Impact of ivermectin mass drug administration on burden of soil-transmitted helminths in onchocerciasis control and elimination programs, Yeki district, southwest Ethiopia.

Community-directed treatment with ivermectin (CDTi) is the primary strategy employed to control and eliminate human onchocerciasis in Ethiopia. After long-term mass distribution for onchocerciasis, ivermectin is expected to have additional benefits beyond the envisioned targets by reducing the burden of other co-endemic parasitic infections as to STHs. To date, studies focused on the collateral impact of CDTi on STH in Ethiopia are scanty. Two community-based cross-sectional surveys (baseline in 1997 and post-CDTi in 2017) were conducted to evaluate the impact of long-term CDTi employed to control and eliminate onchocerciasis on the burden of STH infections in Yeki district of southwest Ethiopia. Stool samples were collected and examined using Ritchie`s concentration and Kato-Katz techniques in the baseline and current study, respectively. Overall, 188(38.3%, 95% Confidence interval (CI) 34.1-42.7%) individuals were positive at least for any of the STH species from 491 study participants in the post-CDTi. The prevalence of A. lumbricoides, hookworms, and T. trichiura was 11.2% (95% CI 8.7-14.3%), 16.3% (95% CI 13.3-19.8%), and 29.9% (95% CI 26.1-34.1%), respectively. Individuals aged 5-9 years had a significantly higher prevalence of A. lumbricoides (Adjusted odds ratio (AOR) 6.5, 95% CI 1.7-25.4), T. trichuria (AOR 8, 95% CI 2.6-25.1), and any STH infection (AOR 5, 95% CI 1.7-14.7) than those of ≥ 51 years. Also, significantly higher prevalences of T. trichuria infection were observed in individuals aged 10-14 years (AOR 4.1, 95% CI 1.7-9.9), 15-20 years (AOR 3.1, 95% CI 1.2-8.1), 21-30 years (AOR 2.4, 95% CI 1.1-5.5), and 31-40 years (AOR 3.2, 95% CI 1.3-7.5) compared with those of ≥ 51 years. The prevalence of A. lumbricoides was significantly higher in males (AOR 0.5, 95% CI 0.3-0.9). Of the 491 study participants, only data from 400 individuals who had not been involved in a mass drug administration (MDA) with other STH anthelmintics were considered in the comparative analysis. Before CDTi, the prevalence of A. lumbricoides, T. trichiura, hookworm, and any STH infection was 47.1% (95% CI 41.6-52.7%), 3.3% (95% CI 1.8-5.9%), 37.9% (95% CI 32.7-43.5%), and 58.8% (95% CI 53.2-64.1%), respectively. Long-term CDTi considerably reduced the prevalences of A. lumbricoides and hookworm by 76.2% and 56.9%, respectively (p < 0.001). Nonetheless, CDTi did not affect the prevalence of T. trichiura infection and, in contrast, it was significantly higher in the current study (P < 0.001). Overall post-CDTi prevalence of any STH infection was considerably lower than reported in the baseline (p < 0.001). It is evidenced that long-term CDTi for onchocerciasis control and elimination had additional benefits by reducing the prevalence of STH infections specifically of A. lumbricoides and hookworm, but had no impact on infections with T. trichuria. Our finding of additional health benefits of large-scale ivermectin administration taking it will aid to increase positive engagement and sustain participation of communities during MDA campaigns, and strengthen governmental and non-governmental organizations (NGOs) support for the undergoing national onchocerciasis elimination program.

Inactivating Effects of Common Laboratory Disinfectants, Fixatives, and Temperatures on the Eggs of Soil Transmitted Helminths.

