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Objective: To assess efficacy of albendazole against Ascaris (A.) lumbrìcoides among school-children at three sites of Rajahmundry, Sundergarh and Wayanad. Methods: Sites were selected based on soil-transmitted helminths prevalence, different sociocultural-geographical characteristics and operational feasibility. 9-12 Years old children from 14 schools were included. The study was conducted in two rounds: baseline & follow up survey. All eligible children found positive for A. lumbricoides at baseline were administered supervised single tablet albendazole 400 mg under the National Deworming Day Initiative. During post-treatment follow-up survey, eligible children who provided second stool sample were included in the final analysis. Stool samples were examined using WHO recommended Kato-Katz technique. Efficacy was estimated based on cure rate (CR) and Fecal Egg Count Reduction Rate (FECRR) among children found positive in baseline and follow-up surveys. Results: 328 Out of 625 (52.5%) were found positive for A. lumbricoides in the baseline survey and 85 out of 178 samples (47.8%) during post-treatment follow-up survey. Overall, the estimated CR was 52.2%. FECRR (95% CI) for albendazole was 72.6% (79.2%-66.0%). The FECRR was highest in East Godaveri [89.7% (96.8%-82.6%)], followed by Sundergarh [86.4% (95.3%-77.5%)] and Wayanad [69% (81.7%-56.4%)]. Conclusions: Our study confirmed overall reduction in FEC although with varying albendazole efficacy for A. lumbricoides infection at three different locations in India. However, these finding may be assessed in context of ongoing MDA under Filaria control program and further studies by in vivo as well as in vitro methods are required to reach to a conclusion on possible resistance if any.

Fascioliasis, only foodborne trematodiasis of worldwide distribution, is caused by Fasciola hepatica and F. gigantica, liver flukes transmitted by freshwater snails. Southern and southeastern Asia is an emerging hot spot of F. gigantica, despite its hitherto less involvement in human infection. In Vietnam, increasing cases have been reported since 1995, whereas only sixteen throughout 1800–1994. A database was created to include epidemiological data of fascioliasis patients from the 63 Vietnam provinces throughout 1995–2019. Case profiles were based on serology, symptoms, eosinophilia, imaging techniques, stool egg finding, and post-specific-treatment recovery. Radio broadcasting about symptoms and costless diagnosis/treatment led patients to hospitals after symptom onset. Yearly case numbers were modelled and spatio-temporally analyzed. Missing data and confounders were assessed. The countrywide spread has no precedent. It started in the central coast, including 53,109 patients, mostly adults and females. Seasonality, linked to vegetable consumption, peaks in June, although the intensity of this peak differs according to relief/climatic zones. Incidence data and logistic regression curves are obtained for the first time in human fascioliasis. Fasciolid hybrids accompanying the spreading F. gigantica flukes, and climate change assessed by risk index correlations, are both ruled out as outbreak causes. Human-guided movements of livestock from an original area prove to be the way used by fasciolids and lymnaeid vectors to expand geographically. Radix viridis, a highly efficient transmitting and colonizing vector, played a decisive role in the spread. The use of irrigated crop fields, widely inhabited by R. viridis, for livestock grazing facilitated the transmission and spread of the disease. General physician awareness and diagnostic capacity improvement proved the successful impact of such knowledge transfer in facilitating and increasing patient infection detection. Information, education and communication to the public by radio broadcasting demonstrated to be very helpful. Fasciola gigantica is able to cause epidemic and endemic situations similar to F. hepatica. The magnitude of the human outbreak in Vietnam is a health wake-up call for southern and southeastern countries of Asia which present the highest human population densities with increasing food demands, uncontrolled livestock inter-country exchange, foreign import practices, and monsoon's increasing climate change impact.

