Search

The United States is experiencing a syndemic of homelessness, substance use disorder, and mental health conditions, which has been further exacerbated by the COVID-19 pandemic. Although it is expected that mitigation strategies will curb community transmission of COVID-19, the unintended consequences of social isolation on mental health and substance use are a growing public health concern. Awareness of changing mental health and substance use treatment needs due to the pandemic is critical to understanding what additional services and support are needed during and post-pandemic, particularly among people experiencing homelessness who have pre-existing serious mental illness or substance use disorder. To evaluate these effects and support our understanding of mental health and substance use outcomes of the COVID-19 pandemic, we conducted a qualitative study where behavioral health providers serving people experiencing homelessness described the impact of COVID-19 among their clients throughout the United States. Behavioral health providers shared that experiencing social isolation worsened mental health conditions and caused some people to return to substance use and fatally overdose. However, some changes initiated during the pandemic resulted in positive outcomes, such as increased client willingness to discuss mental health topics. Our findings provide additional evidence that the social isolation experienced during the pandemic has been detrimental to mental health and substance use outcomes, especially for people experiencing homelessness.

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 As climate change increases global temperatures, heat-related morbidity and mortality are projected to rise. Outdoor workers and those who perform exertional tasks are particularly susceptible to heat-related illness (HRI). Using workers' compensation data, we aimed to describe rates of occupational HRI in California and identify demographic and occupational risk factors to inform prevention efforts. Methods We identified HRI cases during 2000-2017 in the California Workers' Compensation Information System (WCIS) using International Classification of Diseases Ninth and Tenth Revision codes, WCIS nature and cause of injury codes, and HRI keywords. We assigned industry and occupation codes using the NIOSH Industry and Occupation Computerized Coding System (NIOCCS). We calculated HRI rates by sex, age group, year, county, industry, and occupation, and estimated confidence intervals using generalized linear models. Results We identified 15,996 HRI cases during 2000-2017 (6.0 cases/100,000 workers). Workers aged 16-24 years had the highest HRI rate (7.6) among age groups, and men (8.1) had a higher rate than women (3.5). Industry sectors with the highest HRI rates were Agriculture, Farming, Fishing, and Forestry (38.6), and Public Administration (35.3). Occupational groups with the highest HRI rates were Protective Services (56.6) and Farming, Fishing, and Forestry (36.6). Firefighters had the highest HRI rate (389.6) among individual occupations. Conclusions Workers in certain demographic and occupational groups are particularly susceptible to HRI. Additional prevention efforts, including outreach and enforcement targeting high-risk groups, are needed to reduce occupational HRI. Workers' compensation data can provide timely information about temporal trends and risk factors for HRI.

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.

Background The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. Methods We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020–25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. Results Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%–36%) overall, 42% among children (aged Conclusions We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0–27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04–1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15–2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73–17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03–2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 [62%]) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive predictive value (83% [95% confidence interval [CI], 55%–95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.

Large public-health training events may result in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Universal SARS-CoV-2 testing during trainings for the Uganda Population-based HIV Impact Assessment identified 28 of 475 (5.9%) individuals with coronavirus disease 2019 (COVID-19) among attendees; most (89.3%) were asymptomatic. Until COVID-19 vaccine is readily available for staff and participants, effective COVID-19 mitigation measures, along with SARS-CoV-2 testing, are recommended for in-person trainings, particularly when trainees will have subsequent contact with survey participants.

People experiencing homelessness (PEH) are at higher risk for chronic health conditions, but clinical characteristics and outcomes for PEH hospitalized with coronavirus disease 2019 (COVID-19) are not known. We analyzed population-based surveillance data of COVID-19–associated hospitalizations during 1 March to 31 May 2020. Two percent of the people hospitalized with COVID-19 for whom a housing status was recorded were homeless. Of 199 cases in the analytic sample, most were of racial/ethnic minority groups and had underlying health conditions. Clinical outcomes such as ICU admission, respiratory support including mechanical ventilation, and deaths were documented. Hispanic and non-Hispanic black persons accounted for most mechanical ventilation and deaths. Severe illness was common among persons experiencing homelessness who were hospitalized with COVID-19.

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.

