Survey on Non-Human Primates and Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban and Sylvatic Cycles of Yellow Fever and Zika Viruses Following Severe Outbreaks in Southeast Brazil.

In the last decade, Flaviviruses such as yellow fever (YFV) and Zika (ZIKV) have expanded their transmission areas. These viruses originated in Africa, where they exhibit both sylvatic and interhuman transmission cycles. In Brazil, the risk of YFV urbanization has grown, with the sylvatic transmission approaching the most densely populated metropolis, while concern about ZIKV spillback to a sylvatic cycle has risen. To investigate these health threats, we carried out extensive collections and arbovirus screening of 144 free-living, non-human primates (NHPs) and 5219 mosquitoes before, during, and after ZIKV and YFV outbreaks (2015-2018) in southeast Brazil. ZIKV infection was not detected in any NHP collected at any time. In contrast, current and previous YFV infections were detected in NHPs sampled between 2017 and 2018, but not before the onset of the YFV outbreak. Mosquito pools screened by high-throughput PCR were positive for YFV when captured in the wild and during the YFV outbreak, but were negative for 94 other arboviruses, including ZIKV, regardless of the time of collection. In conclusion, there was no evidence of YFV transmission in coastal southeast Brazil before the current outbreak, nor the spread or establishment of an independent sylvatic cycle of ZIKV or urban Aedes aegypti transmission of YFV in the region. In view of the region's receptivity and vulnerability to arbovirus transmission, surveillance of NHPs and mosquitoes should be strengthened and continuous.

Haemagogus leucocelaenus and Haemagogus janthinomys are the primary vectors in the major yellow fever outbreak in Brazil, 2016-2018.

The yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016-2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.

Genomic and structural features of the yellow fever virus from the 2016-2017 Brazilian outbreak.

Southeastern Brazil has been suffering a rapid expansion of a severe sylvatic yellow fever virus (YFV) outbreak since late 2016, which has reached one of the most populated zones in Brazil and South America, heretofore a yellow fever-free zone for more than 70 years. In the current study, we describe the complete genome of 12 YFV samples from mosquitoes, humans and non-human primates from the Brazilian 2017 epidemic. All of the YFV sequences belong to the modern lineage (sub-lineage 1E) of South American genotype I, having been circulating for several months prior to the December 2016 detection. Our data confirm that viral strains associated with the most severe YF epidemic in South America in the last 70 years display unique amino acid substitutions that are mainly located in highly conserved positions in non-structural proteins. Our data also corroborate that YFV has spread southward into Rio de Janeiro state following two main sylvatic dispersion routes that converged at the border of the great metropolitan area comprising nearly 12 million unvaccinated inhabitants. Our original results can help public health authorities to guide the surveillance, prophylaxis and control measures required to face such a severe epidemiological problem. Finally, it will also inspire other workers to further investigate the epidemiological and biological significance of the amino acid polymorphisms detected in the Brazilian 2017 YFV strains.

Análise de genes de Mycobacterium leprae associados com resistência a rifampicina, dapsona e ofloxacin em amostras clínica de pacientes com hanseníase (recidiva) no município do Rio de Janeiro / Analysis of Mycobacterium leprae genes associated with resistance to rifampicin, dapsone and ofloxacin in clinical samples from patients with leprosy (relapse) in Rio de Janeiro

A Hanseníase é causada pelo Mycobacterium leprae (M. leprae) e é um problema de saúde pública em países da Ásia, América Latina e África. O tratamento poliquimioterápico da doença é recomendado pela Organização Mundial da Saúde desde 1982, mas teve implantação gradual no Brasil a partir de 1986, passando a ser o único esquema nacional em 1991. No início dos anos 90, o Ministério da Saúde implantou a dose fixa do tratamento poliquimioterápico (PQT). O uso irregular das drogas (auto-administradas) pode levar ao surgimento de resistência, portanto monitorar a existência de resistência à ação do antibiótico rifampicina é muito importante, pois é a droga mais bactericida da PQT. O alvo da rifampicina é a subunidade beta da RNA polimerase, que é decodificada pelo gene rpoB do M. leprae. Uma substituição no códon da serina (posição 531) pela leucina, causada por uma mutação deste gene, parece ser a principal causa da resistência à rifampicina. Todas as mutações associadas ao rpoB são localizadas nos domínios 500-540 – sistema numérico usado em rpoB de E. coli. As mutações no gene folP, decodificador da dihidropteroato sintetase do M. leprae, foram associadas a resistência à dapsona. A resistência ao ofloxacin tem sido associada à mutação nos genes gyrA e gyrB, que codificam as subunidades a e Beta da DNA girase de várias micobactérias incluindo M. leprae. Avaliamos neste estudo, através da reação em cadeia da polimerase (PCR) e sequenciamento, a presença de mutações nos genes rpoB, folP, gyrA e gyrB em 78 amostras de pacientes provenientes do estado do Rio de Janeiro com hanseníase multibacilar e suspeita de recidiva. Não encontramos nenhuma mutação que indicasse resistência a drogas nos quatro genes estudados, o que possivelmente indica que os casos de recidiva não são causados por resistência medicamentosa e sim por uma nova infecção. Já que a população susceptível ao bacilo, mesmo depois de curada, permanece no local onde foi previamente infectada em contato com as possíveis fontes de transmissão. Esse estudo vem colaborar para o desenvolvimento de critérios laboratoriais para o diagnóstico correto de recidiva, uma vez que não existem, no Brasil, parâmetros técnicos e nem metodologia científica apropriada para aplicação na rede básica do Sistema Único de Saúde.