title: Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases.
abstract: BACKGROUND
  The yellow fever vaccine is regarded as one of the safest attenuated 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 determine the cause of the illnesses.
  
  
  RESULTS
  The first case, in a 5-year-old white girl, was characterised by sudden 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-day illness. The second patient-a 22-year-old black woman-developed a sore throat and fever accompanied by headache, myalgia, nausea, and vomiting 4 days after yellow fever vaccination. She then developed icterus, renal failure, and haemorrhagic diathesis, and died after 6 days of illness. Yellow fever 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 yellow 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, arenaviruses, Leptospira, and hepatitis viruses A-D were negative. Tissue injuries from both patients were typical of wild-type yellow fever.
  
  
  CONCLUSIONS
  These serious and hitherto unknown complications of yellow fever vaccination are extremely rare, but the safety of yellow fever 17DD vaccine needs to be reviewed. Host factors, probably idiosyncratic reactions, might have had a substantial contributed to the unexpected outcome.
authors.affiliation: Instituto Evandro Chagas/Fundação Nacional de Saúde (FUNASA), Belém, Brazil. pedrovasconcelos@iec.pa.gov.br
authors.forename: P F
authors.initials: PF
authors.lastname: Vasconcelos
authors.forename: E J
authors.initials: EJ
authors.lastname: Luna
authors.forename: R
authors.initials: R
authors.lastname: Galler
authors.forename: L J
authors.initials: LJ
authors.lastname: Silva
authors.forename: T L
authors.initials: TL
authors.lastname: Coimbra
authors.forename: V L
authors.initials: VL
authors.lastname: Barros
authors.forename: T P
authors.initials: TP
authors.lastname: Monath
authors.forename: S G
authors.initials: SG
authors.lastname: Rodigues
authors.forename: C
authors.initials: C
authors.lastname: Laval
authors.forename: Z G
authors.initials: ZG
authors.lastname: Costa
authors.forename: M F
authors.initials: MF
authors.lastname: Vilela
authors.forename: C L
authors.initials: CL
authors.lastname: Santos
authors.forename: P M
authors.initials: PM
authors.lastname: Papaiordanou
authors.forename: V A
authors.initials: VA
authors.lastname: Alves
authors.forename: L D
authors.initials: LD
authors.lastname: Andrade
authors.forename: H K
authors.initials: HK
authors.lastname: Sato
authors.forename: E S
authors.initials: ES
authors.lastname: Rosa
authors.forename: G B
authors.initials: GB
authors.lastname: Froguas
authors.forename: E
authors.initials: E
authors.lastname: Lacava
authors.forename: L M
authors.initials: LM
authors.lastname: Almeida
authors.forename: A C
authors.initials: AC
authors.lastname: Cruz
authors.forename: I M
authors.initials: IM
authors.lastname: Rocco
authors.forename: R T
authors.initials: RT
authors.lastname: Santos
authors.forename: O F
authors.initials: OF
authors.lastname: Oliva
authors.forename: C M
authors.initials: CM
authors.lastname: Papaiordanou
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D001344:Autopsy; D001938:Brazil / Q000453:epidemiology; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D017809:Fatal Outcome; D005260:Female; D005334:Fever / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D006261:Headache / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007565:Jaundice / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D010612:Pharyngitis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D016415:Sequence Alignment; D014613:Vaccines, Attenuated / Q000009:adverse effects; D014839:Vomiting / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D022341:Yellow Fever Vaccine / Q000009:adverse effects*; D015005:Yellow fever virus / Q000235:genetics
chemical_list: D004279:DNA, Viral; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine