Correction: Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness.

[This corrects the article DOI: 10.1371/journal.pone.0287412.].

Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil.

INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

Network Profile: Improving Response to Malaria in the Amazon through Identification of Inter-Community Networks and Human Mobility in Border Regions of Ecuador, Peru, and Brazil.

Objectives: Understanding human mobility's role on malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. Design: A community-level network survey. Setting: We collect data on community connectivity along three river systems in the Amazon basin: the Pastaza river corridor spanning the Ecuador-Peru border; and the Amazon and Javari river corridors spanning the Brazil-Peru border. Participants: We interviewed key informants in Brazil, Ecuador, and Peru, including from indigenous communities: Shuar, Achuar, Shiwiar, Kichwa, Ticuna, and Yagua. Key informants are at least 18 years of age and are considered community leaders. Primary outcome: Weekly, community-level malaria incidence during the study period. Methods: We measure community connectivity across the study area using a respondent driven sampling design. Forty-five communities were initially selected: 10 in Brazil, 10 in Ecuador, and 25 in Peru. Participants were recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses were ranked and the 2-3 most connected communities were then selected and surveyed. This process was repeated for a third round of data collection. Community network matrices will be linked with eadch country's malaria surveillance system to test the effects of mobility on disease risk. Findings: To date, 586 key informants were surveyed from 126 communities along the Pastaza river corridor. Data collection along the Amazon and Javari river corridors is ongoing. Initial results indicate that network sampling is a superior method to delineate migration flows between communities. Conclusions: Our study provides measures of mobility and connectivity in rural settings where traditional approaches are insufficient, and will allow us to understand mobility's effect on malaria transmission.

Spatial transferability of an agent-based model to simulate Taenia solium control interventions.

BACKGROUND: Models can be used to study and predict the impact of interventions aimed at controlling the spread of infectious agents, such as Taenia solium, a zoonotic parasite whose larval stage causes epilepsy and economic loss in many rural areas of the developing nations. To enhance the credibility of model estimates, calibration against observed data is necessary. However, this process may lead to a paradoxical dependence of model parameters on location-specific data, thus limiting the model's geographic transferability. METHODS: In this study, we adopted a non-local model calibration approach to assess whether it can improve the spatial transferability of CystiAgent, our agent-based model of local-scale T. solium transmission. The calibration dataset for CystiAgent consisted of cross-sectional data on human taeniasis, pig cysticercosis and pig serology collected in eight villages in Northwest Peru. After calibration, the model was transferred to a second group of 21 destination villages in the same area without recalibrating its parameters. Model outputs were compared to pig serology data collected over a period of 2 years in the destination villages during a trial of T. solium control interventions, based on mass and spatially targeted human and pig treatments. RESULTS: Considering the uncertainties associated with empirical data, the model produced simulated pre-intervention pig seroprevalences that were successfully validated against data collected in 81% of destination villages. Furthermore, the model outputs were able to reproduce validated pig seroincidence values in 76% of destination villages when compared to the data obtained after the interventions. The results demonstrate that the CystiAgent model, when calibrated using a non-local approach, can be successfully transferred without requiring additional calibration. CONCLUSIONS: This feature allows the model to simulate both baseline pre-intervention transmission conditions and the outcomes of control interventions across villages that form geographically homogeneous regions, providing a basis for developing large-scale models representing T. solium transmission at a regional level.

Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness.

Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.

A prospective cohort study linking migration, climate, and malaria risk in the Peruvian Amazon.

Migration is an important risk factor for malaria transmission for malaria transmission, creating networks that connect Plasmodium between communities. This study aims to understand the timing of why people in the Peruvian Amazon migrated and how characteristics of these migrants are associated with malaria risk. A cohort of 2,202 participants was followed for three years (July 2006 - October 2009), with thrice-weekly active surveillance to record infection and recent travel, which included travel destination(s) and duration away. Migration occurred more frequently in the dry season, but the 7-day rolling mean (7DRM) streamflow was positively correlated with migration events (OR 1.25 (95% CI: 1.138, 1.368)). High-frequency and low-frequency migrant populations reported 9.7 (IRR 7.59 (95% CI:.381, 13.160)) and 4.1 (IRR 2.89 (95% CI: 1.636, 5.099)) times more P. vivax cases than those considered non-migrants and 30.7 (IRR 32.42 (95% CI: 7.977, 131.765)) and 7.4 (IRR 7.44 (95% CI: 1.783, 31.066)) times more P. falciparum cases, respectively. High-frequency migrants employed in manual labour within their community were at 2.45 (95% CI: 1.113, 5.416) times higher risk than non-employed low-frequency migrants. This study confirms the importance of migration for malaria risk as well as factors increasing risk among the migratory community, including, sex, occupation, and educational status.