Soil-transmitted helminths (STH) are important and widespread intestinal pathogens of humans and animals. It is presently unknown which inactivating procedures may be universally effective for safe transport, preservation, and disinfection of STH-contaminated specimens, and this lack of knowledge may expose laboratory staff to higher risk of laboratory-acquired infections (LAI's). There are limited data on the efficacy of commonly used disinfectants and fecal fixatives for inactivating the eggs of STH. This work tested five disinfectants for surface cleanup, four storage temperature conditions, and six transport/storage fixatives, to inactivate eggs of three species of STH of animal origin (Ascaris suum "roundworm," Trichuris vulpis "whipworm" and Ancylostoma caninum "hookworm") as surrogates for human STH. Among disinfectants, exposure to 10% povidone-iodine for ≥5 min inactivated 100% of the three species tested, while 5 min exposure to 95% ethanol inactivated T. vulpis and A. caninum eggs. All of the fixatives tested had inactivation effects on A. caninum hookworm eggs within 24 h of exposure, except potassium dichromate, which required 48 h. 95% ethanol for ≥48 h inactivated eggs from all three STH species. Freezing at ≤-20°C for ≥24 h inactivated eggs of T. vulpis and A. caninum, but only freezing at -80°C for ≥24 h inactivated >99% eggs, including A. suum. This work provides an evidence base for health and safety guidelines and mitigation strategies for the handling, storage, and disposal of stool samples containing STH eggs in laboratory, health care, childcare, or veterinary settings. IMPORTANCE This study systematically evaluates common laboratory disinfectants and storage conditions for their effectiveness in inactivating the infective stages of soil-transmitted helminths (STH). Animal-infecting proxy species were chosen to represent three major groups of STH that infect humans: roundworms, whipworms, and hookworms. Previously published work in this area typically focuses on a particular inactivation method, either for a single STH species, or on a subset of closely related species. Because prediagnostic fecal specimens must be regarded as potentially infectious with a mix of species, such information may be of limited utility in a working laboratory. We provide a straightforward summary of storage and disinfection methods that can achieve complete inactivation across a range of STH species, which represents a significant advance for clinical, veterinary and research laboratory biosafety.

Prevalence of soil-transmitted helminth infections, schistosomiasis, and lymphatic filariasis before and after preventive chemotherapy initiation in the Philippines: A systematic review and meta-analysis.

OBJECTIVE: To estimate the impact of preventive chemotherapy on the prevalence and intensity of soil-transmitted helminth (STH) infections, schistosomiasis, and lymphatic filariasis in the Philippines, using systematic review and meta-analysis. METHODS: We included reports reporting prevalence of STH infections, schistosomiasis, or lymphatic filariasis in the Philippines published until 31 March 2021. Peer-reviewed studies were identified in electronic databases. Grey literature reports by the University of the Philippines and the Department of Health were also included. Pooled infection prevalence, before and after the initiation of preventive chemotherapy, stratified by age group, was calculated using the inverse variance heterogeneity model. FINDINGS: A total of 109 reports were included in the review and meta-analysis. Overall prevalence of moderate-heavy intensity Ascaris lumbricoides (6.6%) and Trichuris trichiura (2.7%) infection after initiation of preventive chemotherapy were significantly lower than the prevalence prior to initiation (23.6% for A. lumbricoides and 12.2% for T. trichiura). Prevalence reductions were also found in school and preschool-age children for A. lumbricoides and T. trichiura. Studies conducted after preventive chemotherapy initiation had significantly lower overall prevalence of moderate-heavy intensity schistosomiasis (3.1% vs 0.2%) and of schistosomiasis in school-age children (30.5% vs 1%). Pooled prevalence of lymphatic filariasis prior to preventive chemotherapy initiation was 3.2% across 12 provinces, while currently only two provinces still have prevalence of more than 1%. There were no published studies reporting prevalence of lymphatic filariasis after initiation of preventive chemotherapy. Heterogeneity was high with I2 mostly above 90%. CONCLUSION: The burden of STH infections and schistosomiasis in children were significantly lower in studies conducted following the initiation of preventive chemotherapy. Eliminating morbidity and interrupting transmission, however, may require expanded control initiatives including community-wide treatment, and improved water, sanitation, and hygiene. Lymphatic filariasis burden has decreased since the implementation of preventive chemotherapy, with all but two provinces having reached the elimination of lymphatic filariasis as a public health problem.

Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics.

