Human Soil-transmitted Helminth Research Articles

Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy

Control of soil-transmitted helminths relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human soil-transmitted helminths, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. Here we predict the population dynamics of human soil-transmitted helminth infections and drug resistance during 20 years of regular preventive chemotherapy, using an individual-based model. With the current preventive chemotherapy strategy of mainly targeting children in schools, drug resistance may evolve in soil-transmitted helminths within a decade. More intense preventive chemotherapy strategies increase the prospects of soil-transmitted helminths elimination, but also increase the speed at which drug efficacy declines, especially when implementing community-based preventive chemotherapy (population-wide deworming). If during the last decade, preventive chemotherapy against soil-transmitted helminths has led to resistance, we may not have detected it as drug efficacy has not been structurally monitored, or incorrectly so. These findings highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.

Anthelmintic resistance in soil-transmitted helminths: One-Health considerations

The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals provides comprehensive awareness and potential solutions for issues relating to the health of people, animals, and the environment. This approach has increasingly gained appeal as the standard strategy for tackling emerging infectious diseases, most of which are zoonoses. Treatment with anthelmintics (AHs) without a doubt minimizes the severe consequences of soil-transmitted helminths (STHs); however, evidence of anthelmintic resistance (AR) development to different helminths of practically every animal species and the distinct groups of AHs is overwhelming globally. In this regard, the correlation between the application of anthelmintic drugs in both human and animal populations and the consequent development of anthelmintic resistance in STHs within the context of a One-Health framework is explored. This review provides an overview of the major human and animal STHs, treatment of the STHs, AR development and drug-related factors contributing towards AR, One-Health and STHs, and an outline of some One-Health strategies that may be used in combating AR.

Near-infrared spectroscopy and machine learning algorithms for rapid and non-invasive detection of Trichuris.

Trichuris trichiura (whipworm) is one of the most prevalent soil transmitted helminths (STH) affecting 604-795 million people worldwide. Diagnostic tools that are affordable and rapid are required for detecting STH. Here, we assessed the performance of the near-infrared spectroscopy (NIRS) technique coupled with machine learning algorithms to detect Trichuris muris in faecal, blood, serum samples and non-invasively through the skin of mice. We orally infected 10 mice with 30 T. muris eggs (low dose group), 10 mice with 200 eggs (high dose group) and 10 mice were used as the control group. Using the NIRS technique, we scanned faecal, serum, whole blood samples and mice non-invasively through their skin over a period of 6 weeks post infection. Using artificial neural networks (ANN) and spectra of faecal, serum, blood and non-invasive scans from one experiment, we developed 4 algorithms to differentiate infected from uninfected mice. These models were validated on mice from a second independent experiment. NIRS and ANN differentiated mice into the three groups as early as 2 weeks post infection regardless of the sample used. These results correlated with those from concomitant serological and parasitological investigations. To our knowledge, this is the first study to demonstrate the potential of NIRS as a diagnostic tool for human STH infections. The technique could be further developed for large scale surveillance of soil transmitted helminths in human populations.

Zoonotic helminths of dogs and risk factors associated with polyparasitism in Grenada, West Indies.

Canine soil-transmitted helminths (STHs) cause important zoonoses in the tropics, with varying degrees of intensity of infection in humans and dogs. This study aimed to investigate the prevalence and associated risk factors for STHs in community dogs residing in Grenada, West Indies. In May 2021, 232 canine fecal samples were examined for zoonotic helminths by microscopy (following flotation), and genomic DNA from a subset of 211 of these samples were subjected to multiplex qPCR for the detection and specific identification of hookworms, Toxocara spp. and Strongyloides. Microscopic examination revealed that 46.5% (108/232, 95% CI 40–52.9), 9% (21/232, 95% CI 5.35–12.7) and 5.2% (12/232, 95% CI 2.3–8) of the samples contained eggs of Ancylostoma spp., Toxocara spp. and Trichuris vulpis, respectively. Multiplex qPCR revealed that, 42.2% (89/211, 95% CI 35.5–48.8) were positive for at least 1 zoonotic parasite. Of these, 40.8% (86/211, 95% CI 34.1–47.3) of samples tested positive for Ancylostoma spp., 36% (76/211, 95% CI 29.5–42.9) were positive for A. caninum, 13.3% (28/211, 95% CI 9–18.6) for A. ceylanicum, 5.7% for T. canis (12/211, 95% CI 2.97–8.81) and 1% (2/211, 95% CI 0–2.26) for Strongyloides spp. (identified as S. stercoralis and S. papillosus by conventional PCR-based Sanger sequencing). Using a multiple logistic regression model, a low body score and free-roaming behaviour were significant predictors of test-positivity for these parasitic nematodes in dogs (P < 0.05). Further studies of zoonotic STHs in humans should help elucidate the public health relevance of these parasites in Grenada.

