Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua.

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.

Heat stress and heat strain among outdoor workers in El Salvador and Nicaragua.

BACKGROUND: There is growing attention on occupational heat stress in Central America, as workers in this region are affected by a unique form of chronic kidney disease. Previous studies have examined wet bulb globe temperatures and estimated metabolic rates to assess heat stress, but there are limited data characterizing heat strain among these workers. OBJECTIVE: The aims were to characterize heat stress and heat strain and examine whether job task, break duration, hydration practices, and kidney function were associated with heat strain. METHODS: We used data from the MesoAmerican Nephropathy Occupational Study, a cohort of 569 outdoor workers in El Salvador and Nicaragua who underwent workplace exposure monitoring, including continuous measurement of core body temperature (Tc), heart rate (HR), physical activity, and wet bulb globe temperature (WBGT), over the course of three days in January 2018 - May 2018. Participants represented five industries: sugarcane, corn, plantain, brickmaking, and construction. RESULTS: Median WBGTs were relatively high (>27 °C) at most sites, particularly when work shifts spanned the afternoon hours (e.g., 29.2 °C among plantain workers). Sugarcane workers, especially cane cutters in both countries and Nicaraguan agrichemical applicators, had the highest estimated metabolic rates (medians: 299-318 kcal/hr). Most workers spent little time on break (<10% of the shift), as determined by physical activity data. Overall, sugarcane workers-particularly those in Nicaragua-experienced the highest Tc and HR values. However, a few workers in other industries reached high Tc (>39 °C) as well. Impaired kidney function (estimated glomerular filtration rate <90 mL/min/1.73 m2) was associated with higher Tc and HR values, even after adjustment. SIGNIFICANCE: This is the largest study to-date examining heat stress and strain among outdoor workers in Central America. Workers at sugar companies regularly experienced Tc > 38°C (76.9% of monitored person-days at Nicaraguan companies; 46.5% at Salvadoran companies). Workers with impaired kidney function had higher measures of Tc and HR. IMPACT STATEMENT: This study examined levels of occupational heat stress and heat strain experienced among outdoor workers in five industries in El Salvador and Nicaragua. We characterized heat stress using wet bulb globe temperatures and estimated metabolic rate and heat strain using core body temperature and heart rate. Sugarcane workers, particularly cane cutters and Nicaraguan agrichemical applicators, performed more strenuous work and experienced greater levels of heat strain. Impaired kidney function was associated with higher heart rates and core body temperatures.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.

Point-of-Care Testing in Chronic Kidney Disease of Non-Traditional Origin: Considerations for Clinical, Epidemiological, and Health Surveillance Research and Practice.

Purpose: As the prevalence of chronic kidney disease of non-traditional origin (CKDnt) rises in low-resource settings, there is a need for reliable point-of-care creatinine testing. The purpose of this analysis was to assess the accuracy of two commonly used point-of-care creatinine devices, the i-STAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) in comparison to venipuncture serum creatinine measures. The affordability, sensitivity, specificity, ease of use, and other considerations for each device are also presented. Methods: Three paired data sets were compared. We collected 213 paired i-STAT and venipuncture samples from a community study in Nicaragua in 2015-2016. We also collected 267 paired StatSensor Creatinine and venipuncture samples, including 158 from a community setting in Nicaragua in 2014-2015 and 109 from a Guatemala sugarcane worker cohort in 2017-2018. Pearson correlation coefficients, Bland-Altman plots, and no intercept linear regression models were used to assess agreement between point-of-care devices and blood samples. Results: The i-STAT performed the most accurately, overestimating creatinine by 0.07 mg/dL (95% CI: 0.02, 0.12) with no evidence of proportional bias. The StatSensor Creatinine performed well at low levels of creatinine (Mean (SD): 0.87 (0.19)). Due to proportional bias, the StatSensor Creatinine performed worse in the Nicaragua community setting where creatinine values ranged from 0.31 to 7.04 mg/dL. Discussion: Both devices provide acceptable sensitivity and specificity. Although adequate for routine surveillance, StatSensor Creatinine is less accurate as the values of measured creatinine increase, a consideration when using the point-of-care device for screening individuals at risk for CKDnt. Research, clinical, and screening objectives, cost, ease of use, and background prevalence of disease must all be carefully considered when selecting a point-of-care creatinine device. Conclusion: POC testing can be more accessible in resource-limited settings. The selection of the appropriate device will depend on the use-case.

