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Origin of the Sao Paulo Yellow Fever epidemic of 2017-2018 revealed through molecular epidemiological analysis of fatal cases.

ABSTRACT: The largest outbreak of yellow fever of the 21^st century in the Americas began in 2016, with intense circulation in the southeastern states of Brazil, particularly in sylvatic environments near densely populated areas including the metropolitan region of São Paulo city (MRSP) during 2017-2018. Herein, we describe the origin and molecular epidemiology of yellow fever virus (YFV) during this outbreak inferred from 36 full genome sequences taken from individuals who died following infection with zoonotic YFV. Our analysis revealed that these deaths were due to three genetic variants of sylvatic YFV that belong the South American I genotype and that were related to viruses previously isolated in 2017 from other locations in Brazil (Minas Gerais, Espírito Santo, Bahia and Rio de Janeiro states). Each variant represented an independent virus introduction into the MRSP. Phylogeographic and geopositioning analyses suggested that the virus moved around the peri-urban area without detectable human-to-human transmission, and towards the Atlantic rain forest causing human spill-over in nearby cities, yet in the absence of sustained viral transmission in the urban environment.

SUBMITTER: Cunha MDP

PROVIDER: S-EPMC6938505 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Origin of the São Paulo Yellow Fever epidemic of 2017-2018 revealed through molecular epidemiological analysis of fatal cases.

Cunha Marielton Dos Passos MDP Duarte-Neto Amaro Nunes AN Pour Shahab Zaki SZ Ortiz-Baez Ayda Susana AS Černý Jiří J Pereira Bárbara Brito de Souza BBS Braconi Carla Torres CT Ho Yeh-Li YL Perondi Beatriz B Sztajnbok Jaques J Alves Venancio Avancini Ferreira VAF Dolhnikoff Marisa M Holmes Edward C EC Saldiva Paulo Hilário Nascimento PHN Zanotto Paolo Marinho de Andrade PMA

Scientific reports 20191231 1

The largest outbreak of yellow fever of the 21<sup>st</sup> century in the Americas began in 2016, with intense circulation in the southeastern states of Brazil, particularly in sylvatic environments near densely populated areas including the metropolitan region of São Paulo city (MRSP) during 2017-2018. Herein, we describe the origin and molecular epidemiology of yellow fever virus (YFV) during this outbreak inferred from 36 full genome sequences taken from individuals who died following infect ...[more]

PMID: 31892699

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Project description:BackgroundNew strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and children in developing countries. However, none of these studies was conducted in areas with an undergoing infectious disease epidemic. We have recently experienced an epidemic of yellow fever (YF) in Brazil. Aiming to provide new information on low-cost post-mortem techniques that could be applied in regions at risk for infectious outbreaks, we tested the efficacy of ultrasound-guided MIA (MIA-US) in the diagnosis of patients who died during the epidemic.Methodology/principal findingsIn this observational study, we performed MIA-US in 20 patients with suspected or confirmed YF and compared the results with those obtained in subsequent CAs. Ultrasound-guided biopsies were used for tissue sampling of liver, kidneys, lungs, spleen, and heart. Liver samples from MIA-US and CA were submitted for RT-PCR and immunohistochemistry for detection of YF virus antigen. Of the 20 patients, 17 had YF diagnosis confirmed after autopsy by histopathological and molecular analysis. There was 100% agreement between MIA-US and CA in determining the cause of death (panlobular hepatitis with hepatic failure) and main disease (yellow fever). Further, MIA-US obtained samples with good quality for molecular studies and for the assessment of the systemic involvement of the disease. Main extrahepatic findings were pulmonary hemorrhage, pneumonia, acute tubular necrosis, and glomerulonephritis. One patient was a 24-year-old, 27-week pregnant woman; MIA-US assessed the placenta and provided adequate placental tissue for analysis.ConclusionsMIA-US is a reliable tool for rapid post-mortem diagnosis of yellow fever and can be used as an alternative to conventional autopsy in regions at risk for hemorrhagic fever outbreaks with limited resources to perform complete diagnostic autopsy.

