Mosquito-Borne Viral Diseases: Control and Prevention in the Genomics Era

Mosquito-borne viral diseases are infections transmitted by the bite of infected mosquitoes. The burden of these diseases is highest in tropical and subtropical areas and they disproportionately affect the poorest populations. Since 2014, major outbreaks of dengue, chikungunya, yellow fever and Zika have afflicted populations and overwhelmed health systems in many countries. Distribution of mosquito-borne diseases is determined by complex demographic, environmental and social factors, causing diseases to emerge in countries where they were previously unknown. Coupling genomic diagnostics and epidemiology to innovative digital disease detection platforms raises the possibility of an open, global, digital pathogen surveillance system. Considering pathogen surveillance in mind, real-time sequencing, bioinformatics tools and the combination of genomic and epidemiological data from viral infections can give essential information for understanding the past and the future of an epidemic, making possible to establish an effective surveillance framework on tracking the spread of infections to other geographic regions

Promoting Responsible Research and Innovation (RRI) During Brazilian Activities of Genomic and Epidemiological Surveillance of Arboviruses

Zika infectio

Genomic epidemiology unveils the dynamics and spatial corridor behind the Yellow Fever virus outbreak in Southern Brazil

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013–2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain–Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV

Avaliação epidemiológica e genômica do vírus chikungunya circulante no Rio de Janeiro

Submitted by Repositório Arca ([email protected]) on 2019-05-20T17:55:42Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-05-21T13:53:20Z (GMT) No. of bitstreams: 2 Joilson Xavier dos Santos Junior Avaliação Epidemiológica.. 2019.pdf: 30202823 bytes, checksum: 137f9c4fd5592f4f8d8b9c4964d9915b (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-05-21T13:53:20Z (GMT). No. of bitstreams: 2 Joilson Xavier dos Santos Junior Avaliação Epidemiológica.. 2019.pdf: 30202823 bytes, checksum: 137f9c4fd5592f4f8d8b9c4964d9915b (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2019O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Código de Financiamento 001. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.A febre Chikungunya é uma doença autolimitada causada pelo vírus chikungunya (CHIKV), que é transmitido pela picada de mosquitos hematófagos infectados do gênero Aedes. A maioria dos indivíduos infectados apresentam sintomas dentro de 4 a 7 dias, como febre, exantema maculopapular, poliartralgia e mialgia. Os casos de chikungunya no Brasil são registrados desde que o vírus foi identificado pela primeira vez no país em 2014. Em 2018, o Brasil registrou 87.687 casos prováveis da doença, dos quais, 52.966 casos (60,4%) ocorreram apenas na região Sudeste. O estado do Rio de Janeiro experienciou uma grande epidemia causada pelo CHIKV em 2016, 18.516 casos prováveis. A emergência do CHIKV tem levantado preocupação devido à rápida disseminação do vírus em nova áreas geográficas e às características clínicas associadas à infecção. OBJETIVO: Diante do exposto, o objetivo deste estudo foi investigar a epidemiologia genômica do vírus chikungunya circulante no estado do Rio de Janeiro. MATERIAIS E MÉTODOS: Nós empregamos o método de sequenciamento por nanoporos, que permite a geração de muitos dados em poucas horas. RESULTADOS: Nós geramos com sucesso 11 sequências genômicas do CHIKV a partir de amostras de soro de pacientes sintomáticos residentes em sua maioria (n=6) no município do Rio de Janeiro. As cinco amostras restantes foram de pacientes residentes em quatro municípios vizinhos. As análises filogenéticas, empregando a abordagem do relógio molecular, revelaram que as cepas circulantes no Rio de Janeiro pertenciam ao genótipo africano ECSA e provavelmente este foi introduzido neste estado por volta de julho de 2014. Isto significa que o vírus circulou despercebidamente por 16 meses antes dos primeiros relatos oficias de transmissão autóctone no estado do Rio de Janeiro. CONCLUSÕES: Ambos os dados epidemiológicos e filogenéticos sugerem que as cepas da linhagem ECSA foram introduzidas no Rio de Janeiro a partir dos eventos de dispersão do CHIKV da região Nordeste para outras regiões do Brasil.INTRODUCTION: Chikungunya fever is a self-limited disease caused by chikungunya virus (CHIKV), which is transmitted by the bite of infected hematophagous mosquitoes of the genus Aedes. Most infected individuals present symptoms within 4 to 7 days, such as fever, maculopapular rash, polyarthralgia and myalgia. Cases of chikungunya in Brazil are recorded since the virus was first identified in the country in 2014. In 2018, Brazil reported 87,687 probable cases of the disease, of which 52,966 cases (60.4%) occurred in the Southeast region only. The state of Rio de Janeiro experienced a major epidemic caused by CHIKV in 2016, reporting 18,516 probable cases. The emergence of CHIKV has raised concern due to the rapid spread of the virus into new geographic areas and the clinical features associated with the infection. OBJECTIVE: Thus, the objective of this study was to investigate the genomic epidemiology of chikungunya virus circulating in the state of Rio de Janeiro. MATERIALS AND METHODS: We used the nanopore sequencing method that allows the generation of large amounts of data in a few hours. RESULTS: We successfully generated 11 CHIKV genomic sequences from serum samples from symptomatic patients residing mostly (n = 6) in the city of Rio de Janeiro. The remaining five samples were from patients residing in four neighbouring municipalities. Phylogenetic analyses, using the molecular clock approach, revealed that the strains circulating in Rio de Janeiro belonged to the ECSA African genotype and this genotype was likely introduced in the state around July 2014. This means that the virus circulated unnoticed for 16 months before the first official reports of autochthonous transmission in the state of Rio de Janeiro. CONCLUSIONS: Both epidemiological and phylogenetic data suggest that strains from ECSA lineage were introduced into Rio de Janeiro from CHIKV dispersion events from Northeast region of Brazil to others Brazilian regions