BackgroundInfections caused by both Schistosoma mansoni and Schistosoma haematobium are endemic in Kenya, with over six million children at risk. A national school-based deworming programme was launched in 2012 with the goal of eliminating parasitic worms as a public health problem. This study used a model-based geostatistical (MBG) approach to design and analyse the impact of the programme and inform treatment strategy changes for schistosomiasis (SCH).MethodsA cross-sectional survey of 200 schools across 27 counties of Kenya was utilised. The study design, selection of the schools, and analysis followed the MBG approach, which incorporated historical data on treatment, morbidity, and environmental covariates.ResultsThe overall SCH prevalence was 5.0% (95% CI 4.9%–5.2%) and was estimated, with a high predictive probability of 0.999, to be between 1% and< 10%. The predictive probabilities at county level revealed county heterogeneity, with that of four counties estimated to be between 0% and< 1%, that of 20 counties estimated to be between 1% and< 10%, that of two counties estimated to be between 10% and< 20%, and that of one county estimated to be between 20% and< 50%.ConclusionSCH treatment requirements can now be confidently refined based on the World Health Organization’s guidelines. The four counties with prevalences of between 0% and< 1% may consider suspending treatment only in areas (i.e., sub-counties and wards) where the prevalence is< 1%.

Background: Kenya is endemic for soil-transmitted helminths (STH) with over 6 million children in 27 counties currently at-risk. A national school-based deworming programme (NSBDP) was launched in 2012 with a goal to eliminate parasitic worms as a public health problem. This study used model-based geostatistical (MBG) approach to design and analyse the impact of the NSBDP and inform treatment strategy changes. Methods: A cross-sectional study was used to survey 200 schools across 27 counties in Kenya. The study design, school selection and analysis followed the MBG approach which incorporated historical data on treatment, morbidity and environmental covariates to efficiently predict the helminths prevalence in Kenya. Results: Overall, the NSBDP geographic area prevalence for any STH was estimated to sit between 2 % and 0.999. Species-specific thresholds were between 2 % and 0.999. Conclusions: Based on the World Health Organization guidelines, STH treatment requirements can now be confidently refined. Ten counties may consider suspending treatment and implement appropriate surveillance system, while another 10 will require treatment once every two years, and the remaining seven will require treatment once every year.

The objective of this manuscript is to provide selective examples of the work of the Pan American Health Organization/World Health Organization (PAHO/WHO) Collaborating Centre for Research and Training in Parasite Epidemiology and Control which contribute to the WHO goal of eliminating neglected tropical diseases by 2030. This PAHO/WHO CC specifically aligns its activities with the Sustainable Development Goals and with the goals outlined in the WHO Road Map for Neglected Tropical Diseases 2021-2030. Its role is to contribute to advancing global action on NTDs, primarily through policy development and knowledge translation. Three important projects have recently been completed: 1. Finalizing the Monitoring and Evaluation Framework for the NTD Road Map (published May 2021; this PAHO/WHO CC was a member of the working group); 2. Developing new guidelines for the preventive chemotherapy of Taenia solium taeniasis (published September 2021; this PAHO/WHO CC was co-Chair; and 3. Formulating a policy brief on deworming for adolescent girls and women of reproductive age (published January 2022; this PAHO/WHO CC is co-lead). These projects are the result of the integration of expertise and experience from multiple partners, including from PAHO and WHO (where both organizations provided key leadership), this PAHO/WHO CC, government ministries, civil society organizations and universities, among others. In conclusion, this PAHO/WHO CC contributes timely guidance to country-led evidence-informed public health policy, to cost-effective program implementation and to the identification of priority research topics – all focused, ultimately, on eliminating NTD-attributable morbidity by 2030.

