Primary prevention
Prevention is critical for reducing morbidity and mortality, as there are currently no treatments for the management of yellow fever except for supportive care. Vaccination and avoidance of mosquito bites are the recommended prevention strategies.
Immunisation with the live-attenuated 17D vaccine is recommended in people aged ≥9 months who are travelling to, or living in, areas with risk for yellow fever transmission (e.g., Africa, South America). The vaccine should be administered at least 10 days before travel.[19] Due to the current outbreak in Brazil, the World Health Organization (WHO) recommends yellow fever vaccination for international travellers visiting Brazil.[20][21]
CDC: yellow fever travel information Opens in new window
The UK Medicines and Healthcare products Regulatory Agency (MRHA) has introduced a standardised pre-vaccination checklist to ensure the yellow fever vaccine is indicated for specific travel destinations and to identify existing contraindications or precautions in individuals before vaccination.
MHRA: yellow fever vaccine (Stamaril): new pre-vaccination checklist Opens in new window
Laboratory workers who are at risk of infection should also be vaccinated.[19]
The WHO currently recommends a single primary dose of the vaccine (administered subcutaneously) to confer lifelong immunity; there is no longer a requirement for a 10-year booster.[22] However, while the US Centers for Disease Control and Prevention (CDC)'s Advisory Committee on Immunization Practices (ACIP) agrees that this is adequate for most travellers, it recommends additional doses for the following groups of travellers:[19]
Women who were pregnant when they received their initial dose of vaccine (they should receive one additional dose before their next at-risk travel)
People who received a haematopoietic stem cell transplant after receiving a dose of vaccine (they should receive one additional dose before their next at-risk travel, provided they are sufficiently immunocompetent)
People infected with HIV when they received their last dose of vaccine (they should receive a dose every 10 years if they continue to be at risk of infection).
Furthermore, the ACIP recommendations specify that a booster dose can be considered for travellers who received their last dose ≥10 years ago and who will be in a higher-risk setting based on location, season, duration of travel, and activities (e.g., prolonged periods in endemic areas). Laboratory workers who handle the virus should have antibody titres measured at least every 10 years to determine whether they should receive additional doses of the vaccine.[19] Not all authorities agree with the WHO’s interpretation of the available data.[23]
The WHO recommends that one fifth of the regular dose (fractional dosing) can be used to control an outbreak in cases of vaccine shortages.[24] Fractional dosing has been shown to be effective at inducing seroconversion in patients who were seronegative at baseline, and that titres remained above the threshold for seropositivity at 1 year after vaccination in 97% of participants.[25] One long-term study found that fractional dosing induced a protective response that lasted for more than 10 years after vaccination in 98% of patients (compared to 97% of patients who received the standard dose).[26]
According to the CDC, the vaccine is contraindicated in infants <6 months old, people with an allergy to any of the vaccine components (desensitisation can be performed if immunisation is considered essential), thymus disorder associated with abnormal immune-cell function, symptomatic HIV infection or CD4 count of <200 cells/mm³ (or <15% of total lymphocytes in children ages <6 years), primary immunodeficiencies, malignant neoplasms, organ transplant patients, and patients on immunosuppressive or immunomodulatory therapies. It should be used with caution in infants 6-8 months old, adults ≥60 years old, asymptomatic HIV infection and a CD4 count of 200-499 cells/mm³ (or 15% to 24% of total lymphocytes in children ages <6 years), and pregnant women or women who are breastfeeding.[10]
While the vaccine is considered safe and effective, an increased risk of life-threatening adverse reactions have been reported in patients who are immunosuppressed, have a thymus disorder, or are ≥60 years old. Serious adverse effects include vaccine-related viscerotropic disease (a disease similar to wild-type disease) and neurotropic disease (e.g., meningoencephalitis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, cranial nerve palsies).[19][27] The rate of these events, according to one comprehensive review, is in the order of 0 to 14.6 per million doses; however, an increased rate of complications was noted in people aged ≥60 years, and in immunocompromised people.[27] More common adverse effects include mild systemic effects, such as low-grade fever, headache, and myalgia that begin with days after vaccination, and last 5-10 days.[10] One small study of yellow fever vaccination of patients with multiple sclerosis (MS) showed an increased risk of MS exacerbation, underscoring the need for a careful assessment of the risk-benefit ratio when recommending yellow fever immunisation in these patients.[28] The vaccine causes low-level viraemia in 50% of patients. While this viraemia is usually clinically irrelevant, it can cause significant problems in pregnant or immunocompromised patients.[29][30]
Simultaneous administration of the yellow fever vaccine with the measles mumps rubella vaccine has been shown to result in mutual interference, with lower seroconversion rates for both vaccines than expected.[31] Live viral vaccines should either be given at the same time or spaced by at least 30 days if simultaneous administration is not possible.[10]
Due to the risk of very rare but potentially fatal adverse reactions, the Medicines and Healthcare products Regulatory Agency in the UK recommends the following additional measures:[32]
Do not administer the vaccine to people who have had their thymus gland removed, are taking immunosuppressive or immunomodulating biological drugs, or have a first-degree relative with a family history of yellow fever vaccine-related viscerotropic or neurotropic disease not related to a known medical risk factor
Use caution in patients aged 60 years or older; only administer when there is a significant and unavoidable risk of acquiring yellow fever infection (e.g., travel to an area where there is a current or periodic risk of yellow fever transmission)
Only healthcare professionals who are specifically trained in evaluating the benefits and risks of yellow fever vaccine should administer the vaccine, and only after an individualised assessment of a person's travel itinerary and suitability to receive the vaccine.
Some countries require proof of vaccination before entry.[19] A completed International Certificate of Vaccination or Prophylaxis is valid for the lifetime of the vaccinee, with the requirement for the 10-year booster removed in June 2016. Despite this, physicians and travellers should review the entry requirements for specific countries.
Protection against mosquito bites
Avoidance of mosquito bites reduces the risk of yellow fever. Travellers should be instructed to use an insect repellent on exposed skin to repel mosquitoes in areas of risk. EPA-registered repellents include products containing DEET and picaridin. DEET concentrations of 30% to 50% are effective for several hours. Picaridin, available at 7% and 15% concentrations, requires more frequent application. DEET formulations as high as 50% are recommended for both adults and children over 2 months of age. Infants less than 2 months of age should be protected by using a carrier draped with mosquito netting with an elastic edge for a tight fit. When using sunscreen, the sunscreen should be applied first and then repellent. Repellent should be washed off at the end of the day before going to bed.
Travellers to endemic areas should wear tucked-in long-sleeved shirts, long trousers, and hats to cover exposed skin. Permethrin-containing (e.g., permanone) or other insect repellents should be applied to clothing, shoes, tents, mosquito nets, and other gear for greater protection. Most repellent is generally removed from clothing and gear by a single washing, but permethrin-treated clothing is effective for up to 5 washings. The peak biting time for many mosquito species is dusk to dawn; however, Aedes aegypti, the most effective vector of the yellow fever virus in Africa, feeds during the daytime. The CDC recommends to take extra care to use repellent and protective clothing during daytime, as well as evening and early morning, or to consider avoiding outdoor activities during these times when in areas where yellow fever is a risk.[33]
Secondary prevention
Yellow fever is a notifiable disease in some countries. As the diagnosis of a viral haemorrhagic fever, including yellow fever, may indicate the possibility of bioterrorism, local health authorities should be contacted urgently.[48][49][50]
Patient-to-patient or patient-to-provider transmission does not occur, but patients should be isolated and protected from further mosquito exposure (e.g., staying indoors) for up to 5 days following onset of fever to break the transmission cycle.
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