.': f: ~ t"".

.J :.. ..

.',\ t.!j .":: L. ":,-' '-'

, I':'., • -~-

! ANNEX I LtST OF EQUIPf.!lmT AND SUPPaES FOR VDRL TEX!r (see ;.1.2. (6»

ANNEX II LIST OF EQUIPMEm AND SUPPLIES FOR m TEST (see 5.1.2.(c»

ANNEX III SUGGESTED FORM FOR USE BY CLINICS/:oooroRS WHEN SENDING SPECIMENS TO A LAroRATORY FOR EXAMIN- ATION FOR smcrLtS (OR OTHER TREPO~SES), AND SUGGESTED REPORl'ING FORM FROM THE IAB:>RATORY (see ;.1.2{c»

ANNEX IV NOTE ON PRESERVATION AND TRANSPORT OF SERA IN LtQUID NI'1'ROGEN AT 150°C TO 196°c (see ;.1.2(e»

ANNEX V SUGGESTED SCHEIXJLES FOR THE '1'REATMENT OF smcrLtS ! (see 4.1.1)

ANNEX VI SUGGES'l'ED SCHEIXJI85 FOR THE 'l.'RF.A!rMENT OF GONORmlOEA. IN AREAS OF HIGH RESISTANCE , (see 4.2.4) ANNEX VII SOOGES'l'ED TREATMENT OF SOME DlPORl'ADT SEXUALLY TRANSMI'1'1'ED DIS~ OTHER THAN smcrLtS AND GONORRHOEA (see 4.;)

ANNEX VIII FURM OF CONrACT SLtP USED IN THE UNITED KINGDOM (see 5.;.1 (b»

ANNEX IX MECHANISM OF BUILD-UP OF RESISTANCE OF THE GONOCOCCUS oro ANTIBIOTICS IN THE WES'l'ERl.'l PACIFIC REGION

ANNEX X INTERNM'IONAL ASPECTS OF VENEREAL DISEASE AND TREPONEMATOSES CONTROL .-

ANNEX I

LIST OF EQUIPMENT AND SUPPLIES • FOR VDRL TEST

A. If the VDRL test were introduced into an existing well-equipped serological laborator,y the following particular items would be needed:

Price: U.S.$

1) Electric rotator (Cl~ Adams, A-2271) 71.00 2) Ceramic ring slides "Permaslides" (Cla,y Adams A-1751) 5 doz. 18.00 5) Slide holder (Scientific Products Company, Evanston, Illinois, Cat.no. 66555) or local make (See 1959 Manual for Serologic Tests for Syphilis, page 127) 4) Microscope, monocular or binocular. Magnification lOOx 157.00 5) Anti~en VDRL Wel1come Cardiolipin (for testing of 5000 sera)Burroughs Wellcome Co. Vials of 5 ml 10 x 4.50 45.00 • 6) Tuberculin syringe 1 ml in 1/100 with Luer tip (Omega, Microstat) 5 pieces 2.10 7) Piston rings for above 15 pieces 1.50 8) Needles, Luer lock, bl1Mt point, 100 x 1 1/2" (to deliver 1/60 ml drops)(Unimed S.A.) 1 doz. 0.60 9) Needles, Luer lock, blunt :point, 250 x 1 1/211 (to deliver 1/100 ml drops) 5 doz. 1.50

Total price: 296.70

B. For an independent VDRL laborator,y the total cost would be about U.S. $2825.00 which also includes the general equipment necessar,y in addition to A. above. For more detailed information see document WHO/VI1l'/51S which is available from WHO, Geneva.

• • ... - 67 -

Al-.'NEX II

LIST OF EQUIPMENT AND SUPPLIES FOR FLUORESCENT TREPONENAL ANTIBODY TEST (FrA)

A. Ii' the FTA test were introduced into an existing we11-equipped serological laboratory the following particUlar items would be needed:

Pricet U.5.#

1) Microscope for immunofluorescent ~tions (For details of suitable microscopes see World Health Organizati~ documents INT/VDT/171 available on application to WHO, Geneva 1015.25 2) High quali1;y microscope slides f .inst. Socorex 20 gross 29.25 3) Staining dish (Baird & Tatlock Cat.no. Cl5/784/785) 8 pieces 20.72 4) Plastic tr~s with lid, 32.5 x 11.5 x 1.5 em (Statens Seruminstitut Copenhagen) 6 pieces 52.12 , J 5) FTA BBMgen (Baltimore Biological Lab.)- -- Antigen sufficient for 800 tests. 20 ampoules 20.00 6) Fluorescein labelled anti-human conjugate (Baltimore Biological Lab.) 6 ampoules 7.00 7) Bacto~H~magglutination Buffer 60 vials 15.00 8) Control serum (Statens Seruminstitut, Copenhagen)30 ampoules 5.00

Total price:

B. For an independent FTA laborator,r the total cost would be about U.S. $3000 which also inclu,~es 1;.he. general equipment necessary in addition to A. above. For more detailed information see document WHO/Vm'/3l8 which 'is avauable from WHO, Geneva. - 68 - • ANNEX III

SUGGES!I.'ED FORM FOR USE BY CLINICS/OOCTORS WHEN SENDm:; .. SERDM SPECD4ENS TO A LABORATORY FOR EXAMI~ION FOR SYllHn.rs (OR OTHER TREPONEMATOSES)

REQUEST FOR SEOOLOGICAL EXAMmATION FOR SYPHILIS (TREPONEMATOSES) I • I Doctor's or clinic's name and address: i !

! Patient's name or initials: ! Sex [Ff - [il Birth Date Month Year I - I Venous bloOd. Cord blood Spinal fluid I 0 0 L::7 i , Last blood specimen taken fran patient: Date i { • I ! I Result l 1 ..

I History of syphilis (or other treponema! disease) i Clinical observations: ! yes I i Primary lesion /s T. pallldum / i "---·No found "'---- No Yes .-Yes Secondary .;- T. pallidum <- manifestation~ No found No

I rate I manifestation: Nervous system I Cardiovascular system Skin-lIDlcous membranes Others (specify) Congenital:

II If no anamnestical or clinical symptoms on SyphiliS, which is the diagnosis (tentative): In regard to Treponematoses • In regard to other diseases - 69 -

REPORT ON SEROLOGICAL EXAMINATION FOR SYPHILIS (TRIllPONEMMtlSES) Patient's name or initials ______I Sex 0-0 B1rth Date ___ Month Year --l I VetlQUS blood 0 Cord blood Ll Spinal fluid 0

RESULTS

VDRL qualitative VDRL quantitative

CF test quantitative:

