Helminth Infections Research Articles

Management of paediatric soil-transmitted helminthiasis in a non-endemic area: experience in a reference international health unit.

Soil-transmitted helminth (STH) infections inflict disability worldwide, especially in the poorest communities. Current therapeutic options against STHs show limited efficacy, particularly against Trichuris trichiura. The empirical management of patients coming from high-prevalence areas has been suggested for non-endemic areas. This study aimed to describe the management of STH infections in a non-endemic setting using an individualised approach. We performed a retrospective, descriptive study of all patients up to 16years of age with STH infections attended at an international health unit in a non-endemic area (2014-2018), including all T. trichiura, Necator americanus, Ancylostoma duodenale, and Ascaris lumbricoides infections diagnosed using a formol-ether concentration technique and direct visualisation. Patients were treated according to current international guidelines. Sixty-one stool samples from 48 patients testing positive for STHs were collected, with 96% (46/48) reporting a previous long-term stay in endemic areas. Cure rates with 3-day benzimidazole regimens were 72% for T. trichiura, 40% for hookworms, and 83% for A. lumbricoides. The results were not influenced by any reinfection risk due to the study being performed in a non-endemic area. Patients coming from STH-endemic areas should be evaluated with appropriate diagnostic tools and followed up until cure control results. Cure rates in our cohort were moderate to low, similar to those published in studies in endemic areas. The efficacy of current treatment options is insufficient to recommend a specific empirical approach in high-income countries' healthcare systems.

The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.

The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.

Enrichment of microscopic photographs by utilizing CNN regarding soil-transmitted helminths identification

Soil-transmitted helminth (STH) infection remains a significant global health challenge, affecting millions of people, particularly in developing countries. A convolutional neural network (CNN) approach to optimize the detection of STH infections in microscopic images. The study aims to assess the effectiveness of the CNN model in identifying and classifying STH worm eggs accurately. The research employs MATLAB as the primary tool for conducting experiments and validation tests. By implementing image preprocessing techniques to enhance image quality and applying precise segmentation methods, the CNN model is trained on a dataset of microscopic images to learn and classify STH infections effectively. The validation test results demonstrate that the CNN model achieved a high accuracy rate of 92.31% in classifying STH infections. This accuracy surpasses traditional methods, which are time-consuming and susceptible to human errors. This study underscores the importance of integrating artificial intelligence, particularly CNN, into the healthcare domain to support detecting and diagnosing diseases requiring specialized expertise, such as STH infections. The findings of this research can serve as a valuable reference for researchers, medical practitioners, and data scientists in leveraging artificial intelligence to enhance the quality of healthcare services, leading to positive impacts on society worldwide.

Epigenetic Investigation Related to Gastrointestinal Helminth Resistance and Performance in Cattle

Abstract The objective was to characterize a herd of 73 Nellore heifers, identifying resistant, resilient, and susceptible animals to gastrointestinal helminths, relating the global methylation of the DNA of these animals with the degree of helminthiasis and factors that interfere with performance. Individual count of eggs per gram of feces (EPG), fecal culture for gender identification, weighing and blood sampling were carried out to determine PCV, STP, EOS, IgG, followed by DNA extraction and methylation analysis. The results were: 47% resistant animals, 34% resilient, and 19% susceptible to gastrointestinal helminth infections, with EPG counts of 53, 216, and 841, respectively, showing a statistical difference between all groups. The quantification of DNA methylation was 0.311, 0.245 and 0.178, respectively, for resistant, resilient, and susceptible animals, with a correlation being found between resistance to gastrointestinal helminths and overall DNA methylation. For weight gain, resistant and resilient animals showed higher values than susceptible ones, with a correlation between weight gain and EPG. The same was observed for VG; however, there was no statistical difference to the EOS, PPT, and IgG values. A significant correlation was found between PCV and EPG; quantifications of PCV and methylated DNA, STP and EPG; VG and STP. Therefore, the methodologies used made it possible to identify the animals regarding the degree of infection by gastrointestinal nematodes, making it possible to correlate the resistance of cattle to helminths with the amount of global DNA methylation and its performance.

