Chikungunya seroprevalence in population-based studies: a systematic review and meta-analysis.

BACKGROUND: Seroprevalence studies about chikungunya infection are usually conducted after epidemics to estimate the magnitude of the attack. This study aimed to estimate the seroprevalence of CHIKV by WHO region, considering the periods of introduction of the virus in these regions and its potential to lead to epidemics. METHODS: We systematically reviewed Medline/Pubmed, Embase, Lilacs, Scopus and Web of Science for original articles published up to 2020. Cohort, case-control and cross-sectional studies were eligible for inclusion, based on the results of laboratory diagnosis of previous or previous and recent infection. Those conducted with symptomatic individuals were excluded. RESULTS: 596 articles were identified, 197 full-text were reviewed and 64 were included, resulting in 71 seroprevalences. Most were cross-sectional studies (92%), between 2001 and 2020 (92%), with population of all ages (55%), conducted in Kenya (10.9%), Brazil (9.4%) and French Polynesia (7.8%). The pooled estimates were 24% (95%CI 19-29; I2 = 99.7%; p < 0.00), being 21% (95%CI 13-30; I2 = 99.5%; p < 0.00) for adults, 7% (95%CI 0-23; I2 = 99.7%; p < 0.00) for children and 30% (95%CI 23-38; I2 = 99.7%; p < 0.00) for all ages. The higher seroprevalences were found in African, the Americas and South-East Asian Regions. CONCLUSIONS: The great heterogeneity of seroprevalences points to the persistence of viral circulation. Even where the seroprevalence is high, the population replacement and the absence of vaccines mean that the risk of virus spread and epidemics remains. REGISTRATION: PROSPERO CRD42020166227.

Fetal death as an outcome of acute respiratory distress in pregnancy, during the COVID-19 pandemic: a population-based cohort study in Bahia, Brazil.

BACKGROUND: Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. METHODS: This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. RESULTS: 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). CONCLUSION: Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.

Temporal trends in prevalence and infant mortality of birth defects in Brazil, from 2001 to 2018. / Tendência temporal da prevalência e mortalidade infantil das anomalias congênitas no Brasil, de 2001 a 2018.

Congenital anomalies (CA) are a relevant problem for global public health, affecting about 3% to 6% of newborns worldwide. In Brazil, these are the second main cause of infant mortality. Thus, extensive studies are needed to demonstrate the impact of these anomalies on births and deaths. The present study describes the temporal trends of prevalence and infant mortality due to CA among live births in Brazil and regions, from 2001 to 2018, using the related data between the Live Birth Information System (SINASC, acronym in Portuguese) and the Mortality Information System (SIM, acronym in Portuguese). The prevalence and infant mortality due to CA has increased in Brazil and in most regions, especially in the Northeast and North. CAs in the musculoskeletal system were the most frequent at birth (29.8/10,000 live births), followed by those in the circulatory system (12.7/10,000 live births), which represented the primary cause of death in this group. The applied linkage technique made it possible to correct the national prevalence of CA by 17.9% during the analyzed period, after retrieving the anomalies reported in SIM, thereby proving to be a good tool to improve the quality of information on anomalies in Brazil.

As anomalias congênitas (AC) configuram um relevante problema para a saúde pública global, afetando em média de 3% a 6% dos recém-nascidos em todo o mundo. No Brasil, ocupam a segunda posição entre os principais grupos de causas de óbito infantil. Assim, estudos amplos são necessários para mostrar o impacto das AC na saúde infantil. O presente estudo descreve a tendência temporal da prevalência e da mortalidade infantil por AC entre nascidos vivos (NV) no Brasil e em suas cinco regiões de 2001 a 2018, utilizando dados vinculados entre as bases de dados do Sistema de Informações sobre Nascidos Vivos (SINASC) e do Sistema de Informações sobre Mortalidade (SIM). A prevalência e mortalidade infantil por AC mostrou-se crescente no Brasil na maioria das regiões, principalmente no Norte e no Nordeste. Aquelas do aparelho osteomuscular foram as mais prevalentes ao nascimento (29,8/10.000 NV); as do aparelho circulatório passaram para a segunda posição (12,7/10.000 NV) após a vinculação das bases e representam a primeira causa de morte desse grupo. A técnica de vinculação de dados aplicada corrigiu a prevalência nacional das AC em 17,9% no período analisado, após serem recuperadas as AC notificadas no SIM, mostrando ser uma boa ferramenta para melhorar a qualidade das informações das AC.

