A controlled field trial of plain and aluminium hydroxide-adsorbed cholera vaccines in Surabaya, Indonesia, during 1973-75

Bulletin of the World Health Organization, 56 (4): 619-627( 1978) A controlled field trial of plain and aluminium hydroxide-adsorbed cholera vaccines in Surabaya, Indonesia, during 1973-75 J. SULIANTI SARoso,1 W. BAHRAwI,2 H. WITJAKSONO,3 RATNA L. P. BUDIARSO,4 BROTOWASISTO,5 Z. BEN61,6 W. E. DEWIT-,7 & C. Z. GomEZ 8 A controlled field trial comparing the effectiveness of a plain cholera vaccine with that ofa vaccine adsorbed to aluminium hydroxide was carried out in a cholera-endemic area of Indonesia during 1973-75. Tetanus toxoid adsorbed to aluminium phosphate was used as the control. In vaccinees aged 1-4 years, the adsorbed cholera vaccine provided about 88%Y protection for 6 months following vaccination and still provided about 50°0 protection between 11 and 14 months after vaccination. In the same age group, the plain vaccine provided only 53%/ protection during the first 6 months and no appreciable protection beyond that period. In those aged 5 years and over, both vaccines provided 50-60% pro- tection throughout the period of observation (14 months). Neither vaccine caused any serious side effects. Controlled field trials of conventional cholera vac- cines in the past have indicated their effectiveness to be approximately 5O5/o during the first 6 months in all age groups; no appreciable protection could be observed beyond this period. The improvement of cholera vaccines to achieve a higher level of protec- tion over a longer period has therefore been an im- portant subject for research. A mineral-oil adjuvant vaccine tested in the Philip- pines gave longer-lasting protection than the conven- tional vaccines, but caused very serious reactions (sterile abscesses), indicating the impracticability of this type of vaccine (1, 2). The incorporation of a mineral-oil adjuvant in bacterial vaccines has recently 1 Head, National Institute of Health Research and De- velopment, Ministry of Health, Jakarta, Indonesia. ' Director-General, Department ofCommunicable Diseases Control, Ministry of Health, Jakarta, Indonesia. Provincial Health Services, East Java, Indonesia. National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia. ' Department of Communicable Diseases Control, Ministry of Health, Jakarta, Indonesia. ' WHO Consultant, Andrija Stampar School of Public Health, Zagreb, Yugoslavia. ' WHO Consultant, Epidemiologic Services Laboratory Section, Center for Disease Control, Atlanta, GA, USA. ' WHO Consultant, Food and Drug Administration, Department of Health, Manila, Philippines. been questioned by the WHO Scientific Group on Immunological Adjuvants (3) because of various as- sociated risks. Cholera vaccine adsorbed to aluminium hydroxide was studied by Joo et al. (4, 5), and was shown by Feeley & Pittman (6) to have better potency in the active mouse protection test than conventional vac- cines. These latter authors also demonstrated appre- ciable antibody production in young adult volunteers after parenteral injection of the adjuvant vaccine in two doses 2 weeks apart. No serious local or sys- temic side effects were observed. In a study of vari- ous adjuvants, Verwey et al. (7) showed that a single dose of aluminium hydroxide-adsorbed cholera vac- cine produced higher titres of circulating antibodies over a longer period than the conventional vaccine in rabbits and mice, but they were unable to dem- onstrate better protection by the mouse protection test. No side effects were caused by the adjuvant vaccine in mice after a single subcutaneous injection at various dosages, while other types of adjuvant studied by these workers-various minerals and a vegetable oil with various surfactants-caused serious reactions in the same animal model. Joo et al. (8) also demonstrated better immune responses with an Al(OH)3-adsorbed vaccine than with conventional vaccines in rabbits, mice, and monkeys. 