Profile of COVID-19 in Brazil-risk factors and socioeconomic vulnerability associated with disease outcome: retrospective analysis of population-based registers.

OBJECTIVES: To classify the most up-to-date factors associated with COVID-19 disease outcomes in Brazil. DESIGN: Retrospective study. SETTING: Nationwide Brazilian COVID-19 healthcare registers. PARTICIPANTS: We used healthcare data of individuals diagnosed with mild/moderate (n=70 056 602) or severe (n=2801 380) COVID-19 disease in Brazil between 26 February 2020 and 15 November 2021. MAIN OUTCOME MEASURES: Risk of hospitalisation and mortality affected by demographic, clinical and socioeconomic variables were estimated. The impacts of socioeconomic inequalities on vaccination rates, cases and deaths were also evaluated. RESULTS: 15.6 million SARS-CoV-2 infection cases and 584 761 COVID-19-related deaths occurred in Brazil between 26 February 2020 and 15 November 2021. Overall, men presented a higher odds of death than women (OR=1.14, 95% CI 1.13 to 1.15), but postpartum patients admitted to hospital wards were at increased odds of dying (OR=1.23, 95% CI 1.13 to 1.34) compared with individuals without reported comorbidities. Death in younger age groups was notably higher in most deprived municipalities and also among individuals <40 years belonging to indigenous backgrounds compared with white patients, as shown by descriptive analysis. Ethnic/racial backgrounds exhibited a continuum of decreasing survival chances of mixed-race (OR=1.11, 95% CI 1.10 to 1.12), black (OR=1.34, 95% CI 1.32 to 1.36) and indigenous (OR=1.42, 95% CI 1.31 to 1.54) individuals, while those in most deprived municipalities also presented an increased odds of death (OR=1.38, 95% CI 1.36 to 1.40). Deprivation levels also affect the prompt referral of patients to adequate care. Our results show that the odds of death of individuals hospitalised for less than 4 days is more than double that of patients with close-to-average hospital stays (OR=2.07, 95% CI 2.05 to 2.10). Finally, negative vaccination status also increased the odds of dying from the disease (OR=1.29, 95% CI 1.28 to 1.31). CONCLUSIONS: The data provide evidence that the patterns of COVID-19 mortality in Brazil are influenced by both individual-level health and social risk factors, as well as municipality-level deprivation. In addition, these data suggest that there may be inequalities in the timely provision of appropriate healthcare that are related to municipality-level deprivation.

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.

Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil.

BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).

Assessing the nationwide impact of COVID-19 mitigation policies on the transmission rate of SARS-CoV-2 in Brazil.

COVID-19 is now identified in almost all countries in the world, with poorer regions being particularly more disadvantaged to efficiently mitigate the impacts of the pandemic. In the absence of efficient therapeutics or large-scale vaccination, control strategies are currently based on non-pharmaceutical interventions, comprising changes in population behavior and governmental interventions, among which the prohibition of mass gatherings, closure of non-essential establishments, quarantine and movement restrictions. In this work we analyzed the effects of 707 governmental interventions published up to May 22, 2020, and population adherence thereof, on the dynamics of COVID-19 cases across all 27 Brazilian states, with emphasis on state capitals and remaining inland cities. A generalized SEIR (Susceptible, Exposed, Infected and Removed) model with a time-varying transmission rate (TR), that considers transmission by asymptomatic individuals, is presented. We analyze the effect of both the extent of enforced measures across Brazilian states and population movement on the changes in the TR and effective reproduction number. The social mobility reduction index, a measure of population movement, together with the stringency index, adapted to incorporate the degree of restrictions imposed by governmental regulations, were used in conjunction to quantify and compare the effects of varying degrees of policy strictness across Brazilian states. Our results show that population adherence to social distance recommendations plays an important role for the effectiveness of interventions and represents a major challenge to the control of COVID-19 in low- and middle-income countries.

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.

Mathematical modeling of COVID-19 in 14.8 million individuals in Bahia, Brazil.

