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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 (c and HR values. However, a few workers in other industries reached high Tc (>39 °C) as well. Impaired kidney function (estimated glomerular filtration rate 2) 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.

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.

Background: An epidemic of chronic kidney disease 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 estimated glomerular filtration rate (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 (22.7%), cane cutters (20.3%), irrigators (19.5%), drivers (16.3%), agrichemical applicators (11.6%), seeders/reseeders (6.0%), and seed cutters (3.6%). The mean age 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 (22.2%), while drivers and seeders/reseeders were more likely to take pain medications (26.8% and 26.7%, respectively). Proteinuria was uncommon, while dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33.3%, 22.2%, and 21.4% at late-harvest, respectively). Dipstick leukocyte esterase at late-harvest was associated with a 12.9 mL/min/1.73m2 (95% CI: -18.7, -7.0) lower mean eGFR and 2.8 times (95% CI: 1.8, 4.3) higher mean neutrophil gelatinase-associated lipocalin (NGAL). 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.

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.

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. MKS and DRB were supported by a grant from the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH/NIEHS), award number R01 ES027584. ZEP was supported by NIH/NIEHS award numbers T32 ES014562 and F31 ES030974. JB gratefully acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No 865564 (European Research Council Consolidator Grant EARLY-ADAPT) and 727852 (project Blue-Action), and from the Ministry of Science and Innovation (MCIU) under grant agreements No RYC2018-025446-I (programme Ramón y Cajal) and EUR2019-103822 (project EURO-ADAPT). O.R.-R., J.B., and C.O.-G. acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. The funding sources had no involvement in the conduct of this research or preparation of this manuscript.

Background/Aim: There is an epidemic in Central America of chronic kidney disease of unknown etiology (CKDu), also referred to as Mesoamerican Nephropathy (MeN). MeN prevalence is high among agricu...

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.

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.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.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 mChildren residing in regions of Nicaragua at high risk for MeN may experience subclinical kidney injury prior to occupational exposures.

BACKGROUND: Studies have described Mesoamerican nephropathy among agricultural workers of El Salvador and northwestern Nicaragua. Data on prevalence and risk factors for CKD beyond agricultural workers and in other regions in Nicaragua are sparse. METHODS: We recruited participants from 32 randomly selected communities in the Department of Rivas’s ten municipalities in two phases. In phase 1, we screened participants using a field-based capillary creatinine measuring system and collected self-reported information on lifestyle and occupational, exposure, and health histories. Two years later, in phase 2, we enrolled 222 new participants, performing serum creatinine testing in these participants and confirmatory serum creatinine testing in phase 1 participants. RESULTS: We enrolled 1242 of 1397 adults (89%) living in 533 households (median age 41 years; 43% male). We confirmed CKD (eGFR

The causes of the epidemic of chronic kidney disease (CKD) in Central America, referred to as Mesoamerican Nephropathy (MeN), or CKD of non-traditional etiology (CKDnt), are unknown. Sugarcane work...

In Central America there is an epidemic of chronic kidney disease (CKD) of non-traditional etiology. Few studies have assessed CKD prevalence among non-agricultural workers. We conducted an observa...

Rationale & Objective In Central America, there is a high prevalence of chronic kidney disease (CKD) of nontraditional etiology often observed among agricultural workers. Few studies have assessed CKD prevalence among workers in nonagricultural occupations, which was the objective of this investigation. Study Design Prospective cohort study. Setting & Participants Male and female workers (n = 224) employed by artisanal brickmaking facilities in La Paz Centro, Nicaragua. Predictors Age, sex, education, smoking status, body mass index, alcohol consumption, water consumption, first-degree relative(s) with CKD, years worked, hours worked per week, job category, study visit (baseline and follow-up), and self-reported hypertension and diabetes. Outcomes CKD defined as estimated glomerular filtration rate (eGFR) Analytical Approach A linear mixed-effects model with an unstructured covariance matrix was used to evaluate the association between demographics, occupational risk factors, and eGFR at baseline. The interaction between risk factors and time with change in eGFR was also evaluated. Multivariable logistic regression models were used to evaluate predictors of CKD. Results The CKD prevalence was 12.1% (n = 27), 100% of cases were male, 30% had stage 5 CKD (eGFR Limitations Crude job classification measures, loss to follow-up, self-reported exposures. Conclusions The prevalence of CKD is high in this population of brick workers, suggesting that the epidemic of CKD affecting Mesoamerica is not limited to agricultural workers. These results are consistent with the hypothesis that occupational heat exposure is a risk factor for kidney disease in this region.

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.

