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Background: The control of the Soil-Transmitted Helminths (STH) infections primarily relies on the school-based Preventive Chemotherapy (PCT) with mebendazole. Given the efficacy of ivermectin on STH, the control of the latter is expected to be potentialized in areas where ivermectin is also distributed for onchocerciasis and/or lymphatic filariasis control/elimination. This study aimed to assess the prevalence and intensity of STH in the Lomie Health District where annual school-based deworming campaigns and community-directed treatments with Ivermectin have been underway for almost two decades., Methodology/principal Findings: A quantitative cross-sectional study was conducted in 10 schools of the Lomie Health District, East Region, Cameroon. Stool samples were collected from school-aged children and analysed using the Kato-Katz technique. Semi-structured questionnaires were administered to enrolees to assess compliance with water, sanitation, and hygiene (WASH). Of the 491 children (median age: 9 years; IQR: 7-10) enrolled, 83.9% (95% CI: 80.3-87.1) were infected with at least one STH species. Trichuris trichiura was the predominant species (78.5%), and no hookworm was found. The prevalence trend slightly decreased between 1987 and 2010 (~8%) and remained unchanged since 2010 (p-value = 0.05). Overall, 46.8% and 41.8% of children were heavy-to-moderately infected with Ascaris lumbricoides and T. trichiura. Poor hand hygiene (OR: 2.24, 95% IC: 1.4-3.4, p-value = 0.0002) and the use of river as a source of drinking water (OR: 14.8, 95% IC: 6.9-33.3, p-value = 0.0001) were the main risk factors associated with the STH infection in Lomie Health District., Conclusions/significance: The persistent high prevalence and intensity of STH infection despite 16 years of mebendazole-based PCT and expected collateral impact of ivermectin mass distribution, points to plausible implementation gaps, poor compliance to WASH or sub-optimal efficacy of the anthelminthics used. This study highlights the need to further assess the cause of the persistent high prevalence and implement context-adapted control measures in order to curb STH transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Efon-Ekangouo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting., Competing Interests: JK, TS, ZA, CA, FB, DC, VC, DH, PK, EM, JB, CR, WS, JS, WZ, RN, OC, JB As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation. AM, VZ No competing interests declared, (© 2021, Knee et al.)

Background: Soil-transmitted helminths (STH), i.e., Ascaris lumbricoides, Trichuris trichiura and hookworms are among the most prevalent Neglected Tropical Diseases (NTDs) in Ethiopia. Although pre-school aged children pay a high morbidity toll associated with STH infections, evidence on prevalence, intensity and intervention status is lacking in Ethiopia. This study, therefore, aimed to address these gaps to inform decision made on STH., Methods: We did a community-based cross-sectional study in five districts of Gamo Gofa zone, Southern Ethiopia; in January 2019. Data were collected using pre-tested questionnaire, and the Kato-Katz technique was used to diagnose parasites eggs in stool. Then, collected data were edited and entered into EpiData 4.4.2, and exported to SPSS software (IBM, version 25) for analysis., Results: A total of 2462 PSAC participated in this study. Overall, the prevalence of STH was 23.5% (578/2462) (95% confidence interval (CI) = 21.8%-25.2%). As caris lumbricoides was the most prevalent (18.6%), followed by Trichuris trichiura (9.2%), and hookworms (3.1%). Of the total, 7.4% PSAC were infected with two STH species. Most of the positive cases with STH showed low infection intensities, while 15.1% ascariasis cases showed moderate infection intensities. The study found that 68.7% of PSAC were treated with albendazole. Also, household's level data showed that 39.4% used water from hand-dug well; 52.5% need to travel ≥30 minutes to collect water; 77.5% did not treat water, and 48.9% had no hand washing facility. In addition, almost 93% care givers achieved less than the mean knowledge and practice score (≤5) on STH prevention., Conclusions: This study showed that significant proportions of pre-school aged children are suffering from STH infections despite preventive chemotherapy exist at the study area. Also, gaps in the interventions against STH were highlighted. Thus, a call for action is demanding to eliminate STH among PSAC in Ethiopia by 2030., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Soil transmitted helminths (STH) can affect over 50% of children in some parts of Tanzania. Control measures involve annual deworming campaigns in schools, but re-infection is rapid. This paper presents the design and baseline survey results of an ongoing school-based cluster-randomised controlled trial in Kagera region, NW Tanzania. The trial aims to determine whether the effect of routine deworming on the prevalence of Ascaris lumbricoides and Trichuris trichiura infections among school aged children can be sustained when combined with a behaviour change intervention promoting handwashing with water and soap., Methods: As part of the trial, a total of 16 schools were randomised to receive the intervention (N = 8) or as controls (N = 8). Randomisation was stratified per district and restricted to ensure pre-trial STH prevalence was balanced between study arms. The combination intervention to be tested comprises class-room based teacher-led health education, improvement of handwash stations, coloured nudges to facilitate handwashing and parental engagement sessions. The impact evaluation involves two cross-sectional surveys conducted at baseline and endline. The objectives of the baseline survey were: (i) to confirm whether the deworming campaign was successful, and identify and treat students still infected about 2 weeks after deworming, (ii) to document any baseline differences in STH prevalence between trial arms, and (iii) to assess handwashing behaviours, and access to water and sanitation at school and home. We randomly sampled 35 students per class in Grades 1-6 (an average of 200 children per school), stratified to ensure equal representation between genders. Assenting students were interviewed using a structured questionnaire and asked to provide a stool specimen., Results: Results of the baseline survey conducted about 2 weeks after deworming shows balanced demographic and STH prevalence data across trial arms. We observed a low prevalence of ascariasis (< 5%) as expected; however, the prevalence of trichuriasis was still about 35% in both arms., Conclusion: The randomisation procedure was successful in achieving a balanced distribution of demographic characteristics and helminth infections between trial arms. The intervention is being rolled out. The current deworming treatment regimen may need to be revised with regards to the treatment of trichuriasis., Competing Interests: The authors have declared that no competing interests exists.

