Yellow
Fever Vaccine
Yellow fever
is preventable by a relatively safe, effective vaccine. For all
eligible persons, a single injection of 0.5 mL of reconstituted
vaccine should be administered subcutaneously.
Adverse Reactions
General Events
Reactions to
yellow fever vaccine are generally mild. Vaccine recipients have
reported mild headaches, myalgia, low-grade fevers, or other minor
symptoms that may begin within days after vaccination and last 5-10
days. In clinical trials, the incidence of mild adverse events has
been ~25%, but many events may have been unrelated, as the trials
were not placebo-controlled. Approximately 1% of vaccinees find
it necessary to curtail regular activities. Immediate hypersensitivity
reactions, characterized by rash, urticaria, or asthma or a combination
of these, are uncommon (incidence <0.8 per 100,000 vaccinees)
(9).
Yellow Fever
Vaccine-Associated Neurologic Disease
Historically,
yellow fever vaccine-associated adverse events were seen primarily
among infants and presented as encepha-litis. Since 1992, six cases
of encephalitis among adult recipients of yellow fever vaccine have
been reported to the U.S. Vaccine Adverse Event Reporting System
(VAERS) (10,11; unpublished data, CDC). In addition, 10 cases of
autoimmune neurologic disease have been reported to VAERS, including
patients with Guillian-Barré syndrome and acute disseminated encephalomyelitis.
All patients with yellow fever vaccine-associated neurologic disease
(YEL-AND) had onset of illness 4-27 days after vaccination. All
cases were in first-time vaccine recipients. The risk for YEL-AND
does not appear to be limited to infants, and the overall reported
rate in the United States is estimated to be approximately 0.5 per
100,000 doses distributed.
Yellow Fever
Vaccine-Associated Viscerotropic Disease
A serious adverse
reaction syndrome has been described within the last 10 years among
recipients of yellow fever vaccines produced by several different
manufacturers. This syndrome was previously reported as febrile
multiple organ system failure and is now called yellow fever vaccine-associated
viscerotropic disease (YEL-AVD). Since 1996, 12 cases of YEL-AVD,
a disease that is clinically and pathologically similar to naturally
acquired yellow fever, have been reported in the United States (10,11;
unpublished data, CDC); an additional 24 suspected cases have been
identified worldwide as of August 2006 (12)-22; unpublished data,
CDC). All U.S. cases required intensive care after experiencing
severe illness variably characterized by fever, hypotension, respiratory
failure, elevated hepatocellular enzymes, lymphocytopenia, and thrombocytopenia.
Seven (58%) of the U.S. cases have been fatal. In several cases
for which tissue samples were available, immunohistochemical staining
demonstrated viral antigen in liver, and sometimes other tissues
including lung, kidney, spleen, lymph node, brain, and smooth muscle.
In many cases, tissue samples were not available for histopathologic
review or detection of virus. All cases reported thus far have occurred
in primary vaccinees. Yellow fever vaccines must be considered as
a possible, but rare, cause of YEL-AND that is similar to fulminant
yellow fever caused by wild-type YFV. Crude estimates of the reported
incidence of YEL-AND in the United States indicate an overall reporting
rate of 0.3 - 0.5 cases per 100,000 doses of vaccine distributed.
This frequency appears to be higher for persons older than 60 years
of age; the estimated reporting rate in this group is approximately
1.8 cases per 100,000 doses distributed.
Because of recent
reports of deaths due to yellow fever among unvaccinated travelers
to yellow fever-endemic areas, yellow fever vaccination of travelers
to high-risk areas should be encouraged as a key prevention strategy;
however, because severe adverse events can follow yellow fever vaccination,
physicians should be careful to administer the vaccine only to persons
truly at risk for exposure to yellow fever. Studies are being conducted
to clarify the cause and risk factors for these rare serious adverse
events associated with yellow fever vaccine.
