Prevalence of clinical forms of Chagas disease: a systematic review and meta-analysis - data from the RAISE study.

Background: There is a lack of up-to-date estimates about the prevalence of Chagas disease (ChD) clinical presentations and, therefore, we aimed to assess the prevalence of clinical forms of ChD among seropositive adults, pooling available data. Methods: A systematic review was conducted in Medline, Embase, Biblioteca Virtual em Saúde and Cochrane databases looking for studies published from 1990 to August 2023, which investigated the prevalence of ChD clinical forms among seropositive adults, including: (i) indeterminate phase, (ii) chronic Chagas cardiomyopathy (CCM), (iii) digestive and (iv) mixed (CCM + digestive) forms. Pooled estimates and 95% confidence intervals (CI) were calculated using random-effects models. Studies quality and risk of bias was assessed with the Leboeuf-Yde and Lauritsen tool. Heterogeneity was assessed with the I2 statistic. The study was registered in the PROSPERO database (CRD42022354237). Findings: 1246 articles were selected for screening and 73 studies were included in the final analysis (17,132 patients, 44% men). Most studies were conducted with outpatients (n = 50), followed by population-based studies (n = 15). The pooled prevalence of the ChD clinical forms was: indeterminate 42.6% (95% CI: 36.9-48.6), CCM 42.7% (95% CI: 37.3-48.3), digestive 17.7% (95% CI: 14.9-20.9), and mixed 10.2% (95% CI: 7.9-13.2). In population-based studies, prevalence was lower for CCM (31.2%, 95% CI: 24.4-38.9) and higher for indeterminate (47.2%, 95% CI: 39.0-55.5) form. In meta-regression, age was inversely associated with the prevalence of indeterminate (ß = -0.05, P < 0.001) form, and directly associated with CCM (ß = 0.06, P < 0.001) and digestive (ß = 0.02, P < 0.001) forms. Heterogeneity was overall high. Interpretation: Compared to previous publications, our pooled estimates show a higher prevalence of CCM among ChD seropositive patients, but similar rates of the digestive form. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

The Burden of Chagas Disease in the Contemporary World: The RAISE Study.

Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.

The economic burden of Chagas disease: A systematic review.

BACKGROUND: Chagas disease (CD) is a neglected disease affecting millions worldwide, yet little is known about its economic burden. This systematic review is part of RAISE project, a broader study that aims to estimate the global prevalence, mortality, and health and economic burden attributable to chronic CD and Chronic Chagas cardiomyopathy. The objective of this study was to assess the main costs associated with the treatment of CD in both endemic and non-endemic countries. METHODS: An electronic search of the Medline, Lilacs, and Embase databases was conducted until 31st, 2022, to identify and select economic studies that evaluated treatment costs of CD. No restrictions on place or language were made. Complete or partial economic analyses were included. RESULTS: Fifteen studies were included, with two-thirds referring to endemic countries. The most commonly investigated cost components were inpatient care, exams, surgeries, consultation, drugs, and pacemakers. However, significant heterogeneity in the estimation methods and presentation of data was observed, highlighting the absence of standardization in the measurement methods and cost components. The most common component analyzed using the same metric was hospitalization. The mean annual hospital cost per patient ranges from $25.47 purchasing power parity US dollars (PPP-USD) to $18,823.74 PPP-USD, and the median value was $324.44 PPP-USD. The lifetime hospital cost per patient varies from $209,44 PPP-USD for general care to $14,351.68 PPP-USD for patients with heart failure. DISCUSSION: Despite the limitations of the included studies, this study is the first systematic review of the costs of CD treatment. The findings underscore the importance of standardizing the measurement methods and cost components for estimating the economic burden of CD and improving the comparability of cost components magnitude and cost composition analysis. Finally, assessing the economic burden is essential for public policies designed to eliminate CD, given the continued neglect of this disease.

Time trends in tuberculosis mortality across the BRICS: an age-period-cohort analysis for the GBD 2019.

Background: Tuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019. Methods: We obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Findings: There were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980. Interpretation: BRICS' actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country. Funding: National Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.

Deaths related to Chagas disease and HIV/AIDS coinfection in Brazil: a nationwide population-based analysis.

BACKGROUND: Trypanosoma cruzi/HIV coinfection has been described as a relevant clinical event and an emerging public health problem. Here, we describe the epidemiological patterns of deaths related to Chagas disease and HIV/AIDS coinfection in Brazil from 2000 to 2019. METHODS: We performed a nationwide population-based study using mortality data obtained from the Brazilian Mortality Information System. We included all deaths recorded in Brazil from 2000 to 2019 in which Chagas disease and HIV/AIDS were mentioned on the same death certificate, either as underlying or as associated causes of death. RESULTS: Chagas disease and HIV/AIDS were mentioned on 196/22 663 092 death certificates. HIV/AIDS was the underlying cause in 58.2% (114/196) of deaths and Chagas disease in 33.2% (65/196). The average annual mortality rate was 0.05 deaths/1 000 000 inhabitants (95% CI 0.03 to 0.09). The highest death rates were found among males, those aged 60-69 y, Afro-Brazilians, those with 1-3 y of schooling/study and residents in Chagas disease-endemic regions/states. Respiratory, infectious/parasitic and cardiovascular diseases/disorders were the associated causes of death most commonly mentioned. CONCLUSIONS: Mortality due to Chagas disease and HIV/AIDS coinfection may be largely underestimated in Brazil. Our data further reinforce the importance of screening for T. cruzi infection in HIV-infected patients from Chagas disease-endemic areas. Appropriate clinical management should be ensured for Chagas disease and HIV coinfected patients.