This study was performed to find out the clusters with high parasite infection risk to discuss the geographical pattern. Clusters were detected using SatScan software, which is a statistical spatial scan program using Kulldorff's scan statistic. Information on the parasitic infection cases in Korea 2011-2019 were collected from the Korea Centers for Disease Control and Prevention. Clusters of Ascaris lumbricoides infection were detected in Jeollabuk-do, and T. trichiura in Ulsan, Busan, and Gyeongsangnam-do. C. sinensis clusters were detected in Ulsan, Daegu, Busan, Gyeongsangnam-do, and Gyeongsangbuk-do. Clusters of intestinal trematodes were detected in Ulsan, Busan, and Gyeongsangnam-do. P. westermani cluster was found in Jeollabuk-do. E. vermicularis clusters were distributed in Gangwon-do, Jeju-do, Daegu, Daejeon, and Gwangju. This clustering information can be referred for surveillance and control on the parasitic infection outbreak in the infection-prone areas.

Background: Soil-transmitted helminth (STH) infections remain a public health concern in sub-Saharan Africa. School-based mass drug administration (MDA) using the anthelminthic drug Mebendazole/Albendazole have succeeded in controlling morbidity associated to these diseases but failed to interrupt their transmission. In areas were filarial diseases are co-endemic, another anthelminthic drug (Ivermectin) is distributed to almost the entire population, following the community-directed treatment with ivermectin (CDTI) strategy. Since Ivermectin is a broad spectrum anthelmintic known to be effective against STH, we conducted cross-sectional surveys in two health districts with very contrasting histories of Ivermectin/Albendazole-based PC in order to investigate whether CDTI might have contributed in STH transmission interruption., Methodology: Cross-sectional surveys were conducted in two health districts with similar socio-environmental patterns but with very contrasting CDTI histories (Akonolinga health district where CDTI was yet to be implemented vs. Yabassi health district where CDTI has been ongoing for two decades). Stool samples were collected from all volunteers aged >2 years old and analyzed using the Kato-Katz technique. Infections by different STH species were compared between Akonolinga and Yabassi health districts to decipher the impact of Ivermectin/Albendazole-based MDA on STH transmission., Principal Findings: A total of 610 and 584 participants aged 2-90 years old were enrolled in Akonolinga and Yabassi health districts, respectively. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found, with prevalence significantly higher in Akonolinga health district (43.3%; 95% CI: 38.1-46.6) compared to Yabassi health district (2.5%; 95% CI: 1.1-5.1) (chi-square: 90.8; df: 1; p < 0.001)., Conclusion/significance: These findings (i) suggest that Mebendazole- or Albendazole-based MDA alone distributed only to at-risk populations might not be enough to eliminate STH, (ii) support the collateral impact of Ivermectin/Albendazole MDA on A. lumbricoides and T. trichiura infections, and (iii) suggest that Ivermectin/Albendazole-based PC could accelerate STH transmission interruption., Competing Interests: The authors have declared that no competing interests exist.

To adequately plan mass drug administration campaigns, the Democratic Republic of the Congo (DRC) needs further support for the mapping and monitoring of schistosomiasis (SCH) and soil-transmitted helminths (STH). We conducted a community-based survey in the health districts of Mosango and Yasa Bonga of the Kwilu province, DRC. A stratified two-stage cluster random sampling method was used to include participants into three different strata: Preschool-aged children (PSAC), school-aged children (SAC), and adults who were further subdivided into women of reproductive age (WRA) and other adults. In total, surveyors visited 30 villages, and 1 206 individuals participated in the study. Stool samples were collected to perform duplicate Kato-Katz smears for the detection of SCH and STH infection. Hookworm was the most prevalent infection in both districts, 34.1% (95%CI: 32.0-38.4), followed by A. lumbricoides (2.7%; 95%CI: 1.3-2.9) and T. trichiura (1.9%; 95%CI: 1.1-2.7). We did not find any SCH infection. The prevalence of each STH infection was similar across all risk groups, and the majority of the infected individuals was carrying light intensity infection. Compared to SAC, other adults were equally infected with hookworm. The prevalence of STH infection in SAC guides the MDA implementation because schoolchildren are most at risk and easily accessible program targets if school attendance is high. The current treatment strategy targets PSAC, SAC and WRA. However, this study shows that adults in general could also benefit from deworming. Therefore, community-wide preventive chemotherapy would be the most appropriate choice to control the hookworm burden rapidly., Competing Interests: The authors have declared that no competing interests exist. Author Marleen Boelaert was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

This paper reports the prevalence and intensity of soil-transmitted helminth (STH) infections measured in Zimbabwe before and after a control intervention based on annual deworming of school-age children (SAC) conducted from 2012 to 2018. In 2010, epidemiological data were collected from 13 195 SAC in 255 randomly selected schools in all districts nationwide using, as diagnostic methods, the Kato-Katz and the formal ether stool concentration technique. At follow up, conducted in 2017, only Kato-Katz was performed; specimens were collected from 13 352 children in 336 schools. The data were evaluated using a geospatial approach. The national prevalence of STH infection in SAC was estimated at 5.8% at baseline, with 0.8% of infections of moderate and heavy intensity. Preventive chemotherapy (PC) targeted all 2.5 million children of school age enrolled in Zimbabwe, with coverage ranging from 49% to 85%. At follow up, national prevalence of STH in SAC was estimated at 0.8%; infections of moderate and heavy intensity almost disappeared (0.1% prevalence). As a result, Zimbabwe can suspend deworming activities in 54 districts and reduce the frequency of PC in the remaining six districts. The total amount of albendazole tablets needed will be approximately 100 000 a year., Competing Interests: The authors have declared that no competing interests exist.

Trichuriasis is a serious threat to the economic development of animal husbandry. This research aimed to establish a droplet digital PCR (ddPCR) method to detect Trichuris spp. for the early diagnosis and prevention of trichuriasis in sheep. The real-time quantitative PCR (qPCR) and ddPCR methods were used for the detection of nematodes by targeted amplification of the ITS gene. Each means was evaluated to optimize the limit of detection and reproducibility. For a recombinant plasmid, the qPCR results showed that the detection limit was 31.7 copies per reaction. In contrast to qPCR, ddPCR was able to detect concentrations below 3.17 copies per reaction. Both assays exhibited good reproducibility. However, the ddPCR method was more stable for low-copy-number detection. This new assay was specific for Trichuris spp. and did not cross-react with other relevant gastrointestinal nematodes. A total of 98 clinical samples were tested with both assays. The results showed that the positive rate of ddPCR (80.6%) was higher than that of qPCR (72.4%). This method could be used as an efficient molecular biology tool to test for Trichuris spp. and could be a new valuable tool for the clinical diagnosis and prevention of trichuriasis., (© American Society of Parasitologists 2020.)

