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.

Urban health: an example of a "health in all policies" approach in the context of SDGs implementation.

BACKGROUND: Cities are an important driving force to implement the Sustainable Development Goals (SDGs) and the New Urban Agenda. The SDGs provide an operational framework to consider urbanization globally, while providing local mechanisms for action and careful attention to closing the gaps in the distribution of health gains. While health and well-being are explicitly addressed in SDG 3, health is also present as a pre condition of SDG 11, that aims at inclusive, safe, resilient and sustainable cities. Health in All Policies (HiAP) is an approach to public policy across sectors that systematically takes into account the health implications of decisions, seeks synergies, and avoids harmful health impacts in order to improve population health and health equity. HiAP is key for local decision-making processes in the context of urban policies to promote public health interventions aimed at achieving SDG targets. HiAPs relies heavily on the use of scientific evidence and evaluation tools, such as health impact assessments (HIAs). HIAs may include city-level quantitative burden of disease, health economic assessments, and citizen and other stakeholders' involvement to inform the integration of health recommendations in urban policies. The Barcelona Institute for Global Health (ISGlobal)'s Urban Planning, Environment and Health Initiative provides an example of a successful model of translating scientific evidence into policy and practice with regards to sustainable and healthy urban development. The experiences collected through ISGlobal's participation implementing HIAs in several cities worldwide as a way to promote HiAP are the basis for this analysis. AIM: The aim of this article is threefold: to understand the links between social determinants of health, environmental exposures, behaviour, health outcomes and urban policies within the SDGs, following a HiAP rationale; to review and analyze the key elements of a HiAP approach as an accelerator of the SDGs in the context of urban and transport planning; and to describe lessons learnt from practical implementation of HIAs in cities across Europe, Africa and Latin-America. METHODS: We create a comprehensive, urban health related SDGs conceptual framework, by linking already described urban health dimensions to existing SDGs, targets and indicators. We discuss, taking into account the necessary conditions and steps to conduct HiAP, the main barriers and opportunities within the SDGs framework. We conclude by reviewing HIAs in a number of cities worldwide (based on the experiences collected by co-authors of this publication), including city-level quantitative burden of disease and health economic assessments, as practical tools to inform the integration of health recommendations in urban policies. RESULTS: A conceptual framework linking SDGs and urban and transportplanning, environmental exposures, behaviour and health outcomes, following a HiAP rationale, is designed. We found at least 38 SDG targets relevant to urban health, corresponding to 15 SDGs, while 4 important aspects contained in our proposed framework were not present in the SDGs (physical activity, noise, quality of life or social capital). Thus, a more comprehensive HiAP vision within the SDGs could be beneficial. Our analysis confirmed that the SDGs framework provides an opportunity to formulate and implement policies with a HiAP approach. Three important aspects are highlighted: 1) the importance of the intersectoral work and health equity as a cross-cutting issue in sustainable development endeavors; 2) policy coherence, health governance, and stakeholders' participation as key issues; and 3) the need for high quality data. HIAs are a practical tool to implement HiAP. Opportunities and barriers related to the political, legal and health governance context, the capacity to inform policies in other sectors, the involvement of different stakeholders, and the availability of quality data are discussed based on our experience. Quantitative assessments can provide powerful data such as: estimates of annual preventable morbidity and disability-adjusted life-years (DALYs) under compliance with international exposure recommendations for physical activity, exposure to air pollution, noise, heat, and access to green spaces; the associated economic impacts in health care costs per year; and the number of preventable premature deaths when improvements in urban and transport planning are implemented. This information has been used to support the design of policies that promote cycling, walking, public, zero and low-emitting modes of transport, and the provision of urban greening or healthy public open spaces in Barcelona (e.g. Urban Mobility, Green Infrastructure and Biodiversity Plans, or the Superblocks's model), the Bus Rapid Transit and Open Streets initiatives in several Latin American cities or targeted SDGs assessments in Morocco. CONCLUSIONS: By applying tools such as HIA, HiAP can be implemented to inform and improve transport and urban planning to achieve the 2030 SDG Agenda. Such a framework could be potentially used in cities worldwide, including those of less developed regions or countries. Data availability, taking into account equity issues, strenghtening the communication between experts, decision makers and citizens, and the involvement of all major stakeholders are crucial elements for the HiAP approach to translate knowledge into SDG implementation.