Levels and trends in Chagas disease-related mortality in Brazil, 2000-2019.

Chagas disease remains an important public health problem with high morbidity and mortality in several Latin American countries. This nationwide population-based ecological study analyzes the epidemiological characteristics and time trends of Chagas disease-related mortality in Brazil, 2000-2019. We included all deaths reported in Brazil in which Chagas disease was mentioned in the death certificate either as an underlying or associated cause of death (multiple causes of death). Crude and age-adjusted mortality rates (per 100,000 inhabitants) were calculated and time trends analysis was performed using joinpoint regression models. In the study period, a total of 22,663,092 deaths were recorded in Brazil. Chagas disease was identified in 122,291 deaths (0.54%), 94.788 (77.5%) as an underlying cause and 27,503 (22.5%) as an associated cause. Average annual age-adjusted mortality rate was 3.22 deaths/100,000 inhabitants (95% confidence interval [CI]: 3.14-3.30). Chronic Chagas disease with cardiac involvement was the predominant clinical presentation mentioned. The highest mortality rates were observed in males, age group ≥80 years, black race/skin color, schooling 1-3 years of study, and residents in the Central-West region. Age-adjusted mortality rates showed a significant declining trend at the national level in the period (Average Annual Percent Change: -3.1%; 95% CI: -3.3; -3.0), with different local patterns and a more pronounced reduction in important endemic areas in the past. The findings show that, despite a consistent decline in mortality rates in Brazil over the study period, Chagas disease remains an important and neglected cause of death in the country, showing a marked regional variation that has social and health care implications. In addition to the control measures for disease transmission, it is necessary to guarantee access, coverage, and quality of health care to Chagas disease patients, seeking to prevent the occurrence of severe forms and deaths from the disease.

Changes in malaria patterns in Brazil over 28 years (1990-2017): results from the Global Burden of Disease Study 2017.

BACKGROUND: This study presents the malaria burden in Brazil from 1990 to 2017 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), by analyzing disease burden indicators in federated units of the Legal Amazon and Extra-Amazon regions, as well as describing malaria cases according to Plasmodium species occurring in the country. METHODS: We used estimates from the GBD 2017 to report years of life lost due to premature death (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) for malaria in Brazil, grouped by gender, age group, and Brazilian federated unit, from 1990 to 2017. Results are presented as absolute numbers and age-standardized rates (per 100,000 inhabitants) with 95% uncertainty intervals (UI). RESULTS: At the national level, the age-standardized DALYs rate due to malaria decreased by 92.0%, from 42.5 DALYs per 100,000 inhabitants (95% UI 16.6-56.9) in 1990 to 3.4 DALYs per 100,000 inhabitants (95% UI 2.7-4.7) in 2017. The YLLs were the main component of the total DALYs rate for malaria in 1990 (67.3%), and the YLDs were the main component of the metric in 2017 (61.8%). In 2017, the highest sex-age DALYs rate was found among females in the "< 1-year-old" age group, with a 6.4 DALYs per 100,000 inhabitants (95% UI 1.8-14.7) and among males in the age group of "20 to 24 years old", with a 4.7 DALYs per 100,000 inhabitants (95% UI 3.3-9.9). Within the Brazilian Amazon region, the three federated units with the highest age-standardized DALYs rates in 2017 were Acre [28.4 (95% UI 14.2-39.1)], Roraima [28.3 (95% UI 13.5-40.2)], and Rondônia [24.7 (95% UI 11.4-34.8)]. Concerning the parasite species that caused malaria, 73.5% of the total of cases registered in the period had Plasmodium vivax as the etiological agent. CONCLUSIONS: The results of the GBD 2017 show that despite the considerable reduction in the DALYs rates between 1990 and 2017, malaria remains a relevant and preventable disease, which in recent years has generated more years of life lost due to disability than deaths. The states endemic for malaria in the Amazon region require constant evaluation of preventive and control measures. The present study will contribute to the direction of current health policies aimed at reducing the burden of malaria in Brazil, as knowing the geographical and temporal distribution of the risk of death and disability of this disease can facilitate the planning, implementation, and improvement of control strategies aimed at eliminating the disease.

The burden of tuberculosis and attributable risk factors in Brazil, 1990-2017: results from the Global Burden of Disease Study 2017.

