A One Health Approach to Defining Animal and Human Helminth Exposure Risks in a Tribal Village in Southern India.

The high burden of soil-transmitted helminth infections has been studied in India; however, little data exist on zoonotic helminths, and on animal-associated exposure to soil-transmitted helminths. Our study took place in the Jawadhu Hills, which is a tribal region in Tamil Nadu, India. Using a One Health approach, we included animal and environmental samples and human risk factors to answer questions about the associations among infected household soil, domestic animals, and human risk factors. Helminth eggs were identified by microscopy in animal and soil samples, and a survey about risk factors was administered to the head of the household. Contact with animals was reported in 71% of households. High levels of helminth infections were found across domestic animal species, especially in goats, chickens, and dogs. Helminth eggs were recorded in 44% of household soil (n = 43/97) and separately in 88% of soil near a water source (n = 28/32). Animal contact was associated with 4.05 higher odds of having helminth eggs in the household soil (P = 0.01), and also having a water source at the household was associated with a 0.33 lower odds of having helminth eggs in the household soil (P = 0.04). Soil moisture was a mediator of this association with a significant indirect effect (P < 0.001). The proportion mediated was 0.50. While our work does not examine transmission, these results support consideration of animal-associated exposure to STH and potentially zoonotic helminths in future interventions to reduce helminth burden. Our study provides support for further investigation of the effects of animals and animal fecal matter on human health

Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India.

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project-a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia-allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0-17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3-37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3-0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4-0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167

Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Objective: To explore the combinatorial effect of epigallocatechin-3-gallate (EGCG) and calorie restriction on activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor involved in the antioxidant defense system of aged rats. Methods: Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days. The initial body weight of aged rats was recorded, and the final body weight was measured at the end of the experimental period. Serum lipid and lipoprotein status, oxidative stress markers such as free radicals and malondialdehyde levels, and reduced glutathione were assessed. In addition, RT-PCR and Western blotting analyses were performed. Results: Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status, improving the levels of serum lipid and lipoproteins, upregulating Nrf2 and Bcl2, and downregulating Keap1, cullin3, Bax and cytochrome c in aged rats. Conclusions: Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats. This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging, thereby reducing the risk for age-associated degenerative diseases

Forecasting the effectiveness of the DeWorm3 trial in interrupting the transmission of soil-transmitted helminths in three study sites in Benin, India and Malawi

Funding Information: The DeWorm3 study is funded through a grant to the Natural History Museum, London, from the Bill and Melinda Gates Foundation (OPP1129535). This award is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. Publisher Copyright: © 2021, The Author(s).BACKGROUND: The DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this article, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%. METHODS: Our approach is first to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level, which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of [Formula: see text] prevalence at a point 24 months post-cessation of MDA. RESULTS: Simulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study end point. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but in Benin the heterogeneity between clusters prevents the arm prevalence from being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving complete elimination in an intervention arm, yielding a post-study scenario with widespread elimination but a few 'hot spot' areas of persisting STH transmission. CONCLUSIONS: Our results suggest that geographical heterogeneities in transmission intensity and worm aggregation have a large impact on the effect of MDA. It is important to accurately assess cluster-level, or even smaller scale, heterogeneities in factors which influence transmission and aggregation for a clearer perspective on projecting the outcomes of MDA control of STH and other neglected tropical diseases.Peer reviewe

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020