Precautions
and Contraindications
Age
The risk for
adverse reactions appears to be age related. Infants younger than
6 months of age should not be vaccinated because they are more susceptible
to the serious adverse reaction of YEL-AND (also known as postvaccinal
encephalitis) than are older children (23). Immunization should
be delayed until an infant is at least 9 months of age. (See Chapter
8 for a discussion of yellow fever immunization for infants and
children.) In unusual circumstances, physicians considering vaccinating
infants aged younger than 9 months should contact the Division of
Vector-Borne Infectious Diseases (970-221-6400) or the Division
of Global Migration and Quarantine (404-498-1600) at CDC for advice.
Analysis of
adverse events passively reported to VAERS indicate that persons
older than 60 years of age may be at increased risk for systemic
adverse events following vaccination compared with younger persons.
The risk of any serious adverse event following vaccination has
been estimated at about 4 per 100,000 doses for people aged 60-69
years old and 7.5 per 100,000 doses for people 70 years and older
(24). Travelers older than 60 years should discuss with their physicians
the risks and benefits of vaccination in the context of their destination-
specific risk for exposure to YFV.
History of
Thymus Disease
A history of
thymus disease has recently been identified as a contraindication
to yellow fever vaccine (13). Four (11%) of the 36 vaccine recipients
with YEL-AVD reported worldwide have had a history of diseases involving
the thymus, all of which are extremely rare, suggesting that compromised
thymic function is an independent risk factor for YEL-AVD. One fatal
case in the United States occurred in a 67-year-old woman who had
a history of thymectomy for a malignant thymoma approximately 2
years before vaccination. A second case in the United States occurred
in a 70-year-old man who had a history of hyperthyroidism, myasthenia
gravis, and thymectomy for thymoma 20 years before vaccination.
This patient survived. A third case was reported from Switzerland
and occurred in a 50-year-old man who had a history of thymectomy
due to thymoma 8 years prior to vaccination. This patient also survived.
Most recently, a fatal case (male, age 44 years) of viscerotropic
disease with fulminant hepatic failure temporally associated with
yellow fever vaccine was reported from Colombia. This patient had
a thymectomy due to benign thymoma 2 years before vaccination.
In addition
to concerns about vaccinating elderly travelers, health-care providers
should be careful to ask about a history of thymus disorder, including
myasthenia gravis, thymoma, or prior thymectomy, when screening
a patient before administering yellow fever vaccine. For persons
with such a history, alternative means of prevention should be recommended,
if travel plans cannot be altered to avoid yellow fever-endemic
areas.
Pregnancy
The safety of
yellow fever vaccination during pregnancy has not been well established,
and the vaccine should be administered to pregnant women only if
travel to an area with risk of yellow fever is unavoidable. If international
travel requirements, rather than an increased risk of acquiring
yellow fever, are the only reason to vaccinate a pregnant woman,
efforts should be made to obtain a waiver letter from the traveler's
physician. Pregnant women who must travel to areas where the risk
for yellow fever infection is high should be vaccinated. Despite
the apparent safety of this vaccine, infants born to these women
should be monitored closely for evidence of congenital infection
and other possible adverse effects resulting from yellow fever vaccination.
Since pregnancy may affect immunologic function, if vaccination
of a pregnant woman is deemed necessary, serologic testing to document
a protective immune response to the vaccine can be considered (25;26).
To discuss the need for serologic testing, the appropriate state
health department or CDC's Division of Vector-Borne Infectious Diseases
at 970-221-6400 or Division of Global Migration and Quarantine at
404-498-1600 should be contacted for more information.
Breast-feeding
Whether this
vaccine is excreted in breast milk is not known. There have been
no reports of adverse events or transmission of the vaccine virus
from nursing mother to infant. As a precautionary measure, vaccination
of nursing mothers should be avoided, because of the theoretical
risk of vaccine virus transmission to the breastfed infant. When
travel of nursing mothers to high-risk yellow fever endemic areas
cannot be avoided or postponed, these women should be vaccinated.
