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Objectives: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon., Methods: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred., Results: NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092-0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami)., Conclusion: The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pollution, causing millions of deaths annually, disproportionally affects low- and middle-income countries (LMICs). Mercury ranks among the three main chemicals of major public health concern, and even low levels can cause cardiovascular and nervous outcomes, with children and indigenous populations being especially vulnerable. Nearly 80% of all emissions in South America originate from the Amazon. Brazil, the fifth-largest contributor to global mercury emissions, exemplifies the challenges faced by LMICs in effectively monitoring and addressing mercury exposure/intoxication. Despite having powerful tools such as SINAN (a digital platform for compulsory disease reporting), and Community Health Agents, data reveals significant underreporting, especially in the Amazon. Furthermore, SINAN has important delays in its update: for instance, 196 cases of Munduruku Indigenous people in 2019 have only been included in 2023. In this Personal View, we outline insightful recommendations to enhance public health surveillance and implement enduring, effective strategies to monitor, report and address mercury exposure/intoxication, focusing on the Brazilian Amazon. Although these recommendations are tailored to the challenges of this country, they hold potential for adaptation by other Amazonian countries facing similar issues (high mercury emissions and the presence of vulnerable populations, among others)., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Genetic polymorphisms may influence mercury (Hg) toxicity. The aims of this study were to evaluate individual factors, such as the presence of the GSTP1 rs1695 polymorphism, associated with internal Hg dose and child neurodevelopment in indigenous people from the Brazilian Amazon chronically exposed to Hg. Eighty-two indigenous children were clinically evaluated, hair Hg was measured, and the GSTP1 rs1695 polymorphism was genotyped. The mean age was 4.8 years, the median Hg was 5.5 µg/g, and 93.8% of children exceeded the safe limit (2.0 µg/g). Fish consumption was associated with Hg levels ( p = 0.03). The GSTP1 rs1695 A>G polymorphism was in the Hardy-Weinberg equilibrium and the highest prevalence of the GSTP1 AA genotype (80%) was found in Sawré Aboy, which had the highest Hg levels (10 µg/g) among the studied villages. The Hg levels tended to increase over the years in males and in carriers of the GSTP1 AA genotype (0.69 µg/g and 0.86 µg/g, respectively). Nine children failed the neurodevelopmental test, all of whom had Hg > 2.0 µg/g, and 88.9% carried the GSTP1 AA or AG genotypes, previously associated with the highest internal Hg doses and neurocognitive disorders. The genetic counseling of this population is important to identify the individuals at greater risk for neurodevelopmental disorders resulting from chronic Hg exposure.

Competing Interests: We declare no conflicts of interest. RC and BT contributed equally.

Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82-100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight ( ALAD rs1800435, CYP3A4 rs2740574, CYP3A5 rs776746, CYP3A7 rs2257401, GSTP1 rs1695, MT1A rs8052394, MT1M rs2270836, and MT4 rs11643815) and three ( MT1A rs8052394, MT1M rs2270837, and MT2A rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The MT1A rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 μg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

Despite legal safeguards, the Yanomami community faces challenges such as unauthorized incursions by gold miners, resulting in environmental degradation, particularly from mercury. This jeopardizes the health and food security of indigenous individuals, especially due to the consumption of contaminated fish. Ethnic and racial disparities persist in indigenous healthcare, marked by troubling health indicators such as malnutrition, anemia, and infectious diseases. This cross-sectional study, conducted in October 2022 in the Yanomami Indigenous Territory in the Amazon Forest, Brazil, presented clinical, laboratory, and neurodevelopmental findings in Yanomami children chronically exposed to methylmercury. The results revealed that Yanomami children exhibited weights and heights below expectations (median Z-scores of -1.855 for weight for age and -2.7 for height for age), a high prevalence of anemia (25%), low vaccination coverage (15%), and low IQ (average 68.6). The Total Hair Mercury (Total Hg) levels ranged from 0.16 µg/g to 10.20 µg/g (mean: 3.30 µg/g; median: 3.70 µg/g). Of 117 children tested, 93 children (79.4%) had levels ≥ 2.0 µg/g (had no significant difference between sex). Among the 58 children for whom it was possible to estimate the Total Intelligence Quotient (TIQ), the average value was 68.6, ranging from 42 to 92 points (median: 69.5; standard deviation: 10.5). Additionally, the lowest score on the IQ test was associated with 5 times the risk of having high levels of mercury in their hair, 2,5 fold the risk of having an older age, and almost 8 times the risk of consuming fish, adjusting for nut consumption. Notwithstanding the study's limitations, results suggest that mercury contamination from illegal mining activities on indigenous lands may negatively impact neurodevelopment in older indigenous children, particularly those fish consumers, despite the inherent benefits of fish consumption. Addressing other socio-environmental concerns is crucial for enhancing the overall health of the population.

This is the first report of the distribution of TPMT and NUDT15 single nucleotide polymorphisms and metabolic phenotypes associated with cytotoxicity of thiopurine drugs, in indigenous groups of Brazilian Amazon: Munduruku, Paiter-Suruí and Yanomami. The minor allele frequency (MAF) of NUDT15 rs116855232 did not differ significantly across the groups; TPMT rs1800462 was absent, while rs1800460 and rs1142345 were in strong linkage disequilibrium, and 10- and 30-fold more common in Paiter-Suruí. Indeed, the MAFs in Paiter-Surui (0.193 and 0.188) are the largest report globally. The distribution of combined NUDT15/TPMT metabolic phenotypes differed significantly ( p < 0.0001) and largely (Cramér´s V = 0.37) across cohorts. This has important pharmacogenetic implications: the Clinical Pharmacogenetics Implementation Consortium recommendations to reduce or consider reduction of thiopurine dose applies to 4.4% Yanomami, 5.6% Munduruku, versus 41% Paiter-Suruí. The proportion of Paiter-Suruí at risk of thiopurine intolerance is 3- to 4-fold higher than any other population worldwide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Perini, Basta and Suarez-Kurtz.)

Mercury is one of the most dangerous contaminants on the planet. In recent years, evidence of mercury contamination in the Amazon has significantly increased, notably due to gold-mining activities. Although mercury contamination in fish has consistently been documented, little is known about the risk associated with fish consumption by populations in urban areas of the Amazon. We sampled 1010 fish sold in public markets in six state capitals and 11 additional cities. Mercury levels were determined for each specimen, and the evaluation of the health risks associated with consuming mercury-contaminated fish was conducted according to the methodology proposed by the World Health Organization (WHO). Our study reveals that more than one-fifth (21.3%) of the fish sold in urban centers had mercury levels above the safe limits (≥0.5 µg/g) established by the Brazilian Health Surveillance Agency (ANVISA). The prevalence of Hg contamination ≥0.5 µg/g was approximately 14 times higher in carnivorous than in noncarnivorous fish. The analysis of the risk attributable to fish consumption reveals that daily mercury intake exceeded the reference dose recommended by the U.S. EPA in all population groups analyzed, reaching up to 7 and 31 times in women of childbearing age and children from 2 to 4 years old, respectively. However, these risks are diverse depending on the type of fish consumed and must be considered to formulate appropriate nutritional guidelines for safe fish consumption by the local community.