BackgroundCongregate settings are at risk for coronavirus disease 2019 (COVID-19) outbreaks. Diagnostic testing can be used as a tool in these settings to identify outbreaks and to control transmission.MethodsWe used transmission modeling to estimate the minimum number of persons to test and the optimal frequency to detect small outbreaks of COVID-19 in a congregate facility. We also estimated the frequency of testing needed to interrupt transmission within a facility.ResultsThe number of people to test and frequency of testing needed depended on turnaround time, facility size, and test characteristics. Parameters are calculated for a variety of scenarios. In a facility of 100 people, 26 randomly selected individuals would need to be tested at least every 6 days to identify a true underlying prevalence of at least 5%, with test sensitivity of 85%, and greater than 95% outbreak detection sensitivity. Disease transmission could be interrupted with universal, facility-wide testing with rapid turnaround every three days.ConclusionsTesting a subset of individuals in congregate settings can improve early detection of small outbreaks of COVID-19. Frequent universal diagnostic testing can be used to interrupt transmission within a facility, but its efficacy is reliant on rapid turnaround of results for isolation of infected individuals.

Background. Nicaraguan sugar cane workers have an elevated prevalence of chronic kidney disease of unknown origin (CKDu). CKDu pathogenesis may involve environmental heat exposure along with genera...

BACKGROUND AND OBJECTIVES: Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus disease 2019. METHODS: We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts ( RESULTS: Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval [CI]: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio [OR]: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18). CONCLUSIONS: Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.

Background Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. Methods From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time. Results We identified 47 contacts, median age 24 (3–75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for Conclusions Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

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.

Background In California, state prison inmates are employed to fight wildfires, which involves performing soil-disrupting work. Wildfires have become more common, including areas where Coccidioides, the soil-dwelling fungus that causes coccidioidomycosis, proliferates. However, work practices that place wildland firefighters at risk for coccidioidomycosis have not been investigated. Methods On August 17, 2017, the California Department of Public Health was notified of a cluster of coccidioidomycosis cases among Wildfire A inmate wildland firefighters. We collected data through medical record abstraction from suspected case-patients and mailed a survey assessing potential job task risk factors to Wildfire A inmate firefighters. We described respondent characteristics and conducted a retrospective case-control investigation to assess coccidioidomycosis risk factors. Results Among 198 inmate firefighters who worked on Wildfire A, 112 (57%) completed the survey. Of 10 case-patients (four clinical and six laboratory-confirmed), two were hospitalized. In the case-control analysis of 71 inmate firefighters, frequently cutting fire lines with a McLeod tool (odds ratio [OR]: 5.5; 95% confidence interval [CI]: 1.1-37.2) and being in a dust cloud or storm (OR: 4.3; 95% CI: 1.1-17.4) were associated with illness. Two of 112 inmate firefighters reported receiving coccidioidomycosis training; none reported wearing respiratory protection on this wildfire. Conclusions Wildland firefighters who use hand tools and work in dusty conditions where Coccidioides proliferates are at risk for coccidioidomycosis. Agencies that employ them should provide training about coccidioidomycosis and risk reduction, limit dust exposure, and implement respiratory protection programs that specify where respirator use is feasible and appropriate.

Olfactory and taste dysfunctions have emerged as symptoms of COVID-19. Among individuals with COVID-19 enrolled in a household study, loss of taste and/or smell was the fourth most commonly reported symptom (26/42; 62%), and among household contacts, it had the highest positive predictive value (83%; 95% CI: 55-95%) for COVID-19. These findings support consideration of loss of taste and/or smell in possible case identification and testing prioritization for COVID-19.

