Investigation of patients testing positive for yellow fever viral RNA after vaccination during a mass yellow fever vaccination campaign — Angola, 2016

The yellow fever outbreak declared in Angola in January 2016 soon became the largest recorded yellow fever outbreak in the country’s history. In response, the Angola Ministry of Health, supported by the World Health Organization (WHO), conducted mass yellow fever vaccination campaigns beginning in February 2016 for all persons aged ≥6 months. By June 2016, a total of 11.6 million yellow fever vaccine doses had been distributed among a national population of 25 million. Because of the urgency of distributing vaccine to stop the outbreak, surveillance for cases of yellow fever after vaccination and serious adverse events after immunization (AEFIs) was not implemented. However, CDC and the Angola Field Epidemiology and Laboratory Training Program conducted an investigation of patients with a history of yellow fever vaccination and symptoms of yellow fever disease whose specimens tested positive for yellow fever viral RNA by reverse transcription–polymerase chain reaction (RT-PCR) to assess whether such cases could represent vaccine failure or AEFIs. Although no yellow fever vaccine efficacy studies have been conducted, the vaccine is reliably immunogenic; worldwide, only five postvaccine yellow fever cases have been described (1). Neutralizing antibodies develop by day 10 after vaccination in 80% of yellow fever vaccinees (1). Primary yellow fever vaccine recipients have self-limited, vaccine-derived, physiologic viremia, typically during days 3–4, although this postvaccination viremia can last as long as 2 weeks. Thus, the detection of yellow fever viral RNA by RT-PCR testing before postvaccination day 3 or after day 13 could represent wild-type infection (acquired either before vaccination or later if there is vaccine failure) or yellow fever vaccine-associated viscerotropic disease (YEL-AVD), a rare but serious AEFI in which the vaccine-derived virus proliferates in multiple organs after primary vaccination. The symptoms of YEL-AVD are similar to those of naturally acquired yellow fever, typically beginning by postvaccination day 10; vaccine-derived viremia can persist beyond day 13. The risk for YEL-AVD is 0.3–0.4 cases per 100,000 yellow fever vaccine doses distributed among U.S. travelers; however, risk estimates in the context of mass vaccination campaigns in Africa are limited (2). Therefore, symptom onset within 10 days after vaccination and viremia on or after day 3 could represent YEL-AVD, physiologic viremia, or yellow fever after vaccine failure.