~(Am) (200) inh1bition qualitat1ve quantitative

, TPI qualitative

! For doctor or clinic: I

r - 7& - •

ANNEX IV

NarE ON PRESERVATION AND TRANSPORT OF SERA IN LIQUID NITROOEN AT - 15000 TO - 19600

by

T. GurHE Division of Communicable Diseases World Health Organ:ization, Geneva, Switzerland

fucperience has shown that the use of solid C~. (dr,r-ice) for serum II preservation is expensive and not ver,y practical and that the cost of freeze-drying under field conditions is prohibitive. The use of thermo­ insulated jars and wet ice is not alwa,ys sufficient to prevent important changes in the temperature-of -specimens and the denaturation of sera; and normal. shipment of specimens by air or surface mail has been shown sometimes to entail repeated freezings and thawings - known to be deleterious to antibodies. •

Deep-freezing by liquid gases at ver,y low temperatures for the inert preservation of biological material has, over the past decades, been gradual~ extended from being mainly a research tool to becoming also the basis for many practical techniques. Outstanding examples with the application of liquid nitrogen, for instance, are its use for the pre­ servation at - lSOoC to - 1960 C of bull sperm for artificial insemination in animal husbandly programmes, for the banking of whole blood for trans­ ," fusion purposes, and for the establishment of ~-culture collections of bacteria, parasites, viruses, tissue cell lines, etc., thus ensuring instant availability of' uncontaminated, unaltered reference material. Modern cr,yogenic techniques involving low temperature of this order can also be useful~ applied to the long-distance transport of human serum. This note brie~ describes the successful adaptation for this purpose of liquid nitrogen transporter-refrigerator original~ used for the preservation of bull sperm. The transporter-refrigerator that has been developed (LR-IOA-6)a is a superinsulated double-walled container made of alumint~, which gives

li.rhe Union Carbide Company Europa SA, Geneva, Switzerland, provided valuable assistance in all phases of the development of this equipment for serum transport. Acknowledgement for valuable technical advice is also made to Professor A.P. Rinfret of the Linde Research Laboratories, Tonawanda, N.Y., USA; to Dr. S. Christiansen, Scientific Adviser, WHO Serological Reference Centre, Copenhagen; and to Dr. H.A. Nielsen, Director, Treponematoses Department, Statens Seruminstltut, Copenhagen, Denmark. - 74·- •

it structural strength and light weight. Fig. 1 shows its external aspect. Its small sue, carrying handle and carrying frame facilitate ! portability. A slotted ring cap surrounding the top of the neck tube proVides a convenient method of suspending inside the container six canisters each holding a number of ampoule racks. A porous plug of low heat-conduction material reduces liquid nitrogen loss due to evaporation and protects the neck tube. Fig. 2 shows a cross-section of the refrigerator-transporter with its different elements. Fig.:3 shows how the ampoules are clipped in the rack, and hoW the rack is inserted into the canister; and Fig. 4 shows insertion of a canister into the refrigerator-transporter. The measurements and technical specifications are given in the table. The LR-10A-6 has a liquid nitrogen capacity of 9.4 litres with canisters, racks and ampoules inserted. The low eVaporation rate of liquid nitrogen (0.55 litre per d~) gave a holding time without nitrogen refill of more than three weeks on the avera~ e.g. in 12 long-distance air • transports of sera between Nigeria (Lagos) and Denmark (Copenhagen) or France (Paris). Liquid nitrogen can now be obtained from any o~gen factory in most large cities at the price of a few cents per litre. The canisters with the ampoule racks should be inserted very • slowly into the container for freezing (at approximately 10 cm per minute) so as to avoid boiling of the nitrogen. The correct insertion and removal technique must be learned b,y experience. Experiments have been conducted on the use of serologically inert, freeze-resistant and steriluable low-pressure polyetqylene or poly­ pro~lene tubes with an airtight screw sto~r to contain the serum specimens. A standard tube is now available~,in packages of 100, sterilued b,y irradiation. The tubes are pre-labelled, and different coloured labels for aliquots of the same serum can be used. The tubes are numbered b,y the use of a "Tech Pen"** which has freeze­ resistant ink. We have found these to be a practical replacement for glass ampoules previously used. There is no risk of explosion with the LR-10A-6, and it is accepted b,y public carriers for air shipment under IATA regulationsc. The air freight cost is reasonable. The purchase cost of this refrigerator­ transporter is also reasonable.

*Nunc A/S, Roskilde, Denmark **Mark-Tex Corp., Englewood, New Jersey, U.S.A. cInternational Air Transport Association (1965) LATA regulations relating to the carriage of restricted articles b,y air, Montreal, Section IV N, Article 1275. This article allows the carriage of up to 50 litres ! of liquid non-pressurued nitrogen on passenger and cargo aircraft. -11- •

The equipment described above has been found to provide a"practical, efficient, safe and economical method of "bringing the field into the . 1aborator,y" for immunological investigations. It allows serological specimens to be frozen in situ, mirrllnizing the risk of specimen infection and of protein denaturation. The ready availability of such "base-line" biological material also permits accurate evaluation qy an overseas reference laborator,y of serological test performance in a local field laboratory working under tropical conditions. In addition, this equipment makes it possible for scient:Li'ic measurement procedures to be established for comparative studies of the influence of time and temperature exposures on serum components and antibodies under given conditions. Such evidence as is available suggests that the eutectic temperature of human serum is in the neighbourhood of -60OC and that pre8erved serum 1s not inert above that temperature; there is also evidence that some serum components become denatured at -40°C. Since laboratories throughout the world continue to store serum collections· at temperatures of _:WoC or higher in conveniently available commercial food refrigerators, further funda­ mental research in this area appears to be needed. (A fuller article on this subject has been published in Arch. Immuno1. There expo 1966, ,!!, 889). •

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Epidemiological Epidemiological Symptomatic Symptomatic

Asymptomatic Asymptomatic Over Over Clinical Clinical

Cardiovascular Cardiovascular opportunity opportunity with with

Late Late

Early Early Primary. secondary. secondary. Primary. Late Late

Latent. Latent.

Congenital~ Congenital~

visceral visceral

2 2

Up Up

to to

kg kg

Syphilis Syphilis

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pregnancy. pregnancy.

• •

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Therapy Therapy

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age age

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32 32

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therapy. therapy.

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SUGGESTED SUGGESTED

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Total Total

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given given

units units into into

dose dose

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units units

In In units units

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ANNEX ANNEX

10 10

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......

