4KIO4 Rosemary Street
Chevy Chase, Maryland 20015
April 6, 1°70

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Dr. Joshua Lederberg
Department of Genetics
School of Medicine
Stanford University

Stanford, California 94405
Dear Dr. Lederberg:

There has been some delay in the receipt of your xeroxed copies
mailed at Palo ‘lto on March 24th. I retired from the Pan American Sanitary
Bureau eleven years ago. I can best be reached at my home address, as
@iven above.

In regard to 'Yellow Fever Still Survives in Jungies of Africa, Brazil,”
I have the following comments.

Paragraph 2: Walter Reed did not himself participate as a subject
in the yellow fever experiments in Havana in 1900-1901.

Paragraph 4: Yellow fever is a harmless disease of monkeys in Africa
and of the Cebus monkeys in the Americas. The infection is much more vide~
spread in Africa than you have suggested, occurring from Senegal to Ethiopia
South of the Sahara. In the Americas, jungle yellow fever has occurred
since 1947 on the island of Trinidad and in all of the countries on the
mainland of the Americas excepting Canada, the United States, El Salvador,
Uruguay, and Chile. The aegypti mosquito does not flourish under modern
conditions in the northern ports of our Atlantic Toast. In previous times
when so many sailing ships came up from the Caribbean, the aegypti mosquito
was often brought at the beginning of summer into American ports which had
numerous water barrels on the docks for fire control. These vermitted the
mosquito to establish itself and spread about while waiting for a later shiv
to bring in active cases to start a summer and fall outbreak.

Paragraph 6: The decision to attempt the eradication of Aedes aegypti
was only secondarily related to the Rio outbreak of 1928-1929, The finding
of a silent rural aegypti-transmitted yellow fever in 1930-1931 and the dis-
covery of jungle yellow fever in 1932 were largely responsible for the exploita-
tion of the possibility of aegypti eradication, which was first observed in
some of the cities of Northeast Brazil in 1932-19%%, The original eradica-
tion efforts were in Brazil and Bolivia. Experience in Brazil showed that
the complete elimination of the aegypti mosquito was in the long run much more
economical than even a halfhearted attempt to maintain a service for the pro-
tection of the larger cities from yellow fever. In 1941 Bolivia declared the
eradication of aegyvti in its territory and in 192 presented a resolution at
the Eleventh Pan American Sanitary Conference urging the other countries of
the Americas to organize eradication programs. Both urban and jungle yellow
fever had been found in Bolivia in 1932-1933, Also, it should be noted that
beginning in 1934 jungle yellow fever moved from the Amazon Valley to the
watershed of the Paraguay-Parana Rivers, and during the next seven years svept
through the forested areas of all of the states of Southern Brazil, of Fara-
guay, and of Northeastern Argentina.
MN

Dr. Joshua Lederberg April 6, 1°70

During World War II there was no serious extension of the eradication
effort to other countries, but great progress “as made in the eradication of
aegypti in a number of Brazilian states. In 1944 jungle yellow fever started
another sweep from the Amazon Valley into the southern states and into north-
ern Argentina in many of the areas which had suffered on the previous excur-
sions ten years earlier.

In 1947 Brazil presented a resolution at the annual meeting of the
Pan American Health Organization in Buenos Aires. This resolution committed
the Pan American Sanitary Bureau to the coordination of efforts for the ver-
manent solution of the problem of “yellow fever through the eradication of
the aegypti mosauito, such coordination to consist of aid in the solution
of such legal, technical, and financial problems as might arise. There were
no dissenting voices to this proposal, and tne corresponding document was
signed by Dr. Thomas Parran, the official delegate of the United States at
the meeting.