Resurgence of Dengue Virus Serotype 3 in Minas Gerais, Brazil: A Case Report

This report provides a detailed overview of the resurgence of DENV-3 in the state of Minas Gerais, Brazil, which is a concerning scenario in the context of dengue, a mosquito-borne viral disease. Historically, Brazil has grappled with dengue epidemics caused primarily by the DENV-1 and DENV-2 serotypes. However, in 2023, a significant shift in this pattern was observed as DENV-3 made a notable resurgence. This resurgence was characterized by the increase in DENV-3 cases within the country and the region of the Americas. Given the absence of sustained DENV-3 circulation in Brazil in previous years, this situation poses a significant risk, making the population highly susceptible to a potential novel epidemic. In November 2023, a 31-year-old male patient in Belo Horizonte exhibited symptoms of acute febrile syndrome. Multiplex RT-qPCR using the Kit Molecular ZC D-Tipagem confirmed DENV-3 infection, suggesting a likely autochthonous case, as the patient reported no travel history. To promptly assess this resurgence, we applied the nanopore sequencing technology. This allowed for the rapid characterization of the initial DENV-3 case isolated in Minas Gerais in 2023, representing a 13-year interval since the serotype’s previous documented circulation in that state. This case report underscores the critical importance of proactive monitoring and the swift implementation of targeted control strategies to address the evolving dynamics of dengue, with a specific emphasis on the resurgence of DENV-3 in the state

Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence

Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism’s homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4+ and CD8+ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells

Epidemiology and evolution of Zika virus in Minas Gerais, Southeast Brazil

Autochthonous Zika virus (ZIKV) transmission in Brazil was first identified in April 2015 in Brazil, with the first ZIKV-associated microcephaly cases detected in October 2015. Despite efforts on understanding ZIKV transmission in Brazil, little is known about the virus epidemiology and genetic diversity in Minas Gerais (MG), the second most populous state in the country. We report molecular and genomic findings from the main public health laboratory in MG. Until January 2020, 26,817 ZIKV suspected infections and 86 congenital syndrome cases were reported in MG state. We tested 8552 ZIKV and microcephaly suspected cases. Ten genomes were generated on-site directly from clinical samples. A total of 1723 confirmed cases were detected in Minas Gerais, with two main epidemic waves; the first and larger epidemic wave peaked in March 2016, with the second smaller wave that peaked in March 2017. Dated molecular clock analysis revealed that multiple introductions occurred in Minas Gerais between 2014 and 2015, suggesting that the virus was circulating unnoticed for at least 16 months before the first confirmed laboratory case that we retrospectively identified in December 2015. Our findings highlight the importance of continued genomic surveillance strategies combined with traditional epidemiology to assist public health laboratories in monitoring and understanding the diversity of circulating arboviruses, which might help attenuate the public health impact of infectious diseases