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per per

as as

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nbO nbO daily daily

daily. daily. of of

of of

of of

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4.8-6.0 4.8-6.0

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of of

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units units

V V

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to to

fot fot

fot fot

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SOOOES'l'ED SCHEIlJIm; FOR THE TREA1'MENT OF : GONORRHOEA IN AREAS OF HIGH RESISTANcE23

I: SOME SUGGESTED SINGLE SESSION PROCElXJRES OF PARrICUIAR VAWE IN PUBLIC HEAI4'H PROGRAMMES

Schedule COIIIIJIent Cost in pence to U. K. hos'Dita1.a* 1. Aqueous lXl'oca1ne Very large injections (10 ml). 51.6 with penicillin 4.8 mega lXl'obenecid units (with 1.0 gm of (1 gm lXl'obenecid probenecid 1 costs 8.4 pen~l 2. Aqueous lXl'oca1ne No blood. level data available in 40.2 with penicillin 3 mega unit this dosage. lXl'obenecid. fortified by one mega Smaller injection possible. unit of crystall1ne (8.5 - 12 ml) penicillin G (with 1.0 Htgher peak level. PJD of ~'benecid) • ,. AqueOUlt benzyl 51 .9.(including penicillin 5 mega Complete success in Greenland78 ,.4 for lidocaine units in 0.5 per cent. Even smaller injection (8 ml.) and 8.4 for lidocaine plus 1.0 gm probenecid of probenecid. 4. Aqueous lXl'ocaine Also smaller injection (lj ml.). With phenoxymethyl penicillin 2.4 mega As yet untried in areaS of high penicillln 38.5; units plus 2 gm of resistance. with penethiclllin I phenoxymethyl methyl Added oral therapy could be used 49.3; with I peniclllin, phene- with larger lnjections as in ampicillin 68·9 . I I thicl11ln or 1.0 gm (1) am (2). (including 21.6 for, ampicillin by mouth forprocalne plus probenecid 1 gm. pencillin and 8.4 for p;J:'Obenecid). I 5· Chloromycet1n Effective but risks of toxicity 79.0 succlnate 1 sm. too great for general use. 6. KaD8.JlG"C1n:2'.. Op Effect1ve so far where used. 000.0 Very expensive. 7. Spect1nomycin 4 gm. As successful as 2.4 mega units Not yet on general of lXl'oca1ne penicillin in tEA. market. May need further evalustion ln a If and when it ls, hlgh reSistance area. is not expected I to be cheap. *For comparison 1.2 mega units of procaine penicillin costs 10.8 pence. (Schedules 2-7 may be repeated on second day in females). •

• •

II: SOME SUGGEBl'ED SCHEDULES INVOLVING ONLY ONE ORAL roSE TAKEN AWAY FROM THE CLINIC • aJ. l''O.l.lOW- 'lIP n'&s Cost in pence to 8chedule dose U.K. hosP1tal.s* 8. Aqueous· procaine 2 mega units (1.25 g)' For use should 160.9 with penicUl1n 4.8 mega phenox;ymethyl Schedule 1 . probenecid units (with peGt.cillln with prove ine:f':f'ec- probenecid 19m) o. 5 gill probenecid tive • 1 ai'ter 6 bours, . 9· ditto 1.25 gill. phenethici- ditto 80.0 with llin with 0.; gill probenecid probenecid a1'ter 6 hours

10. ditto 1.0 gill ampicillin ditto 94.8 with with 0.; gin probenecid probenecid a1'ter 6-8 hours ;;.; with • 11. Fortified aqueous ! 2 mega units (l.2?g) .For use should procaine peni- phenoxymethy1 peni- Schedule 2 probenecid cillln (3 mega cUl1n with O.;gm prove inef':fec- un!ts of procaine probenecid a1'ter tive. penicillin, 1 mega 6 hours un!t of crystalline penicillin G) with 1 gin probenecid i .12. ditto 1.2; gill phenethi- ditto 74.6 with cillin with 0.5 gin probenecid probenecid after 6 hours

. 13. ditto 1.0 gill ampicillin ditto 89.4 with with 0.5 gm of probenecid probenecid a1'ter 6.8 hours ! 14. Aqueous procaine 1.0 gill of ampicillin : For use should I 73.2 including penicillin 2.4 gill plus 0.; gin Schedule 4 38.9 for plus 1.0 gm probenecid prove ineffec- ampicillin + ampicillin plus tive 12.7 for 1.0 gill probenecid I probenecid * Fl:n' canpartson 1.2 mega units of procaine penicilJ.1n costs 10.8 pence. (Schedules 11-14 may be repeated on the second day in females) .. 80 .. •

III: POSSIBLE MULTIPLE DOSAGE_ SCHEDULES

Schedule Comment 15. queous -c:rystalline penicillin Used with complete success i.m. 2 mega units t.d.s. (24 on promis~~ous women in mega) plus 2.0 gm probenecid Australia • Admission to (16 gm) twice dail.f for 4 dqs hospital necessar,y. 16. Aqueous procaine penici in Used yith success in ar 2.4 mega i.m. plus 1.0 gm East1 • 5 tablets to be probenecid half-an-hour before taken aw~ qy patient are injection and three sub­ not an antibiotic sequent doses of 0.5 gm 6-hourlY (Total 2.5 gm) i 17. Ampicillin, oral 1.Ogm plus Good results in Far ast 116.6 or 500 mgm four times a ~ 8-16 capsules to be taken 194.4 for I for 1 dq for males (~ ~s aw~ qy patient. females I, for-females) .. 18. Ditto plus 19m probenec d Ditto-plus 6 probenecid 144.5 for males; 1 b.d. for 2 dqs tablets to be taken aw~ 222.1 for I qy patient. females • E:rythrorrucin oral 1.0 gm Few reports from ar East. 90.2 for es; plus 500 mgm q.d.s. for 1 day Sensitivi~-tests2~ would 170.4 for (Total 5.0 gm) . indicate lik€lihood of females (2 d8\f - 5.0 gm for success. 8-16 tablets to females) be taken awq qy patient. ! 20. Tetrac,ycline hydrochloride Complete success in Far 127.7 I (oral) 1.5 gm plus 500 mgm Eastll but will not reach q.d.s. for 4 ~s (9.S.gm) same re~ated resistant ! strains?l. 2 • Chloramphenicol oral ot recommended for routine 14.4 500 mgm q.d.s. for 1 da3 use on account of toxici~. (can be extended to -2 da¥s For the occasional multiple in females) failure case onlY. By far the cheapest 6-14 capsules taken awaY by patient.

1. For comparison 1.2 mega units of procaine penicillin costs 10.8 pence. • 2. First dose MBJ" be replaced qy injection of 500 mgm of ampicillin at additional cost of 21.8 pence. • (For both males and females unless otherwise stated) • - 81 -

ANNEX VII • SUGGESTED TREATMENT OF SOME IMPORTANT SEXUALLY TRANSMrrrED DISEASES OTHER THAN SYPHILIS AND GONORRHOEA

1. CHANCROID

Caused b,y the bacillus H. ducr~i, there are no readily available practical tests for the pathological confirmation of this condition as the organism is difficult to grow, smear diagnosis is unsatisfactory and the antigen for skin testing (DmelCos) is no longer cOllll!lercially available. It responds to sulphonamides, streptomYcin, the tetraqycline group of antibiotics, erythromrcin, chloramphenicol and penicillin in high doses, but sulphonamides are preferred as they are inactive against syphilis, and chloramphenicol is precluded on grounds of toxici41.