BACKGROUND: Tuberculosis (TB) continues to be an important cause of fatal and non-fatal burden in Brazil. In this study, we present estimates for TB burden in Brazil from 1990 to 2017 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017). METHODS: This descriptive study used GBD 2017 findings to report years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of TB in Brazil by sex, age group, HIV status, and Brazilian states, from 1990 to 2017. We also present the TB burden attributable to independent risk factors such as smoking, alcohol use, and diabetes. Results are reported in absolute number and age-standardized rates (per 100,000 inhabitants) with 95% uncertainty intervals (UIs). RESULTS: In 2017, the number of DALYs due to TB (HIV-negative and HIV-positive combined) in Brazil was 284,323 (95% UI: 240,269-349,265). Among HIV-negative individuals, the number of DALYs was 196,366 (95% UI: 189,645-202,394), while 87,957 DALYs (95% UI: 50,624-146,870) were estimated among HIV-positive individuals. Between 1990 and 2017, the absolute number and age-standardized rates of DALYs due to TB at the national level decreased by 47.0% and 68.5%, respectively. In 2017, the sex-age-specific TB burden was highest among males and in children under-1 year and the age groups 45-59 years. The Brazilian states with the highest age-standardized DALY rates in 2017 were Rio de Janeiro, Pernambuco, and Amazonas. Age-standardized DALY rates decreased for all 27 Brazilian states between 1990 and 2017. Alcohol use accounted for 47.5% of national DALYs due to TB among HIV-negative individuals in 2017, smoking for 17.9%, and diabetes for 7.7%. CONCLUSIONS: GBD 2017 results show that, despite the remarkable progress in reducing the DALY rates during the period, TB remains as an important and preventable cause of health lost to due premature death and disability in Brazil. The findings reinforce the importance of strengthening TB control strategies in Brazil through integrated and multisectoral actions that enable the access to prevention, early diagnosis, and timely treatment, with emphasis on high-risk groups and populations most vulnerable to the disease in the country.

Burden of schistosomiasis-related mortality in Brazil: epidemiological patterns and spatial-temporal distribution, 2003-2018.

OBJECTIVE: To characterise the epidemiological patterns and the spatial-temporal distribution of schistosomiasis-related mortality in Brazil from 2003 to 2018. METHODS: A national population-based ecological study that used official data from the Mortality Information System. The data included all deaths recorded in Brazil from 2003 to 2018 in which schistosomiasis was mentioned in the death certificate as an underlying or associated cause of death (multiple causes). The municipalities of residence were used as units of geographic analysis, and standardised and smoothed mortality rates (per 100 000 inhabitants) were calculated using the local empirical Bayes method. Spatial autocorrelation was evaluated using global and local Moran indexes. To analyse the spatial dependence, the Getis-Ord G and Gi* statistics were used. RESULTS: During the study period, 18 421 113 deaths were recorded in Brazil. Schistosomiasis was mentioned in 11 487 deaths (proportional mortality: 0.06%); for 8141 deaths (70.87%), it was listed as the underlying cause, and for 3346 deaths (29.13%), it was listed as an associated cause. The mean mortality rate was 0.38 deaths/100 000 inhabitants. Individuals ≥ 70 years of age (RR: 115.34, 95% CI: 68.56-194.03) and residents in the Northeast region (RR: 10.81, 95% CI: 5.95-19.66) presented higher risks related to schistosomiasis. Municipalities with high mortality rates were identified in all regions, and high-risk clusters were found in municipalities located in the Northeast and Southeast regions of the country. CONCLUSIONS: Schistosomiasis remains an important cause of death in persistently endemic areas in Brazil, particularly in those with a high prevalence of the disease and a marked parasite load.

OBJECTIF: Caractériser les profils épidémiologiques et la distribution spatio-temporelle de la mortalité liée à la schistosomiase au Brésil de 2003 à 2018. MÉTHODES: Une étude écologique nationale basée sur la population qui a utilisé les données officielles du système d'information sur la mortalité. Les données incluaient tous les décès enregistrés au Brésil de 2003 à 2018 dans lesquels la schistosomiase était mentionnée dans le certificat de décès comme cause sous-jacente ou associée (causes multiples) de décès. Les municipalités de résidence ont été utilisées comme unités d'analyse géographique et les taux de mortalité normalisés et lissés (pour 100.000 habitants) ont été calculés à l'aide de la méthode empirique locale de Bayes. L'autocorrélation spatiale a été évaluée à l'aide d'indices de Moran globaux et locaux. Pour analyser la dépendance spatiale, les statistiques de Getis-Ord G et Gi* ont été utilisées. RÉSULTATS: Au cours de la période d'étude, 18.421.113 décès ont été enregistrés au Brésil. La schistosomiase a été mentionnée dans 11.487 décès (mortalité proportionnelle: 0,06%); pour 8.141 décès (70,87%), elle a été répertoriée comme la cause sous-jacente et pour 3.346 décès (29,13%), comme cause associée. Le taux de mortalité moyen était de 0,38 décès/100.000 habitants. Les personnes âgées de ≥70 ans (RR: 115,34 ; IC95%: 68,56 à 194,03) et les résidents de la région du Nord-Est (RR: 10,81 ; IC95%: 5,95 à 19,66) présentaient des risques plus élevés liés à la schistosomiase. Des municipalités présentant des taux de mortalité élevés ont été identifiées dans toutes les régions et des grappes à haut risque ont été trouvées dans des municipalités situées dans les régions du nord-est et du sud-est du pays. CONCLUSIONS: La schistosomiase reste une cause importante de mortalité dans les zones d'endémie persistante du Brésil, en particulier dans celles à forte prévalence de la maladie et à forte charge parasitaire.

