Epidemiological profile of a cohort of symptomatic pregnant women with suspected Zika virus infection in the State of São Paulo, Brazil, 2015-2018. / Perfil epidemiológico de uma coorte de gestantes sintomáticas com suspeita de Zika no estado de São Paulo, 2015-2018.

OBJECTIVE: To describe the epidemiological profile of pregnant women with suspected Zika virus infection, reported on the Center for Strategic Information for Health Surveillance System, in the state of São Paulo, Brazil, its range of abnormalities and/or pregnancy outcomes. METHODS: Descriptive epidemiological study of a cohort of symptomatic pregnant women with suspected Zika virus infection and their pregnancy outcomes, living in the state of São Paulo, reported between 2015-2018. RESULTS: Of the 2,329 pregnant women studied, 29.3% were confirmed to have the infection, almost half of them were single (44.8%), the majority of them were white woman (74.2%), with complete high school education (53.6%), and concentrated in the northeast region of the state. The proportion of newborns with central nervous system abnormalities was approximately 4.0%. CONCLUSION: The results found characterize Zika virus transmission in the state of São Paulo and may support public health actions in places with higher risk of disease transmission.

The role of pregnant women with rash in the Zika virus sentinel surveillance.

INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS: Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

The role of pregnant women with rash in the Zika virus sentinel surveillance

Abstract INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

The role of pregnant women with rash in the Zika virus sentinel surveillance

INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

Descriptive report of cases of congenital syndrome associated with Zika virus infection in the state of São Paulo, Brazil, from 2015 to 2017. / Descrição dos casos de síndrome congênita associada à infecção pelo ZIKV no estado de São Paulo, no período 2015 a 2017.

OBJECTIVE: to characterize cases of congenital syndrome associated with Zika virus infection (CZS) and other infectious etiologies, resident in the state of São Paulo, Brazil, from October 30, 2015, to June 30, 2017. METHODS: this was a descriptive study of suspected cases of CZS and other infectious etiologies notified on the Public Health Events Registry. RESULTS: 960 cases were investigated up to epidemiological week 26/2017, and 146 were confirmed for congenital infection; of these, 59 (40.4%) were confirmed for congenital infection without etiological identification and 87 (59.6%) with laboratory confirmation, of which 55 were congenital syndrome associated with Zika virus and 32 were congenital syndrome associated with other infectious agents. CONCLUSION: this study enabled the detection of 23.9% CZS cases among suspected cases of infectious etiology.

Descrição dos casos de síndrome congênita associada à infecção pelo ZIKV no estado de São Paulo, no período 2015 a 2017 / Descripción de los casos de síndrome congénita asociada a la infección por el virus Zika en el estado de São Paulo, Brasil, en el período de 2015 a 2017 / Descriptive report of cases of congenital syndrome associated with Zika virus infection in the state of São Paulo, Brazil, from 2015 to 2017

Objetivo: caracterizar os casos de síndrome congênita associada à infecção pelo ZIKV (SCZ) e outras etiologias infeciosas, residentes no estado de São Paulo, Brasil, no período de 30 de outubro de 2015 a 30 de junho de 2017. Métodos: estudo descritivo dos casos suspeitos de SCZ e outras etiologias infecciosas notificados no Registro de Eventos em Saúde Pública. Resultados: foram investigados 960 casos até a semana epidemiológica 26/2017, sendo confirmados 146 para infecção congênita; destes, 59 (40,4%) foram confirmados para infecção congênita sem identificação etiológica e 87 (59,6%) com confirmação laboratorial, sendo 55 com SCZ e 32 com síndrome congênita associada a outros agentes infecciosos. Conclusão: este estudo permitiu detectar 23,9% de casos de SCZ entre os casos suspeitos de etiologia infecciosa.