Background:There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers.Objectives:To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria.Methods:We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR).Results:eGFR varied by job and decreased during the harvest in seed cutters (−8·6 ml/min/1·73 m2), irrigators (−7·4 ml/min/1·73 m2), and cane cutters (−5·0 ml/min/1·73 m2), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g.Conclusions:The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are ...

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.Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI.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.AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL.Kidney function trajectory and development of CKD over 12 months.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.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/1.73mFollow-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.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.

El tabaco es un estimulante del sistema nervioso central que muchos estudiantes universitarios usan con el fin de relajarse, aun conociendo los efectos nocivos y dañinos que este produce. El consumo de tabaco en los países en desarrollo constituye un problema de salud pública cuya iniciación generalmente ocurre en la adolescencia, donde más de la mitad de los jóvenes al llegar a ser adultos poseen hábito tabáquico. El tabaco es tan adictivo como la droga pura, ya que se trata de un producto psicoactivo que afecta los procesos químicos del cerebro y del sistema nervioso. Además tiene reconocidos efectos nocivos sobre el sistema respiratorio, dañando gravemente bronquios y pulmones, llegando a producir bronquitis crónicas, enfisema y cáncer pulmonar, entre otras. Los fumadores, además de dañar su propia salud, perjudican a los que los rodean. Es notorio que lo que se ha denominado "tabaquismo pasivo" es peligroso para quienes lo sufren, justificándose plenamente las medidas de protección que se han adoptado en los diversos entornos en que se producen estas situaciones. Es necesario destacar que reviste suma gravedad el hecho de que las mujeres fumen durante el embarazo, debido a que pueden llegar a tener partos prematuros, mayor incidencia de abortos, mortalidad perinatal, niños con bajo peso de nacimiento, entre otros problemas.

Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers.Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers.In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG).Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers.Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.

Background A lack of advanced healthcare information systems and validated scientific cohorts in Nicaragua makes it difficult to estimate disease prevalences and other public health statistics. Although there is concern of an “epidemic” of chronic kidney disease (CKD) in this country, statistics regarding its magnitude are derived from only a small number of non-representative studies. Budgetary constraints and the logistical problems of maintaining a study cohort make longitudinal studies difficult. The Rivas Cohort was created to measure disease burden of CKD and other public health priorities in the Department of Rivas, Nicaragua. Using primarily volunteer research students and technologic innovation including GPS, digital photography and point of care biochemical analysis, the ability to establish a longitudinal chronic disease cohort is demonstrated. Methods Subjects were recruited from consecutive adjacent households in thirty-two randomly selected communities in the ten municipalities that comprise the Department of Rivas in southern Pacific coastal Nicaragua. The study was conducted in two phases. In the first phase, subjects were enrolled into the cohort and consented for future re-contact. In Phase II, conducted two years later, attempts were made to re-contact 400 of these subjects for additional data collection. Demographic, lifestyle, occupational, exposure and health data was collected for both phases of the study. Blood and urine testing and height, weight and blood pressure measurements were also performed. GPS coordinates of homes were recorded and maps of remote communities created. Results Of 1397 adults living in 533 households approached for participation a total of 1242 (89 %) were enrolled in the cohort. The median age is 41 years and 43 % are male, demographics in agreement with Nicaraguan census data for the Department of Rivas. During Phase II we attempted to re-contact 400 subjects for a follow-up study of CKD. It was possible to re-contact 84 % of these participants and of those re-contacted 95 % agreed to participate in the follow-up study. Of subjects that were not successfully re-contacted the majority had either moved (32) or were not at home (22) at the time of the study team visits. Conclusion The Rivas Cohort Study enrolled a representative sample of 1242 adults living in the Department of Rivas, Nicaragua. The high re-contact and participation rates at two years suggests that the cohort is suitable for long-term studies and presents opportunities for investigations of disease prevalence, incidence, treatment and other public health matters. GPS coordinates and maps are available for future researchers who wish to use the cohort for additional studies. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0320-9) contains supplementary material, which is available to authorized users.