Temporal trends and spatial distribution of leprosy-related mortality in the state of Tocantins, Brazil, 2000-2015. / Tendência temporal e distribuição espacial da mortalidade relacionada à hanseníase no estado do Tocantins, 2000-2015.

Objective to describe temporal trends and spatial distribution patterns of leprosy-related deaths in the state of Tocantins, Brazil, 2000-2015. Methods this study was based on Mortality Information System (SIM) data; mortality coefficient temporal trend analysis was performed using joinpoint regression and descriptive spatial analysis, taking the state's 139 municipalities as geographic units of analysis. Results 201 leprosy-related deaths were identified in Tocantins; average mortality coefficient was 0.7 deaths/100,000 inhabitants; mortality tended to increase significantly (5.4% Annual Percentage Change - 95% CI 2.0; 8.9); the average annual crude mortality coefficient ranged from 0.00 to 6.83 deaths/100,000 inhabitants, while the smoothed indicator ranged from 0.00 to 2.42 deaths/100,000 inhabitants. Conclusion leprosy mortality showed a rising trend and heterogeneous spatial distribution in Tocantins, with the need to strengthen leprosy surveillance and control measures.

Tendência temporal e distribuição espacial da mortalidade relacionada à hanseníase no estado do Tocantins, 2000-2015 / Las tendencias temporales y la distribución espacial de la mortalidad relacionada con la lepra en el estado de Tocantins, Brasil, 2000-2015 / Temporal trends and spatial distribution of leprosy-related mortality in the state of Tocantins, Brazil, 2000-2015

Objetivo: relatar descrever as tendências temporais e padrões de distribuição espacial dos óbitos relacionados à hanseníase no estado do Tocantins, Brasil, 2000-2015. Métodos: estudo baseado em dados do Sistema de Informações sobre Mortalidade (SIM); realizou-se análise de tendência temporal dos coeficientes de mortalidade pela regressão joinpoint e análise espacial descritiva utilizando-se os 139 municípios do estado como unidades geográficas de análise. Resultados: foram identificados 201 óbitos relacionados à hanseníase no Tocantins; o coeficiente médio de mortalidade foi de 0,7 óbitos/100 mil habitantes; a mortalidade apresentou tendência de aumento significativo (annual percentual change (APC) de 5,4% - IC95% 2,0;8,9); o coeficiente de mortalidade bruto médio anual variou de 0,00 a 6,83 óbitos/100 mil hab., enquanto o indicador suavizado variou de 0,00 a 2,42 óbitos/100 mil hab. Conclusão: a mortalidade por hanseníase apresentou tendência de aumento e distribuição espacial heterogênea no Tocantins, com a necessidade de fortalecimento das medidas de vigilância e controle da doença.

Objetivo: describir las tendencias temporales y los patrones de distribución espacial de las muertes relacionadas con la lepra en el estado de Tocantins, Brasil, 2000-2015. Métodos: estudio basado en datos del Sistema de Información de Mortalidad (SIM); análisis de la tendencia temporal de los coeficientes de mortalidad mediante la regresión de los puntos de inflexión y el análisis espacial descriptivo utilizando las 139 municipalidades del estado como unidades geográficas de análisis. Resultados: se identificaron 201 muertes relacionadas con la lepra en Tocantins; el coeficiente de mortalidad promedio fue de 0.7 muertes/100 mil habitantes; la mortalidad tendió a aumentar significativamente (Cambio porcentual anual de 5.4% - IC 95% 2.0; 8.9); el coeficiente de mortalidad bruto anual promedio varió de 0.00 a 6.83 muertes/100 mil habitantes, mientras que el indicador suavizado varió de 0.00 a 2.42 muertes/100 mil habitantes. Conclusión: la mortalidad por lepra mostró una tendencia de aumento y una distribución espacial heterogénea y la necesidad de fortalecer las medidas de control de la enfermedad.

Objective: to describe temporal trends and spatial distribution patterns of leprosy-related deaths in the state of Tocantins, Brazil, 2000-2015. Methods: this study was based on Mortality Information System (SIM) data; mortality coefficient temporal trend analysis was performed using joinpoint regression and descriptive spatial analysis, taking the state's 139 municipalities as geographic units of analysis. Results: 201 leprosy-related deaths were identified in Tocantins; average mortality coefficient was 0.7 deaths/100,000 inhabitants; mortality tended to increase significantly (5.4% Annual Percentage Change - 95% CI 2.0; 8.9); the average annual crude mortality coefficient ranged from 0.00 to 6.83 deaths/100,000 inhabitants, while the smoothed indicator ranged from 0.00 to 2.42 deaths/100,000 inhabitants. Conclusion: leprosy mortality showed a rising trend and heterogeneous spatial distribution in Tocantins, with the need to strengthen leprosy surveillance and control measures.

Burden of Chagas disease in Brazil, 1990-2016: findings from the Global Burden of Disease Study 2016.