Abstract Background Establishment of efficient control programs for strongyloidiasis, the infection by Strongyloides stercoralis, is among the World Health Organization (WHO) targets for 2030. Ivermectin is a drug of choice for strongyloidiasis, but its weight-based administration can be unfeasible in remote areas. We evaluated a WHO tablet pole for administration of ivermectin in school-age children living in remote villages in Ecuador. Methods Children were enrolled in 16 villages in Esmeraldas Province of Ecuador, between July 2021 and June 2022. The pole identified four height intervals corresponding to ivermectin doses going from one to four tablets. For each child, we calculated the dose (µg/kg) administered with both weight-based and pole-based administration. Results were classified as follows: optimal dose, acceptable, overdose, underdose. Agreement between the two methods for estimating the number of tablets was assessed with Cohen’s kappa coefficient. Estimations were reported with 95% confidence intervals (CIs). Results Total of 778 children (47.3% female) were enrolled, with median age of 9.59 years (interquartile range: 7.42‒11.22). Optimal dose was achieved for a higher proportion of children when assessed with weight (37.9%) than with pole (25.7%). Underdose and overdose were more frequent with the pole (8.3% and 19.2% children, respectively) than with the weight-based (3.7% and 6.0%, respectively) administration. Agreement between weight-based and pole-based administration was moderate: 0.56 (95% CI 0.51, 0.61). The two methods indicated the same number of tablets in 71.6% (95% CI 0.684, 0.748) cases. Conclusions In our setting, the tablet pole could be a valid alternative. The tool needs further evaluation in different populations. Graphical Abstract

Madagascar is one of the countries with the highest burden of schistosomiasis worldwide. The release from the WHO of the new 2021–2030 neglected tropical disease (NTD) roadmap alongside with the schistosomiasis guidelines sets the ambitious goal of eliminating schistosomiasis as a public health problem worldwide. In Madagascar, implementation barriers exist. This paper has the objective of identifying strengths, weaknesses, opportunities and threats in order to build on their basis practices and policies that can help the country to align with the international global health agenda and reach the ambitious goal set by the WHO.

BackgroundSoil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool.MethodsWe performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design.Principal findingsKato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity.Conclusions/significanceWe confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs.Trial registrationClinicalTrials.gov NCT03465488.

Kenya is among the countries endemic for soil-transmitted helminthiasis (STH) with over 66 subcounties and over 6 million individuals being at-risk of infection. Currently, the country is implementing mass drug administration (MDA) to all the at-risk groups as the mainstay control strategy. This study aimed to develop and analyze an optimal control (OC) model, from a transmission interruption model, to obtain an optimal control strategy from a mix of three strategies evaluated. The study used the Pontryaginʼs maximum principle to solve, numerically, the OC model. The analysis results clearly demonstrated that water and sanitation when implemented together with the MDA programme offer the best chances of eliminating these tenacious and damaging parasites. Thus, we advocate for optimal implementation of the combined mix of the two interventions in order to achieve STH elimination in Kenya, and globally, in a short implementation period of less than eight years.

Abstract Background The diagnosis of strongyloidiasis is challenging. Serological tests are acknowledged to have high sensitivity, but issues due to cross-reactions with other parasites, native parasite antigen supply and intrinsic test variability do occur. Assays based on recombinant antigens could represent an improvement. The aim of this study was to assess the sensitivity and specificity of two novel immunoglobulin (Ig)G and IgG4 enzyme-linked immunosorbent assays (ELISAs) based on the recombinant antigens NIE/SsIR for the diagnosis of strongyloidiasis. Methods This was a retrospective diagnostic accuracy study. We included serum samples collected from immigrants from strongyloidiasis endemic areas for whom there was a matched result for Strongyloides stercoralis on agar plate culture and/or PCR assay, or a positive microscopy for S. stercoralis larvae. For the included samples, results were also available from an in-house indirect fluorescent antibody test (IFAT) and a commercial (Bordier ELISA; Bordier Affinity Products SA) ELISA. We excluded: (i) samples with insufficient serum volume; (ii) samples from patients treated with ivermectin in the previous 6 months; and (iii) sera from patients for whom only routine coproparasitology was performed after formol–ether concentration, if negative for S. stercoralis larvae. The performance of the novel assays was assessed against: (i) a primary reference standard, with samples classified as negative/positive on the basis of the results of fecal tests; (ii) a composite reference standard (CRS), which also considered patients to be positive who had concordant positive results for the IFAT and Bordier ELISA or with a single “high titer” positive result for the IFAT or Bordier ELISA. Samples with a single positive test, either for the IFAT or Bordier ELISA, at low titer, were considered to be “indeterminate,” and analyses were carried out with and without their inclusion. Results When assessed against the primary reference standard, the sensitivities of the IgG and IgG4 ELISAs were 92% (95% confidence interval [CI]: 88–97%) and 81% (95% CI: 74–87%), respectively, and the specificities were 91% (95% CI: 88–95%) and 94% (95% CI: 91–97%), respectively. When tested against the CRS, the IgG ELISA performed best, with 78% sensitivity (95% CI: 72–83%) and 98% specificity (95% CI: 96–100%), when a cut-off of 0.675 was applied and the indeterminate samples were excluded from the analysis. Conclusion The NIE-SsIR IgG ELISA demonstrated better accuracy than the IgG4 assay and was deemed promising particularly for serosurveys in endemic areas. Graphical abstract