Background: The effect of nutritional supplements on the re-infection rate of species-specific soil-transmitted helminth infections in school-aged children remains complex and available evidence on the subject matter has not been synthesized., Methods: The review included randomised controlled trials (RCTs) and cluster RCTs investigating food supplements on school-aged children between the age of 4-17 years. A search for RCTs was conducted on eight databases from inception to 12th June 2019. Cochrane Risk of Bias tool was used to assess the risk of bias in all included studies. Meta-analysis and narrative synthesis were conducted to describe and analyze the results of the review. Outcomes were summarized using the mean difference or standardized mean difference where appropriate., Results: The search produced 1,816 records. Six studies met the inclusion criteria (five individually RCTs and one cluster RCT). Four studies reported data on all three STH species, while one study only reported data on Ascaris lumbricoides infections and the last study reported data on only hookworm infections. Overall, the risk of bias in four individual studies was low across most domains. Nutritional supplementation failed to statistically reduce the re-infection rates of the three STH species. The effect of nutritional supplements on measures of physical wellbeing in school-aged children could not be determined., Conclusions: The findings from this systematic review suggest that nutritional supplements for treatment of STH in children should not be encouraged unless better evidence emerges. Conclusion of earlier reviews on general populations may not necessarily apply to children since children possibly have a higher re-infection rate., Competing Interests: The authors have declared that no competing interests exist.

Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine., Competing Interests: The authors have declared that no competing interests exist.

Background: The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed., Methods: We selected countries from World Health Organization (WHO)'s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed., Results: Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1-64.7%) for any STH, 23.2% (13.7-32.7%) for Ascaris lumbricoides, 21.01% (9.7-32.3%) for Trichuris trichiura and 18.2% (10.9-25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3-21.3%) for any STH, 6.9% (1.3-12.5%) for A. lumbricoides, 5.3% (1.06-9.6%) for T. trichiura and 8.1% (4.0-12.2%) for hookworm infections., Conclusions: Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.

Background: Baseline mapping of soil-transmitted helminth (STH) infections among school age children (SAC) in 2008-2009 found high or moderate prevalence in 13 of the 14 districts in Sierra Leone. Following these surveys, mass drug administration (MDA) of mebendazole/albendazole was conducted biannually at national level targeting pre-school children (PSC) aged 12-59 months and intermittently at sub-national level targeting SAC. In addition, MDA with ivermectin and albendazole for eliminating lymphatic filariasis (LF) has been conducted nationwide since 2010 targeting individuals over 5 years of age. Each MDA achieved high coverage, except in 2014 when all but one round of MDA for PSC was cancelled due to the Ebola emergency. The objective of the current study was to determine the prevalence and intensity of STH infections among SAC after a decade of these deworming campaigns., Methods: Seventy-three schools in 14 districts were purposefully selected, including 39 schools from the baseline surveys, with approximately two sites from each of low, moderate and high prevalence categories at baseline per district. Fresh stool samples were collected from 3632 children aged 9-14 years (male 51%, female 49%) and examined using the Kato Katz technique., Results: The prevalence of STH infections in Sierra Leone decreased in 2016 compared to 2008: Ascaris lumbricoides 4.4% (95% confidence interval [CI]: 3.7-5.1%) versus 6.6% (95% CI: 0-25%), Trichuris trichiura 0.7% (95% CI: 0.5-1.1%) versus 1.8% (95% CI: 0-30.2%), hookworm 14.9% (95% CI: 13.8-16.1) versus 38.5% (95% CI: 5.4-95.1%), and any STH 18.3% (95% CI:17.0-19.5%) versus 48.3% (CI: 5.4-96.3%), respectively. In 2016, no district had high hookworm prevalence and four districts had moderate prevalence, compared with eight and four districts respectively in 2008. In 2016, the arithmetic mean hookworm egg count in all children examined was light: 45.5 eggs per gram (EPG) of faeces, (95% CI:\ 35.96-55.07 EPG); three (0.08%) children had heavy infections and nine (0.25%) children had moderate infections., Conclusions: Sierra Leone has made considerable progress toward controlling STH as a public health problem among SAC. As LF MDA phases out (between 2017 and 2021), transition of deworming to other platforms and water and sanitation strategies need to be strengthened to maintain STH control and ultimately interrupt transmission.

Trichuris suis infection in pigs is ubiquitous in intensive and extensive farms, which causes potential threat to human health. The objective of this research was to investigate the prevalence of T. suis in pigs in Hunan province. Total 2,267 fresh fecal samples distributed in 28 pig farms from 7 different administrative regions (Hunan province) were evaluated for the existence of T. suis eggs using saturated NaCl floating method. The average infection rate of T. suis in pigs was 8.91% in Hunan province. To determine genetic variation of the gained T. suis isolates in the present study, the internal transcribed spacer (ITS) regions from nuclear ribosomal DNA (rDNA) of 7 T. suis isolates were cloned and analyzed. Nucleotide diversities were 1.0-3.5% and 0-3.8% for ITS-1 and ITS-2, respectively. Phylogenetic analyses indicated that all isolates collected in the present study and T. suis available in Genbank generated a monophyletic clade. The present investigation revealed high infection rates of T. suis in pigs in Hunan province, which shed light on making effective measures to prevent and control T. suis infection in pigs in Hunan province.

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The recombinant WAP protein (rTm-WAP49), as well as a single, highly conserved repeat within WAP (fragment 8) expressed as an Na-GST-1 fusion protein (rTm-WAP-F8+Na-GST-1), generate a strong T helper type 2 (Th2) immune response when delivered as subcutaneous vaccines formulated with Montanide ISA 720. Oral challenge with T. muris infective eggs following vaccination led to a significant reduction in worm burden of 48% by rTm-WAP49 and 33% by rTm-WAP-F8+Na-GST-1. The cellular immune correlates of protection included significant antigen-specific production of Th2 cytokines IL-4, IL-9, and IL-13 by cells isolated from the vaccine-draining inguinal lymph nodes, parasite-draining mesenteric lymph nodes, and spleen in mice vaccinated with either rTm-WAP49 or rTm-WAP-F8+Na-GST-1. The humoral immune correlates included a high antigen-specific ratio of IgG1 to IgG2a, without eliciting an IgE-mediated allergic response. Immunofluorescent staining of adult T. muris with WAP antisera identified the worm's pathogenic stichosome organ as the site of secretion of native Tm-WAP protein into the colonic mucosa. Given the high sequence conservation for the WAP proteins from T. muris and T. trichiura, the results presented here support the WAP protein to be further evaluated as a potential human whipworm vaccine candidate., Competing Interests: The authors have declared that no competing interests exist.

