Yellow fever presently occurs only in Africa and South America.
Two forms of yellow fever--urban and jungle--are
epidemiologically distinguishable. Clinically and etiologically
they are identical (1,2).
Urban yellow fever is an epidemic viral disease of humans
transmitted from infected to susceptible persons by Aedes aegypti
mosquitoes, which breed in domestic and peridomestic containers
(e.g., water jars, barrels, drums, tires, tin cans) and thus in
close association with humans. In areas where Ae. aegypti has
been eliminated or suppressed, urban yellow fever has
disappeared. In the early 1900s, eradication of Ae. aegypti in a
number of countries, notably Panama, Brazil, Ecuador, Peru,
Bolivia, Paraguay, Uruguay, and Argentina, led to the
disappearance of urban yellow fever. The last documented Ae.
aegypti-borne yellow fever epidemic in the western hemisphere
occurred in Trinidad in 1954. Ae. aegypti is suspected to have
played a role in transmission in outbreaks occurring in Bolivia
in 1989 and 1990, but that role was not proven. However, periodic
reinfestations of some countries have occurred in recent years
(Brazil, Bolivia, Ecuador, Panama). Other countries remain
infested, including areas of Venezuela, Colombia, and the
Guyanas, which include enzootic areas for jungle yellow fever. In
West Africa, Ae. aegypti-transmitted epidemics continue to occur
and involve human populations both in towns and in rural villages
Jungle yellow fever is an enzootic viral disease transmitted
among nonhuman primate hosts by various mosquito vectors. It is
currently observed only in forest-savannah zones of tropical
Africa and in forested areas of South America but occasionally
extends into parts of Central America and the island of Trinidad.
In South America, approximately 100-300 cases are reported
annually, mainly among men with occupational exposures in
forested areas; however, the disease is believed to be greatly
underreported. In Africa, epidemics involving tree-hole-breeding
mosquito vectors affect tens of thousands of persons at intervals
of a few years, but few cases are officially reported. Sometimes
the disease is not detected in an area for years but then will
reappear. Delineation of affected areas depends on surveillance
of animal reservoirs and vectors, accurate diagnosis, and prompt
reporting of all human cases. The jungle yellow fever cycle may
be active but unrecognized in forested areas of countries within
the yellow fever endemic zone (Figure 1).
Urban yellow fever can be prevented by eradicating Ae. aegypti
mosquitoes or by suppressing their numbers to the point that they
no longer perpetuate infection. Jungle yellow fever can most
effectively be prevented by vaccination of human populations at
risk of exposure.
YELLOW FEVER VACCINE
Yellow fever vaccine is a live, attenuated virus preparation
made from the 17D yellow fever virus strain (4). The 17D vaccine
is safe and effective (5). The virus is grown in chick embryos
inoculated with a seed virus of a fixed-passage level. The
vaccine is a freeze-dried supernate of centrifuged embryo
homogenate, packaged in 1-dose and 5-dose vials for domestic use.
Vaccine should be stored at temperatures between 5 C (41 F) and
-30 C (-22 F)--preferably frozen, below 0 C (32 F)--until it is
reconstituted by the addition of diluent sterile, physiologic
saline supplied by the manufacturer. Multiple-dose vials of
reconstituted vaccine should be held at 5 C-10 C (41 F-50 F);
unused vaccine should be discarded within 1 hour after
Persons living or traveling in endemic areas
Persons greater than or equal to 9 months of age traveling
to or living in areas of South America and Africa where yellow
fever infection is officially reported should be vaccinated.
These areas are listed in the "Bi-Weekly Summary of Countries
with Areas Infected with Quarantinable Diseases," available in
state and local health departments. Information on known or
probably infected areas is also available from the World Health
Organization (WHO) and Pan American Health Organization offices
or the Division of Vector-Borne Infectious Diseases, Center for
Infectious Diseases, CDC, Fort Collins, Colorado, telephone (303)
221-6400. Vaccination is also recommended for travel outside the
urban areas of countries that do not officially report the
disease but that lie in the yellow fever endemic zone (shaded
area, Figure 1). The actual areas of yellow fever virus activity
far exceed the infected zones officially reported; in recent
years, fatal cases of yellow fever have occurred among
unvaccinated tourists visiting rural areas within the yellow
fever endemic zone (6).
2. Infants less than 9 months of age and pregnant women should
be considered for vaccination if traveling to areas experiencing
ongoing epidemic yellow fever when travel cannot be postponed and
a high level of prevention against mosquito exposure is not
feasible. However, in no instance should infants less than 4
months of age receive yellow fever vaccine because of the risk of
encephalitis (see Precautions and Contraindications).
3. Laboratory personnel who might be exposed to virulent yellow
fever virus by direct or indirect contact or by aerosols should
also be vaccinated.
