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 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. FINDINGS: 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. INTERPRETATION: 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.

[Ilheus arbovirus in wild birds (Sporophila caerulescens and Molothrus bonariensis)]. / Arbovírus Ilheus em aves silvestres (Sporophila caerulescens e Molothrus bonariensis).

OBJECTIVE: To report the first Ilheus arboviruses isolated from wild birds and analyze its public health impact. METHODS: Wild birds and mammals were captured using mist nets and Tomahawk traps, respectively. Blood samples were drawn from these animals and inoculated intracerebrally in Swiss suckling mice found in the Parque Ecológico do Tietê, Brazil. The isolates were identified by serological tests, such as hemagglutination, hemagglutination inhibition, complement fixation and neutralization. Besides virus isolation, serum samples were also tested for the presence of hemagglutination inhibition antibodies. RESULTS: Two strains of Ilheus virus were isolated from the bird species Sporophila caerulescens and Molothrus bonariensis. Specific antibodies to Ilheus virus were detected in serum samples of some birds (Columbina talpacoti, Geopelia cuneata, Sicalis flaveola and Molothrus bonariensis), marmosets (Callithrix jacchus and Callithrix penicillata) and coati (Nasua nasua). CONCLUSIONS: Virus isolation and detection of specific antibodies in serum samples of local, migratory and captive birds, captive marmosets and wild coati corroborate the circulation of Ilheus virus in the Parque Ecológico do Tietê. The migrating behavior of some species of wild birds, like Sporophila caerulescens, enables the virus spread to other regions. Taking into consideration its human pathogenicity and the presence of the virus in this area, local authorities should be aware of the risk of infecting the local community.

Human disease caused by an arbovirus closely related to Ilheus virus: report of five cases.

We report five cases of human disease caused by arbovirus in 5 patients from the State of São Paulo, Brazil, residing in the municipalities of Osasco, Atibaia, Guarujá, and the capital São Paulo, respectively. One of the patients resides in São Luis, capital of the State of Maranhão. The sites of infection probably were the states of Paraná and Goiás, both in cave regions, the State of Amazonas, and Rondônia in two cases. Laboratory tests for malaria were negative and 1 patient showed a positive serum reaction for leptospirosis. Serum samples from the acute and convalescent phases were tested by hemagglutination inhibition, complement fixation, and neutralization in mice. Acute phase samples were inoculated into suckling mice by the intracerebral route. A close antigenic relationship was observed between the five agents isolated and the flavivirus Ilheus. Serologic tests demonstrated the absence of antibodies in all samples from the 5 patients during convalescence and even for more than 1 year after infection in 1 of them.

Jungle yellow fever: clinical and laboratorial studies emphasizing viremia on a human case.

The authors report the clinical, laboratorial and epidemiological aspects of a human case of jungle yellow fever. The patient suffered from fever, chills, sweating, headaches, backaches, myalgia, epigastric pains, nausea, vomiting, diarrhea and prostration. He was unvaccinated and had been working in areas where cases of jungle yellow fever had been confirmed. Investigations concerning the yellow fever virus were performed. Blood samples were collected on several days in the course of the illness. Three of these samples (those obtained on days 5, 7 and 10) were inoculated into suckling mice in attempt to isolate virus and to titrate the viremia level. Serological surveys were carried out by using the IgM Antibodies Capture Enzyme Linked Immunosorbent Assay (MAC-ELISA), Complement Fixation (CF), Hemagglutination Inhibition (HI) and Neutralization (N) tests. The yellow fever virus, recovered from the two first samples and the virus titration, showed high level of viremia. After that, specific antibodies appeared in all samples. The interval between the end of the viremia and the appearance of the antibodies was associated with the worsening of clinical symptoms, including bleeding of the mucous membrane. One must be aware of the risk of having a urban epidemics in areas where Aedes aegypti is found in high infestation indexes.

Iguape: a newly recognized flavivirus from São Paulo State, Brazil.

A new virus, SP An 71686, was isolated from sentinel mice exposed in a forest area in Iguape county, São Paulo state, Brazil, in 1979. The results suggest [hemagglutination inhibition (HI), complement fixation, neutralization, and ELISA] that SP An 71686 virus is a new arbovirus and that it demonstrates some cross-reactivity with other members of the family Flaviviridae, but can be differentiated from them. Although there is an intensive circulation of several arboviruses in the area, the only diagnosed cases of human disease were caused by Rocio virus during and after the epidemic of encephalitis that occurred in 1975-1977, one case of febrile illness by Caraparu virus in 1983, and by subtype IF of Venezuelan equine encephalitis virus in soldiers during jungle survival training in 1990. Wild animals had a prevalence of SP An 71686 HI monotype antibodies: 46% of birds captured in 1990, 40% in 1991 and 19.5% in 1992. These results suggested that wild birds may play a role in the virus transmission cycle. Mammals (rodents and marsupials) must also be considered potential hosts. However, the virus reservoir-vector relationships need further studies which would help to clarify the ecology of this virus.