Soil transmitted helminths (STHs) are major human pathogens that infect over a billion people. Resistance to current anthelmintics is rising and new drugs are needed. Here we combine multiple approaches to find druggable targets in the anaerobic metabolic pathways STHs need to survive in their mammalian host. These require rhodoquinone (RQ), an electron carrier used by STHs and not their hosts. We identified 25 genes predicted to act in RQ-dependent metabolism including sensing hypoxia and RQ synthesis and found 9 are required. Since all 9 have mammalian orthologues, we used comparative genomics and structural modeling to identify those with active sites that differ between host and parasite. Together, we found 4 genes that are required for RQ-dependent metabolism and have different active sites. Finding these high confidence targets can open up in silico screens to identify species selective inhibitors of these enzymes as new anthelmintics.

Individual responses to a single oral dose of albendazole indicate reduced efficacy against soil-transmitted helminths in an area with high drug pressure.

BACKGROUND: Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment. METHODOLOGY/PRINCIPAL FINDINGS: We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People's Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites. CONCLUSIONS/SIGNIFICANCE: We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018.

Persicaria strigosa (R.Br.) Nakai: a natural anthelmintic?

Persicaria strigosa (R.Br.) Nakai. (Family Polygonaceae) is an important plant of Assam, having several ethnobotanical uses. Tribal communities consume leaf extracts to cure helminth infection. The present study investigated the antioxidant, phytochemicals, and anthelmintic activity of P. strigosa. Total phenolic and flavonoid contents were estimated following standard methods. Antioxidant properties were analyzed by TAC, FRAP, DPPH, ABTS, and TBARS assays. Anthelmintic activity of plant was investigated in Paramphistomum sp. treated with 5 mg/mL, and paralysis and death times were recorded. The most potent solvent extract was performed GC-MS analysis to identify the phytocompounds. Plant extract-treated parasites were further analyzed for biochemical changes. Additionally, molecular docking was performed to study the binding affinities between phytocompounds and enzymes. P. strigosa showed rich phenolics, flavonoids, and antioxidant properties. Ethyl acetate and methanolic extracts showed more powerful antioxidant properties than other extracts. In vitro anthelmintic study found ethyl acetate and diethyl ether the most active extracts. Treated parasites showed a significant decrease in enzyme activity. The highest inhibition was observed in AchE, followed by MDH, LDH, ALP, and ACP. GC-MS study identified 12 probable compounds from the ethyl acetate extract of P. strigosa. Molecular docking showed the strongest binding affinity between the phytocompounds and AchE enzyme (- 7.6 kcal/mol). Overall, compounds C6, C7, and C12 showed better binding affinity compared to other compounds. The in vitro helminth bioassays and biochemical analysis suggest Persicaria strigosa a possible anthelmintic agent. However, isolation and characterization of bioactive compound(s) may promise new drug candidates for helminth infections.

Antiparasitic Properties of Propolis Extracts and Their Compounds.

Propolis is a bee product that has been used in medicine since ancient times. Although its anti-inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti-parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa, studies carried out with the protozoa Trypanosoma spp. and Leishmania spp. have demonstrated promising results in vitro and in vivo. However, there are fewer studies for Plasmodium spp., the etiological agent of malaria and less so for helminths, particularly for Fasciola spp. and Schistosoma spp. Despite the favorable in vitro results with propolis, helminth assays need to be further investigated. However, propolis has shown itself to be an excellent natural product for parasitology, thus opening new paths and approaches in its activity against protozoa and helminths.

Efficacy of Mebendazole and Praziquantel against Soil-Transmitted Helminths and Schistosoma mansoni Infections among Schoolchildren in Northwest Ethiopia.

BACKGROUND: Soil-transmitted helminths (STHs) and Schistosoma mansoni are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited. OBJECTIVE: This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and Schistosoma mansoni parasites. METHODS: A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for Schistosoma mansoni with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and S. mansoni parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel. RESULTS: Among 422 participants, the prevalence of STHs, hookworm, Ascaris lumbricoides, and S. mansoni was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against A. lumbricoides increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against S. mansoni-infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs. CONCLUSION: The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and A. lumbricoides are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat S. mansoni. Therefore, single-dose praziquantel to S. mansoni and redosing of single-dose mebendazole to A. lumbricoides and hookworm infections can be used for treatment purposes.

