A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil.

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Detection of a new yellow fever virus lineage within the South American genotype I in Brazil.

Nucleotide sequences of two regions of the genomes of 11 yellow fever virus (YFV) samples isolated from monkeys or humans with symptomatic yellow fever (YF) in Brazil in 2000, 2004, and 2008 were determined with the objective of establishing the genotypes and studying the genetic variation. Results of the Bayesian phylogenetic analysis showed that sequences generated from strains from 2004 and 2008 formed a new subclade within the clade 1 of the South American genotype I. The new subgroup is here designated as 1E. Sequences of YFV strains recovered in 2000 belong to the subclade 1D, which comprises previously characterized YFV strains from Brazil. Molecular dating analyses suggested that the new subclade 1E started diversifying from 1D about 1975 and that the most recent 2004-2008 isolates arose about 1985.

[Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009]. / Febre amarela silvestre: reemergência de transmissão no estado de São Paulo, Brasil, 2009.

OBJECTIVE: To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. METHODS: This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. RESULTS: Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. CONCLUSIONS: The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but further studies are required to clarify the dynamics of the spread of this disease.

Yellow fever epizootics in non-human primates, São Paulo state, Brazil, 2008-2009.

Since 2000, the expansion of Sylvatic Yellow Fever (YF) has been observed in the southeast of Brazil, being detected in areas considered silent for decades. Epizootics in non-human primates (NHPs) are considered sentinel events for the detection of human cases. It is important to report epizootic events that could have impact on the conservation status of susceptible species. We describe the epizootics in NHPs, notified in state of São Paulo, Brazil, between September 2008 to August 2009. Ninety-one epizootic events, involving 147 animals, were reported in 36 counties. Samples were obtained from 65 animals (44.2%). Most of the epizootics (46.6%) were reported between March and April, the same period during which human cases of YF occurred in the state. Biological samples were collected from animals found dead and were sent to Instituto Adolfo Lutz, in São Paulo. Two samples, collected in two counties without an indication for YF vaccination, were positive for the virus. Another 48 animals were associated with YF by clinical-epidemiological linkage with laboratory confirmed cases. Because the disease in human and NHPs occurred in the same period, the detection of the virus in NHPs did not work as sentinel, but aided in the delineation of new areas of risk.

Isolation of yellow fever virus (YFV) from naturally infected Haemagogus (Conopostegus) leucocelaenus (diptera, cukicudae) in São Paulo State, Brazil, 2009.

After detecting the death of Howlers monkeys (genus Alouatta) and isolation of yellow fever virus (YFV) in Buri county, São Paulo, Brazil, an entomological research study in the field was started. A YFV strain was isolated from newborn Swiss mice and cultured cells of Aedes albopictus - C6/36, from a pool of six Haemagogus (Conopostegus) leucocelaenus (Hg. leucocelaenus) mosquitoes (Dyar & Shannon) collected at the study site. Virus RNA fragment was amplified by RT-PCR and sequenced. The MCC Tree generated showed that the isolated strain is related to the South American I genotype, in a monophyletic clade containing isolates from recent 2008-2010 epidemics and epizootics in Brazil. Statistical analysis commonly used were calculated to characterize the sample in relation to diversity and dominance and indicated a pattern of dominance of one or a few species. Hg. leucocelaenus was found infected in Rio Grande do Sul State as well. In São Paulo State, this is the first detection of YFV in Hg. leucocelaenus.

Febre amarela silvestre: reemergência de transmissão no estado de São Paulo, Brasil, 2009* / Yellow fever: reemerging in the state of São Paulo, Brazil, 2009

