Fast surveillance response reveals the introduction of a new yellow fever virus sub-lineage in 2021, in Minas Gerais, Brazil

BACKGROUND In Brazil, the yellow fever virus (YFV) is maintained in a sylvatic cycle involving wild mosquitoes and non-human primates (NHPs). The virus is endemic to the Amazon region; however, waves of epidemic expansion reaching other Brazilian states sporadically occur, eventually causing spillovers to humans. OBJECTIVES To report a surveillance effort that led to the first confirmation of YFV in NHPs in the state of Minas Gerais (MG), Southeast region, in 2021. METHODS A surveillance network was created, encompassing the technology of smartphone applications and coordinated actions of several research institutions and health services to monitor and investigate NHP epizootics. FINDINGS When alerts were spread through the network, samples from NHPs were collected and YFV infection confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and genome sequencing at an interval of only 10 days. Near-complete genomes were generated using the Nanopore MinION sequencer. Phylogenetic analysis indicated that viral genomes were related to the South American genotype I, clustering with a genome detected in the Amazon region (state of Pará) in 2017, named YFVPA/MG sub-lineage. Fast YFV confirmation potentialised vaccination campaigns. MAIN CONCLUSIONS A new YFV introduction was detected in MG 6 years after the beginning of the major outbreak reported in the state (2015-2018). The YFV strain was not related to the sub-lineages previously reported in MG. No human cases have been reported, suggesting the importance of coordinated surveillance of NHPs using available technologies and supporting laboratories to ensure a quick response and implementation of contingency measures to avoid YFV spillover to humans.

Fatores associados à gravidade dos eventos adversos pós-vacinação contra a febre amarela durante o maior surto da doença registrado no Brasil, 2016-2017 / Factores asociados a la gravedad de los eventos adversos posvacunación contra la fiebre amarilla durante el mayor brote de la enfermedad registrado en Brasil, 2016-2017 / Factors associated with severity of adverse events following yellow fever vaccination during the biggest outbreak of the disease recorded in Brazil, 2016-2017

Resumo Objetivo: analisar características, incidência e fatores associados aos eventos adversos graves (EAGs) pós-vacinação contra febre amarela durante surto da doença no Brasil (2016-2017). Métodos: estudo de caso-controle, com dados do Sistema de Informações do Programa Nacional de Imunizações (SI-PNI); foram considerados casos os EAGs, e controles os eventos adversos não graves (EANGs). Resultados: foram analisados 135 casos de EAG e 1.058 controles; dos 135 EAGs, 79 (58,5%) eram homens, e a mediana de idade dos casos, 28 anos (intervalo interquartílico: 9-49); a incidência de EAG em janeiro de 2017 chegou a 1,3 caso por 100 mil doses aplicadas; houve associação estatística com o sexo masculino (odds ratio [OR]=1,73; IC95% 1,20;2,48), ser primovacinado (OR=1,65; IC95% 1,01;2,71), e ter idade ≥60 anos, tomando-se por referência os menores de 5 anos (OR=4,4; p-valor <0,02). Conclusão: EAG pela vacina da febre amarela apresentou maior chance de ocorrer em homens, idosos e primovacinados.

Resumen Objetivo: analizar características, incidencia y factores asociados a eventos adversos graves (EAG) posvacunación contra la fiebre amarilla durante brote de la enfermedad en Brasil (2016-2017). Métodos: estudio de caso-control, con datos del Sistema de Informaciones del Programa Nacional de Inmunizaciones (SI-PNI); se consideraron casos los EAG, y controles los eventos adversos no graves (EANG). Resultados: se analizaron 135 casos de EAG y 1.058 controles; de los 135 EAG, 79 (58,5%) eran hombres, con edad promedio de 28 años [rango intercuartílico: 9-49]; la incidência en enero de 2017 llegó a 1,3 caso por 100 mil dosis aplicadas; ocurrió asociación estadística con el sexo masculino (odds ratio [OR]=1,73 - IC95% 1,20;2,48), ser primovacunado (OR=1,65 - IC95% 1,01;2,71), y tener ≥60 años de edad tomando como referencia a los menores de 5 años (OR=4,4; p-valor <0,02). Conclusión: EAG por la vacuna de la fiebre amarilla presentó mayor probabilidad de ocurrir en hombres, ancianos y primovacunados.

