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In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (“A1” class) from cases with other illnesses (“C” class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI (“A1” and “C” classes) as compared to primary vaccines without YEL-AEFI [PV(day 3–28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in “A1” as compared to “C” class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate “A1” from “C”. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify “A1” followed by VEGF as branch nodes to discriminate Wild Type YFV infection (“C(WT-YFV)”) from cases with other illnesses (“C*”). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Made available in DSpace on 2022-04-28T17:21:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 National Institutes of Health USA CRP-ICGEB RESEARCH GRANT 2020 Project Oswaldo Cruz Foundation Brazilian Ministry of Health Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) European Union's Horizon 2020 research and innovation programme-project EpiPose South African Department of Science and Innovation South African Medical Research Council under the BRICS JAF Australian Research Council Laureate Fellowship The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant of concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96 per cent of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, and diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforce reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect the emergence and spread of other VOCs that might threaten global health. Inst Oswaldo Cruz, Lab Flavivirus, Fundacao Aswaldo Cruz, FIOCRUZ,IOC, Av Brasil 4365, BR-21040360 Rio De Janeiro, RJ, Brazil Univ Fed Minas Gerais, Inst Ciencias Biol, Lab Genet Celular & Mol, Av Pres Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil Univ Campus Biomed Roma, Dept Sci & Technol Humans & Environm, Via Alvaro Portillo 21, I-00128 Rome, Italy Organizacao Pan Amer Saude, Organizacao Mundial Saude, Lote 19 Ave Nacoes, BR-70312970 Brasilia, DF, Brazil Univ KwaZulu Natal, Coll Hlth Sci, Sch Lab Med & Med Sci, KwaZulu Natal Res Innovat & Sequencing Platfom KR, 238 Mazisi Kunene Rd, ZA-4041 Durban, South Africa Stellenbosch Univ, Ctr Epidem Response & Innovat CERI, Sch Data Sci & Computat Thinking, Banhoek Rd & Joubert St, ZA-7600 Stellenbosch, South Africa Univ Bern, Inst Social & Prevent Med, Hochschulstr 6, CH-3012 Bern, Switzerland Fundacao Ezequiel Dias, Lab Cent Saude Publ Estado Minas Gerais, Rua Conde Pereira Carneiro,80 Gameleira, BR-30510010 Belo Horizonte, MG, Brazil Univ Sao Paulo, Blood Ctr Ribeirao Preto, Ribeirao Preto Med Sch, R Quintino Bocaiuva 470, BR-14015160 Ribeirao Preto, SP, Brazil Butantan Inst, Ave Doutor Vital Brasil 1500, Sao Paulo, SP, Brazil Sao Paulo State Univ UNESP, Sch Agr Sci, R Quintino Bocaiuva 470, BR-05508900 Botucatu, SP, Brazil Univ Sao Paulo, Sch Anim Sci & Food Engn, Dept Vet Med, R Quintino Bocaiuva 470, Sao Paulo, Brazil Univ Sao Paulo, Ctr Genom Func ESALQ, R Quintino Bocaiuva 470, Piracicaba, SP, Brazil Fundacao Oswaldo Cruz, Biomanguinhos, Av Brasil 4365, BR-21040360 Rio De Janeiro, RJ, Brazil Coordenacao Geral Labs Saude Publ, Minist Saude CGLAB SVS MS, Secretaria Vigilancia Saude, Esplanada Ministerios Bloco G Edificio Sede, BR-70058900 Brasilia, DF, Brazil Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Private Bag X7, ZA-4013 Congella, South Africa Univ Washington, Dept Global Hlth, Schmitz Hall 1410 NE Campus Pkway Box 355852, Seattle, WA 98195 USA Univ Oxford, Dept Zool, Peter Medawar Bldg,1a Mansfield Rd, Oxford, England Univ Sydney, Sch Life & Environm Sci, Sydney Inst Infect Dis, Sydney, NSW, Australia Univ Sydney, Sch Med Sci, Sydney, NSW, Australia Univ Lisbon, Biosyst & Integrat Sci Inst BioISI, P-1749016 Lisbon, Portugal Sao Paulo State Univ UNESP, Sch Agr Sci, R Quintino Bocaiuva 470, BR-05508900 Botucatu, SP, Brazil National Institutes of Health USA: U01 AI151698 CRP-ICGEB RESEARCH GRANT 2020 Project: CRP/BRA20-03 CRP-ICGEB RESEARCH GRANT 2020 Project: CRP/20/03 Oswaldo Cruz Foundation: VPGDI-027-FIO-20-2-2-30 Brazilian Ministry of Health: SCON2021-00180 CNPq: 426559/2018-5 FAPERJ: E-26/202.930/2016 FAPERJ: E-26/202.248/2018(238504) FAPERJ: E26/202.665/2019(247400) European Union's Horizon 2020 research and innovation programme-project EpiPose: 101003688 South African Medical Research Council under the BRICS JAF: 2020/049 Australian Research Council Laureate Fellowship: FL170100022