Descrever a investigação do surto de febre amarela silvestre e as principais medidas de controle realizadas no estado de São Paulo. MÉTODOS: Estudo descritivo do surto de febre amarela silvestre na região sudoeste do estado, entre fevereiro e abril de 2009. Foram avaliados casos suspeitos e confirmados em humanos e primatas não humanos. A investigação entomológica, em ambiente silvestre, envolveu captura em solo e copa de árvore para identificação das espécies e detecção de infecção natural. Foram realizadas ações de controle de Aedes aegypti em áreas urbanas. A vacinação foi direcionada para residentes dos municípios com confirmação de circulação viral e nos municípios contíguos, conforme recomendação nacional. RESULTADOS: Foram confirmados 28 casos humanos (letalidade 39,3%) em áreas rurais de Sarutaiá, Piraju, Tejupá, Avaré e Buri. Foram notificadas 56 mortes de primatas não humanos, 91,4% do gênero Alouatta sp. A epizootia foi confirmada laboratorialmente em dois primatas não humanos, sendo um em Buri e outro em Itapetininga. Foram coletados 1.782 mosquitos, entre eles Haemagogus leucocelaenus, Hg. janthinomys/capricornii, Sabethes chloropterus, Sa. purpureus e Sa. undosus. O vírus da febre amarela foi isolado de um lote de Hg. leucocelaenus procedente de Buri. A vacinação foi realizada em 49 municípios, com 1.018.705 doses aplicadas e o registro de nove eventos adversos graves pós-vacinação. CONCLUSÕES: Os casos humanos ocorreram entre fevereiro e abril de 2009 em áreas sem registro de circulação do vírus da febre amarela há mais de 60 anos. A região encontrava-se fora da área com recomendação de vacinação, com alto percentual da população suscetível. A adoção oportuna de medidas de controle permitiu a interrupção da transmissão humana em um mês, assim como a confirmação da circulação viral em humanos, primatas não humanos e mosquitos. Os isolamentos facilitaram a identificação das áreas de circulação viral, mas são importantes novos estudos para esclarecer a dinâmica de transmissão da doença...

A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Yellow fever epizootics in non-human primates, São Paulo state, Brazil, 2008-2009 / Epizootias de febre amarela em primatas não humanos no estado de São Paulo, Brasil, 2008-2009

Since 2000, the expansion of Sylvatic Yellow Fever (YF) has been observed in the southeast of Brazil, being detected in areas considered silent for decades. Epizootics in non-human primates (NHPs) are considered sentinel events for the detection of human cases. It is important to report epizootic events that could have impact on the conservation status of susceptible species. We describe the epizootics in NHPs, notified in state of São Paulo, Brazil, between September 2008 to August 2009. Ninety-one epizootic events, involving 147 animals, were reported in 36 counties. Samples were obtained from 65 animals (44.2%). Most of the epizootics (46.6%) were reported between March and April, the same period during which human cases of YF occurred in the state. Biological samples were collected from animals found dead and were sent to Instituto Adolfo Lutz, in São Paulo. Two samples, collected in two counties without an indication for YF vaccination, were positive for the virus. Another 48 animals were associated with YF by clinical-epidemiological linkage with laboratory confirmed cases. Because the disease in human and NHPs occurred in the same period, the detection of the virus in NHPs did not work as sentinel, but aided in the delineation of new areas of risk.

Desde 2000, vem sendo observada a expansão da febre amarela (FA) no Sudeste do Brasil, sendo detectados casos em áreas consideradas silenciosas por décadas. Epizootias em primatas não humanos (NHPs) são considerados eventos sentinela para a detecção de casos humanos. É importante relatar eventos epizoóticos que podem ter impacto sobre o estado de conservação de espécies sensíveis. Descrevemos as epizootias, notificadas em NHPs no estado de São Paulo, Brasil, entre setembro de 2008 a agosto de 2009. Noventa e um eventos epizoóticos, envolvendo 147 animais, foram notificados em 36 municípios. As amostras foram obtidas a partir de 65 animais (44,2%). A maioria das epizootias (46,6%) foram registradas entre março e abril, no mesmo período no qual YF em que casos humanos ocorreram no estado. As amostras biológicas foram coletadas de animais encontrados mortos e enviadas ao Instituto Adolfo Lutz, em São Paulo. Duas amostras, coletadas em dois municípios, sem indicação para a vacinação de febre amarela, foram positivos para o vírus. Outros 48 animais foram associados com FA por vínculo clínico-epidemiológico com casos confirmados laboratorialmente. Devido a doença em humanos e NHPs terem ocorrido no mesmo período, a detecção do vírus em NHPs não funcionou como sentinela, mas ajudou no processo de delimitação de novas áreas de risco.

