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BACKGROUND: Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. METHODS: We conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3-5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. RESULTS: We found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (ß = -2.3; 95% CI: -3.9, -0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (ß = -3.1; 95% CI: -5.0, -1.2 and -2.3; 95% CI: -4.5, -0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. CONCLUSION: Our findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex - neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

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Studies suggest that acute pesticide poisonings (APP) may be linked with long-term neurological effects. To examine long-term neurological and psychological distress symptoms associated with having experienced an APP, we conducted a cross-sectional study of 300 conventional and organic smallholder farmers from Zarcero County, Costa Rica, May-August 2016. We collected self-reported data on sociodemographic characteristics, occupational history, pesticide exposure, APPs, neurological and psychological distress symptoms (using the Brief Symptom Inventory (BSI)). Adjusted logistic regression models were fit. A total of 14% of the farmers (98% male) reported experiencing at least one APP during their lifetime. Self-reported APP was associated with neurological symptoms during the 12 months prior to interview (e.g., fainting (Odds Ratio: 7.48, 95% Confidence Interval: 1.83, 30.74), shaking hands (3.50; 1.60, 7.60), numbness/tingling in hands or feet (3.23; 1.66, 6.32), insomnia (2.53; 1.34, 4.79), accelerated heartrate (2.42; 1.03, 5.47), dizziness (2.38; 1.19, 4.72), increased irritability/anger (2.37; 1.23, 4.55), low energy (2.33; 1.23, 4.46), and difficulty concentrating (2.01; 1.05, 3.85)). Farmers who reported an APP in the ten years prior to interview experienced increased odds of abnormal BSI scores for hostility (4.51; 1.16, 17.70) and paranoid ideation (3.76; 0.99, 18.18). Having experienced an APP may be associated with long-term neurological and psychological distress symptoms.

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OBJECTIVE: Estimates of pesticide exposure among applicators from low- and middle-income countries (LMICs) are scarce, and exposure assessment methods are sometimes costly or logistically unfeasible. We examined the variability in weeklong pesticide exposure among applicators in Costa Rica and its predictors. METHODS: We conducted a cross-sectional survey among 221 pesticide applicators from organic, sustainable and conventional farms in 2016. We administered structured questionnaires to assess pesticide application practices at two time points (4-6 weeks apart). We adapted an existing algorithm to fit the context of smallholders and derive weekly pesticide exposure scores. We used linear mixed-effect models to examine within-worker and between-worker score variability. We then identified sociodemographic and occupational predictors of weekly pesticide exposure scores. RESULTS: We observed high within-worker and between-worker variability in weekly pesticide exposures (eg, up to 180-fold and 70-fold differences in average weekly exposures within and between workers, respectively; intraclass correlation coefficient=0.4). Applicators working on conventional and sustainable farms had exposure scores twofold and 1.5-fold higher than those working in organic farms, respectively. Farm workers who received training on pesticide use had weekly pesticide exposure scores of 33% (95% CI 1% to 55%) lower than those who did not receive any training. CONCLUSIONS: In this study of applicators from smallholder farms in Costa Rica, we determined the importance of collecting questionnaire data on self-reported pesticide use repeatedly due to its high variability within workers and absence of application records. Our questionnaire-based exposure algorithm could allow the calculation of semiquantitative estimates of average pesticide exposure for applicators from other LMICs.