The first aim must be to exclUde s,yphilis by repeated dark-field and • serum tests, the latter over a period of three months. Only normal saline should be applied to the sores while the dark-field examinations are being carried out. Sulphonamides (e.g., sulphadiaz ine, sulphathiaz ole) should be given by mouth, 1.0 gm four times a da.Y" for 7 days, following an initial loading dose of 2.0 gm. Long-acting preparations have also been used. Local antiseptics or antibiotics may be applied once the dark-field examina­ tions have been completed. The unilocular buboes should be aspirated if th~ become fluctuant before bursting, and tetracycline (500 mgm orally four times a day) or strepto!l\Y"cin (1.. 0 gm b,y injection daily) should be used in severe cases, in those complicated by phage dena or when response is tarctv or inadequate.

In circumstances in which no dark-field facilities are available, or if follow-up is unlikely, the patient should also receive adequate treatment for syphilis (e .. g., two injections of 2.4 mega units of procaine penicillin with aluminium monostearate (PA}!) or of benzathine penicillin a lTeek apart) in addition to sulphonamides b,y mouth.

2. LTI1PHOGRANULOHA VENEREID-l (Nicolas-Favre)

Both skin and complement-fixation tests can be used to aid diagnosis of this condition which is caused by a virus of the psittacosis-trachoma group. It responds to sulphonamides; the tetracyclines, erythroIqy"cin and triace41l oleandOmYcin - and experimentally to the s,ynthesized chemotherapeutic anti-viral substance named 17025. Chlorampenicol is less active and penicillin only weakly so. Streptol1\Ycin and carbomrcin in conventional doses have no effect. -82- •

Either sulphonamides (e.g., sulphadiazine or sulphathiazole) given 1.0 gm four times a ~ by mouth after an initial loading dose of 2.0 gm for 10-15 ~s, or'oxytetraqycline, chlortetraqycline or tetraqycline 500 IIIgI11 four times a ~ orally for the same time, can be given. Erythro­ nurcin and triacewl oleandonurcin have been reported as satisfactory in a like dosage. The newer tetraqyclines (demetb,ylchlortetraqycline, metaqycline, clomocycline, doxyqyc1ine) are presumabl¥ effective in appropriately modified dosage but no reports are yet available.

The multilocular buboes should be aspirated before bursting if and when the individual gland groups become fluctuant. The results of treat­ ment are usuall¥ good in earl¥ cases of climatic bubo but a repeated course (using an alternative) is sometimes necessary. The same treatment should be used in late cases, but the results are less good and repeated treatments after a lapse of seven ~s ~ have to be given. Dilatation will be required in cases of rectal stricture and surgery ~ be necessary especiall¥ in cases complicated tv recto-vaginal fistulae, esthiomene, etc.

B. GRANULOMA INGUINALE (Donovanosis) c

Caused by Donovania granulomatis the diagnosiS can be confirmed by the finding of the organism in tissue smears obtained by biopsy using Wright's or Giemsa stains or in tissue sections with silver or other • staining methods. It responds to streptol11.Ycin, the tetracyclines, carbonurcin, erythroll\Y'cin, triacewl oleandoll\Y'cin and chloramphenicol. Sulphonamides have no effect, while that of penicillin is only slight. Antimo~ preparations, previously used, have been entirely replaced by antibiotics.

Streptonurcin by injection has given good results when 4.0 gm is given daily in divided dosage for five da,ys, as have chlortetraqycline, oxy­ tetraqycline or tetraqycline when 500 mgm has been administered orall¥ four times a d~ for 12-15 d~s. Ocqasionall¥ a longer period will be required. ErythrOll\Y'cin ~ be used in the same dosage and the newer tetracyclines in appropriate dosage over the same treatment time are presumably effective.

4. TRICHOMONIASIS

A vaginitis due to T. vaginalis is the commonest cause of a vaginal discharge and frequentl¥ accompanies other venereal conditions. The protozoal organism is also responsible for some cases of non-gonococcal urethritis in the male. ..

• • - 83 -

Treatment is by means of metronidazole ore.J.4r 200 mgm three times .. a day for one week and cures will be obtained in ninety per cent. of females and in even more of males. The vaginal infestation may be followed by vaginal thrush for which nystatin or other fungicidal pessaries may be required. The regular male partner should also be treated if possible and certainly when the female has repeated relapses.

Although there are no reports of any adverse effects of metronida­ zole on the foetus the information to refute the possibility is as yet incomplete and it is recommended that it should not be given in the first trimester when reliance has then to be placed on one of the many types of pessary (Hydrargaphen, acetarsol, etc.) inserted two nightly for two or more weekS, which were previously used as a routine before tbe introduction of metronidazole.

5. NON-GONOCOCCAL URETHRrlIS

The diagnosis of this condition of males is still by exclusion • of N. gonorrhoea and Trichomonas vaginalis. The role of the virus of the psittacosis lymphogranuloma venereum - trachoma group (found in some cases) or of T. strain mycoplasma is not yet suffiCiently established for routine testing to be justifiable or practicable.

In its treatment, except in those cases in which T. vaginalis is found when metronidazole should be used, the tetracyclines give the best results in a dosage of 250 mgm four times a day (see Table). It is important, partiCularly in areas in which resistance of the gonococcus to tetracyclines is developing, that gonorrhoea be first excluded by urethral smear with or without culture as this dosage may well prove insufficient to cure gonorrhoea, although it may temporarily suppress it.

6. SUMMARY

Treatment of Chancroid, L~hogranuloma Venereum (Nicolas-Favre), Granuloma Inguinale (Donovanosis , Trichomoniasis and Non-gonococcal urethritis is reviewed in the present paper. Suggestions are made for therapy of these sexually transmitted diseases. - 84 • ..

BIBLIOORAPHY

King, A. and Nicol, C.S. (1964) "Venereal Diseases", Cassell, London

Willcox, R.R. (1956) "1"farit1me Venereal Diseases Control", WHO Regional Office for Europe pp. 54-77 Willcox, R.R. (1964) "Textbook of Venereal Diseases and Treponematoses", second edition, Heinemann, London and C.C. Thomas, Springfield, Illinois, U.S.A.

