Population attributable fractions of mortality in people living with HIV: roles of delayed antiretroviral therapy, hepatitis coinfections and social factors.

OBJECTIVES: Despite free access to antiretroviral therapy (ART) from 1996 onward, and treatment for all people living with HIV (PLWHIV) from 2013, mortality in Brazil has not homogeneously decreased. We investigated to what extent delayed ART, hepatitis coinfections and sociodemographic factors predict all-cause mortality in Brazilian PLWHIV. DESIGN: We included PLWHIV at least 18 years, with complete CD4 cell count data, followed up between 2007 and 2015 in Brazil. METHODS: After multiple imputation, an extended Cox model helped estimate the effects of fixed and time-varying covariates on mortality. RESULTS: The study population (n = 411 028) were mainly male (61%), white (55%), 40 years or less (61%), heterosexually HIV infected (71%), living in the Southeast region (48%) and had basic education (79%). Hepatitis C virus and hepatitis B virus coinfection prevalences were 2.5 and 1.4%, respectively. During a 4-year median follow-up, 61 630 deaths occurred and the mortality rate was 3.45 (95% confidence interval: 3.42-3.47) per 100 person-years. Older age, male sex, non-white ethnicity, illiteracy/basic education and living outside the Southeast and Central-West regions were independently associated with increased mortality. The main modifiable predictors of mortality were delayed ART (i.e. CD4 cell count <200 cells/µl at ART initiation) (adjusted population attributable fraction: 14.20% [95% confidence interval: 13.81-14.59]), being ART-untreated (14.06% [13.54-14.59]) and ART-treated with unrecorded CD4 at ART initiation (5.74% [5.26-6.21]). Hepatitis C virus and hepatitis B virus coinfections accounted for 2.44 [2.26-2.62] and 0.42% [0.31-0.53] of mortality, respectively. CONCLUSION: The current study demonstrates that besides early ART and coinfection control, actions targeting males, non-whites and illiterate people and those with basic education are important to reduce avoidable deaths among Brazilian PLWHIV.

The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births.

BACKGROUND: In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates. METHODS AND FINDINGS: We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data. CONCLUSIONS: This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.

Evaluation of Plasmodium vivax malaria recurrence in Brazil.

BACKGROUND: Control of vivax malaria in endemic areas requires management of recurrence. The Brazilian National Malaria Surveillance System (SIVEP-Malária) records every case of malaria in Brazil, but is not designed to differentiate between primary and recurrent infections. The aim of this study was to explore whether the information provided by SIVEP-Malária could be used to identify Plasmodium vivax recurrences, its risk factors and evaluate the effectiveness of short course primaquine (7-9 days: total dose 3-4.2 mg/kg) in preventing relapses. METHODS: In this observational retrospective cohort study, data matching of SIVEP-Malária records was undertaken using bloom filters to identify potential recurrences defined as microscopically-confirmed P. vivax episodes from the same individual occurring within a year. Generalized Estimation Equation (GEE) models were used to determine predictors of recurrence. Extended Cox-based conditional Prentice-Williams-Peterson models (PWP) models were used to evaluate time to recurrence. RESULTS: Between June 1, 2014 and May 31, 2015, 26,295 episodes fulfilled the criteria of potential recurrence among 154,970 reported malaria episodes. Age ≤ 3 years, being male, literate, not-indigenous and having domestic working activities were identified as risk factors for recurrence. There was no difference in time to recurrence or recurrence frequency between patients treated with 14-day or 7-9 day primaquine regimens (HR = 1.02, 0.96-1.09) and RR = 0.97 (0.90-1.04), respectively. The use of chloroquine alone was associated with a 1.43 (1.29-1.58, p < 0.0001) increased risk of P. vivax recurrence compared to patients who used chloroquine combined with short-course primaquine, the Brazilian standard of care. This was RR = 2.06 (1.48-2.86, p < 0.0001), RR = 1.90 (1.60-2.25, p = 0.0001) and RR = 1.14 (1.00-1.29, p = 0.05) for recurrences occurring between 3-28, 29-60 and > 60 days, respectively. PWP models showed that the time to recurrence was longer in recipients of both primaquine and artemisinin-based combination therapy (ACT) compared to patients treated with chloroquine alone or with concomitant primaquine, HR = 2.2 (1.62-2.99, p < 0.0001), HR = 1.27 (0.97-1.66, p = 0.08), respectively. CONCLUSION: Short course primaquine was as effective as 14-day regimens and associated with a halving of the risk and delay in time to recurrence of P. vivax infections in comparison to chloroquine alone. The study demonstrates the feasibility of using record linkage on routine surveillance data to identify potential P. vivax recurrences, associated risk factors and impact of treatment.