In Utero Exposure to Metals and Birth Outcomes in an Artisanal and Small-Scale Gold Mining Birth Cohort in Madre de Dios, Peru.

BACKGROUND: Few birth cohorts in South America evaluate the joint effect of minerals and toxic metals on neonatal health. In Madre de Dios, Peru, mercury exposure is prevalent owing to artisanal gold mining, yet its effect on neonatal health is unknown. OBJECTIVES: We aimed to determine whether toxic metals are associated with lower birth weight and shorter gestational age independently of antenatal care and other maternal well-being factors. METHODS: Data are from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort, which enrolled pregnant women in Madre de Dios prior to their third trimester and obtained maternal and cord blood samples at birth. We use structural equation models (SEMs) to construct latent variables for the maternal metals environment (ME) and the fetal environment (FE) using concentrations of calcium, iron, selenium, zinc, magnesium, mercury, lead, and arsenic measured in maternal and cord blood, respectively. We then assessed the relationship between the latent variables ME and FE, toxic metals, prenatal visits, hypertension, and their effect on gestational age and birth weight. RESULTS: Among 198 mothers successfully enrolled and followed at birth, 29% had blood mercury levels that exceeded the U.S. Centers for Disease Control and Prevention threshold of 5.8µg/L and 2 mothers surpassed the former 5-µg/dL threshold for blood lead. The current threshold value is 3.5µg/dL. Minerals and toxic metals loaded onto ME and FE latent variables. ME was associated with FE (ß=0.24; 95% CI: 0.05, 0.45). FE was associated with longer gestational age (ß=2.31; 95% CI: -0.3, 4.51) and heavier birth weight. Mercury exposure was not directly associated with health outcomes. A 1% increase in maternal blood lead shortened gestational age by 0.05 d (ß=-0.75; 95% CI: -1.51, -0.13), which at the 5-µg/dL threshold resulted in a loss of 3.6 gestational days and 76.5g in birth weight for newborns. Prenatal care visits were associated with improved birth outcomes, with a doubling of visits from 6 to 12 associated with 5.5 more gestational days (95% CI: 1.6, 9.4) and 319g of birth weight (95% CI: 287.6, 350.7). DISCUSSION: Maternal lead, even at low exposures, was associated with shorter gestation and lower birth weight. Studies that focus only on harmful exposures or nutrition may mischaracterize the dynamic maternal ME and FE. SEMs provide a framework to evaluate these complex relationships during pregnancy and reduce overcontrolling that can occur with linear regression. https://doi.org/10.1289/EHP10557.

The impact of sustained malaria control in the Loreto region of Peru: a retrospective, observational, spatially-varying interrupted time series analysis of the PAMAFRO program.

Background: Although malaria control investments worldwide have resulted in dramatic declines in transmission since 2000, progress has stalled. In the Amazon, malaria resurgence has followed withdrawal of Global Fund support of the Project for Malaria Control in Andean Border Areas (PAMAFRO). We estimate intervention-specific and spatially-explicit effects of the PAMAFRO program on malaria incidence across the Loreto region of Peru, and consider the influence of the environmental risk factors in the presence of interventions. Methods: We conducted a retrospective, observational, spatial interrupted time series analysis of malaria incidence rates among people reporting to health posts across Loreto, Peru between the first epidemiological week of January 2001 and the last epidemiological week of December 2016. Model inference is at the smallest administrative unit (district), where the weekly number of diagnosed cases of Plasmodium vivax and Plasmodium falciparum were determined by microscopy. Census data provided population at risk. We include as covariates weekly estimates of minimum temperature and cumulative precipitation in each district, as well as spatially- and temporally-lagged malaria incidence rates. Environmental data were derived from a hydrometeorological model designed for the Amazon. We used Bayesian spatiotemporal modeling techniques to estimate the impact of the PAMAFRO program, variability in environmental effects, and the role of climate anomalies on transmission after PAMAFRO withdrawal. Findings: During the PAMAFRO program, incidence of P. vivax declined from 42.8 to 10.1 cases/1000 people/year. Incidence for P. falciparum declined from 14.3 to 2.5 cases/1000 people/year over this same period. The effects of PAMAFRO-supported interventions varied both by geography and species of malaria. Interventions were only effective in districts where interventions were also deployed in surrounding districts. Further, interventions diminished the effects of other prevailing demographic and environmental risk factors. Withdrawal of the program led to a resurgence in transmission. Increasing minimum temperatures and variability and intensity of rainfall events from 2011 onward and accompanying population displacements contributed to this resurgence. Interpretation: Malaria control programs must consider the climate and environmental scope of interventions to maximize effectiveness. They must also ensure financial sustainability to maintain local progress and commitment to malaria prevention and elimination efforts, as well as to offset the effects of environmental change that increase transmission risk. Funding: National Aeronautics and Space Administration, National Institutes of Health, Bill and Melinda Gates Foundation.