Return of the founder Chikungunya virus to its place of introduction into Brazil is revealed by genomic characterization of exanthematic disease cases

Submitted by Sandra Infurna ([email protected]) on 2020-03-10T15:58:07Z No. of bitstreams: 1 MartaGiovanetti_LCAlcantara_etal_IOC_2020.pdf: 1148514 bytes, checksum: 32d98df74817f86ea43988acd886f4e0 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-10T16:31:16Z (GMT) No. of bitstreams: 1 MartaGiovanetti_LCAlcantara_etal_IOC_2020.pdf: 1148514 bytes, checksum: 32d98df74817f86ea43988acd886f4e0 (MD5)Made available in DSpace on 2020-03-10T16:31:16Z (GMT). No. of bitstreams: 1 MartaGiovanetti_LCAlcantara_etal_IOC_2020.pdf: 1148514 bytes, checksum: 32d98df74817f86ea43988acd886f4e0 (MD5) Previous issue date: 2019Laboratório Central de Saúde Pública. Departamento de Virologia, Salvador, BA, Brasil.Laboratório Central de Saúde Pública. Departamento de Virologia, Salvador, BA, Brasil.Ministério da Saúde. Coordenação Geral de Vigilância de Arboviroses (CGARB). Brasília, DF, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Genética Celular e Molecular. Belo Horizonte, MG, Brasil / University of KwaZulu- Natal, Durban. College of Health Sciences. KwaZulu-Natal Research Innovation and Sequencing Platform. Durban, South Africa.Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Laboratório Central de Saúde Pública. Departamento de Virologia, Salvador, BA, Brasil.Universidade Estadual de Feira de Santana. Feira de Santana, BA, Brasil / Secretaria de Saúde de Feira de Santana. Feira de Santana, BA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Coordenação Geral dos Laboratórios de Saúde Pública. Brasília, DF, Brasil.Organização Pan-Americana da Saúde/Organização Mundial da Saúde. Brasília, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância de Doenças Transmissíveis. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Universidade Federal do Mato Grosso do Sul. MS, Brasil / Fundação Oswaldo Cruz. Coordenação de Saúde Laboratórios de Vigilância e Referência. Rio de Janeiro, RJ, Brasil.University of Oxford. Oxford, UK.University of KwaZulu- Natal, Durban. College of Health Sciences. KwaZulu-Natal Research Innovation and Sequencing Platform. Durban, South Africa.University of Oxford. Oxford, UK.University of KwaZulu- Natal, Durban. College of Health Sciences. KwaZulu-Natal Research Innovation and Sequencing Platform. Durban, South Africa / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.University of Oxford. Department of Zoology. Oxford, UK.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Genética Celular e Molecular. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, BrasilMinistério da Saúde. Coordenação Geral de Vigilância de Arboviroses (CGARB). Brasília, DF, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, BrasilBetween June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances

Short report: Introduction of chikungunya virus ECSA genotype into the Brazilian Midwest and its dispersion through the Americas.

Since introduction into Brazil in 2014, chikungunya virus (CHIKV) has presented sustained transmission, although much is unknown about its circulation in the midwestern states. Here, we analyze 24 novel partial and near complete CHIKV genomes from Cuiaba, an urban metropolis located in the Brazilian midwestern state of Mato Grosso (MT). Nanopore technology was used for sequencing CHIKV complete genomes. Phylogenetic and epidemiological approaches were used to explore the recent spatio-temporal evolution and spread of the CHIKV-ECSA genotype in Midwest Brazil as well as in the Americas. Epidemiological data revealed a reduction in the number of reported cases over 2018-2020, likely as a consequence of a gradual accumulation of herd-immunity. Phylogeographic reconstructions revealed that at least two independent introductions of the ECSA lineage occurred in MT from a dispersion event originating in the northeastern region and suggest that the midwestern Brazilian region appears to have acted as a source of virus transmission towards Paraguay, a bordering South American country. Our results show a complex dynamic of transmission between epidemic seasons and suggest a possible role of Brazil as a source for international dispersion of the CHIKV-ECSA genotype to other countries in the Americas