"

•

• .. - 85 -

!l!ABlB: BESUIJl'S OF ~ OF HON-GO~ tmE'.l'lIBI'1'IS . . UsOO24 DlFFERE1'I1' TREADfENT METHOm

o· I Usual 1 ~ , Ih'lI8 dosage i Treated Followed Retreated retreated. i (gill) j 6 ! T~cycJ.ine & oleand~c1n 106 I 82 12 14.6 Oxytetracycline I 82 I 5-6 85 13 15·9 Limecycllne 4·9 ! 101 I 65 11 16.9 I TetracycJ.1ne hydrocbloride 6 I 124 108 20 18·5 . Chl~etracycllne 5-6 I 115 106 2) 18.5 :S~in 10-2) 134 I, 123 25 20·3 1 TriacetyloleandOllG'Cin 6 100 85 19 22.4 Istreptomycin + sulphonamides I 1.0+ 150 I! 113 31 27.4 ! 8-12 i f Erythromycin 6 207 177 49 21·7 I Te1;racycJ.ine pbosphate* 4 150 130 36 27.7 I A.B.o.B. 2.4 t 58 I 54 20 37.0 I Sulphonam1des I i 8-28 I 215 195 73 37.4 • I Penicill1n 1-3.6; mega-! 70 65 26 40.0 units' Chloramphenicol 5-6 0/ 39 37 16 Ito. 5 . I Spect1nomycin + 1.6 +! 4-2 34 15 4-4.1 1 sulphOllBDl1des 10 ! Streptomycin + I, 1-4. j 164- 141 65 46.1 Metronidazole , I 70 58 28 48.3 Am1nitrozol.e , \ 49 22 , 1:~2.1 1 45 48.9 ISpect1nomyc1n 1.6 30 26 . 14 I 53·8 I ICompound 11025 ! 2 13 13 7 53.8 ; I Novobiocin •, 6-12 40 36 I 20 55·6 . Nalidixic ·ac1d 28 10 • 8 , 62.5 I ! Amp1c1ll1n ! I I I 6 12 I 12 , 8 66·7 ,I I Placebo I - , 29 22 I 15 68.2 ,I I I I I I I, ' Totals I I - 12113 11819 569 31·3 i , i ~1th and without 4 mgm. ometh;.vl prednisolone . +With and without phenyl butazone - 86 - .. ANNEX VIII

MINISTRY OF HEALTH QUARTERLY RErURN CODES FOR DIAGNOSIS

~- A (i) Syphilis, primary. C (i) Chancroid. A (ii) ~hilis, secondary. C (ii) ~mphogranuloma venereum. A (iii) Syphilis, latent in 1st year (Syn. ~mphogranuloma :ingu:inale). ot: infection. C (iii) Granuloma inguinale. A (iv) Syphilis, cardiovascular. (Syn. Granuloma venereum). A (v) Syphilis, ot: the nervous C (iv) Non-gonococcal uret~iti8 system. (males only). A (vi) Syphilis, all other late or C (v) Non-gonococcal urethritis with latent stages. arthritis (males only). A (vii) Syphilis ~ congenital (under C (vi) Trichomonal :infestations. 1 year. C (vii) Late or latent treponematoses A (viii) SyphiliS~ congenital (over presumed to be non-syphilitic. 1 year • C (viii) Other conditions requiring treatment with:in the centre. C (ix) Conditions requiring no B (i) Gonorrhoea, Post-pubertal treatment with:in the centre. infections. C (x) Undiagnosed conditions. B (ii) Gonorrhoea, Vulvo-vag:initis. .. B (iii) Gonorrhoea, Ophthalmia neonatorum. ------(COUNTER FOIL KEPT IN (FORM GIVEN TO PATIENT TO GIVE J CLINIC) TO CONTACT)

DATE ______PLEASE MAKE SURE YOU BRING THIS FCRM "11TH YOU WHEN YOU ATTEND REF.NO. ______HOSPITAL OF ORIGIN:

DIAGNOSIS ______ST. MARY'S HOSPITAL, PADDINGTON, W.2 Dr. ______RESULT ______and Dr. ______

MALES & MONDAYS TO FRIDAYS SATURDAYS FEMALES) 10 A.M. TO 7 P.M. 10 A.M. TO 1 P.M. NO APPOINTMENT REQUIRED REF. NO DIAGNOSIS .. . _----- (MINISTRY OF HEALTH CODE) DATE ______------(BACK OF CONTACT SLIP REl'URNED TO ISSUING HOSPITAL IF CONTACT IS SEEN ELSE.WHERE) PLEASE RETURN TO ISSUING HOSPITAL

HOSPITAL, - "87- .

.ANNEX IX

MECHANISM OF BUILD-UP RESISTANCE OF GONOCOCCW TO AN'l'IBIOl'ICS IN THE WESTERN PACIFIC REXlION

A scheme was presented to the Sem:inar* (see Fig. IV) which takes into account a number of observations relating to the resistance of the gonococcus to antibiotics in parts of the Western Pacific Region, where it is generalll" agreed that the bulk of infections is contracted from prostitutes66, 67.

Facts to be taken into account

High failure rates to treatment are being reported follo~large doses of penicillin amongst the extra-territorial Armed ForcesS7, 77. A high proportion of less sensitive strains of gonococci to penicillin and other antibiotic! hav~ ~ ~~ted amongst mixed and problem strains from prostitutes and others 5, 2, , • Transf~r gf. resistant organiSms affecting the Armed Forces trom one area to the otherL, 7 has been alleged.

In the home populations, on the other hand, evidence regarding severe resistance is harder to obtainS7• Resistance is less marked in vitro in unselected than in selected strains?!, although relativeJ¥ fewhave been examined67• Although llI8DY civilian doctors are apparentJ¥ satisfied with the results obtained with penicillin treatment high failure rates are obtained in quite a number of instances. These rates can be explained by the inadequate doses used57• For example, a 50-70 per cent. failure rate was reported in one Japanese clinic visited, where 600 000 units of procaine penicillin was being given dai~ for 5 dqys. Amongst the National Armed Forces of one countr,y where 300 000 units of procaine penicillin was administered da~ for one week57 high· failure' ratesYere also observed. There is le~s talk of ~S~ resistant organisms being carried tree. ODe area to 'another by tourists 7.

Prostitutes serving extra-territorial Armed Forces

It is postulated that there are two overlapping prostitute populations (see Figure IV). The smaller one consists large~ of known prostitutes working mainl¥ in bars and clubs and serving the extra-territorial forces. The second and higher prostitutes group consists mainJ¥ of unknown clandestine prostitutes catering for the ver,y nmch larger home population. There is a degree of overlap between the two groups, SOIlle girls working at times in either capaciq •

. ~ and large, the group serving the Armed Forces consists of known pros­ titutes being first traced as a result of conta!;;t-tracing and then subsequentl¥ subjected tore~ medical examinatiOlls5, 5, B, 12. These examinations, owing to absence

*~ Dr. R.R. W1llcox. - ee - frequent~ inadequate67 • Doses of penicillin given to the girls are often not commensurate with those required for the male partner, and epidemio­ logical treatment is by no ~ans alw~s employed if the unsatisfactor,y tests should prove to be negative6 • Some prostitutes are given regular propb;ylac­ tic treatment2, 12, 15, 67 often with inadequate doses or with repositor,y penicillins producing low serum levels.

