Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Healthcare-associated infections on the intensive care unit in 21 Brazilian hospitals during the early months of the coronavirus disease 2019 (COVID-19) pandemic: An ecological study.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis and may have affected healthcare-associated infection (HAI) prevention strategies. We evaluated the impact of the COVID-19 pandemic on HAI incidence in Brazilian intensive care units (ICUs). METHODS: In this ecological study, we compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (prepandemic period) in 21 Brazilian hospitals. We used the Wilcoxon signed rank-sum test in a pairwise analysis to compare the following differences between the pandemic and the prepandemic periods: microbiologically confirmed central-line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 central line and ventilator days, respectively), the proportion of organisms that caused HAI, and antibiotic consumption (DDD). RESULTS: We detected a significant increase in median CLABSI incidence during the pandemic: 1.60 (IQR, 0.44-4.20) vs 2.81 (IQR, 1.35-6.89) (P = .002). We did not detect a significant difference in VAP incidence between the 2 periods. In addition, we detected a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida spp during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. We did not detect a significant change in ceftriaxone, piperacillin-tazobactam, meropenem, or vancomycin consumption between the studied periods. CONCLUSIONS: There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we detected an increase in the proportion of CLABSI caused by E. faecalis and Candida spp during this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.

Predicting SARS-CoV-2 Variant Spread in a Completely Seropositive Population Using Semi-Quantitative Antibody Measurements in Blood Donors.

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

SARS-CoV-2 seropositivity and COVID-19 among 5 years-old Amazonian children and their association with poverty and food insecurity.

BACKGROUND: The epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2-48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9-8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4-9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2-2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8-3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and-even more markedly-of having had clinically apparent COVID-19 by the age of 5 years. CONCLUSIONS/SIGNIFICANCE: Childhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease.

Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.

Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil.

BACKGROUND: The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection. METHODS: We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants. RESULTS: From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included. CONCLUSIONS: Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

Access to colposcopy in the State of São Paulo, Brazil: probabilistic linkage study of administrative data.

Cervical cancer screening is a multistage process, therefore access to both the primary test and subsequent diagnostic procedures is essential. Considering women undergoing screening on the public health system in the State of São Paulo, Brazil, we aimed to estimate the proportion of women accessing colposcopy within six months of an abnormal smear result. We retrieved records from two administrative databases, the Information System on Uterine Cervical Cancer (SISCOLO) that contains smear results and the Outpatient Information System of the Brazilian Unified National Health System (SIA/SUS) that records colposcopies. A reference cohort consisted of women, aged 25 years or older, with an abnormal smear result between May 1, 2014, and June 30, 2014. We excluded prevalent cases. We linked the reference cohort and records in the SIA/SUS extending to December 31, 2014. After excluding prevalent cases, 1,761 women with abnormal cytology results were left. A total of 700 (39.8%) women were linked to a colposcopy record within the follow-up period; this dropped to 671 (38.1%) women when follow-up was censored at six months. We could notice a slightly higher attendance in women living in the metropolitan region of São Paulo compared with residents of the rest of the state. We found no association between colposcopy attendance and age or cytology class. These results emphasize that access to colposcopy in the public health system in São Paulo is limited. This compromises the quality of screening, and the issue needs to be prioritized in service planning.

Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020-2021.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant has been hypothesized to cause more severe illness than previous variants, especially in children. Successive SARS-CoV-2 IgG serosurveys in the Brazilian Amazon showed that age-specific attack rates and proportions of symptomatic SARS-CoV-2 infections were similar before and after Gamma variant emergence.

