Yellow Fever

Yellow fever is a life-threatening viral infection transmitted by mosquitoes in parts of Africa and South America. In urban areas, yellow fever is primarily a disease of humans and is transmitted from person to person by Aedes mosquitoes, which breed in man-made water containers, such as jars, barrels, cisterns, and discarded tires. Because Aedes mosquitoes proliferate in densely populated areas, large outbreaks may occur. However, except during epidemics, yellow fever is rare in urban settings.

In the jungle, yellow fever is mainly a disease of non-human primates and is transmitted by a variety of mosquito species. Human cases occur sporadically, chiefly among those who work in the jungle, such as loggers. In the humid or semi-humid savannahs of Africa, an intermediate situation exists, wherein both monkeys and humans are infected and the disease occurs in many small villages simultaneously, but not at the levels seen in urban epidemics. This has been the pattern for most yellow fever outbreaks reported in recent years.

The incubation period ranges from three to six days. Initial symptoms may include fever, chills, headache, muscle aches, backache, loss of appetite, nausea and vomiting, which usually subside in three or four days. However, after initial improvement, approximately one person in six enters a second, toxic phase characterized by recurrent fever, vomiting, listlessness, jaundice, kidney failure, and hemorrhage, leading to death in up to half of the cases. There is no treatment except for supportive care.

Yellow fever vaccine (YF-VAX; Aventis Pasteur Inc.) should be given at least ten days prior to arriving in a yellow-fever-endemic area and must be administered at an approved yellow fever vaccination center, which gives each vaccinee a fully validated International Certificate of Vaccination. The vaccine is given as a single 0.5 cc subcutaneous injection. A booster dose is recommended every 10 years for those who remain at risk. Reactions to the vaccine, which are generally mild, may include headaches, muscle aches, low-grade fevers, or discomfort at the injection site. Severe allergic reactions to yellow fever vaccine are uncommon and occur principally in those allergic to eggs.

Rarely, yellow fever vaccine may lead to multiple organ system failure, similar to yellow fever caused by wild-type virus, or to neurologic illness.  A recent report indicates that those with a history of thymus disease or thymectomy are at highest risk for developing multiple organ system failure and should not be given yellow fever vaccine (see Rachel Barwick Eidex, History of thymoma and yellow fever vaccination, in the Lancet, Sept. 11, 2004). Limited data also suggest that serious adverse reactions occur more commonly among the elderly and among those receiving yellow fever vaccine for the first time (see Emerging Infectious Diseases and the Centers for Disease Control).

In November 2007, four laboratory-confirmed deaths were reported from yellow fever vaccine given in Peru as part of a mass immunization campaign after an earthquake. All four persons received vaccine from the same lot, manufactured by Bio-Manguinos in Brazil (widely used in South America, but not the United States). The vaccine strain caused infection of multiple organ systems, which is a known but rare complication of yellow fever vaccine. The reason why this occurred at a much higher rate than expected with this particular lot could not be determined. See the Pan-American Health Organization for further information.

Because yellow fever vaccine contains live virus, it should not in general be given to those with any of the following:

• Age less than 6 months
• Thymus disorder
• Malignant neoplasm
• Primary immunodeficiency
• Transplantation
• Immunosuppressive or immunomodulatory therapies
• Symptomatic HIV infection or CD4 lymphocyte count less than 15% total (or less than 200/mm3 for age greater than 6 years)
• Allergy to vaccine components

The individuals listed above should avoid traveling to areas where yellow fever is actively transmitted.

Caution should be exercised before giving yellow vaccine to the following groups:

• Age 6-8 months
• Age 60 years and older
• Pregnancy
• Breastfeeding
• Asymptomatic HIV infection and CD4 lymphocyte count 15-24% total (or 200-499/mm3 for age greater than 6 years)

Physicians considering yellow fever vaccine for pregnant women or infants between the ages of six and nine months because of special circumstances should contact the Division of Vector-Borne Infectious Diseases (telephone: 970-221-6400) or the Division of Global Migration and Quarantine (telephone: 404-498-1600) at CDC for advice. Because of the risk of encephalitis, infants less than six months of age should never be given yellow fever vaccine. Vaccination of nursing mothers should be avoided when possible. Short-term (less than two weeks) use of corticosteroids is not a contraindication to receiving yellow fever vaccine. Because yellow fever vaccine is produced in chick embryos, it should not be given to those with a history of allergy to eggs.

If a country which is not infected with yellow fever requires proof of immunization and immunization is contraindicated as above, the traveler's physician should supply a waiver letter, preferably written on letterhead stationary and bearing the stamp used by official immunization centers to validate the International Certificate of Vaccination (see the Centers for Disease Control).

Yellow fever vaccine may be administered with vaccines for hepatitis A, hepatitis B, typhoid (Typhim Vi), meningococcus, measles, or smallpox. There are no data regarding co-administration with rabies or Japanese encephalitis vaccines.

Insect protection measures are essential when traveling to areas infected with yellow fever.

From the World Health Organization

Yellow fever vaccine: WHO position paper (PDF) (excellent review for physicians)

Yellow fever vaccine

Yellow fever (background)

Yellow fever fact sheet

Safety of yellow fever vaccine

Yellow fever endemic zones, Africa and Americas, 2000

Countries at risk for yellow fever and having at least one outbreak, 1985-2002

From the Centers for Disease Control (CDC)

Yellow Fever (Yellow Book)

Map of Yellow Fever Infected Countries in Africa

Map of Yellow Fever Infected Countries in the Americas

From the Pan American Health Organization (PAHO)

Update on Yellow Fever in the Americas

From Health Canada

Yellow Fever Vaccination Centres in Canada