Genetic polymorphisms may be involved with mercury levels and signs and symptoms of intoxication from this exposure. Therefore, the aims were to describe the frequency of the GSTP1 polymorphism and to evaluate its effects on mercury levels and neurological signs in three Munduruku indigenous villages in the Brazilian Amazon. One-hundred-and-seven indigenous (over 12 years old) were included and genotyped (rs1695) using a TaqMan validated assay. Then, associations were evaluated by binary logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 27.4 ± 13.9 years old, 52.3% were male, mean hair mercury concentration was 8.5 ± 4.3, exceeding the reference limit (≥6.0 µg/g), and were different among the three villages: 13.5 ± 4.6 µg/g in Sawré Aboy , 7.4 ± 2.3 µg/g in Poxo Muybu and 6.9 ± 3.5 µg/g in Sawré Muybu . The minor allele frequency of GSTP1 G was significantly different among the villages: 57% Sawré Muybu, 21% Poxo Muybu and 15% Sawré Aboy. Finally, after adjustment, GSTP1 GG and GA genotypes were associated with lower levels of Hg (OR = 0.13; CI95% = 0.03-0.49) and abnormal somatosensory signs (OR = 3.7; 95%IC = 1.5-9.3), respectively. In conclusion, monitoring this population is imperative to identify individuals at higher risk of developing signs of chronic mercury exposure based on the genetic profile.

Objective: The current study aimed to characterise the food profile of Yanomami indigenous children according to the degree of food processing and its associated factors., Design: This is a cross-sectional study with Yanomami indigenous children aged 6 to 59 months. Socio-demographic, maternal and infant data were collected through a standardised questionnaire. The food profile was obtained by using a list of thirty-four foods to verify the child's consumption of these foods on the day preceding the interview. Foods were classified according to the degree of processing based on the NOVA system (in natura or minimally processed, processed culinary ingredients, processed and ultra-processed). In natura and minimally processed foods were subdivided into 'regional' and 'urban' foods. Poisson regression analysis was applied to estimate the associated factors according to the 90 % CI., Setting: Three villages (Auaris, Maturacá and Ariabú) in the Yanomami indigenous territory, in the Brazilian Amazon., Participants: In total, 251 Yanomami children aged 6 to 59 months were evaluated., Results: The prevalence of consumption of 'regional' and 'urban' in natura or minimally processed foods was 93 % and 56 %, respectively, and consumption of ultra-processed foods was 32 %. Ultra-processed food consumption was 11·6 times higher in children of Maturacá and 9·2 times higher in Ariabú when compared with the children of Auaris and 31 % lower in children who had mothers with shorter stature., Conclusion: Despite the high frequency of consumption of in natura and minimally processed foods, the consumption of ultra-processed foods was substantial and was associated with demographic and maternal factors in Yanomani indigenous children under 5 years of age.

The aim of this study was to assess the health risk attributable to the consumption of mercury-contaminated fish for the urban and non-urban populations living in the Roraima state, Amazon, Brazil. Seventy-five fish specimens distributed across twenty different species, comprising four trophic levels (i.e., herbivore, omnivore, detritivore, and carnivore), were collected at four locations in the Branco River Basin. The fish samples were sent to the Toxicology Laboratory at Evandro Chagas Institute to determine the total-Hg levels by using the cold vapor atomic system (CVAAS). The total-Hg levels ranged from 0 to 3.159 µg/g. The average concentration in non-carnivorous species ( n = 32) was 0.116 µg/g, and among carnivorous fish ( n = 43), it was 0.869 µg/g. The weighted average of contamination levels for all samples was 0.545 µg/g. The health risk assessment was conducted according to the methodology proposed by the World Health Organization and different scenarios of human exposure were considered, based on three levels of fish consumption (low: 50 g/day; moderate: 100 g/day and high: 200 g/day). Women of childbearing age ingest 5 to 21 times more mercury than the dose considered safe by the U.S. EPA and intake a dose from 2 to 9 times higher than the safe dose proposed by FAO/WHO. Children under 5 years of age ingest from 18 to 75 times the dose proposed by the U.S. EPA and from 8 to 32 more mercury than the limit proposed by FAO/WHO. In summary, regardless of the level of fish consumption, type of residency (urban or non-urban), and the subset of the population analyzed, anyone who consumes fish from the locations sampled is at high risk attributable to mercury ingestion, with the only exception of adult men, who consume an average of 50 g of fish per day.

In recent decades, widespread and uncontrolled use of mercury (Hg) in artisanal small-scale gold mining has released thousands of tons of mercury-contaminated waste in the Amazon biome, endangering the largest tropical rainforest worldwide. In this study, we assessed and compared blood Hg levels in individuals living in urban and riverine areas in the lower Tapajós basin and examined the association between Hg exposure and specific biochemical parameters. In total, 462 adults from eight riverine communities and one urban area were assessed. Overall, 75.6% of the participants exhibited Hg concentrations exceeding the safe limit (10 µg/L). Hg exposure was higher in the riverine population (90%) than in urban areas (57.1%). Mean Hg levels were 21.8 ± 30.9 µg/L and 50.6 µg/L in urban and riverine residents, respectively. The mean Hg level was higher in those aged 41-60 years in both urban and riparian areas, with riparian residents exhibiting a mean double that of urban residents. The highest glucose and hepatic biomarker levels were detected in the urban area, whereas the highest levels of renal biomarker occurred in the riverine population. Our results indicate that Hg contamination remains a persistent challenge for the urban population of Santarém, a major city in the Brazilian Amazon.

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages ( Sawré Muybu , Poxo Muybu , and Sawré Aboy ) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants' median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0-22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal-Wallis test with p -value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13-4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18-3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06-9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.