The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.

Brazil has experienced some of the highest numbers of COVID-19 cases and deaths globally and from May 2021 made Latin America a pandemic epicenter. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of virus transmission dynamics at the national scale. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and a bordering country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed under an absence of effective restriction measures, there was a local emergence and onward international spread of Variants of Concern (VOC) and Variants Under Monitoring (VUM), including Gamma (P.1) and Zeta (P.2). In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the usefulness and need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring that provides a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies.

Objective To estimate the effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech), against symptomatic covid-19 in the elderly population of São Paulo state, Brazil during widespread circulation of the gamma variant. Design Test negative case-control study. Setting Community testing for covid-19 in São Paulo state, Brazil. Participants 43 774 adults aged ≥70 years who were residents of São Paulo state and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 29 April 2021. 26 433 cases with symptomatic covid-19 and 17 622 test negative controls with covid-19 symptoms were formed into 13 283 matched sets, one case with to up to five controls, according to age, sex, self-reported race, municipality of residence, previous covid-19 status, and date of RT-PCR test (±3 days). Intervention Vaccination with a two dose regimen of CoronaVac. Main outcome measures RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Results Adjusted vaccine effectiveness against symptomatic covid-19 was 24.7% (95% confidence interval 14.7% to 33.4%) at 0-13 days and 46.8% (38.7% to 53.8%) at ≥14 days after the second dose. Adjusted vaccine effectiveness against hospital admissions was 55.5% (46.5% to 62.9%) and against deaths was 61.2% (48.9% to 70.5%) at ≥14 days after the second dose. Vaccine effectiveness ≥14 days after the second dose was highest for the youngest age group (70-74 years)—59.0% (43.7% to 70.2%) against symptomatic disease, 77.6% (62.5% to 86.7%) against hospital admissions, and 83.9% (59.2% to 93.7%) against deaths—and declined with increasing age. Conclusions Vaccination with CoronaVac was associated with a reduction in symptomatic covid-19, hospital admissions, and deaths in adults aged ≥70 years in a setting with extensive transmission of the gamma variant. Vaccine protection was, however, low until completion of the two dose regimen, and vaccine effectiveness was observe to decline with increasing age among this elderly population.

BackgroundA two-dose regimen of ChAdOx1 coronavirus disease 19 (Covid-19) vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of severe acute respiratory syndrome 2 (SARS-CoV-2).MethodsWe conducted a test-negative case-control study to estimate the effectiveness of ChAdOx1 vaccine in adults aged 60 years or older during a Gamma-variant-associated epidemic in São Paulo state, Brazil, between 17 January and 2 July 2021. Cases and matched test-negative controls were individuals, identified from surveillance databases, who experienced an acute respiratory illness and underwent SARS-CoV-2 RT-PCR testing. We used conditional logistic regression to estimate the effectiveness by dose against RT-PCR-confirmed Covid-19, Covid-19 hospitalization, and Covid-19-related death.Results61,164 individuals were selected into matched case-control pairs. Starting ≥28 days after the first dose, adjusted effectiveness of a single dose of ChAdOx1 was 33.4% (95% CI, 26.4 to 39.7) against Covid-19, 55.1% (95% CI, 46.6 to 62.2) against hospitalization, and 61.8% (95% CI, 48.9 to 71.4) against death. Starting ≥14 days after the second dose, the adjusted effectiveness of the two-dose schedule was 77.9% (95% CI, 69.2 to 84.2) against Covid-19, 87.6% (95% CI, 78.2 to 92.9) against hospitalization, and 93.6% (95% CI, 81.9 to 97.7) against death.ConclusionsCompletion of the ChAdOx1 vaccine schedule afforded significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant transmission.