3726 - 619 - J. SULIANTI SAROSO ET AL. The present report describes the results of a con- trolled field study on the effectiveness ofan Al(OH),- adsorbed cholera vaccine and its parent conven- tional vaccine. The study was performed in Sura- baya, Indonesia jointly by the Government of Indonesia and the World Health Organization dur- ing the period 1973-1975. POPULATION AND AREA Surabaya municipality The municipality is the capital of the East Java Province and the second largest city in Indonesia, with approximately 1.5 million inhabitants accord- ing to the 1971 national census. Eleven out of 16 subdistricts belonging to the old city and having a population density of 19 000/km2 were selected for the study (Fig. 1). The ethnic groups are mainly Fig. 1. Sketch map of Surabaya Municipality to show the subdistricts (hatched areas) in which vaccination was carried out. HC = health clinic; GGH = Govern- ment General Hospital; NGH = Naval General Hospital. Javanese and Madurese, with a few Chinese and Arabs. The principal religion is Moslem. In the 11 subdistricts, approximately 60%. of the population are of a low socioeconomic status and live in inade- quate environmental conditions. The most prevalent illnesses are respiratory infections, diarrhoea, and skin diseases. Cholera endemicity The available data on bacteriologically proved cholera cases in Surabaya between 1970 and 1972 showed an incidence of 74, 23, and 60 cases per 100 000 population. The incidence of epidemics was highest during the dry season from May to July, and lowest during the rainy season from November to January. A preliminary survey in a selected community be- fore initiation of the trial showed that approximately 15%y of confirmed cholera cases occurred in the 1-4-year age group. The above information indicated that cholera was endemic in Surabaya, and it was expected that more active surveillance and improvement of laboratory examinations would detect and confirm all cases occurring during the follow-up period of the trial. Population movements The population ofSurabaya is generally permanent and seasonal migration is negligible. The inhabitants live mainly in the centre of the municipality and were accessible to the project workers. Facilities Facilities for epidemiological enquiries and statis- tical services were available in the Provincial Health Service Office. Hospitals and some health centres with beds provided adequate facilities for proper treatment of cholera cases (see Fig. 1) A regional public health laboratory staffed by trained bacterio- logists and technicians was available for diagnostic work. PRINCIPLES OF THE STUDY Ethical principles A community selected by the Government gave its approval for the trial and volunteers were vac- cinated after they had given their informed consent. Treatment of acute diarrhoeal diseases, including suspected cholera, was helped by the availability of adequate supplies and facilities. 620 FIELD TRIAL OF CHOLERA VACCINES Randomization of vaccination Vaccination was carried out according to the prin- ciples of controlled field trials, using the " double- blind" technique. The vaccines were coded with a letter by the manufacturing laboratory, the "Hu- man " Institute, Budapest: G for the plain cholera vaccine, R for the Al(OH),-adsorbed cholera vac- cine, and Y for the control inoculation (adsorbed tetanus toxoid). The tetanus toxoid was of some health benefit because of the high incidence of tetanus in the trial population. MATERIALS AND METHODS Vaccines An Al(OH)3-adsorbed cholera vaccine containing 1.6 mg Al(OH)3 per ml and a conventional cholera vaccine (plain vaccine) were prepared from the same parent batch of bivalent cholera vibrio suspension. Both vaccines contained 16 x 109 vibrio cells per ml. Details of the production techniques and laboratory tests of both cholera vaccines are given in the accompanying paper by Jo6 & Csizer (see pages 615-618 of this issue). Tetanus toxoid adsorbed to aluminium phosphate was used as the control inoculation. Vaccination campaign The campaign was carried out by 360 vaccination teams, each composed of one vaccinator and one recorder. One supervisor was assigned to each group of nine teams and one coordinator to every six super- visors. A single subeutaneous dose of 0.5 ml was given to all volunteers regardless of age. The vaccination was confined to a population of low socioeconomic status in areas with inadequate living conditions where cholera was more prevalent. To achieve the highest possible coverage, vaccination was offered after working hours in house-to-house visits, and also at small gatherings such as those at the houses of community leaders. The