Preventive chemotherapy interventions for the control of soil-transmitted helminthiases (STH) and schistosomiasis scaled up from a global coverage level of around 5% in the year 2000 to a coverage that surpassed 60% in the year 2019. The present paper analyses the concomitant reduction in the number of disability-adjusted life years (DALYs) lost due to STH and schistosomiasis during the same period, from 6.3 to 3.5 million DALYs. The cumulative gain during the 19-year period was estimated at over 26 million DALYs. Given the low cost of the intervention, our study suggests that deworming for STH and schistosomiasis is one of the most cost-effective public health interventions.

Abstract Background Implementation of control programmes for Strongyloides stercoralis infection is among the targets of the World Health Organization Roadmap to 2030. Aim of this work was to evaluate the possible impact in terms of economic resources and health status of two different strategies of preventive chemotherapy (PC) compared to the current situation (strategy A, no PC): administration of ivermectin to school-age children (SAC) and adults (strategy B) versus ivermectin to SAC only (strategy C). Methods The study was conducted at the IRCCS Sacro Cuore Don Calabria hospital, Negrar di Valpolicella, Verona, Italy, at the University of Florence, Italy, and at the WHO, Geneva, Switzerland, from May 2020 to April 2021. Data for the model were extracted from literature. A mathematical model was developed in Microsoft Excel to assess the impact of strategies B and C in a standard population of 1 million subjects living in a strongyloidiasis endemic area. In a case base scenario, 15% prevalence of strongyloidiasis was considered; the 3 strategies were then evaluated at different thresholds of prevalence, ranging from 5 to 20%. The results were reported as number of infected subjects, deaths, costs, and Incremental-Effectiveness Ratio (ICER). A 1-year and a 10-year horizons were considered. Results In the case base scenario, cases of infections would reduce dramatically in the first year of implementation of PC with both strategy B and C: from 172 500 cases to 77 040 following strategy B and 146 700 following strategy C. The additional cost per recovered person was United States Dollar (USD) 2.83 and USD 1.13 in strategy B and C, respectively, compared to no treatment in the first year. For both strategies, there was a downtrend in costs per recovered person with increasing prevalence. The number of adverted deaths was larger for strategy B than C, but cost to advert one death was lower for strategy C than B. Conclusions This analysis permits to estimate the impact of two PC strategies for the control of strongyloidiasis in terms of costs and adverted infections/deaths. This could represent a basis on which each endemic country can evaluate which strategy can be implemented, based on available funds and national health priorities.

Abstract Background Soil-transmitted helminths (STHs) are a major cause of poor health in low- and middle-income countries. In particular, hookworm is known to cause anaemia in children and women of reproductive age (WRA). One goal of the World Health Organization’s (WHO) 2030 roadmap for neglected tropical diseases is to reduce STH-related morbidity in WRA. As a minimal intervention, the WHO recommends deworming adolescent girls annually during human papilloma virus vaccination programmes and WRA during pregnancy and lactation. These routine interventions are low cost and can be implemented even by the most basic health services in endemic countries. In this study we use a cohort model to investigate the potential impact on STH-related morbidity in WRA. Results Annual deworming treatment of adolescent girls reduces the prevalence of moderate- and heavy-intensity infections in this age group by up to 60% in moderate transmission settings and by 12–27% in high transmission settings. Treatment of WRA during pregnancy and lactation on its own has a small (