Chagas disease continues to be an important cause of morbidity, mortality and disability in several Latin American countries, including Brazil. Using findings from the Global Burden of Disease Study 2016 (GBD, 2016), we present years of life lost, years lived with disability, and disability-adjusted life years due to Chagas disease in Brazil, by sex, age group, and Brazilian states, from 1990 to 2016. Results are reported in absolute numbers and age-standardized rates (per 100,000 population) with 95% uncertainty intervals. In 2016, 141,640 disability-adjusted life years (95% uncertainty intervals: 129,065-155,941) due to Chagas disease were estimated in Brazil, with a relative reduction of 36.7% compared with 1990 (223,879 disability-adjusted life years (95% uncertainty intervals: 209,372-238,591)). Age-standardized disability-adjusted life year rates declined at the national level (-69.7%) and in all Brazilian states between 1990 and 2016, but with different regional patterns. The decrease in the disability-adjusted life year rates was driven primarily by a consistent reduction in the years of life lost rates, the main component of total disability-adjusted life years for Chagas disease. The highest fatal and non-fatal burden due to Chagas disease was observed among males, the elderly, and in those Brazilian states encompassing important endemic areas for vector transmission in the past. Despite the consistent reduction in its burden during the period, Chagas disease is still an important and neglected cause of health lost due to premature mortality and disability in Brazil. Efforts should be made to maintain the political interest and sustainability of surveillance and control actions for Chagas disease, prevent the risk of re-emergence of vector transmission in endemic areas, and provide health care to chronically infected individuals, including early diagnosis and treatment interventions.

Burden of leishmaniasis in Brazil and federated units, 1990-2016: Findings from Global Burden of Disease Study 2016.

BACKGROUND: The study presents estimates for the burden of visceral leishmaniasis (VL) and cutaneous and mucocutaneous leishmaniasis (CML) in Brazil and its 27 federated units using data from the Global Burden of Disease Study (GBD) 2016. METHODOLOGY: We report the incidence, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) for leishmaniasis in Brazil from 1990 to 2016. The metrics are presented as age-standardized rates per 100,000 inhabitants with their respective uncertainty intervals (95%UI) and relative percentages of change. PRINCIPAL FINDINGS: The age-standardized incidence rate of leishmaniasis decreased 48.5% from 1990 (71.0, 95%UI 24.3-150.7) to 2016 (36.5, 95%UI 24.7-50.9), whereas the age-standardized DALY increased 83.6% over the studied period from 12.2 (95%UI 7.9-18.8) to 22.4 (95%UI 13.3-36.2). The age-standardized incidence rate and YLL for VL increased by 52.9% and 108% from 1990 to 2016, respectively. Considering CML, the age-standardized incidence rate and YLD decreased by 51% and 31.8% respectively for the same period. For VL, similar profiles for male and female were observed, with YLL and DALY increasing over time; with males presenting slightly higher values. The highest YLL rates were among "under 1-year old" children, which increased 131.2% from 1990 to 2016. Regarding CML, the highest values of YLD and DALY were verified among males, and YLD values showed a similar profile, with rates increasing with age. The VL burden increased in some states in the Northeast and Southeast regions and decreased for CML in some Northern states. CONCLUSION: The increase of VL burden over the study period might be associated with the difficulties in controlling the disease spread. Information regarding the weight of VL and CML, including the death and disability tolls that they cause, highlights the impact of these neglected diseases on public health and the importance of effective prevention and treatment.

The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational analysis from the Global Burden of Disease Study 2016.

BACKGROUND: Neglected Tropical Diseases (NTDs) are important causes of morbidity, disability, and mortality among poor and vulnerable populations in several countries worldwide, including Brazil. We present the burden of NTDs in Brazil from 1990 to 2016 based on findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016). METHODOLOGY: We extracted data from GBD 2016 to assess years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NTDs by sex, age group, causes, and Brazilian states, from 1990 to 2016. We included all NTDs that were part of the priority list of the World Health Organization (WHO) in 2016 and that are endemic/autochthonous in Brazil. YLDs were calculated by multiplying the prevalence of sequelae multiplied by its disability weight. YLLs were estimated by multiplying each death by the reference life expectancy at each age. DALYs were computed as the sum of YLDs and YLLs. PRINCIPAL FINDINGS: In 2016, there were 475,410 DALYs (95% uncertainty interval [UI]: 337,334-679,482; age-standardized rate of 232.0 DALYs/100,000 population) from the 12 selected NTDs, accounting for 0.8% of national all-cause DALYs. Chagas disease was the leading cause of DALYs among all NTDs, followed by schistosomiasis and dengue. The sex-age-specific NTD burden was higher among males and in the youngest and eldest (children <1 year and those aged ≥70 years). The highest age-standardized DALY rates due to all NTDs combined at the state level were observed in Goiás (614.4 DALYs/100,000), Minas Gerais (433.7 DALYs/100,000), and Distrito Federal (430.0 DALYs/100,000). Between 1990 and 2016, the national age-standardized DALY rates from all NTDs decreased by 45.7%, with different patterns among NTD causes and Brazilian states. Most NTDs decreased in the period, with more pronounced reduction in DALY rates for onchocerciasis, lymphatic filariasis, and rabies. By contrast, age-standardized DALY rates due to dengue, visceral leishmaniasis, and trichuriasis increased substantially. Age-standardized DALY rates decreased for most Brazilian states, increasing only in the states of Amapá, Ceará, Rio Grande do Norte, and Sergipe. CONCLUSIONS/SIGNIFICANCE: GBD 2016 findings show that, despite the reduction in disease burden, NTDs are still important and preventable causes of disability and premature death in Brazil. The data call for renewed and comprehensive efforts to control and prevent the NTD burden in Brazil through evidence-informed and efficient and affordable interventions. Multi-sectoral and integrated control and surveillance measures should be prioritized, considering the population groups and geographic areas with the greatest morbidity, disability, and most premature deaths due to NTDs in the country.