In line with the 1000-day initiative and the Sustainable Development Goals (SDG) 2 and 3, we present a cross-sectional analysis of maternal health, infant nutrition, and methylmercury exposure within hard-to-reach indigenous communities in the state of Pará, Brazilian Amazon. We collected data from all women of childbearing age (i.e., 12-49) and their infants under two years old in three Munduruku communities ( Sawré Muybu , Sawré Aboy , and Poxo Muybu ) along the Tapajos River. We explored health outcomes through interviews, vaccine coverage and clinical assessment, and determined baseline hair methylmercury (H-Hg) levels. Hemoglobin, infant growth (Anthropometric Z scores) and neurodevelopment tests results were collected. We found that 62% of women of childbearing age exceeded the reference limit of 6.0 μg/g H-Hg (median = 7.115, IQR = 4.678), with the worst affected community ( Sawré Aboy ) registering an average H-Hg concentration of 12.67 μg/g. Half of infants aged under 24 months presented with anemia. Three of 16 (18.8%) infants presented H-Hg levels above 6.0 µg/g (median: 3.88; IQR = 3.05). Four of the 16 infants were found to be stunted and 38% of women overweight, evidencing possible nutritional transition. No infant presented with appropriate vaccination coverage for their age. These communities presented with an estimated Infant Mortality Rate (IMR) of 86.7/1000 live births. The highest H-Hg level (19.6 µg/g) was recorded in an 11-month-old girl who was found to have gross motor delay and anemia. This already vulnerable indigenous Munduruku community presents with undernutrition and a high prevalence of chronic methylmercury exposure in women of childbearing age. This dual public health crisis in the context of wider health inequalities has the potential to compromise the development, health and survival of the developing fetus and infant in the first two critical years of life. We encourage culturally sensitive intervention and further research to focus efforts.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages ( Sawré Muybu, Poxo Muybu, and Sawré Aboy ), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 μg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p -value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

To describe the factors associated to stunting in <5-year-old Yanomami Brazilian children, and to evaluate the association of short maternal stature to their offspring's stunting. A cross-sectional study carried out in three villages in the Yanomami territory. We performed a census, in which all households with children < 5-years-old were included. The length/height-for-age z-score <-2 standard deviations was used to classify the children as stunted. Short maternal height was defined as <145 cm for adult women, and <-2 standard deviations of the height-for-age z-score for adolescent women. We used adjusted Poisson regression models to estimate prevalence ratios (PR) along the 90% confidence interval. We evaluated 298 children. 81.2% of children suffered from stunting and 71.9% of the mothers from short stature. In the bivariate analysis, a significant association of stunting with short maternal stature, gestational malaria and child's place of birth were observed. Considering the variables of the children under five years of age, there were significant associations with age group, the child's caregiver, history of malaria, pneumonia, and malnutrition treatment. In the adjusted hierarchical model, stunting was 1.22 times greater in the offspring of women with a short stature (90% CI: 1.07-1.38) compared to their counterparts. Brazilian Amazonian indigenous children living in a remote area displayed an alarming prevalence of stunting, and this was associated with short maternal height, reinforcing the hypothesis of intergenerational chronic malnutrition transmission in this population. In addition, children above 24 months of age, who were born in the village healthcare units and who had had previous treatment in the past for stunting presented higher rates of stunting in this study.

This paper is an exploratory study that examines the illegal goldmining impacts on Munduruku communities' "Good-Living" ( Xipan Jewewekukap ) and explores the possible relationship between chronic methylmercury (MeHg) exposure and the worsening mental health conditions in three villages in the Middle-Tapajós River, Brazilian Amazon. The region has been experiencing a long-lasting threat of goldminers' invasions. A total of 109 people were interviewed and evaluated. Total mercury (THg) exposure levels were evaluated through hair samples analysis, from which MeHg exposure levels were calculated. The Geriatric Depression Scale-Short Form (GDS-SF) was used as a screening tool in order to assess mental health indicators. Brief non-structured interviews were carried out to investigate how goldmining is impacting the communities Good-Living. A Poisson regression model was used to estimate the possible association between mental health indicators (assessed through the GDS-SF) and the following independent variables: (i) mercury exposure level (<10.0 μg/g vs. ≥10.0 μg/g), (ii) self-reported nervousness, (iii) self-reported irritability, (iv) age group, and (v) monthly income. The analysis revealed high levels of mercury in hair samples (median: 7.4 µg/g, range 2.0-22.8; 70% and 28% of the participants had THg levels ≥6.0 and ≥10.0 µg/g, respectively) and pointed to a tendency in which higher levels of methylmercury exposure (Hg ≥ 10.0 µg/g) could be linked to worse mental health indicators. Although the GDS-SF has presented limitations due to the Munduruku sociocultural context, our findings suggest a tendency of worse mental health indicators in participants presenting high levels of MeHg exposure. Despite this limitation, the qualitative approach indicates an evident association between the impacts of goldmining and the Munduruku people's decreasing autonomy to maintain a Good-Living on their own terms, pointing to the importance of carrying out new investigations, especially considering longitudinal studies with qualitative methodologies and ethnographic approaches., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4-23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD , while the others were all wild type. Minor allele frequency ( ALAD G ) and heterozygous genotype ( ALAD CG ) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.

Fish serves as the principal source of animal protein for the indigenous people of the Amazon, ensuring their food and nutritional security. However, gold mining causes mercury (Hg) contamination in fish, and consequently increases health risks associated with fish consumption. The aim of this study was to assess the health risk attributed to the consumption of mercury-contaminated fish by Munduruku indigenous communities in the Middle-Tapajós Region. Different fish species were collected in the Sawré Muybu Indigenous Land to determine mercury levels. The health risk assessment was carried out according to the World Health Organization (WHO 2008) methodology and different scenarios were built for counterfactual analysis. Eighty-eight fish specimens from 17 species and four trophic levels were analyzed. Estimates of Hg ingestion indicated that the methylmercury daily intake exceeds the U.S. EPA (United States Environmental Protection Agency) (2000) reference dose from 3 to 25-fold, and up to 11 times the FAO (Food and Agriculture Organization)/WHO (2003) dose recommendation. In all situations analyzed, the risk ratio estimates were above 1.0, meaning that the investigated Munduruku communities are at serious risk of harm as a result of ingestion of mercury-contaminated fish. These results indicate that, at present, fish consumption is not safe for this Munduruku population. This hazardous situation threatens the survival of this indigenous population, their food security, and their culture.

Objective: To estimate the incidence, mortality and lethality rates of COVID-19 among Indigenous Peoples in the Brazilian Amazon. Additionally, to analyze how external threats can contribute to spread the disease in Indigenous Lands (IL). Methods: The Brazilian Amazon is home to nearly half a million Indigenous persons, representing more than 170 ethnic groups. As a pioneer in heading Indigenous community-based surveillance (I-CBS) in Brazil, the Coordination of the Indigenous Organizations of the Brazilian Amazon (COIAB) started to monitor Indigenous COVID-19 cases in March of 2020. Brazil's Ministry of Health (MOH) was the main source of data regarding non-Indigenous cases and deaths; to contrast the government's tally, we used the information collected by I-CBS covering 25 Special Indigenous Sanitary Districts (DSEI) in the Brazilian Amazon. The incidence and mortality rates of COVID-19 were calculated using the total number of new cases and deaths accumulated between the 9th and 40th epidemiological weeks. We studied (a) the availability of health care facilities to attend to Indigenous Peoples; (b) illegal mines, land grabbing, and deforestation to perform a geospatial analysis to assess how external threats affect Indigenous incidence and mortality rates. We used the Generalized Linear Model (GLM) with Poisson regression to show the results. Results: MOH registered 22,127 cases and 330 deaths, while COIAB's survey recorded 25,356 confirmed cases and 670 deaths, indicating an under-reporting of 14 and 103%, respectively. Likewise, the incidence and mortality rates were 136 and 110% higher among Indigenous when compared with the national average. In terms of mortality, the most critical DSEIs were Alto Rio Solimões, Cuiabá, Xavante, Vilhena and Kaiapó do Pará . The GLM model reveals a direct correlation between deforestation, land grabbing and mining, and the incidence of cases among the Indigenous. Conclusion: Through this investigation it was possible to verify that not only the incidence and mortality rates due to COVID-19 among Indigenous Peoples are higher than those observed in the general population, but also that the data presented by the federal government are underreported. Additionally, it was evident that the presence of illegal economic activities increased the risk of spreading COVID-19 in ILs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fellows, Paye, Alencar, Nicácio, Castro, Coelho, Silva, Bandeira, Lourival and Basta.)