Geographic analysis and estimation of hepatitis C cases in migrant populations living in Spain: is a country-based screening strategy appropriate?

BACKGROUND: Spain needs to increase the number of new known cases in order to achieve the goal of eliminating hepatitis C virus (HCV) by 2030. The aim of this study was to estimate the number of HCV cases among the migrant population in Spain and propose different scenarios for micro-elimination strategies, targeting the most relevant migrant groups. METHODOLOGY: this epidemiological and demographic cross-sectional descriptive study employed a systematic approach to estimate the number of migrants infected by HCV in Spain. Estimates are based on demographic data and details the size of the foreign-born population living in every Spanish province and the anti-HVC+ prevalence rates in their respective countries of origin. RESULTS: in Spain, there are 100,268 estimated cases of anti-HCV+ among the total adult migrant population who live in the country. The estimated cases of anti-HCV+ among migrants from moderate-high endemic countries with a prevalence of ≥ 2%, > 3%, > 4% and > 5% are 48,979, 48,029, 24,176 and 15,646, respectively. The anti-HCV+ endemic countries (≥ 2%) that contribute to the highest number of estimated cases in Spain are Romania, Italy, Pakistan, Ukraine, Senegal, Russia and Nigeria. The autonomous communities with the highest prevalence and number of estimated anti-HCV+ cases among migrant population are Catalonia, Valencian Community, Madrid and Andalusia, respectively. CONCLUSION: these data show the need to establish HCV screening strategies for the migrant population in Spain and, particularly, in the most affected areas. The strategy should target those migrant communities with a higher prevalence and a higher number of estimated cases, such as people from Eastern Europe, Sub-Saharan Africa and Pakistan.

Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy.

RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.

Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers.

BACKGROUND: In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. PREDICTORS: Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. OUTCOMES & MEASUREMENTS: Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-ß-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR). RESULTS: Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non-field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, -0.6 to 6.7) mL/min/1.73 m(2), respectively. LIMITATIONS: Surrogate exposure measure, loss to follow-up. CONCLUSIONS: Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.

Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.

BACKGROUND: Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. RESULTS: Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common. LIMITATIONS: CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method. CONCLUSIONS: Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.

Urine biomarkers of kidney injury among adolescents in Nicaragua, a region affected by an epidemic of chronic kidney disease of unknown aetiology.

BACKGROUND: An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. METHODS: Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio] were assessed. Biomarker concentrations were compared by school using linear regression models. RESULTS: Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. CONCLUSIONS: Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents.

HIV testing policies for migrants and ethnic minorities in EU/EFTA Member States.

BACKGROUND: In the context of an European Centre for Disease Prevention and Control (ECDC) research project, our objective was to describe current recommendations regarding HIV testing and counselling targeting migrants and ethnic minorities in the European Union/European Economic Area/European Free Trade Association (EU/EEA/EFTA) Member States. METHODS: An on-line survey was conducted among 31 EU/EEA/EFTA Member States. The survey inquired on the existence of specific HIV testing and counselling recommendations or policies for migrants and/or ethnic minorities and the year of their publication. Additionally, we performed a review of national recommendations, guidelines or any other policy documents retrieved from an Internet search through the different countries' competent bodies. RESULTS: Twenty-nine (94%) country representatives responded the survey, and 28 documents from 27 countries were identified. National guidelines on HIV testing are heterogeneous and tailored, according to the epidemiological situation. Twenty-two countries identify migrants and four countries identify ethnic minorities as particularly vulnerable to HIV. Sixteen countries explicitly recommend offering an HIV test to migrants/ethnic minorities. Guidelines especially target people originating from HIV endemic countries, and benefits of HIV early detection are highlighted. HIV testing is not mandatory in any country, but some countries overtly facilitate this practice. CONCLUSION: Benefits of HIV testing in migrants and ethnic minorities, at both individual and community levels are recognized by many countries. In spite of this, not all countries identify the need to test these groups.