B. Vaccination for international travel.
For purposes of international travel, yellow fever vaccines
produced by different manufacturers worldwide must be approved by
WHO and administered at an approved Yellow Fever Vaccination
Center. State and territorial health departments have the
authority to designate nonfederal vaccination centers; these can
be identified by contacting state or local health departments.
Vaccinees should receive an International Certificate of
Vaccination completed, signed, and validated with the center's
stamp where the vaccine is given. Vaccination for international
travel may be required under circumstances other than those
specified herein. Some countries in Africa require evidence of
vaccination from all entering travelers. Some countries may waive
the requirements for travelers coming from noninfected areas and
staying less than 2 weeks. Because requirements may change, all
travelers should seek current information from health
departments. Travel agencies, international airlines, and/or
shipping lines should also have up-to-date information. Some
countries require an individual, even if only in transit, to have
a valid International Certificate of Vaccination if s/he has been
in countries either known or thought to harbor yellow fever
virus. Such requirements may be strictly enforced, particularly
for persons traveling from Africa or South America to Asia.
Travelers should consult Health Information for International
Travel 1989 (7) to determine requirements and regulations for
C. Primary vaccination.
For persons of all ages, a single subcutaneous injection of 0.5
ml of reconstituted vaccine is used.
D. Booster doses.
The International Health Regulations require revaccination at
intervals of 10 years. Revaccination boosts antibody titer;
however, evidence from several studies (8-10) suggests that
yellow fever vaccine immunity persists for at least 30-35 years
and probably for life.
Reactions to 17D yellow fever vaccine are generally mild. After
vaccination, 2%-5% of vaccinees have mild headaches, myalgia,
low-grade fevers, or other minor symptoms for 5-10 days. Fewer
than 0.2% of the vaccinees curtail regular activities. Immediate
hypersensitivity reactions, characterized by rash, urticaria,
and/or asthma, are uncommon (incidence less than 1/1,000,000) and
occur principally among persons with histories of egg allergy.
Although greater than 34 million doses of vaccine have been
distributed, only two cases of encephalitis temporally associated
with vaccinations have been reported in the United States; in one
fatal case, 17D virus was isolated from the brain.
PRECAUTIONS AND CONTRAINDICATIONS
Infants less than 4 months of age are more susceptible to
serious adverse reactions (encephalitis) than older children. The
risk of this complication appears to be age-related; whenever
possible, vaccination should be delayed until age 9 months.
Although specific information is not available concerning
adverse effects of yellow fever vaccine on the developing fetus,
pregnant women theoretically should not be vaccinated, and travel
to areas where yellow fever is present should be postponed until
after delivery. If international travel requirements constitute
the only reason to vaccinate a pregnant woman, rather than an
increased risk of infection, efforts should be made to obtain a
waiver letter from the traveler's physician (see section D.
Hypersensitivity). Pregnant women who must travel to areas where
the risk of yellow fever is high should be vaccinated. Under
these circumstances, for both mother and fetus, the small
theoretical risk from vaccination is far outweighed by the risk
of yellow fever infection.
Altered immune states.
Infection with yellow fever vaccine virus poses a theoretical
risk of encephalitis to patients with immunosuppression in
association with acquired immunodeficiency syndrome (AIDS) or
other manifestations of human immunodeficiency virus (HIV)
infection, leukemia, lymphoma, generalized malignancy, or to
those whose immunologic responses are suppressed by
corticosteroids, alkylating drugs, antimetabolites, or radiation.
Such patients should not be vaccinated. If travel to a yellow
fever-infected zone is necessary, patients should be advised of
the risk, instructed in methods for avoiding vector mosquitoes,
and supplied with vaccination waiver letters by their physicians.
Low-dose (10 mg prednisone or equivalent) or short-term (less
than 2 weeks) corticosteroid therapy or intra-articular, bursal,
or tendon injections with corticosteroids should not be
immunosuppressive and constitute no increased hazard to
recipients of yellow fever vaccine. Persons who have had
previously diagnosed asymptomatic HIV infections and who cannot
avoid potential exposure to yellow fever virus should be offered
the choice of vaccination. Vaccinees should be monitored for
possible adverse effects. Since the vaccination of such persons
may be less effective than that for non-HIV-infected persons,
their neutralizing antibody response to vaccination may be
desired before travel. For such determinations, the appropriate
state health department or CDC ((303) 221-6400) may be contacted.
Family members of immunosuppressed persons, who themselves have
no contraindications, may receive yellow fever vaccine.
Live yellow fever vaccine is produced in chick embryos and
should not be given to persons hypersensitive to eggs; generally,
persons who are able to eat eggs or egg products may receive the
vaccine. If international travel regulations are the only reason
to vaccinate a patient hypersensitive to eggs, efforts should be
made to obtain a waiver. A physician's letter stating the
contraindication to vaccination has been acceptable to some
governments. (Ideally, it should be written on letterhead
stationary and bear the stamp used by health department and
official immunization centers to validate the International
Certificate of Vaccination.) Under these conditions, the traveler
should also obtain specific and authoritative advice from the
embassy or consulate of the country or countries s/he plans to
visit. Waivers of requirements obtained from embassies or
consulates should be documented by appropriate letters and
retained for presentation with the International Health
Certificate. If vaccination of an individual with a questionable
history of egg hypersensitivity is considered essential because
of a high risk of exposure, an intradermal test dose may be
administered under close medical supervision.
