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The current recommendations for yellow fever vaccination are summarized.
Sources: CDC. Adverse events associated with 17D-derived yellow fever vaccination—United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2002;51:989-993; CDC. Yellow fever vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR Morb Mortal Wkly Rep. 2002;51:RR-17.
After 7 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) were reported to the Advisory Committee on Immunization Practices (ACIP) in June 2001, enhanced surveillance was initiated. Between June 20, 2001, and August 31, 2002, 2 patients with severe adverse events consistent with YEL-AVD and 4 with yellow fever-associated neurotropic disease (YEL-AND) were reported. All were vaccinated in the United States with the 17D-derived yellow fever vaccine, and all recovered, after hospitalization, without sequelae. Of the 12 cases of YEL-AVD reported worldwide since this complication was first recognized in 1996, 5 were persons younger than 50 years of age. The onset of YEL-AVD occurred 1 to 6 days after vaccination.
These and other observations were taken into account in the development of the latest ACIP recommendations for yellow fever vaccination, some of which follow.
1. Persons older than 9 months traveling to or living in areas of South America and Africa that lie within the yellow-fever endemic zone should be vaccinated regardless of whether the infection is officially reported or not in those areas and without regard to whether urban or rural areas are being visited.
2. Because of concern of an increased risk of adverse reactions, travelers older than 65 years "should discuss with their physicians the risks and benefits of vaccination in the context of their destination-specific risk for exposure to yellow fever." However, "yellow fever vaccination . . . should be encouraged as a key prevention strategy."
3. A valid International Certificate of Yellow Fever Vaccination may be required by certain countries if the traveler has been in countries known or thought to have yellow fever—even if the traveler was only in transit.
1. Travel to infected areas with infants 6 thru 8 months old should be avoided because of an increased risk of YEL-AND (encephalitis); travel to endemic/epidemic zones should be postponed or avoided whenever possible.
2. With infants 6 thru 8 months old with unavoidable exposure to an environment with an increased likelihood of infection, such as active endemic or epidemic transmission, vaccination "might be considered."
3. Because of the risk of YEL-AND, infants younger than 6 months old should in no instance be vaccinated.
Pregnancy and Nursing
1. The safety of yellow fever vaccination during pregnancy has not been established and should only be performed if travel to an endemic area is unavoidable and if an increased risk of exposure exists. Fetal infection with YF17D occurs at a low rate and has not been associated with congenital abnormalities.
2. If international travel requirements, rate than increased risk of infection, is the only reason to vaccinate a pregnant woman, vaccination should be avoided and a waiver letter should be provided. The traveler with a waiver should contact the country’s consulate prior to travel.
3. Because postvaccination seroconversion may be reduced in pregnancy, serological tests to evaluate immune response should be considered.
4. Because of a theoretical risk of transmission of the vaccine virus, vaccination of nursing mothers should be avoided, but if travel to high-risk areas cannot be avoided or postponed, vaccination can be performed.
1. Lab personnel who might be exposed to virulent yellow fever virus or to concentrated preparations of the 17D vaccine strain should be vaccinated.
Altered Immune Status
1. Patients with AIDS, symptomatic HIV infection, leukemia, lymphoma, "generalized malignancy," or who are receiving immunosuppressive therapy including radiotherapy, alkylating drugs, antimetabolites, or highdose and/or prolonged courses of corticosteroid therapy should not be vaccinated.
2. "Low-dose (ie, 20 mg prednisone or equivalent/day), short-term (ie, less than 2 weeks) systemic corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be sufficiently immunosuppressive to constitute an increased hazard to recipients of yellow fever vaccine."
3. Individuals who have asymptomatic HIV infection, do not have AIDS, have "established laboratory verification of adequate immune system function," and who cannot avoid potential exposure to yellow fever virus should be offered the choice of vaccination.
4. If international travel requirements, rate than increased risk of infection, is the only reason to vaccinate an asymptomatic HIV-infected person, vaccination should be avoided and a waiver letter should be provided.
