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
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
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
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
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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
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1032 AMERICAN JOURNAL OF PUBLIC HEALTH Aug., 1947
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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.