Aug., 1947 Yellow Fever Vaccination, Simple or Associated with Vaccination Against Smallpox, of the Populations of French West Africa by the Method of the Pasteur Institute of Dakar MRDICIN-GE1NE1RAL MAURICE PELTER Dakar, French West Africa [HE absence of yellow fever in the neurotropic virus of the mouse, first by French territories of West Africa the procedure of Sellards-Laigret (vac- is now almost entirely the result of cine phosphate in three injections), and mass vaccinations of both the European later by the Laigret process (vaccine. and native population. Since 1941, phosphate mixed with egg yolk). This about 15 million vaccinations were per- mode of vaccination proved its effcacy, formed-a figure which corresponds but the practical difficulties involved almost to the total populations under were an obstacle to its large diffusion. census in those territories. Convinced that only the vaccination A control campaign of such magni- of the native masses could remove the tude has only been possible on account danger of propagation of yellow fever, of the simplicity of the method of pre- the Pasteur Institute of Dakar sought paration and application of the vaccine a simpler method which could be more used. The method was developed at the easily given wide application. Its Pasteur Institute of Dakar by Messrs. M. primary object was to replace sub- Peltier, C. Durieux, HI. Jonchere, and cutaneous inoculation, which requires E. Arquie. The difficulties of war times a considerable number of syringes and rendered impossible any widespread needles rigorously sterilized, with in- publication of these important works, oculation by the simple application of and it seems appropriate now to draw virus to cutaneous scarifications. attention to them. The passage of the pantropic virus The first experiments with this mode to the organism through contact with of vaccination date from 1939 and the the shaven or scarified skin had been papers relating to them have been pub- obtained previously in the Macacus lished in the French scientific rhesus in 1928 by H. Beeuwkes3 and journals.' 2 Vaccination against yellow also by E. Marchoux.4 (ever, however, had been practiced in The Pasteur Institute of Dakar ex- the French territories of Western Africa perimented with the process of pene- since 1934, the vehicle being the tration of the neurotropic virus of the'  Vol. 37 YELLOW FEVER 102 7 mouse through scarification. The first except in some cases a slight feverish experiments were made in November, condition. 1938, on young Macacus rhesus mon- The sero-protection test performed a keys. The virus utilized was the month later showed that immunity neurotropic virus of the French strain against yellow fever had been acquired at the. 238th passage. in 90 per cent of the cases. One drop of a glycerine suspension On the other hand, all the subjects of the powder of the dried virulent that were receptive to the smallpox mouse brain was deposited upon scar- vaccine virus presented vesicles in the ifications made on the abdomen. The same proportion as those observed when virus was detected in the blood of the the same vaccine was used alone, that animals from the 4th to the 8th days. is, in 16 per cent of subjects already No febrile reaction was observed. The vaccinated several times against small- test of sero-protection made 30 days pox and 81 per cent of subjects sup- after the experiment proved strongly posedly never before to have been positive. vaccinated. The antivariolic vaccine The same procedure wis then re- used in this experiment, which was per- peated on man and the results were formed on 741 persons, was prepared identical. For the first six subjects who from a culture made by H. Plotz. were thus inoculated (all volunteers), These first experiments led to the the virus was found in the circulation following definite conclusions: around the 4th, 5th, or 6th day after vaccination. Only one showed a slight 1. The neurotropic yellow fever virus ap- reaction of fever during the 7th day. plied to cutaneous scarifications penetrates into the organism and produces immunity against Subsequent tests in all the series gave yellow fever. positive sero-protection. 2. The association of the neurotropic Thus the idea occurred of associating antiamarillic virus with the antivariolic vac- the yellow fever virus with the Jen- cine makes it possible to obtain protection nerian virus in order to achieve with against both yellow fever and smallpox. 