Mapping survey of schistosomiasis and soil-transmitted helminthiases towards mass drug administration in The Gambia.

BACKGROUND: A national mapping survey of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was conducted in The Gambia in May, 2015. The survey aimed at establishing endemicity of schistosomiasis and soil-transmitted helminthiases to inform decisions on program planning and implementation of mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: A cross-section of 10,434 eligible school aged children (SAC), aged 7 to 14 years old were enrolled in the survey. The participants were randomly sampled from 209 schools countrywide using N/50, where N = total eligible children per school. Stool, and urine samples were provided by each child and examined for schistosomiasis and soil-transmitted helminthic infections using double Kato-Katz, urine filtration, dipstick techniques and CCA rapid test kits. Data were managed using online LINKS system enabling real-time data availability and access. Epi Info version 3.5.3 and health mapper version 4.3.2 were used to generate outputs of endemicity and distribution. Descriptions of mapped districts for MDA eligibility and frequency were done with reference to WHO PC strategy recommendations. Mapping results indicated that nationally, the prevalence of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was 4.3% and 2.5% respectively. In terms of distribution STH are more common in Western Region One (WR1) at 4.1% prevalence, then Lower River Region (LRR) 3.6%, and Western Region Two (WR2) 3.0%. In contrast, SCH indicated much higher prevalence in Central River Region (CRR) at a rate of 14.2%. This is within medium prevalence range, and is followed by Upper River Region (URR) at 9.4%, which is within low prevalence range. At the district level, schistosomiasis prevalence seems to be highest in Niani district (22%) in CRR. Banjul island, the capital city, seems to have the highest prevalence of STH (up to 55%), followed by Kombo South with 22% prevalence. Schistosoma haematobium characterised by haematuria, was the most dominant infection of schistosomiasis discovered followed by Schistosoma mansoni which reported in 0.1% of infections. Out of 42 districts mapped 14, or 38%, of them are co-endemic for soil-transmitted helminthiases (ascariasis, trichuriasis, and hook-worm infections) and schistosomiasis (S. haematobium and S. mansoni). CONCLUSIONS: We identified that 24/42(57%) districts mapped in The Gambia are endemic for schistosomiasis expressing the need for preventive chemotherapy. Twenty (47%) of the districts mapped are endemic for STH. However, only two STH endemic districts namely Banjul (55%) and Kombo South (22%) were within rates eligible for mass drug administration.

High-content approaches to anthelmintic drug screening.

Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges. The lack of in vitro life cycle culture protocols requires harvesting worms from vertebrate hosts or vectors, limiting assay throughput. Once worms are removed from the host environment, established anthelmintics often show no obvious phenotype - raising concerns about the predictive value of many in vitro assays. However, with recent progress in understanding how anthelmintics subvert host-parasite interactions, and breakthroughs in high-content imaging and machine learning, in vitro assays have the potential to discern subtle cryptic parasite phenotypes. These may prove better endpoints than conventional in vitro viability assays.

A strong effect of individual compliance with mass drug administration for lymphatic filariasis on sustained clearance of soil-transmitted helminth infections.

BACKGROUND: The impact of semiannual mass drug administration (MDA) with albendazole (ALB; 400 mg) alone on lymphatic filariasis (LF) and soil-transmitted helminth (STH) infections was assessed during two trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of Congo. The collected data were analyzed to evaluate the effect of compliance with ALB treatment on STH infections. METHODS: STH infections were diagnosed with duplicate Kato-Katz thick smears and the results are reported as eggs per gram of stool. All subjects with at least two STH infection assessments were included in the analyses. We used parametric survival models to assess the influence of compliance with ALB treatment on the probability of (i) achieving sustained clearance of an STH infection, and (ii) acquiring an STH infection during the follow-up. RESULTS: Out of 2658 subjects included in the trials, data on 202 participants (701 person-years; PY) with hookworm infection, 211 (651 PY) with Ascaris lumbricoides infection and 270 (1013 PY) with Trichuris trichiura infection were available to calculate the probability of achieving sustained clearance of infection. The effect of ALB was dose related for all three STH. For hookworm, the time required for sustained clearance was longer (4.3 years, P < 0.001) for participants who took zero doses per year and shorter (3.4 years, P = 0.112) for participants who took two doses per year compared to those who took one dose per year (3.7 years). For Ascaris, the time required to obtain sustained clearance followed the same pattern: 6.1 years (P < 0.001) and 3.2 years (P = 0.004) vs 3.6 years for, zero, two and one dose per year, respectively. For Trichuris, less time was required for sustained clearance (4.2 years, P < 0.001) for fully compliant participants, i.e. those who took two doses per year, than for those who only took one dose per year (5.0 years). ALB was more effective in achieving sustained clearance of STH infection in subjects with light baseline infection intensities compared to those with higher egg counts. CONCLUSION: Our results illustrate the importance of MDA compliance at the level of the individual with respect to the STH benefit provided by semiannual ALB MDA, which is used for the elimination of LF in Central Africa.