Human fatal yellow fever. Immunohistochemical detection of viral antigens in the liver, kidney and heart.

An immunohistochemical method to detect yellow fever antigen was developed using immune sera from rabbits and hamsters and hyperimmune ascitic fluid from mice. A search for the antigen was carried out in liver, kidney and heart in three fatal cases of yellow fever. In the liver it was present in the cytoplasm of hepatocytes, Councilman bodies and Kupffer cells. Yellow fever antigen was also detected in renal tubular epithelium and in groups of myocardial fibers. These findings suggest that viral replication occurs at sites other than the liver. Since yellow fever shares many features with other haemorrhagic fevers the use of immunohistochemistry can impart a significant improvement in the accuracy of its histopathological diagnosis.

Preliminary characterization of a new virus isolated from the spinal fluid of patients with meningitis in São Paulo, Brazil.

A total of 138 patients with the age of 4 months to 57 years were attended in different hospitals of São Paulo State with aseptic meningitis. A probable new agent was isolated from the cerebrospinal fluid of 35 of 53 specimens examined. Replication of the agent with similar characteristics was detected by CPE produced in the MDCK cell line. Virus-like particles measuring about 40 nm in diameter were observed by negative staining electron microscopy. No hemagglutinating activity was detected at pH 7.2 by using either human, guinea pig, chicken and at pH ranged 6.0-7.2 with goose red blood cells. The agent was not pathogenic to newborn or adult mice. Virus infectivity as measured by CPE was sensitive to chloroform and not inhibited by BuDR, suggesting that agent is an enveloped virus with RNA genome.

Identification of new Guama and Group C serogroup bunyaviruses and an ungrouped virus from Southern Brazil.

From 1975 to 1978, 36 viruses were recovered from humans, bats, birds, sentinel mice and hamsters, and from mosquitoes collected in Coastal Brazil in the state of São Paulo. Identifications of 22 of these 36 viruses have been reported. Six of the remaining 14 isolates were shown to be Guama serogroup bunyaviruses. Two of these six were strains of a newly recognized virus for which the name Cananeia virus is proposed; another is a second newly recognized Guama serogroup virus for which the name Itimirim virus is proposed; a fourth is a strain of Bertioga virus and the other two are strains of Guaratuba virus. Before these studies Guaratuba virus was considered an ungrouped bunyavirus, but cross testing by complement-fixation demonstrated that this virus, and Mirim virus as well, should be considered members of the Guama serogroup. Another six viruses were shown to be strains of a single, newly recognized Group C bunyavirus for which the name Bruconha virus is proposed. Two strains of a single virus were shown by electron microscopy to belong to the family Bunyaviridae, but serologic relationships with other members of this family of viruses were not found; the name Enseada virus is proposed for this newly recognized agent.

Isolation of St. Louis encephalitis virus in South Brazil.

Eight strains of a flavivirus identified as St. Louis encephalitis (SLE) virus were isolated from wild rodents, birds, and sentinel mice in three locations in the State of São Paulo, Brazil from 1967--1969. No illness attributable to SLE virus infection was detected among the local inhabitants, although about 5% of the local population had neutralizing antibodies to this virus.

Emergence of a new arbovirus disease in Brazil. II. Epidemiologic studies on 1975 epidemic.

In April, 1975, an outbreak of human encephalitis caused by Rocio virus, a new flavivirus, occurred in the coastal region of southern São Paulo, Brazil. The epidemic started during the second half of March, 1975, and ended in June, 1975. A total of 465 cases with 61 deaths were recorded, and the overall attack rate was 15 per thousand population. The mortality rate was two per thousand inhabitants and the overall case-fatality rate was 13%. However, the case-fatality rate was markedly decreased when adequate hospital care was provided. The number of cases in the 15--30 years age group was higher than in the other age groups and the rate was higher in males than in females. Lack of evidence of person-to-person transmission, based on a study of families involved in the epidemic and on the antigenic relationship to other mosquito-borne flaviviruses, suggested that the virus was transmitted by a vector and that wild animals were involved in the virus cycle.

Emergence of a new arbovirus disease in Brazil. I. Isolation and characterization of the etiologic agent, Rocio virus.

In April, 1975, an epidemic of human encephalitis was detected in several counties in the State of São Paulo, Brazil; the epidemic continued into 1976. A virus was isolated from central nervous system (CNS) tissues of a 39-year-old male who died on December 8, 1975; the virus was found to be a new flavivirus for which the name Rocio virus is proposed. Nine further isolations of Rocio virus were obtained from CNS tissues of 17 patients who died with clinical symptoms of encephalitis. Isolations of virus and serologic evidence of Rocio virus infection in a significant proportion of the encephalitis patients suggested that Rocio virus was the etiologic agent of the epidemic. Rocio virus was isolated only from patients who died within 5 days of onset of illness. The virus was isolated from two sentinel mice exposed in the epidemic zone and from a rufous collared sparrow (Zonotrichia capensis) collected in the area.