Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016-2019.

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.

Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis.

BACKGROUND: On Nov 11, 2015, the Brazilian Ministry of Health declared a Public Health Emergency of National Concern in response to an increased number of microcephaly cases, possibly related to previous Zika virus outbreaks. We describe the course of the dual epidemics of the Zika virus infection during pregnancy and microcephaly in Brazil up to Nov 12, 2016, the first anniversary of this declaration. METHODS: We used secondary data for Zika virus and microcephaly cases obtained through the Brazilian Ministry of Health's surveillance systems from Jan 1, 2015, to Nov 12, 2016. We deemed possible Zika virus infections during pregnancy as all suspected cases of Zika virus disease and all initially suspected, but later discarded, cases of dengue and chikungunya fever. We defined confirmed infection-related microcephaly in liveborn infants as the presence of a head circumference of at least 2 SDs below the mean for their age and sex, accompanied by diagnostic imaging consistent with an infectious cause, or laboratory, clinical, or epidemiological results positive for Zika virus or STORCH (infectious agents known to cause congenital infection, mainly syphilis, toxoplasmosis, cytomegalovirus, and herpes simplex virus). We excluded cases of congenital anomalies or death without microcephaly. We analyse the spatial clustering of these diseases in Brazil to obtain the kernel density estimation. FINDINGS: Two distinct waves of possible Zika virus infection extended across all Brazilian regions in 2015 and 2016. 1 673 272 notified cases were reported, of which 41 473 (2·5%) were in pregnant women. During this period, 1950 cases of infection-related microcephaly were confirmed. Most cases (1373 [70·4%]) occurred in the northeast region after the first wave of Zika virus infection, with peak monthly occurrence estimated at 49·9 cases per 10 000 livebirths. After a major, well documented second wave of Zika virus infection in all regions of Brazil from September, 2015, to September, 2016, occurrence of microcephaly was much lower than that following the first wave of Zika virus infection, reaching epidemic levels in all but the south of Brazil, with estimated monthly peaks varying from 3·2 cases to 15 cases per 10 000 livebirths. INTERPRETATION: The distribution of infection-related microcephaly after Zika virus outbreaks has varied across time and Brazilian regions. Reasons for these apparent differences remain to be elucidated. FUNDING: None.

Pathology of congenital Zika syndrome in Brazil: a case series.

BACKGROUND: Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. METHODS: In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. FINDINGS: Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. INTERPRETATION: These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. FUNDING: None.

Seroprevalence and factors associated with SARS-CoV-2 infection among education workers after the first wave: the first cross-sectional study in Brazil.

BACKGROUND: The school community was heavily impacted by the Covid-19 pandemic, especially with the long time of school closures. This study aimed to analyze the seroprevalence of SARS-CoV-2 antibodies and possible factors associated with seropositivity for COVID-19 in teachers and other school staff, and to estimate the fraction of asymptomatic individuals by sex and age group. METHODS: We conducted a serological survey of SARS-CoV-2 infections. An analytical cross-sectional study was conducted in Fortaleza, Brazil. Teachers and other staff members from pre-schools to universities of higher education to were investigated. RESULTS: A total of 1,901 professionals participated in the study, of which 1,021 were staff and 880 were teachers. The seroprevalence of SARS-CoV-2 was 8.0% (152/1901). In the seropositive group, 48.3% were asymptomatic. There was a predominance of women (68.4%); and, 47.1% of the participants were between 31 and 45 years old. There was an increase in prevalence with increasing age. An inverse relationship was found for education level: more professionals with less education tested positive for COVID-19. The presence of an infected person living in the same household was significantly associated with positive results for COVID-19 among the professionals. CONCLUSIONS: This is the first study to report the seroprevalence of IgG against SARS-CoV-2 in Brazilian educational staff after the first wave of the disease. In this study, the seroprevalence was much lower than that in the general population. During school reopening, a small fraction of school workers showed serologically detectable signs of SARS-CoV-2 exposure.

Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis.

BACKGROUND: In 2006, Brazil began routine immunization of infants <15 wk of age with a single-strain rotavirus vaccine. We evaluated whether the rotavirus vaccination program was associated with declines in childhood diarrhea deaths and hospital admissions by monitoring disease trends before and after vaccine introduction in all five regions of Brazil with varying disease burden and distinct socioeconomic and health indicators. METHODS AND FINDINGS: National data were analyzed with an interrupted time-series analysis that used diarrhea-related mortality or hospitalization rates as the main outcomes. Monthly mortality and admission rates estimated for the years after rotavirus vaccination (2007-2009) were compared with expected rates calculated from pre-vaccine years (2002-2005), adjusting for secular and seasonal trends. During the three years following rotavirus vaccination in Brazil, rates for diarrhea-related mortality and admissions among children <5 y of age were 22% (95% confidence interval 6%-44%) and 17% (95% confidence interval 5%-27%) lower than expected, respectively. A cumulative total of ~1,500 fewer diarrhea deaths and 130,000 fewer admissions were observed among children <5 y during the three years after rotavirus vaccination. The largest reductions in deaths (22%-28%) and admissions (21%-25%) were among children younger than 2 y, who had the highest rates of vaccination. In contrast, lower reductions in deaths (4%) and admissions (7%) were noted among children two years of age and older, who were not age-eligible for vaccination during the study period. CONCLUSIONS: After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil. The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine. These real-world data are consistent with evidence obtained from clinical trials and strengthen the evidence base for the introduction of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.