A One Health approach toward the control and elimination of soil-transmitted helminthic infections in endemic areas

Soil-transmitted helminths (STHs) pose significant health challenges, particularly in developing countries. Over 2 billion people are estimated to have been infected with at least one STH species. These parasites rely on the soil for part of their life cycle and are transmitted to humans through ova ingestion or skin penetration. Key risk factors include poor water, sanitation, hygiene practices, limited healthcare access, and poverty. Globally, STHs are primarily controlled through chemo-preventive deworming of high-risk groups in moderate (where prevalence of STHs is between 20 % and 50 %) to highly endemic areas (prevalence >50 %). Despite the use of deworming to control the STHs in endemic areas, infections still occur. The aim of this article is to explore the potential for enhancing STH control and elimination as Neglected Tropical Diseases (NTDs) in endemic areas through an integrated approach—the One Health approach. The current control program has a single strategy of chemoprophylaxis; in the integrated approach to control of STHs, the parasite control strategies besides being based on the epidemiology of the parasite (endemicity), also include strategies based on the biology (transmission cycle) of the parasites and human behavior patterns in endemic areas. Through the involvement of local communities, healthcare authorities, and stakeholders, participatory approaches foster collaborative efforts to devise and implement control measures. By integrating this integrated approach into existing healthcare and educational initiatives, more effective results can be achieved. The promotion of health education, clean water access, improved sanitation, and hygiene awareness can further enhance control strategies and reduce STH prevalence sustainably. Here, we highlight the benefits of adopting an integrated (One Health) approach to tackle STHs in endemic areas. Through community empowerment and multi-sectorial collaboration, we can strengthen our collective efforts to combat STHs and alleviate the burden of these NTDs.

Penyuluhan dan Pemberian Obat Cacing Sebagai Upaya Pencegahan Kecacingan Bagi Siswa Kelas IV/A di UPT SPF SD Negeri Pannara

Intestinal diseases caused by transmission from worms as a source of helminthiasis generally occur in areas with subtropical and tropical climate conditions which have a wet climate and lack of awareness among the public regarding maintaining health and sanitation of the surrounding environment. Around 60 percent of Indonesians experience worm infections. The largest age group is 5-14 years old. The prevalence figure is 60 percent, 21 percent of which attack elementary school age children. This disease can be spread by eggs in human waste found in soil and water, therefore awareness of clean and sanitary living is very influential, the process or pattern of feces disposal is also very influential in the spread of this worm. The high rate of soil contamination by Ascaris, which reaches &gt;70%, can also be caused by feces that are thrown anywhere, such as in bushes or around houses close to where you live. Preventing recurrent infections is very important by practicing clean and healthy living habits such as avoiding contact with soil that may be contaminated with human feces, washing hands with soap and water before handling food, protecting food from soil and washing or heating food that falls on the floor. Several researchers have shown that school age is a group that is often affected by worm infections because they are often in contact with soil. Apart from the government, the role of teachers and parents is very important in providing understanding or knowledge about worms so that they are more disciplined. The aim of community service is to provide knowledge and understanding to class IV/A students at SD N Pannara regarding the dangers of worms and how to prevent them and administer worm medicine.

Soil-transmitted helminth infections and anemia in children attending government run schools on Samosir Island, Indonesia

BackgroundWorldwide, >654 million children live in regions where soil-transmitted helminth (STH) infections are endemic. These parasites cause a variety of symptoms, including anemia. MethodsIn May 2023, fecal and blood samples were collected from children aged 6 to 11 years attending government run (public) elementary schools in the Simanindo and Ronggur Nihuta sub-districts of Samosir Island, Indonesia where a twice a year mass drug administration (MDA) program is currently in place. A questionnaire was administered to students' parents or adult family members on possible risk factors for STH infections. Qualitative data were collected through in-depth interviews and focus group discussions. ResultsIn total, 187 and 221 children in Simanindo and Ronggur Nihuta provided samples, respectively. The STH infection prevalence in Simanindo was 4.8% (9/187) and the infection prevalence in Ronggur Nihuta was 5.9% (13/221). In Simanindo, all infections were caused by Trichuris trichiura (n = 9), and in Ronggur Nihuta infections were caused by Ascaris lumbricoides (n = 6), Trichuris trichiura (n = 5), and A. lumbricoides + T. trichiura (n = 2). Three children had anemia but were negative for STH infections. While the results of the parent/adult questionnaires indicated access to a generally safe water supply and septic system, information from the in-depth interviews and focus groups revealed that the local water supply becomes greatly diminished during the dry season. ConclusionsWhile MDA has been shown to effectively control roundworms and hookworms, additional measures to control trichuriasis are needed. There is also a need for the government to invest in improving the public water supply infrastructure.