Trichuris trichiura (whipworm) is one of the four major soil-transmitted helminth infections of man, affecting an estimated 465 million people worldwide. An effective vaccine that induces long-lasting protective immunity against T. trichiura would alleviate the morbidity associated with this intestinal-dwelling parasite, however the lack of known host protective antigens has hindered vaccine development. Here, we show that vaccination with ES products stimulates long-lasting protection against chronic infection in male C57BL/6 mice. We also provide a framework for the identification of immunogenic proteins within T. muris ES, and identify eleven candidates with direct homologues in T. trichiura that warrant further study. Given the extensive homology between T. muris and T. trichiura at both the genomic and transcriptomic levels, this work has the potential to advance vaccine design for T. trichiura.

Objective: To determine the prevalence of schistosomiasis (SCH) and soil-transmitted helminths (STH) in the Democratic Republic of Congo, and to assess the capacity of the local health centres for diagnosis and treatment., Methods: Cross-sectional school-based survey in two health districts in the Province of Kwilu. We collected a stool and a urine sample for parasitological examination. Urine filtration and duplicate Kato-Katz thick smears were used for the diagnosis of SCH. Health centres were evaluated using a structured questionnaire., Results: In total, 526 children participated in the study and the overall prevalence of Schistosoma mansoni infection was 8.9% (95% CI: 3.5-13.2) in both districts. The prevalence was higher in Mosango (11.7%; 95% CI: 8.9-14.8) than Yasa Bonga district (6.2%; 95% CI: 1.1-11.4). Urine filtration showed that Schistosoma haematobium infection was not present. The combined STH infection prevalence was 58.1% in both districts; hookworm infection was the most common STH found in 52.9% (95% CI: 29.3-62.4) of subjects, followed by Ascaris lumbricoides 9.3% (95% CI: 5.8-15.5) and Trichuris trichiura 2.1% (95% CI: 0.9-4.9). Mixed STH infections were observed as well as SCH-STH coinfection., Conclusion: Further mapping of both SCH and STH burden is needed, and coverage of preventive chemotherapy in school-aged children should be increased., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the resident dog population. These results suggest that the triple dose albendazole 400mg treatment regime achieved a significant reduction in the level of taeniasis whilst simultaneously reducing the STH burden within the village. The increased STH prevalence detected between MDAs reflects the need for behavioural changes and a sustained chemotherapy programme, which may also need to include the resident dog population., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa., (© 2017 The Authors.)

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25-50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent.

The morbidity due to Ascaris lumbricoides and Trichuris trichiura is caused by infections of moderate and heavy intensity while hookworm infections of all intensities are recognized to cause morbidity. This study aims to evaluate the effect of repeated rounds of preventive chemotherapy on the proportion of soil-transmitted helminth (STH) infections causing morbidity. We identified studies from 17 countries, reporting changes in the proportion of STH infection causing morbidity between baseline and follow-up. In the studies identified, the average proportion of individuals with STH infections of moderate and heavy intensity was of 14% at baseline and was on average reduced to 2% by the intervention (i.e., 85% reduction). There was an average reduction of 73% after the first year of treatment, which reached almost 80% after 5 years and over 95% in 10 years of deworming interventions. The reduction in hookworm prevalence was 57% after 12 months reaching 78% after 5 years. We consider the results presented in this study especially useful for decision makers as it demonstrates the effectiveness of preventive chemotherapy in reducing STH prevalence and morbidity. We encourage the implementation of deworming programs to achieve the goal, set by WHO for 2020, to eliminate STH morbidity in children., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Preventive chemotherapy with albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible., Methods: In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) albendazole-ivermectin; (ii) albendazole-mebendazole; (iii) albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment., Results: For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7-64.0; ERR: 98.6 %, 95 % CI: 97.8-99.2) compared to the other treatment arms. Children treated with albendazole-oxantel pamoate or albendazole-ivermectin had fewer moderate infections compared to children treated with albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3-46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3-42.3) and 25.0 % for hookworms (95 % CI: 15.5-36.6)., Conclusion: The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the albendazole plus oxantel pamoate and albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections., Trial Registration: Current Controlled Trials ISRCTN80245406.

• On the basis of research evidence, worm infections are important global child health conditions causing chronic disability that lasts from childhood into adulthood (Table 1). (2)(3) Evidence Quality: B • On the basis of research evidence, the major worm infections found in developing countries include ascariasis, trichuriasis, hookworm infection, and schistosomiasis; toxocariasis, enterobiasis, and cysticercosis are also found in poor regions of North America and Europe. (4)(9)(13) Evidence Quality: B • On the basis of expert consensus, children and adolescents are often vulnerable to acquiring large numbers of worms, ie, high-intensity infections (Fig 1)(21)(22)(23) Evidence Quality: D • On the basis of expert consensus and research evidence, moderate and heavy worm burdens cause increased morbidity because of growth and intellectual stunting in children and adolescents. Many of these effects may result from helminth-induced malnutrition. (21)(22)(23) Evidence Quality: C • On the basis of expert consensus and research evidence, worm infections are also commonly associated with eosinophilia. (48) (49) Evidence Quality: B • On the basis of research evidence as well as consensus, helminthes can cause inflammation in the lung (asthma), gastrointestinal tract (enteritis and colitis), liver (hepatitis and fibrosis), and urogenital tract. (7)(21)(22)(23)(27)(28)(40)(41)(43) Evidence Quality: B • On the basis of research evidence, microscopy techniques for diagnosis of worm infections in children often exhibit suboptimal sensitivities and specificities, necessitating new or improved diagnostic modalities such as polymerase chain reaction. (54)(55) Evidence Quality: A • On the basis of research evidence and expert consensus, mass drug administration (“preventive chemotherapy”) has becomea standard practice for ministries of health in low- and middle-income countries to control intestinal helminth infections and schistosomiasis. (67)(68) Evidence Quality: B.