Tendências e padrões espaço-temporais da mortalidade relacionada à hanseníase no Estado da Bahia, Nordeste do Brasil, 1999-2014 / Spatiotemporal patterns of leprosy-related mortality in Bahia state, northeastern Brazil, 1999-2014

Resumo Introdução A hanseníase é uma condição negligenciada, com alta carga de morbimortalidade, especialmente em áreas mais desfavoráveis. O objetivo deste estudo foi analisar as tendências e os padrões espaço-temporais da mortalidade relacionada à hanseníase no estado da Bahia, 1999-2014. Objetivo Analisar tendências e padrões espaço-temporais da mortalidade relacionada à hanseníase no Estado da Bahia de 1999 a 2014. Método Estudo de base populacional com dados secundários de mortalidade. Incluíram-se todos os óbitos em que a hanseníase foi mencionada como causa de morte. Resultados Foram registrados 1.152.262 óbitos, dos quais a hanseníase foi identificada em 481 (0,04%) casos, resultando em coeficiente bruto médio anual de mortalidade de 0,21 óbito/100 mil habitantes (intervalo de confiança [IC] de 95%: 0,13-0,29). Hanseníase não especificada (87,73%, ou 422/481) e complicações da hanseníase (6,44%, ou 31/481) foram as formas clínicas mais comumente mencionadas. O risco de óbito relacionado à hanseníase foi maior entre os homens (risco relativo [RR]: 2,38; IC 95%: 0,19-0,46), em idosos (RR: 74,79; IC 95%: 9,57-582,20) e na região oeste do Estado (RR: 4,08; IC 95%: 2,33-7,15). A mortalidade apresentou tendência temporal de aumento significativo no período ( Average Annual Percentual Change [AAPC] 7,3; IC 95%: 4,5 a 10,3), assim como a mortalidade proporcional (AAPC 5,3; IC 95%: 2,2 a 8,3). Conclusões A hanseníase representa uma causa negligenciada de óbito no Estado da Bahia. Apresenta tendências espaço-temporais desiguais nas regiões de saúde, com riscos associados, principalmente, à população masculina e idosa.

Abstract Background Leprosy is a neglected condition with a high mortality burden, especially in poorer areas. The objective of this study was to analyze temporal trends and spatiotemporal patterns of mortality related to leprosy in the state of Bahia, 1999-2014. Objective To analyze the spatiotemporal trends and patterns of mortality associated with leprosy in the state of Bahia, Brazil, from 1999 to 2014. Method Population-based study utilizing secondary mortality data including all deaths, in which leprosy was mentioned, recorded in the state of Bahia from 1999 to 2014. Results From a total of 1,152,262 deaths, leprosy was identified in 481 (0.04%) cases, resulting in a mean annual gross mortality rate of 0.21 deaths/100,000 inhabitants (95% confidence interval [CI]: 0.13-0.29). Unspecified leprosy (87.73%; 422/481) and leprosy complications (6.44%; 31/484) were the most commonly reported clinical forms. Risk of death associated with leprosy was higher among men (relative risk [RR]: 2.38; 95% CI; 0.19-0.46), elderly (RR: 74.79; 95% CI; 9.57-582.20), and in the eastern region of the state (RR: 4.08; 95% CI; 2.33-7.15). Overall mortality rates showed a significant increase during the observation period (Average Annual Percentage Change [AAPC] 7.3, 95% CI; 4.5-10.3), as well as proportional mortality (AAPC 5.3; 95% CI; 2.2-8.3). Conclusions Leprosy is a neglected cause of death in the state of Bahia. The disease presents unequal regional spatiotemporal trends, with risks associated mainly in males and older age groups.

Leprosy and gender in Brazil: trends in an endemic area of the Northeast region, 2001-2014.

OBJECTIVE To analyze, stratifield by gender, trends of the new case leprosy detection rates in the general population and in children; of grade 2 disability, and of proportion of multibacillary cases, in the state of Bahia, Brazil from 2001 to 2014. METHODS A time series study based on leprosy data from the National Information System for Notifiable Diseases. The time trend analysis included Poisson regression models by infection points (Joinpoint) stratified by gender. RESULTS There was a total of 40,054 new leprosy cases with a downward trend of the overall detection rate (Average Annual Percent Change [AAPC = -0.4, 95%CI -2.8-1.9] and a non-significant increase in children under 15 years (AAPC = 0.2, 95%CI -3.9-4.5). The proportion of grade 2 disability among new cases increased significantly (AAPC = 4.0, 95%CI 1.3-6.8), as well as the proportion of multibacillary cases (AAPC = 2.2, 95%CI 0.1-4.3). Stratification by gender showed a downward trend of detection rates in females and no significant change in males; in females, there was a more pronounced upward trend of the proportion of multibacillary and grade 2 disability cases. CONCLUSIONS Leprosy is still highly endemic in the state of Bahia, with active transmission, late diagnosis, and a probable hidden endemic. There are different gender patterns, indicating the importance of early diagnosis and prompt treatment, specifically in males without neglecting the situation among females.