Context-dependent roles of B cells during intestinal helminth infection.

The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.

Statistical Regression Model of Water, Sanitation, and Hygiene; Treatment Coverage; and Environmental Influences on School-Level Soil-Transmitted Helminths and Schistosome Prevalence in Kenya: Secondary Analysis of the National Deworming Program Data.

According to the Kenya National School-Based Deworming program launched in 2012 and implemented for the first 5 years (2012-2017), the prevalence of soil-transmitted helminths (STH) and schistosomiasis substantially reduced over the mentioned period among the surveyed schools. However, this reduction is heterogeneous. In this study, we aimed to determine the factors associated with the 5-year school-level infection prevalence and relative reduction (RR) in prevalence in Kenya following the implementation of the program. Multiple variables related to treatment, water, sanitation, and hygiene (WASH) and environmental factors were assembled and included in mixed-effects linear regression models to identify key determinants of the school location STH and schistosomiasis prevalence and RR. Reduced prevalence of Ascaris lumbricoides was associated with low (< 1%) baseline prevalence, seven rounds of treatment, high (50-75%) self-reported coverage of household handwashing facility equipped with water and soap, high (20-25°C) land surface temperature, and community population density of 5-10 people per 100 m2. Reduced hookworm prevalence was associated with low (< 1%) baseline prevalence and the presence of a school feeding program. Reduced Trichuris trichiura prevalence was associated with low (< 1%) baseline prevalence. Reduced Schistosoma mansoni prevalence was associated with low (< 1%) baseline prevalence, three treatment rounds, and high (> 75%) reported coverage of a household improved water source. Reduced Schistosoma haematobium was associated with high aridity index. Analysis indicated that a combination of factors, including the number of treatment rounds, multiple related program interventions, community- and school-level WASH, and several environmental factors had a major influence on the school-level infection transmission and reduction.

When Secretomes Meet Anthelmintics: Lessons for Therapeutic Interventions.

Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite interface have been increasingly recognized. It is now common to hypothesize that parasite-derived molecules (PDMs) are essential mediators used by parasites to establish and remain in their hosts. Suppression of PDM release has been reported for two anthelmintic drug classes, the benzimidazoles and macrocyclic lactones, the mechanisms of action of which remain incompletely resolved. We propose that bringing together recent insights from different streams of parasitology research, for example, immunoparasitology and pharmacology, will stimulate the development of new ways to alter the host-parasite interface in the search for novel anthelmintic strategies.

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

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

Individual adherence to mass drug administration in neglected tropical disease control: A probability model conditional on past behaviour.

We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA)-which we refer to as 'adherence' and 'non-adherence'. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs).