This prostitute group, because of demand, can command higher p~ than those serving the home population and, because of this and because they are subject to regular medical examinations, often with the prospect of en.. forced admission to hospital if found to be infected6?, there is a higher incentive to conceal venereal disease. Many therefore seek regular treat­ ment from private practitioners (without tests) and there is much self­ treatment with antibiotics, and in some areas also with vaginal tab1ets67• ConsequentlY these women become living culture media for the selection and breeding of the more resistant organisms72 • Their male contacts have repeated exposures and ver,y high attack rates. Self-treatment with antibiotics ~ be indulged in before or after exposure. Infection qy resistant organisms bred in the women is common and failure rates to treatment are high6?, 77. "Feedback" of the resistant organisms to the promiscuous female pool is considerable from further exposures qy these males when incubating the disease and qy those not cured by treatment68 • Such feedback is intensified when the failure rates are high68 and the resist­ ant organisms are thus nurtured, perpetuated and circulated. Some such strains undoubte~ will be introduced into the prostitute populations of oth~r areas when the troops go elsewhere for rest and recreation (R and R areas)6 • Prostitutes serving the home population This is the larger group consisting mainly of unknown clandestine pros­ titutes but there is overlap with the smaller group as there is some mobili~ between the two. Moreover, there is some cross-transfer of organisms between the two groups qy the national consorts, pimps and ponces of the girls concerned. However, the resistant organisms become somewhat diluted owing to the difference in size of the two prostitute populations.

In most areas the bulk of gonococcal infections in male civilians is treated qy private practitianers, who perform little contact-tracing 51, 67 and hence the girls remain large~ unknown. The girls of this group are like~ to receive less p~ than the smaller group with, of course, some exceptions, as the home population will have found means of avoiding the inflated prices charged to visitors. Also as these girls are not regularly medic~ examined and threatened with compulsor,y admission to hospital, they have less incentive to conceal disease when present. Consequent~ they receive fewer subcurative doses of antibiotics and~ although their gonorrhoea rate ~ be higher than that of the first groups , there is like~ to be less resistance in the organisms they carr,y.

• - 89 -

M the secom group serves the much larger home popul.ation, where III8llY ... of the men are living with their wives, the home population consequent~ has a considerab1y 10wer ind.ividua1 exposure rate with prostitutes. A more marked "step-down" of resistance, or only a s10w bui1d-up therefore occurs, as the resistant organisms are further considerably diluted into the genera1 popu1ation. M a resu1t there are 10wer fai1ure rates to treatment and 1ess II feedbacktl •

Some gonorrhoea is exported by seamen and tourists and this will arise from both groups of prostitutes but particu1ar~ from the aver1apping sector (highly paid c1andestine prostit~e~ who remain unknown because of scanty internationa1 contact-tracing ,7) Hence, highly resistant organisms are apparent~ 1ess camno~ found. in these persons on their return home or at the next port of' ca11 than are encountered in the extra­ territoria1 forces.

The 10gica1 p1ace of attack to attempt to combat the situation of mounting gonococca1 resistance to antibiotics in the Western Pacific Region wou14 be at the point of' bu11d-up between the prostitutes and extra- territoria1 forces. The Seminar proposed that a p110t study shou1d be undertaken to this end (see 5.6.4(a)) .

• - 90 -

.ANNEX X

SOME INTERNATIONAL ASPECTS OF VENEREAL DISEASE AND TREPONEMATOSES CONTROL

T. Guthe and O. Ids~e

1. DEVELOP~IENTS AND POLICIES

The First World Health Assemb~ in 1948 decided that, in the programme against venereal infections, priori~ should be given to the control of earl,y syphilis, with gonorrhoea, chancroid, ~mphogranuloma venerewn, and granuloma inguinale considered in their order of relative importance. With the introduction of highl,y effective penicillin and other antibiotic theraPf in syphilis and gonorrhoea, there was at the time a hopeful outlook for control of syphilis and gonorrhoea through case-finding, treatment, and epidemiological efforts - national~ and internationally. Within the frame­ work of the statutor,y obligations of WHO to promote improved health, this was seen to be best achieved inter alia through advisor,y services, assistance in establishing training facilities, fellowships, etc., to be provided to governments, and through serological standardization, evaluation of anti­ biotic treatment, co-ordination of research and maintaining constructive relations with non-governmental international organizations active in the venereal disease field (WHO, 1948). This programme was extended qy the Second World Health Assemb~ to include non-venereal endemic treponematoses of childhood (yaws, pinta and "endemic" syphilis). In view of the micro­ biological, immunological and other relationships of the treponema! diseases and their similar response to antibiotic treatment, and considering their world distribution and social and economic significance in developing and developed countries (WHO, 1950), it appeared logical to consider an epidemio­ logical outlook on treponematoses as a whole and not on~ to focus attention on the medical aspects of one treponema1 disease. The WHO progranme has been - and continue to be - guided qy the advice of relevant expert committees and subcommittees and draws on information from special stuqy groups, s,ymposia, regional seminars, etc. The functions of WHO in the venereal disease (and treponematoses) field should be seen against this background.

2. STANDARDlZATION OF METHODS, TECHNIQUES AND REAGEmS

(i) It was early recognized that the lack of an international, agreed terminology on lesions and stages of yaws seriously hampered the inter­ national yaws-control activities which soon were undertaken on an increasing scale. Both epidemio1og:lcal work and reporting suffered from the innumerable syno~ of s,ymptoms and lesions which were - 9l -

iDdiscriminate~ used. This problem was countered by the appearance • of an international nomenclature of yaws lesions, recommended at the Second International Conference on Yaws in EnUSU, Nigeria, in 1957 (Hackett, 1957). In syphiliS, gonorrhoea and the other venereal diSeases WHO has consistetrl;~ encour~ed the application at terms and classification of symptoms and lesions in accordance with modern views on etiology and immunological stages of the d1s.ease. These aspects are reflected in part, but not entire~, in the Revised International ClaSsification of Diseases (WHO, 1967).

(11) It had early been shown that, when using the same dosage of penicillin 'there were great differences in the duration of levels of peniCillin in the blood and tissues resulting from the injection of penicillin preparations of different origin and of different types. It was strongly emphasized by the Expert CODIIlittee on Venereal Diseases and Treponematoses in 1952 that long-acting penicillin rep­ resented the drug of choice for use in venereal disease and trepone­ matoses programmes, notably procaine benzylpenicillin in oil with aluminium mono stearate (PAM), and dibenzyletbylened1amine penicillin or benzathine penicillin (DEED). PAM preparations must meet certain i minimum requirements (WHO, 1953) proposed by the said committee in co­ operation with the ~lHO Expert Committees on the International Pharmaco­ poeia (WHO, 19528) and Biological Standardization (WHO, 1952b). Since then such minimum requirements have been improved through the \,ffiO research programme (WHO, 1964J WHO, 1968). An International Reference Preparation of PAM was established in 1962 (WHO, 1963&). A suitable blood-level penicillin duration test 1n rabbits was developed which forms the basis for revised requirements for such preparations and a penicillin assay method with known limits of confidence was also developed (WHO, 1964 ) • Minimum requirements of PAM have since been formulated in a a number of countries.