COVID-19 and CKD: Employment, Food Security and Healthcare in El Salvador.

Background: In Central America, the COVID-19 pandemic coexists with a devastating epidemic of chronic kidney disease of unknown origin. The consequences of these overlapping health crises remain largely unknown. Methods: We assessed vulnerability to and impact of the first wave of COVID-19 on participants in a cohort study of chronic kidney disease (CKD) in El Salvador (n = 229). Participants were contacted by phone during August and September 2020. We queried changes to employment, healthcare access, household income and food security due to the pandemic (from March 2020 until the time of the interview) and COVID-19-associated symptoms during that time. Findings: We reached 94% of the cohort (n = 215). Nearly 40% of participants reported an unexpected change in employment or work activities and 8.8% reported new unemployment due to the pandemic. Participants with CKD (n = 27) had higher odds of reporting new income insecurity, food insecurity, and reductions in medical care access due to the pandemic. COVID-19-associated symptoms (an approximation of disease) were reported in 7.0% (n = 15). Participants with CKD were more likely to report COVID-19-associated symptoms compared to those without CKD, although these differences were not statistically significant. Conclusions: Overall, participants with CKD suffered greater economic consequences as a result of the pandemic and may have experienced higher incidence of COVID-19 disease, although laboratory diagnostics would be required to draw this conclusion. Longitudinal analyses are required to comprehensively evaluate the implications of the pandemic for individuals with CKD in Central America.

Prospective association between e-cigarette use frequency patterns and cigarette smoking abstinence among adult cigarette smokers in the United States.

AIMS: To estimate the association of longitudinal patterns of e-cigarette use with cigarette smoking abstinence, after accounting for time-dependent confounding and selection bias. DESIGN: Secondary analysis of longitudinal national cohort data. Using marginal structural models and four waves of the population assessment of tobacco and health (wave 1, 2013-14; wave 2, 2014-15; wave 3, 2015-16; wave 4, 2016-18), we estimated the association of vaping frequency across waves 2 and 3 with 12-month sustained cigarette smoking abstinence at wave 4, adjusting for time-dependent confounders at waves 1 and 2 and selection bias due to drop-out with inverse probability of treatment and censoring weights. SETTING: United States. PARTICIPANTS/CASES: A total of 5699 adults (18+ years) who smoked cigarettes and did not vape at wave 1. MEASUREMENTS: The exposure was vaping frequency at waves 2 and 3 (non-use, non-daily use, daily use), representing nine possible combinations of vaping frequency across two waves. Non-use at both waves was the exposure reference group. The primary outcome was sustained 12-month cigarette smoking abstinence at wave 4. FINDINGS: Among 5699 adults who smoked cigarettes at wave 1, a total of 560 (9.8%) reported smoking abstinence at wave 4. Compared with nonuse at both waves, daily vaping at both waves [risk ratio (RR) = 3.82, 95% confidence interval (CI) = 2.59-5.64] and non-use at wave 2 followed by daily vaping at wave 3 (RR = 2.50, 95% CI = 1.66-3.77) were positively associated with smoking abstinence; non-daily vaping at both waves was inversely associated with smoking abstinence (RR = 0.28, 95% CI = 0.11-0.75). Results persisted after accounting for misclassification of e-cigarette use and cigarette smoking abstinence and after restricting to participants with plans to quit smoking. CONCLUSIONS: In a US cohort of adult smokers, longitudinal patterns of vaping frequency appear to predict smoking abstinence, even after accounting for several sources of systematic error. Consistent daily vaping is associated with increased chances of cigarette smoking abstinence, while consistent non-daily vaping is associated with decreased chances of smoking abstinence.

High prevalence of chronic kidney disease of unknown etiology among workers in the Mesoamerican Nephropathy Occupational Study.