The current global strategy for the control of soil-transmitted helminthiasis emphasises periodic administration of anthelminthic drugs to at-risk populations. However, this approach fails to address the root social and ecological causes of soil-transmitted helminthiasis. For sustainable control, it has been suggested that improvements in water, sanitation and hygiene behaviour are required. We designed a 5-year multi-intervention trial in Menghai county, Yunnan province, People's Republic of China. Three different interventions were implemented, each covering a village inhabited by 200-350 people. The interventions consisted of (i) initial health education at study inception and systematic treatment of all individuals aged ≥2 years once every year with a single dose of albendazole; (ii) initial health education and bi-annual albendazole administration; and (iii) bi-annual treatment coupled with latrine construction at family level and regular health education. Interventions were rigorously implemented for 3 years, whilst the follow-up, which included annual albendazole distribution, lasted for 2 more years. Before the third round of treatment, the prevalence of Ascaris lumbricoides was reduced by only 2.8% in the annual treatment arm, whilst bi-annual deworming combined with latrine construction and health education resulted in a prevalence reduction of 53.3% (p<0.001). All three control approaches significantly reduced the prevalence of Trichuris trichiura and hookworm, with the highest reductions achieved when chemotherapy was combined with sanitation and health education. The prevalence of T. trichiura remained at 30% and above regardless of the intervention. Only bi-annual treatment combined with latrine construction and health education significantly impacted on the prevalence of Taenia spp., but none of the interventions significantly reduced the prevalence of Strongyloides stercoralis. Our findings support the notion that in high-endemicity areas, sustainable control of soil-transmitted helminth infections necessitates measures to reduce faecal environmental contamination to complement mass drug administration. However, elimination of soil-transmitted helminthiasis will not be achieved in the short run even with a package of interventions, and probably requires improvements in living conditions, changes in hygiene behaviour and more efficacious anthelminthic drugs and treatment regimens., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The apparent monthly prevalence of endoparasite infections was measured from 20,991 dogs that had fecal examinations performed upon presentation to the Veterinary Hospital of the University of Pennsylvania between 1984 and 2007. In the period from 1984 to 1991, the mean monthly prevalence of endoparasites was 5.32% for ascarids, 9.80% for hookworms, 9.64% for whipworms, 1.84% for tapeworms (Dipylidium caninum), 4.59% for Giardia species, and 3.04% for coccidia. Based on Student's t tests, the prevalence of ascarids (1.99%), hookworms (1.48%), whipworms (2.33%), and tapeworms (0.29%) were found to be significantly lower in the period from 2000 to 2007. Plots of the smoothed monthly averages revealed that the declines in prevalence occurred shortly after the introduction of modern heartworm and flea preventatives to the commercial market. In the latter study period, 79.8% of dogs were on monthly heartworm prevention and 74.0% were on monthly flea prevention. There were no significant differences in the prevalence of either Giardia species or coccidia species between study time periods. Overall, the findings suggest that heartworm and flea preventatives have had cascade effects on endoparasite prevalence in the population of well-cared-for dogs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Two new studies report genomic data on three species of whipworm, soil-transmitted parasitic worms responsible for trichuriasis. These genomes provide insights into host-pathogen interactions and potential for new drug targets for helminth therapy.

Background: Soil-transmitted helminths (STH) - a class of parasites that affect billions of people - can be mitigated using mass drug administration, though reinfection following treatment occurs within a few months. Improvements to water, sanitation and hygiene (WASH) likely provide sustained benefit, but few rigorous studies have evaluated the specific WASH components most influential in reducing infection. There is a need for alternative analytic approaches to help identify, characterize and further refine the WASH components that are most important to STH reinfection. Traditional epidemiological approaches are not well-suited for assessing the complex and highly correlated relationships commonly seen in WASH., Methodology: We introduce two recursive partitioning approaches: classification and regression trees (C&RT) and conditional inference trees (CIT), which can be used to identify complex interactions between WASH indicators and identify sub-populations that may be susceptible to STH reinfection. We illustrate the advantages and disadvantages of these approaches utilizing school- and household-level WASH indicators gathered as part of a school-based randomized control trial in Kenya that measured STH reinfection of pupils 10 months following deworming treatment., Principal Findings: C&RT and CIT analyses resulted in strikingly different decision trees. C&RT may be the preferred approach if interest lies in using WASH indicators to classify individuals or communities as STH infected or uninfected, whereas CIT is most appropriate for identifying WASH indicators that may be causally associated with STH infection. Both tools are well-suited for identifying complex interactions among WASH indicators., Conclusions/significance: C&RT and CIT are two analytic approaches that may offer valuable insight regarding the identification, selection and refinement of WASH indicators and their interactions with regards to STH control programs; however, they represent solutions to two distinct research questions and careful consideration should be made before deciding which approach is most appropriate.

Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5-19 years (51.8 %) and 20-35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5-19 years [odd ratio (OR) = 5.68; 95% CI: 2.71-11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon.

The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.

Soil-transmitted helminthiasis (STH), among the most common neglected tropical diseases, is a major public health problem in Malaysia with a possible impact on the nutritional status and school participation of rural children. This study was carried out among Aboriginal schoolchildren, living in an endemic area for STH in Malaysia, to determine the possible relationship between intestinal helminthiasis and school absenteeism. We also evaluated whether successful treatment of the infection will affect school attendance among the subjects. Stool analysis revealed that more than 90% of the subjects were infected with at least 1 helminth species, with Ascaris lumbricoides and Trichuris trichiura infections being most prevalent. Infection of moderate-to-heavy worm burdens, low level of fathers' education and anaemia were identified as the significant predictors of high absenteeism among the subjects (P<0·05). Following treatment of the infected children, it was found that school absenteeism was reduced significantly (P<0·01). In conclusion, STH continues to have significant impacts on public health, particularly in rural communities with a negatively significant effect on the school participation of Aboriginal children. A school-based de-worming programme should be introduced and incorporated in the current educational assistance targeted towards the Aboriginal communities, under the auspices of the government.

Interleukin (IL) 33, a member of the IL-1 family, is the ligand of ST2 that is expressed mainly on activated Th2 cells and mast cells. IL-33 can skew a predominantly Th1 cell population to a mainly Th2 cells phenotype in vivo. IL-33 messenger RNA is expressed early during infection of the intestinal-dwelling nematode Trichuris muris in mice. IL-33 treatment enhances resistance to Trichuris infection. IL-33 also effectively attenuates sepsis by mobilising the innate cells, neutrophils, to the site of infection, helping to clear the pathogens. Thus, IL-33 may be evolutionally preserved for the host defence against infections. IL-33 can reduce an ongoing atherosclerosis in ApoE(-/-) mice and attenuate adipocytes mainly by inducing the production of type II cytokines. In contrast, IL-33 can also exacerbate allergy and the inflammation in collagen-induced or serum-induced arthritis. Hence, IL-33 is a double-edged sword, and targeting IL-33 should be approached with caution.