Access to colposcopy in the State of São Paulo, Brazil: probabilistic linkage study of administrative data / Acesso à colposcopia no Estado de São Paulo, Brasil: um estudo de relacionamento probabilístico de dados administrativos / Acceso a la colposcopía en el Estado de São Paulo, Brasil: estudio de vinculación probabilística con datos administrativos

Cervical cancer screening is a multistage process, therefore access to both the primary test and subsequent diagnostic procedures is essential. Considering women undergoing screening on the public health system in the State of São Paulo, Brazil, we aimed to estimate the proportion of women accessing colposcopy within six months of an abnormal smear result. We retrieved records from two administrative databases, the Information System on Uterine Cervical Cancer (SISCOLO) that contains smear results and the Outpatient Information System of the Brazilian Unified National Health System (SIA/SUS) that records colposcopies. A reference cohort consisted of women, aged 25 years or older, with an abnormal smear result between May 1, 2014, and June 30, 2014. We excluded prevalent cases. We linked the reference cohort and records in the SIA/SUS extending to December 31, 2014. After excluding prevalent cases, 1,761 women with abnormal cytology results were left. A total of 700 (39.8%) women were linked to a colposcopy record within the follow-up period; this dropped to 671 (38.1%) women when follow-up was censored at six months. We could notice a slightly higher attendance in women living in the metropolitan region of São Paulo compared with residents of the rest of the state. We found no association between colposcopy attendance and age or cytology class. These results emphasize that access to colposcopy in the public health system in São Paulo is limited. This compromises the quality of screening, and the issue needs to be prioritized in service planning.

A triagem do câncer de colo uterino é um processo que envolve múltiplas etapas. É essencial o acesso ao teste primário e aos procedimentos diagnósticos subsequentes. Com foco nas mulheres que fazem triagem no sistema de saúde pública no Estado de São Paulo, Brasil, buscamos estimar a proporção daquelas que acessam a colposcopia dentro de seis meses após um resultado anormal no teste de Papanicolau. Recuperamos os registros de duas bases de dados administrativos: o Sistema de Informação do Controle do Câncer do Colo do Útero (SISCOLO), que contém os resultados de Papanicolau, e o Sistema de Informação Ambulatorial do Sistema Único de Saúde (SIA/SUS), com os registros das colposcopias. Uma coorte de referência foi constituída de mulheres com idade de 25 anos ou mais com Papanicolau anormal entre 1º de maio de 2014 e 30 de junho de 2014. Excluímos casos prevalentes. Relacionamos a coorte de referência aos registros no SIA/SUS, estendendo até 31 de dezembro de 2014. Após a exclusão dos casos prevalentes, restaram 1.761 mulheres com citologia anormal. Setecentas delas (39,8%) foram relacionadas a um registro de colposcopia dentro do período de seguimento; esse número diminuiu para 671 (38,1%) quando o seguimento foi censurado aos seis meses. Foi observada uma cobertura ligeiramente maior entre mulheres residentes na Grande São Paulo, em comparação com mulheres residentes do interior do estado. Não houve associação entre realização de colposcopia e idade ou classe citológica. Os resultados destacam o acesso restrito à colposcopia no sistema público de saúde no Estado de São Paulo. O cenário compromete a qualidade da triagem, e a questão deve ser priorizada no planejamento dos serviços.

Las pruebas de detección del cáncer cervical forman parte de un proceso multietapa. El acceso a tanto el test primario, como a los subsiguientes procedimientos de diagnóstico, es esencial. Considerando a las mujeres que se realizan las pruebas de detección en el sistema público de la salud en el Estado de São Paulo, Brasil, el objetivo del estudio fue estimar la proporción de mujeres que acceden a una colposcopía dentro de los seis meses, tras el resultado anormal en una citología. Recuperamos los registros de dos bases de datos administrativas: el Sistema de Información del Cáncer de Cuello de Útero (SISCOLO), que contiene resultados citológicos, y el Sistema de Información Ambulatoria del Sistema Único de Salud (SIA/SUS), que registra colposcopías. La cohorte de referencia consistía en mujeres, con 25 años de edad o mayores, quienes recibieron un resultado anormal en su citología entre el 1º mayo de 2014 y el 30 de junio 2014. Excluimos los casos prevalentes. Vinculamos la cohorte de referencia y los registros en la SIA/SUS, extendiéndolos hasta el 31 de diciembre 2014. Tras excluir los casos prevalentes, quedaron 1.761 mujeres con resultados citológicos anormales; 700 (39.8%), vinculados a un registro de colposcopía dentro del periodo de seguimient. Esta cifra cayó a 671 (38.1%) cuando el seguimiento fue censurado a los seis meses. Se observó una participación ligeramente superior en mujeres que viven en la región metropolitana de la gran São Paulo, comparada con los residentes del resto del estado. No hubo asociación entre la participación en la colposcopía y edad o tipo de citología. Estos resultados resaltan que el acceso a la colposcopía en el sistema público de São Paulo es limitado. Esto compromete la calidad de las pruebas de detección por lo que se necesita darles prioridad en la planificación de los servicios sanitarios.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals.