Community-wide mass drug administration for soil-transmitted helminths – risk of drug resistance and mitigation strategies

Mass drug administration programs for the control of soil-transmitted helminths (STH) in humans most commonly utilize a single class of drugs; the benzimidazoles. Most such programs focus on the treatment of pre-school and school aged children attending schools, although there is increasing interest in the potential utility of community-wide MDA to reduce infection intensity within communities and possibly to interrupt STH transmission. In animals, mass treatment with benzimidazoles leads to the rapid selection of parasites containing resistance-encoding single nucleotide polymorphisms (SNP) and the potential emergence of resistance in parasite species that infect humans is of major potential public health concern. As programs scale up delivery of anthelmintics and consider expanding treated populations, monitoring of drug efficacy and the potential emergence of anthelmintic resistance with sensitive diagnostic tools is critical to ensure the continued success of STH control programs. In particular, as programs consider the adoption of community-wide deworming, there is concern that such a strategy may increase the risk of drug resistance by limiting the number of untreated individuals which serve as a refugia of unexposed worm populations. We review the literature for evidence of drug resistance in human STH infections and explore risks and mitigation strategies for emergence of drug resistance in the context of community-wide deworming.

A systematic review and meta-analysis of human and zoonotic dog soil-transmitted helminth infections in Australian Indigenous communities.

Soil-transmitted helminths (STH) infect 1.5 billion people and countless animals worldwide. In Australian Indigenous communities, STH infections have largely remained endemic despite control efforts, suggesting reservoirs of infection may exist. Dogs fulfil various important cultural, social and occupational roles in Australian Indigenous communities and are populous in these settings. Dogs may also harbour zoonotic STHs capable of producing morbidity and mortality in dogs and humans. This review provides an overview of human and zoonotic STH infections, identifies the Australian Indigenous locations affected and the parasite species and hosts involved. The meta-analysis provides estimates of individual study and pooled true prevalence of STH infections in Australian Indigenous communities and identifies knowledge gaps for further research on zoonotic or anthroponotic potential. A systematic literature search identified 45 eligible studies documenting the presence of Strongyloides stercoralis, Trichuris trichiura, Ancylostoma caninum, Ancylostoma duodenale, Ancylostoma ceylanicum, undifferentiated hookworm, and Ascaris lumbricoides. Of these studies, 26 were also eligible for inclusion in meta-analysis to establish true prevalence in the light of imperfect diagnostic test sensitivity and specificity by Rogan-Gladen and Bayesian methods. These studies revealed pooled true prevalence estimates of 18.9% (95% CI 15.8-22.1) for human and canine S. stercoralis infections and 77.3% (95% CI 63.7-91.0) for canine A. caninum infections indicating continued endemicity, but considerably more heterogenous pooled estimates for canine A. ceylanicum infections, and A. duodenale, undifferentiated hookworm and T. trichiura in humans. This review suggests that the prevalence of STHs in Australian Indigenous communities has likely been underestimated, principally based on imperfect diagnostic tests. Potential misclassification of hookworm species in humans and dogs due to outdated methodology, also obscures this picture. High-quality contemporary studies are required to establish current true prevalence of parasite species in all relevant hosts to guide future policy development and control decisions under a culturally sound One Health framework.

Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique.

ABSTRACT.Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the β-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhiça district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the β-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance.

Interactions of Caenorhabditis elegans β-tubulins with the microtubule inhibitor and anthelmintic drug albendazole.

Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad-spectrum anthelmintic drug class used for their control. Benzimidazole resistance is now widespread in many species of parasitic nematodes in livestock globally and an emerging concern for the sustainable control of human soil-transmitted helminths. β-tubulin is the major benzimidazole target, although other genes may influence resistance. Among the 6 Caenorhabditis elegans β-tubulin genes, loss of ben-1 causes resistance without other apparent defects. Here, we explored the genetics of C. elegans β-tubulin genes in relation to the response to the benzimidazole derivative albendazole. The most highly expressed β-tubulin isotypes, encoded by tbb-1 and tbb-2, were known to be redundant with each other for viability, and their products are predicted not to bind benzimidazoles. We found that tbb-2 mutants, and to a lesser extent tbb-1 mutants, were hypersensitive to albendazole. The double mutant tbb-2 ben-1 is uncoordinated and short, resembling the wild type exposed to albendazole, but the tbb-1 ben-1 double mutant did not show the same phenotypes. These results suggest that tbb-2 is a modifier of albendazole sensitivity. To better understand how BEN-1 mutates to cause benzimidazole resistance, we isolated mutants resistant to albendazole and found that 15 of 16 mutations occurred in the ben-1 coding region. Mutations ranged from likely nulls to hypomorphs, and several corresponded to residues that cause resistance in other organisms. Null alleles of ben-1 are albendazole-resistant and BEN-1 shows high sequence identity with tubulins from other organisms, suggesting that many amino acid changes could cause resistance. However, our results suggest that missense mutations conferring resistance are not evenly distributed across all possible conserved sites. Independent of their roles in benzimidazole resistance, tbb-1 and tbb-2 may have specialized functions as null mutants of tbb-1 or tbb-2 were cold or heat sensitive, respectively.

Detection of six soil-transmitted helminths in human stool by qPCR- a systematic workflow.

Soil-transmitted helminths (STH) infect up to one-quarter of the global population, with a significant associated disease burden. The main human STH are: Ancylostoma spp. and Necator americanus (hookworms); Ascaris lumbricoides, Trichuris trichiura, and Strongyloides stercoralis. The aim of this study was to establish a scalable system for stool STH multiplex quantitative real-time polymerase chain reactions (qPCR). Stool samples collected in Fiji and preserved in potassium dichromate were transferred to Melbourne at ambient temperature. Samples were washed to remove potassium dichromate and DNA was extracted with the Mini-Beadbeater-24 and a column-based kit. A SYBR green qPCR to detect the vertebrate mitochondrial gene was used as a DNA extraction control. Samples were tested using a probe-based multiplex qPCR targeting A. lumbricoides, T. trichiura and S. stercoralis, and in a second multiplex reaction to detect hookworms to the species level (A. duodenale, A. ceylanicum, N. americanus). An internal amplification control in both multiplex assays was included to prevent false-negative results due to PCR inhibitors. Samples were homogenised for a single cycle of 40 seconds to release STH DNA and washed stool was stored for up to 15 weeks at -30°C without compromising DNA. Our multiplex qPCR detected multiple species of STH without reduced sensitivity compared to singleplex. qPCR data from 40 stools was validated against STH-positive stools determined by microscopy. We have developed and validated an efficient and staged system for detecting six clinically important STH affecting humans that could be easily implemented without advanced automation in any qPCR-capable laboratory.

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Epidemiology of soil-transmitted helminth infections in Semarang, Central Java, Indonesia.

Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2–12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2–93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02–1.29], p = 0.02). Adults in age groups 51–60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84–4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30–6.26], p<0.001, respectively) compared to 6–12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17–4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77–2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27–1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10–2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58–0.91], p = 0.01) were all household factors significantly associated with an increased odds of infection. Infection with STH was not significantly associated with the gastrointestinal illness (p>0.05), BMI or Hb levels; however, one third of all 2–12 year olds surveyed were found to be anaemic (i.e. Hb concentrations below 110g/l or 115g/l for children under 5 and 5 years or older, respectively), with a greater proportion of school-age children at risk. Knowledge and behaviour related to hygiene and gastrointestinal diseases varied widely and were generally not associated with STH infection. The study revealed that STH infection remains endemic in Central Java despite ongoing deworming programs. Current control efforts would benefit from being re-evaluated to determine a more effective way forward.

The Control of Zoonotic Soil-Transmitted Helminthoses Using Saprophytic Fungi.

Soil-transmitted helminths (STHs) are parasites transmitted through contact with soil contaminated with their infective eggs/larvae. People are infected by exposure to human-specific species or animal species (zoonotic agents). Fecal samples containing eggs of Ascaris suum or Lemurostrongylus sp. were sprayed with spores of the soil saprophytic filamentous fungi Clonostachys rosea (CR) and Trichoderma atrobrunneum (TA). The antagonistic effect was assessed by estimating the viability of eggs and their developmental rate. Compared to the controls (unexposed to fungi), the viability of the eggs of A. suum was halved in CR and decreased by two thirds in TA, while the viability of the eggs of Lemurostrongylus sp. was reduced by one quarter and one third in CR and TA treatments, respectively. The Soil Contamination Index (SCI), defined as the viable eggs that attained the infective stage, reached the highest percentages for A. suum in the controls after four weeks (66%), with 21% in CL and 11% in TA. For Lemurostrongylus sp., the values were 80%, 49%, and 41% for control, CR and TA treatments, respectively. We concluded that spreading spores of C. rosea or T. atrobrunneum directly onto the feces of animal species represents a sustainable approach under a One Health context to potentially reduce the risk of zoonotic STHs in humans.