After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.

Background: The Guarani-Kaiowá are Brazil's second-largest indigenous group. Average annual tuberculosis (TB) incidence rates among the Guarani-Kaiowá are nearly 400/100,000 in Mato Grosso do Sul state, ten times the national average. Although stigma is considered crucial for TB control in indigenous communities, few studies have investigated TB stigma among indigenous populations. This study sought to understand the role of TB-related stigma and perceptions of TB in maintaining hyperendemic TB transmission in the Guarani-Kaiowá communities., Methods: Various forms of stigma were explored through semi-structured interviews with 19 patients, 11 relatives, and 23 community members. Patients were identified from the registry of the healthcare service. Community members, selected by snowball sampling, were matched by gender and village of residence. Interviews were conducted in Guarani and Portuguese and later translated into English. Framework analysis was performed using NVivo., Results: Traditional beliefs of a weakening of the body allowing the disease to enter were common, but the exact mechanism of transmission was unknown. Strong community/public stigma associated TB with uncleanliness, abuse, and irresponsibility. Anticipated stigma led to significant treatment delays for fear of exclusion and losing employment. While most patients felt supported by their families, nearly all patients related experienced/enacted stigma in the community such as gossip, avoidance, and social exclusion, leading to long-lasting internalized/self-stigma. Secondary stigmatization of relatives was widespread, and blanket latent TB infection (LTBI) treatment of patients' households was a contributing factor in treatment delay. The healthcare service unnecessarily added to stigmatization by enforcing separate utensils and sleeping arrangements for patients., Conclusions: Our findings suggest that stigma is a driver for treatment delay and continued transmission of TB in the community. The stigmatization of TB was rooted in a poor understanding of TB transmission, partly because of incorrect orientation by the healthcare service. Interventions to reduce TB-associated stigma are urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study aimed to analyze the factors associated with likely TB deaths, likely TB-related deaths and deaths from other causes. Understanding the factors associated with mortality could help the strategy to End TB, especially the goal of reducing TB deaths by 95% between 2015 and 2035., Methods: A retrospective, population-based cohort study of the causes of death was performed using a competing risk model in patients receiving treatment for TB. Patients had started TB treatment in Brazil 2008-2013 with any death certificates dated in the same period. We used three categories of deaths, according to ICD-10 codes: i) probable TB deaths; ii) TB-related deaths; iii) deaths from other causes., Results: In this cohort, 39,997 individuals (14.1%) died, out of a total of 283,508 individuals. Of these, 8,936 were probable TB deaths (22.4%) and 3,365 TB-related deaths (8.4%), illustrating high mortality rates. 27,696 deaths (69.2%) were from other causes. From our analysis, factors strongly associated with probable TB deaths were male gender (sHR = 1.33, 95% CI: 1.26-1.40), age over 60 years (sHR = 9.29, 95% CI: 8.15-10.60), illiterate schooling (sHR = 2.33, 95% CI: 2.09-2.59), black (sHR = 1.33, 95% CI: 1.26-1.40) and brown (sHR = 13, 95% CI: 1.07-1.19) color/race, from the Southern region (sHR = 1.19, 95% CI: 1.10-1.28), clinical mixed forms (sHR = 1.91, 95% CI: 1.73-2.11) and alcoholism (sHR = 1.90, 95% CI: 1.81-2.00). Also, HIV positive serology was strongly associated with probable TB deaths (sHR = 62.78; 95% CI: 55.01-71.63)., Conclusions: In conclusion, specific strategies for active surveillance and early case detection can reduce mortality among patients with tuberculosis, leading to more timely detection and treatment., Competing Interests: The authors declare that they have no competing interests.

Artisanal small-scale gold mining (ASGM) is the main source of anthropogenic mercury emissions and contamination in Latin America. In the Brazilian northern Amazon, ASGM has contaminated the environment and people over the past century. The main contamination route is through fish consumption, which endangers the food security and livelihoods of traditional communities. Our study aims to assess the potential toxicological health risks caused by the consumption of Hg-contaminated fish across five regions in Amapá State. We sampled 428 fish from 18 sites across inland and coastal aquatic systems. We measured the total mercury content in fish samples, and the results were applied to a mercury exposure risk assessment targeting three distinct groups (adults, women of childbearing age, and children). Mercury contamination was found to exceed the World Health Organization's safe limit in 28.7% of all fish samples, with higher prevalence in inland zones. Moreover, the local preference for carnivorous fish species presents a serious health risk, particularly for communities near inland rivers in the region. This is the first study to provide clear recommendations for reducing the mercury exposure through fish consumption in Amapá State. It builds scientific evidence that helps decision-makers to implement effective policies for protecting the health of riverine communities.

Objective: to investigate access to health services for tuberculosis (TB) diagnosis and treatment among indigenous peoples in Rondônia State, Brazil, 2009-2011., Methods: we conducted a cross-sectional study with indigenous people attending Indigenous Health Care Units (Casai) between October 2009 and February 2011; geographical, economical and functional dimensions of access to TB services were evaluated through interviews and then described., Results: 52 indigenous people with TB were interviewed; in the geographical dimension, lack of transportation, distance and lack of health professionals were the main obstacles; in the economic dimension, 15 indigenous people reported cost/expense as a barrier to access; in the functional dimension, 21 arrived at the Casai using their own means; 24 reported that the time between first symptoms and arriving at the Casai was > 30days; 25 reported that time between first consultation and starting treatment was >30 days; treatment was supervised in 22 cases., Conclusion: the difficulties found in accessing health services in the dimensions we analyzed can contribute to TB continuing to be transmitted in indigenous villages.