The decline in mortality due to acute complications of diabetes mellitus in Brazil, 1991-2010.

BACKGROUND: Mortality from acute complications of diabetes, a predominantly preventable condition, although controlled in high income countries, remains a major challenge for low/middle income countries. The aim of this study is to describe trends in mortality from acute complications of diabetes between 1991 and 2010 in Brazil, a period during which a national health system was implemented offering broad access to diabetes treatment. METHODS: We obtained the number of deaths listed in the Brazilian Mortality Information System between 1991 and 2010 as due to acute complications of diabetes (ICD-9 250.1, .2, or .3 and ICD-10 E10-14.0 or 1), corrected this number for ill-defined causes of death and incompleteness in mortality reporting, and calculated mortality rates standardized to the world's population. We describe mortality trends with Joinpoint regressions. RESULTS: Over this 20 year period, mortality due to the acute complications of diabetes fell 70.9 % (95 % CI 67.2 to 74.5 %), from 8.42 (95 % CI 8.27 to 8.57) deaths per 100000 inhabitants in 1991 to 2.45 (95 % CI 2.38 to 2.52) per 100000 in 2010. The reduction occurred in men and women, in all age groups, and in all regions of Brazil. CONCLUSIONS: Mortality from acute complications of diabetes in Brazil has declined markedly in parallel with the implementation of a national health system providing access to insulin and organization of health care. Further decline is possible and necessary.

[Deaths with leprosy as the underlying cause recorded in Brazil: use of data base linkage to enhance information]. / Óbitos registrados com causa básica hanseníase no Brasil: uso do relacionamento de bases de dados para melhoria da informação.

This study sought to describe the characteristics of deaths with leprosy as the underlying cause recorded in the Mortality Information System (SIM) and compare these characteristics with the groups of cases where the cause of death was reported, or failed to be reported, in the National Case Registration Database (Sinan). Deaths with leprosy as the underlying cause occurring in Brazil in the 2004-2009 period, and cases of leprosy from 1975 to 2010 were included. The probabilistic bases of SIM and Sinan were compared. Of the 1,463 deaths from leprosy recorded in SIM, 44.2% were not recorded in Sinan. Of the total number of deaths, the majority were men (72.5%), aged 60 or older (56.6%), occurring in hospitals (65.3%) and with due care (45.8%). Of the 820 deaths identified in Sinan, 92% were patients with multibacillary disease, 45.2% were discharged as cured by Sinan and 38.9% died. Deaths due to leprosy were found on SIM that were not notified to Sinan. The data base linkage enabled identification of ancillary records and inconsistencies between the systems.

Óbitos registrados com causa básica hanseníase no Brasil: uso do relacionamento de bases de dados para melhoria da informação / Deaths with leprosy as the underlying cause recorded in Brazil: use of data base linkage to enhance information

O presente estudo objetivou descrever as características dos óbitos que tiveram como causa básica a hanseníase, registrados no Sistema de Informações sobre Mortalidade (SIM), e comparar estas características entre os grupos de óbitos cujos casos foram notificados e não notificados no Sistema de Informação sobre Agravos de Notificação (Sinan). Foram incluídos os óbitos com causa básica hanseníase, ocorridos no Brasil no período 2004-2009, e os casos registrados de hanseníase entre 1975-2010. Realizou-se o relacionamento probabilístico das bases do SIM e Sinan. Dos 1.463 óbitos por hanseníase registrados no SIM, 44,2% não foram encontrados no Sinan. Do total dos óbitos, a maioria foi de homens (72,5%), com 60 ou mais anos de idade (56,6%), ocorridos em hospitais (65,3%) e com assistência (45,8%). Dos 820 óbitos identificados no Sinan, 92% foram multibacilares, 45,2% tinham alta por cura no Sinan e 38,9%, óbito. Foram encontrados óbitos por hanseníase que estão registrados no SIM, mas não foram notificados no Sinan. O relacionamento das bases permitiu identificação de subregistros e inconsistências entre os sistemas.