Abstract Objective: to analyze characteristics, incidence and factors associated with serious adverse events (SAEs) following yellow fever vaccination during an outbreak of the disease in Brazil (2016-2017). Methods: this was a case-control study using data from the National Immunization Program Information System (SI-PNI); SAE were considered to be cases, and non-serious adverse events (NSAE) were considered to be controls. Results: we analyzed 135 SAE cases and 1,058 controls; of the 135 SAE, 79 (58.5%) were males and median age was 28 years [09-49]; incidence in January 2017 reached 1.3 case per 100,000 vaccine doses administered; there was statistical association with males (Odds Ratio [OR]=1.73 - 95%CI 1.20;2.48), primary vaccination (OR=1.65 - 95%CI 1.01;2.71), and being 60 years of age or older taking as reference those aged under 5 (OR=4.4; p-value <0.02). Conclusion: SAE owing to yellow fever vaccine showed a greater chance of occurring in men, the elderly and primary vaccination.

Raiva humana no Brasil: estudo descritivo, 2000-2017 / La rabia humana en Brasil: estudio descriptivo, 2000-2017 / Human rabies in Brazil: a descriptive study, 2000-2017

Objetivo: descrever o perfil epidemiológico da raiva humana no Brasil. Métodos: estudo descritivo dos casos de raiva humana notificados em 2000-2017; estimou-se a incidência e distribuição espacial. Resultados: 188 casos humanos observados, na maioria homens (66,5%), residentes rurais (67,0%), menores de 15 anos de idade (49,6%), com exposição mais frequente por mordedura (81,9%); o período 2000-2008 apresentou maior frequência (85,6%), com 46,6% dos casos envolvendo cães e 45,9% morcegos; incubação mediana de 50 dias, seguida de sintomatologia predominante de febre (92,6%), agitação (85,2%), parestesia (66,7%) e disfagia/paralisia (51,9%); a maioria (70,2%) não fez profilaxia, os demais (29,8%) realizaram-na de forma inoportuna e/ou incompleta; 13 pacientes foram tratados pelo Protocolo de Recife e dois sobreviveram. Conclusão: houve redução na incidência de raiva humana e mudança no perfil epidemiológico, predominando casos transmitidos por morcegos; sugere-se investigar casos secundários e viabilizar a profilaxia pré-exposição em populações sob maior risco de acidentes com morcegos.

Objetivo: describir el perfil epidemiológico de la rabia humana en Brasil. Métodos: descripción de los casos en 2000-2017, con estimación de la incidencia y distribución espacial. Resultados: se observaron 188 casos humanos, la mayoría de hombres (66,5%), residentes rurales (67,0%), menores de 15 años de edad (49,6%), con exposición más frecuente por mordedura (81,9%); el período 2000-2008 presentó mayor frecuencia (85,6%), con un 46,6% de los casos involucrando a perros y 45,9% a murciélagos; la incubación promedio fue de 50 días, seguida de sintomatología predominante de fiebre (92,6%), agitación (85,2%), parestesia (66,7%) y disfagia/parálisis (51,9%); la mayoría (70,2%) no hizo profilaxis y los demás (29,8%) la realizaron de forma inoportuna y/o incompleta; se trataron 13 pacientes con el Protocolo de Recife y dos sobrevivieron. Conclusión: hubo reducción en la incidencia de rabia humana y cambio en el perfil epidemiológico, predominando casos transmitidos por murciélagos; se sugiere investigar casos secundarios y viabilizar la profilaxis preexposición en poblaciones de mayor riesgo a accidentes por murciélagos.

