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YELLOW FEVER

Yellow fever is a viral disease that has caused large epidemics in Africa and the Americas. It can be recognized from historic texts stretching back 400 years. Infection causes a wide spectrum of disease, from mild symptoms to severe illness and death. The "yellow" in the name is explained by the jaundice that affects some patients.

WHO estimates an annual incidence of 200,000 cases, most of which occur in sub-Saharan Africa (Robertson SE, JAMA 276, 10/9/96).

• In 1995, WHO reported 440 cases of yellow fever in Peru with a case fatality rate of 38%, the largest outbreak in South America in 40 years (WHO: WER 70, No. 32, 8/11/95).

Cause: The disease is caused by the yellow fever virus, flavivirus group.

Symptoms: incubation period of three to six days.

There are then two disease phases.

the first, "acute", phase is normally characterized by fever, muscle pain (with prominent backache), headache, shivers, loss of appetite, nausea and/or vomiting. After three to four days most patients improve and their symptoms disappear.

However, 15% enter a "toxic phase" within 24 hours. Fever reappears and several body systems are affected. The patient rapidly develops jaundice and complains of abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes and/or stomach. Once this happens, blood appears in the vomit and faeces. Kidney function deteriorates; this can range from abnormal protein levels in the urine (albuminuria) to complete kidney failure with no urine production (anuria). Half of the patients in the "toxic phase" die within 10-14 days. The remainder recover without significant organ damage.

Differential  diagnosis:  malaria, typhoid, rickettsial diseases, haemorrhagic viral fevers (e.g. Lassa), arboviral infections (e.g. dengue), leptospirosis, viral hepatitis and poisoning (e.g. carbon tetrachloride).

Blood tests (serology assays)

Regions affected: The virus is constantly present with low levels of infection (i.e. endemic) in some tropical areas of Africa and the Americas.

Thirty-three countries, with a combined population of 508 million, are at risk in Africa. These lie within a band from 15°N to 10°S of the equator. In the Americas, yellow fever is endemic in nine South American countries and in several Caribbean islands. Bolivia, Brazil, Colombia, Ecuador and Peru are considered at greatest risk.

There are 200,000 estimated cases of yellow fever (with 30,000 deaths) per year.

Transmission: Humans and monkeys are the principal animals to be infected. The virus is carried from one animal to another (horizontal transmission) by a biting mosquito (the vector). The mosquito can also pass the virus via infected eggs to its offspring (vertical transmission). The eggs produced are resistant to drying and lie dormant through dry conditions, hatching when the rainy season begins. Therefore, the mosquito is the true reservoir of the virus, ensuring transmission from one year to the next.

Several different species of the Aedes and Haemogogus (S. America only) mosquitoes transmit the yellow fever virus.

Infection of humans: There are three types of transmission cycle for yellow fever: sylvatic, intermediate and urban. All three cycles exist in Africa, but in South America, only sylvatic and urban yellow fever occur.

o                                Sylvatic (or jungle) yellow fever: In tropical rainforests, yellow fever occurs in monkeys that are infected by wild mosquitoes. The infected monkeys can then pass the virus onto other mosquitoes that feed on them. These infected wild mosquitoes bite humans entering the forest resulting in sporadic cases of yellow fever. The majority of cases are young men working in the forest (logging, etc).

o                                 

o                                Intermediate yellow fever: In humid or semi-humid savannahs of Africa, small-scale epidemics occur. These behave differently from urban epidemics; many separate villages in an area suffer cases simultaneously, but fewer people die from infection. Semi-domestic mosquitoes infect both monkey and human hosts. This area is often called the "zone of emergence", where increased contact between man and infected mosquito leads to disease.

o                                Urban yellow fever: Large epidemics can occur when migrants introduce the virus into areas with high human population density. Domestic mosquitoes (of one species, Aedes aegypti) carry the virus from person to person; no monkeys are involved in transmission. These outbreaks tend to spread outwards from one source to cover a wide area.

Treatment: There is no specific treatment for yellow fever. Supportive treatment only

Prevention: Vaccination is the single most important measure for preventing yellow fever.. Mosquito control measures can be used to prevent virus transmission until vaccination has taken effect.