This study sought to describe the characteristics of deaths with leprosy as the underlying cause recorded in the Mortality Information System (SIM) and compare these characteristics with the groups of cases where the cause of death was reported, or failed to be reported, in the National Case Registration Database (Sinan). Deaths with leprosy as the underlying cause occurring in Brazil in the 2004-2009 period, and cases of leprosy from 1975 to 2010 were included. The probabilistic bases of SIM and Sinan were compared. Of the 1,463 deaths from leprosy recorded in SIM, 44.2% were not recorded in Sinan. Of the total number of deaths, the majority were men (72.5%), aged 60 or older (56.6%), occurring in hospitals (65.3%) and with due care (45.8%). Of the 820 deaths identified in Sinan, 92% were patients with multibacillary disease, 45.2% were discharged as cured by Sinan and 38.9% died. Deaths due to leprosy were found on SIM that were not notified to Sinan. The data base linkage enabled identification of ancillary records and inconsistencies between the systems.

Gender inequalities in non communicable disease mortality in Brazil.

The relative burden due to non communicable diseases (NCD) is increasing worldwide and has been shown to be generally greater for men than women. The objective of this paper is to describe gender differences in NCD mortality rates and trends in Brazil. Standardized mortality rates for the years 1991-2010 were corrected for sub notification and ill defined causes of death and calculated using sex specific five year age grades. Trends in standardized mortality were studied using joinpoint regression models. In 2010, rates for NCDs (men: 479/100000; women: 333/100000) and for most major NCD categories (cardiovascular diseases, cancer, chronic respiratory diseases and other chronic diseases) were higher for men than women. Age standardized mortality rates declined for both sexes over the period, beginning in 1993 and attenuating in more recent years. From its peak in 1993 to 2010, the unconditional probability of dying between the ages of 30 and 70 due to one of the four principal NCD groupings decreased for men from 32.3% to 22.8%; for women, from 23.5% to 15.4%. In conclusion, age standardized NCD mortality, though decreasing dramatically over the past two decades in Brazil, remains notably greater in men than in women and, this difference, in relative terms, will increase if these trends continue.

Desigualdades de gênero na mortalidade por doenças crônicas não transmissíveis no Brasil / Gender inequalities in non communicable disease mortality in Brazil

A carga de doença atribuída às doenças crônicas não transmissíveis (DCNT) está aumentando globalmente, sendo em geral maior em homens. O objetivo deste artigo é descrever os diferenciais por gênero na mortalidade e tendências por DCNT no Brasil. Taxas padronizadas de mortalidade foram calculadas para os anos 1991-2010 após correção por subregistro e causas mal definidas, empregando faixas etárias de cinco anos específicas para homens e mulheres. As tendências foram analisadas com modelos de regressão joinpoint. Em 2010 as taxas para todas as DCNTs (homens: 479/100000; mulheres: 333/100000) e para os principais grupos de DCNTs (doenças cardiovasculares, câncer, doenças crônicas respiratórias e outra doenças crônicas) eram mais altas em homens. Entre 1991-2010, observou-se um declínio nas taxas padronizadas de mortalidade, em homens e mulheres, iniciando em 1993, e tornado-se menos intenso em anos recentes. A probabilidade incondicional de morrer entre as idades de 30 e 70 devido a um dos quatro principais grupos de DCNTs baixou de 1993 até 2010 de 32,3% para 22,8% em homens, e de 23,5% para 15,4% em mulheres. Concluindo, apesar do notável declínio nas taxas padronizadas de mortalidade por DCNT nas últimas duas décadas, o predomínio em homens persiste e, a se manter essa tendência, em termos relativos, irá aumentar.