3. The two immunities establish themselves only one operation a combined vacci- simultaneously and independently of each nation against oyellow fever and other in the same manner as they would un- smallpox. der two separate vaccinations. The two vaccine viruses were mixed at the moment of application and sus- However, before making current pended in glycerine. The combined practice of this method of vaccination vaccinations were performed first on in the African bush, the Pasteur the Macacus rhesus and then' on man. Institute of Dakar decided to make On the latter, the operations were per- sure once more that the neurotropic formed in- the beginning under en- virus present in the peripheral circula- vironmental conditions that facilitated tion a few days after vaccination could surveillance, in the Navy at Dakar and not, through passage by the Stegomyia, in the village schools; and subsequently, regain its pantropic properties and attention was gradually directed to sub- bring about outbreaks of yellow fever jects of both sexes and all ages, in- in the neighborhood of the vaccinated cluding more than 50 children from subjects. six months to one year old. A test for Already a certain number of authors sero-protection made before the ex- had observed that the neurotropic virus, periment made it possible to retain only after a great number of mouse passages, those subjects who presented a negative does not pass easily to the mosquito, test. No severe-reaction was observed, and, whenever it happens to pass, there 10.28 1AMERICAN JOURNAL OF PUBLIC HEALTH Aug., 1947 is no evidence that the strain returns Other mixed vaccination campaigns to its original viscerotropic types.-9 embodying scores of thousands of ini- The Pasteur Institute thought it. habitants of the Ivory Coast and the advisable, nevertheless, to pursue the Sudan were carried out in 1940 and experiments to a conclusion by working 1941 under the direction of the Pasteur under optimum conditions, i.e., by Institute of Dakar with the cooperation operating in Dakar during the season of the personnel of the -Assistance which is the most favorable to the Medical Indigene (Office of Medical development of the natural infection of Assistance to the Natives). The results that mosquito-the hot and humid part obtained were as good- as those secured of the-year which is the yellow fever in the first experiments.1-1-2 season in Senegal. The facility and safety of the new The results of this last experiment method having thus been established, were published in March, 1939.10 Even and in view of the numerous dangers under those optimum conditions, it has- confronting the troops stationed in been confirmed beyond any doubt that: French West Africa, the public au- 1. It is almost- impossible for the neuro- thorities decided in the latter part of tropic virus to develop or even to maintain 1941 to make vaccination against yellow itself in the Stegomyia. fever by. the method of the Pasteur 2. When, by any chance, the neurotropic Institute of Dakar compulsory for all virus is so maintained the Stegomyia is un- able to transmit it by biting, even to the most the 'military and civilian populations sensitive of the animals-the Macacus rhesus- of those regions. It was further decided and much less to man. that the yellow fever vaccination should be associated with the vac'cination In view of the above results, vacci- a against smallpox each time the ad- nation campaign comprising 100,000 ministration of the latter was deemed inhabitants of Senegal was- authorized necessary. and undertaken during the months of The Services d'Hygiene et de May, June, and July, 1939. Those Prophylaxie (Bureau of Public Health vaccinations were performed in a re- and Prophylaxis) were already organ- gion where no case of yellow fever had ized to administer Vccinations to all been noticed for a long time, with a the native population within a period view to observing more easily any ac- of 4 years. A 4 year plan of mixed cidents that might occur both among vaccinations was then' started and the vaccinated individuals and their carried almost to completion, in spite neighbors. The vaccines were-very well of all the difficulties inherent in the tolerated. The neighboring population war and post-war periods of 1942-1946. was very carefully observed, and no On January 1, 1946, the total of simple manifestation of yellow fever, not even and mixed vaccinations against yellow the slightest, has been noticed despite fever reached the figure 14,330,735 for the prevalent breeding of the Stegomyia. a total population of about 16 million The results of the vaccination against inhabitants. smallpox were controlled 8 days after Table J gives the details for each performance. The