Background Mass vaccination is being used in response to coronavirus disease (COVID-19) epidemics, including those driven by emerging variants of concern. We evaluated the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19 in the elderly population of Sao Paulo State, Brazil during widespread circulation of the P.1 variant. Methods We conducted a test-negative, case-control study of adults ≥70 years of age from Sao Paulo State from January 17 to April 29, 2021, during which vaccination with a two-dose regimen of CoronaVac was implemented. We identified RT-PCR-confirmed COVID-19 cases as well as controls who had a symptomatic illness with a negative RT-PCR test from national surveillance and state vaccination databases. Controls were pair-matched to cases by age category, sex, self-report race, municipality, prior COVID-19 status, and date of RT-PCR testing. We estimated vaccine effectiveness, adjusted for age and comorbidities, using conditional logistic regression. Findings We selected 7,950 matched pairs with a mean age of 76 years from 26,433 COVID-19 cases and 17,622 test-negative controls. Adjusted vaccine effectiveness was 18.2% (95% CI, 0.0 to 33.2) and 41.6% (95% CI, 26.9 to 53.3) in the period 0-13 and ≥14 days, respectively, after the 2nd dose. Administration of a single vaccine dose was not associated with reduced odds of COVID-19. Vaccine effectiveness ≥14 days after the 2nd dose declined with increasing age and was 61.8% (95% CI 34.8 to 77.7), 48.9% (95% CI 23.3 to 66.0) and 28.0% (95% CI 0.6 to 47.9) among individuals 70-74, 75-79 and ≥80 years of age, respectively (pinteraction = 0.05). Interpretation CoronaVac was 42% effective in the real-world setting of extensive P.1 transmission, but significant protection was not observed until completion of the two-dose regimen and vaccine effectiveness declined with increasing age. These findings underscore the need to maintain non-pharmaceutical interventions when mass vaccination with CoronaVac is used as part of an epidemic response. Funding Pan American Health Organization. Research in context Evidence before this study We searched Pubmed for articles published from inception of the pandemic until May 10, 2021, with no language restrictions, using the search terms “vaccine”, “COVID-19”, “SARS-CoV-2”, “elderly”, “age”, “older”. Randomised controlled trials (RCTs) have yielded varying estimates (51-84%) for the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19. Current evidence is lacking on whether CoronaVac or other COVID-19 vaccines are effective against disease caused by the SARS-CoV-2 variant of concern, P.1, or in a setting of extensive P.1 circulation. No studies have reported the real-world effectiveness of CoronaVac and other inactivated vaccines among elderly individuals, a population that was underrepresented in RCTs of these vaccines. Added value of this study In a population-based matched test-negative case-control study, we found that a two-dose regimen of CoronaVac had an effectiveness of 42% in preventing symptomatic COVID-19 among adults ≥70 years of age during an epidemic associated with widespread P.1 variant transmission. Significant protection was not observed until the period ≥14 days after administration of the second dose. We observed a significant decline in vaccine effectiveness with increasing age in the elderly population. Implications of all the available evidence In the setting of extensive P.1 transmission, the effectiveness of CoronaVac in adults ≥70 years of age was similar to that observed in RCTs conducted in younger populations prior to the emergence of P.1. These findings provide supportive evidence for the use of this vaccine in countries that are experiencing P.1-associated epidemics. However, significant protection was not detected until after administration of the second dose, indicating that vaccination in countries where CoronaVac supplies are constrained may need to prioritize completion of the two dose regimen among the highest risk populations. The delay in achieving vaccine-mediated protection also underscores the need to initiate and maintain non-pharmaceutical interventions when mass vaccination with CoronaVac is used in a response to an epidemic. National immunisation programs should optimise the vaccination of the very elderly (≥80 years), accounting for specific vaccines or vaccination schemes.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. Methods We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. Findings For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. Interpretation Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Funding Fundacao Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundacao de Vigilância em Saude do Amazonas

