Yellow Fever Vaccination Simple or the Pasteur Institute of Dakar by nikeborome

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									                                                                       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'
                                      [1026]
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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