Challenges and opportunities for the adoption of molecular diagnostics for anthelmintic resistance

Anthelmintic resistance is a significant threat to livestock production systems worldwide and is emerging as an important issue in companion animal parasite management. It is also an emerging concern for the control of human soil-transmitted helminths and filaria. An important aspect of managing anthelmintic resistance is the ability to utilise diagnostic tests to detect its emergence at an early stage. In host-parasite systems where resistance is already widespread, diagnostics have a potentially important role in determining those drugs that remain the most effective. The development of molecular diagnostics for anthelmintic resistance is one focus of the Consortium for Anthelmintic Resistance and Susceptibility (CARS) group. The present paper reflects discussions of this issue that occurred at the most recent meeting of the group in Wisconsin, USA, in July 2019. We compare molecular resistance diagnostics with in vivo and in vitro phenotypic methods, and highlight the advantages and disadvantages of each. We assess whether our knowledge on the identity of molecular markers for resistance towards the different drug classes is sufficient to provide some expectation that molecular tests for field use may be available in the short-to-medium term. We describe some practical aspects of such tests and how our current capabilities compare to the requirements of an ‘ideal’ test. Finally, we describe examples of drug class/parasite species interactions that provide the best opportunity for commercial use of molecular tests in the near future. We argue that while such prototype tests may not satisfy the requirements of an ‘ideal’ test, their potential to provide significant advances over currently-used phenotypic methods warrants their development as field diagnostics.

Immunopathology and modulation induced by hookworms: From understanding to intervention.

Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million disability-adjusted life years lost annually. As with many other neglected tropical diseases, no international surveillance mechanisms that show accurate data on the prevalence of hookworm infection are in place, thus hindering strategies to control parasite transmission. In this review, we unravel the current knowledge in immunopathology and immunoregulation of hookworm infection and present discoveries in drug therapies based on the capability of hookworms to regulate inflammation to treat allergic, inflammatory and metabolic diseases. Additionally, we highlight potential vaccine development and treatments and propose avenues for further inquiry.

Zoonotic Ancylostomiasis: An Update of a Continually Neglected Zoonosis.

Hookworm infections are classified as the most impactful of the human soil-transmitted helminth (STH) infections, causing a disease burden of ∼4 million disability-adjusted life years, with a global prevalence of 406-480 million infections. Until a decade ago, epidemiological surveys largely assumed Necator americanus and Ancylostoma duodenale as the relevant human hookworm species implicated as contributing to iron-deficiency anemia. This assumption was based on the indistinguishable morphology of the Ancylostoma spp. eggs in stool and the absence of awareness of a third zoonotic hookworm species, Ancylostoma ceylanicum. The expanded use of molecular diagnostic assays for differentiating hookworm species infections during STH surveys has now implicated A. ceylanicum, a predominant hookworm of dogs in Asia, as the second most common hookworm species infecting humans in Southeast Asia and the Pacific. Despite this, with the exception of sporadic case reports, there is a paucity of data available on the impact of this emerging zoonosis on human health at a population level. This situation also challenges the current paradigm, necessitating a One Health approach to hookworm control in populations in which this zoonosis is endemic. Here, we have summarized the available research studies and case reports on human A. ceylanicum infections in Southeast Asia and the Pacific after 2013 using a systematic review approach. We summarized eight research articles and five clinical case studies, highlighting the importance of future in-depth investigation of zoonotic A. ceylanicum infections using sensitive and cost-effective diagnostic tools.

Piloting a surveillance system to monitor the global patterns of drug efficacy and the emergence of anthelmintic resistance in soil-transmitted helminth control programs: a Starworms study protocol

To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the β-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH.

Piloting a surveillance system to monitor the global patterns of drug efficacy and the emergence of anthelmintic resistance in soil-transmitted helminth control programs: a Starworms study protocol.

To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the β-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH.

Toxocariasis: A neglected infection for the Anthropocene epoch.