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported.MethodsWe performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection.FindingsFor the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case- control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate.InterpretationEvidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.FundingFundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of ManausResearch in ContextEvidence before this studyWe searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms “P.1” AND “vaccine” AND “SARS-CoV-2”. Additionally, we searched for “CoronaVac” AND “SARS-CoV-2”. Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date.No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission.Added value of this studyThis study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2).Implications of all the available evidenceThese findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.

Objetivo: Apresentar a varredura espacial como instrumento para identificar clusters de dengue e fatores associados à epidemias em Belo Horizonte/MG. Métodos: Estudo ecológico, com casos de dengue notificados entre 2007 e 2010. Para identificação de clusters utilizou-se a estatística de varredura espacial Scan. A regressão logística investigou a associação entre clusters e o índice de infestação predial (IIP), proporção de imóveis verticalizados (PIV), densidade de ovos de Ae. aegypti (DO), cobertura de visitas de agentes de endemia e densidade populacional. Resultados: Ocorreram 76.592 casos de dengue e identificados 5 clusters por período: em 2007/2008 os agregados concentraram 30% da população e 67% dos casos; 2008/2009 agruparam 13% da população e 60% dos casos e em 2009/2010 concentraram 34% da população e 62% dos casos. Houve associação com IIP em 2007/2008 (OR=5,0; p

The Northeast region of Brazil registered the second highest incidence proportion of chikungunya fever in 2019. In that year an outbreak consisting of patients presented with febrile disease associated with joint pain were reported by the public primary health care service in the city of Natal, Rio Grande do Norte state, in March 2019. At first, the aetiological agent of the disease was undetermined. Since much is still unknown about chikungunya virus (CHIKV) genomic diversity and evolutionary history in this northeasternmost state, we used a combination of portable whole genome sequencing, molecular clock, and epidemiological analyses that revealed the re-introduction of the CHIKV East-Central-South-African (ECSA) lineage into Rio Grande do Norte. We estimated CHIKV ECSA lineage was first introduced into Rio Grande do Norte in early June 2014, while the 2019 outbreak clade diverged around April 2018 during a period of increased chikungunya incidence in the Southeast region, which might have acted as a source of virus dispersion towards the Northeast region. Together, these results confirm the ECSA lineage continues to spread across the country through interregional importation events likely mediated by human mobility.HIGHLIGHTSCHIKV ECSA lineage introduction into Rio Grande do Norte state, Northeast Brazil, was estimated to early June 2014At least two CHIKV importation events occurred in Rio Grande do Norte state, BrazilThe 2019 chikungunya outbreak in Rio Grande do Norte was likely caused by a second event of CHIKV introduction imported from Rio de Janeiro state.

BackgroundBrazil has experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continual struggle with effective control and public health preparedness. Brazil is a world leader in real-time genomic surveillance of arboviruses, although such technology and expertise remains inaccessible for the vast majority of local researchers and public health workers. In 2019, we led field and classroom initiatives for the genomic surveillance of DENV in Brazil.MethodsOxford Nanopore MinION technology was used for sequencing, focusing on generating DENV1 and DENV2 complete genomes. Using phylogenetic and epidemiological approaches conducted in real-time during a training program and subsequently through online channels, we explored the recent spatio-temporal evolution and spread of these viruses in Brazil.FindingsIn the years following the Zika virus epidemic (2017-2018) reporting was at an all-time low, and significant increases in reported cases and deaths in 2019 did not reflect a higher case fatality ratio. Estimated transmission potential and reporting of other arboviruses suggests that neither arboviral reporting saturation nor climatic factors can easily explain the post-Zika period and resurgence in 2019 (respectively). Phylogenetic analysis revealed complex patterns of transmission, with lineage co-circulation and replacement, in which the North and the Southeast acted as sources of dispersion to other regions. We identified two lineages within the already reported DENV2 BR-4 clade, for which the effective reproduction number had seasonal signatures alike reported cases, with a temporal increase towards 2019 mirroring the large epidemic that year.InterpretationWe describe the recent evolution and diffusion of DENV1 and DENV2 in Brazil. Importantly, the surveillance outputs and training initiative here described serve as proof-of-concept of the potential of portable sequencing for both research and local capacity building in the area of genomic surveillance of arboviruses.FundingDecit, SCTIE, BrMoH, CNPq, CAPES, EU Horizon 2020 through ZIKAlliance and STARBIOS2.