Febre amarela silvestre: reemergencia de transmissao no estado de Sao Paulo, Brasil, 2009 / Fiebre amarilla silvestre: re emergencia de transmision en el estado de Sao Paulo, Brasil, 2009 / Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009

OBJETIVO Descrever a investigação do surto de febre amarela silvestre e as principais medidas de controle realizadas no estado de São Paulo. MÉTODOS Estudo descritivo do surto de febre amarela silvestre na região sudoeste do estado, entre fevereiro e abril de 2009. Foram avaliados casos suspeitos e confirmados em humanos e primatas não humanos. A investigação entomológica, em ambiente silvestre, envolveu captura em solo e copa de árvore para identificação das espécies e detecção de infecção natural. Foram realizadas ações de controle de Aedes aegypti em áreas urbanas. A vacinação foi direcionada para residentes dos municípios com confirmação de circulação viral e nos municípios contíguos, conforme recomendação nacional. RESULTADOS Foram confirmados 28 casos humanos (letalidade 39,3%) em áreas rurais de Sarutaiá, Piraju, Tejupá, Avaré e Buri. Foram notificadas 56 mortes de primatas não humanos, 91,4% do gênero Alouatta sp . A epizootia foi confirmada laboratorialmente em dois primatas não humanos, sendo um em Buri e outro em Itapetininga. Foram coletados 1.782 mosquitos, entre eles Haemagogus leucocelaenus , Hg. janthinomys/capricornii , Sabethes chloropterus , Sa. purpureus e Sa. undosus . O vírus da febre amarela foi isolado de um lote de Hg. leucocelaenus procedente de Buri. A vacinação foi realizada em 49 municípios, com 1.018.705 doses aplicadas e o registro de nove eventos adversos graves pós-vacinação. CONCLUSÕES Os casos humanos ocorreram entre fevereiro e abril de 2009 em áreas sem registro de circulação do vírus da febre amarela há mais de 60 anos. A região encontrava-se fora da área com recomendação de vacinação, com alto percentual da p...

OBJETIVO Describir la investigación de brote de fiebre amarilla silvestre y las principales medidas de control realizadas en el estado de Sao Paulo. MÉTODOS Estudio descriptivo del brote de fiebre amarilla silvestre en la región suroeste del Estado, entre febrero y abril de 2009. Se evaluaron casos sospechosos y confirmados en humanos y primates no humanos. La investigación entomológica, en ambiente silvestre, involucró capturo en suelo y copa de árboles para identificación de las especies y detección de infección natural. Se realizaron acciones de control de Aedes aegypti en áreas urbanas. La vacunación fue direccionada a residentes de los municipios con confirmación de circulación viral y en los municipios contiguos, siguiendo recomendación nacional. RESULTADOS Se confirmaron 28 casos en humanos (letalidad 39,3%) en áreas rurales de Sarutaiá, Pirajú, Tejupá, Avaré y Buri. Se notificaron 56 muertes de primates no humanos, 91,4% del género Allouatta sp. La epizootia fue confirmada laboratorialmente en dos primates no humanos siendo uno de Buri y el otro de Itapetininga. Se colectaron 1.782 mosquitos, entre ellos Haemagogus leucocelaenus, Hg. janthinomys/capricornii, y Sabethes chloropterus, Sa. purpureus y Sa. undosus. El virus de la fiebre amarilla fue aislado de un lote de Hg. leucocelaenus procedente de Buri. La vacunación fue realizada en 49 municipios, con 1.018.705 dosis aplicadas y el registro de nueve eventos adversos graves post-vacunación. CONCLUSIONES Los casos humanos ocurrieron entre febrero a abril de 2009 en áreas sin registro de circulación del virus de la fiebre amarilla por más de 60 años. La región se encontraba fuera del área de recomendación de vacunación, con alto porcentaje de población susceptible. La adopción oportuna de medidas de control permitió ...