Brazilian red propolis exhibits antiparasitic properties in vitro and reduces worm burden and egg production in an mouse model harboring either early or chronic Schistosoma mansoni infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used in folk medicine for thousands of years and, in the past few decades, it has attracted renewed interest. Although propolis has been traditionally used in many communities worldwide against parasitic diseases, its effect against Schistosoma mansoni infection remains unclear. AIM OF THE STUDY: To demonstrate the effects of Brazilian red propolis on Schistosoma mansoni ex vivo and in an animal model of schistosomiasis. MATERIALS AND METHODS: In vitro, we monitored phenotypic and tegumental changes as well as the effects of the crude extract of propolis on pairing and egg production. In a mouse infected with either immature (early infection) or adult (chronic infection) worms, propolis was administered by oral gavage and we studied the influence of this natural product on worm burden and egg production. RESULTS: Propolis 25 µg/mL reduced motility and caused 100% mortality of adult parasites ex vivo. Further analysis revealed a pronounced reduction in oviposition after exposure to propolis at sub-lethal concentrations. In addition, scanning electron microscopy showed morphological alterations in the tegument of schistosomes. In the animal model, propolis markedly reduced worm burden and egg production in both early and chronic S. mansoni infection when compared to untreated control animals. CONCLUSIONS: The efficacy of Brazilian red propolis in both in vitro and in vivo studies suggests its potential anthelmintic properties against S. mansoni infection.

Revisiting the adequacy of infection criteria recommended in VICH GL 7 for anthelmintic effectiveness studies: Retrospective simulations.

Studies conducted to support registration or approval of veterinary anthelmintics generally follow study design recommendations provided by the VICH (International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products), "Efficacy of Anthelmintics: General Requirements" (VICH GL7). For dose confirmation studies, VICH GL7 provides recommendations for determining that the control animals had an adequate infection "to permit the appropriate standards of efficacy to be met with acceptable statistical and biological certitude/confidence." In the simulation studies described in this report, we investigated the performance of one method, the statistical criterion given in Section 4.5 of VICH GL7, for evaluating the adequacy of infection in anthelmintic studies, in combination with the conventional criterion of a minimum of six adequately infected animals. We conducted numerical simulations, based on parasite data from previously conducted dose confirmation studies in dogs and cattle, to investigate how the statistical criterion impacts adequacy of infection determinations when used with the conventional criterion at various sample sizes. Simulation studies in common nematode species in both dogs and cattle indicated that under certain circumstances the statistical criterion can guard against overinterpreting the evaluation of adequacy of infection as sample size is increased. However, the statistical criterion may be overly restrictive for samples with adequate infection but containing multiple zero parasite counts and adding it to the conventional criterion does not provide any additional benefit when the sample contains no zero counts. It is important for investigators designing efficacy studies to understand the potential impact this criterion may have when establishing adequacy of infection criteria in study protocols.

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

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

Gender differences in the perceived need for community-wide deworming: Formative qualitative research from the DeWorm3 study, India.

Current soil-transmitted helminth (STH) programs target morbidity control with school-based deworming. Increasing interest in steering neglected tropical disease (NTD) programmes from morbidity control towards disease elimination has prompted evaluation of strategies that may interrupt transmission. The feasibility of interrupting transmission of STH with community-wide deworming is being tested in the ongoing DeWorm3 cluster randomized trial. Gender-based perspectives about susceptibility to infection and need for treatment have been shown to influence both health-seeking behaviour and health outcomes. We carried out a qualitative study among men and women in the community to understand their knowledge, beliefs, and attitudes about STH infections and community-wide mass drug administration (cMDA). Eight semi-structured focus group discussions were conducted among men and women residing in the DeWorm3 study site in India-Vellore and Tiruvannamalai districts of Tamil Nadu. Thematic coding was used to analyse the transcripts in ATLAS.ti 8.0. Both men and women in this study demonstrated a high level of STH knowledge but some men had misconceptions that intestinal worms were beneficial. Men and women shared several similar beliefs and attitudes regarding STH treatment. Both believed that adults were likely to have STH infections and both reported that stigma prevented them from seeking treatment. Influenced by gender norms, women were more likely to associate STH infections with inadequate sanitation and hygiene, while men were more likely to believe that those engaged in agricultural work were at risk. Both genders reported a positive attitude towards cMDA for STH. Barriers to cMDA implementation differed by gender; women expressed concern regarding side-effects and drug quality while men were concerned that treatment coverage may be affected due to the absence of people during the day when the drug is distributed. Both men and women perceived the treatment of adults for STH infections to be important, however, the perceived barriers to participating in cMDA differed by gender in this community. The study identified key messages to be incorporated in communication and outreach strategies for cMDA programmes.