By the early 1960s practically all of the nations and territories of
the Western Hemisphere, with the exception of the United States, had organized
serious efforts for the eradication of the yellow fever and dengue mosquito,
Aedes aegypti. Eradication was successfully completed and certified after
rather extensive and independent checking of the situation by the Pan American
Health Organization for the following countries: Argentina, Uruguay, Paraguay,
Brazil, Bolivia, Chile, Peru, Ecuador, Guyana, and French Guiana in South
America, and Panama, Costa Rica, El Salvador, Honduras, Nicaragua, Guatemala,
British Honduras, and Mexico in Middle America,

In addition to these certified countries, Colombia was cleared, excent
for a small area adjacent to Venezuela, and the island of Trinidad, both of
which areas have suffered repeated reinfestations.

Since 1958 when the first series of eradication certifications were
made, the governing bodies of the Pan American Health Organization have con-
sistently year after year voted resolutions urging the remaining countries
to complete the eradication of aegypti, not only for their own protection
but also to protect the quite considerable investment already made in the
eradication effort. The United States participated in all of these meetings,
never once taking exception to the proposed measures. The records show year
after year unanimous accevtance of the provosed resolutions.

In 1961 a severe attack was made by Mexico on the failure of the
United States to eradicate Aedes aepypti during the discussion at the annual
meeting of the Pan American Health Organization. In 1962 the Mexican Govern-
ment put the eradication of Aedes aegypti on the agenda for the meeting of
the President of Mexico with President Kennedy.

In 1°57 the wave of jungle yellow fever, which had been moving up
through Panama and Central America since 1948, crossed the border between
Guatemala and Mexico. Mexico then had eradicated the Aedes aegypti mosauito
in its territory but realized that its land frontier and small boat inter-
change with the United States would make it very difficult to maintain free-
dom of aegypti unless the United States lived un to the obligation established
Dr. Joshua Lederberg April 6, 1970

through the united action of all of the nations of the Americas since 1°47.

The Mexican initiatives in 1961-1962 led to a policy discussion at a very

high level in the United States Government. As a result, the Surgeon General

was authorized to commit the United States to the eradication of Aedes
aegypti in the southern states, in Puerto Rico, and in the Virgin Islands

at the meeting of the Pan American Sanitary Conference in Minneapolis in

August 1962.

Some years ago El Salvador was found to be reinfested after some

seven or eight years of freedom from Aedes aegypti. The investigation made
by the representative of the Pan American Health Organization suggested very
strongly that the reinfestation had probably come through the importation of

used automobile tires from the United States. The Government of El Salvador
made a request to the United States for assistance in undertaking anew the
eradication of aegypti. Nothing came of this initiative and the infestation
is reported to have spread to Honduras and Guatemala. In the meantime, in
1967, the northern part of Brazil was reinfested, most probably by small
coastal boats running contraband from the Caribbean to the mouth of the Amazon.

In 1963 the Congress of the United States made $4,000,000 available
for the initial organization of the aegypti eradication program; this money
became available in October of that year. In the following years budgets
were increased with the result that by 1°69 some *56,000,000 had been appro-
priated for this effort. Detailed statistical reports of the work done have
never been published. The’ reports to the Pan American Health Organization
have consisted of simple revorts by years and counties as to the presence of
aegypti and as to whether or not work was being carried out in individual
counties,

The United States Government did request a survey of the situation by
the Pan American Health Organization a couple of years ago. An evaluation
was made by a three-man group of exverienced Latin American mosquito workers,
but the report of this group has never been published.

In anticipation of eventually facing up to the eradication of Aedes
aegypti, the Surgeon General of the Public Health Service authorized in 1957
a pilot eradication project in Pensacola. This pilot project covered, I
believe, a four-year period. And apparently the technique. later used in
the United States program was that developed in Pensacola. By abandoning
its eradication effort, the United States has placed in jeovardy the first
regional eradication effort in which the nations of the Americas undertook
a permanent solution of a continental problem. The fact that the United
States has not had yellow fever for many years is quite beside the voint.