Government interventions and control policies to contain the first COVID-19 outbreak: An analysis of evidence.

BACKGROUND: The overarching aim of this study was to evaluate the effectiveness over time of government interventions and policy restrictions and the impact of determinants on spread and mortality during the first-wave of the COVID-19 pandemic, globally, regionally and by country-income level, up to 18 May 2020. METHODS: We created a global database merging World Health Organization daily case reports (from 218 countries/territories) with other socio-demographic and population health measures from 21 January to 18 May 2020. A four-level government policy interventions score (low to very high) was created based on the Oxford Stringency Index. RESULTS: Our results support the use of very high government interventions to suppress both COVID-19 spread and mortality effectively during wave one globally compared to other policy levels of control. Similar trends in virus propagation and mortality were observed in all country-income levels and specific regions. CONCLUSIONS: Rapid implementation of government interventions was needed to contain the first wave of the COVID-19 outbreak and to reduce COVID-19-related mortality.

Risk of lead exposure from wild game consumption from cross-sectional studies in Madre de Dios, Peru.

Background: Studies have shown elevated blood lead levels (BLL) in residents of remote communities in the Amazon, yet sources of lead exposure are not fully understood, such as lead ammunition consumed in wild game. Methods: Data was collected during two cross-sectional studies that enrolled 307 individuals in 26 communities. Regression models with community random effects were used to evaluate risk factors for BLLs, including diet, water source, smoking, sex, age, and indigenous status. The All-Ages Lead Model (AALM) from the Environmental Protection Agency (EPA) was used to estimate background and dose from wild game consumption. Findings: Indigenous status and wild game consumption were associated with increased BLLs. Indigenous participants had 2.52 µg/dL (95% CI: 1.95-3.24) higher BLLs compared to non-indigenous. Eating wild game was associated with a 1.41 µg/dL (95% CI: 1.20-1.70) increase in BLLs. Two or more portions per serving were associated with increased BLLs of 1.66 µg/dL (95% CI: 1.10-2.57), compared to smaller servings. Using the AALM, we estimate background lead exposures to be 20 µg/day with consumption of wild game contributing 500 µg/meal. Lastly, we found a strong association between BLLs and mercury exposure. Interpretation: Consumption of wild game hunted with lead ammunition may pose a common source of lead exposure in the Amazon. Communities that rely on wild game and wild fish may face a dual burden of exposure to lead and mercury, respectively.

Non-local validated parametrization of an agent-based model of local-scale Taenia solium transmission in North-West Peru.

The pork tapeworm, Taenia solium, is the cause of a preventable zoonotic disease, cysticercosis, affecting both pigs and humans. Continued endemic transmission of T. solium is a major contributor of epilepsy and other neurologic morbidity, and the source of important economic losses, in many rural areas of developing countries. Simulation modelling can play an important role in aiding the design and evaluation of strategies to control or even eliminate transmission of the parasite. In this paper, we present a new agent based model of local-scale T. solium transmission and a new, non-local, approach to the model calibration to fit model outputs to observed human taeniasis and pig cysticercosis prevalence simultaneously for several endemic villages. The model fully describes all relevant aspects of T. solium transmission, including the processes of pig and human infection, the spatial distribution of human and pig populations, the production of pork for human consumption, and the movement of humans and pigs in and out in several endemic villages of the northwest of Peru. Despite the high level of uncertainty associated with the empirical measurements of epidemiological data associated with T. solium, the non-local calibrated model parametrization reproduces the observed prevalences with an acceptable precision. It does so not only for the villages used to calibrate the model, but also for villages not included in the calibration process. This important finding demonstrates that the model, including its calibrated parametrization, can be successfully transferred within an endemic region. This will enable future studies to inform the design and optimization of T. solium control interventions in villages where the calibration may be prevented by the limited amount of empirical data, expanding the possible applications to a wider range of settings compared to previous models.