OBJECTIVES: We investigated a nationwide outbreak of severe rotavirus gastroenteritis in Nicaragua in children under 5 years old, leading to many consultations, hospitalizations, and deaths. We questioned whether a vaccine might have prevented these illnesses and deaths, sought to identify risk factors for death, and developed a clinical profile of children hospitalized with diarrhea. METHODS: We conducted a case-control study to determine whether children who died had access to routine immunizations, a proxy predicting access to a rotavirus vaccine. We identified risk factors for death among children who died in the outbreak compared with surviving age-matched controls with diarrhea. We collected stools, clinical data, and immunization data on children hospitalized for diarrhea to test for rotavirus, develop the profile, and forecast future access to a rotavirus vaccine. RESULTS: The outbreak from February to April 2005 caused 47 470 consultations and 52 deaths. Approximately 80% of cases and controls and 60% of children hospitalized with diarrhea had access to routine immunizations and would likely have had access to a rotavirus vaccine. With a vaccine efficacy of 85%, up to 51% of severe rotavirus cases and up to 68% of deaths could have been prevented if a rotavirus vaccine were available as part of routine child-hood immunizations. Study of 35 case-control pairs indicated that severe illnesses, malnutrition, and care by traditional healers were risk factors for death. Rotavirus was found in 42% of samples from hospitalized children and was associated with severe disease and dehydration. CONCLUSIONS: The impact of the seasonal outbreaks of rotavirus disease could be diminished with a rotavirus vaccine, improvements in oral rehydration programs, and training of traditional healers in the proper management of children with acute diarrhea.OBJETIVOS: Se investigó un brote nacional de gastroenteritis grave por rotavirus en niños menores de 5 años de edad que provocó numerosas consultas, hospitalizaciones y muertes en Nicaragua. Se analizó si la vacunación habría evitado estos casos de enfermedad y fallecimiento, se buscaron factores de riesgo de muerte y se elaboró un perfil clínico de los niños hospitalizados con diarrea. MÉTODOS: Se realizó un estudio de casos y controles para determinar si los niños que murieron tuvieron acceso a programas de vacunación, como medida indirecta del acceso a la vacuna contra rotavirus. Se identificaron los factores de riesgo de muerte en los niños que fallecieron durante el brote en comparación con los controles con diarrea sobrevivientes, emparejados según la edad. Se tomaron muestras de heces fecales, datos clínicos y de vacunación de los niños hospitalizados con diarrea para realizar el diagnóstico de rotavirus, elaborar el perfil clínico y pronosticar el acceso futuro a una vacuna contra rotavirus. RESULTADOS: El brote ocurrido entre febrero y abril de 2005 ocasionó 47 470 consultas y 52 muertes. Aproximadamente 80% de los casos y controles y 60% de los niños hospitalizados con diarrea tuvieron acceso a la vacunación programada y posiblemente tuvieron acceso a una vacuna contra rotavirus. Si en los programas de vacunación se hubiera dispuesto de una vacuna de 85% de eficacia, se hubieran prevenido hasta 51% de los casos graves de rotavirus y hasta 68% de las muertes. El estudio de 35 pares de casos y controles demostró que la enfermedad grave, la desnutrición y la atención por curanderos tradicionales fueron los factores de riesgo de muerte. Se encontró rotavirus en 42% de las muestras de niños hospitalizados, asociado con la enfermedad grave y la deshidratación. CONCLUSIONES: El efecto de los brotes estacionales de la enfermedad por rotavirus podría reducirse mediante la vacunación contra rotavirus, el perfeccionamiento de los programas de rehidratación oral y el entrenamiento de los curanderos tradicionales en el tratamiento correcto de los niños con diarrea aguda.

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.Cross-sectional family-based study.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.CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women.Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid.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; P0.001) 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.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.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.

In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers.Longitudinal cohort study.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.Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake.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-β-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR).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.Surrogate exposure measure, loss to follow-up.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.

In a hospital and health center-based study in Nicaragua, fluid intake during the 24 hours before being seen by a clinician was statistically associated with decreased risk for hospitalization of dengue fever patients. Similar results were obtained for children

As part of an investigation of a 1995 outbreak of leptospirosis in Nicaragua, a cross-sectional serologic survey was conducted in the town of El Sauce. Of 566 persons, 85 (15%) were positive for IgM anti-Leptospira antibodies, indicating recent leptospirosis infection. Asymptomatic leptospirosis infection was common, with only 25 (29.4%) of the 85 seropositive inhabitants reporting a febrile illness in the 2 months before the survey. Multivariable analysis revealed that having an indoor water source remained independently protective against leptospirosis. Gathering wood was independently associated with infection. These findings suggest that asymptomatic infection with Leptospira is common in endemic areas of Leptospira transmission. Improvement in water sanitation and behavioral modifications to reduce environmental exposure may reduce the risk of leptospirosis in endemic regions.