The study aimed to describe clinical and sociodemographic characteristics, estimate incidence, and analyze factors associated with dropout and death during treatment of TB cases reported in indigenous children and adolescents in Brazil from 2006 to 2016. A historical case series was performed on incidence according to age bracket and major geographic region, and multinomial logistic regression was used to explain factors associated with treatment dropout and death. Of the 2,096 reported cases, 88.2% evolved to cure, 7.2% dropped out of treatment, and 4.6% evolved to death. There was a predominance of cases in boys 15-19 years of age and a higher proportion of deaths (55.7%) in children < 4 years. Considering indigenous children and adolescents with TB in Brazil as a whole, mean incidence was 49.1/100,000, ranging from 21.5/100,000 to 97.6/100,000 in the Northeast and Central, respectively. Cases with insufficient and irregular follow-up showed higher odds of dropout (OR = 11.1; 95%CI: 5.2-24.8/OR = 4.4; 95%CI: 1.9-10.3) and death (OR = 20.3; 95%CI: 4.9-84.9/OR = 5.1; 95%CI: 1.2-22.7). Cases in retreatment (OR = 2.4; 95%CI: 2.08-8.55) and with HIV coinfection (OR = 8.2; 95%CI: 2.2-30.9) were also associated with dropout. Extrapulmonary (OR = 1.8; 95%CI: 1.1-3.3) and mixed clinical forms (OR = 5.6; 95%CI: 2.8-11.4), age < 4 years (OR = 3.1; 95%CI: 1.5-6.4), and cases from the North (OR = 2.8; 95%CI: 1.1-7.1) and Central (OR = 2.8; 95%CI: 1.1-7.0) were associated with death. TB control in indigenous children and adolescents cannot be achieved without investments in research and development and without reducing social inequalities.

This study evaluates the nutritional status of children and women of an indigenous Yanomamigroup, and seeks to clarify associated factors. It was a cross-sectional study, carried out in 17 villages, in 2014. For evaluation of nutritional status we used 2006 growth standards to assign height-for-age (stunting)Z-scores (Z), weight-for-age Z (underweight) and weight-for-height Z (wasting and overweight), using the software WHO-Anthro and WHO-AnthroPlus. Short stature (SS) was defined as values lower 145cm for mothers over the age of 18. The Poisson regression was made in R software. Among children under 60 months the prevalences were: stunting 83.8%; underweight 50%; wasting 5.4%; and overweight 2.7%. In 59.5% of the children there was severe stunting, and 68.1% of the mothers were SS. Prevalence ratio (PR) for severe stunting was higher in age group 36-59 months, in comparison with age group 0.1-23 (PR = 1.3; CI 95%: 1.1-2.3), as did also children of mothers with SS, when compared to the children of mothers without SS (PR = 2.1; CI 95%; 1.2-3.6). The alarming rates of stunting and severe stunting reveal the seriousness of the nutritional situation children. The association of severe stunting in infants and in mothers reflects the intergenerational nature of the problem.

Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population., Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test)., Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity., Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

The Mato Grosso do Sul State (MS) has the second-largest indigenous population and the highest incidence rates of TB among indigenous people in Brazil. However, little is known about the risk factors associated with active TB in indigenous people in the region, especially regarding socioeconomic factors. The aim of this study is to assess the effect of the Family Allowance Program (BFP) and of other predictors of active TB in a high-risk indigenous population in Brazil. We conducted a case-control study with incident TB cases matched by age and by village of residence (1:2 proportion) between March 2011 and December 2012. We used a conditional logistic regression for data analysis. A total of 153 cases and 306 controls were enrolled. The final model included the following risk factors: alcohol consumption (low-risk use OR=2.2; 95% CI 1.1-4.3; risky use OR=2.4; 95% CI 1.0-6.0; dependent/ damaging use OR=9.1; 95% CI 2.9-29.1); recent contact with a TB patient (OR=2.0; 95% CI 1.2-3.5); and male sex (OR=1.9; 95% CI 1.1-3.2). BFP participation (OR=0.5; 95% CI 0.3-0.6) and BCG vaccination (OR=0.5; 95% CI 0.3-0.9) were found to be protective factors against TB. Although the BFP was not designed to target TB-affected households specifically, our findings reveal the importance of the BFP in preventing one of the most important infectious diseases among adults in indigenous villages in Brazil. This result is in line with the End-TB strategy, which identifies social protection, poverty alleviation and targeting other determinants of TB as key actions.

In the Brazilian Amazon, where the majority of Yanomami villages are settled, mercury (Hg) exposure due to artisanal small-scale gold mining (ASGM) has been reported since the 1980s. This study assessed mercury exposure in the Yanomami reserve and whether the level of contamination was related to the ASGM geographical location. It was conducted using a cross-sectional study of 19 villages. Direct interviews were performed and hair samples were used as a bioindicator of Hg exposure. The Prevalence-Ratio (PR) was estimated as an indicator of association between ASGM geographical locations and human exposure to mercury. Mercury levels (239 hair samples) ranged between 0.4 and 22.1 μg·g -1 and presented substantial differences amongst the villages. In the Waikas-Aracaça region, where current ASGM was reported, we observed the highest Hg concentrations (median = 15.5 μg·g -1 ). Almost all participants presented with hair-Hg levels >6 μg·g -1 (prevalence = 92.3%). In the Paapiu region, we observed the lowest concentrations (median = 3.2 μg·g -1 ; prevalence = 6.7%). Our findings showed that the Waikas Ye'kuana and Waikas Aracaca villages presented with 4.4 (PR = 4.4; Confidence Interval (CI) 95% = 2.2⁻9.0) and 14.0 (PR = 14.0; CI 95% = 7.9⁻24.9) times higher prevalence of hair-Hg concentration, respectively, compared with Paapiu. Considering seasonal variation of Hg-exposure, the lowest concentrations were observed during the wet season (June⁻September) and the highest in the dry season (December⁻April). Our study suggests that there is an association between mercury exposure and ASGM geographical locations.

Objective: To estimate the rate of drug resistance among pulmonary tuberculosis (PTB) cases in the state of Mato Grosso do Sul, Brazil, and specifically in the border areas with Paraguay and Bolivia, as well as to identify associated risk factors., Method: The present cross-sectional, epidemiological study focused on PTB cases recorded between January 2007 and December 2010 in the State Reportable Disease Information System with results of susceptibility tests to rifampicin, isoniazid, ethambutol, and streptomycin. Dependent variables were development of resistance to a single drug or any combination of drugs. Independent variables were being a new or treated case, living in border areas, presence/absence of diabetes, and history of alcoholism., Results: There were 789 TBP cases with susceptibility testing. The following characteristics were associated with resistance: treated case (P = 0.0001), border region (P = 0.0142), alcoholism (P = 0.0451), and diabetes (P = 0.0708). The rates of combined, primary, and acquired resistance for the state were 16.3%, 10.6%, and 39.0%, vs. 22.3%, 19.2%, and 37.5% for the border region. The rates of combined, primary, and acquired multidrug resistance for the state were 1.8%, 0.6%, and 6.3%, vs. 3.1%, 1.2%, and 12.5% for the border region., Conclusions: In the border region, the state should investigate drug resistance in all patients with respiratory symptoms, determine the pattern of resistance in confirmed cases, adopt directly observed treatment for cases of PTB, and develop health actions together with neighboring countries. Across the state, the levels of acquired resistance should be monitored, with investigation of resistance in all treated cases and implementation of directly observed treatment especially among patients with diabetes or alcoholism.