Adult Exposures to Toxic Trace Elements as Measured in Nails along the Interoceanic Highway in the Peruvian Amazon.

Deforestation, artisanal and small-scale gold mining (ASGM), and the rapid development related to highway expansion cause opportunities for toxic trace element exposure in the Amazon region of Madre de Dios (MDD), Peru, one of the most biologically diverse places in the world. The objective of this study was to assess the exposure to arsenic, cadmium, lead, and mercury among adults in Madre de Dios. In total, 418 adult (18+ years) participants in the Investigacion de Migracion, Ambiente, y Salud (IMAS) (Migration, Environment, and Health Study) participated in this study. Consent, survey data, and biospecimens were collected between August and November 2014. Nail elements were measured by inductively coupled plasma sector field mass spectrometry. Differences by selected individual and household characteristics and local land uses were tested using one-way ANOVAs and linear mixed models. Adults in ASGM-affected areas had higher nail arsenic and nail cadmium than their non-ASGM counterparts. Higher household fish consumption was positively associated with nail mercury and nail lead. The results indicate that adult exposure to arsenic, cadmium, lead, and mercury is heterogeneous across Madre de Dios, and the exposures related to ASGM communities and fish consumption suggest that exposures from artisanal and small-scale mining are environmentally widespread. Further investigation is warranted to ascertain potential health impacts.

CystiHuman: A model of human neurocysticercosis.

INTRODUCTION: The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. METHODS: This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. RESULTS AND DISCUSSION: Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence.

Amazon forests capture high levels of atmospheric mercury pollution from artisanal gold mining.

Mercury emissions from artisanal and small-scale gold mining throughout the Global South exceed coal combustion as the largest global source of mercury. We examined mercury deposition and storage in an area of the Peruvian Amazon heavily impacted by artisanal gold mining. Intact forests in the Peruvian Amazon near gold mining receive extremely high inputs of mercury and experience elevated total mercury and methylmercury in the atmosphere, canopy foliage, and soils. Here we show for the first time that an intact forest canopy near artisanal gold mining intercepts large amounts of particulate and gaseous mercury, at a rate proportional with total leaf area. We document substantial mercury accumulation in soils, biomass, and resident songbirds in some of the Amazon's most protected and biodiverse areas, raising important questions about how mercury pollution may constrain modern and future conservation efforts in these tropical ecosystems.

Global, regional, and national burden of aortic aneurysm, 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.

AIMS: This study aimed at evaluating the age, sex, and country-income patterns in aortic aneurysm disease burden, analysing trends in mortality and years of life lost (YLLs), as well as their causal drivers and risk factors, using the 2017 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2017). METHODS AND RESULTS: We described the temporal, global, and regional (195 countries) patterns of aortic aneurysm (thoracic and abdominal) mortality, YLLs, their drivers [sociodemographic index (SDI), healthcare access and quality index (HAQ index)] and risk factors using the GBD 1990-2017. Correlation and mixed multilevel modelling between aortic aneurysm mortality, YLLs, HAQ index and other variables were applied. From 1990 to 2017, a global declining trend in age-standardized aortic aneurysm mortality was found [2.88 deaths/100 000 (95% uncertainty intervals, UI 2.79 to 3.03) in 1990 and 2.19 deaths/100 000 (95% UI 2.09 to 2.28) in 2017]. Among high-income countries (HICs) a consistent declining Spearman's correlation between age-standardised aortic aneurysm mortality, SDI (HICs; 1990 rho: 0.57, P ≤ 0.001; 2017 rho: 0.41, P = 0.001) and HAQ index was observed (HICs; 1990 rho: 0.50, P <0.001; 2016 rho: 0.35, P = 0.006); in comparison with low- and middle-income countries where correlation trends were weak and mixed. At a global level, higher HAQ index was related with lower aortic aneurysm mortality and YLLs [mortality, coef: -0.05, 95% confidence interval (CI): -0.06, -0.04; YLLs, coef: -0.94, 95% CI: -1.17, -0.71]. CONCLUSIONS: Age-standardized aortic aneurysm mortality declined globally between 1990 and 2017. Globally, age-standardized aortic aneurysm mortality and YLLs were related to changes in SDI and HAQ index levels, while country-level income-related variations were also observed.