Objective: to describe the epidemiological profile of human rabies in Brazil. Methods: this is a descriptive study of human rabies cases reported in 2000-2017, with an estimate of incidence and spatial distribution. Results: 188 cases were studied, mostly males (66.5%), rural residents (67.0%), children under 15 years (49.6%), with biting being the most frequent form of exposure (81.9%); frequency was highest in the period 2000-2008 (85.6%), with 46.6% of cases involving dogs and 45.9% bats; median incubation was 50 days, followed by, predominantly, symptoms of fever (92.6%), agitation (85.2%), paresthesia (66.7%), and dysphagia/paralysis (51.9%); the majority (70.2%) did not have prophylaxis and for the rest (29.8%) who did have prophylaxis, it was untimely and/or incomplete; 13 patients were treated according to the Recife Protocol, and two survived. Conclusion: human rabies incidence reduced and its epidemiological profile changed, with predominance of cases transmitted by bats; we suggest that secondary cases be investigated, and that pre-exposure prophylaxis be made available to populations at greater risk of accidents involving bats.

First isolation of West Nile virus in Brazil

BACKGROUND Serological evidence of West Nile virus (WNV) infection has been reported in different regions of Brazil from equine and human hosts but the virus had never been isolated in the country. OBJECTIVES We sought to identify the viral etiology of equine encephalitis in Espírito Santo state. METHODS We performed viral culture in C6/36 cells, molecular detection of WNV genome, histopathology and immunohistochemistry from horse cerebral tissue. We also carried out sequencing, phylogenetic analysis and molecular clock. FINDINGS Histopathologic analysis from horse cerebral tissue showed injury related to encephalitis and WNV infection was confirmed by immunohistochemistry. The virus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from brain tissue and subsequently isolated in C6/36 cells. WNV full-length genome was sequenced showing the isolated strain belongs to lineage 1a. The molecular clock indicated that Brazilian WNV strain share the same common ancestor that were circulating in US during 2002-2005. MAIN CONCLUSIONS Here we report the first isolation of WNV in Brazil from a horse with neurologic disease, which was clustered into lineage 1a with others US WNV strains isolated in beginning of 2000's decade.

Frequency of histopathological changes in Howler monkeys ( Alouatta sp. ) naturally infected with yellow fever virus in Brazil

Abstract: INTRODUCTION: Due to the importance that Howler monkeys have on the yellow fever (YF) epidemiological sylvatic cycle in Brazil, more accurate morphological diagnostic criteria needs to be established, especially considering the differences that may exist between the genera of Brazilian non-human primates (NHPs) involved in yellow fever virus (YFV) epizootics. METHODS: Records of YF epizootics in NHPs in Brazil between 2007 and 2009 were obtained from the Brazilian Ministry of Health database to select YF positive (n=98) Howler monkeys (Alouatta sp.) for this study. The changes described in the histopathological reports were categorized by organ and their frequencies calculated. RESULTS: The most frequent lesions observed in the animals with YF were hepatocyte apoptosis (Councilman body formation), midzonal hepatocyte necrosis, steatosis, liver hemorrhage, inflammatory mononuclear cell infiltration of the liver, renal acute tubular necrosis and interstitial nephritis. Midzonal hepatocyte necrosis, steatosis and hemorrhage presented positive correlations with apoptosis of hepatocytes, suggesting strong YFV pathogenic effect association; they were also the main histopathological changes in the Alouatta sp. A pronounced negative correlation between apoptosis of hepatocytes and hepatic mononuclear cell infiltration pointed to significant histopathological differences between YFV infection in Howler monkeys and humans. CONCLUSIONS: The results warn that NHPs may exhibit different response patterns following YFV infection and require a more careful diagnosis. Presumptive diagnosis based on primate histopathological lesions may contribute to public health service control.