The relative burden due to non communicable diseases (NCD) is increasing worldwide and has been shown to be generally greater for men than women. The objective of this paper is to describe gender differences in NCD mortality rates and trends in Brazil. Standardized mortality rates for the years 1991-2010 were corrected for sub notification and ill defined causes of death and calculated using sex specific five year age grades. Trends in standardized mortality were studied using joinpoint regression models. In 2010, rates for NCDs (men: 479/100000; women: 333/100000) and for most major NCD categories (cardiovascular diseases, cancer, chronic respiratory diseases and other chronic diseases) were higher for men than women. Age standardized mortality rates declined for both sexes over the period, beginning in 1993 and attenuating in more recent years. From its peak in 1993 to 2010, the unconditional probability of dying between the ages of 30 and 70 due to one of the four principal NCD groupings decreased for men from 32.3% to 22.8%; for women, from 23.5% to 15.4%. In conclusion, age standardized NCD mortality, though decreasing dramatically over the past two decades in Brazil, remains notably greater in men than in women and, this difference, in relative terms, will increase if these trends continue.

Monitoramento da doença renal crônica terminal pelo subsistema de Autorização de Procedimentos de Alta Complexidade: Apac: Brasil, 2000 a 2006 / Monitoring End Stage Renal Disease through the High Complexity Procedures Authorization Subsystem: Apac: in Brazil, 2000-2006

Este estudo descreve dados gerados pelo Subsistema de Autorização de Procedimento de Alta Complexidade de Terapia Renal Substitutiva (Apac-TRS) 2000-2006 e avalia seu potencial para monitoramento da doença renal crônica terminal no Brasil. Após concatenar 2.192 arquivos da Apac-TRS e excluir pacientes repetidos, analisou-se o perfil epidemiológico dos ingressos em TRSsegundo idade, sexo, região, tratamento e causa da doença renal. Identificaram-se 148.284 pacientes em tratamento dialítico no período, sendo a incidência estimada em 119,8/1.000.000 habitantes/ano no Brasil, variando de 143,6/1.000.000/ano na Região Sul a 66,3/1.000.000/ano na Região Norte. Hipertensão foi a causa em 32.571 (22,0%), diabetes mellitus em 20.412 (13,8%), glomerulonefrites em 10.654 (7,2%) e causa indeterminada em 66.439 (44.8 %) dos casos. A incidência foi estável no período, exceto para as faixas etárias acima de 65 anos, em que se observou aumento. Apesar das limitações inerentes aos bancos de dados administrativos, a base Apac-TRS tem potencial para ser utilizada no monitoramento da doença renal crônica terminal.

This study describes data available at the High Complexity Procedures Authorization Subsystem on Renal Replacement Therapy (Apac/TRS) from 2000 to 2006 and evaluates its potential use for monitoring end stage chronic renal disease patients in Brazil. After gathering 2,192 Apac files and excluding repeated records, we have analyzed the epidemiological profile of patients initiating Renal Replacement Therapy according to age, sex, region, treatment and cause of renal disease. We have identified 148,284 patients in dialysis during the period of the study. The incidence rate was estimated as 119,8/1,000,000 inhabitants/year, varying from 143,6/1,000,000/year in the South of Brazil to 66,3/1,000,000/year in the North of the country. Hypertension was the listed cause of renal disease in 32,571 cases (22%), followed by diabetes mellitus in 20,414 cases (13.8%) and glomerulonephritis in 10,654 cases (7.2%). Undetermined cause accountedfor 66,439 of all cases (44.8%). Incidence was stable, except for those patients over 65, among whom incidence has increased. The data available at Apac/TRS demonstrate that, despite limitations due to its administrative nature, the system is potentially useful for monitoring end stage chronic renal disease patients.

[Impact on tuberculosis incidence rates of removal of repeat notification records]. / Efeito da remoção de notificações repetidas sobre a incidência da tuberculose no Brasil.

OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal of improper duplicate records from the notification system. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records were identified through probabilistic record linkage and classified into six mutually exclusive categories and then kept, combined or removed from database. RESULTS: Of all TB records, 73.7% had no duplicate, 18.9% were duplicate, 4.7% were triplicate, and 2.7% were quadruplicate or more. Of all repeat records, 47.3% were classified as transfer in/out; 23.6% return after default, 16.4% true duplicates, 10% relapse, 2.5% inconclusive and 0.2% had missing data. These proportions were different in Brazilian states. Removal of improper duplicate records reduced TB incidence rate per 100.000 inhabitants by 6.1% in the year 2000 (from 44 to 41.3), 8.3% in 2001 (from 44.5 to 40.8), 9.4% in 2002 (from 45.8 to 41.5), 9.2% in 2003 (from 46.9 to 42.6) and 8.4% in 2004 (from 45.4 to 41.6). CONCLUSIONS: The study results indicate that the observed tuberculosis incidence rates represent estimates that would be closer to the actual rates than those obtained from the raw database at state and country level. The use of record linkage approach should be promoted for better quality of notification system data.

Efeito da remoção de notificações repetidas sobre a incidência da tuberculose no Brasil / Impact on tuberculosis incidence rates of removal of repeat notification records

OBJETIVO: Avaliar o impacto nas taxas de incidência de tuberculose com a exclusão de registros indevidamente repetidos no sistema de notificação. MÉTODOS: Foram analisados dados do Sistema de Informação de Agravos de Notificação do Ministério da Saúde, referentes ao período de 2000 a 2004. Os registros repetidos foram identificados por pareamento probabilístico e classificados em seis categorias excludentes que determinaram suas remoções, vinculações ou permanências na base. RESULTADOS: Verificou-se que 73,7 por cento das notificações eram únicas, 18,9 por cento formavam duplas, 4,7 por cento triplas e 2,7 por cento grupos de quatro ou mais registros. Dentre os registros repetidos, 47,3 por cento foram classificados como transferência entre unidades de saúde, 23,6 por cento reingresso, 16,4 por cento duplicidade verdadeira, 10 por cento recidiva, 2,5 por cento foram inconclusivos e 0,2 por cento tinham dados incompletos. Essas percentagens variaram entre estados. A exclusão de registros indevidamente repetidos resultou em redução na taxa de incidência por 100.000 habitantes de 6,1 por cento em 2000 (de 44 para 41,3), 8,3 por cento em 2001 (de 44,5 para 40,8), 9,4 por cento em 2002 (de 45,8 para 41,5), 9,2 por cento em 2003 (de 46,9 para 42,6) e 8,4 por cento em 2004 (de 45,4 para 41,6). CONCLUSÕES: Os resultados sugerem que as taxas observadas de incidência de tuberculose representem estimativas mais próximas do que seriam os valores reais do que as obtidas com a base em seu estado bruto, tanto em nível nacional como estadual. A prática de pareamento de registros de notificação de tuberculose deve ser estimulada e mantida para melhoria da qualidade dos dados de notificação.

OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal of improper duplicate records from the notification system. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records were identified through probabilistic record linkage and classified into six mutually exclusive categories and then kept, combined or removed from database. RESULTS: Of all TB records, 73.7 percent had no duplicate, 18.9 percent were duplicate, 4.7 percent were triplicate, and 2.7 percent were quadruplicate or more. Of all repeat records, 47.3 percent were classified as transfer in/out; 23.6 percent return after default, 16.4 percent true duplicates, 10 percent relapse, 2.5 percent inconclusive and 0.2 percent had missing data. These proportions were different in Brazilian states. Removal of improper duplicate records reduced TB incidence rate per 100.000 inhabitants by 6.1 percent in the year 2000 (from 44 to 41.3), 8.3 percent in 2001 (from 44.5 to 40.8), 9.4 percent in 2002 (from 45.8 to 41.5), 9.2 percent in 2003 (from 46.9 to 42.6) and 8.4 percent in 2004 (from 45.4 to 41.6). CONCLUSIONS: The study results indicate that the observed tuberculosis incidence rates represent estimates that would be closer to the actual rates than those obtained from the raw database at state and country level. The use of record linkage approach should be promoted for better quality of notification system data.