For almost 2 decades, large areas of Central America have been impacted by an under-recognised epidemic of chronic kidney disease (CKD) of unknown causes whose victims are disproportionately young men of working age.1–5 Although exact figures are unavailable, based on estimates from our group, the death toll has likely reached at least 20 000. El Salvador, for example, has the highest overall mortality from kidney disease in the world (with Nicaragua and Honduras also included in the 10 highest countries), and CKD is the second leading cause of mortality among men of working age in the country.4 ,6 Furthermore, similar excesses of CKD of unknown cause have been reported in Sri Lanka,7 India8 and Egypt,9 where many of the epidemiological characteristics appear to be similar to the epidemic in Central America. Despite its scientific and public health importance and its potential global reach, we have found that most health researchers and public health practitioners are unaware of this epidemic. Our goal in this editorial is to provide a brief overview of the epidemiological, aetiological and public health dimensions of the epidemic. We are part of a multidisciplinary and multinational team of researchers whose involvement began in 2009 when we were selected to conduct research to search for the cause(s) of excess CKD by the participants of a mediation process managed by the Compliance Advisor/Ombudsman Office, an independent recourse mechanism for the World Bank10 aimed at responding to complaints from project-affected communities with the goal of providing a mechanism for representatives of the communities to sit at the table with recipients of World Bank private sector loans and address issues raised in the complaints. The participants included a sugar cane company in Nicaragua and a group of more than 2000 sick ex-workers and their families. During …

Summary The prevalence of soil-transmitted helminthiasis is close to half the population in Central America, with the marginalized peri-urban poor disproportionately affected. Previous single province helminth surveys conducted in Nicaragua have shown Ascaris lumbricoides to be the predominant species. In 2005, we conducted a cross-sectional study of 880 children in 10 Nicaraguan primary schools located in four provinces. We aimed to establish the prevalence and intensity of soiltransmitted helminth infections and to investigate the factors associated with helminthiasis. Almost half (46%) of the children were infected with soil-transmitted helminths. Tichuris trichiura was the most common infective species (34.7%). The prevalence and intensity of helminthiasis was heterogeneous in the provinces, with children educated in peri-urban schools most affected. Healthy policies are required that favour the peri-urban poor who have inadequate and declining access to water and sanitation.

OBJECTIVES: We investigated a nationwide outbreak of severe rotavirus gastroenteritis in Nicaragua in children under 5 years old, leading to many consultations, hospitalizations, and deaths. We questioned whether a vaccine might have prevented these illnesses and deaths, sought to identify risk factors for death, and developed a clinical profile of children hospitalized with diarrhea. METHODS: We conducted a case-control study to determine whether children who died had access to routine immunizations, a proxy predicting access to a rotavirus vaccine. We identified risk factors for death among children who died in the outbreak compared with surviving age-matched controls with diarrhea. We collected stools, clinical data, and immunization data on children hospitalized for diarrhea to test for rotavirus, develop the profile, and forecast future access to a rotavirus vaccine. RESULTS: The outbreak from February to April 2005 caused 47 470 consultations and 52 deaths. Approximately 80% of cases and controls and 60% of children hospitalized with diarrhea had access to routine immunizations and would likely have had access to a rotavirus vaccine. With a vaccine efficacy of 85%, up to 51% of severe rotavirus cases and up to 68% of deaths could have been prevented if a rotavirus vaccine were available as part of routine child-hood immunizations. Study of 35 case-control pairs indicated that severe illnesses, malnutrition, and care by traditional healers were risk factors for death. Rotavirus was found in 42% of samples from hospitalized children and was associated with severe disease and dehydration. CONCLUSIONS: The impact of the seasonal outbreaks of rotavirus disease could be diminished with a rotavirus vaccine, improvements in oral rehydration programs, and training of traditional healers in the proper management of children with acute diarrhea.

During February and March 2005, one of the largest national recorded outbreaks of severe acute gastroenteritis occurred in Nicaragua, affecting ≥64,000 individuals and causing ≥56 deaths, predominantly in children under 5 years of age. Through a nationwide laboratory-based study, stool samples were collected and investigated for rotavirus. Of 108 stool samples examined, 72 (67%) were positive for rotavirus. While 69% (50/72) of the positive samples were found in children less than 2 years of age, 50% (6/12) of the adult samples were positive. A mutated G4P[8] strain was the most commonly recognized strain (85%), followed by mixed G strains (8%) and G9P[8] (7%) strains. Phylogenetic analysis of the VP7 gene revealed that the G4 strains belonged to the emerging lineage Ic and was distantly related to the ST3 and VA70 G4 strains. Secondary structure predictions of the VP7 G4 protein revealed an insert of an asparagine residue in position 76, which, combined with additional mutations, surprisingly modified two downstream β-sheets at amino acid positions 80 to 85 and 115 to 119. The 2005 G4P[8] strain compared to a G4P[8] strain from 2002 had a substitution of an asparagine residue for threonine (Asn→Thr) at position 96 within antigenic region A, thus eliminating a potential glycosylation site. The mutated G4 virus was introduced in Nicaragua after 2002 and probably emerged from Brazil, Argentina, or Uruguay.