Objective: To analyze the quality of records for live births and infant deaths and to estimate the infant mortality rate for skin color or race, in order to explore possible racial inequalities in health., Methods: Descriptive study that analyzed the quality of records of the Live Births Information System and Mortality Information System in Rondônia, Brazilian Amazonian, between 2006-2009. The infant mortality rates were estimated for skin color or race with the direct method and corrected by: (1) proportional distribution of deaths with missing data related to skin color or race; and (2) application of correction factors. We also calculated proportional mortality by causes and age groups., Results: The capture of live births and deaths improved in relation to 2006-2007, which required lower correction factors to estimate infant mortality rate. The risk of death of indigenous infant (31.3/1,000 live births) was higher than that noted for the other skin color or race groups, exceeding by 60% the infant mortality rate in Rondônia (19.9/1,000 live births). Black children had the highest neonatal infant mortality rate, while the indigenous had the highest post-neonatal infant mortality rate. Among the indigenous deaths, 15.2% were due to ill-defined causes, while the other groups did not exceed 5.4%. The proportional infant mortality due to infectious and parasitic diseases was higher among indigenous children (12.1%), while among black children it occurred due to external causes (8.7%)., Conclusions: Expressive inequalities in infant mortality were noted between skin color or race categories, more unfavorable for indigenous infants. Correction factors proposed in the literature lack to consider differences in underreporting of deaths for skin color or race. The specific correction among the color or race categories would likely result in exacerbation of the observed inequalities., Objetivo: Analisar a qualidade dos registros de nascidos vivos e de óbitos infantis e estimar a taxa de mortalidade infantil segundo cor ou raça, a fim de explorar iniquidades étnico-raciais em saúde., Métodos: Estudo descritivo que analisou a qualidade dos registros do Sistema de Informações sobre Nascidos Vivos e do Sistema de Informações sobre Mortalidade em Rondônia, Amazônia brasileira, entre 2006-2009. As taxas de mortalidade infantil foram estimadas nas categorias de cor ou raça, pelo método direto, e corrigidas por: (1) distribuição proporcional dos óbitos com cor ou raça ignorada; e (2) aplicação de fatores de correção. Efetuou-se também o cálculo da mortalidade proporcional por causas e grupos etários., Resultados: Entre 2008-2009, a captação de nascimentos e óbitos melhorou em relação aos anos de 2006-2007, requerendo fatores de correção menores para estimar a taxa de mortalidade infantil. O risco de morte de crianças indígenas (31,3/1.000 nascidos vivos) foi maior que o registrado nos demais grupos de cor ou raça, excedendo em 60% a mortalidade infantil média no estado (19,9/1.000 nascidos vivos). As crianças pretas apresentaram as maiores taxas de mortalidade infantil neonatal, enquanto as indígenas apresentaram as maiores taxas de mortalidade infantil pós-neonatal. Observou-se que 15,2% dos óbitos indígenas foram por causas mal definidas, enquanto nos demais grupos não ultrapassaram 5,4%. A mortalidade infantil proporcional por doenças infecciosas e parasitárias foi maior entre indígenas, ao passo que entre crianças pretas, sobressaíram as causas externas (8,7%)., Conclusões: Observaram-se expressivas iniquidades na mortalidade infantil entre as categorias de cor ou raça, com situação mais desfavorável às crianças indígenas. Os fatores de correção propostos na literatura não consideram diferenças na subenumeração de óbitos entre as categorias de cor ou raça. A correção específica entre as categorias de cor ou raça provavelmente resultaria em exacerbação das iniquidades observadas.

Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity. Odds ratios were used as the association measures. The incidence of hepatotoxicity was 19.7% for all patients. The risk of hepatotoxicity was almost four times higher in indigenous patients, comparing to non-indigenous. We identified a new nonsynonymous single nucleotide polymorphism of NAT2 in indigenous patients. In total, 54.6% of the patients expressed a slow acetylation phenotype profile. The frequency of the null genotype of GSTM1 was higher in non-indigenous patients (p = 0.002), whereas no significant differences in relation to polymorphisms of CYP2E1 were observed between the groups. Hepatotoxicity was associated with patients older than 60 and indigenous (OR = 26.0; 95%CI:3.1-217.6; OR = 3.8; 95%CI:1.3-11.1, respectively). Furthermore, hepatotoxicity was associated with a slow acetylation profile in indigenous patients (OR = 10.7; 95%CI:1.2-97.2). Our findings suggest that there are distinct acetylation profiles in the Brazilian population, emphasizing the importance of pharmacogenetic analyses for achieving personalized therapeutic schemes and better outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To examine spatial-temporal distribution and risk of suicide, as well as trends in suicide mortality rates, in the indigenous and non-indigenous population of the state of Mato Grosso do Sul, Brazil., Methods: Data were obtained from the Information Department of the Brazilian Unified Health System. Deaths recorded as voluntary self-inflicted injuries (ICD-10 codes X60.0 to X84.9) were considered suicide. Suicide rates were estimated and adjusted by age in the population > 9 years of age. Kernel analysis was used to assess the spatial distribution of suicide cases, while trend analysis was carried out using a non-parametric test (Mann-Kendall)., Results: The suicide risk among the indigenous population was 8.1 (95%CI 7.2-9.0) times higher than in the non-indigenous population. For indigenous residents in the 15-24 age group, the risk was 18.5 (95%CI 17.5-19.6) times higher than in the non-indigenous population. The majority of indigenous cases were concentrated in a few villages in reservation areas, mainly occupied by Guarani-Kaiowá and Guarani-Ñandeva groups. Rate patterns remained stable over time in both groups., Conclusion: Suicide is a serious public health problem in Mato Grosso do Sul, and has had an alarming and disproportionate impact on the indigenous population for more than a decade.

Introduction: Recent studies have shown a high incidence and prevalence of latent tuberculosis infection (LTBI) in indigenous populations around the World. We aimed to estimate the prevalence and annual risk of infection (ARI) as well as to identify factors associated with LTBI in an indigenous population from the Brazilian Amazon., Methods: We conducted a cross-sectional study in 2011. We performed tuberculin skin tests (TSTs), smears and cultures of sputum samples, and chest radiographs for individuals who reported cough for two or more weeks. Associations between LTBI (TST ≥5mm) and socio-demographic, clinical, and epidemiological characteristics were investigated using Poisson regression with robust variance. Prevalence ratio (PR) was used as the measure of association., Results: We examined 263 individuals. The prevalence of LTBI was 40.3%, and the ARI was 2.4%. Age ≥15 years [PR=5.5; 95% confidence interval (CI): 3.5-8.6], contact with tuberculosis (TB) patients (PR=3.8; 95% CI: 1.2-11.9), previous TB history (PR=1.4; 95% CI: 1.2-1.7), and presence of Bacillus Calmette-Guérin (BCG) scar (PR=1.9, 95% CI: 1.2-2.9) were associated with LTBI., Conclusions: Although some adults may have been infected years prior, the high prevalence of infection and its strong association with age ≥15 years, history of TB, and recent contact with TB patients suggest that the TB transmission risk is high in the study area.