tests for sero-pro- annual operation. tection, carried out only on subjects These results were submitted to the who had had negative tests before the Quarantine Commission of UNRRA by experiment, followed 6 weeks after Surgeon General Peltier. It was agreed vaccination. Among the 1,630 sera thus that an experimental study would be tested, 1,559 were found positive, or made under the auspices of UNRRA in 95.6 per cent. order to ascertain the value of the pro- Vol. 37 YELLOW FEVER 1029 cedure so as to permit the eventual oculated men should continue to lead official recognition of the Dakar method a normal life but would, from the of immunization in the matter of in- military point of view, be kept almost ternational sanitary regulations. at rest for a period of one week, This experiment took place in France particularly on the 4th and 5th days after vaccination. TABLE 1 These prescriptions were followed in Yellow Fever Vaccinations by Scarification regard to the groups B and C, which Civilian Population showed only the usual slight reactions (Total French West Africa and Togo) to such operations, namely, a rise of Population = About 16 Milion Inhabitants temperature and headache, in about 10 Simple per cent to 12 per cent of the cases. Mixed On the other hand, the men con- Vaccine Vaccines Total 1939 2,760 98,873 101,633 stituting Group A, due to some mis- 1940 64,982 232,675 297,657 understanding, were subjected to a 1941 371,097 1,128,868 1,499,965 1942 281,468 2,585,340 2,866,808 severe physical effort which included a 1943 459,339 2,475,883 2,935,222 march on foot of 15 kilometers on hilly 1944 391,066 3,265,510 3,656,576 1945 538,684 2,434,190 2,972,874 terrain and a stop of several hours in Total 2,109,396 12,221,339 14,330,735 the hot sun. This fact presumably was NOTE: The total, taken on December 21, 1945, of responsible for the reactions observed the yellow fever vaccinations performed among the on the 4th and 5th days, which were Military (Navy and Air CorPS included) amounted to 232,357. much more numerous-up to 35 per cent of the subjects. No serious reaction, in July, 1945, in accordance with the however, was registered. protocol drafted by the experts of the As regards the results of the vacci- Quarantine Commission and accepted nation against smallpox (Group B), 36 by the French sanitary and military definite reactions characterized by the authorities. It was performed on 600 development of vesicles, were noted. We men of a division destined for the thus had 16 per cent of positive re- French Expeditionary Corps of the Far sults, which is indeed a very good pro- East. The men chosen had never been portion since all the subjects had out of France nor had they ever been already been vaccinated against small- submitted to any vaccination against pox several times before. The vaccine yellow fever. Their ages varied from used was the dried vaccine of the In- 21 to 30 years. stitut de Vaccine de Paris (Vaccine The subjects were divided into three Institute of Paris). groups, as follows: In order to determine the results of the yellow fever vaccination, blood Group A: To be immunized by scarifica- samples were ta1sen 35 days after in- tion with yellow fever vaccine prepared by the Pasteur Institute of Dakar. oculation. Moreover, blood serum was Group B: To be immunized by scarification obtained also from 30 non-vaccinated with the Dakar yellow fever vaccine mixed jnen of the same regiment who had with the vaccine against smallpox. never been out of France. Group C: To be immunized by hypodermic Each sample of serum was divided inoculation with vaccine 17-D. between three ampoules, of which one All of the said operations were per- was destined for the Pasteur Institute formed in the presence of representatives of Dakar, and the other two for of the UNRRA CommisRn. UNRRA. The laboratories did not The reactions were very carefully know the origins of the sera. observed. It was agreed that the in- Finally, UNRRA announced that on 1030 AMERICAN JOURNAL OF PUBLIC HEALTH A ulg;-, 1947 the subjects who had received the yellow at first, and then with infusorial earth, fever vaccine of Dakar alone, the sero- to which powdered Kaolin is later protection test had been positive in added. To one measured volume of 98.94 per cent of the cases. On the sub- brain powder two volumes of sterile jects thathad received the yellow fever inert powder are added. The mixture vaccine of Dakar and the vaccine thus obtained is again dehydrated under against smallpox at the same time, the vacuum at -25° C. for 24- hours. A sero-protection test was positive in