Vaccine

Yellow Fever Vaccine (YF-VAX^®, Aventis) is an subcutaneous injectable, attenuated, live-virus vaccine.

This immunization has almost 100% efficacy, while the case-fatality rate for the disease is more than 60% in nonimmune adults.

The vaccine is available only at approved centers or vaccination centers designated by health departments.

Indications for Vaccination

Validated proof of yellow fever immunization may be officially required under International Health Regulations as a condition for entry (see "International Certificate of Vaccination" and "Special Considerations").

• At this time, yellow fever is the only internationally regulated immunization.

WHO recommends this immunization for travel outside the urban areas of countries in the yellow fever endemic zone, even if these countries have not officially reported the disease and do not require evidence of immunization upon entry.

• When a country is labeled as "endemic" for yellow fever, it usually means that there are mosquitoes in rural areas that could potentially transmit the virus, but no recent human cases of yellow fever have been reported.
• When a country is labeled as "infected" with yellow fever, it means that country's health officials have reported human cases to WHO.

CDC's vaccination recommendations (for purposes of protecting travelers' health, as opposed to meeting entry requirements) are reported on a country-by-country basis in Health Information for International Travel.

• CDC recommends yellow fever immunization for some countries that do not lie in the so-called endemic zone and excludes some that do lie in the endemic zone.
• For some countries, CDC notes that risk is limited to certain areas.
• Updates about risk and requirement changes as reported by WHO are noted in CDC's Blue Sheet.

ADMINISTRATION: YELLOW FEVER VACCINE

Note: This immunization contains no preservatives and must be administered immediately (< 1 hour) after reconstitution. Unused vaccine should be discarded within 1 hour of reconstitution.

Pediatric (4-8 months) 

Do not give to infants younger than 9 months of age unless they are at particularly high risk

.Use the same dose, route and schedule noted under "Pediatric (> 9 months)."

• Never immunize infants younger than 4 months of age.

Pediatric (> 9 months)

Dose/Route

0.5 mL, subcutaneous.

Schedule

Primary: Single dose.

Booster: Every 10 years, for purposes of both protecting the traveler and meeting entry requirements.

Adult

Dose/Route

0.5 mL, subcutaneous.

Schedule

Primary: Single dose.

Booster: Every 10 years, for purposes of both protecting the traveler and meeting entry requirements.

SIDE EFFECTS

Reactions generally are mild.

Fever, headache, and muscle ache may occur 5-14 days after immunization.

Per manufacturer, in rare instances encephalitis has developed in very young infants.

In the elderly and in the immune suppressed, the vaccine may lead to disease transmission with fatal outcome.

PRECAUTIONS AND CONTRAINDICATIONS

General

Never immunize children younger than 4 months of age.

Infants younger than 9 months of age should not be immunized for yellow fever unless they are at particularly high risk.

• Yellow fever vaccine is generally contraindicated for children younger than the age of 6 months because of a high incidence of vaccine-associated encephalitis. However, because some countries or situations demand it, ACIP and WHO make specific recommendations based on the infant's age. Consider postponing vaccination in persons with moderate or severe illness, with or without a fever, until recovery, to minimize potential adverse effects Anaphylactic reaction to a previous dose contraindicates further immunization.

Anaphylactic reaction to a vaccine constituent contraindicates the use of vaccines containing that substance.

• History of anaphylaxis or proven sensitivity to egg or egg protein is usually a contraindication, but a medical waiver letter should be offered.
• Per AAP, less severe egg or feather allergies are not contraindications to administration of this vaccine and do not usually require skin testing.
• For the protocol on scratch testing and intradermal testing, refer to AAP: 2000 Red Book, p. 36.¹
• Yellow fever vaccine contains gelatin.

Compromised Immunity

Per WHO, this vaccine is recommended for HIV-seropositive individuals who are asymptomatic.