Tendência temporal da prevalência e mortalidade infantil das anomalias congênitas no Brasil, de 2001 a 2018 / Temporal trends in prevalence and infant mortality of birth defects in Brazil, from 2001 to 2018

Resumo As anomalias congênitas (AC) configuram um relevante problema para a saúde pública global, afetando em média de 3% a 6% dos recém-nascidos em todo o mundo. No Brasil, ocupam a segunda posição entre os principais grupos de causas de óbito infantil. Assim, estudos amplos são necessários para mostrar o impacto das AC na saúde infantil. O presente estudo descreve a tendência temporal da prevalência e da mortalidade infantil por AC entre nascidos vivos (NV) no Brasil e em suas cinco regiões de 2001 a 2018, utilizando dados vinculados entre as bases de dados do Sistema de Informações sobre Nascidos Vivos (SINASC) e do Sistema de Informações sobre Mortalidade (SIM). A prevalência e mortalidade infantil por AC mostrou-se crescente no Brasil na maioria das regiões, principalmente no Norte e no Nordeste. Aquelas do aparelho osteomuscular foram as mais prevalentes ao nascimento (29,8/10.000 NV); as do aparelho circulatório passaram para a segunda posição (12,7/10.000 NV) após a vinculação das bases e representam a primeira causa de morte desse grupo. A técnica de vinculação de dados aplicada corrigiu a prevalência nacional das AC em 17,9% no período analisado, após serem recuperadas as AC notificadas no SIM, mostrando ser uma boa ferramenta para melhorar a qualidade das informações das AC.

Abstract Congenital anomalies (CA) are a relevant problem for global public health, affecting about 3% to 6% of newborns worldwide. In Brazil, these are the second main cause of infant mortality. Thus, extensive studies are needed to demonstrate the impact of these anomalies on births and deaths. The present study describes the temporal trends of prevalence and infant mortality due to CA among live births in Brazil and regions, from 2001 to 2018, using the related data between the Live Birth Information System (SINASC, acronym in Portuguese) and the Mortality Information System (SIM, acronym in Portuguese). The prevalence and infant mortality due to CA has increased in Brazil and in most regions, especially in the Northeast and North. CAs in the musculoskeletal system were the most frequent at birth (29.8/10,000 live births), followed by those in the circulatory system (12.7/10,000 live births), which represented the primary cause of death in this group. The applied linkage technique made it possible to correct the national prevalence of CA by 17.9% during the analyzed period, after retrieving the anomalies reported in SIM, thereby proving to be a good tool to improve the quality of information on anomalies in Brazil.

Complex network analysis of arboviruses in the same geographic domain: Differences and similarities.

Arbovirus can cause diseases with a broad spectrum from mild to severe and long-lasting symptoms, affecting humans worldwide and therefore considered a public health problem with global and diverse socio-economic impacts. Understanding how they spread within and across different regions is necessary to devise strategies to control and prevent new outbreaks. Complex network approaches have widespread use to get important insights on several phenomena, as the spread of these viruses within a given region. This work uses the motif-synchronization methodology to build time varying complex networks based on data of registered infections caused by Zika, chikungunya, and dengue virus from 2014 to 2020, in 417 cities of the state of Bahia, Brazil. The resulting network sets capture new information on the spread of the diseases that are related to the time delay in the synchronization of the time series among different municipalities. Thus the work adds new and important network-based insights to previous results based on dengue dataset in the period 2001-2016. The most frequent synchronization delay time between time series in different cities, which control the insertion of edges in the networks, ranges 7 to 14 days, a period that is compatible with the time of the individual-mosquito-individual transmission cycle of these diseases. As the used data covers the initial periods of the first Zika and chikungunya outbreaks, our analyses reveal an increasing monotonic dependence between distance among cities and the time delay for synchronization between the corresponding time series. The same behavior was not observed for dengue, first reported in the region back in 1986, either in the previously 2001-2016 based results or in the current work. These results show that, as the number of outbreaks accumulates, different strategies must be adopted to combat the dissemination of arbovirus infections.

Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study.

BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

Socioeconomic risk markers of congenital Zika syndrome: a nationwide, registry-based study in Brazil.

While it is well known that socioeconomic markers are associated with a higher risk of arbovirus infections, research on the relationship between socioeconomic factors and congenital Zika syndrome (CZS) remains limited. This study investigates the relationship between socioeconomic risk markers and live births with CZS in Brazil. We conducted a population-based study using data from all registered live births in Brazil (Live Births Information System) linked with the Public Health Event Record from 1 January 2015 to 31 December 2018. We used logistic regression models to estimate the OR and 95% CIs of CZS based on a three-level framework. In an analysis of 11 366 686 live births, of which 3353 had CZS, we observed that live births of self-identified black or mixed race/brown mothers (1.72 (95% CI 1.47 to 2.01) and 1.37 (95% CI 1.24 to 1.51)) were associated with a higher odds of CZS. Live births from single women compared with married women and those from women with less than 12 years of education compared with those with more than 12 years of education also had higher odds of CZS. In addition, live births following fewer prenatal care appointments had increased odds of CZS in the nationwide data. However, in the analyses conducted in the Northeast region (where the microcephaly epidemic started before the link with Zika virus was established and before preventive measures were known or disseminated), no statistical association was found between the number of prenatal care appointments and the odds of CZS. This study shows that live births of the most socially vulnerable women in Brazil had the greatest odds of CZS. This disproportionate distribution of risk places an even greater burden on already socioeconomically disadvantaged groups, and the lifelong disabilities caused by this syndrome may reinforce existing social and health inequalities.

Population-based surveillance for congenital zika virus syndrome: a latent class analysis of recorded cases from 2015-2018.

OBJECTIVE: This study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases. METHODS: A retrospective cohort study using routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan-Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months. RESULTS: We followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8-18.0) and other abnormalities (HR = 11.6; IC95%8.6-15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4-10.6) and macrocephaly (HR = 6.6; IC95%4.5-9.7) compared with normal head size. CONCLUSION: Abnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses.

The triple epidemics of arboviruses in Feira de Santana, Brazilian Northeast: Epidemiological characteristics and diffusion patterns.

Arboviruses are diseases of worldwide importance in the field of communicable diseases. In Brazil, the reemergence of dengue and the emergence of chikungunya and Zika since 2014 have led to epidemic waves of great magnitude and rapid spread. However, their diffusion patterns vary and change over time. This study analyzes the spatial diffusion of the simultaneous circulation of three arboviruses transmitted by the same vector in a large urban space over two epidemic waves in consecutive years. An ecological study of spatial and temporal aggregates on the occurrence of dengue, chikungunya, and Zika, from 2014 to 2019, in Feira de Santana, Bahia State, was carried out using data of cases reported to the national surveillance system. Four different methods were used to analyze the spatial diffusion: Kernel Estimation with sequential maps, cumulative nearest-neighbor ratios (NNI) over time, spatial correlograms and local autocorrelation changes (LISA) over time. From 2014-2019, there were 21,723 confirmed cases of arboviruses. The highest incidences were among women (496.9, 220.2, and 91.0 cases/100,000 women for dengue, chikungunya and Zika respectively). By age group, the highest incidences were from ages 10-19 years old (609.3 dengue cases/100,000), from 60 and more (306.7 chikungunya cases/100,000), and from 0-9 years old (124.1 Zika cases/100,000 inhabitants). The temporal distribution demonstrated two epidemic waves of simultaneous circulation in 2014 and 2015. Kernel maps indicate that arboviruses spread to neighboring areas near the first hotspots, suggesting an expansion diffusion pattern. The NNI, spatial correlograms and LISA changes results suggest expansion patterns for the three arboviruses in all periods. The spatial diffusion pattern of dengue, Zika, and chikungunya in the 2014-2015 epidemics in Feira de Santana was expansion. These findings are useful to guide prevention measures and reduce occurrence in other areas.