Background: In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability., Methods and Findings: We conducted a systematic review and meta-analysis to assess the effect of sanitation (i.e., access and use of facilities for the safe disposal of human urine and feces) on infection with soil-transmitted helminths. PubMed, Embase, ISI Web of Science, and the World Health Organization Library Database were searched without language restrictions and year of publication (search performed until December 31, 2010). Bibliographies of identified articles were hand-searched. All types of studies reporting data on sanitation availability (i.e., having access at own household or living in close proximity to sanitation facility), or usage, and soil-transmitted helminth infections at the individual level were considered. Reported odds ratios (ORs) of the protective effect of sanitation on soil-transmitted helminth infections were extracted from the papers or calculated from reported numbers. The quality of published studies was assessed with a panel of criteria developed by the authors. Random effects meta-analyses were used to account for observed heterogeneity. Thirty-six publications, consisting of 39 datasets, met our inclusion criteria. Availability of sanitation facilities was associated with significant protection against infection with soil-transmitted helminths (OR  =  0.46 to 0.58). Regarding the use of sanitation, ORs of 0.54 (95% confidence interval [CI] 0.28-1.02), 0.63 (95% CI 0.37-1.05), and 0.78 (95% CI 0.60-1.00) were determined for T. trichiura, hookworm, and A. lumbricoides, respectively. The overall ORs, combining sanitation availability and use, were 0.51 (95% CI 0.44-0.61) for the three soil-transmitted helminths combined, 0.54 (95% CI 0.43-0.69) for A. lumbricoides, 0.58 (95% CI 0.45-0.75) for T. trichiura, and 0.60 (95% CI 0.48-0.75) for hookworm., Conclusions: Despite a number of limitations (e.g., most studies used a cross-sectional design and were of low quality, with potential biases and considerable heterogeneity), our results reveal that sanitation is associated with a reduced risk of transmission of helminthiases to humans. Access to improved sanitation should be prioritized alongside preventive chemotherapy and health education to achieve a durable reduction of the burden of helminthiases.

Objective: To understand the main risk factors of Trichuris trichiura infection in plots carrying out the integrated control of parasitic diseases., Methods: The simple and multiple unconditional logistic regression were applied to analyze related data from the database of baseline survey in demonstration plots carrying out the integrated control of parasitic diseases., Results: The results of simple logistic regression analysis suggested that the effects of 7 factors to Trichuris trichiura infection were significant (all P values were less than 0.05), namely drinking water resources, toilet type, fertilization type of farmland, fertilization type of vegetable field, washing hands after defecation, eating raw vegetables, melons and fruits and taking anthelminthic before examination. Among the factors above, eating raw vegetables, melons and fruits was of high risk (OR = 2.302), washing hands after defecation and taking anthelminthic before examination were two protection factors (with OR of 0.904 and 0.664, respectively). Compared to feces of human and livestock, fertilizing chemical fertilizer and compound fertilizer in farmland and vegetable field showed more obvious protection effect (with OR of 0.864 and 0.854, respectively). Drinking well water and spring water were two protection factors (with OR of 0.843 and 0.567, respectively). Simple toilet indoor and biogas pool also showed protection effect (with OR of 0.576 and 0.687, respectively). Multivariate analysis showed that four factors including eating raw vegetables, melons and fruits, fertilization type of farmland, fertilization type of vegetable field and taking anthelminthic before examination were determined to be the main influencing factors of Trichuris trichiura infection., Conclusions: The main influencing factors of Trichuris trichiura infection in demonstration plots for the integrated control of parasitic diseases include eating raw vegetables, melons and fruits and fertilization type of farmland and vegetable field. Besides those, taking anthelminthic could reduce Trichuris trichiura infection of the population, meanwhile, sanitary water supply and latrine improvement could also reduce the risk of infection.

Helminths in pigs have generally received little attention from veterinary parasitologists, despite Ascaris suum, Trichuris suis, and Oesophagostomum sp. being common worldwide. The present paper presents challenges and current research highlights connected with these parasites. In Danish swine herds, new indoor production systems may favour helminth transmission and growing knowledge on pasture survival and infectivity of A. suum and T. suis eggs indicates that they may constitute a serious threat to outdoor pig production. Furthermore, it is now evident that A. suum is zoonotic and the same may be true for T. suis. With these 'new' challenges and the economic impact of the infections, further research is warranted. Better understanding of host-parasite relationships and A. suum and T. suis egg ecology may also improve the understanding and control of human A. lumbricoides and T. trichiura infections. The population dynamics of the three parasites are well documented and may be used to study phenomena, such as predisposition and worm aggregation. Furthermore, better methods to recover larvae have provided tools for quantifying parasite transmission. Thus, an on-going study using helminth naïve tracer pigs has surprisingly demonstrated that soil infectivity with A. suum and T. suis increases during the first 2-3 years after pasture contamination. Though all three helminth species stimulate the Th2 arm of the immune system, Oesophagostomum seems weakly immunogenic, perhaps via specific modulation of the host immune system. A. suum and T. suis potently modulate the host immune response, up-regulating Th2 and down-regulating Th1. As a consequence, A. suum may compromise the efficacy of certain bacterial vaccines, whereas T. suis, which establish only short-term in humans, is a favourite candidate for down-regulating autoimmune Th1-related diseases in man. Some basic research findings have offered new possibilities for future sustainable control measures. For example, the heredity of host resistance to A. suum and T. suis is so high that breeding for resistant pigs may be a possibility. Experimental studies have demonstrated that fermentable dietary carbohydrates have an antagonistic effect on Oesophagostomum and to a lesser extent on T. suis and A. suum, whereas egg-destroying microfungi may be used to inactivate the hard-shelled A. suum and T. suis eggs in the environment. Helminth control in Denmark has previously relied solely on anthelmintic treatment in herds with low helminth transmission. When indoor transmission rates increase, or in outdoor herds with high pasture contamination levels, medication may advantageously be combined with sustainable control measures, such as selected pig genomes, bioactive forages, and egg-destroying microfungi., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To assess the following associations between the second and third trimesters of pregnancy: (i) the intensity of soil-transmitted helminth (STH) infection and haemoglobin/anaemia, (ii) the effect of mebendazole treatment on the occurrence of STH infection, and (iii) the effect of mebendazole treatment on haemoglobin/anaemia., Methods: Data originated from a trial of 1042 pregnant women recruited in their second trimester and followed to delivery. Baseline assessments included socio-demographic/health information from questionnaires, haemoglobin/anaemia from HemoCue ascertainment of fingerprick blood, and the presence and intensity of STH (Ascaris lumbricoides, hookworms and Trichuris trichiura) infections from Kato-Katz examination. All women were given iron supplements; half were randomly allocated to receive single dose 500 mg mebendazole, and half, placebo. Haemoglobin/anaemia and STH infection status were determined again in the third trimester of pregnancy., Results: Complete information was available from 935 (89.7%) women. Mebendazole significantly reduced the prevalence and intensity of all three STH infections. Higher intensities of hookworm and Trichuris infections in the second trimester were associated with a higher risk of anaemia in the third trimester. Overall, women with moderate/heavy Trichuris infection were found to be at a higher risk of anaemia; the highest risk was observed among those with moderate/heavy hookworm co-infection (adjusted OR = 2.77; 95% CI: 1.26, 6.11). Mebendazole treatment did not reduce the risk of anaemia., Conclusion: Higher intensities of both Trichuris and hookworm infections are associated with anaemia in pregnancy. The importance of Trichuris infections during pregnancy requires renewed attention., (© 2011 Blackwell Publishing Ltd.)