(iii) International reference preparations of cardiolipin and lecithin were established by the Expert Committee on Biological Standardization in 1951 (WHO, 1952bl WHO, 1960a) and distributed to national laboratories from the International Laboratory for Biological staildards, Copenhagen. They were replaced several times later in accordance with international collaborative serolOgical assays (WHO, 1959). Furthermore, an Inter­ national Standard for reactive Human Syphilitic Serum was established in 1959 {WHO, 1959, Bentzon and Krag, 1958}.

(iv) WHO organized for several years international co-Operative studies of the TPI test between leading laboratories of several countries to ensure the greatest possible uniformity of results. More recently international assays of the Fl'A test were organiz ed. between labora­ tories in the WHO regions. Another WHO-sponsored research project has contributed to simpllf'y1ng Fl'A procedures so that finger-prick blood. dried. on special absorbent paper ("rondelles") can be sent by ordinary mail to a base laboratory in the same or another country for immuno­ fluorescent testing. The method is use:f'uJ. within given limits, parti­ • cularly in children in whom venipunctures would not have been poSsible . - -92 -

(v) The decrease in susceptibility of Nt gonorrhoea to penicillin (and streptoll\Ycin and tetracyclines) observed during recent years in .. SOlll8 areas has suggested that uniform laboratory procedures should be available for determination of drug resistance of circUlating strains in different parts of the world. The vJHO Expert Committee on Gonococ­ cal Infections in its first report thought it was most urgent that such a procedure should first be established in the case of penicillin (WHO, 1965b). For this purpose., the following steps were taken:

(a) Three WHO international reference strains of N. gonorrhoea, available to national laboratories, were established at the Neisseria Department of WHO International Reference' Centre, Copenhagen (WHO, 19615b; WHO 1965). In 1966, 18 laboratories in different countries had received these strains the sensiti­ vity of which to penicillin are re-assessed at mtervals (Reyn, 1968).

(b) A provisional reference method (medium and teclmique) for determination of susceptibility of N. gonorrhoea to penicillm was devised for international use qy the ~flR) Expert Committee on Gonococcal Infections in 1962 ~O, 1965b) and several inter-laboratory assays were organized by WHO.

5. WHO INTENSIFIED RESEARCH PROORAMME L

5.1 Reference centres, collaborating laboratories and research

The following lines have been followed:

(i) Establishment of 1.,1}lO Reference Centres, particularly suitable (a) for standardization of methods, reagents and techniques as referred to above and for related studies, (b) for basic and applied research on venereal infections and treponematoses. Such centres are: The International Treponematoses Laboratory Centre, Johns Hopkins University, Baltimore; WHO Serological Reference Laboratory, State Seruminstitut, Copenhagen; WHO Serological Reference Laboratory, Communicable Disease Centre, Atlanta; vrno International Reference Centre for Gonococci, State Serum Institute, CQpenhagenj Endemic Treponematoses Centre, Institut Fournier, Paris.

(ii) Stimulation and co-ordination of research in existing collabo­ rating institutions and laboratories in several countries. Technical problems are concurrently brought up for investigation within a research programme framework outlined by expert committees, special stuqy groups, etc.

(iii) Undertakmg of epidemiological and methodological studies in WHO-assisted field projects of advisory or research nature m different countries. - 93 -

(iv), Research ent su~to the institutions concerned,. and contracting for certain tec cal services to WHO., , '

It is obvious that the WHO research pZ'oSrammes on 'syph1lis and on endemic treponematoses b&ve feat~s in common due. to their many a1m1lar medical, seroJ.og1cal, epidem1oJ.og1cal and other aspects.

3.2 ExChange of scientific information

( i) The research and related operational and institutional. studies have provided the basis for pUblications of about 200" scientific papers I 10 monographs or special publications and some hundreds of teclm1cal documents, the distribution of which to scientists and health YOrkers in many countrieS bas been undertaken by WHO. Related opinions, ideas and OOlllllents between research workers have subsequently been suggested, advanced or co-ardinated by WHO.

(.11) MeetingS of scientific 'WOrkers and scientific study groups on medical, laboratory, epidetnioJ.ogical, public health and other aspects of venereal infections (and treponematoses) organized by WHO have sti­ mulated and strengthened international co-operation in research work.

(11i) Organization or sP2DSoripg by WHO of spPOsia, seminars and: other international conferences J has promoted VI1l! control by special problems· of medical, laboratory, epidem1oJ.ogical and other nature related to venereal disease control. are discussed.

(lv) Dissemination of information by guides, manuals etc. in venereal disease and tl"eponematoses has been undertaken, taking into account experience acquired in dif'1"erent countr1es and a1m1ng at obtaining 1IlO1'e uniform methods and techniques. '

(v) Committees subeommittees etc. ly aim at periodically advtsing the World Health Organization on technical poJ.icles and particular subjects and also proVide valuable lnf01"'Dl4t1 en on all. aspects of venereal disease; control for health administrations.

4. WHO ASSISTANCE TO GOVERNMENTS (i) Demonstration projects in venereal disease control under- tak~n by governments, in about 40 countries, mostJ,y in developing areas, have been assisted by WHO, with emphasis placed on case­ finding, treatment, epid~ological and laborator,y techniques, health education, etc. Several projects were close~ associated with the maternal and child health progr8llll1les (WHO, 1957). In endemic tre­ ponematoses WHO /llaBS campaigris projects were assisted in 45 cOWltries and areas 1950-1968, in which more than 150 lllillion people were examined and 45 lllillion people treated with long-acting penicillin • .. (ii) Advisory service to governments. WHO long-tem advisors have often been provided at the request for assistance by governments. On the other hand short-term consultants have been increasingly made available for special purposes in recent years, e.g., epidemiological and laborator,y evaluations, project planning, outlining of control activities, etc. (iii) Technical information has been offered as a part of project assistance, but also directly on special request or is included in the distribution of concurrent technical documentation (4.2 above) in the research progr8lllllle.

5. TRAINING AND EDUCATION

(i) From 1948 and onwards some 550 individual fellowships, training grants etc. have been awarded by WHO for the study of clinical, epidemio­ logical, laborator,y and health education aspects of venereal diseases and endemic treponematoses, either at institutions abroad or at field projects undertaken by health administrations. Also some 150 short-term fellowships have been granted for group training or for participation in regional or international meetings on venereal disease and endemic treponematoses control.

(ii) In the training part of the programme medical officers, serologists and technicians (individual or group training) may attend the daily routine work at laboratories acting as WHO reference centres and at field projects; special training courses may be organized or participation in training Courses of multisubject nature on epidemiology laborator,y aspects etc. may be arranged, e.g. the course at the Serum Reference Bank, Institute of Epidemiology and Immunology in 1968, Prague, and in fluorescent technique at the State Serum Institute, Copenhagen, in1966.