How Brazil can hold back COVID-19. / Como o Brasil pode deter a COVID-19.

This article presents the strategies and actions adopted by the Brazilian Ministry of Health to hold back COVID-19. The response to the disease was immediate and occurred prior to the first case being detected in Brazil. Provision of information and communication to the population and the press was adopted as a fundamental strategy for addressing the epidemic. Guidance provided to the population has been clear, stressing the importance of coronavirus transmission prevention measures. Efforts have been directed towards strengthening health surveillance and health care, as well as boosting research, development and innovation. Actions have targeted human resource training and expanding coverage afforded by the Brazilian National Health System (SUS). Protecting health workers is a priority. All SUS health workers, managers and directors are dedicated to preserving the health and life of each and every Brazilian citizen.

COVID-19 in Brazil: evolution of the epidemic up until epidemiological week 20 of 2020. / COVID-19 no Brasil: evolução da epidemia até a semana epidemiológica 20 de 2020.

Objective to describe the evolution of COVID-19 in Brazil up until epidemiological week 20 of 2020. Methods this is an ecological study based on data and official documents from the Brazilian Ministry of Health and international organizations; comparisons were made between Brazil and other countries and incidence and mortality rates were calculated. Results by the end of epidemiological week 20, 233,142 cases, and 15,633 deaths had been confirmed for Brazil as a whole and 3,240 (58.2%) of the country's municipalities had reported at least one case; Brazil was at an earlier phase of the pandemic when compared to other countries, except Russia and Turkey, regarding cumulative cases, and except Canada regarding cumulative deaths; the highest rates were found in Brazil's Northern Region states, where Amazonas state had the highest incidence rates(4,474.6/1,000,000) and mortality rates (331.8/1,000,000). Conclusion Brazil is one of the countries with the highest number of confirmed cases and deaths, with marked regional differences.

COVID-19 in Brazil: advantages of a socialized unified health system and preparation to contain cases.

The outbreak of new coronavirus disease 2019 (COVID-19) reported for the first time in Wuhan, China in late December 2019 have rapidly spread to other countries and it was declared on January 30, 2020 as a public health emergency of international concern (PHEIC) by the World Health Organization. Before the first COVID-19 cases were reported in Brazil, several measures have been implemented including the adjustment of legal framework to carry out isolation and quarantine. As the cases increased significantly, new measures, mainly to reduce mortality and severe cases, have also been implemented. Rapid and robust preparedness actions have been undertaken in Brazil while first cases have not yet been identified in Latin-American. The outcome of this early preparation should be analyzed in future studies.

COVID-19 epidemic in Brazil: Where are we at?

OBJETIVE: To analyze the trends of COVID-19 in Brazil in 2020 by Federal Units (FU). METHOD: Ecological time-series based on cumulative confirmed cases of COVID-19 from March 11 to May 12. Joinpoint regression models were applied to identify points of inflection in COVID-19 trends, considering the days since the 50th confirmed case as time unit. RESULTS: Brazil reached its 50th confirmed case of COVID-19 in 11 March 2020 and, 63 days after that, on May 12, 177,589 cases had been confirmed. The trends for all regions and FU are upward. In the last segment, from the 31st to the 63rd day, Brazil presented a daily percentage change (DPC) of 7.3% (95%CI= 7.2;7.5). For the country the average daily percentage change (ADPC) was 14.2% (95%CI: 13.8;14.5). The highest ADPC values were found in the North, Northeast and Southeast regions. CONCLUSIONS: In summary, our results show that all FUs in Brazil present upward trends of COVID-19. In some FUs, the slowdown in DPC in the last segment must be considered with caution. Each FU is at a different stage of the pandemic and, therefore, non-pharmacological measures should be adopted accordingly.

International collaboration networks for the surveillance of congenital anomalies: a narrative review. / Redes internacionais de colaboração para a vigilância das anomalias congênitas: uma revisão narrativa.