Yellow fever virus (YFV) causes a clinical syndrome of acute hemorrhagic hepatitis. YFV transmission involves non-human primates (NHP), mosquitoes and humans. By late 2016, Brazil experienced the largest YFV outbreak of the last 100 years, with 2050 human confirmed cases, with 681 cases ending in death and 764 confirmed epizootic cases in NHP. Among affected areas, Bahia state in Northeastern was the only region with no autochthonous human cases. By using next generation sequence approach, we investigated the molecular epidemiology of YFV in NHP in Bahia and discuss what factors might have prevented human cases. We investigated 47 YFV positive tissue samples from NHP cases to generate 8 novel YFV genomes. ML phylogenetic tree reconstructions and automated subtyping tools placed the newly generated genomes within the South American genotype I (SA I). Our analysis revealed that the YFV genomes from Bahia formed two distinct well-supported phylogenetic clusters that emerged most likely of an introduction from Minas Gerais and Espírito Santo states. Vegetation coverage analysis performed shows predominantly low to medium vegetation coverage in Bahia state. Together, our findings support the hypothesis of two independent YFV SA-I introductions. We also highlighted the effectiveness of the actions taken by epidemiological surveillance team of the state to prevented human cases., Author summary Between 2016 and 2018, Brazil witnessed the largest YFV outbreak since years, with 2.154 cases and 745 deaths. Here we report the introduction of the virus in the state of Bahia suggesting two independent introductions from Minas Gerais and Espirito Santo. We also highlight the actions taken by epidemiological surveillance division that may have prevent human infections.

The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics. IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

Objetivo: investigar os casos de febre maculosa, verificar os aspectos relacionados à assistência à saúde e caracterizar o perfil epidemiológico desses e do ambiente de infecção. Métodos: estudo descritivo dos casos confirmados de FM entre janeiro e novembro de 2017. Foi elaborado um formulário semiestruturado para coleta dos dados. Para as análises epidemiológicas, foram utilizados os programas EpiInfoTM 7 e Qgis® 2.18.1. Foram calculadas frequências, medidas de tendência central, dispersão e indicadores de oportunidade de assistência. Nos ambientes prováveis de infecção, foram realizadas coletas de carrapatos que foram identificados e submetidos à pesquisa de Rickettsia do grupo da FM. Resultados: foram confirmados 15 casos de FM; desses, a maioria foi do sexo masculino (93%) com média de 42 anos de idade; 10 evoluíram para óbito. Todos apresentaram febre, 13(87%) cefaleia e 12(80%) mialgia. Apresentaram mediana e média de evolução para óbito pela doença de 6 dias (1 a 9), oportunidades de hospitalização, tratamento, diagnóstico e notificação de 4,5(0 a 8); 7(0 a 26); 9(DP±6) e 33(DP±45) dias, respectivamente. Para assistência à saúde, 14(93%) casos procuraram atendimento mais de duas vezes, com tempo de internação de 4,5 dias (0 a 8 dias). O hospital foi o serviço procurado, exclusivamente, no quarto atendimento. Dengue e FM foram as hipóteses diagnósticas mais frequentes. Foram coletados 250 espécimes de carrapatos em quatro municípios, sendo em um município identificado Amblyomma sculptum naturalmente infectados. Conclusões: foram assinaladas condições assistenciais pouco sensíveis à ocorrência da FM, o que, provavelmente, colaborou para ocorrência de óbitos, além da necessidade de sensibilização de equipes de saúde e vigilância quanto à ocorrência da FM na região.

The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5&prime, UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espirito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espirito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics.IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

International audience; 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.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics., info:eu-repo/semantics/published