COVID-19 is affecting healthcare resources worldwide, with lower and middle-income countries being particularly disadvantaged to mitigate the challenges imposed by the disease, including the availability of a sufficient number of infirmary/ICU hospital beds, ventilators, and medical supplies. Here, we use mathematical modelling to study the dynamics of COVID-19 in Bahia, a state in northeastern Brazil, considering the influences of asymptomatic/non-detected cases, hospitalizations, and mortality. The impacts of policies on the transmission rate were also examined. Our results underscore the difficulties in maintaining a fully operational health infrastructure amidst the pandemic. Lowering the transmission rate is paramount to this objective, but current local efforts, leading to a 36% decrease, remain insufficient to prevent systemic collapse at peak demand, which could be accomplished using periodic interventions. Non-detected cases contribute to a ∽55% increase in R0. Finally, we discuss our results in light of epidemiological data that became available after the initial analyses.

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.

Case Fatality Rate Related to Microcephaly Congenital Zika Syndrome and Associated Factors: A Nationwide Retrospective Study in Brazil †.

BACKGROUND: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child's health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child-maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015-2017. METHODS: Population-based study developed by linkage of three information systems. We estimate frequencies of cases, deaths, case fatality rate related to microcephaly/CZS according to child and maternal characteristics and causes of death. Multivariate logistic regression models were applied. RESULTS: The microcephaly/CZS case fatality rate was 10% (95% CI 9.2-10.7). Death related to microcephaly/CZS was associated to moderate (OR = 2.15; 95% CI 1.63-2.83), and very low birth weight (OR = 3.77; 95% CI 2.20-6.46); late preterm births (OR = 1.65; 95% CI 1.21-2.23), Apgar < 7 at 1st (OR = 5.98; 95% CI 4.46-8.02) and 5th minutes (OR = 4.13; 95% CI 2.78-6.13), among others. CONCLUSIONS: A high microcephaly/CZS case fatality rate and important factors associated with deaths related to this syndrome were observed. These results can alert health teams to these problems and increase awareness about the factors that may be associated with worse outcomes.

Interdependence between confirmed and discarded cases of dengue, chikungunya and Zika viruses in Brazil: A multivariate time-series analysis.

The co-circulation of different arboviruses in the same time and space poses a significant threat to public health given their rapid geographic dispersion and serious health, social, and economic impact. Therefore, it is crucial to have high quality of case registration to estimate the real impact of each arboviruses in the population. In this work, a Vector Autoregressive (VAR) model was developed to investigate the interrelationships between discarded and confirmed cases of dengue, chikungunya, and Zika in Brazil. We used data from the Brazilian National Notifiable Diseases Information System (SINAN) from 2010 to 2017. There were three peaks in the series of dengue notification in this period occurring in 2013, 2015 and in 2016. The series of reported cases of both Zika and chikungunya reached their peak in late 2015 and early 2016. The VAR model shows that the Zika series have a significant impact on the dengue series and vice versa, suggesting that several discarded and confirmed cases of dengue could actually have been cases of Zika. The model also suggests that the series of confirmed and discarded chikungunya cases are almost independent of the cases of Zika, however, affecting the series of dengue. In conclusion, co-circulation of arboviruses with similar symptoms could have lead to misdiagnosed diseases in the surveillance system. We argue that the routinely use of mathematical and statistical models in association with traditional symptom-surveillance could help to decrease such errors and to provide early indication of possible future outbreaks. These findings address the challenges regarding notification biases and shed new light on how to handle reported cases based only in clinical-epidemiological criteria when multiples arboviruses co-circulate in the same population.

Impact evaluation of Zika epidemic on congenital anomalies registration in Brazil: An interrupted time series analysis.

This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil. We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies. We obtained monthly data from Brazilian Live Birth Information System and used two outcome definitions: 1) rate of congenital malformation of the brain and eye (likely to be affected by Zika and its complications) 2) rate of congenital malformation not related to the brain or eye unlikely to be causally affected by Zika. The period between maternal infection with Zika and diagnosis of congenital abnormality attributable to the infection is around six months. We therefore used September 2015 as the interruption point in the time series, six months following March 2015 when cases of Zika started to increase. For the purposes of this analysis, we considered the period from January 2010 to September 2015 to be "pre-Zika event," and the period from just after September 2015 to December 2017 to be "post-Zika event." We found that immediately after the interruption point, there was a great increase in the notification rate of congenital anomalies of 14.9/10,000 live births in the brain and eye group and of 5.2/10,000 live births in the group not related with brain or eye malformations. This increase in reporting was in all regions of the country (except in the South) and especially in the Northeast. In the period "post-Zika event", unlike the brain and eye group which showed a monthly decrease, the group without brain or eye malformations showed a slow but significant increase (relative to the pre-Zika trend) of 0.2/10,000 live births. These findings suggest an overall improvement in the registration of birth malformations, including malformations that were not attributed to Zika, during and after the Zika epidemic.