Epizootias em primatas não humanos durante reemergência do vírus da febre amarela no Brasil, 2007 a 2009 / Epizootics in nonhuman primates during reemergence of yellow fever virus in Brazil, 2007 to 2009

Objetivo: descrever e analisar a mudança do perfil epidemiológico da febre amarela silvestre no Brasil – que passa a ocorrer fora da Amazônia – a partir de 1999, quando a detecção do vírus em primatas permitiu a aplicação oportuna de novas medidas de vigilância. Metodologia: este estudo faz uma análise descritiva das epizootias em primatas notificadas ao Ministério da Saúde (MS) entre 2007 e 2009; para captação dos dados, foram utilizadas a Ficha de Notificação de Epizootia do Sistema de Informação de Agravos de Notificação (Sinan) e planilha de notificação diária. Resultados: No período, foram notificadas 1.971 epizootias em primatas, sendo 73 no ano de 2007, 1.050 em 2008 e 848 em 2009; essas epizootias ocorreram em 520 municípios de 19 estados; do total de epizootias notificadas, 209 (10,6 por cento) foram confirmadas para febre amarela. Conclusão: as informações aqui discutidas são fundamentais para o aperfeiçoamento da vigilância e a consolidação da notificação de epizootias em primatas, como instrumento de prevenção de casos humanos da doença.

Objective: to describe and analyze the change in the epidemiological profile of sylvatic yellow fever – whose cases began to occur outside the Amazon region, in Brazil – from 1999, when the detection of the virus in primates has led to the timely implementation of new surveillance measures. Methodology: this study is a descriptive analysis of epizootics in primates notified to the Ministry of Health between 2007 and 2009; data were captured using the Epizootic Notification Form of the Brazilian Information System for Notifiable Diseases (Sinan) and daily reporting spreadsheet. Results: from 1,971 epizootics reported during the period, 73 occurred in 2007, 1,050 in 2008, and 848 in 2009; and 209 (10.6 per cent) were confirmed for yellow fever; these epizootics have been registered in 520 municipalities of 19 states. Conclusion: the information discussed herein is fundamental for improving the surveillance and consolidating the notification of epizootics in primates, as a tool for preventing human cases of the disease.

Identificação das espécies de roedores reservatórios de hantavírus no sul e sudeste brasileiro: (Nota Prévia) / Identification of hantavirus rodent reservoirs species in south and southeastern Brazil: (Previous Note)

BACKGROUNS: Hantavirus is a genus belonging to the Bunyaviridae family. Human infection occurs mainly by inhalation of aerosols formed from wild rodent droppings. The objectives of this study were to identify the species of rodent reservoirs of hantavirus that cause the cardiopulmonary syndrome in the southern and southeastern regions of Brazil; to understand the eco-epidemiology of this virus and the wild rodents' systematics. MATERIAL AND METHODS: Rodents were captured using Sherman traps distributed throughout natural environments and around human settlements in localities were hantavirus cardiopulmonary syndrome was detected. After species identification, biometric measures were taken of each animal. Samples of blood, liver, kidney, spleen, heart and lung were preserved in liquid nitrogen and sent to the laboratory. Blood samples were tested for IgG antibodies for hantavirus using an enzyme-linked immunosorbent assay (ELISA). Voucher specimens are available at the Instituto Adolfo Lutz collection. RESULTS: A total of 4,069 rodents, belonging to 22 species, were captured. From these rodents, 201 had IgG antibodies for hantavirus. The number of positive specimens per number of captured rodents according to the natural environments studied is the following: a) Mainland: Bolomys lasiurus (130/1187), Oximicterus ruttilans (1/6), Thalpomys lasiotis (0/2), Oligoryzomys stramineus (0/1), Oryzomys nitidus (0/24), Pseudoryzomys simplex (0/14), Calomys tener (22/910), Calomys callosus (2/107); b) Atlantic rainforest: Bolomys sp (1/51), Brucepattersonius soricinus (0/16), Oximicterus quaestor (0/15), Thaptomys nigrita (1/59), Delomys dorsalis (0/1), Delomys sublineatus (0/4) Oligoryzomys delticola (0/5), Oryzomys capito (0/3), Oryzomys ratticeps (0/7), Calomys laucha (0/26); c) Both habitats: Akodon sp (14/910), Oligoryzomys nigripes (28/360), Rattus rattus (0/9), Mus musculus (2/352). Oligoryzomys nigripes was more frequent in the Atlantic rainforest. Bolomys lasiurus showed the highest capture index (44%) and the highest antibody prevalence among mainland species (10.9%). In the Atlantic rainforest, Akodon sp was the most captured species (45,4%) and Oligoryzomys nigripes showed the highest antibody prevalence (7,8%). CONCLUSIONS:Antibody prevalence indicates Bolomys lasiurus as the reservoir of hantavírus in the mainland regions of São Paulo and Minas Gerais and Oligoryzomys nigripes in the Atlantic rainforest of São Paulo, Rio Grande do Sul, Paraná and Santa Catarina. Species belonging to the genus Akodon and Calomys showed lower prevalence, and complementary studies are needed to clarify their role in hantavirus epidemiology.