BACKGROUND: There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. METHODS: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. RESULTS: We enrolled 499 T. cruzi-seropositive donors (age 48±10 years, 52% male), 488 T. cruzi-seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). CONCLUSIONS: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

Cohort profile update: the main and new findings from the SaMi-Trop Chagas cohort.

The SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic areas of Chagas disease, including 1,959 patients with chronic Chagas cardiomyopathy. In this article we updated the results of the project, adding information from the second cohort visit. Trypanosoma cruzi-seropositive patients were enrolled from the primary care Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for the second visit was the participation in the baseline evaluation. Of 1,959 participants at the baseline assessment, 1,585 (79.9%) returned after two years for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to 18.2% when it was stratified by certain clinical characteristics. A lower age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment were associated with lower mortality. There was an improvement in most quality of life domain scores. Participants have also reported fewer signs and symptoms and greater use of medication. The second follow-up visit will be complete in Oct 2021.

Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis.

OBJECTIVE: To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. METHODS: Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. RESULTS: Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. CONCLUSION: The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy.

Higher risk of death from COVID-19 in low-income and non-White populations of São Paulo, Brazil.

INTRODUCTION: Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. METHODS: We conducted a cross-sectional study using hospitalised severe acute respiratory infections notified from March to August 2020 in the Sistema de Monitoramento Inteligente de São Paulo database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple data sets for individual-level and spatiotemporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour and comorbidities. RESULTS: Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared with patients living in the 5% wealthiest areas (OR: 1.60, 95% CI 1.48 to 1.74) and were more likely to be hospitalised between April and July 2020 (OR: 1.08, 95% CI 1.04 to 1.12). Black and Pardo individuals were more likely to be hospitalised when compared with White individuals (OR: 1.41, 95% CI 1.37 to 1.46; OR: 1.26, 95% CI 1.23 to 1.28, respectively), and were more likely to die (OR: 1.13, 95% CI 1.07 to 1.19; 1.07, 95% CI 1.04 to 1.10, respectively) between April and July 2020. Once hospitalised, patients treated in public hospitals were more likely to die than patients in private hospitals (OR: 1.40%, 95% CI 1.34% to 1.46%). Black individuals and those with low education attainment were more likely to have one or more comorbidities, respectively (OR: 1.29, 95% CI 1.19 to 1.39; 1.36, 95% CI 1.27 to 1.45). CONCLUSIONS: Low-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to quality healthcare, ability to self-isolate and the higher prevalence of comorbidities.

Prolonged presence of replication-competent SARS-CoV-2 in mildly symptomatic individuals: A report of two cases.

It has been estimated that individuals with COVID-19 can shed replication-competent virus up to a maximum of 20 days after initiation of symptoms. The majority of studies that addressed this situation involved hospitalized individuals and those with severe disease. Studies to address the possible presence of SARS-CoV-2 during the different phases of COVID-19 disease in mildly infected individuals, and utilization of viral culture techniques to identify replication-competent viruses, have been limited. This report describes two patients with mild forms of the disease who shed replication-competent virus for 24 and 37 days, respectively, after symptom onset.

Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort.

Chagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel's classification. We selected the simplest combination that most accurately reproduced the panel's results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.