Project description:Yellow fever (YF) is a zoonotic arthropod-borne disease that is caused by the yellow fever virus (YFV) and characterized by a sylvatic and urban cycle. Its most severe presentation is manifested as a hemorrhagic disease, and it has been responsible for thousands of deaths in the last decades. This study describes the public health approaches taken to control the 2016-2017 YF outbreak in nonhuman primates (NHPs) that took place in the northeastern region of São Paulo state, Brazil. NHPs recovered from the field were necropsied, and YF diagnoses were made at the Laboratory of Molecular Virology, Ribeirão Preto Medical School and the Center of Pathology, Adolfo Lutz Institute of São Paulo. NHP samples were inoculated into Vero cells for YFV isolation. RNA extraction was performed directly from NHP tissues and tested by RT-qPCR. YFV-positive samples were confirmed by sequencing. Based on the rapid RT-qPCR results, surveillance actions were implemented in the entire region. Confirmatory histopathology and immunohistochemistry for YFV were also performed. Among nine NHPs, gross hepatic involvement was observed in six animals, five of which were YFV-RT-qPCR-positive. One YFV was isolated from the serum of an infant NHP. YFV RNA sequences diverged from the virus responsible for the last epizootic that occurred in São Paulo state, but it was similar to the current Brazilian epizootic. Public health actions included dissemination of information on YF transmission, investigation of the probable location of NHP infection, characterization of the environment, and subsequent creation of the blueprint from which prevention and control measures were implemented. The YFV sylvatic cycle occurred in the periurban areas of the northeastern region of São Paulo state, but no human cases were reported during this period, showing that integrated actions between human, animal, and environmental health professionals were critical to restrain the virus to the sylvatic cycle.

Project description:To estimate the prevalence of one month psychotropic drug use in São Paulo, Brazil, and to assess the gap treatment between the presence of mental disorders and psychotropic drug users.A probabilistic sample of non-institutionalized individuals from the general population of São Paulo (n = 2336; turnout: 84.5%) who were 15 years or older were interviewed by a trained research staff, applying the Composite International Diagnostic Interview 2.1 (CIDI WHO) (depression, anxiety-phobia, OCD\PTSD, alcoholism sections), and an inventory investigating psychotropic drug use during the 12-month and one-month periods immediately preceding the interview. Logistic models were fitted to investigate associations between psychotropic drug use as well as socio-demographic and clinical variables.The one month prevalence of psychotropic drug use in São Paulo was 5.89%, the most commonly used drugs were antidepressants (3.15%) and tranquilizers (2.67%). A higher consumption of psychotropic drugs (overall, antidepressants and tranquilizers) was observed among women (OR:2.42), older individuals (OR:1.04), individuals with higher levels of formal education (1.06), and individuals with a family (OR:2.29) or personal history of mental illness (OR:3.27). The main psychotropic drug prescribers were psychiatrists (41%), followed by general practitioners (30%); 60% of psychotropic drugs were obtained through a government-run dispensing program. Most individuals who obtained a positive diagnosis on the CIDI 2.1 during the previous month were not using psychotropic medication (85%). Among individuals with a diagnosis of moderate to severe depression, 67.5% were not on any pharmacological treatment.There is a change in the type of psychotropic more often used in São Paulo, from benzodiazepines to antidepressants, this event is observed in different cultures. The prevalence of use is similar to other developing countries. Most of the patients presenting a psychiatric illness in the month prior to testing were not receiving any sort of psychiatric medication. This may be explained by a failure to identify cases in primary care, which could be improved (and access to treatment could be facilitated) if professionals received more specialized training in managing cases with mental health problems.

Dataset Information

Origin of the Sao Paulo Yellow Fever epidemic of 2017-2018 revealed through molecular epidemiological analysis of fatal cases.

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Origin of the São Paulo Yellow Fever epidemic of 2017-2018 revealed through molecular epidemiological analysis of fatal cases.

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