Hanseníase em menores de 15 anos em área hiperendêmica da região norte do Brasil / Leprosy in children under 15 years old in a hyperdemetic area of the northern region of Brazil

Palmas é a capital mais hiperendêmica para hanseníase no Brasil, com transmissão ativa e persistência de focos de transmissão. O objetivo do estudo foi descrever o perfil clínico e epidemiológico da hanseníase em menores de 15 anos avaliados pelo Protocolo Complementar de Investigação Diagnóstico para menores de 15 anos de idade (PCID < 15 anos) em Palmas, Tocantins. Realizou-se um estudo descritivo dos casos diagnosticados e avaliados pelo PCID < 15 anos entre 2016 e 2017. Foram avaliados 71 casos pelo protocolo. Desses, 83,10% tinham nervos acometidos, 92,96% multibacilares, 38,03% com grau 1 ou 2 de incapacidade. O escore OMP variou entre 1 e 6 em 22,54% dos casos. O tempo de aparecimento dos sinais e sintomas foi de 6 meses a 1 ano em 35,21% dos casos. 73,24% tinham pessoas com problema de pele na família; 87,32% tinham pessoas com hanseníase na família. Entre 1 e 26 lesões/manchas de pele foi constatada em 88,73% com perda de sensibilidade. A presença de 1 ou 2 cicatrizes de BCG foi registrada em 90,14% dos casos. A busca dos contatos de casos confirmados e a avaliação em tempo oportuno é crucial para o diagnóstico precoce da hanseníase em crianças e adolescentes, pois só assim será possível diminuir as fontes de infecção, interromper a cadeia de transmissão, prevenir incapacidades físicas, psicológicas e sociais(AU).

Palmas is the most hyperendemic capital for leprosy in Brazil, with active transmission and persistence of transmission focus. The objective of this study was to describe the clinical and epidemiological profile of leprosy in children younger than 15 years evaluated by Complementary Diagnostic Investigation Protocol for children under 15 years of age (PCID<15 years) in Palmas, Tocantins. A descriptive study of the cases diagnosed and evaluated by PCID <15 years between 2016 and 2017 was carried out. A total of 71 cases were evaluated by protocol. Of these, 83.10% had affected nerves, 92.96% multibacillary, 38.03% with degree 1 or 2 of disability. The OMP score ranged from 1 to 6 in 22.54% of the cases. The time of onset of the signs and symptoms was from 6 months to 1 year in 35.21% of the cases. 73.24% had people with skin problems in the family; 87.32% people with leprosy in the family. Between 1 and 26 lesions / skin patches were observed in 88.73% with loss of sensitivity. The presence of 1 or 2 BCG scars was recorded in 90.14% of the cases. The search for confirmed case contacts and timely evaluation is crucial for the early diagnosis of leprosy in children and adolescents, since only then it will be possible to reduce the sources of infection, interrupt the transmission chain, prevent physical, psychological and social disabilities(AU).

Leprosy and gender in Brazil: trends in an endemic area of the Northeast region, 2001-2014 / Hanseníase e gênero no Brasil: tendências em área endêmica da região Nordeste, 2001-2014

ABSTRACT OBJECTIVE To analyze, stratifield by gender, trends of the new case leprosy detection rates in the general population and in children; of grade 2 disability, and of proportion of multibacillary cases, in the state of Bahia, Brazil from 2001 to 2014. METHODS A time series study based on leprosy data from the National Information System for Notifiable Diseases. The time trend analysis included Poisson regression models by infection points (Joinpoint) stratified by gender. RESULTS There was a total of 40,054 new leprosy cases with a downward trend of the overall detection rate (Average Annual Percent Change [AAPC = -0.4, 95%CI -2.8-1.9] and a non-significant increase in children under 15 years (AAPC = 0.2, 95%CI -3.9-4.5). The proportion of grade 2 disability among new cases increased significantly (AAPC = 4.0, 95%CI 1.3-6.8), as well as the proportion of multibacillary cases (AAPC = 2.2, 95%CI 0.1-4.3). Stratification by gender showed a downward trend of detection rates in females and no significant change in males; in females, there was a more pronounced upward trend of the proportion of multibacillary and grade 2 disability cases. CONCLUSIONS Leprosy is still highly endemic in the state of Bahia, with active transmission, late diagnosis, and a probable hidden endemic. There are different gender patterns, indicating the importance of early diagnosis and prompt treatment, specifically in males without neglecting the situation among females.