To investigate the incidence of dengue virus (DENV) infection in Nicaragua, a 2-year prospective study was conducted in schoolchildren 4-16 years old in the capital city of Managua. Blood samples were collected before the rainy season in 2001, 2002 and 2003, and were assayed for DENV-specific antibodies. Participants were monitored for dengue-like illness, and acute and convalescent blood samples were collected from suspected dengue cases. In 2001 and 2002, 602 and 397 students were recruited, respectively, and paired annual serum samples were available from 467 and 719 participants in 2001-2002 and 2002-2003, respectively. The overall seroprevalence of anti-DENV antibodies was 91%, increasing from 75% at age 4 to 100% at age 16. The incidence of DENV infection was 12% in Year 1 and 6% in Year 2 (P < 0.001). During Year 1, four laboratory-confirmed dengue cases were detected, with one DENV2 isolate; during Year 2, there were six confirmed dengue cases, with one DENV1 isolate. These and additional circulating serotypes were confirmed by plaque reduction neutralisation test. This study demonstrates surprisingly high transmission of DENV in urban Nicaragua.

Several factors limited HIV transmission during the 1980s, includ-ing a ten-year civil war accompanied by an economic blockade by the United States of America (USA), which isolated the country for several years; a relatively controlled commercial sex industry; low infection rates for injecting drug users; and a ban on the commercial sale of blood. In the late 1990s, however, the spread of HIV rapidly increased.

From July to December 1998, a hospital- and health center-based surveillance system for dengue was established at selected sites in Nicaragua to better define the epidemiology of this disease. Demographic and clinical information as well as clinical laboratory results were obtained, and virus isolation, reverse transcriptase-polymerase chain reaction, and serologic assays were performed. World Health Organization criteria were used to classify disease severity; however, a number of patients presented with signs of shock in the absence of thrombocytopenia or hemoconcentration. Therefore, a new category was designated as "dengue with signs associated with shock" (DSAS). Of 1,027 patients enrolled in the study, 614 (60%) were laboratory-confirmed as positive cases; of these, 268 (44%) were classified as dengue fever (DF); 267 (43%) as DF with hemorrhagic manifestations (DFHem); 40 (7%) as dengue hemorrhagic fever (DHF); 20 (3%) as dengue shock syndrome (DSS); and 17 (3%) as DSAS. Interestingly, secondary infection was not significantly correlated with DHF/DSS, in contrast to previous studies in Southeast Asia. DEN-3 was responsible for the majority of cases, with a minority due to DEN-2; both serotypes contributed to severe disease. As evidenced by the analysis of this epidemic, the epidemiology of dengue can differ according to geographic region and viral serotype.

In October 1995, epidemic "hemorrhagic fever," without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7-132.3), have household rodents (MOR, 10.4; 95% CI, 1.1-97.1), or own dogs with titers >/=400 to Leptospira species (MOR, 23.4; 95% CI, 3.6-infinity). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs.

Results Of the 285 rotavirus cases, 265 (93%) required hospitalization; 251 (88%) received intravenous hydration. A single rotavirus strain (G2P(4)) was identified in 88% of the cases. Among cases and controls, respectively, 18% and 12% were unvacci- nated, 12% and 15% received 1 dose of RV5, 15% and 17% received 2 doses, and 55% and 57% received 3 doses. Vaccination with 3 doses was associated with a lower risk of rotavirus diarrhea requiring overnight admission or intravenous hydration (odds ratio (OR), 0.54; 95% confidence interval (CI), 0.36-0.82). Of the 285 rotavirus cases, 191 (67%) were severe and 54 (19%) were very severe. A progressively lower risk of severe (OR, 0.42; 95% CI, 0.26-0.70) and very severe rotavirus diarrhea (OR, 0.23; 95% CI, 0.08-0.61) was observed after RV5 vaccination. Thus, effectiveness of 3 doses of RV5 against rotavirus disease requiring admission or treatment with intravenous hydra- tion was 46% (95% CI, 18%-64%); against severe rotavirus diarrhea, 58% (95% CI, 30%-74%); and against very severe rotavirus diarrhea, 77% (95% CI, 39%-92%). Conclusion Vaccination with RV5 was associated with a lower risk of severe rota- virus diarrhea in children younger than 2 years in Nicaragua but to a lesser extent than that seen in clinical trials in industrialized countries.

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.