Gastrointestinal parasites of the Indian Flying Fox Pteropus medius in Nagpur City: a seasonal study through faecal sample analysis

The Indian Flying Fox Pteropus medius, among the largest Indian fruit eating bats, is commonly observed with unhurried wing beats at dusk and tends to roost during the day in sizable, noisy colonies situated on trees within bustling towns and villages. Notably, these colonies are prevalent in busy areas of Nagpur city, particularly on expansive Banyan Trees Ficus bengalensis and Pangom Oil Trees Millettia pinnata, owing to the consistent availability of fruits and flowers throughout the year. This study focuses on evaluating gastrointestinal helminth infection in fruit-eating bats during the summer, monsoon, and winter seasons in Nagpur city, Maharashtra. A total of 58 samples were collected, processed, and examined using the double sedimentation technique. Of these, 46 samples (80.01%) tested positive for Ascaris spp. eggs, with a higher percentage during the monsoon season. Additionally, during the peak summer season, a juvenile flying fox from one of the colonies was rescued in a dehydrated state, displaying crusty scab-like lesions on the wing’s anterior and posterior regions. Subsequent examination revealed the presence of the ectoparasite Macronyssus spp. on body of the juvenile Indian Flying Fox.

Soil-transmitted helminthiasis among school-aged children in selected primary schools in southwest Nigeria: a cross-sectional study

This cross-sectional study was conducted to determine the prevalence and intensity of infection of soil-transmitted helminths among school-aged children in Ife Central and Ife East Local Government Areas, Osun State, Nigeria. Fresh stool samples were collected from 324 pupils, comprising 162 males and 162 females (aged 5-12 years). The preserved fecal samples were processed using a modified Kato-Katz technique. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20. Of the 324 fecal samples examined, 79 (24.4%) tested positive for helminth eggs. The eggs were identified as Ascaris lumbricoides, with a prevalence of 22.2%, and hookworm; with a prevalence of 3.7%. Double infections were observed in 5 (1.5%) pupils. Private schools had a slightly higher prevalence (24.7%) than did public schools (24.1%). Sex-related prevalence was higher among males (25.9%) than females (22.8%), and no significant difference existed in the prevalence level between the sexes (p &gt; 0.05). This study concluded that STH infection remains a public health risk among children in the study area.

Prevalence of Malaria and Helminth Infections and Their Link to Knowledge on Preventive Strategies among Asymptomatic Pupils in Rural-urban Cameroon

Aim: The aim of our study was to investigate the prevalence of malaria and helminth infection among asymptomatic primary school children in rural and urban Yaoundé-Cameroon, to assess pupils’ knowledge about malaria and STH infection, and to evaluate the association between this knowledge and actual disease prevalence.&#x0D; Study Design: This study was a cross-sectional and was carried out between October 2019 and December 2019 in six primary schools in the Centre region of Cameroon.&#x0D; Methodology:Pupils in classes 3 to six were recruited for the study. Blood and stool samples were collected and analysed to determine pupils’ disease prevalence. Questionnaires following the KAP and health belief model frameworks were administered to evaluate pupils’ health literacy in malaria and helminths.&#x0D; Results: 457 pupils from rural and urban zones participated in this study. 245 (53.6 %) were female and 212 (46.4 %) were male. The prevalence of anaemia was higher in urban than rural zones. Total malaria prevalence was 17.7%. Malaria parasitaemia prevalence classified according to settings revealed rural zones at 28.6% and urban zones at 13.9%. STH infection showed a total prevalence of 4.8% and 7.9% and 3.7% in rural and urban zones respectively. The prevalence of co-infection was 1.2%. Health-literacy gaps in malaria and helminths were identified. Schooling in rural settings and being older were predictors for having a good knowledge of the diseases. However, having good knowledge was not significantly associated to actual malaria parasitaemia or STH prevalence.&#x0D; Conclusion: Insights from this study are essential for the implementation of successful, sustainable and targeted health-promotion strategies to improve the health and well-being of pupils.

IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease.

Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.

Assessing the effectiveness of fenbendazole supramolecular complexes against schistosomiasis, monieziosis and parabronemosis in sheep

Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.