BACKGROUND: Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. METHODS: Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. RESULTS: Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. CONCLUSION: Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

e-Cigarette Use and Combustible Cigarette Smoking Initiation Among Youth: Accounting for Time-Varying Exposure and Time-Dependent Confounding.

BACKGROUND: Youth e-cigarette use is associated with the initiation of combustible cigarette smoking, but prior studies have rarely accounted for time-varying measures of e-cigarette exposure or time-dependent confounding of e-cigarette use and smoking initiation. METHODS: Using five waves of the Population Assessment of Tobacco and Health (2013-2019), we estimated marginal structural models with inverse probability of treatment and censoring weights to examine the association between time-varying e-cigarette initiation and subsequent cigarette smoking initiation among e-cigarette- and cigarette-naïve youth (12-17 years) at baseline. Time-dependent confounders used as predictors in inverse probability weights included tobacco-related attitudes or beliefs, mental health symptoms, substance use, and tobacco-marketing exposure. RESULTS: Among 9,584 youth at baseline, those who initiated e-cigarettes were 2.4 times as likely to subsequently initiate cigarette smoking as youth who did not initiate e-cigarettes (risk ratio = 2.4, 95% confidence interval [CI] = 2.1, 2.7), after accounting for time-dependent confounding and selection bias. Among youth who initiated e-cigarettes, more frequent vaping was associated with greater risk of smoking initiation (risk ratio ≥3 days/month = 1.8, 95% CI = 1.4, 2.2; 1-2 days/month = 1.2; 95% CI = 0.93, 1.6 vs. 0 days/month). Weighted marginal structural model estimates were moderately attenuated compared with unweighted estimates adjusted for baseline-only confounders. At the US population level, we estimated over half a million youth initiated cigarette smoking because of prior e-cigarette use over follow-up. CONCLUSIONS: The association between youth vaping and combustible cigarette smoking persisted after accounting for time-dependent confounding. We estimate that e-cigarette use accounts for a considerable share of cigarette initiation among US youth. See video abstract at, http://links.lww.com/EDE/B937.

Assessing Smoke-Free Housing Implementation Approaches to Inform Best Practices: A National Survey of Early-Adopting Public Housing Authorities.

Secondhand smoke (SHS) exposure causes chronic illness and occurs at a higher prevalence in low-income communities than the general public. In 2018, the U.S. Department of Housing and Urban Development (HUD) instituted a smoke-free housing rule for Public Housing Authorities (PHAs) to address persistent health inequities. However, the success of smoke-free housing requires evidence to inform effective implementation approaches. A mixed-methods, cross-sectional survey was conducted in a national sample of PHAs. Questions focused on housing officials' use of specific implementation strategies. Adjusted odds ratios were used to assess associations between implementation approaches and variations among PHAs (i.e., region, size, or recency of policy adoption). Qualitative analyses were conducted to assess the perceived effectiveness of implementation strategies. Resident engagement, staff training, and smoking cessation support were the most frequently used implementation strategies. Engagement with local stakeholders was cited less frequently. Enforcement actions were limited with no violations referred to housing court. Support for policy adherence was identified as a sixth implementation strategy. While most PHAs used at least some evidence-informed implementation strategies, a lack of a systematic approach may limit overall effectiveness. Further research is required to resolve implementation barriers experienced disproportionately by a subset of PHAs, and to inform a best practice implementation framework that meets the needs of a heterogeneous population.

Ecological super-spreaders drive host-range oscillations: Omicron and risk space for emerging infectious disease.

The unusual genetic diversity of the Omicron strain has led to speculation about its origin. The mathematical modelling platform developed for the Stockholm Paradigm (SP) indicates strongly that it has retro-colonized humans from an unidentified nonhuman mammal, likely originally infected by humans. The relationship between Omicron and all other SARS-CoV-2 variants indicates oscillations among hosts, a core part of the SP. Such oscillations result from the emergence of novel variants following colonization of new hosts, replenishing and expanding the risk space for disease emergence. The SP predicts that pathogens colonize new hosts using pre-existing capacities. Those events are thus predictable to a certain extent. Novel variants emerge after a colonization and are not predictable. This makes it imperative to take proactive measures for anticipating emerging infectious diseases (EID) and mitigating their impact. The SP suggests a policy protocol, DAMA, to accomplish this goal. DAMA comprises: DOCUMENT to detect pathogens before they emerge in new places or colonize new hosts; ASSESS to determine risk; MONITOR to detect changes in pathogen populations that increase the risk of outbreaks and ACT to prevent outbreaks when possible and minimize their impact when they occur.