campaign was accomplished within 2 weeks, from 7 to 21 May 1973. Side effects Reactions were observed for 72 h after vaccina- tion in sample populations of 1649 and 1659 who received the plain and the AI(OH)3-adsorbed vac- cines, respectively, in Wonokromo subdistrict. Pain, erythema, swelling, and induration at the site of injection were considered local reactions, while head- ache, malaise, and inability to work were taken to indicate a systemic reaction. Follow-up of cases Persons who developed acute diarrhoea were en- couraged to visit the health centres by community leaders as well as by the follow-up teams. Persons with diarrhoea who attended the health centres or were admitted to hospital and from whom Vibrio cholerae was isolated were recorded as having chol- era. Ten days after the completion of the vaccination campaign, a follow-up was initiated to detect cholera cases. Stool specimens were taken from those sus- pected of having cholera by rectal swab using Cary- Blair transport medium. When a positive culture was obtained, an epidemiologist visited the patient's household to search for other possible cases. The follow-up was performed by three epidemiologists and six medical assistants from 1 June 1973 to 31 May 1975. Statistical analysis In order to compare incidence rates and to study the effectiveness of the cholera vaccines, z tests com- paring the differences between proportions, chi- square tests, and analysis of variance, assuming a Poisson distribution and employing a V7x;+1/2 and Arcsin transformation for percentage, were applied. The z tests and chi-square tests were used for study- ing reactions to the two cholera vaccines. RESULTS Population vaccinated A total of 470 000 people were vaccinated. As shown in Table 1, the numbers vaccinated with the plain cholera vaccine, the Al(OH)3-adsorbed chol- era vaccine, and tetanus toxoid were 156 300, 155 600, and 158 500, respectively. The populations in the three groups were found to be comparable with regard to age and sex. Effectiveness of the cholera vaccines Throughout the 2 years of follow-up, the pre- dominant cholera vibrio was V. cholerae, biotype eltor, serotype Inaba. The confirmed cholera cases and attack rates at 6-month intervals after vaccina- tion are shown in Table 2. While the average attack rate per 100 000 population in the control group during the first three 6-month periods was about 23.3, that of the last 6 months showed a significant falling off to 8.2, which makes it difficult to draw any conclusions as to the effectiveness of the two cholera vaccines during that period. During the 11th 621 622 J. SULTANTI SAROSO ET AL. N _ O- CO O COLD C 0 I-* CM N 0 zX,o~~~ 14o M M0 bO- W 0 N _ _ T- o0.5~~~~~~~~~~~ m 0~~~ ~~~ _00 0 CO CO a% CId,Oi C I C COco 0>Q Z O ° CO O CO CO CO C ONsN NN-r t 0O 0 O 0Cm t0 CO m mCO "I CO X~~~~~~~F0no: _ ZD r-zPNCD Z C4 0 0 C CO 0 Co COn -iDO CO N 0 j Co - N N N co 0.0 la oCO 0 o oo CO m O C 0co 0W , 0 : o CD ) o0~~~~~~~~~~~ >e z LO_ _wO <> z COOt . Co O 0CO co 0 CO0 CO C N COO CO CO) '-r ) N0 r CO N C O CO O L 00Z CO COO-C CO -O CO ND Ntc9°1z CO e. ae0 co co CO COcco0CO C CO oN CO w ~ ~ ~ -N ~ ' > CO CO CO Cmusa O CO Co co 0 C ~ 6 CON0 -0F1 'I 0 C CN CO CoCOCo 10MNCO CO CO CO CO CO U) ' - COCo o ae N X Co0 C - W CO CO v- r - _ O 0 6 uo coi o5 aaZ c ad coZ P4 uzi 'i _ 4_ CO C ._~~~~~~~~~~~~C CO CO CO N Ns 0 N N CD TDNO_ O On Cco CO _ CO CO C - co C-O CO o o E0 n -a- N tN 0u- uo N N o o O <>6 COO CO COc ou-t CO COcc CO CO CO N O C NO o 0) CO C CO COr 0 -N - _ O v- v- CO4 0 z~~~~~~~~~~~~ C> o co CO COM COt CO COM - co N CO 0 CO ~~~~~cOco M SO)C0O CO CO CO CO Nl Nl r- '-(D~~~~~ ~~~~~~~~~~~~~~~~~~~~CE CO NCO O N C O C O C CO4 N 0 0 0L 6WOCO C CO COCO CO CO CO COO ' CO CO Nv- CON 0 CO N N NCOo COO 01 o co2. o Z o- o~~r- v-W CO -o N ~~~~~~~~~~~~~~~~~0 N~UNl CO CO L O CO CO CO r0 FIELD TRIAL OF CHOLERA VACCINES Table 2. Number of cholera cases and attack rates per 100 000 vaccinees at intervals of 6 months Follow-up period after vaccination Vaccine Number 1-6 months 7-12 months 13-18 months 19-24 months vaccinated _______ Cases Attack Cases Attack Cases Attack Cases Attackrate rate rate rate Plain 156 300 18 11.5 19 12.2 17 10.9 12 7.6 Adsorbed 155 600 10 6.4 20 12.9 14 9.0 19 12.2 Tetanus toxoid(control) 158 500 37 23.3 30 18.9 34 21.5 13 8.2 to the 14th month there was