A potential role of protein extractions from Metagonimus yokogawai in amelionating inflammation in patients with ankylosing spondylitis

Helminth infections and their components has been recognized to have a positive impact on the immune system. This study aimed to investigate the potential of Metagonimus yokogawai-derived proteins (MYp) to provide protection against ankylosing spondylitis (AS) through modulation of immune responses. The cytotoxicity of MYp at various doses was first assessed using MTS and flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from AS patients, and the production of inflammatory cytokines was analyzed through flow cytometry. In the experiments with SKG mice, MYp or vehicle was administered and inflammation was evaluated through immunohistochemistry and enzyme-linked immunosorbent assay. The results showed that MYp did not decrease cell viability of PBMCs even after 48 h. Additionally, the frequencies of IFN-γ and IL-17A producing cells were significantly reduced after MYp treatment in the PBMC cultures. Furthermore, MYp treatment significantly suppressed arthritis and enthesitis in the SKG mouse model. The results suggest the first evidence that MYp can effectively alleviate clinical symptoms and restore cytokine balance in patients with AS.

Evaluation of Anthelmintic Activity of Caesalpinia Pulcherrima Leaf Extract by In-Silico and In-Vitro Studies

The Greek term for "helminthes" means "worm." Human-infecting parasites fall into one of two categories: keepsakes or heirlooms. Heirlooms are parasites that have been passed down from African ancestors, while souvenirs are parasites that humans have picked up from animals through migration, evolution, and agricultural activities. These helminthic infections are the most prevalent human infectious agents in poor nations. The helminthic parasite affects around 2 billion people worldwide, or more than 25% of the total population. It is a big problem in developing nations, particularly for young people. Therefore, the goal of the current study was to extract the plant's active ingredients and test the crude extract's anti-helminthic properties. In this study, we worked on the ceasalpeniapulcherima plant with a focus on natural remedies for the treatment of helmintiasis. The chief scientist of Sri Konda Laxman Telangana State Horticulture University, Floriculture Research Station, Rajndranagar, authenticated the true nature of the plant. Water and ethanol were utilized in the extraction procedure. To find out what chemicals are in the alcoholic extract, a screening test is performed on it. The flavonoid test on the extract came out positive. Using Albendazole as the prescribed medication, the anthelmintic action was carried out on Indian earthworms. In Indian earth worms, we found that alcoholic extract exhibits good antihelmintic action. By Insilco studies we found the interaction of flavanoids with antihelmentic proteins. Key Word: Helminthes, ceasalpeniapulcherima, flavonoids, extractioin, in silico study.

Evaluation of reference genes for gene expression analysis by real-time quantitative PCR (qPCR) in different tissues from mice infected by Ascaris suum

Human ascariasis is the most prevalent helminth infection, affecting 445 million people worldwide. To better understand the impact of the immune system on the pathophysiology of individuals infected with Ascaris suum, mice have been used as experimental models. The RT-qPCR technique is a critical auxiliary tool of investigation used to quantify mRNA levels. However, proper normalization using reference genes is essential to ensure reliable outcomes to avoid analytical errors and false results. Despite the importance of reference genes for experimental A. suum infection studies, no specific reference genes have been identified yet. Therefore, we conducted a study to assess five potential reference genes (GAPDH, 18s, ACTB, B2M, and HPRT1) in different tissues (liver, lungs, small and large intestines) affected by A. suum larval migration in C57BL/6j mice. Tissue collection was carried out to analyze parasite burden and confirm the presence of larvae during the peak of migration in each tissue. Upon confirmation, we analyzed different genes in the tissues and found no common gene with stable expression. Our results highlight the importance of analyzing different genes and using different software programs to ensure reliable relative expression results. Based on our findings, B2M was ranked as the ideal reference gene for the liver, while 18S was the most stable gene in the lung and small intestine. ACTB, or a combination of ACTB with GAPDH, was deemed suitable as reference genes for the large intestine due to their stable expression and less variation between the control and infected groups. To further demonstrate the impact of using different reference genes, we normalized the expression of a chemokine gene (CXCL9) in all tissues. Significant differences in CXCL9 expression levels were observed between different groups in all tissues except for the large intestine. This underscores the importance of selecting appropriate reference genes to avoid overestimating target gene expression levels and encountering normalization-related issues that can lead to false results. In conclusion, our study highlights the significance of using reliable reference genes for accurate RT-qPCR analysis, especially in the context of A. suum infection studies in different tissues. Proper normalization is crucial to ensure the validity of gene expression data and avoid potential pitfalls in interpreting results.

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides.