Objective: This study analysed clinical and sociodemographic aspects and follow-up for notified cases of tuberculosis (TB) and explored inequalities in incidence rates and outcome by colour or race and the geographic macro-regions of Brazil., Methods: This paper reports the results of a population-based descriptive epidemiological study of all notified cases of TB in Brazil during the period from 01/01/2008 to 31/12/2011. We analysed sociodemographic and clinical variables according to colour or race (white, black, Asian, mixed, and indigenous) and geographic macro-regions of the country (North, Northeast, Central-West, South, and Southeast)., Results: During the study period, the average incidence of TB in Brazil was 36.7 cases per 100,000 inhabitants, with the highest rates occurring in the North and Southeast regions. The analysis of TB notifications by colour or race revealed that the indigenous population presented the highest incidence rates in all macro-regions except the South, where higher rates were reported in black patients. 'Cured' was the most frequently reported treatment outcome for all skin colour categories. The highest cure rate occurred among the indigenous population (76.8%), while the lowest cure rate occurred among the black population (70.7%). Rates of treatment default were highest among blacks (10.5%) and lowest among the indigenous population (6.9%). However, the fatality rate was similar across race categories, varying between 2.8% and 3.8% for whites and the indigenous population, respectively. The lowest cure rates were observed when follow-up was inadequate (58.3%), and the highest was observed when the follow-up was classified as excellent (96.8%)., Conclusions: This study revealed that-apart from the heterogeneous distribution of TB among the Brazilian macro-regions-ethnic-racial inequalities exist in terms of clinical-epidemiological characteristics and incidence rates as well as follow-up for cases undergoing treatment. The highest rates of TB occurred among the indigenous people.

In developing countries, pneumonia is the leading cause of sickness and mortality in childhood, especially among vulnerable groups. The scope of this study was to analyze the factors associated with pneumonia in Yanomami children hospitalized for Ambulatory Care Sensitive Conditions (ACSC). Hospital admissions were divided into two groups: i) pneumonia; and ii) other causes, according to the Brazilian ACSC list. Adjusted hospitalization rates were estimated and unconditional logistic regression was used to analyze factors associated with pneumonia. Over 90% of the registered cases were considered ACSC. The adjusted rate of ACSC was 18.6/1000. The odds ratio of hospitalization for pneumonia was 2.7 (CI: 1.3-5.4) times higher in children aged between 0.1 and 5.9 months; 1.9 (CI: 1.1-3.3) times higher in children who were hospitalized for 8-14 days; and three (CI: 1.2-7.5) times higher in children with a secondary diagnosis of malnutrition. The excess of avoidable hospitalizations is a clear indication of the low quality of care and limited accessibility to primary health care in indigenous territories, which is contrary to the assistance model proposed by the indigenous healthcare subsystem in Brazil, which should in theory focus on welfare technologies based on primary health care.

Objective: To analyze explanations for tuberculosis and therapeutic itineraries of Brazilian indigenous people., Methods: Case study with a qualitative-descriptive approach. We conducted semi-structured interviews with 11 Munduruku indigenous, including direct observation of treatment for tuberculosis in the municipality of Jacareacanga, south-western region of the state of Para, Brazil. To identify explanations for tuberculosis and therapeutic itineraries, we performed thematic content analysis., Results: Traditional medicine was the first therapeutic option chosen by the indigenous. However, biomedicine was also employed, which indicates a circulation between different therapeutic contexts and health concepts among the Munduruku. The explanations provided ranged from recognition of the signs and symptoms specific to tuberculosis to the attribution of the disease to a spirit that leaves the body and wanders in the woods, returning ill into the body. Unlike the biomedical model, which links tuberculosis transmission strictly to interpersonal contact, in closed spaces without natural lighting and ventilation (preferably domestic environments), the Munduruku associate the disease to an indirect contact between people socially distant (enemies or adversaries) in public and open places., Conclusions: The explanations made by the indigenous are unique and deserve the attention of those who are responsible for developing health public policies, as well as of the teams who work on the villages. To guarantee an efficient control of tuberculosis in these regions, it is necessary that the developed actions integrate biomedicine knowledge and the traditional medicine of the indigenous people, in addition to respecting and welcoming local culture manifestations.

Approximately 10% of the Brazilian indigenous population lives in the state of Mato Grosso do Sul (MS), where a large number of new cases of tuberculosis (TB) are reported. This study was conducted to assess TB occurrence, transmission and the utility of TB diagnosis based on the Ogawa-Kudoh (O-K) culture method in this remote population. The incidence of TB was estimated by a retrospective review of the surveillance data maintained by the Notifiable Diseases Surveillance System for the study region. The TB transmission pattern among indigenous people was assessed by genotyping Mycobacterium tuberculosis isolates using the IS 6110 restriction fragment length polymorphism (RFLP) technique. Of the 3,093 cases identified from 1999-2001, 610 (~20%) were indigenous patients (average incidence: 377/100,000/year). The use of the O-K culture method increased the number of diagnosed cases by 34.1%. Of the genotyped isolates from 52 indigenous patients, 33 (63.5%) belonged to cluster RFLP patterns, indicating recently transmitted TB. These results demonstrate high, on-going TB transmission rates among the indigenous people of MS and indicate that new efforts are needed to disrupt these current transmissions.

Objective: To describe the epidemiological situation and the incidence of tuberculosis and to investigate the factors associated with treatment default in the Amazonian municipalities located in the northern Brazilian international border., Methods: This retrospective study employed sociodemographic, clinical, and epidemiological tuberculosis data recorded in the Brazilian Notifiable Diseases Information System (SINAN) between 2001 and 2010. Logistic regression was used to identify factors associated with treatment default., Results: Tuberculosis affected mostly indigenous peoples (51.9%), males (57.9%), and people aged 25-44 years (31.4%). The predominant clinical presentation was pulmonary (89.7%), yet in 24.5% of the cases the patients did not undergo sputum smear microscopy, and only half received supervised treatment. In 70.0% of the cases notified, patients were discharged as cured. Treatment default was recorded in 10.0% of the patients. Of all deaths, 4.1% were by tuberculosis and other causes, and 1.7% by multidrug-resistant tuberculosis. The average incidence by race/color was greater among indigenous peoples, ranging from 202.3/100 000 in 2001 to 65.6/100 000 in 2010. Treatment default was associated with failure to perform the follow-up smear at the second, fourth, and sixth months (OR = 11.9, 95%CI: 7.4-19.0); with resuming treatment after default (OR = 3.0, 95%CI: 1.5-5.9); and with living in specific subregions, particularly the Alto Solimões region (OR = 6.7, 95%CI: 4.6-9.8)., Conclusions: The present results show a high incidence of tuberculosis in the Amazon portion of the northern Brazilian international border, especially among indigenous peoples. Considering the socio-cultural specificities of these populations and the poor tuberculosis control in this area, the authors of the study conclude that the integration of different national health systems is both necessary and urgent.