6. CO-OPERATION WITH orHER INTERNATIONAL ORGANlZATIONS

(i) The material assistance given by UNICEF since 1948 has been of basic importance for the undertaking of mass-campaigns against endemic trepone­ matoses and venereal diseases recommended by WHO, and counselled by UNICEF/WHO Committee on Health Policy and WHO expert committees. The emphasiS laid by UNICEF on maternal and child health also supported comprehensive assist­ ance in some venereal disease control programmes. (ii) Co-operation with the International Union against Venereal Diseases and Treponematoses (IUVDT) has stimulated venereal disease control activities and programmes in a number of countries. (iii) The International League of Dermatological Societies (ILDS) has been assisted by WHO in the organization of the Eleventh, Twelfth and Thirteenth International Congresses of Dermatology. - 95 -

7. INTERNATIONAL AGREEMENTS

(i) The Brussels Agreement of 1924 relating to venereal infections in seafarers was the first health agreement to provide treatment facilities and medical care on an international basis. In 1946 the WHO Interim Commission assumed responsibili~ for the administration of this agreement and in 1948 the World Health Organization itself assumed that responsiblli~. Since then a tremendous expansion of the world's merchant fleet has taken place. It has increased great4' the social and economic importance of the health of seafarers, both on board and ashore. Following WHO consultations with governments, international organizations, several WHO committees, the Joint WHO/ILO Conunittee on the H;ygiene of Seafarers etc., the Thirteenth World Health Assemb4' in 1960 (WHO, 1960b) approved a set of technical definitions and minimal standards for the functioning of the agreement. A World Director of Venereal Disease Treatment Centres at Ports was published by WHO in 1951, 1959 and 1961, and an International Medical Guide for Ships in 1967. (ii) In 1951 WHO took over the co-ordination of the control measures of the International Rhine River Anti-Venereal Disease Commission until these activities were terminated in 1953, following a marked decline in the incidence of venereal infections among Rhine boatmen.

8. CONCLUSION

The international work of WHO in venereal disease and treponematoses control started in 1948, under hopeful prospects. There was at that time a ver,y high incidence of venereal infections in most countries after the Second World War and an extensive problem of endemic treponematoses of childhood (yaws, pinta, "endemic" syphilis) in countries striving for economic and social development. The means to combat these conditions seemed at hand with the development and widening production of long­ acting penicillins, notab4' PAM (1948) and later DBED (1951). The remark­ able effectiveness of penioillin treatment of syphilis. and gonorrhoea suggested at the time that a revolution in venereal disease programmes might take place and that control was now a matter on4' of improving diagnostic, case-finding and health education methods and strengthening treatment facilities. There were great achievements in these fields during the years that followed, and WHO pJ.a;yed a certain role in stimu­ latfng, encouraging, implementing, co-ordinating, and evaluating relevant national and international efforts and activities. However, events in the last decades have not fulfilled the hopeful outlook of 15-20 years ago. It has become clear that there are shortcomings in application and that venereal diseases cannot be treated out of existence by drugs alone. The avai1abili~ and wide use of effective therapy could not halt the spread of venereal infection favoured by the profound changes in the social and human environment which followed the great economic and tech­ nical expansions of recent years. Venereal disease has indeed proved to - 9b -

be much more of a social problem than a medical and puplic health one, as compared even to a few years ago. The shrinking importance of the medical and public health aspects :in this new situation has already been discussed at this seminar.

International epidemiological problems have emerged as a consequence of the enormous increase in :inter-countr,y and :inter...cont:inental population movements (e.g. migration and tourism) and spread of disease has been greatq facilitated by easy and fast means of t~ansportation. There is obvio~ need for improving and strengthening international co-operation in venereal disease control, particularq contact and case-finding between countries. In this connexion, two particular questions I!Ia¥ be posed a (a) Haw can countries best adjust their health activities to activities required :in such international co-operation? and (b) what role should WHO assume in encouraging and assisting relevant national efforts in developing and developed countries? ThiS seminar ~ wish to consi~r the practical and other aspects of these questions in the Western Pacific Region, questions of capital importance in the improvement of VD control?

fl; REFERENCES . • Beutzou, M. W. & Krag, P. (1958) WHO unpublished worldng. document WHO/J£/439

HacJtett, c. J. (1957) Wl.d Hl.th Org. MonoE' Ser'! No. 36 Reyn, A. (19(58) WHO unpublished worldng document WHo/Vrlr/68.351/WHO/vm/F&.S/ GON/68.22/WHO/ANTIB/68.24 Worl.d Heal.th Organisation (1948) Off. Ree. Wld Hlth Org.! 13

Worl.d Heal.th Organization (1950) Off. Ree. Wl.d Hlth Org., g1,

World Heal.th Organization (1952a) WHO unpublished working document WHO/PHAP.M/ 250 World Heal.th Organisation (1952b) Wl.d Hlth Org. teehn. ReP. Ser., .2£ 1Iorl.d Health OrganiSation (1953) Wl.d Hlth Org. teehn. Rep. Ser., .22. World Health Organization (1957) Wl.d Hlth Org. teehn. Rep. Ser., 115

Worl.d Health Organization (1959) Wl.d Hlth Org. teehn. Rep. Ser., 172

Worl.d Heal.th Organisation (l960a) Wld Hlth Org. teehn. Rep. Ser., 190

World Hea1th Organisation (1960b) Off. Ree. Wl.d Hlth Org., 1Qg

World Health Organization (l963a) Wl.d. Hlth Org. techno Rep. Ser., g,22

Worl.d Health Organization (l963b) Wl.d Hlth Org. techno Rep. Ser., 262

Worl.d Heal.th Organisation (1964) Wl.d Hlth Org. teehn. Rep. Ser., 274

Worl.d Heal.th OrganiJation (l965) WHO unpublished working document WHO/Vrlr/RES/GON/9.65

World Health Organisation (l967) International Cl.ass1fication of 1965 Revision

World Health Organisation (l968) Wl.d Hlth Org. techno Rep. Ser., ~ - 98 -

The purpose of the WHo/VIYr/RES,'WHO/VDr and WHO/Vm'/RES/G~ informa­ tion series of documents is to acquaint interested research and public health workers, as well as WHO staff, with the progress of treponematoses research and control, by means ofl

(1) summaries of some rel~vantproblems on ftmdamental, epidemio­ logical and other aspects;

(2) field project reports and other communications on particular research and control aspects which would not normally be published by WHO or elsewhere; (3) papers that mzq eventually appear in print but, on account of their :iJI1nediate interest or importance, deserve to be made known without dela,y. The mention of manufacturing companies or of their proprietary products does not in;>ly that they are recommended or endorsed by the World Health Orgaru.zation. . ..

t