Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases

Background The yellow fever vaccine is regarded as one of the safest attenu ated virus vaccines. with few side-effects or adverse events. We report the occurrence of two fatal cases of haemorrhagic fever associated with yellow fever 17DD substrain vaccine in Brazil. Methods We obtained epidemiological, serological, virological, pathological , immunocytochemical, and molecular biological data on the two cases to det ermine the cause of the illnesses. Findings The first case, in a 5-year-old white girl, was characterised by s udden onset of fever accompanied by headache. malaise, and vomiting 3 days after receiving yellow fever and measles-mumps-rubella vaccines. Afterwards she decompensated with icterus and haemorrhagic signs and died after a 5-d ay illness. The second patient-a 22-year-old black woman-developed a sore t hroat and fever accompanied by headache, myalgia, nausea, and vomiting 4 da ys after yellow fever vaccination. She then developed icterus, renal failur e, and haemorrhagic diathesis, and died after 6 days of illness. Yellow fev er virus was recovered in suckling mice and C6/36 cells from blood in both cases, as well as from fragments of liver, spleen, skin, and heart from the first case and from these and other viscera fragments in case 2. RNA of ye llow fever virus was identical to that previously described for 17D genomic sequences. IgM ELISA tests for yellow fever virus were negative in case 1 and positive in case 2; similar tests for dengue, hantaviruses, arenaviruse s, Leptospira, and hepatitis viruses A-D were negative. Tissue injuries fro m both patients were typical of wild-type yellow fever. Interpretation These serious and hitherto unknown complications of yellow f ever vaccination are extremely rare. but the safety of yellow fever 17DD va ccine needs to be reviewed. Host factors, probably idiosyncratic reactions, might have had a substantial contributed to the unexpected outcome.