Objetivo: caracterizar los casos sospechosos de síndrome congénita asociada a la infección por virus Zika (SCZ) y otras etiologías infecciosas residentes en el estado de São Paulo, Brasil, en el período de 30 de octubre de 2015 a 30 de junio de 2017. Métodos: estudio descriptivo de los casos sospechosos de síndrome congénita asociada a la infección por el virus Zika y otras etiologías infecciosas notificadas en el Registro de Eventos en Salud Pública. Resultados: se han investigado 960 casos hasta la semana epidemiológica 26/2017, siendo confirmados 146 para la infección congénita; de estos, 59 fueron confirmados para infección congénita sin identificación etiológica y 87 con identificación etiológica, siendo 55 síndrome congénita asociados al virus Zika y 32 síndrome congénita asociado a otros agentes infecciosos. Conclusión: este estudio permitió detectar una tasa del 23,9% de casos de SCZ entre los casos sospechosos de etiología infecciosa.

Objective: to characterize cases of congenital syndrome associated with Zika virus infection (CZS) and other infectious etiologies, resident in the state of São Paulo, Brazil, from October 30, 2015, to June 30, 2017. Methods: this was a descriptive study of suspected cases of CZS and other infectious etiologies notified on the Public Health Events Registry. Results: 960 cases were investigated up to epidemiological week 26/2017, and 146 were confirmed for congenital infection; of these, 59 (40.4%) were confirmed for congenital infection without etiological identification and 87 (59.6%) with laboratory confirmation, of which 55 were congenital syndrome associated with Zika virus and 32 were congenital syndrome associated with other infectious agents. Conclusion: this study enabled the detection of 23.9% CZS cases among suspected cases of infectious etiology.

Probable transfusion-transmitted Zika virus in Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.

First Complete Genome Sequence of Zika Virus (Flaviviridae, Flavivirus) from an Autochthonous Transmission in Brazil.

We report here the genome sequence of Zika virus, strain ZikaSPH2015, containing all structural and nonstructural proteins flanked by the 5' and 3' untranslated region. It was isolated in São Paulo state, Brazil, in 2015, from a patient who received a blood transfusion from an asymptomatic donor at the time of donation.

São Paulo urban heat islands have a higher incidence of dengue than other urban areas

Urban heat islands are characterized by high land surface temperature, low humidity, and poor vegetation, and considered to favor the transmission of the mosquito-borne dengue fever that is transmitted by the Aedes aegypti mosquito. We analyzed the recorded dengue incidence in Sao Paulo city, Brazil, in 2010-2011, in terms of multiple environmental and socioeconomic variables. Geographical information systems, thermal remote sensing images, and census data were used to classify city areas according to land surface temper- ature, vegetation cover, population density, socioeconomic status, and housing standards. Of the 7415 dengue cases, a majority (93.1%) mapped to areas with land surface temperature >28 ◦ C. The dengue incidence rate (cases per 100,000 inhabitants) was low (3.2 cases) in high vegetation cover areas, but high (72.3 cases) in low vegetation cover areas where the land surface temperature was 29 ± 2 ◦ C. Interestingly, a multiple cluster analysis phenogram showed more dengue cases clustered in areas of land surface temperature >32 ◦ C, than in areas characterized as low socioeconomic zones, high population density areas, or slum-like areas. In laboratory experiments, A. aegypti mosquito larval development, blood feeding, and oviposition associated positively with temperatures of 28-32 ◦ C, indicating these temperatures to be favorable for dengue transmission. Thus, among all the variables studied, dengue incidence was most affected by the temperature.

São Paulo urban heat islands have a higher incidence of dengue than other urban areas.

Urban heat islands are characterized by high land surface temperature, low humidity, and poor vegetation, and considered to favor the transmission of the mosquito-borne dengue fever that is transmitted by the Aedes aegypti mosquito. We analyzed the recorded dengue incidence in Sao Paulo city, Brazil, in 2010-2011, in terms of multiple environmental and socioeconomic variables. Geographical information systems, thermal remote sensing images, and census data were used to classify city areas according to land surface temperature, vegetation cover, population density, socioeconomic status, and housing standards. Of the 7415 dengue cases, a majority (93.1%) mapped to areas with land surface temperature >28°C. The dengue incidence rate (cases per 100,000 inhabitants) was low (3.2 cases) in high vegetation cover areas, but high (72.3 cases) in low vegetation cover areas where the land surface temperature was 29±2°C. Interestingly, a multiple cluster analysis phenogram showed more dengue cases clustered in areas of land surface temperature >32°C, than in areas characterized as low socioeconomic zones, high population density areas, or slum-like areas. In laboratory experiments, A. aegypti mosquito larval development, blood feeding, and oviposition associated positively with temperatures of 28-32°C, indicating these temperatures to be favorable for dengue transmission. Thus, among all the variables studied, dengue incidence was most affected by the temperature.