Onchocerciasis and lymphatic filariasis are two neglected tropical diseases caused by filarial nematodes that utilize insect vectors for transmission to their human hosts. Current control strategies are based on annual or biannual mass drug administration (MDA) of the drugs Ivermectin or Ivermectin plus Albendazole, respectively. These drug regimens kill the first-stage larvae of filarial worms (i.e., microfilariae) and interrupt the transmission of infections. MDA programs for these microfilaricidal drugs must be given over the lifetime of the filarial adult worms, which can reach 15 years in the case of Onchocerca volvulus. This is problematic because of suboptimal responses to ivermectin in various endemic regions and inefficient reduction of transmission even after decades of MDA. There is an urgent need for the development of novel alternative treatments to support the 2030 elimination goals of onchocerciasis and lymphatic filariasis. One successful approach has been to target Wolbachia, obligatory endosymbiotic bacteria on which filarial worms are dependent for their survival and reproduction within the human host. A 4-6-week antibiotic therapy with doxycycline, for example, resulted in the loss of Wolbachia that subsequently led to extensive apoptosis of somatic cells, germline, embryos, and microfilariae, as well as inhibition of fourth-stage larval development. However, this long-course regimen has limited use in MDA programs. As an alternative approach to the use of bacteriostatic antibiotics, in this study, we focused on autophagy-inducing compounds, which we hypothesized could disturb various pathways involved in the interdependency between Wolbachia and filarial worms. We demonstrated that several such compounds, including Niclosamide, an FDA-approved drug, Niclosamide ethanolamine (NEN), and Rottlerin, a natural product derived from Kamala trees, significantly reduced the levels of Wolbachia in vitro. Moreover, when these compounds were used in vivo to treat Brugia pahangi-infected gerbils, Niclosamide and NEN significantly decreased adult worm survival, reduced the release of microfilariae, and decreased embryonic development depending on the regimen and dose used. All three drugs given orally significantly reduced Wolbachia loads and induced an increase in levels of lysosome-associated membrane protein in worms from treated animals, suggesting that Niclosamide, NEN, and Rottlerin were effective in causing drug-induced autophagy in these filarial worms. These repurposed drugs provide a new avenue for the clearance of adult worms in filarial infections.

Host gastric corpus microenvironment facilitates Ascaris suum larval hatching and infection in a murine model.

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals.

Protocol for spatial prediction of soil transmitted helminth prevalence in the Western Pacific region using a meta-analytical approach

BackgroundSoil transmitted helminth (STH) infections are estimated to impact 24% of the world’s population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR).MethodsThe protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps.DiscussionThis protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence’s and can be used to inform resource allocation in combating this neglected tropical disease.Trial registrationOpen Science Framework: osf.io/qmxcj.

"Our desire is to make this village intestinal worm free": Identifying determinants of high coverage of community-wide mass drug administration for soil transmitted helminths in Benin, India, and Malawi.

Soil-transmitted helminth infections (STH) are associated with substantial morbidity in low-and-middle-income countries, accounting for 2.7 million disability-adjusted life years annually. Current World Health Organization guidelines recommend controlling STH-associated morbidity through periodic deworming of at-risk populations, including children and women of reproductive age (15-49 years). However, there is increasing interest in community-wide mass drug administration (cMDA) which includes deworming adults who serve as infection reservoirs as a method to improve coverage and possibly to interrupt STH transmission. We investigated determinants of cMDA coverage by comparing high-coverage clusters (HCCs) and low-coverage clusters (LCCs) receiving STH cMDA in three countries. A convergent mixed-methods design was used to analyze data from HCCs and LCCs in DeWorm3 trial sites in Benin, India, and Malawi following three rounds of cMDA. Qualitative data were collected via 48 community-level focus group discussions. Quantitative data were collected via routine activities nested within the DeWorm3 trial, including annual censuses and coverage surveys. The Consolidated Framework for Implementation Research (CFIR) guided coding, theme development and a rating process to determine the influence of each CFIR construct on cMDA coverage. Of 23 CFIR constructs evaluated, we identified 11 constructs that differentiated between HCCs and LCCs, indicating they are potential drivers of coverage. Determinants differentiating HCC and LCC include participant experiences with previous community-wide programs, communities' perceptions of directly observed therapy (DOT), perceptions about the treatment uptake behaviors of neighbors, and women's agency to make household-level treatment decisions. The convergent mixed-methods study identified barriers and facilitators that may be useful to NTD programs to improve cMDA implementation for STH, increase treatment coverage, and contribute to the successful control or elimination of STH. The parent trial was registered at clinicaltrials.gov (NCT03014167).

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.