Soil-transmitted helminth (STH) infections cause significant morbidity in children and women of reproductive age. The World Health Organization (WHO) recommends preventive chemotherapy (PC) of at-risk populations with anthelminthics to control these infections. Historically, STH are very intensively transmitted in Pemba Island (Zanzibar). A survey conducted in 1994 in 12 schools estimated a STH prevalence near to 100%. This extremely high prevalence induced the introduction of PC in the island; initially, however, PC was not regularly administered because of difficulties linked to drug procurement. A second STH survey, conducted in 2011, in 24 schools estimated a prevalence of STH of 89%; after this survey, PC was regularly administered until 2018. We conducted a survey in 2021 using the same method as that used in 2011. The prevalence of STH was evaluated at 80% (95% CI 78.1-81.5) and most of the STH cases were due to Trichuris trichiura. More than 32% (95% CI 30.3-34.0) of the children investigated had infections of moderate or heavy intensity. PC has been conducted for over 25 years in Pemba Island. However, despite its beneficial impact, both the prevalence and the intensity of STH infections remain high, and the intervention has been insufficient in controlling STH morbidity. This is probably due to a combination of irregular PC, climatic conditions favourable to STH transmission, the low sensitivity of T. trichiura to benzimidazoles, high population density and poor sanitation. Improvement of sanitation coverage remains a key measure to permanently reduce the prevalence and intensity of STH. Possible changes to the present PC approaches to better control STH in Pemba would be (i) to assure high coverage in all schools, (ii) to use mebendazole instead of albendazole given its better activity on T. trichiura and (iii) to use a combination of ivermectin and mebendazole to further increase anthelminthic efficacy on T. trichiura.

Abstract Background Soil-transmitted helminthiases (STH) are part of the group of neglected tropical diseases traditionally treated with preventive chemotherapy interventions. In recent years, drug donations have been essential to expanding preventive chemotherapy and achieving progressive control of morbidity from STH. This study aims to evaluate the need for anthelminthic medicines during 2020–2030. Methods To estimate the need for anthelminthic medicines, we considered three different scenarios: (1) the control programmes continues to expand coverage and maintains the frequency of drug administration established at baseline; (2) the programmes continues to expand coverage but adapts the frequency of drug administration when the STH prevalence is reduced and (3) the STH programme becomes self-sustainable in some endemic countries. Results We estimate that the number of anthelmintic medicines needed to treat school-aged children will increase by 40% by 2025 and by 52% by 2030 if countries do not change the frequency of preventive chemotherapy (scenario 1); that the number of tablets needed will reduce by 32.4% by 2025 and by 49.1% in 2030 if endemic countries reduce the frequency of preventive chemotherapy (scenario 2); and drug donations could be reduced by 54.4% by 2025 and 74.4% by 2030 if some endemic countries could become independent in drug procurement (scenario 3). Conclusions The number of anthelmintic medicines needed to achieve elimination of morbidity due to STH in school-aged children will decline during 2020–2030. The decline will be substantial if a number of “upper-middle income” countries in which STH are endemic procure, as expected, anthelminthic medicines independently.

Abstract 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.

Soil-transmitted helminth (STH) infections are among the most common neglected tropical diseases worldwide causing high morbidity and mortality rates in endemic areas. Preventive chemotherapy (PC) programmes and health education are recommended by the World Health Organization (WHO) to reduce the impact of STH in endemic countries. Following our role as WHO collaborating centre (WHO CC ITA-116), we have developed a WebGIS and a dataset to support PC programmes to monitor the impact of STH control. This vHealth presentation shows the potentiality of these tools in improving communication among WHO’s regional and country offices, Ministries of Health, pharmaceutical industries and other partners.