Accuracy of the SD BIOLINE Dengue Duo for rapid point-of-care diagnosis of dengue.

BACKGROUND: Rapid diagnosis tests (RDTs) are easy to carry out, provide fast results, and could potentially guide medical treatment decisions. We investigated the performance of a commercially available RDT, which simultaneously detects the non-structural 1 (NS1) dengue virus (DENV) antigen, and IgM and IgG DENV antibodies, using representative serum samples from individuals in a dengue endemic area in Salvador, Brazil. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the accuracy of the SD BIOLINE Dengue Duo RDT (Abbott, Santa Clara, USA; former Alere Inc, Waltham, USA) in a random collection of sera. Samples included acute-phase sera from 246 laboratory-confirmed dengue cases and 108 non-dengue febrile patients enrolled in a surveillance study for dengue detection, 73 healthy controls living in the same surveillance community, and 73 blood donors. RDT accuracy was blindly assessed based on the combined results for the NS1 and the IgM test components. The RDT sensitivity was 46.8% (38.6% for the NS1 component and 13.8% for the IgM component). Sensitivity was greater for samples obtained from patients with secondary DENV infections (49.8%) compared to primary infections (31.1%) (P: 0.02) and was also influenced by the result in the confirmatory dengue diagnostic test, ranging from 39.7% for samples of cases confirmed by IgM-ELISA seroconversion between paired samples to 90.4% for samples of cases confirmed by a positive NS1-ELISA. The RDT specificity was 94.4% for non-dengue febrile patients, 87.7% for the community healthy controls, and 95.9% for the blood donors. CONCLUSIONS/SIGNIFICANCE: The SD BIOLINE Dengue Duo RDT showed good specificities, but low sensitivity, suggesting that it may be more useful to rule in than to rule out a dengue diagnosis in dengue endemic regions.

Effect of an intervention in storm drains to prevent Aedes aegypti reproduction in Salvador, Brazil.

BACKGROUND: Aedes aegypti, the principal vector for dengue, chikungunya and Zika viruses, is a synanthropic species that uses stagnant water to complete its reproductive cycle. In urban settings, rainfall water draining structures, such as storm drains, may retain water and serve as a larval development site for Aedes spp. reproduction. Herein, we describe the effect of a community-based intervention on preventing standing water accumulation in storm drains and their consequent infestation by adult and immature Ae. aegypti and other mosquitoes. METHODS: Between April and May of 2016, local residents association of Salvador, Brazil, after being informed of water accumulation and Ae. aegypti infestation in the storm drains in their area, performed an intervention on 52 storm drains. The intervention consisted of placing concrete at the bottom of the storm drains to elevate their base to the level of the outflow tube, avoiding water accumulation, and placement of a metal mesh covering the outflow tube to avoid its clogging with debris. To determine the impact of the intervention, we compared the frequency at which the 52 storm drains contained water, as well as adult and immature mosquitoes using data from two surveys performed before and two surveys performed after the intervention. RESULTS: During the pre-intervention period, water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains also decreased after the intervention. CONCLUSION: This study exemplifies how a simple intervention targeting storm drains can result in a major reduction of water retention, and, consequently, impact Ae. aegypti larval populations. Larger and multi-center evaluations are needed to confirm the potential of citywide structural modifications of storm drains to reduce Aedes spp. infestation level.

Storm drains as larval development and adult resting sites for Aedes aegypti and Aedes albopictus in Salvador, Brazil.