a sudden increase in cases, which coincided with the dry season of April- July. The number of confirmed cholera cases detected in the municipality of Surabaya during that period accounted for approximately 60% of the total num- ber of confirmed cases detected during the 2-year follow-up period. After this period of high incidence, the number of cases was insufficient for a reliable evaluation of effectiveness. Thus, in the 2-year fol- low-up period, only the data covering the first 14 months after vaccination can be effectively evaluated. To evaluate the effectiveness of the two cholera vaccines, the number of confirmed cholera cases, the attack rates per 100 000 vaccinated population, and the effectiveness of the vaccines were grouped ac- cording to age and at given intervals after vaccina- tion. The results are shown in Table 3. The Al(OH)B- adsorbed vaccine appeared to be more protective over a longer period of time than the plain vaccine, but within each 6-month period there were too few cases to allow statistically valid conclusions. Over the whole 14-month period in those aged 1-4 years, the difference between the two vaccines was mar- ginally significant, having a probability ranging from 0.02 to 0.1, depending on the statistical tests em- ployed. It is apparent that the protective patterns of both vaccines depend on the age group. In the 1-4-year age group, both vaccines showed sharply declining trends in protection. On the other hand, in those older than 4 years, steady and lasting (approxi- mately 50%/) protection was shown by both vac- cines during the first 14 months. The differences between each of the two vaccines and the control in all age groups were significant during the first 6 months (probability 0.01 for both vaccines) and during months 13-14 (probability 0.02 to 0.05 for the plain vaccine and 0.01 for the Al(OH)s-ad- sorbed vaccine). Thus the data indicate that both cholera vaccines gave a significant level of protection for 1 year after vaccination in all age groups. Side effects The various reactions among those vaccinated with the two cholera vaccines are shown in Table 4. Local reactions were common, approximately 50%. of those vaccinated developing such reactions on the first day. Systemic reactions were less frequent, with about 10°/ of vaccinees reporting headache and malaise. On the first day, there was very little difference in the pattern of reactions between those vaccinated with the plain vaccine and those vaccinated with the adsorbed vaccine. After the first day, local reactions disappeared fairly quickly from the plain vaccine group, but not so quickly from the group given the adsorbed vaccine. The differences in the percentages with local reactions in the two groups were signifi- cant at 48 and at 72 hours. At 72 hours, 20-30% of the adsorbed vaccine group were still experienc- ing local reactions. There was little, if any, difference in the pattern of systemic reactions caused by the two vaccines. The nature of the reactions and the degree of discomfort produced by the vaccines are shown in Table 5. In general, there were few severe reactions with either vaccine, with the possible exception of swelling of the axillary glands after 72 hours. The plain vaccine produced swelling of the axillary glands in 0.5%., while the Al(OH)3-adsorbed vaccine caused the same reaction in 1.5% of those observed and its incidence tended to increase slightly during the observation period. 623 J. SULIANTI SAROSO ET AL. .4 ciCl7ct- Ir 0-) 0) co co 0) co N co _0 1 cn 0 .- C. O 6 i o U 00 _e 0 0 (V CO N _ N t U) oo 't co 0) um N CV) 0 N 0 N~ N1 N a) N rl N U) C'I(V)-o N6 66 cl 6 0) CD)c', 0) co CD '- U) w _- N U) U) 00, X CD oo w0 cv N U) C.) Ct.U) N .) 