We performed a cross-sectional parasitological survey to assess the prevalence of protozoa and helminth infection among 275 school-age children (SAC) living in rural and peri-urban areas located in different ecological zones of the Department of La Paz, Bolivia. Public health activities for the control of STH, based on the biannual administration of mebendazole to preschool and school children are implemented at national level since 1986.We found an overall prevalence of 82.2% for intestinal parasites, including protozoa (80%) and helminths (23.3%). Blastocystis and Entamoeba coli were the most prevalent protozoa (found in 44% and 20.7% of the SAC enrolled); as for helminths, Ascaris lumbricoides and Hymenolepis nana were diagnosed in 14.5% and 3.3% of the children, respectively, followed by Trichuris trichiura 1.4%, Enterobius vermicularis 1.4%, Strongyloides stercoralis 0.7% and hookworms 0.7%.Molecular characterization of Blastocystis positive samples evidenced three different subtypes (ST1, ST2, ST3) highlighting the risk of transmission also from animal reservoir. We found a significant difference in the distribution of intestinal parasitic infection (IPIs) by ecological zone (44/74. 59% in Andean highlands, 94/170, 88% in tropical lowlands and 88/94, 94% in the Yungas, p

Abstract The World Health Organization recommends deworming to reduce soil‐transmitted helminth (STH)‐attributable morbidity in women of reproductive age, including pregnant and lactating women, to reduce blood loss, iron deficiency anaemia and nutrient malabsorption. This study assessed the impact of maternal postpartum deworming with albendazole approximately 1 day after delivery on infant milk intake among a subset of 216 randomly selected mother–infant pairs recruited into a large trial in Peru. Infant milk intake was measured using the deuterium‐oxide method at 1‐ and 6‐month postpartum. Maternal STH infection was measured at 6‐month postpartum. At 1‐month postpartum, mean intake was 756 ± 16 and 774 ± 18 mL day−1 in the albendazole and placebo groups, respectively (mean difference: −18 mL day−1; 95% CI: −65, 30). At 6‐month postpartum, mean intake was 903 ± 16 and 908 ± 18 mL day−1 in the albendazole and placebo groups, respectively (mean difference: −5 mL day−1; 95% CI: −52, 43). There was no statistically significant difference in milk intake between groups at either time point. At 6‐month postpartum, mothers infected with Trichuris trichiura had infants with higher milk intakes (adjusted mean difference: 70 mL day−1; 95% CI: 20, 120) compared with uninfected mothers. However, there was no statistically significant difference in infant milk intake between mothers who had moderate‐and‐heavy intensity infection compared with the comparison group (mothers with no and light intensity infection). A lower prevalence and intensity of infection, and inclusion of uninfected mothers in both arms of the trial, resulting in effect dilution, may explain the null findings.

BackgroundAlbendazole (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 findingsWe 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/significanceWe 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 registrationThe study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018.

Neglected tropical diseases (NTDs) remain a significant cause of morbidity and mortality in many low-income and middle-income countries. Several NTDs, namely lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH) and trachoma, are predominantly controlled by preventive chemotherapy (or mass drug administration), following recommendations set by the WHO. Over one billion people are now treated for NTDs with this strategy per year. However, further investment and increased domestic healthcare spending are urgently needed to continue these programmes. Consequently, it is vital that the cost-effectiveness of preventive chemotherapy is understood. We analyse the current estimates on the cost per disability-adjusted life year (DALY) of the preventive chemotherapy strategies predominantly used for these diseases and identify key evidence gaps that require further research. Overall, the reported estimates show that preventive chemotherapy is generally cost-effective, supporting WHO recommendations. More specifically, the cost per DALY averted estimates relating to community-wide preventive chemotherapy for lymphatic filariasis and onchocerciasis were particularly favourable when compared with other public health interventions. Cost per DALY averted estimates of school-based preventive chemotherapy for schistosomiasis and STH were also generally favourable but more variable. Notably, the broader socioeconomic benefits are likely not being fully captured by the DALYs averted metric. No estimates of cost per DALY averted relating to community-wide mass antibiotic treatment for trachoma were found, highlighting the need for further research. These findings are important for informing global health policy and support the need for continuing NTD control and elimination efforts.