second test for sterility is made. 97.93 per cent of the cases. The powder, verified sterile, is then Consequently, in accord with the divided between ampoules with the aid opinion expressed by the Quarantine of a measuring spoon. Each measuring Commission, the Standing Technical spoon corresponds to 1/10 of a brain Committee on Health of UNRRA un- and represents 100 doses of vaccine, animously decided to acknowledge the each whole brain thus giving 1,000 doses validity of the vaccine of the Pasteur of vaccine. The vaccine titer is the Institute of Dakar from the inter- amount which will kill a mouse with national standpoint. regularity at a dilution corresponding The following are the details of the to one' part fresh virus in one million preparation and .utilization of the parts. vaccine: The ampoules of vaccines, sealed under vacuum, are stored at a temp- 1. Preparation of the Vaccine- erature of -4° C. The potency of the The virus used is of the French strain vaccine' persists for 2 months after which has actually been carried to the leaving the laboratory, provided it is 256th-258th passage in mouse brain. A kept in an icebox. The vaccine may be dried mouse brain preserved in vacuum transported at ordinary temperatures, and cold storage is finely ground up in if for not more than several -days. 5 ml. of physiological salt solution. The resulting suspension is centrifuged and 2. How to Use- the supernatant fluid is inoculated in At the moment of using, the contents doses of 0.03 Xl. into as many' mice as of an ampoule of 100 doses is poured necessary. Only those mice that show into a mortar. There is then 'added, definite paralysis on the 4th and 5th drop by drop, 2 ml. of a gum solution, days after inoculations are sacrificed. stirring continuously with a shaker. The The brains are then removed. Controls gum solution has proved to be far for sterility are made by inoculating superior to glycerine. In fact, the gum culture media under aerobic and is much less fluid and dries rapidly. anaerobic conditions. Each brain is After two to three minutes, a thin film placed in a numbered small glass tube is formed which keeps the virus fixed placed in a refrigerator at -25° C. upon the scarified region. The solution When all the brains have been re- used is of gum arabic harvested in moved and frozen, they are placed in Senegal, saturated, -rigorously neutral- a vacuum chamber with calcium ized, filtered, and sterilized. chloride and put into the refrigerator For the mixed vaccination, the anti- at -25°C. The vacuum chamber is smallpox vaccine virus most generally connected with an oil pump wvhich pro- employed is the dried vaccine prepared duces a vacuum and permits perfect by the Vaccine Institute of Paris. The desiccation after a period of 3 to 4 days. two viruses fre carefully mixed in the The dried brains known to be sterile mortar before the admixture of the are very finely ground in a mortar, alone gum solution. Vol.37 YELLOW FEVER 1031 The percautions to be taken at the scarification. In the majority of the gatherings for vaccination are the same cases the virus had been placed in sus- as those recommended for the practice pension in glycerine and not in gum. of Jennerian vaccination in the tropical It is, therefore, essential that the regions. The vaccination campaigns operations of vaccination be well ought to be carried out, as far as pos- organized and supervised. Actually, this sible, during the least hot seasons, at service is well organized and the re- the first hours of the day and always sults seem to indicate that the large in the shade. majority of the inhabitants of the With the vaccine style, two drops regions in which vaccination has been of vaccinal suspension are deposited on practised are definitely in a state of the deltoid region. Through each drop, immunity against yellow fever virus. two parallel scarifications of 0.5 cm. in An inquiry has just been made con- length are made. Surveillance of the cerning the native populations of two vaccinated persons should be exercised villages of Senegal, one having been for about 5 minutes to make sure that vaccinated four years ago, and the other they do not wipe off the vaccine. When seven years ago. For the first village, the gum has dried entirely, the sur- 85.9 per cent of the 106 sera taken at veillance my cease. random showed a ,positive sero-pro- It is, therefore, evident that the tection test (after four years). For the operation is very simple, requiring a second village, vaccinated seven years minimum of material, and that it can ago, there were 82 per cent positive be carried