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Pesticides are used globally in agriculture and pose a threat to the health of farmers, communities, and the environment. Smallholder farmers in low- and middle-income countries have generally a low socio-economic status and educational level. Consequently, they are particularly vulnerable to negative impacts of pesticides on their health, yields, or land. In a Knowledge, Attitude, and Practices study, we compared the pest management practices between a market-oriented farming system in Zarcero County, Costa Rica, and a subsistence-based farming system in Wakiso District, Uganda. We conducted a cross-sectional survey among smallholder farmers from Costa Rica (n = 300) in 2016 and from Uganda (n = 302) in 2017. We enrolled conventional and organic farmers, but also farmers with mixed practices and non-applicators of any pest management strategy. We found that the majority of pesticides used in both case studies are classified as highly hazardous by the World Health Organization. While more than 90% of smallholder farmers from both countries were aware of the negative health effects of pesticide exposure, <11% in Costa Rica and <2% in Uganda reported using personal protective equipment every time they handled or applied pesticides. Hygiene and other safe use practices were not adopted by all farmers (<61%), especially among farmers applying more hazardous pesticides. Conventional farmers from Costa Rica (14%) and Uganda (19%) reported disposing pesticide residuals into rivers. Using a logistic regression we found that organic farmers were more likely to having been trained on safe pesticide use practices. Using a robust regression, we observed that smallholder household income was primarily driven by education and not directly by the use of synthetic pesticides. Our results suggest that negative effects of pesticides can be managed over the whole life cycle, from purchase, via storage and application to residual and waste management by fostering professionalization of farmers. We advise future safe use and handling interventions to consider the pesticide use-related socioeconomic and demographic findings highlighted in this paper.

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Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 µg/g (3.52) and 0.24 µg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects.

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BACKGROUND: Pesticide use is increasing in low- and middle-income countries (LMICs) including Costa Rica. This increase poses health risks to farm owners, farm workers, and communities living near agricultural farms. OBJECTIVE: We aimed to examine the health effects associated with occupational pesticide exposure in farm owners and workers from conventional and organic smallholder farms in Costa Rica. METHODS: We conducted a cross-sectional study involving 300 owners and workers from organic and conventional horticultural smallholder farms in Zarcero County, Costa Rica. During the baseline study visit, we administered a structured, tablet-based questionnaire to collect data on sociodemographic characteristics, pesticide exposure, and health conditions (eg, respiratory and allergic outcomes and acute pesticide intoxication symptoms) and administered a neurobehavioral test battery (eg, Finger Tapping Test and Purdue Pegboard); we measured blood pressure, anthropometry (height, weight, and waist circumference), and erythrocytic acetylcholinesterase activity and also collected urine samples. In addition, a functional neuroimaging assessment using near-infrared spectroscopy was conducted with a subset of 50 study participants. During the follow-up study visit (~2-4 weeks after the baseline), we administered participants a short questionnaire on recent pesticide exposure and farming practices and collected hair, toenail, and urine samples. Urine samples will be analyzed for various pesticide metabolites, whereas toenails and hair will be analyzed for manganese (Mn), a biomarker of exposure to Mn-containing fungicides. Self-reported pesticide exposure data will be used to develop exposure intensity scores using an exposure algorithm. Furthermore, exposure-outcome associations will be examined using linear and logistic mixed-effects regression models. RESULTS: Fieldwork for our study was conducted between May 2016 and August 2016. In total, 113 farm owners and 187 workers from 9 organic and 83 conventional horticultural smallholder farms were enrolled. Data analyses are ongoing and expected to be published between 2019 and 2020. CONCLUSIONS: This study is one of the first to examine differences in health effects due to pesticide exposure between farm owners and workers from organic and conventional smallholder farms in an LMIC. We expect that this study will provide critical data on farming practices, exposure pathways, and how occupational exposure to pesticides may affect farm owners and workers' health. Finally, we hope that this study will allow us to identify strategies to reduce pesticide exposure in farm owners and workers and will potentially lay the groundwork for a future longitudinal study of health outcomes in farm owners and workers exposed to pesticides. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10914.

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OBJECTIVES: The extractive industries have contributed to the economic and social development of Latin America and the Caribbean for centuries. We have undertaken a narrative review to assess the role of the health authority in the decision-making process as it relates to extractive industry projects. METHODS: A narrative literature review was conducted with a keyword search conducted using PubMed, Scientific Electronic Library Online and Google. This was complemented with manual searches of relevant journals and reference lists of primary articles. RESULTS: A broad body of literature from Latin America and the Caribbean region provides evidence that the public health of communities engaged in extractive industry is not being assured and that significant gaps exist in aligning public and private sector efforts to improve health. CONCLUSIONS: Inclusion of the health authority in impact assessment has the potential to result in lasting positive effects on communities involved directly and indirectly in the extractive industry, while preventing a large range of potential adverse health impacts.

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