Objective to identify international congenital anomaly surveillance collaboration networks, to list the programs that compose them and to compare their main characteristics. Methods this was a narrative literature review by means of a MEDLINE database search (via PubMed) and searches involving websites, reports and official documents. Results six international congenital anomaly surveillance collaboration networks were identified (ECLAMC, ICBDSR, EUROCAT, BINOCAR, SEAR-NBBD and ReLAMC), comprised of 98 programs present in 58 different countries on all continents, except Africa; the main characteristics regarding type of surveillance, coverage and location were discussed in a comparative manner. Conclusion international collaborative networks are important players for congenital anomaly surveillance, contributing to the understanding of the global epidemiological scenario of these conditions, in addition to acting both to strengthen individual existing programs and also to create surveillance initiatives in unassisted regions.

Congenital anomalies from the health surveillance perspective: compilation of a list based on ICD-10. / Anomalias congênitas na perspectiva da vigilância em saúde: compilação de uma lista com base na CID-10.

OBJECTIVE: To propose a list of congenital anomalies having corresponding codes in the International Statistical Classification of Diseases and Related Health Problems, 10thRevision (ICD-10), with the aim of applying it in health surveillance. METHODS: In December 2019, the following data sources were searched: ICD-10; ICD-11; anomalies monitored by three surveillance programs; and a database of rare diseases (Orphanet). Anomalies were retrieved from these data sources, processed to check for correspondence with ICD-10 and reviewed manually to compile the list. RESULTS: 898 codes were identified, of which 619 (68.9%) were contained in ICD-10 Chapter XVII. Of the 279 codes contained in other chapters, 19 were exclusive to the ICD-11 search, 72 to the surveillance programs, 79 to Orphanet and 36 to the search for terms in ICD-10. CONCLUSION: The codes contained in ICD-10 Chapter XVII do not capture the totality of congenital anomalies, indicating the need to adopt an expanded list.

Genomic and Epidemiological Surveillance of Zika Virus in the Amazon Region.

Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.

Health surveillance at the SUS: development, effects and perspectives. / Vigilância em Saúde no SUS - construção, efeitos e perspectivas.

This article analyses the process of construction of Health Surveillance in Brazil concerning the political, historical and organizational context of this component of the Unified Health System (UHS), by means of its historical view and presentation of the advances, limits, setbacks and perspectives. Throughout trajectory of Health Surveillance, its objects of study and intervention have been expanded, strengthening the integration among the different areas of surveillance, increasing its capacity for prediction and intervention. It evolved from surveillance of people, to surveillance of diseases and now to surveillance of health risks, promoting greater articulation of HS professionals with agents of endemics and Family Health Teams. The first National Health Surveillance Conference, in February 2018, provided opportunities for discussion and formulation of proposals aimed at strengthening HS, expanding its scope of actions with a view to achieving a comprehensive care model. Adequate and audacious alternatives are necessary so that there are no setbacks in the financing modalities in order to maintain and expand the advances achieved in the field of Health Surveillance in Brazil.

Este artigo analisa o processo de construção da Vigilância em Saúde/VS no Brasil abordando o contexto político, histórico e organizacional deste componente do Sistema Único de Saúde, por meio do resgate histórico e apresentação dos avanços, limites, retrocessos e perspectivas. Ao longo da trajetória da VS, seus objetos de estudo e intervenção vêm se ampliando, fortalecendo a integração entre as diversas áreas da vigilância, aumentando sua capacidade de predição e intervenção. Evoluiu-se da vigilância das pessoas, para a das doenças e agora para a de riscos à saúde. A convocação da 1ª Conferência Nacional de Vigilância em Saúde, a ser realizada em 2018, oportuniza revisão e formulação de proposições voltadas para o fortalecimento da VS, expansão do seu escopo de ações e busca de alternativas adequadas e arrojadas, que garantam que a nova modalidade de financiamento do SUS aprovada em 2017, de fato, venha reforçar os avanços conquistados por este no campo da Saúde Coletiva.

Seroprevalence and factors associated with SARS-CoV-2 infection among education workers after the first wave: the first cross-sectional study in Brazil

ABSTRACT Background: The school community was heavily impacted by the Covid-19 pandemic, especially with the long time of school closures. This study aimed to analyze the seroprevalence of SARS-CoV-2 antibodies and possible factors associated with seropositivity for COVID-19 in teachers and other school staff, and to estimate the fraction of asymptomatic individuals by sex and age group. Methods: We conducted a serological survey of SARS-CoV-2 infections. An analytical cross-sectional study was conducted in Fortaleza, Brazil. Teachers and other staff members from pre-schools to universities of higher education to were investigated. Results: A total of 1,901 professionals participated in the study, of which 1,021 were staff and 880 were teachers. The seroprevalence of SARS-CoV-2 was 8.0% (152/1901). In the seropositive group, 48.3% were asymptomatic. There was a predominance of women (68.4%); and, 47.1% of the participants were between 31 and 45 years old. There was an increase in prevalence with increasing age. An inverse relationship was found for education level: more professionals with less education tested positive for COVID-19. The presence of an infected person living in the same household was significantly associated with positive results for COVID-19 among the professionals. Conclusions: This is the first study to report the seroprevalence of IgG against SARS-CoV-2 in Brazilian educational staff after the first wave of the disease. In this study, the seroprevalence was much lower than that in the general population. During school reopening, a small fraction of school workers showed serologically detectable signs of SARS-CoV-2 exposure.