Objective: To describe the sociodemographic and clinical-epidemiological characteristics of tuberculosis cases and identify associated factors with abandoning treatment and death whilst undergoing treatment., Methods: Epidemiological study based on cases of tuberculosis recorded in indigenous and non-indigenous individuals according to race/color in Mato Grosso do Sul, Midwestern Brazil, between 2001 and 2009. Descriptive analysis of the cases was carried out according to the variables of sex, age group, residence, type of test used in the diagnosis, clinical form, supervised treatment and final status, according to race/color. Univariate/multivariate logistic regression analyses were used to identify predictors of abandoning treatment and death, using odds ratio as a measure of association. A time series of incidence according to race/color was constructed., Results: In the period, 6,962 new cases of tuberculosis were registered, 15.6% being among indigenous. The illness was predominantly found in men and adults (20-44 years old) in all groups. Most of the indigenous patients lived in rural areas (79.8%) and 13.5% of the records in indigenous occurred in children aged < 10 years. The average incidence in the state was 34.5/100,000 inhabitants, being 209.0, 73.1, 52.7, 23.0 and 22.4 in indigenous, and those with yellow, black, white and brown skin, respectively. Patients aged 20 to 44 years (OR = 13.3, 95%CI 1.9;96.8), male (OR = 1.6, 95%CI 1.1;2.3) and of black race/color (OR = 2.5, 95%CI 1.0;6.3) were associated with abandoning treatment, while patients aged > 45 years (OR = 3.0, 95%CI 1.2;7.8) and with the mixed form (OR = 2.3, 95%CI 1.1;5.0) showed association with death. Although they only account for 3.0% of the population, the indigenous were responsible for 15.6% of cases recorded during the period., Conclusions: Major inequalities in the tuberculosis illness process were found between the categories studied. Incidence in the indigenous population was consistently higher than recorded in any other group, reaching more than six times the national average. It was among those with black and brown skin that the worst treatment results were observed, as they were twice as likely to abandon treatment as the indigenous. Poor program performance was strongly associated with abandoning treatment and death. It is thought that as long as there is no reduction in poverty inequalities in health indicators will remain.

Objective: To analyze mortality rates and to describe the demographic and epidemiological characteristics of suicides recorded in the state of Amazonas., Methods: A descriptive and retrospective study has been carried out with emphasis on municipalities, which have shown, simultaneously, a high mortality rates and a high proportion of self-reported indigenous population, based on 2005 - 2009 data as provided by the Informatics Department of the Unified National Health System., Results: Among the general population of the state of Amazonas, the mortality rate, by suicide, of 4.2/100.000 inhabitants has been reported, similar to that of Manaus (4.6/100.000 inhabitants). In contrast, at Tabatinga (25.2/100.000 inhabitants), at São Gabriel da Cachoeira (27.6/100.000 inhabitants) and at Santa Isabel do Rio Negro (36.4/100.000 inhabitants), municipalities, where the proportion of self-reported indigenous population is high, besides the taxes being notably higher, it was observed that most of the suicides has occurred among men; among young men aged between 15 - 24 years; at home; by hanging; during "weekend" and among the indigenous population., Discussion: Our findings have unveiled that suicide comes forth as a serious public health issue in some municipalities in the state of Amazonas, further indicating that the event occurs within very specific contexts, and that the dimension and the magnitude of the problem can be even more serious among populations or in territories exclusively inhabited by indigenous people.

We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1- or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-α, IL-12p40 and IFN-γ production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

Objective: Assess the epidemiological aspects of tuberculosis in Brazilian indigenous children and actions to control it., Methods: An epidemiological study was performed with 356 children from 0 to 14 years of age in Rondônia State, Amazon, Brazil, during the period 1997-2006. Cases of TB reported to the Notifiable Diseases Surveillance System were divided into indigenous and non-indigenous categories and analyzed according to sex, age group, place of residence, clinical form, diagnostic tests and treatment outcome. A descriptive analysis of cases and hypothesis test (χ²) was carried out to verify if there were differences in the proportions of illness between the groups investigated., Results: A total of 356 TB cases were identified (125 indigenous, 231 non-indigenous) of which 51.4% of the cases were in males. In the indigenous group, 60.8% of the cases presented in children aged 0-4 years old. The incidence mean was much higher among indigenous; in 2001, 1,047.9 cases/100,000 inhabitants were reported in children aged < 5 years. Pulmonary TB was reported in more than 80% of the cases, and in both groups over 70% of the cases were cured. Cultures and histopathological exams were performed on only 10% of the patients. There were 3 cases of TB/HIV co-infection in the non-indigenous group and none in the indigenous group. The case detection rate was classified as insufficient or fair in more than 80% of the indigenous population notifications, revealing that most of the diagnoses were performed based on chest x-ray., Conclusions: The approach used in this study proved useful in demonstrating inequalities in health between indigenous and non-indigenous populations and was superior to the conventional analyses performed by the surveillance services, drawing attention to the need to improve childhood TB diagnosis among the indigenous population.

Objective: To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê., Methods: Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê., Results: Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%)., Conclusions: The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.

With the intention of improve knowledge on the epidemiological situation of tuberculosis (TB) among vulnerable populations in Brazil, our objective was to analyze sociodemographic characteristics and operational indicators related to TB control, comparing indigenous and non-indigenous people, in Rondônia. We conducted a retrospective and descriptive epidemiological study of new TB cases reported between 1997, January 1st and 2006, December 31st. We excluded duplicate records and those for whom the results of treatment was change in diagnosis and transfer. TB cases were classified into two categories: indigenous and non-indigenous people and analysis was performed according to sex, age, origin (urban /rural), State of residence, clinical form, diagnostic tests, monitoring indicators and results of treatment. Altogether 4832 cases were reported, with 322 cases (6.7%) in indigenous people. There was a male predominance (ratios: 1.7 to 1.3 in non-indigenous and indigenous people). The majority of cases for indigenous people (82.6%) was in rural area and there was high concentration of cases (36.0%) in children < 15 years. The analysis of diagnostic tests showed a predominance of smear positive in non-indigenous (56.1%) and smear negative and smear not performed in indigenous people (31.7% and 35.4% respectively, P value=0.0001). There was difference in the monitoring in relation to smear of second month (6.1% positivity, P value = 0.0001) and exam at least one contact (69.6%, P value = 0.017) for non-indigenous. On the other hand, DOTS was more associated with indigenous people cases (23.6%, P value = 0.0001). Stands out the predominance of cure in both groups, with bigger concentration in indigenous people (90.4%, P value = 0.0001) and higher rate of noncompliance in non-indigenous (14.7%, P value = 0.0001). The approach showed useful for elucidate inequalities and has exceeded the usual analysis carried out surveillance on services that aim to delineate the epidemiological situation based only on rates or absolute values.