Brazilian spotted fever: real-time PCR for diagnosis of fatal cases.

Suspicion of Brazilian spotted fever (BSF) should occur in endemic regions upon surveillance of the acute febrile icteric hemorrhagic syndrome (AFIHS). However, limitations associated with currently available laboratory tests pose a challenge to early diagnosis, especially in fatal cases. Two real-time PCR (qPCR) protocols were evaluated to diagnose BSF in 110 fatal AFIHS cases, collected in BSF-endemic regions in 2009-2010. Of these, 24 were positive and 86 negative by indirect immunofluorescence (IFA) assay (cut-off IgG and/or IgM ≥ 128). DNA from these samples was used in the qPCR protocols: one to detect Rickettsia spp. (citrate synthase gene) and another to determine spotted fever group (SFG) Rickettsia species (OmpA gene). Of the 24 IFA-positive samples, 5 (21%) were positive for OmpA and 9 (38%) for citrate synthase. In the IFA-negative group (n=86), OmpA and citrate synthase were positive in 23 (27%) and 27 (31%), respectively. These results showed that the 2 qPCR protocols were about twice as sensitive as the IFA test alone (93% concordance). In conclusion, qPCR is a sensitive method for the diagnosis of fatal BSF cases and should be considered for routine surveillance of AFIHS in places like Brazil, where spotted fever-related lethality is high and other endemic diseases like dengue and leptospirosis can mislead diagnosis.

Features of Brazilian spotted fever in two different endemic areas in Brazil.

Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most important rickettsiosis and the only reportable tick-borne disease in Brazil. In Brazil, the hard tick Amblyomma cajennense is the most important BSF vector; however, in São Paulo State, A. aureolatum was also recognized as a vector species in remaining Atlantic forest areas near the metropolitan area of São Paulo city. We analyzed clinical and epidemiological features of BSF cases from two distinct areas where A. cajennense (Area 1) and A. aureolatum (Area 2) are the incriminated vectors. The clinical features demonstrate the same severity pattern of BSF in both endemic areas. Differences in seasonality, patient characteristics (median age and gender), and epidemiological risk factors (animals host contact and vegetation characteristics) were observed and possibly could be attributed to the characteristics of each vector and their typical biological cycle (hosts and environment).

Evaluation of dengue NS1 antigen detection for diagnosis in public health laboratories, São Paulo State, 2009.

The present work evaluated the diagnostic accuracy of detection of Dengue NS1 antigen employing two NS1 assays, an immunochromatographic assay and ELISA, in the diagnostic routine of Public Health laboratories. The results obtained with NS1 assay were compared with virus isolation and, in a subpopulation of cases, they were compared with the IgM-ELISA results obtained with convalescent samples. A total of 2,321 sera samples were analyzed by one of two NS1 techniques from March to October 2009. The samples were divided into five groups: groups I, II and III included samples tested by NS1 and virus isolation, and groups IV and V included patients with a first sample tested by NS1 and a second sample tested by IgM-ELISA. Sensitivity, specificity, positive and negative predictive values, Kappa Index and Kappa Concordance were calculated. The results showed that NS1 testing in groups I, II and III had high sensitivity (98.0%, 99.5% and 99.3%), and predictive values and Kappa index between 0.9 - 1.0. Groups IV and V only had Kappa Concordance calculated, since the samples were analyzed according to the presence of NS1 antigen or IgM antibody. Concordance of 92.1% was observed when comparing the results of NS1-negative samples with IgM-ELISA. Based on the findings, it is possible to suggest that the tests for NS1 detection may be important tools for monitoring the introduction and spread of Dengue serotypes.