Risk of mortality for small newborns in Brazil, 2011-2018: A national birth cohort study of 17.6 million records from routine register-based linked data.

BACKGROUND: Preterm birth (<37 weeks), low birth weight (LBW,<2500g), and small for gestational age (SGA,<10th centile of birth weight for gestational age and sex) are markers of newborn vulnerability with a high risk of mortality. We estimated the prevalence of phenotypes combining these three markers and quantified the mortality risk associated with them. METHODS: Population-based cohort study using routine register-based linked data on all births and deaths in Brazil from January 1, 2011, to December 31, 2018. We estimated the prevalence of preterm, LBW, and SGA individually and for phenotypes combining these characteristics. The mortality risk associated with each phenotype: early neonatal, late neonatal, neonatal, post-neonatal, infant, 1-4 years, and under five years was quantified using mortality rates and hazard ratios (HRs) with 95% confidence interval (CI) were estimated using Cox proportional hazard models. FINDINGS: 17,646,115 live births were included. Prevalence of preterm birth, LBW and SGA were 9.4%, 9.6% and 9.2%, respectively. Neonatal mortality risk was 16-fold (HR=15.9; 95% CI:15.7-16.1) higher for preterm compared to term, 3 times higher (HR=3.4; (95% CI:3.3-3.4) for SGA compared to adequate for gestational age (AGA), and >25 times higher for LBW (HR=25.8; (95% CI:25.5-26.1) compared to normal birth weight (NBW). 18% of all live births were included in one of the small vulnerable newborn phenotypes. Of those 8.2% were term-SGA (4.7%NBW, 3.5%LBW), 0.6% were term-AGA-LBW, 8.3% preterm-AGA (3.8%NBW, 4.5%LBW) and 1.0% preterm-SGA-LBW. Compared to term-AGA-NBW, the highest mortality risk was for preterm-LBW phenotypes (HR=36.2(95%CI 35.6-36.8) preterm-AGA-LBW, HR=62.0(95%CI 60.8-63.2) preterm-SGA-LBW). The increased mortality risk associated with vulnerable newborn phenotypes was highest in the first month of life, with attenuated but continued high risk in the post-neonatal period and 1-4 years of age. INTERPRETATION: Our findings support the value of using more detailed phenotypes to identify those at highest risk. More granular data can inform care at the individual level, advance research, especially for prevention, and accelerate progress towards global targets such as the Sustainable Development Goals. FUNDING: Wellcome Trust.

Associations between cesarean delivery and child mortality: A national record linkage longitudinal study of 17.8 million births in Brazil.