0 o 0 N coC.) r- co co I? - _ N0U4(V) C. NC.) co PvN co U) N co co C.f) (v) - C1 0 o U) co0 N UC) 0 0 rlv C.I) 0 cv UD 0 N1 U) N- co m0) 0 0 N 0 1- DISCUSSION The results of previous controlled field trials have shown that in the youngest age group (0-4 or 0-9 years of age), the greatest protection following one subcutaneous dose of conventional cholera vaccine occurred in the first 3 months; thereafter the effec- tiveness declined sharply (9-11). Mosley et al. (9) reported that even when two doses were given at an interval of 4 weeks it was not possible to observe protection beyond the first 3 months, although the peak titre during the first 3 months was higher than that elicited by a single dose of the same vaccine. In those older than 4 or 9 years of age, the effectiveness of the vaccines observed during the first 3 months declined relatively slowly during the following months (1, 9-11). The above difference in protective patterns be- tween the very young and the older age groups has been explained by the presence of basic immunity in the older individuals, as shown by seroepidemio- logical studies in a cholera-endemic area (Dacca, Bangladesh), where the rise in vibrocidal antibodies with age was shown to correlate closely with the fall in the cholera case rate with age (9, 12). It has therefore been assumed that older age groups in a cholera-endemic area respond to a single dose of a test vaccine as to a secondary or booster stimulus, because of repeated exposure to cholera antigens through natural infection and/or mass anti-cholera vaccinations, while the younger age group responds to cholera vaccination as to a primary stimulus. It is therefore important that evaluation of the effec- tiveness of cholera vaccines should be based on data from young children rather than older persons, since field trials can only be performed in cholera-endemic areas. On the basis of this consideration, some trials of cholera vaccines have been carried out by vac- cinating only young volunteers (9, 13, 14). The protection of approximately 80% observed with the conventional vaccine in the young age group during the first 3 months of the present trial is intermediate between that observed after one and two doses of conventional vaccine in the same age group in 1966-1967 in Dacca (9); in that trial one and two doses provided approximately 30%. and 91% effectiveness, respectively. It is possible, there- fore, that the conventional vaccine used in the pres- ent trial may have been a little more potent than that used in the Dacca trial. This assumption is supported by the results of the active mouse pro- tection test, which showed that the relative potency 624 , zoB 0N _ 0) 0) U) U) (O 0) 0.i 0)c._ .0 .0 ~0 D) C) c ._ c ._ .5 00 X CD0, X 0 co a, + U) 0 _ U) IT 'IA OC.,( '0, C4) - o X,- % * Z 0 0-c- OG, 6 ( z C) a, 6 m Z ci .LW 0 0'r-* 4 co ~U) 00c (Nc Ct o N N No.C400 co -'- Q a 0 Co C., cor e)o U) 0 E CL cn (D 0) m c .0 cDi U) a) C.) Co U) a) C. a) a) C Co Co a) U) Co C.) Co a)Q) c f._ C) ._ CL v r- 04 N- 0 co(v O,.- Oa, C_oua,~ NU)L a,c = O 0) Co _ ._ oco FIELD TRIAL OF CHOLERA VACCINES Table 4. Percentages of vaccinated volunteers with specific side reactions 1-9 years of age 10 + years of age Reaction vaccine After After After After After After 24 h 48 h 72 h 24 h 48 h 72 h Local Pain Plain 41.8 19.1 7.6 56.8 25.5 12.1 Adsorbed 41.3 30.7 25.6 51.7 40.4 29.1 Erythema Plain 41.0 13.8 4.4 57.8 26.0 8.8 Adsorbed 44.4 30.3 22.8 54.1 40.8 24.9 Swelling Plain 36.9 11.4 5.5 45.6 16.3 6.9 Adsorbed 36.6 24.8 18.0 43.7 29.1 19.2 Induration Plain 32.0 17.1 8.1 27.2 16.7 11.2 Adsorbed 31.1 36.2 33.7 34.7 33.3 28.8 Systemic Headache Plain 8.2 1.7 1.8 11.7 3.8 2.6 Adsorbed 6.1 3.1 1.6 7.2 3.5 1.8 Malaise Plain 4.4 0.8 0.7 7.2 3.1 2.3 Adsorbed 3.6 1.7 1.6 4.5 2.2 2.3 of the vaccine in the Dacca trial was 0.72, com- pared with 1.2 for the vaccine used in the present trial (see p. 000 of this issue). There was no detect- able protection during the second 3 months in either the Dacca trial or the present trial. Although the difference between the conventional vaccine and the Al(OH)3-adsorbed vaccine in the level of protection afforded the young age group was only marginally significant during the first 14 months of observation, the protection shown by the adsorbed vaccine surpassed that of the conventional vaccine at any given interval during that period, which is a strong indication of the superiority of the adsorbed vaccine. It is also certain that the dif- ference is directly attributable to the aluminium hydroxide adjuvant, since both vaccines were pre- pared from the same parent bivalent bulk of vibrio suspension. The protection given by the adsorbed vaccine was compared with that shown by a mineral-oil adjuvant vaccine tested in 1964 in the Philippines. The latter vaccine showed a level of protection of 32% during the first 3 months, 54%/ during the second 3 months, 44%O during the first 6 months, and