out in the shortest space of tests among 72 sera taken. time. Finally, this method of scarifica- These results of long duration ob- tion is in general well accepted by the tained in the bush, far from the African population, who, on the other conditions realized in the laboratory, hand, often fear the subcutaneous are excellent and indicate the confidence injections. one may place upon the wide use of the Those are the reasons that assured above mentioned method, carried out the success of the method of the Pasteur with the periodicity of vaccinations Institute of Dakar. French Africa is every four years. beginning to reap the fruits of the ef- fort. The cases of recognized yellow REFERENCES fever have progressively decreased de- Arquie, E. Penetration du C., Jonchere, neurotrope 1. Peltier, M., Durieux, H., and spite the regular investigations made par voie cutanee. Vaccinationvirus amaril la Fievre mixte contre variole. (Note Preliminaire) concerning all febrile affections more or Jaune et laParis. Meeting May 9, 1939,Bull. Acad. de med., Vol. 12, less suspected and the practice of 17:657, 1939. viscerotomy. 2. Peltier, M., Durieux, C., Jonchere, H., and Arquie, E. Vaccination mixte contre la Fievre Jaune Thus there were 17 confirmed cases et le variole sur des ponulations indigenes du Senegal. Acad. de med., Paris. Meeting Dec. 20, 1940 in 1941, 10 in 1942, 12 in 1943, 2 in Bull. 123, 7-8:137, 1940. Vol. 1944, only one doubtful case in 1945, 3. Beeuwkes, H. Conference de la Fievre Jaune, and none at all during the first semester Dakar. 1928. E. Compt. rend. Acad. d. sc., 187: 4. Marchoux, of 1946. Among these cases of yellow 260, 1928. fever, 6 were in individuals who were pathi. Roubaud, E., and Stefanopoulo, G. Bull. Soc. 5. exot., 26:305, 1933. supposed to have been vaccinated by Martin. TheNelson, Lloyd, of NeurotropricFrobisher, 6. Davis, Transmission Wray, and Yellow the Dakar method. Fever virus by Stegomyia Mosquitoes. J. Exper. Med., It is probable that almost all of these 56:853-865, 1932. Durieux, C., and cases have to do with persons hostile to vaccination antiamarile com-orte-t-elle Advier, Ml. dans 7. Mathis, C., des dangers La the vaccination who deliberately wiped et ou les less regions ou le Fievre Jaune renit endemicuement off the vaccines immediately after the 1934. Bull.Stegomyias med., Paris, 112, 35:387, 1934. Acad. de abondent? Meeting Nov. 6, 1032 AMERICAN JOURNAL OF PUBLIC HEALTH Aug., 1947 8. Ibid. (Second note) Meeting Dec. 3, 1935, 114, personnes recemment vaccinees, est-elle possible dans 39:S10, 1935. les regions ou ce moustique existe en abondance? 9. Mathis, M. Sur le pouvoir infectant des Rev. de Immuxol., 2:172-175 (Mar.), 1939. Macacus rhesus -vaccines contre la Fievre Jaune. 11. Peltier, M. Vaccination antiamartle simple ou Bul. Soc. patl. ecxo., 26, 311 (Feb.), 1933. associee a la vacination antivariolique par scarifica 10. Peltier, M., Durieux, C., Jonchere, H., and tion. Med. Tropkiak, 1st year, 1941, No. 5. Arquie, E. La Transmission par piqure de Stregomyia, 12. Durieux, C. Rqpports de PInstitut Pasteur de du virus amaril neurotrope present dans le sang des Dakar, 1941-1942. Chinese Public Health Association Is Established The Chinese Pblic Health Associa- six editions by the American Public tion was organized in May, 1947, dur- Health Association, had been translated ing the Nanking meeting of the Chinese into Chinese. This report has been Medical Association with which the new adopted as an official statement by the group is affiliated, although it- is an National Health Administration of autonomous association of public health China. It was recalled that much of workers in China, including engineers, the text of this report had been prepared nurses, and others outside the medical in agreement with representatives of the profession. P. Z. King, M.D., the Vice medical staff of the British Ministry of Minister for Public Health, was elected Health, that the epidemiologic informa- President, and the Secretary is Yu tion contained in the report had been Huan-wen, M.D., Professor of Public approved for distribution through U.N. Health, National Central Medical Col- R.R.A. channels, that the text had been lege, Nanking. approved in principle by the American It was reported at the meeting of the Red Cross, and by-the Surgeon General, association that the Chinese translation United States Army, and that it is of the report on the Control of Com- official with the U. S. Public Health municable Diseases, published through Service and United States Navy.
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