In vractically every problem, the solution of which would reouire the joint
effort of many nations, there are almost certainly some to whom the problem
at issue is of less concern than to others. An eradication effort must be
worked on at least a regional basis. The threat of the United States to the
other countries of the continent is one of reinfestation.

We can glory today in the fact that during the vast twenty-five years
there has been only one vort infected with yellow fever virus; this occurred
at Port-of-Spain, Trinidad, in 1954, The resultant cuarantine reputedly cut
the income of this island by %2%,000,000 to $28,000,000.
Dr. Joshua Lederberg April 6, 1°70

So long as the cities adjacent to jungle yellow fever areas are free
of aegypti the threat of yellow fever to the United States is admittedly verv
low. Should the reinfestation of Brazil hadbeem permitted to spread through-
out that enormous country, it would be most difficult to recreate the conditions
which permitted the initiation of the eradication of aegypti there in the 1°%0s.
(As a matter of statistical interest, the Brazilian campaign from 1941 up to
the certification of eradication in 1958 gives the number of house visits made
to achieve eradication at 617,000,000. Today with a greatly increased vomla-
tion and the exaggerated movement of population to cities and towns, the effort
would have to be considerably greater.)

After the above diversion, I would turn for a moment to your sixth
paragraph. Your comment that yellow fever is still reported to the extent
of a dozen cases a year is quite misleading. Jungle yellow fever strikes the
individual who goes into forests; it oftentimes strikes the settler at the
periphery of the settlement. As you know, yellow fever is a disease which
strikes hard in the beginning and in many cases leaves little opportunity of
getting to town for medical care. Jungle yellow fever is a veripheral dis-
ease that occurs all too often in a forgotten segment of the population.
Furthermore, yellow fever is one disease which is seldom revorted in the
Americas in the absence of microscopic examination of liver tissue or from
the isolation of virus in animals. To have a due apvreciation of what is
hapnening to the exposed population, it is necessary to examine the cumula-
tive distribution of yellow fever over a five or ten-year period with mav
pins of various colors for individual years.

Hscaping to your ninth varagraph, I would point out that the aim of
total eradication is not too ambitious. The cost and difficulty of maintain-
ing an effective aegypti control program over a period of years is so great
that one cannot today recommend it for the degree of risk the United States
is running. Once eradication has been accomplished, the prevention of rein-
festation depends on peripheral expansion of the eradicated ares.

I have mentioned above how all of South America excepting the northern
fringe of the continent was cleared of Aedes aegypti. I for one would not
recommend a partial program in the United States at the present time, excent
possibly an island-wide program for Puerto Rico or a program along the Mexico-
United States border, for two purposes: first, to protect Mexico from reinfes-
tations, of which they have registered nine, the last being in October 1969,
and, second, to demonstrate the possibility of aegypti eradication in the
United States. The conditions on one side of the Rio Grande are not too cif-
ferent from those on the other side but that eradication can be undertaken
with assurance on this side of the border.

The occurrence of large-scale dengue epidemics in the Caribbean and
in Venezuela in 196% and 1964 has been followed by a second outbreak in 1969,
It has been shown that there are more than one strain of dengue virus in the
Americas, which has led those familiar with the hemorrhagic fever of Asia to
anticipate the possibility of a similar reaction here at some time in the
future.
Dr. Joshua Lederberg April 6, 1970

You mention in the next paragraph the outbreak of yellow fever in
Senegal in 1965. It has apparently been outdistanced by a flareun of yellow
fever in 1969 in Nigeria, Niger, Dahomey, Upper Volta, and probably other
countries just south of the Sahara.

I have far exceeded the comments I expected to make on the basis of
this article. I shall then not attempt to comment on the second article
referring to CBW facilities. I realize fully that it is difficult for one
in your position to know all the details of the wide variety of subjects
which you cover. I, of course, feel that my comments could have been more
useful if made before the article went to press.

Sincerely yours,

f. . ‘
Bei fhe, ”

Fred L. Soper