DELINEAMENTO DO PROBLEMA: Os hantavirus formam um gênero da família Bunyaviridae . A infecção humana ocorre, principalmente, pela inalação de aerossóis formados a partir de excretas de roedores silvestres infectados. Os objetivos deste trabalho foram identificar as espécies de roedores reservatórios de hantavírus causadores de síndrome cardiopulmonar nas regiões Sul e Sudeste do Brasil; e compreender a ecoepidemiologia desses vírus e a sistemática de roedores silvestres. MATERIAL E MÉTODOS: Em locais onde ocorreram casos de síndrome cardiopulmonar por hantavírus, foram realizadas capturas de roedores silvestres com auxílio de armadilhas tipo Sherman, distribuídas nos diversos biomas e ambientes domiciliares, peridomiciliares e silvestres. Após identificação sistemática da espécie, medidas biométricas foram tomadas de cada animal. Amostras de sangue, fígado, rim, baço, coração e pulmão foram conservadas em nitrogênio líquido e levadas para o laboratório. O sangue foi testado pela técnica imunoenzimática (ELISA) para detecção de anticorpos IgG para hantavírus. As carcaças dos roedores foram depositadas na coleção do Instituto Adolfo Lutz. RESULTADOS: Foram capturados 4.069 roedores, de 22 espécies. Desses, 201 roedores apresentaram anticorpos IgG para hantavírus. As espécies e os respectivos números de roedores positivos por capturados, de acordo com os biomas estudados foram: a) cerrado: Bolomys lasiurus (130/1187), Oximicterus ruttilans (1/6), Thalpomys lasiotis (0/2), Oligoryzomys stramineus (0/1), Oryzomys nitidus (0/24), Pseudoryzomys simplex (0/14), Calomys tener (22/910), Calomys callosus (2/107), b) Mata Atlântica: Bolomys sp (1/51), Brucepattersonius soricinus (0/16), Oximicterus quaestor (0/15), Thaptomys nigrita (1/59), Delomys dorsalis (0/1), Delomys sublineatus (0/4) Oligoryzomys delticola (0/5), Oryzomys capito (0/3), Oryzomys ratticeps (0/7), Calomys laucha (0/ 26); c) nos dois biomas: Akodon sp (14/910), Oligoryzomys nigripes (28/360), Rattus rattus (0/9), Mus musculus (2/352). Oligoryzomys nigripes foi consideravelmente mais freqüente na mata atlântica. Bolomys lasiurus apresentou maior índice de captura (44%) e de prevalência de anticorpos entre espécies de cerrado (11%), enquanto na mata atlântica, Akodon sp foi a mais capturada (45%) e Oligoryzomys nigripes apresentou maior soropositividade (8%). CONCLUSÕES: Baseando-se na prevalência de anticorpos, Bolomys lasiurus foi identificado como reservatório de hantavírus nas regiões de cerrado de São Paulo e Minas Gerais e Oligoryzomys nigripes nas regiões de mata atlântica de São Paulo, Rio Grande do Sul, Paraná e Santa Catarina. Espécies do gênero Akodon e Calomys mostraram baixas soroprevalências e requerem novos estudos para esclarecer seu papel na epidemiologia do hantavírus.