Background: Sanitation affects health, especially that of young children. Residents of Salvador, in Northeast Brazil, have had a high prevalence of intestinal parasites. A citywide sanitation intervention started in 1996 aimed to raise the level of sewer coverage from 26% to 80% of households., Objectives: We evaluated the impact of this intervention on the prevalence of Ascaris lumbricoides, Trichuris trichuria, and Giardia duodenalis infections in preschool children., Methods: The evaluation was composed of two cross-sectional studies (1998 and 2003-2004), each of a sample of 681 and 976 children 1-4 years of age, respectively. Children were sampled from 24 sentinel areas chosen to represent the range of environmental conditions in the study site. Data were collected using an individual/household questionnaire, and an environmental survey was conducted in each area before and after the intervention to assess basic household and neighborhood sanitation conditions. Stool samples were examined for the presence of intestinal parasites. The effect of the intervention was estimated by hierarchical modeling, fitting a sequence of multivariate regression models., Findings: The prevalence ofA. lumbricoides infection was reduced from 24.4% to 12.0%, T. trichuria from 18.0% to 5.0%, and G. duodenalis from 14.1% to 5.3%. Most of this reduction appeared to be explained by the increased coverage in each neighborhood by the sewage system constructed during the intervention. The key explanatory variable was thus an ecological measure of exposure and not household-based, suggesting that the parasite transmission prevented by the program was mainly in the public (vs. the domestic) domain., Conclusion: This study, using advanced statistical modeling to control for individual and ecological potential confounders, demonstrates the impact on intestinal parasites of sanitation improvements implemented at the scale of a large population.

Accumulating evidence suggests that the regulation of gene expression by histone lysine methylation is crucial for several biological processes. The histone lysine methyltransferase G9a is responsible for the majority of dimethylation of histone H3 at lysine 9 (H3K9me2) and is required for the efficient repression of developmentally regulated genes during embryonic stem cell differentiation. However, whether G9a plays a similar role in adult cells is still unclear. We identify a critical role for G9a in CD4(+) T helper (Th) cell differentiation and function. G9a-deficient Th cells are specifically impaired in their induction of Th2 lineage-specific cytokines IL-4, IL-5, and IL-13 and fail to protect against infection with the intestinal helminth Trichuris muris. Furthermore, G9a-deficient Th cells are characterised by the increased expression of IL-17A, which is associated with a loss of H3K9me2 at the Il17a locus. Collectively, our results establish unpredicted and complex roles for G9a in regulating gene expression during lineage commitment in adult CD4(+) T cells.

Trichuris muris is a laboratory model for the human whipworm Trichuris trichiura which infects approximately 1 billion people in tropical and sub-tropical countries. The development of a vaccine would control trichuriasis by promoting the acquisition of immunity during childhood, thereby reducing faecal egg output by the community into their environment. Resistance to T. muris, defined as expulsion of the parasite prior to patency, requires the development of a T helper 2 (Th2) response during a primary infection. To our knowledge this is the first study to describe the protective immune response in the peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and colonic mucosa following s.c. vaccination against T. muris. Susceptible AKR mice were either vaccinated with T. muris excretory-secretory product (ES) in incomplete Freund's adjuvant (IFA) (ES/IFA) or injected with PBS in IFA (PBS/IFA) and for protection experiments were infected with embryonated infective T. muris eggs 10 days later. The ES/IFA vaccine induced the proliferation of PLN cells and their production of Th2 cytokines and the Th1-associated cytokine IFN-gamma. Following a challenge infection, the ES/IFA vaccination offered susceptible mice complete protection. While MLN-derived IFN-gamma was produced by infected mice following either ES/IFA vaccination or PBS/IFA, the protection of susceptible mice by ES/IFA was characterised by the production of MLN-derived Th2 cytokines. Goblet cell hyperplasia and the influx and alternative activation of macrophages were observed locally in the gut post-challenge infection. The rate of epithelial turnover did not appear to be increased by vaccination, suggesting that there are differences in the mechanisms of expulsion between 'natural resistance' and 'vaccinated resistance'. High levels of serum IgG1 and cell-bound IgG1 in the colon of mice protected by the ES/IFA vaccine suggest that antibody may be involved in vaccination-induced worm expulsion., ((c) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric infections, including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of nematode infection., Methods: Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the nematode, Trichuris muris, and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after infection., Results: The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)-stained intestinal goblet cells was observed in Muc2-deficient mice, as infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status., Conclusions: Mucins are an important component of innate defense in enteric infection; this is the first demonstration of the important functional contribution of mucins to host protection from nematode infection., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To determine spatial patterns of co-endemicity of schistosomiasis mansoni and the soil-transmitted helminths (STHs) Ascaris lumbricoides, Trichuris trichiura and hookworm in the Great Lakes region of East Africa, to help plan integrated neglected tropical disease programmes in this region., Method: Parasitological surveys were conducted in Uganda, Tanzania, Kenya and Burundi in 28 213 children in 404 schools. Bayesian geostatistical models were used to interpolate prevalence of these infections across the study area. Interpolated prevalence maps were overlaid to determine areas of co-endemicity., Results: In the Great Lakes region, prevalence was 18.1% for Schistosoma mansoni, 50.0% for hookworm, 6.8% for A. lumbricoides and 6.8% for T. trichiura. Hookworm infection was ubiquitous, whereas S. mansoni, A. lumbricoides and T. trichiura were highly focal. Most areas were endemic (prevalence >or=10%) or hyperendemic (prevalence >or=50%) for one or more STHs, whereas endemic areas for schistosomiasis mansoni were restricted to foci adjacent large perennial water bodies., Conclusion: Because of the ubiquity of hookworm, treatment programmes are required for STH throughout the region but efficient schistosomiasis control should only be targeted at limited high-risk areas. Therefore, integration of schistosomiasis with STH control is only indicated in limited foci in East Africa.