BACKGROUND: There is an increasing use of cesarean delivery (CD) based on preference rather than on medical indication. However, the extent to which nonmedically indicated CD benefits or harms child survival remains unclear. Our hypothesis was that in groups with a low indication for CD, this procedure would be associated with higher child mortality and in groups with a clear medical indication CD would be associated with improved child survival chances. METHODS AND FINDINGS: We conducted a population-based cohort study in Brazil by linking routine data on live births between January 1, 2012 and December 31, 2018 and assessing mortality up to 5 years of age. Women with a live birth who contributed records during this period were classified into one of 10 Robson groups based on their pregnancy and delivery characteristics. We used propensity scores to match CD with vaginal deliveries (1:1) and prelabor CD with unscheduled CD (1:1) and estimated associations with child mortality using Cox regressions. A total of 17,838,115 live births were analyzed. After propensity score matching (PSM), we found that live births to women in groups with low expected frequencies of CD (Robson groups 1 to 4) had a higher death rate up to age 5 years if they were born via CD compared with vaginal deliveries (HR = 1.25, 95% CI: 1.22 to 1.28; p < 0.001). The relative rate was greatest in the neonatal period (HR = 1.39, 95% CI: 1.34 to 1.45; p < 0.001). There was no difference in mortality rate when comparing offspring born by a prelabor CD to those born by unscheduled CD. For the live births to women with a CD in a prior pregnancy (Robson group 5), the relative rates for child mortality were similar for those born by CD compared with vaginal deliveries (HR = 1.05, 95% CI: 1.00 to 1.10; p = 0.024). In contrast, for live births to women in groups with high expected rates of CD (Robson groups 6 to 10), the child mortality rate was lower for CD than for vaginal deliveries (HR = 0.90, 95% CI: 0.89 to 0.91; p < 0.001), particularly in the neonatal period (HR = 0.84, 95% CI: 0.83 to 0.85; p < 0.001). Our results should be interpreted with caution in clinical practice, since relevant clinical data on CD indication were not available. CONCLUSIONS: In this study, we observed that in Robson groups with low expected frequencies of CD, this procedure was associated with a 25% increase in child mortality. However, in groups with high expected frequencies of CD, the findings suggest that clinically indicated CD is associated with a reduction in child mortality.

Using the Robson classification to assess caesarean section rates in Brazil: an observational study of more than 24 million births from 2011 to 2017.

BACKGROUND: Applying the Robson classification to all births in Brazil, the objectives of our study were to estimate the rates of caesarean section delivery, assess the extent to which caesarean sections were clinically indicated, and identify variation across socioeconomic groups. METHODS: We conducted a population-based study using routine records of the Live Births Information System in Brazil from January 1, 2011, to December 31, 2017. We calculated the relative size of each Robson group; the caesarean section rate; and the contribution to the overall caesarean section rate. We categorised Brazilian municipalities using the Human Development Index to explore caesarean section rates further. We estimated the time trend in caesarean section rates. RESULTS: The rate of caesarean sections was higher in older and more educated women. Prelabour caesarean sections accounted for more than 54 % of all caesarean deliveries. Women with a previous caesarean section (Group 5) made up the largest group (21.7 %). Groups 6-9, for whom caesarean sections would be indicated in most cases, all had caesarean section rates above 82 %, as did Group 5. The caesarean section rates were higher in municipalities with a higher HDI. The general Brazilian caesarean section rate remained stable during the study period. CONCLUSIONS: Brazil is a country with one of the world's highest caesarean section rates. This nationwide population-based study provides the evidence needed to inform efforts to improve the provision of clinically indicated caesarean sections. Our results showed that caesarean section rates were lower among lower socioeconomic groups even when clinically indicated, suggesting sub-optimal access to surgical care.

Impact of COVID-19 pandemic on time series of maternal mortality ratio in Bahia, Brazil: analysis of period 2011-2020.

BACKGROUND: Most studies on the effects of SARS-CoV-2 infection have been conducted with adults and non-pregnant women. Thus, its impacts on maternal health are not yet fully established. This study aimed to verify the relationship between the maternal mortality ratio and the incidence of COVID-19 in the State of Bahia, Brazil, 2020. METHODS: This time-series study used publicly available information in Brazil, to obtain data on maternal deaths and live births in Bahia, State, from January 1, 2011, to December 31, 2020. The time trend of Maternal Mortality Ratio (MMR) was analysed through polynomial regression, of order 6. Expected MMR, monthly (Jan-Dec) and annual values for 2020, were predicted by the additive Holt-Winters exponential smoothing algorithm, with 95% confidence interval, based on the time series of the MMR from 2011 to 2019, and the accuracy of the forecasts for 2020 was assessed by checking the smoothing coefficients and the mean errors. According to the statistical forecast, the MMR values ​​recorded in the year 2020 were compared to those expected. RESULTS: In 2020, the annual MMR in Bahia, Brazil, was 78.23/100,000 live births, 59.46% higher than the expected ratio (49.06 [95% CI 38.70-59.90]). The increase in maternal mortality ratio relative to expected values was observed throughout the 2020 months; however, only after May, when the COVID-19 epidemic rose sharply, it exceeded the upper limit of the 95% CI of the monthly prediction. Of the 144 registered maternal deaths in 2020, 19 (13.19%) had COVID-19 mentioned as the cause of death. CONCLUSIONS: Our study revealed the increase in maternal mortality, and its temporal relationship with the incidence of COVID-19, in Bahia, Brazil, in 2020. The COVID-19 pandemic may be directly and indirectly related to this increase, which needs to be investigated. An urgent public health action is needed to prevent and reduce maternal deaths during this pandemic, in Brazil.