In 2014, panel physicians from the International Organization for Migration (IOM), who conduct Department of State-required predeparture examinations for U.S.-bound refugees at resettlement sites in Uganda, noticed an unusually high number of Congolese refugees with enlarged spleens, or splenomegaly. Many conditions can cause splenomegaly, such as various infections, liver disease, and cancer. Splenomegaly can result in hematologic disturbances and abdominal pain and can increase the risk for splenic rupture from blunt trauma, resulting in life-threatening internal bleeding. On CDC's advice, panel physicians implemented an enhanced surveillance and treatment protocol that included screening for malaria (through thick and thin smears and rapid diagnostic testing), schistosomiasis, and several other conditions; treatment of any condition identified as potentially associated with splenomegaly; and empiric treatment for the most likely etiologies, including malaria and schistosomiasis. CDC recommended further treatment for malaria with primaquine after arrival, after glucose-6-phosphate dehydrogenase testing, to target liver-stage parasites. Despite this recommended treatment protocol, 35 of 64 patients with available follow-up records had splenomegaly that persisted beyond 6 months after resettlement. Among 85 patients who were diagnosed with splenomegaly through abdominal palpation or ultrasound at any point after resettlement, 53 had some hematologic abnormality (leukopenia, anemia, or thrombocytopenia), 16 had evidence of current or recent malaria infection, and eight had evidence of schistosomiasis. Even though primaquine was provided to a minority of patients in this cohort, it should be provided to all eligible patients with persistent splenomegaly, and repeated antischistosomal therapy should be provided to patients with evidence of current or recent schistosomiasis. Given substantial evidence of familial clustering of cases, family members of patients with known splenomegaly should be proactively screened for this condition.

In 2010, the World Health Assembly set three milestones for measles prevention to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).* In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),† with the objective of eliminating measles§ in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals.

In January 2017, two local health departments notified the California Department of Public Health (CDPH) of three cases of coccidioidomycosis among workers constructing a solar power installation (solar farm) in southeastern Monterey County. Coccidioidomycosis, or Valley fever, is an infection caused by inhalation of the soil-dwelling fungus Coccidioides, which is endemic in the southwestern United States, including California. After a 1-3 week incubation period, coccidioidomycosis most often causes influenza-like symptoms or pneumonia, but rarely can lead to severe disseminated disease or death (1). Persons living, working, or traveling in areas where Coccidioides is endemic can inhale fungal spores; workers who are performing soil-disturbing activities are particularly at risk. CDPH previously investigated one outbreak among solar farm construction workers that started in 2011 and made recommendations for reducing risk for infection, including worker education, dust suppression, and use of personal protective equipment (2,3). For the current outbreak, the CDPH, in collaboration with Monterey County and San Luis Obispo County public health departments, conducted an investigation that identified nine laboratory-confirmed cases of coccidioidomycosis among 2,410 solar farm employees and calculated a worksite-specific incidence rate that was substantially higher than background county rates, suggesting that illness was work-related. The investigation assessed risk factors for potential occupational exposures to identify methods to prevent further workplace illness.

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.

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.

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.

The extent of the innate immune response is regulated by many positively and negatively acting signaling proteins. This allows for proper activation of innate immunity to fight infection while ensuring that the response is limited to prevent unwanted complications. Thus mutations in innate immune regulators can lead to immune dysfunction or to inflammatory diseases such as arthritis or atherosclerosis. To identify novel innate immune regulators that could affect infectious or inflammatory disease, we have taken a comparative genomics RNAi screening approach in which we inhibit orthologous genes in the nematode Caenorhabditis elegans and murine macrophages, expecting that genes with evolutionarily conserved function also will regulate innate immunity in humans. Here we report the results of an RNAi screen of approximately half of the C. elegans genome, which led to the identification of many candidate genes that regulate innate immunity in C. elegans and mouse macrophages. One of these novel conserved regulators of innate immunity is the mRNA splicing regulator Eftud2, which we show controls the alternate splicing of the MyD88 innate immunity signaling adaptor to modulate the extent of the innate immune response.

To reveal regulators of innate immunity, we used RNAi assays to monitor the immune response when genes are inhibited in Caenorhabditis elegans and mouse macrophages. Genes that altered innate immune responsiveness in C. elegans were validated in murine macrophages, resulting in the discovery of 11 genes that regulate the innate immune response in both systems and the subsequent identification of a protein interaction network with a conserved role in innate immunity regulation. We confirmed the role of four of these 11 genes in antimicrobial gene regulation using available mutants in C. elegans . Several of these genes ( acy-1 , tub-2 , and tbc-1 ) also regulate susceptibility to the pathogen Pseudomonas aeruginosa . These genes may prove critical to understanding host defense and represent potential therapeutic targets for infectious and immunological diseases.