5. Because seroconversion rates after vaccination of asymptomatic HIV-infected persons is reduced, measurement of their neutralizing antibody response to vaccination should be considered prior to travel.
1. Because the vaccine is produced in chick embryos, yellow fever vaccine should not be administered to individuals with hypersensitivity to eggs.
2. If international travel requirements, rather than increased risk of infection, is the only reason to vaccinate an individual with egg hypersensitivity, vaccination should be avoided and a waiver letter should be provided.
3. If vaccination is considered essential because of a high risk of exposure and the history of egg allergy is questionable, an intradermal test dose can be administered according to the instructions contained in the package insert.
Simultaneous Administration of Other Vaccines and Chloroquine
1. Available evidence indicates that yellow fever vaccine may be administered simultaneously with the following vaccines: measles, smallpox, BCG, hepatitis A, hepatitis B, Typhim Vi, and Menomune, as well as with immune serum globulin given in the usual IM dose.
2. No data exist regarding possible interference between yellow fever and rabies or Japanese encephalitis vaccines.
3. Chloroquine administration does not interfere with the antibody response to yellow fever vaccine.
1. While evidence indicates that immunity to yellow fever virus induced by vaccination persists for 30-35 years (and probably for life), international health regulations require revaccination at intervals of 10 years.
Comment by Stan Deresinski, MD, FACP
It is estimated that approximately 200,000 cases of yellow fever occur throughout the world each year. Illness may range from subclinical to fatal; no specific antiviral therapy is available and the fatality rate of severe yellow fever is approximately 20%.
The live, attenuated vaccine available in the United States is derived from the 17D-204 strain of yellow fever virus. Active solicitation of symptom reports from vaccinees participating in trials yields an incidence of mild adverse events, mostly influenza-like symptoms, in less than 25%, resulting in approximately 1% curtailing their regular activities. Immediate hypersensitivity reactions occur at an estimated incidence of 1 in 130,000 to 1 in 250,000 vaccine recipients; while these predominantly occur in individuals with egg hypersensitivity, it is possible that the gelatin stabilizer in the vaccine preparation may play a role in some cases.
Transient vaccine strain viremia commonly occurs in healthy individuals during the first week after vaccination and ordinarily is not associated with adverse consequences. However, YEL-AND manifesting as encephalitis may occur at an incidence estimated at less than 1 in 8 million vaccine recipients, with much higher rates occurring in infants. 17D virus has been isolated from the brain of at least 1 victim. YEL-AVD has, to date, exclusively occurred after primary vaccination. The estimated incidence in the United States is 1 in 400,000 doses distributed. The most severe forms of the illness are characterized by the development of multiorgan system failure.
The Centers for Disease Control (CDC) requests that they promptly receive reports of patients suspected of having YEL-AND or YEL-AVD. Report forms are available at www.vaers.org and can be submitted by fax at 877-721-0366, by mail (PO Box 1100, Rockville, MD 20849-1100), or by phone (800-822-7967). Additional information is available at www.cdc.gov/ncidod/dvbid/yellowfever/index.htm and at www.cdc.gov/travel, as well as at 970-221-6400 and 404-498-1600. The latter 2 numbers for, respectively, the CDC’s Divisions of Vector-Borne Infectious Diseases and the Division of Global Migration and Quarantine, can also be called to arrange for serological testing to determine serological responses to yellow fever vaccination in asymptomatic HIV-infected and in pregnant individuals in whom vaccination is indicated.
Editor’s Note: A physician’s letter stating the contraindication to vaccination has been acceptable to certain governments outside the United States. Ideally, the letter should be written on letterhead stationary and bear the stamp used by health department and official vaccination centers to validate the International Certificate of Vaccination. When planning to use a waiver letter, the traveler should also obtain specific and authoritative advice from the embassy or consulate of the country or countries she or 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.
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.