Yellow Fever Vaccine

Key Information

• Yellow Fever (YF) virus is transmitted to humans through the bite of an infected mosquito causing acute febrile hemorrhagic illness.

• YF disease is endemic and intermittently epidemic in sub-Saharan Africa and tropical South America and not in Asia.

• YF is a vaccine-preventable disease and the vaccine is highly immunogenic. It is a safe vaccine. The protective immunity persists for more than 10 years following vaccination.

• Routine YF vaccination is not recommended in India but considered for certain groups of people.

• YF vaccine is given only at approved vaccination centers. International health regulations have set the requirements for proof of YF vaccination when traveling to specific endemic countries.

Virology & Epidemiologic Backgrounds

Yellow fever (YF) is a mosquito-borne acute viral hemorrhagic disease caused by an RNA virus from the family of Flaviviridae. Mosquitoes become infected with the virus when they bite an infected human and non-human primates. The virus is transmitted to humans through the bite of an infected mosquito, primarily by the Aedes aegypti female mosquito. The incubation period is 3 to 6 days. Humans infected with YF virus experience the highest levels of viremia and are infectious to mosquitoes shortly before the onset of fever and for 3 to 5 days afterward

YF occurs year-round, predominantly in rural areas of sub-Saharan Africa (32 countries) and South America (13 countries), but not in Asia. In endemic areas, where the virus is present in monkeys is a potential risk to humans. Sustained transmission is not possible in India because the recognized mosquito vectors & the potential reservoirs are not present.

Spectrum of Clinical Illness

Clinical presentation varies in severity from asymptomatic to fatal. When symptomatic, YF is typically characterized by an acute onset of an undifferentiating febrile flu-like illness. In about 85% of cases, the disease resolves when the acute symptoms subside. For others, after a brief remission lasting anywhere between hours to a day, symptoms worsen, and the disease advances, eventually leading to renal failure, hemorrhagic symptoms, and thrombocytopenia. Treatment is symptomatic and supportive. The WHO estimates, an estimated 200,000 people become infected each year, with up to 30,000 deaths annually. Older adults and those with compromised immune systems are most at risk for serious complications.

Risk Factors for a Traveler Acquiring YF Disease

This depends upon various factors that would include: immunization status, use of personal protection measures against mosquito bites, travel history & location, duration of exposure, the local rate of virus transmission, and activities while traveling. The risk for acquiring YF is low for most travelers, particularly those staying in highly developed major urban areas.

Treatment

Vaccine Preventable Disease

A fatal case of YF continues to be reported among unimmunized travelers to endemic regions; vaccination is the only way to prevent YF disease. Those who live in areas populated by infected mosquitoes and those who haven’t been vaccinated for YF are at risk. Prevention measures against YF should include, also protection against mosquito bites.

YF vaccine is a live-attenuated virus (17D strain) by serial passages in chicken embryo tissue culture. The vaccine preparation is lyophilized, kept under cold-chain conditions, and is considered extremely safe. A single-dose administration (subcutaneous or intramuscular) provides protection for at least 10 years or longer. More than 80% of persons immunized develop neutralizing antibodies 10 days after vaccination and more than 99% by 28 days after vaccination and immunity persists >10 years.

According to a notification by DGHS and Ministry of Health and Family Welfare, a single dose of yellow fever vaccine confers lifelong immunity and there is no need of booster doses unless any special circumstances prevail.⁶

Special conditions which warrant additional regular/booster doses: ⁷

• Expectant mothers who took the YF vaccine single dose during their pregnancy (irrespective of trimester) should receive an additional dose prior to their travel to a risk prone area.
• Persons who received a hemopoietic stem cell transplant following a single dose of YF vaccine and are adequately immuno competent to be vaccinated should be revaccinated before travelling to an endemic region.
• Additional booster doses every 10 years is advised for people with HIV, Lab workers who handle wild type YF virus with insufficient YF specific antibody titers, travelers with a prolonged stay in an endemic area during peak transmission season or ongoing outbreak.

YF vaccine may be given at the same time as most other vaccines. The side effects are benign and transient in nature; may include a low-grade fever, mild headache, and fatigue.

The Centers for Disease Control (CDC) recommends for all people 9 months or older traveling to or from certain countries with an endemic disease or those living in those regions. Nursing mothers traveling with an infant who is 6 to 8 months old should either postpone travel to these areas if possible or talk to your doctor about vaccination. The decision to immunize infants below 9 months of age must balance the risk of exposure with the risk of vaccine-associated encephalitis at this vulnerable specific age group.

The IAP Advisory Committee on Vaccines & Immunization Practices 2020 - 21 (the ACVIP) recommends the YF vaccine for high-risk category children under special circumstances. India imports the YF vaccine to overcome vaccine shortages and the vaccine is available only at the designated center. One should refer to the website for an updated list of Government Yellow Fever Vaccination Centers with contact information. For complete prescribing information, consult the product leaflet or information contained within Health Ministry authorized product monographs. (http://www.mohfw.nic.in/WriteReadData/l892s/54495385931449119270.pdf)

YF is unique among diseases in that there are international health regulations which outline the requirements for proof of vaccination when traveling to specific areas. In recent months, the WHO placed the southern African countries like Zambia and Namibia on high alert because of a ‘worst YF outbreak in 30 years’ occurring at the present time. Many of these, and other countries, will demand a YF certificate from travelers as a condition of entry to their country. Individuals planning to travel internationally and for more detailed information on the YF vaccine, including adverse events, precautions, and contraindications visit the CDC website (wwwnc.cdc.gov/travel/).

In summary:

• YF is a serious febrile hemorrhagic illness with dreadful complications and it is a vaccine preventable disease.

• Apart from vaccination, disease prevention measures should include personnel protection against mosquito bites.

• Under regulations set out by the WHO, anyone travelling to a country or area where there is a risk of contracting YF disease, must have an International Certificate of Vaccination, before travelling.

Complications

The vaccine is contraindicated in people who have an allergic reaction to eggs or chicken proteins and in people who are immunocompromised. YF vaccine, like all live-virus vaccines, should be avoided during pregnancy. Pregnancy and breastfeeding are precautions to yellow fever vaccine administration because rare cases of in utero or breastfeeding transmission of the vaccine virus have been documented. Refer Table for vaccination precautions and contraindications.

Table: Precautions and Contraindications to vaccine Administration

Yellow fever vaccine is the only vaccine that is contra indicated during breast feeding.⁴

Yellow fever vaccine is the only vaccine that is contra indicated in individuals allergic to egg protein.

Endemic areas for yellow fever as per Jan 2023 by WHO ⁵

Dosage Forms & Strength

• ADULT DOSE
  • injection [17D-204 strain]

    ≥4.74 log10 plaque-forming units/0.5mL

    Prophylaxis: 0.5 mL SC ≥10 days before travel

• PEDIATRIC DOSE
  • injection [17D-204 strain]

    ≥4.74 log10 plaque-forming units/0.5mL

    >6 months (off-label): 0.5 mL SC x 1 dose ≥10 days before travel

    >9 months: 0.5 mL SC x 1 dose ≥10 days before travel