OBJECTIVE To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. METHODS This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. RESULTS Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. CONCLUSIONS The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but ...

Isolation of yellow fever virus (YFV) from naturally infectied Haemagogus (Conopostegus) leucocelaenus (diptera, cukicudae) in São Paulo State, Brazil, 2009 / Isolamento do vírus da Febre Amarela de mosquitos naturalmente infectados Haemagogus (Conopostegus) leucocelaenus (Diptera, Culicidae), São Paulo, Brasil, 2009

After detecting the death of Howlers monkeys (genus Alouatta) and isolation of yellow fever virus (YFV) in Buri county, São Paulo, Brazil, an entomological research study in the field was started. A YFV strain was isolated from newborn Swiss mice and cultured cells of Aedes albopictus - C6/36, from a pool of six Haemagogus (Conopostegus) leucocelaenus (Hg. leucocelaenus) mosquitoes (Dyar & Shannon) collected at the study site. Virus RNA fragment was amplified by RT-PCR and sequenced. The MCC Tree generated showed that the isolated strain is related to the South American I genotype, in a monophyletic clade containing isolates from recent 2008-2010 epidemics and epizootics in Brazil. Statistical analysis commonly used were calculated to characterize the sample in relation to diversity and dominance and indicated a pattern of dominance of one or a few species. Hg. leucocelaenus was found infected in Rio Grande do Sul State as well. In São Paulo State, this is the first detection of YFV in Hg. leucocelaenus.

Após a detecção de morte de macacos Bugios (gênero Alouatta) e isolamento do vírus da Febre Amarela (YFV) no município de Buri, Estado de São Paulo, Brasil, foi iniciada uma investigação entomológica em campo. Uma cepa de YFV foi isolada em camundongos recém-nascidos e cultura de células de Aedes albopictus - C6/36, a partir de um lote de seis mosquitos Haemagogus (Conopostegus) leucocelaenus (Hg leucocelaenus) Dyar & Shannon coletados no local de estudo. RNA do vírus foi amplificado por RT-PCR e seqüenciado. A topologia gerada indica que a cepa isolada está relacionada ao genótipo South American I, em clado monofilético englobando isolados recentes de epidemias e epizootias entre 2008 e 2009. Análises estatísticas geralmente usadas caracterizaram a amostra em relação à diversidade e dominância, indicando dominância relativa de uma ou poucas espécies. Hg. leucocelaenus foi detectado infectado também no Rio Grande do Sul. No Estado de São Paulo trata-se da primeira detecção do YFV em Hg leucocelaenus.

Ocorrência de Dengue no Estado de Säo Paulo, Brasil, de 1986 a 1996 / Occurence of dengue in Säo Paulo State, Brazil from 1986 to 1996

Desde 1986 casos de dengue vêm sendo detectados no Estado de Säo Paulo. De abril de 1986 a agosto de 1996, foram testadas 61.816 amostras de casos suspeitos, dos quais 21.891 foram confirmados, sendo 20.70 autóctones. A confirmaçäo foi feita por sorologia específica e/ou isolamento de vírus, critérios adotados pela Secretaria de Saúde do Estado de Säo Paulo. A incidência de dengue no período de 1987 a 1996 variou de 0,14 a 20,20 por 100.000 habitantes. As maiores incidências ocorreram nos veröes de 1990/1991, 1995 e 1996. Nestes anos a transmissäo ocorreu em 59, 101 e 114 municípios do Estado, o que representa 18,0(por cento), 24,3(por cento) e 27,3(por cento) dos municípios com infestaçäo domiciliar por Aedes aegypti. O sorotipo 1 foi o único identificado em casos autóctones até 1996, quando ocorreram dois isolamentos de Dengue tipo 2. Os dados apresentados analisam as atividades do sistema de vigilância epidemiológica relacionadas com a detecçäo de casos e diagnóstico laboratorial