BACKGROUND: Dengue (DENV), Chikungunya (CHIKV), Zika (ZIKV), as well as yellow fever (YFV) viruses are transmitted to humans by Aedes spp. females. In Salvador, the largest urban center in north-eastern Brazil, the four DENV types have been circulating, and more recently, CHIKV and ZIKV have also become common. We studied the role of storm drains as Aedes larval development and adult resting sites in four neighbourhoods of Salvador, representing different socioeconomic, infrastructure and topographic conditions. RESULTS: A sample of 122 storm drains in the four study sites were surveyed twice during a 4-month period in 2015; in 49.0 % of the visits, the storm drains contained water. Adults and immatures of Aedes aegypti were captured in two of the four sites, and adults and immatures of Aedes albopictus were captured in one of these two sites. A total of 468 specimens were collected: 148 Ae. aegypti (38 adults and 110 immatures), 79 Ae. albopictus (48 adults and 31 immatures), and 241 non-Aedes (mainly Culex spp.) mosquitoes (42 adults and 199 immatures). The presence of adults or immatures of Ae. aegypti in storm drains was independently associated with the presence of non-Aedes mosquitoes and with rainfall of ≤ 50 mm during the preceding week. CONCLUSIONS: We found that in Salvador, one of the epicentres of the 2015 ZIKV outbreak, storm drains often accumulate water and serve as larval development sites and adult resting areas for both Ae. aegypti and Ae. albopictus. Vector control campaigns usually overlook storm drains, as most of the effort to prevent Ae. agypti reproduction is directed towards containers in the domicile environment. While further studies are needed to determine the added contribution of storm drains for the maintenance of Aedes spp. populations, we advocate that vector control programs incorporate actions directed at storm drains, including regular inspections and use of larvicides, and that human and capital resources are mobilized to modify storm drains, so that they do not serves as larval development sites for Aedes (and other) mosquitoes.

Spatial Distribution of Dengue in a Brazilian Urban Slum Setting: Role of Socioeconomic Gradient in Disease Risk.

BACKGROUND: Few studies of dengue have shown group-level associations between demographic, socioeconomic, or geographic characteristics and the spatial distribution of dengue within small urban areas. This study aimed to examine whether specific characteristics of an urban slum community were associated with the risk of dengue disease. METHODOLOGY/PRINCIPAL FINDINGS: From 01/2009 to 12/2010, we conducted enhanced, community-based surveillance in the only public emergency unit in a slum in Salvador, Brazil to identify acute febrile illness (AFI) patients with laboratory evidence of dengue infection. Patient households were geocoded within census tracts (CTs). Demographic, socioeconomic, and geographical data were obtained from the 2010 national census. Associations between CTs characteristics and the spatial risk of both dengue and non-dengue AFI were assessed by Poisson log-normal and conditional auto-regressive models (CAR). We identified 651 (22.0%) dengue cases among 2,962 AFI patients. Estimated risk of symptomatic dengue was 21.3 and 70.2 cases per 10,000 inhabitants in 2009 and 2010, respectively. All the four dengue serotypes were identified, but DENV2 predominated (DENV1: 8.1%; DENV2: 90.7%; DENV3: 0.4%; DENV4: 0.8%). Multivariable CAR regression analysis showed increased dengue risk in CTs with poorer inhabitants (RR: 1.02 for each percent increase in the frequency of families earning ≤1 times the minimum wage; 95% CI: 1.01-1.04), and decreased risk in CTs located farther from the health unit (RR: 0.87 for each 100 meter increase; 95% CI: 0.80-0.94). The same CTs characteristics were also associated with non-dengue AFI risk. CONCLUSIONS/SIGNIFICANCE: This study highlights the large burden of symptomatic dengue on individuals living in urban slums in Brazil. Lower neighborhood socioeconomic status was independently associated with increased risk of dengue, indicating that within slum communities with high levels of absolute poverty, factors associated with the social gradient influence dengue transmission. In addition, poor geographic access to health services may be a barrier to identifying both dengue and non-dengue AFI cases. Therefore, further spatial studies should account for this potential source of bias.

Development of a New Mosquito Retention System for the BG-Malaria Trap To Reduce The Damage To Mosquitoes.

The BG-Malaria trap was recently modified from the BioGents BG-Sentinel trap to collect Anopheles species, including Anopheles darlingi. However, the captured mosquitoes often lose their hind legs in the collector bag, making them difficult to identify. To develop a new collector system that is capable of maintaining the integrity of the mosquitoes collected in the BG-Malaria trap, we conducted a study in the municipalities of Belém (Pará State [PA]) and Porto Velho (Rondônia State [RO]), Brazil, using carbon dioxide-baited BG-Malaria traps with 4 different mosquito collector systems: standard, no bag, rigid short, and rigid long. Results indicated significant differences among the numbers of mosquitoes captured in the 4 different collectors (P < 0.05). Additionally, significantly fewer insects (P < 0.05) were damaged using the rigid short and rigid long collectors than by using the standard and no-bag collectors. We observed that the longer the insects remained in the collector, the higher the number of damaged insects; this effect was the greatest in the standard collector. The results of this study indicate that rigid long collectors were the best suited for use in the BG-Malaria trap.