Evaluation of dengue NS1 antigen detection for diagnosis in public health laboratories, São Paulo State, 2009 / Avaliação da detecção do antígeno NS1 para diagnóstico de dengue nos Laboratórios de Saúde Pública, Estado de São Paulo, 2009

The present work evaluated the diagnostic accuracy of detection of Dengue NS1 antigen employing two NS1 assays, an immunochromatographic assay and ELISA, in the diagnostic routine of Public Health laboratories. The results obtained with NS1 assay were compared with virus isolation and, in a subpopulation of cases, they were compared with the IgM-ELISA results obtained with convalescent samples. A total of 2,321 sera samples were analyzed by one of two NS1 techniques from March to October 2009. The samples were divided into five groups: groups I, II and III included samples tested by NS1 and virus isolation, and groups IV and V included patients with a first sample tested by NS1 and a second sample tested by IgM-ELISA. Sensitivity, specificity, positive and negative predictive values, Kappa Index and Kappa Concordance were calculated. The results showed that NS1 testing in groups I, II and III had high sensitivity (98.0 percent, 99.5 percent and 99.3 percent), and predictive values and Kappa index between 0.9 - 1.0. Groups IV and V only had Kappa Concordance calculated, since the samples were analyzed according to the presence of NS1 antigen or IgM antibody. Concordance of 92.1 percent was observed when comparing the results of NS1-negative samples with IgM-ELISA. Based on the findings, it is possible to suggest that the tests for NS1 detection may be important tools for monitoring the introduction and spread of Dengue serotypes.

Esse estudo avaliou a acurácia do diagnóstico por detecção do antígeno NS1 do vírus Dengue empregando-se ensaios em dois formatos, imunocromatográfico e ELISA, na rotina diagnóstica dos laboratórios de Saúde Pública. Compararam-se os resultados de NS1 com os resultados de isolamento viral e, em parte dos casos, foi feita a comparação com os resultados de IgM-ELISA, obtidos nas segundas amostras. Um total de 2.321 amostras de soros, obtidas no período de março a outubro de 2009, foram analisadas por uma das duas técnicas NS1. As amostras foram divididas em cinco grupos: I, II e III, que incluíram amostras analisadas por testes NS1 e por isolamento de vírus. Os grupos IV e V incluíram pacientes com a primeira amostra processada por NS1 e segunda por IgM-ELISA. Foram analisadas sensibilidade, especificidade, valor preditivo positivo e negativo, concordância e índice Kappa. Os resultados mostraram que os grupos I, II e III apresentaram alta sensibilidade (98,0 por cento, 99,5 por cento e 99,3 por cento), valores preditivos e índice Kappa entre 0,9 - 1,0. Nos grupos IV e V, apenas concordância foi calculada, dado que as amostras foram analisadas quanto à presença de antígeno NS1 ou de anticorpos IgM. Comparando-se os resultados negativos de NS1 com IgM-ELISA houve 92,1 por cento de concordância. Com base nas constatações feitas, é possível sugerir que a detecção de NS1 pode ser importante ferramenta para monitorar a introdução e disseminação dos sorotipos de Dengue.

Brazilian spotted fever: a case series from an endemic area in southeastern Brazil: epidemiological aspects.

Brazilian spotted fever (BSF) is the most important tick-borne disease in Brazil and is caused by Rickettsia rickettsii and transmitted by the Ixodid tick Amblyomma cajennense, its main vector. We present epidemiologic aspects of a case series of patients admitted to the Hospital das Clínicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by a fourfold rise in indirect immunofluorescence (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. Seasonal variation of case occurrence seems to be associated with the life cycle of the tick. The recent reemergence of cases seems to be associated with the growing numbers of the capybara (Hydrochaeris hydrochaeris) and their expansion into urban areas.

Brazilian spotted fever: a case series from an endemic area in southeastern Brazil: clinical aspects.

This case series study is based on a retrospective review of medical records and case notification files of patients admitted to The Hospital das Clínicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by fourfold rise in indirect immunofluorescence assay (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. A median lethality of 41.9 % was observed between 1985 and 2004. The case-fatality ratio of 30 % in our study, lower than the overall São Paulo state ratio, could be explained by a higher index of suspicion and a larger experience in our hospital, a regional referral center for BSF. The presence of the classical triad of fever, rash, and headache as described in RMSF was observed in fever than half (35.2%) of our patients.