SIMULTANEOUS ADMINISTRATION OF OTHER VACCINES
Determination of whether to administer yellow fever vaccine and
other immunobiologics simultaneously should be made on the basis
of convenience to the traveler in completing the desired
vaccinations before travel and on information regarding possible
interference. The following will help guide these decisions.
Studies have shown that the serologic response to yellow fever
vaccine is not inhibited by the administration of certain other
vaccines concurrently or at various intervals of a few days to 1
month. Measles and yellow fever vaccines have been administered
in combination with full efficacy of each of the components;
Bacillus Calmette Guerin (BCG) and yellow fever vaccines have
been administered simultaneously without interference.
Additionally, severity of reactions to vaccination has not been
amplified by the concurrent administration of yellow fever and
other live virus vaccines (11). If live virus vaccines are not
given concurrently, 4 weeks should elapse between sequential
Some data have indicated that persons given yellow fever and
cholera vaccines simultaneously or 1-3 weeks apart had lower than
normal antibody responses to both vaccines (12,13). Unless there
are time constraints, cholera and yellow fever vaccines should be
administered at a minimal interval of 3 weeks. If the vaccines
cannot be administered at least 3 weeks apart, the vaccines can
be given simultaneously or at any time within the 3-week
Hepatitis B and yellow fever vaccine may be given concurrently
(14). No data exist on possible interference between yellow fever
and typhoid, paratyphoid, typhus, plague, rabies, or Japanese
In a prospective study of persons given yellow fever vaccine
and 5 cc of commercially available immune globulin, no alteration
of the immunologic response to yellow fever vaccine was detected
when compared with controls (15). Although chloroquine inhibits
replication of yellow fever virus in vitro, it does not adversely
affect antibody responses to yellow fever vaccine in humans
receiving antimalaria prophylaxis (16).
Strode GK, ed. Yellow fever. New York: McGraw Hill, 1951.
World Health Organization Expert Committee on Yellow Fever.
Third report WHO tech rep, ser no. 4791, 1971.
3. Nasidi A, Monath TP, DeCock K, et al. Urban yellow fever
epidemic in western Nigeria, 1987. Trans R Soc Trop Med Hyg
4. Smithburn KC, Durieux C, Koerber R, et al. Yellow fever
vaccination. WHO monograph series no. 30. Geneva, 1956.
5. Wisseman CL Jr, Sweet BH. Immunological studies with group B
arthropod-borne viruses. III. Response of human subjects to
revaccination with 17D strain yellow fever vaccine. Am J Trop Med
6. Rodhain F, Hannoun C, Jousset FX, Ravisse P. Isolement du
virus de la fievre jaune a Paris a partir de deux cas humains
importes. Bull Soc Pathol Exot 1979;72:411-5.
7. CDC. Health information for international travel 1989.
Atlanta: CDC, 1989; HHS publication no. (CDC)89-8280.
8. Groot H, Ribeiro RB. Neutralizing and
haemagglutination-inhibiting antibodies to yellow fever 17 years
after vaccination with 17D vaccine. Bull WHO 1962;27:669-707.
9. Poland JD, Calisher CH, Monath TP, Downs WG, Murphy K.
Persistence of neutralizing antibody 30-35 years after
immunization with 17D yellow fever vaccine. Bull WHO
10. Rosenzweig EC, Babione RW, Wisseman CL Jr. Immunological
studies with group B arthropod-borne viruses. IV. Persistence of
yellow fever antibodies following vaccination with 17D strain
yellow fever vaccine. Am J Trop Med Hyg 1963;12:230-5.
11. Tauraso NM, Myers MG, Nau EV, et al. Effect of interval
between inoculation of live smallpox and yellow fever vaccines on
antigenicity in man. J Infect Dis 1972;126:363-71.
12. Felsenfeld O, Wolf RH, Gyr K, et al. Simultaneous vaccination
against cholera and yellow fever. Lancet 1973;1:457-8.
13. Gateff C. Influence de la vaccination anticholoerique sur
l'immunisation antiamarile associee. Bull Soc Pathol Exot
14. Yvonnet B, Coursaget P, Deubel V, et al. Simultaneous
administration of hepatitis B and yellow fever vaccines. J Med
15. Kaplan JE, Nelson DB, Schonberger LB, et al. The effect of
immune globulin on trivalent oral polio and yellow fever
vaccinations. Bull WHO 1984;62:585-90.
16. Tsai TF, Bolin RA, Lazuick JS, et al. Chloroquine does not
adversely affect the antibody response to yellow fever vaccine. J
Infect Dis 1986;154:726.