Per CDC, the decision to immunize immunocompromised patients with yellow fever vaccine should be based on a physician's evaluation of the patient's state of immunosuppression weighed against the risk of exposure to the virus. This includes patients with immunosuppression related to HIV infection, AIDS, leukemia, lymphoma, or generalized malignancy or to administration of corticosteroids, alkylating drugs, antimetabolites or radiation.

• Per AAP, wait at least 1 month before administering a live-virus vaccine to nonimmunocompromised patients who have received high systemically absorbed doses of corticosteroids for > 2 weeks. For AAP recommendations on live-virus vaccination of corticosteroid recipients, see 2000 Red Book, p. 61.

The vaccine may be given to family members of immunocompromised persons who themselves have no contraindications.

This live-virus vaccine may be given to patients with leukemia in remission whose chemotherapy has been terminated for at least 3 months.

For HIV-infected patients, see "HIV- or AIDS-Infected Travelers."

• Persons with asymptomatic HIV who cannot avoid exposure should be offered the choice of immunization.
• In late 1997, Toussaint, Wiktor, Tsai, et al reported that HIV-positive children have a poor response to yellow fever vaccine (Pediatric Infectious Disease Journal 16, No. 12, 12/19/97).

If yellow fever vaccine is contraindicated because of an underlying medical condition, a medical waiver letter should be offered.

Pregnancy and Lactation

This vaccine should not be given in pregnancy except under extreme circumstances because it is a live virus.

• It should be given to a pregnant woman only when the journey is necessary and the risk of contracting the disease is substantial.
• Per WHO, yellow fever vaccine may be given after the sixth month of pregnancy when justified epidemiologically.

Breast-feeding mothers may receive this immunization.

If yellow fever vaccine is contraindicated because of pregnancy, a medical waiver letter should be offered.

COMPATIBILITY

Based on theoretical concerns, ACIP recommends that, whenever possible, the yellow fever vaccine be administered either concurrently with, or at least 28 days apart from, other live-antigen vaccines (e.g., MMR, varicella, oral typhoid, or OPV).

It should be given 3 weeks apart from cholera immunization, but if time does not permit this, it may be given simultaneously or at any time within the 3-week interval.

• Per AAP, it is preferable to give this vaccine at least 3 weeks apart from cholera vaccine.

Live-virus vaccines can interfere with the response to a tuberculin test. Tuberculin testing can be done either on the same day that live-virus vaccines are administered or 4-6 weeks later.

The ACIP states that although yellow fever is a live-antigen vaccine, it may be administered concurrently with, or at any interval before or after, IG for hepatitis A prophylaxis.

Per package insert, vaccination with yellow fever vaccine should be deferred for 8 weeks following blood or plasma transfusion.

SPECIAL CONSIDERATIONS

According to WHO, yellow fever (like plague and cholera) is a quarantinable disease.

Entry Requirements

While many countries have no entry requirements, others may require an International Certificate of Vaccination from travelers arriving from all countries; from countries/areas that lie in the so-called endemic zone; from countries/areas that are actually infected; or from countries that are maintained on a list and regarded as infected (although this information may be inaccurate).

Immunization must be given not less than 10 days and no more than 10 years prior to planned date of entry (it is valid for 10 years), and it must be entered and validated in the specific section of the International Certificate of Vaccination.

Unvaccinated persons for whom immunization is required for entry may, upon arrival, be subject to vaccination, medical follow-up and/or quarantine. In some cases entry may be denied.

• A major concern is that travelers may be vaccinated by local health authorities using contaminated needles and syringes and be exposed to the risk of contracting hepatitis B, HIV, or other blood-borne diseases.

Exemption from requirements may be made on the basis of age or medical contraindication.

• Some countries exempt infants younger than 6 months or 1 year of age. Consult individual country requirements for specific age exemptions.
• If immunization is medically contraindicated, note it in the space provided on the Certificate, give the traveler an exemption letter (see "Immunization Exemption Letter: Yellow Fever" ), and encourage the traveler to contact the country's embassy to ensure the exemption will be honored upon arrival.

Travel on military orders may entail requirements in excess of those stated for civilian travel; the appropriate military medical facility should be contacted to determine requirements.

From Encompass

Dr Assad