Trichuris muris is a natural mouse model of the human gastrointestinal nematode parasite Trichuris trichiura and it is well established that a T helper type 2-dominated immune response is required for worm expulsion. Macrophages accumulate in the large intestine of mice during infection and these cells are known to express the mannose receptor (MR), which may act as a pattern recognition receptor. The data presented here show for the first time that T. muris excretory/secretory products (E/S) induce bone-marrow-derived macrophages (BMDM) to produce several cytokines and have MR-binding activity. Using alternatively activated BMDM from MR knockout mice it is shown that the production of interleukin-6 partially depends on the MR. Infection of MR knockout mice with T. muris reveals that this receptor is not necessary for the expulsion of the parasite because MR knockout mice expel parasites with the same kinetics as wild-type animals and have similar cytokine responses in the mesenteric lymph nodes. Furthermore, despite acting to reduce serum levels of proinflammatory mediators, absence of the MR does not lead to increased gut inflammation after T. muris infection when assessed by macrophage influx, goblet cell hyperplasia and crypt depth. This work suggests that, despite binding components of T. muris E/S, the MR is not critically involved in the generation of the immune response to this parasite.

Background: Soil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug efficacy estimates are scarce., Methodology/principal Findings: In the present study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0% [95% confidence interval (CI): 82.4-83.6%]) and the ether-based concentration technique (76.6% [95% CI: 75.8-77.3%]). McMaster was the least sensitive (61.7% [95% CI: 60.7-62.6%]) and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85-0.93; p<0.0001). However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus), followed by the ether-based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample). Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators., Conclusions/significance: The results of this study demonstrated that McMaster is a promising technique when making use of FEC to monitor drug efficacy in Trichuris.

This study describes baseline prevalence and intensity of soil-transmitted helminth infections as well as baseline anthropometric and school performance data among public elementary school children in 6 sentinel provinces in the Philippines. Stratified cluster sampling was used to select 6 provinces, where grade 3 elementary school pupils were surveyed. Secondary anthropometric data and achievement test results of the immediate past academic year were examined. Overall cumulative prevalence and proportion of heavy intensity infections for the 6 selected provinces were 54.0% and 23.1%, respectively. These recent findings further support the need for mass treatment to be given at least twice a year. The findings of the study also demonstrate the relationship that exists between worm burden and nutritional status. Strategies focusing on mass treatment integration, environmental sanitation, personal hygiene, and health education should be developed to control soil-transmitted helminth infections and their detrimental effects.

Background: Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children., Methods and Findings: A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0-5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments., Conclusion: Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection.

Mexico established national health weeks (NHWs) in the early 1980s to promote childhood vaccinations. Because of the cumulative worldwide peer-reviewed scientific evidence, the recommendations of the World Health Organization and other international organisations, the political will of the Mexican government and the infrastructure provided by the NHWs, deworming was added to the NHWs in 1993. In addition to the Ministry of Health, several other government organisations participated in administering the deworming component. Tens of millions of school-age and preschool children between the ages of 2 years and 14 years now receive deworming (a single 400 mg dose of albendazole) approximately every 8 months. Between 1993 and 1998 evaluations were carried out in over 90,000 children to determine the effect of NHWs on the prevalence of geohelminth infections. In 1993, the overall prevalence of Ascaris was 20% and that of Trichuris was 15%. Prevalences decreased significantly over time (p <0.001). Treatment efficacy for Ascaris ranged from 91.6% to 85.3%, and for Trichuris, from 97.9% to 42.6%. In 1998, after conducting 12 NHWs with deworming, the respective prevalences were Ascaris 8% and Trichuris 11%. The experience of Mexico in integrating albendazole into its NHWs shows how deworming can be delivered to large numbers of at-risk children using an existing infrastructure. The NHW approach may be generalisable in other countries with successful national vaccination campaigns. The challenge remaining is to sustain the deworming programme until other longer-term behavioural, environmental and socioeconomic changes can be implemented.

IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.

Objective: To assess the prevalence of helminth infections and their associated risks in a community using both wastewater and human excreta in agriculture and aquaculture., Methods: A cross-sectional study was conducted in a peri-urban area in Hanoi, Vietnam. Data on the demography, socioeconomics and sanitation were collected from a survey of 400 agricultural households. Parasitological examination for the eggs of Ascaris sp., Trichuris sp. and hookworm was performed on single stool specimens obtained from study household members' 15-70 years and 0-72 months of age., Results: Of 807 stool samples collected from 620 adults and 187 children, 39% were infected with helminths. The prevalence of infections with Ascaris sp., Trichuris sp. and hookworm was 21.6%, 9.8% and 21.8%, respectively. Univariate and multivariate analyses showed that being an adult, female gender, living in a household without a latrine, excreta composted for less than 1 month and use of fresh human excreta were significantly associated with co-infection with all three helminths. Being an adult was an independent determinant for infections with individual helminths. The absence of a latrine and use of stored urine for irrigation were associated with an increased risk of Ascaris infection. Risk factors for Trichuris infection were inadequately composted excreta and year-round wastewater contact; risk factors for hookworm infection were female gender, household without a latrine and use of fresh human excreta., Conclusion: Wastewater exposure did not pose a major risk for helminth infection in this community. Instead, lack of sanitation facilities and use of fresh or inadequately composted human excreta in agriculture were important risk factors.