zero between 7 and 18 months after vaccination. In comparison, levels of effectiveness of 84%, 100%, 84%, and 61%, respectively, were observed during the same periods with the Al(OH)5-adsorbed vaccine, indicating that this vaccine may give longer-lasting protection. The similar degree of protection conferred by the plain and the adsorbed vaccines in those older than 4 years of age can probably be explained by the booster effect of vaccination in this age group, as discussed above. Although no seroepidemiological study was carried out in the present trial, the very high incidence of cholera in the young age group compared with the older age group among those given tetanus toxoid (approximately 4.6: 1) indicates that the older age group possessed appreciable anti- cholera immunity before the trial. With regard to side effects, there was no indica- tion that the adsorbed vaccine was less reactogenic than the plain vaccine. As far as systemic reactions are concerned, there were no significant differences between the two vaccines, although the adsorbed vaccine caused a slightly higher number of prolonged local reactions than the plain vaccine. The adsorbed vaccine caused no long-lasting local induration dur- ing an observation period of 72 h following vac- cination, nor did any severe reaction come to our notice during further follow-up. Although aluminium hydroxide and aluminium phosphate have proved safe when used with other antigens such as tetanus toxoid, diphteria toxoid, and DPT, it would be desirable to observe local reactions to the cholera adjuvant vaccines systematically and for a longer period in future trials. 625 J. SULIANTI SAROSO ET AL. Table 5. Nature of reactions in persons vaccinated (all age groups) After 24 h After 48 h After 72 h Reaction Plain Adsorbed Plain Adsorbed Plain Adsorbedvaccine vaccine vaccine vaccine vaccine vaccine No. % No. % No. % No. % No. % No. % Local Pain-total observed 864 829 1378 1360 1299 1265 Minor pain 392 45.4 358 43.2 296 21.5 459 33.8 130 10.0 331 26.1 Could not lie on the arm 44 5.1 32 3.9 17 1.2 39 2.8 4 0.3 17 1.4 Could notsleep 10 1.2 10 1.2 7 0.5 5 0.4 3 0.2 4 0.3 Erythema-total observed 859 825 1379 1359 1301 1263 Less than 10 cm 442 51.4 417 50.5 290 21.0 503 37.0 92 7.0 300 23.7 More than 10 cm 5 0.6 3 0.4 8 0.6 1 0.1 2 0.2 5 0.4 Swelling-total observed 856 829 1374 1348 1294 1256 In erythema area only 331 38.6 318 38.4 169 12.3 323 24.0 70 5.4 196 15.6 Beyond erythema area 25 2.9 14 1.7 21 1.5 35 2.6 5 0.4 19 1.5 Affecting % of limb 3 0.4 7 0.8 4 0.3 6 0.4 2 0.1 2 0.2 Axillary glands 6 0.7 4 0.5 6 0.5 8 0.6 6 0.5 19 1.5 Systemic Headache-total observed 814 779 1324 1298 1252 1203 Slight 78 9.6 44 5.6 33 2.5 34 2.6 35 2.8 16 1.3 Severe 8 1.0 10 1.3 7 0.5 10 0.8 4 0.3 5 0.4 Malaise-total observed 829 799 1368 1349 1290 1262 Not needing to go to bed 39 4.7 24 3.0 21 1.6 14 1.0 10 0.8 10 0.8 Needing togoto bed 10 1.2 6 0.8 6 0.4 7 0.5 10 0.8 11 0.9 Shivering, delirium 3 0.4 4 0.5 4 0.3 6 0.5 2 0.1 5 0.4 Inability to work-total observed 844 798 1341 1318 1252 1211 Unable to work 16 1.9 16 2.0 12 0.9 14 1.1 6 0.5 4 0.3 ACKNOWLEDGEMENTS The authors acknowledge the cooperation of the Health Authorities of Indonesia and Western Java and the assistance received from the World Health Organization in the planning and analysis of the results of this study. RJ2SUMm ESSAI CONTROLE SUR LE TERRAIN DE VACCINS ANTICHOLE'RIQUES A SURABAYA (INDONESIE) DE 1973 A 1975 (VACCIN SIMPLE ET VACCIN ADSORBE PAR L'HYDROXYDE D'ALUMINIUM) Un essai contr6le sur le terrain aux fins de comparer effectu6 dans une region d'endemie cholerique en Indo- l'efficacite d'un vaccin anticholerique simple et d'un nesie en 1973-1975. Une anatoxine tetanique adsorb6e vaccin adsorbe par l'hydroxyde d'aluminium a ete par le phosphate d'aluminium a ete employee aux fins de 626 FIELD TRIAL OF CHOLERA VACCINES 627 contr6le. Le vaccin anticholerique adsorbe a assure la protection a 88% des enfants de 1 a 4 ans pendant 6 mois apres la vaccination, proportion qui est tomb6e a 50% au cours de la pdriode posterieure de 11 a 14 mois a la vaccination. Dans le meme groupe d'age, le vaccin simple n'a procure qu'une protection a 53% pendant les 6 premiers mois, et celle-ci est devenue presque nulle au-dela de cette p6riode. 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