Food security and emerging infectious disease: risk assessment and risk management.

Climate change, emerging infectious diseases (EIDs) and food security create a dangerous nexus. Habitat interfaces, assumed to be efficient buffers, are being disrupted by human activities which in turn accelerate the movement of pathogens. EIDs threaten directly and indirectly availability and access to nutritious food, affecting global security and human health. In the next 70 years, food-secure and food-insecure countries will face EIDs driving increasingly unsustainable costs of production, predicted to exceed national and global gross domestic products. Our modern challenge is to transform this business as usual and embrace an alternative vision of the biosphere formalized in the Stockholm paradigm (SP). First, a pathogen-centric focus shifts our vision of risk space, determining how pathogens circulate in realized and potential fitness space. Risk space and pathogen exchange are always heightened at habitat interfaces. Second, apply the document-assess-monitor-act (DAMA) protocol developing strategic data for EID risk, to be translated, synthesized and broadcast as actionable information. Risk management is realized through targeted interventions focused around information exchanged among a community of scientists, policy practitioners of food and public health security and local populations. Ultimately, SP and DAMA protect human rights, supporting food security, access to nutritious food, health interventions and environmental integrity.

Emerging infectious disease: An underappreciated area of strategic concern for food security.

Emerging infectious diseases (EIDs) increasingly threaten global food security and public health. Despite technological breakthroughs, we are losing the battle with (re)emerging diseases as treatment costs and production losses rise. A horizon scan of diseases of crops, livestock, seafood and food-borne illness suggests these costs are unsustainable. The paradigm of coevolution between pathogens and particular hosts teaches that emerging diseases occur only when pathogens evolve specific capacities that allow them to move to new hosts. EIDs ought to be rare and unpredictable, so crisis response is the best we can do. Alternatively, the Stockholm Paradigm suggests that the world is full of susceptible but unexposed hosts that pathogens could infect, given the opportunity. Global climate change, globalized trade and travel, urbanization and land-use changes (often associated with biodiversity loss) increase those opportunities, making EID frequent. We can, however, anticipate their arrival in new locations and their behaviour once they have arrived. We can 'find them before they find us', mitigating their impacts. The DAMA (Document, Assess, Monitor, Act) protocol alters the current reactive stance and embodies proactive solutions to anticipate and mitigate the impacts of EID, extending human and material resources and buying time for development of new vaccinations, medications and control measures.

Climate Trends at a Hotspot of Chronic Kidney Disease of Unknown Causes in Nicaragua, 1973-2014.

An ongoing epidemic of chronic kidney disease of uncertain etiology (CKDu) afflicts large parts of Central America and is hypothesized to be linked to heat stress at work. Mortality rates from CKDu appear to have increased dramatically since the 1970s. To explore this relationship, we assessed trends in maximum and minimum temperatures during harvest months between 1973 and 2014 as well as in the number of days during the harvest season for which the maximum temperature surpassed 35 °C. Data were collected at a weather station at a Nicaraguan sugar company where large numbers of workers have been affected by CKDu. Monthly averages of the daily maximum temperatures between 1996 and 2014 were also compared to concurrent weather data from eight Automated Surface Observing System Network weather stations across Nicaragua. Our objectives were to assess changes in temperature across harvest seasons, estimate the number of days that workers were at risk of heat-related illness and compare daily maximum temperatures across various sites in Nicaragua. The monthly average daily maximum temperature during the harvest season increased by 0.7 °C per decade between 1973 and 1990. The number of days per harvest season with a maximum temperature over 35 °C increased by approximately five days per year between 1974 and 1990, from 32 days to 114 days. Between 1991 and 2013, the number of harvest days with a maximum temperature over 35 °C decreased by two days per year, and the monthly average daily maximum temperature decreased by 0.3 °C per decade. Comparisons with weather stations across Nicaragua demonstrate that this company is located in one of the consistently hottest regions of the country.

Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. METHODS: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. RESULTS: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. CONCLUSIONS: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.

An underappreciated misclassification mechanism: implications of nondifferential dependent misclassification of covariate and exposure.

Misclassification is a pervasive problem in assessing relations between exposures and outcomes. While some attention has been paid to the impact of dependence in measurement error between exposures and outcomes, there is little awareness of the potential impact of dependent error between exposures and covariates, despite the fact that this latter dependency may occur much more frequently, for example, when both are assessed by questionnaire. We explored the impact of nondifferential dependent exposure-confounder misclassification bias by simulating a dichotomous exposure (E), disease (D) and covariate (C) with varying degrees of non-differential dependent misclassification between C and E. We demonstrate that under plausible scenarios, an adjusted association can be a poorer estimate of the true association than the crude. Correlated errors in the measurement of covariate and exposure distort the covariate-exposure, covariate-outcome and exposure-outcome associations creating observed associations that can be greater than, less than, or in the opposite direction of the true associations. Under these circumstances adjusted associations may not be bounded by the crude association and true effect, as would be expected with nondifferential independent confounder misclassification. The degree and direction of distortion depends on the amount of dependent error, prevalence of covariate and exposure, and magnitude of true effect.

Biomarkers of kidney injury among children in a high-risk region for chronic kidney disease of uncertain etiology.

BACKGROUND: Mesoamerican Nephropathy (MeN), a form of chronic kidney disease of uncertain etiology, is a leading cause of death in Central America. The disease often presents in young adult male agricultural workers and progresses rapidly. Given the young age at presentation, we hypothesized that children in Central America experience subclinical kidney injury prior to working life. METHODS: We assessed specimens from a cross-sectional study of youth, aged 7-17 years, predominantly residing in a high-risk region of Nicaragua (n = 210). We evaluated urinary concentrations and risk factors for kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40). We evaluated the association between biomarkers and contemporaneous eGFR and compared biomarker concentrations with reference values from healthy children in other countries. RESULTS: Median uNGAL, uIL-18, and uKIM-1 concentrations exceeded healthy reference values. A one-year increase in age was associated with 40% increase in odds of being in the highest quartile of uNGAL (OR 1.4; (95%CI 1.2, 1.5); p < 0.0001). Youth who reported ever experiencing dysuria had 2.5 times the odds of having uNGAL concentrations in the top quartile (OR 2.5; (95%CI 1.4, 4.6); p = 0.003). Girls had significantly higher concentrations of all biomarkers than boys. Nine percent of children demonstrated low eGFR (≤ 100 ml/min/1.73 m2), while 29% showed evidence of hyperfiltration (eGFR ≥ 160 ml/min/1.73 m2), both potentially indicative of renal dysfunction. CONCLUSIONS: Children residing in regions of Nicaragua at high risk for MeN may experience subclinical kidney injury prior to occupational exposures.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.

Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity. We analyzed pooled and stratified exposure and outcome data from Navajo (n = 68) and Nicaraguan (n = 47) men of similar age and health status in order to characterize urinary concentrations of metals, compare concentrations with the US National Health and Nutrition Examination Survey (NHANES) male population, and examine the associations with biomarkers of autoimmunity. Urine samples were analyzed for metals via inductively coupled plasma mass spectrometry (ICP-MS) at the US Centers for Disease Control and Prevention. Serum samples were examined for antinuclear antibodies (ANA) at 1:160 and 1:40 dilutions, using an indirect immunofluorescence assay and for specific autoantibodies using enzyme-linked immunosorbent assay (ELISA). Logistic regression analyses evaluated associations of urinary metals with autoimmune biomarkers, adjusted for group (Navajo or Nicaraguan), age, and seafood consumption. The Nicaraguan men had higher urinary metal concentrations compared with both NHANES and the Navajo for most metals; however, tin was highest among the Navajo, and uranium was much higher in both populations compared with NHANES. Upper tertile associations with ANA positivity at the 1:160 dilution were observed for barium, cesium, lead, strontium and tungsten.