Heterogeneity in the Effectiveness of Non-pharmaceutical Interventions During the First SARS-CoV2 Wave in the United States.

Background: Attempts to quantify effect sizes of non-pharmaceutical interventions (NPI) to control COVID-19 in the US have not accounted for heterogeneity in social or environmental factors that may influence NPI effectiveness. This study quantifies national and sub-national effect sizes of NPIs during the early months of the pandemic in the US. Methods: Daily county-level COVID-19 cases and deaths during the first wave (January 2020 through phased removal of interventions) were obtained. County-level cases, doubling times, and death rates were compared to four increasingly restrictive NPI levels. Socio-demographic, climate and mobility factors were analyzed to explain and evaluate NPI heterogeneity, with mobility used to approximate NPI compliance. Analyses were conducted separately for the US and for each Census regions (Pacific, Mountain, east/West North Central, East/West South Central, South Atlantic, Middle Atlantic and New England). A stepped-wedge cluster-randomized trial analysis was used, leveraging the phased implementation of policies. Results: Aggressive (level 4) NPIs were associated with slower COVID-19 propagation, particularly in high compliance counties. Longer duration of level 4 NPIs was associated with lower case rates (log beta -0.028, 95% CI -0.04 to -0.02) and longer doubling times (log beta 0.02, 95% CI 0.01-0.03). Effects varied by Census region, for example, level 4 effects on doubling time in Pacific states were opposite to those in Middle Atlantic and New England states. NPI heterogeneity can be explained by differential timing of policy initiation and by variable socio-demographic county characteristics that predict compliance, particularly poverty and racial/ethnic population. Climate exhibits relatively consistent relationships across Census regions, for example, higher minimum temperature and specific humidity were associated with lower doubling times and higher death rates for this period of analysis in South Central, South Atlantic, Middle Atlantic, and New England states. Conclusion and Relevance: Heterogeneity exists in both the effectiveness of NPIs across US Census regions and policy compliance. This county-level variability indicates that control strategies are best designed at community-levels where policies can be tuned based on knowledge of local disparities and compliance with public health ordinances.

Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru.

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 µg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.

Validation of a spatial agent-based model for Taenia solium transmission ("CystiAgent") against a large prospective trial of control strategies in northern Peru.

BACKGROUND: The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. METHODS/PRINCIPAL FINDINGS: We validated CystiAgent against results from the Ring Strategy Trial (RST)-a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. CONCLUSIONS/SIGNIFICANCE: The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment.

Intensity and frequency of extreme novel epidemics.

Observational knowledge of the epidemic intensity, defined as the number of deaths divided by global population and epidemic duration, and of the rate of emergence of infectious disease outbreaks is necessary to test theory and models and to inform public health risk assessment by quantifying the probability of extreme pandemics such as COVID-19. Despite its significance, assembling and analyzing a comprehensive global historical record spanning a variety of diseases remains an unexplored task. A global dataset of historical epidemics from 1600 to present is here compiled and examined using novel statistical methods to estimate the yearly probability of occurrence of extreme epidemics. Historical observations covering four orders of magnitude of epidemic intensity follow a common probability distribution with a slowly decaying power-law tail (generalized Pareto distribution, asymptotic exponent = -0.71). The yearly number of epidemics varies ninefold and shows systematic trends. Yearly occurrence probabilities of extreme epidemics, Py, vary widely: Py of an event with the intensity of the "Spanish influenza" (1918 to 1920) varies between 0.27 and 1.9% from 1600 to present, while its mean recurrence time today is 400 y (95% CI: 332 to 489 y). The slow decay of probability with epidemic intensity implies that extreme epidemics are relatively likely, a property previously undetected due to short observational records and stationary analysis methods. Using recent estimates of the rate of increase in disease emergence from zoonotic reservoirs associated with environmental change, we estimate that the yearly probability of occurrence of extreme epidemics can increase up to threefold in the coming decades.