Phylogenetic analysis reveals a new introduction of Yellow Fever virus in São Paulo State, Brazil, 2023.

Yellow Fever (YF) is a viral arbovirosis of Public Health importance. In Brazil, surveillance is focused mainly on detecting epizootic events of Platyrrhini. Herein, we compared the detection and phylogenetic analysis of YF virus in two neotropical primates (NTP), a Callithrix detected in the previous epidemic period (2016-2020), and a Callicebus nigrifons, showing a new introduction of YF in 2023. This paper illustrates the importance of joint actions of laboratory and field teams to ensure quick response to Public Health emergencies, such as the intensification of vaccination of susceptible human populations.

Análise de algoritmo diagnóstico de febre amarela em amostras de primatas não humanos encaminhadas ao Centro de Patologia do Instituto Adolfo Lutz / Analysis of a diagnostic algorithm for yellow fever in primate samples non-humans sent to the Pathology Center of Instituto Adolfo Lutz

O Centro de Patologia do Instituto Adolfo Lutz (CPA-IAL) é credenciado pelo Ministério da Saúde como laboratório de referência macrorregional para a vigilância epidemiológica de febre amarela (FA) em seres humanos e primatas não humanos (PNH) do Brasil, atuando por meio de análise histopatológica e imuno-histoquímica (IHQ). Até o ano de 2018, ambos os exames eram aplicados a todas as amostras de PNH recebidas para a pesquisa de FA. Em 2019, implantou-se um algoritmo diagnóstico baseado na triagem pelas características histopatológicas observadas no tecido hepático, possibilitando a racionalização do uso da IHQ. Objetivo: Avaliar a aplicação do algoritmo diagnóstico comparado ao período que antecedeu sua implantação. Métodos: Estudo retrospectivo de relatórios anatomopatológicos de PNH emitidos, entre 2018 e 2019, no CPA-IAL para determinação de índices de performance diagnóstica do exame histopatológico na vigilância epidemiológica de febre amarela, avaliação da sensibilidade do exame imuno-histoquímico para amostras com autólise de moderada a avançada e comparação da mediana de tempo decorrido para emissão dos relatórios em cada período. Resultados: Não houve diferença estatisticamente significante na performance da detecção de FA por histologia e IHQ entre os períodos pré e pós algoritmo; houve importante redução na quantidade de exames IHQ solicitados e no tempo de liberação dos relatórios (p<0,0001). Conclusões: O algoritmo resultou em desempenho semelhante, redução do tempo de liberação oportuno para a vigilância epidemiológica do agravo e da quantidade de reações IHQ realizadas, portanto, apresentando-se adequado para o diagnóstico de febre amarela em PNH no CPA-IAL.

Differential Yellow Fever Susceptibility in New World Nonhuman Primates, Comparison with Humans, and Implications for Surveillance.

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Yellow fever surveillance challenge: Investigation of a marmoset non-autochthonous case.

Yellow fever (YF) surveillance in Brazil is focused mainly on the detection of epizootic events regarding New World non-human primates (NWNHP). We present a challenging case of a Callitrichidae (Callithrix spp) kept as a domiciliated pet that lived in the urban area of São Paulo municipality and was positive to YF virus by RT-qPCR and immunohistochemistry. After investigation, it was the first occurrence of non-autochthonous YF case of NWNHP described, with probable place of infection in the North shore of São Paulo state. This case illustrates the importance of coordinated laboratorial and field actions, and risks posed by transit of wildlife.

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

Genomic evidence of yellow fever virus in Aedes scapularis, southeastern Brazil, 2016.

The southeastern region of Brazil has recently experienced the largest yellow fever disease outbreak in decades. Since July 2016 epizootic events were reported in São Paulo state's north region, where 787 Culicidae were captured as part of public health surveillance efforts and tested using real-time quantitative PCR. One Aedes scapularis pool collected in November 2016 in an agriculture area in Urupês city tested positive for YFV-RNA. Using a validated multiplex PCR approach we were able to recover a complete virus genome sequence from this pool. Phylogenetic analysis of the novel strain and publicly available data indicates that the belongs to the South American genotype 1 clade circulating in Sao Paulo state and is basal to the recent outbreak clade in southeast Brazil. Our findings highlight the need of additional studies, including vector competence studies, to disentangle the role of Aedes scapularis in yellow fever transmission in the Americas.

Yellow fever surveillance challenge: Investigation of a marmoset non-autochthonous case

Yellow fever (YF) surveillance in Brazil is focused mainly on the detection of epizootic events regarding New World non-human primates (NWNHP). We present a challenging case of a Callitrichidae (Callithrix spp) kept as a domiciliated pet that lived in the urban area of São Paulo municipality and was positive to YF virus by RT-qPCR and immunohistochemistry. After investigation, it was the first occurrence of non-autochthonous YF case of NWNHP described, with probable place of infection in the North shore of São Paulo state. This case illustrates the importance of coordinated laboratorial and field actions, and risks posed by transit of wildlife.

Classificação epidemiológica dos municípios do Estado de São Paulo segundo o Programa de Vigilância e Controle da Leishmaniose Visceral, 2017 / Epidemiological classification of the municipalities of the Stat e of São Paulo according to the Visceral Leishmaniasis Control and Surveillance Program, 2017

Foi realizado um estudo descritivo dos casos de Leishmaniose Visceral (LV) notificados no período de 1999 a 2017 no Estado de São Paulo (ESP). Para a classificação epidemiológica dos municípios com transmissão humana de LV foram seguidas as recomendações do Ministério da Saúde1 que considera: "Municípios com transmissão recente aqueles que apresentaram o primeiro registro da doença nos últimos três anos" e "Municípios endêmicos aqueles que apresentam transmissão contínua de LV humana há pelo menos três anos

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.