Immunosuppression
Infection with
yellow fever vaccine virus poses a theoretical risk for travelers
with immunosuppression in association with HIV infection; leukemia,
lymphoma, or generalized malignancy; with a history of thymus disease
or thymectomy; or who are receiving corticosteroids, alkylating
drugs, antimetabolites, or radiation. There is a single report of
a 53-year-old patient with undiagnosed HIV infection who had a low
CD4שׂ count (108 cells/mm3) and who developed YEL-AND and died
of meningoencephalitis (27). Other HIV-infected people with CD4
counts above 200 cells/mm3 have been successfully vaccinated without
serious adverse effects from the vaccine. Immunosuppressed patients
who are unable to effectively resist viral infections should not
be vaccinated. If travel to a yellow fever-endemic zone is necessary
for such individuals, patients should be advised of the risks posed
by such travel, instructed in methods for avoiding vector mosquitoes,
and supplied with vaccination waiver letters by their physicians.
Low-dose (i.e., 20 mg prednisone or equivalent/day); short-term
(i.e., less than 2 weeks) systemic corticosteroid therapy or intra-articular,
bursal, or tendon injections with corticosteroids; and intranasal
corticosteroids are not thought to be sufficiently immunosuppressive
to constitute an increased hazard to recipients of yellow fever
vaccine (see Chapter 9).
Persons who
are HIV-infected but do not have AIDS or other symptomatic manifestations
of HIV infection, who have established laboratory verification of
adequate immune system function (e.g., CD4שׂ T lymphocyte cell
counts >200/mm3), and who cannot avoid potential exposure to
YFV should be offered the vaccination and monitored closely for
possible adverse effects (23). If international travel requirements
are the only reason to vaccinate an asymptomatic HIV-infected person,
rather than an increased risk for acquiring yellow fever, efforts
should be made to obtain a waiver letter from the traveler's physician.
Family members of immunosuppressed or HIV-infected persons who themselves
have no contraindications can receive yellow fever vaccine.
Data regarding
seroconversion rates after yellow fever vaccination among asymptomatic
HIV-infected persons are limited, but indicate that the seroconversion
rate among such persons may be reduced (23). Because vaccination
of asymptomatic HIV-infected persons might be less effective than
that of persons not infected with HIV, measurement of the neutralizing
antibody response to vaccination should be considered before travel.
Physicians should consult the applicable state health department
or CDC's Division of Vector-Borne Infectious Diseases at 970-221-6400
or Division of Global Migration and Quarantine at 404-498-1600,
for more information.
Hypersensitivity
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. However, some
egg-sensitive persons are not allergic to cooked eggs and may not
know they are susceptible to allergic reactions following raw eggs
or egg-containing vaccines. If vaccination of a person with a questionable
history of egg or chicken hypersensitivity is considered essential
because of high risk for acquiring yellow fever, an intradermal
test dose of vaccine may be administered under close medical supervision.
Specific directions for vaccine skin testing are found in the vaccine
package insert. In some instances, small test doses of vaccine administered
intradermally have led to an antibody response. Gelatin is used
as a stabilizer in several vaccines, including yellow fever vaccine,
and might be the stimulus for some allergic reactions to yellow
fever vaccine. If international travel regulations are the only
reason to vaccinate a traveler hypersensitive to eggs or gelatin,
efforts should be made to obtain a waiver.
Simultaneous
Administration of Other Vaccines and Drugs
Studies have
shown that the immune response to yellow fever vaccine is not inhibited
by administration of certain other live, attenuated vaccines concurrently
or at various intervals of a few days to 1 month (1) (see Chapter
1).
A prospective
study of persons given yellow fever vaccine along with 5 mL of commercially
available immune globulin showed no alteration of the immunologic
response to yellow fever vaccine when compared with controls (28).
Although chloroquine inhibits replication of YFV in vitro, it does
not adversely affect antibody responses to yellow fever vaccine
in persons receiving the drug as antimalarial prophylaxis (29).
Source
Centers
for Disease Control and Prevention
National Center for Infectious Diseases, Division of Global Migration
and Quarantine
http://www.cdc.gov/
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