Zika virus outbreak in Brazil.

Zika virus (ZIKV) infection is spreading rapidly within the Americas after originating from an outbreak in Brazil. We describe the current ZIKV infection epidemic in Brazil and the neurological symptoms arising. First cases of an acute exanthematic disease were reported in Brazil's Northeast region at the end of 2014. In March 2015, autochthonous ZIKV was determined to be the causative agent of the exanthematic disease. As cases of neurological syndromes in regions where ZIKV, dengue and/or Chikungunya viruses co-circulate were reported, ZIKV was also identified in the cerebrospinal fluid of patients with acute neurological syndromes and previous exanthematic disease. By the end of September 2015, an increasing number of infants with small head circumference or microcephaly were noted in Brazil's Northeast which was estimated to be 29 cases between August and October. ZIKV was identified in blood and tissue samples of a newborn and in mothers who had given birth to infants with microcephaly and ophthalmological anomalies. In 2015, there were an estimated 440,000 - 1,300,000 Zika cases in Brazil. There have been 4,783 suspected cases of microcephaly, most of them in the Northeast of Brazil associated with 76 deaths. The Ministry of Health is intensifying control measures against the mosquito Aedes aegypti and implemented intensive surveillance actions. Further studies are needed to confirm the suspected association between ZIKV infection and microcephaly; to identify antiviral, immunotherapy, or prophylactic vaccine; to introduce diagnostic ELISA testing. Clinical and epidemiological studies must be performed to describe viral dynamics and expansion of the outbreak.

Microcephaly in Pernambuco State, Brazil: epidemiological characteristics and evaluation of the diagnostic accuracy of cutoff points for reporting suspected cases. / Microcefalia no Estado de Pernambuco, Brasil: características epidemiológicas e avaliação da acurácia diagnóstica dos pontos de corte adotados para notificação de caso.

The increase in the number of reported cases of microcephaly in Pernambuco State, and Northeast Brazil, characterized an epidemic that led the Brazilian Ministry of Health to declare a national public health emergency. The Brazilian Ministry of Health initially defined suspected cases as newborns with gestational age (GA) ≥ 37 weeks and head circumference (HC) ≤ 33cm, but in December 2015 this cutoff was lowered to 32cm. The current study aimed to estimate the accuracy, sensitivity, and specificity of different cutoff points for HC, using ROC curves, with the Fenton and Intergrowth (2014) curves as the gold standard. The study described cases reported in Pernambuco from August 8 to November 28, 2015, according to sex and GA categories. The Fenton and Intergrowth methods provide HC growth curves according to GA and sex, and microcephaly is defined as a newborn with HC below the 3rd percentile in these distributions. Of the 684 reported cases, 599 were term or post-term neonates. For these, the analyses with ROC curves show that according to the Fenton criterion the cutoff point with the largest area under the ROC curve, with sensitivity greater than specificity, is 32cm for both sexes. Using the Intergrowth method and following the same criteria, the cutoff points are 32cm and 31.5cm for males and females, respectively. The cutoff point identified by the Fenton method (32cm) coincided with the Brazilian Ministry of Health recommendation. Adopting Intergrowth as the standard, the choice would be 32cm for males and 31.5cm for females. The study identified the need to conduct critical and on-going analyses to evaluate cutoff points, including other characteristics for microcephaly case definition.

Characteristics of the first cases of microcephaly possibly related to Zika virus reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. / Características dos primeiros casos de microcefalia possivelmente relacionados ao vírus Zika notificados na Região Metropolitana de Recife, Pernambuco.

OBJECTIVE: to describe the first cases of microcephaly possibly related to Zika virus in live born babies reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. METHODS: this was a descriptive case series study (cases reported between August 1st and October 31st 2015), using medical record data and data from a questionnaire answered by the mothers of the babies. RESULTS: 40 microcephaly cases were confirmed, distributed in eight municipalities within the Metropolitan Region, with Recife itself having the highest concentration of cases (n=12); median head circumference was 29 cm, median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers reported rash during pregnancy, 20 in the first trimester and 7 in the second trimester, as well as itching, headache, myalgia and absence of fever. CONCLUSION: the majority of the cases bore the characteristics of congenital infection; the clinical condition of the majority of mothers suggested Zika virus infection during pregnancy.