Zika Virus Congenital Syndrome and MTOR gene variants: insights from a family of dizygotic twins.

Congenital Zika virus syndrome (CZS) is associated with damage to neural progenitor cells by ZIKA virus infection. There are no accurate statistics on the percentage of pregnant mothers who have had babies affected by the syndrome. Few cases of discordant twins have been described in the literature and, therefore, we hypothesize that the genetic background of the progeny and/or mother may play a role in the fate of the syndrome. We performed a complete exome sequencing in a set of dizygotic individuals and their parents. After that, we selected discordant variants on the MTOR gene between the affected and unaffected twin and we observed a mutation (rs2295079), placed in a region restricted to proximal 5'-UTR, as a strong possible causal variant. In addition, in most brain tissues (including fetal brain) evaluated for expression quantitative trait loci (eQTL), this locus is strongly correlated with post-translational modifications of histones (promoter and enhancer marks) and hypersensitivity to DNAse I (open chromatin mark). Taken together, our data suggest that changes in the MTOR gene may be related to CZS. Additional functional studies should be carried out to prove how and why a MTOR mutation can predispose the fetus to the syndrome.

Seroprevalence of Chikungunya virus and living conditions in Feira de Santana, Bahia-Brazil.

BACKGROUND: Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033). CONCLUSIONS/SIGNIFICANCE: The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.

Classification algorithm for congenital Zika Syndrome: characterizations, diagnosis and validation.

Zika virus was responsible for the microcephaly epidemic in Brazil which began in October 2015 and brought great challenges to the scientific community and health professionals in terms of diagnosis and classification. Due to the difficulties in correctly identifying Zika cases, it is necessary to develop an automatic procedure to classify the probability of a CZS case from the clinical data. This work presents a machine learning algorithm capable of achieving this from structured and unstructured available data. The proposed algorithm reached 83% accuracy with textual information in medical records and image reports and 76% accuracy in classifying data without textual information. Therefore, the proposed algorithm has the potential to classify CZS cases in order to clarify the real effects of this epidemic, as well as to contribute to health surveillance in monitoring possible future epidemics.

New Insights on the Zika Virus Arrival in the Americas and Spatiotemporal Reconstruction of the Epidemic Dynamics in Brazil.

Zika virus (ZIKV) became a worldwide public health emergency after its introduction in the Americas. Brazil was implicated as central in the ZIKV dispersion, however, a better understanding of the pathways the virus took to arrive in Brazil and the dispersion within the country is needed. An updated genome dataset was assembled with publicly available data. Bayesian phylogeography methods were applied to reconstruct the spatiotemporal history of ZIKV in the Americas and with more detail inside Brazil. Our analyses reconstructed the Brazilian state of Pernambuco as the likely point of introduction of ZIKV in Brazil, possibly during the 2013 Confederations Cup. Pernambuco played an important role in spreading the virus to other Brazilian states. Our results also underscore the long cryptic circulation of ZIKV in all analyzed locations in Brazil. Conclusions: This study brings new insights about the early moments of ZIKV in the Americas, especially regarding the Brazil-Haiti cluster at the base of the American clade and describing for the first time migration patterns within Brazil.