The epidemiological situation of tuberculosis in Spain according to surveillance and hospitalization data, 2012-2020.

BACKGROUND: Before the COVID-19 pandemic, tuberculosis (TB) was the leading cause of death from a single infectious agent. In Spain, TB notifications are registered through the National Epidemiological Surveillance Network (RENAVE). The Minimum Basic Data Set (CMBD) provides information on TB hospital discharges. This study aims to assess both registries to complete the picture of TB in order to improve national control strategies and make further progress toward its elimination. METHODS: A retrospective study was performed considering CMBD´s hospital discharges with TB as first diagnosis and notifications to RENAVE between 2012 and 2020. After describing the records of both systems and their differences by using descriptive and multivariate analysis, annual incidences rates were calculated in order to evaluate temporal trends and geographical patters. RESULTS: According to the CMBD database, there were 29,942 hospitalizations due to TB (65% pulmonary forms and 66% male) during the study period. RENAVE collected 44,520 reported cases, mostly males (62%) with pulmonary forms (72%). Young children were similar in both groups, showing the high frequency of hospitalization in this group. Almost all autonomous communities showed a downward trend, especially Asturias. Hospitalizations in 2020 were analyzed by month separately, and comparing with previous years, the impact of the COVID-19 pandemic can be seen. CONCLUSIONS: A decreasing trend on TB incidence was observed in Spain since 2012, although this trend might change after COVID-19 pandemic. The analysis of both databases, CMBD and RENAVE, has contributed to improve our knowledge of TB in Spain and will help improve the control of this disease.

Chronic kidney disease in Nicaragua: a qualitative analysis of semi-structured interviews with physicians and pharmacists.

BACKGROUND: Northwestern Nicaragua has a high prevalence of chronic kidney disease (CKD) of unknown cause among young adult men. In addition, frequent occurrence of urinary tract infections (UTI) among men and a dysuria syndrome described by sugarcane workers as "chistata" are both reported. This study examines health professionals´ perceptions regarding etiology of these conditions and their treatment approaches, including use of potentially nephrotoxic medications. METHODS: Nineteen in-person semi-structured interviews were conducted in November 2010 among ten physicians and nine pharmacists practicing in the region. RESULTS: Health professionals perceived CKD as a serious and increasing problem in the region, primarily affecting young men working as manual laborers. All interviewees regarded occupational and environmental exposure to sun and heat, and dehydration as critical factors associated with the occurrence of CKD. These factors were also considered to play a role in the occurrence of chistata in the region. Health professionals indicated that reluctance among workers to hydrate might be influenced by perceptions of water contamination. Symptoms often were treated with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and antibiotics. Physicians acknowledged that the diagnosis of UTI usually was not based on microbial culture and opined that the use of potentially nephrotoxic medications may be contributing to CKD. CONCLUSIONS: Interviews provided evidence suggesting that medications such as diuretics, antibiotics and NSAIDs are widely used and sold over the counter for symptoms that may be related to dehydration and volume depletion. These factors, alone or in combination, may be possible contributors to kidney damage. Acute kidney damage coupled with volume depletion and exposures including medications and infectious agents should be further evaluated as causal factors for CKD in this region.

HIV testing and counselling for migrant populations living in high-income countries: a systematic review.