St. Louis encephalitis virus: first isolation from a human in São Paulo State, Brazil.

This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a febrile human case suspected to be dengue, in São Pedro, São Paulo State. A MAC-ELISA done on the patient's acute and convalescent sera was inconclusive and hemagglutination inhibition test detected IgG antibody for flaviviruses. An indirect immunofluorescent assay done on the C6/36 cell culture inoculated with the acute serum was positive for flaviviruses but negative when tested with dengue monoclonal antibodies. RNA extracted from the infected cell culture supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus primers and directly sequenced. Results of BLAST search indicated that this sequence shares 93% nucleotide similarity with the sequence of SLEV (strain-MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was identified as the cause of human disease, it is necessary to improve surveillance in order to achieve early detection of this agent in the state of São Paulo and in Brazil. This finding is also an alert to health professionals about the need for more complete clinical and epidemiological investigations of febrile illnesses as in the reported case. SLEV infections can be unrecognized or confused with other ones caused by an arbovirus, such as dengue.

St. Louis encephalitis vírus: first isolation from a human in São Paulo state, Brasil

O presente estudo relata o isolamento do vírus da encefalite São Luis (SLEV) de um caso febril humano suspeito de dengue, em São Pedro, Estado de São Paulo. MAC-ELISA realizado com soros das fases aguda e convalescente foi inconclusivo e anticorpos IgG foram detectados por inibição da hemaglutinação para flavivirus. Imunofluorescência indireta com cultura de células C6/36 inoculadas com soro da fase aguda foi positivo para flavivirus mas negativo quando testado com anticorpos monoclonais para dengue. O RNA extraído de cultura de células infectadas foi amplificado na presença de primers universais para o gênero Flavivirus, deduzidos de uma região da proteína não estrutural 5 e diretamente sequenciado. Os resultados da pesquisa no BLAST indicaram que a seqüência apresenta 93% de similaridade de nucleotídeos com a seqüência de SLEV (cepa MS1.7), confirmado por RT-PCR, realizado com primers específicos para SLEV. O fato de SLEV ter sido identificado como a causa de doença humana indica a necessidade de aprimorar a vigilância a fim de detectar precocemente esse agente no Estado de São Paulo e no Brasil. Esse caso é também um alerta para os profissionais de saúde sobre a necessidade de investigações clínicas e epidemiológicas mais completas sobre doenças febris como no caso relatado. Infecções por SLEV podem não ser reconhecidas ou confundidas com outras causadas por arbovírus como a dengue.

Febre amarela silvestre no Estado de São Paulo, Brasil: casos humanos autóctones / Jungle yellow fever in São Paulo state, Brazil: human autochthonous cases

Os autores relatam a ocorrência e os dados resultantes das investigações de casos humanos de Febre Amarela (FA) silvestre no estado de São Paulo. Em 2000, 7 casos suspeitos de FA silvestre foram confirmados, 5 importados de outros Estados e 2 provavelmente autóctones, de áreas localizadas às margens do Rio Grande, à noroeste do estado de São Paulo. Quatro deles evoluiram para óbito. Inquérito sorológico foi realizado em 630 habitantes de 13 municípios ribeirinhos e pesquisa entomológica foi feita nas áreas suspeitas de transmissão autóctone. A confirmação desses casos foi feita por testes sorológicos clássicos, isolamento de vírus e técnicas moleculares. As 7 amostras de soros resultaram positivas em pelo menos uma das técnicas empregadas. Todas as amostras foram reagentes no teste de MAC-ELISA. Obteve-se isolamento de vírus a partir de amostras de soros de 4 pacientes e nenhum isolamento de mosquitos. O inquérito sorológico com 630 soros, mostrou 5,23 por cento de prevalência de anticorpos para o vírus FA. A detecção de 2 casos autóctones no estado de São Paulo confirma a tendência de deslocamento da transmissão da Febre Amarela para o Sul do Brasil. A presença de anticorpos para FA em população de áreas sem transmissão recente, revela risco de reurbanização da doença