RESUMO OBJETIVO Analisar, segundo gênero, as tendências temporais dos coeficientes de detecção de casos novos de hanseníase na população geral e em crianças, do coeficiente de grau 2 de incapacidade física e da proporção de casos multibacilares no estado da Bahia, no período de 2001 a 2014. MÉTODOS Estudo de série temporal baseado em dados epidemiológicos relativos à hanseníase oriundos do Sistema de Informação de Agravos de Notificação. A análise de tendência temporal incluiu modelos de regressão de Poisson por pontos de inflexão (Joinpoint), considerando-se a dimensão de gênero. RESULTADOS Dos 40.054 casos notificados no período, verificou-se tendência de redução no coeficiente de detecção geral (Average Annual Percent Change [AAPC] = -0,4; IC95% -2,8-1,9) e aumento em menores de 15 anos sem significância estatística (AAPC = 0,2; IC95% -3,9-4,5). Para o coeficiente de detecção com grau 2 de incapacidade física, a tendência foi de aumento significativo (AAPC = 4,0; IC95% 1,3-6,8), assim como nos casos multibacilares (AAPC = 2,2; IC95% 0,1-4,3). A análise estratificada por gênero indicou tendência de redução dos coeficientes de detecção entre as mulheres e de manutenção entre os homens, sem significância estatística. Em relação ao coeficiente de detecção em menores de 15 anos, a tendência de redução é mais acentuada nas mulheres do que entre os homens. As mulheres apresentaram tendência mais acentuada de aumento na proporção de casos multibacilares e do coeficiente de detecção de grau 2 de incapacidade. CONCLUSÕES O estado da Bahia mantém alta endemicidade, transmissão ativa, diagnóstico tardio e provável endemia oculta de hanseníase. Há um padrão diferencial segundo gênero, tornando central o diagnóstico e tratamento oportuno com estratégias diferenciadas para os homens, sem desconsiderar a situação entre as mulheres.

Oral health conditions in leprosy cases in hyperendemic area of the Brazilian Amazon.

Leprosy is a hyperendemic chronic condition in the Rondônia State . Despite the significant impact of oral health on the quality of life and clinical evolution of leprosy patients, systematic evaluation of oral health status has been neglected. To analyze the dental-clinical profile, self-perceived oral health and dental health service access of leprosy cases in the municipality of Cacoal in Rondônia State , North Brazil, from 2001 to 2012. A descriptive, cross-sectional study design was performed based on dental evaluation and standardized structured instruments. We investigated clinically assessed and self-perceived oral health status, as well as dental health service access. A total of 303 leprosy cases were included; 41.6% rated their oral health as good, and 42.6% reported being satisfied with their oral health. Self-reported loss of upper teeth was 45.5%. The clinical evaluation revealed that 54.5% had active caries. Most (97.7%) cases reported having been to the dentist at least once in their life and 23.1% used public health services. The poor standard of oral health in this population may increase the risk for leprosy reactions, consequently reducing quality of life. Low access to public health dental services and poor self-perceived oral health reinforce the need to achieve comprehensive health care in this population.

Social determinants of leprosy in a hyperendemic State in North Brazil.

OBJECTIVE: To identify the socioeconomic, demographic, operational, and health service-related factors associated with the occurrence of leprosy in a hyperendemic State in North Brazil. METHODS: This is an ecological study based on secondary data from the Sistema de Informações de Agravos de Notificação in municipalities of the State of Tocantins from 2001 to 2012. Units of analysis were the 139 municipalities of the State. Negative binomial log linear regression models were used to estimate incidence rate ratios. RESULTS: In bivariate analysis, the incidence rate ratios were significantly higher for municipalities with higher income ratio of the poorest 20.0% (1.47; 95%CI 1.19-1.81) and better Municipal Human Development Index (1.53; 95%CI 1.14-2.06). In multivariate analysis, the incidence rate ratios were significantly higher in municipalities with higher proportion of immigrants (1.31; 95%CI 1.11-1.55) and higher proportion of households with waste collection (1.37; 95%CI 1.11-1.69). There was a significant reduction in the incidence rate ratio with increased coverage of the Bolsa Família Program (0.98; 95%CI 0.96-0.99). CONCLUSIONS: Control programs need to focus on activities in municipalities of greater social vulnerability with intersectoral investment for the improvement of the living conditions of the population. OBJETIVO: Identificar fatores socioeconômicos, demográficos, operacionais e de serviços de saúde associados à ocorrência da hanseníase em um estado hiperendêmico do norte do Brasil. MÉTODOS: Estudo ecológico com dados secundários do Sistema de Informações de Agravos de Notificação em municípios do estado do Tocantins de 2001 a 2012. As unidades de análise foram os 139 municípios do estado. Modelos de regressão log linear binomial negativa foram utilizados para estimar as razões de taxas de incidência. RESULTADOS: Na análise bivariada, a razão de taxa de incidência foi significativamente maior para os municípios com maior razão de renda dos 20,0% mais pobres (1,47; IC95% 1,19-1,81) e melhor Índice de Desenvolvimento Humano Municipal (1,53; IC95% 1,14-2,06). Na múltipla, a razão de taxa de incidência foi significativamente superior em municípios com maior concentração de imigrantes (1,31; IC95% 1,11-1,55) e proporção de domicílios com coleta de lixo (1,37; IC95% 1,11-1,69). Houve redução significativa da razão de taxa de incidência com o aumento da cobertura do programa bolsa família (0,98; IC95% 0,96-0,99). CONCLUSÕES: Os programas de controle precisam focar as atividades em municípios de maior vulnerabilidade social com investimentos intersetoriais para a melhoria das condições de vida da população.