BACKGROUND: The barriers to HIV testing and counselling that migrants encounter can jeopardize proactive HIV testing that relies on the fact that HIV testing must be linked to care. We analyse available evidence on HIV testing and counselling strategies targeting migrants and ethnic minorities in high-income countries. METHODS: Systematic literature review of the five main databases of articles in English from Europe, North America and Australia between 2005 and 2009. RESULTS: Of 1034 abstracts, 37 articles were selected. Migrants, mainly from HIV-endemic countries, are at risk of HIV infection and its consequences. The HIV prevalence among migrants is higher than the general population's, and migrants have higher frequency of delayed HIV diagnosis. For migrants from countries with low HIV prevalence and for ethnic minorities, socio-economic vulnerability puts them at risk of acquiring HIV. Migrants have specific legal and administrative impediments to accessing HIV testing-in some countries, undocumented migrants are not entitled to health care-as well as cultural and linguistic barriers, racism and xenophobia. Migrants and ethnic minorities fear stigma from their communities, yet community acceptance is key for well-being. CONCLUSIONS: Migrants and ethnic minorities should be offered HIV testing, but the barriers highlighted in this review may deter programs from achieving the final goal, which is linking migrants and ethnic minorities to HIV clinical care under the public health perspective.

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.

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.

A population-based controlled experiment assessing the epidemiological impact of digital contact tracing.

While Digital contact tracing (DCT) has been argued to be a valuable complement to manual tracing in the containment of COVID-19, no empirical evidence of its effectiveness is available to date. Here, we report the results of a 4-week population-based controlled experiment that took place in La Gomera (Canary Islands, Spain) between June and July 2020, where we assessed the epidemiological impact of the Spanish DCT app Radar Covid. After a substantial communication campaign, we estimate that at least 33% of the population adopted the technology and further showed relatively high adherence and compliance as well as a quick turnaround time. The app detects about 6.3 close-contacts per primary simulated infection, a significant percentage being contacts with strangers, although the spontaneous follow-up rate of these notified cases is low. Overall, these results provide experimental evidence of the potential usefulness of DCT during an epidemic outbreak in a real population.

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.

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers.

Background: An epidemic of CKD in Central America predominantly affects males working in certain industries, including sugarcane. Urinary tract infections are commonly diagnosed among men in Nicaragua, who often receive antibiotics and nonsteroidal anti-inflammatory drugs for urinary symptoms. Methods: We followed 251 male Nicaraguan sugarcane workers in seven job tasks over one harvest and measured urine dipstick parameters, kidney injury biomarkers, and eGFR. We administered a questionnaire about urinary symptoms, health-related behaviors, and medication history. We cultured urine in a subset of workers. Results: The study population was composed of factory workers (23%), cane cutters (20%), irrigators (20%), drivers (16%), agrichemical applicators (12%), seeders/reseeders (6%), and seed cutters (4%). The mean age of participants was 33.9 years, and mean employment duration was 10.1 years. Cane cutters reported higher proportions of urinary-related symptoms compared with agrichemical applicators, irrigators, and seeders/reseeders. Seed cutters were more likely to take antibiotics (22%), whereas drivers and seeders/reseeders were more likely to take pain medications (27% and 27%, respectively). Proteinuria was uncommon, whereas dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33%, 22%, and 21% at late harvest, respectively). Dipstick leukocyte esterase at late harvest was associated with a 12.9 ml/min per 1.73 m2 (95% CI, -18.7 to -7.0) lower mean eGFR and 2.8 times (95% CI, 1.8 to 4.3) higher mean neutrophil gelatinase-associated lipocalin. In general, workers who reported urinary-related symptoms had higher mean kidney injury biomarker levels at late harvest. None of the workers had positive urine cultures, including those reporting urinary symptoms and/or with positive leukocyte esterase results. Amoxicillin, ibuprofen, and acetaminophen were the most commonly used medications. Conclusions: Job task is associated with urinary symptoms and dipstick leukocyte esterase. Urinary tract infection is misdiagnosed based on leukocyte esterase, which may be an important predictor of kidney outcomes.

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.

Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case-control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to Leptospira and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96-10.0, P = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of Leptospira. No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu within a few years. A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.