While ascariasis, trichuriasis, and hookworm infection dominate global efforts to control human soil-transmitted helminth infections, a picture is unfolding to suggest that toxocariasis is now a fourth and perhaps equally important parasitic disease. Toxocara eggs are widespread in the environment and practically ubiquitous in the soils of many subtropical and tropical regions of Asia, Africa, and the Americas. Human zoonotic infection is also highly prevalent in these areas, based on serologic studies to detect anti-Toxocara antibodies. The relevance of these findings to human and animal disease burden estimates is still largely unknown, but some studies implicate exposure to Toxocara eggs and larvae to both pulmonary disease leading to asthma, and neurologic disease resulting in epilepsy and cognitive delays. On that basis, human toxocariasis may emerge as one of the most important neglected parasitic infections of humans. With anticipated global warming and urbanization associated with our modern human-transformed geological epoch, known as the Anthropocene, it is likely that toxocariasis will become a dominant infection and one widely prevalent in our future and projected mega-cities.

An integrated health delivery platform, targeting soil-transmitted helminths (STH) and canine mediated human rabies, results in cost savings and increased breadth of treatment for STH in remote communities in Tanzania

BackgroundAchieving the Sustainable Development Goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires innovative control strategies.This proof-of-concept study examined the effectiveness of integrating control programs for two NTDs: mass drug administration (MDA) for soil-transmitted helminths in humans and mass dog rabies vaccination (MDRV).MethodsThe study was carried out in 24 Tanzanian villages. The primary goal was to demonstrate the feasibility of integrating community-wide MDA for STH and MDRV for rabies. The objectives were to investigate the popularity, participation and cost and time savings of integrated delivery, and to investigate the reach of the MDA with respect to primary school-aged children and other community members. To implement, we randomly allocated villages for delivery of MDA and MDRV (Arm A), MDA only (Arm B) or MDRV only (Arm C).ResultsCommunity support for the integrated delivery was strong (e.g. 85% of focus group discussions concluded that it would result in people getting “two for one” health treatments). A high proportion of households participated in the integrated Arm A events (81.7% MDA, 80.4% MDRV), and these proportions were similar to those in Arms B and C. These findings suggest that coverage might not be reduced when interventions are integrated. Moreover, in addition to time savings, integrated delivery resulted in a 33% lower cost per deworming dose and a 16% lower cost per rabies vaccination.The median percentage of enrolled primary school children treated by this study was 76%. However, because 37% of the primary school aged children that received deworming treatment were not enrolled in school, we hypothesize that the employed strategy could reach more school-aged children than would be reached through a solely school-based delivery strategy.ConclusionsIntegrated delivery platforms for health interventions can be feasible, popular, cost and time saving. The insights gained could be applicable in areas of sub-Saharan Africa that are remote or underserved by health services. These results indicate the utility of integrated One Health delivery platforms and suggest an important role in the global campaign to reduce the burden of NTDs, especially in hard-to-reach communities.Trial registrationclinicaltrials.gov NCT03667079, retrospectively registered 11th September 2018.

Metabolomic profiling of the excretory-secretory products of hookworm and whipworm.

Soil-transmitted helminths infect billions of people, livestock and companion animals worldwide, and chronic infections with these nematodes represent a major health burden in many developing countries. On the other hand, complete elimination of parasitic helminths and other infectious pathogens has been implicated with rising rates of autoimmune and allergic disorders in developed countries. Given the enormous health impact of these parasites, it is surprising how little is known about the non-protein small metabolites of the excretory-secretory products (ESP), including their composition and pharmacological properties. We sought proof-of-concept that Nippostrongylus brasiliensis and Trichuris muris, rodent models of two of the most important human soil-transmitted helminths, secrete small metabolites and that some of these metabolites may have specific pharmacological functions. N. brasiliensis and T. muris ESP were collected from adult worms and filtered using a 10kDa cut-off membrane to produce excretory-secretory metabolites (ESM). The ESM were analysed using targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry for polar and non-polar small metabolites. ESM from both N. brasiliensis and T. muris contained small molecules. A total of 54 small molecules (38 polar metabolites and 16 fatty acids) were identified, 36 known polar metabolites from N. brasiliensis and 35 from T. muris. A literature review of the identified compounds revealed that 17 of them have various demonstrated pharmacological activities. N. brasiliensis and T. muris secrete polar and non-polar small molecules with as many as 17 metabolites known to exhibit various pharmacological activities.