BackgroundSoil transmitted helminths (STH) are a common infection among pregnant women in areas with poor access to sanitation. Deworming medications are cheap and safe; however, the health benefit of deworming during pregnancy is not clear.Methods / principal findingsWe created a retrospective cohort of more than 800,000 births from 95 Demographic and Health Survey datasets to estimate the impact of deworming medicine during routine antenatal care (ANC) on neonatal mortality and low birthweight. We first matched births on the probability of receiving deworming during ANC. We then modeled the birth outcomes with the matched group as a random intercept to estimate the effect of deworming during antenatal care after accounting for various risk factors. We also tested for effect modification of soil transmitted helminth prevalence on the impact of deworming during ANC. Receipt of deworming medication during ANC was associated with a 14% reduction in the risk of neonatal mortality (95% confidence interval = 10-17%, n = 797,772 births), with no difference between high and low transmission countries. In low transmission countries, we found an 11% reduction in the odds of low birth weight (95% confidence interval = 8-13%) for women receiving deworming medicine, and in high transmission countries, we found a 2% reduction in the odds of low birthweight (95% confidence interval = 0-5%).Conclusions / significanceThese results suggest a substantial health benefit for deworming during ANC that may be even greater in countries with low STH transmission.

BackgroundStrongyloides stercoralis is a soil-transmitted helminth (STH) that affects approximately 600 million people worldwide. Interventions targeting S. stercoralis have not been implemented yet. Specific treatment (ivermectin) could be included in already ongoing preventive chemotherapy (PC) campaigns targeting other STHs. The aim of this study was to estimate the quantity of ivermectin needed for an integrated STH/S. stercoralis control program.Methododology/principal findingsOur study estimates the number of school- age children (SAC) (the main focus of STH deworming campaigns) in need of PC with ivermectin. The normal approximation of the binomial distribution was adopted to calculate the hypothetical prevalence distribution in each endemic country. Considering prevalence thresholds for PC equal to 10%, 15%, and 20%, we estimated the number of SAC in need of treatment. We adjusted the estimates accounting for ivermectin distributed in lymphatic filariasis and onchocerciasis elimination programs and excluded from our calculation areas where Loa loa is endemic. The global number of SAC that should be targeted in PC campaigns was estimated at 283.9 M (95% CI: 163.4-368.8), 207.2 M (95% CI: 160.9-380.7), and 160.7 M (95% CI: 86.6-225.7) when the threshold for intervention was set to 10%, 15%, and 20%, respectively. India, China, Indonesia, Bangladesh, and Nigeria accounted for about 50% of the global SAC would have to be covered by PC intervention.Conclusions/significanceOur analysis may support endemic countries to evaluate the ivermectin quantity needed for integrating strongyloidiasis in the existing STH programs. These estimates might also show to generic drug manufacturers the size of the potential market for ivermectin and encourage its production.

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.

BackgroundEfforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality.MethodologyDuring four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections.ResultsAcross the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets. In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected.Conclusion/significanceIn these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality.

Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low- and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infections, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infections, resulting in an important reduction in STH-attributable morbidity in children, while additional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved.

BackgroundThe key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation.MethodologyWe compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses.Principal findingsWe compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries.Conclusions and significanceAgreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.

Background: Schistosomiasis is one of the most prevalent neglected tropical diseases (NTDs) with an estimated 229 million people requiring preventive treatment worldwide. Recommendations for preventive chemotherapy strategies have been made by the World Health Organization (WHO) whereby the frequency of treatment is determined by the settings prevalence. Despite recent progress, many countries still need to scale up treatment and important questions remain regarding optimal control strategies. This paper presents a systematic review of the economic evaluations of human schistosomiasis interventions. Methods: A systematic review of the literature was conducted on 22nd August 2019 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. The focus was economic evaluations of schistosomiasis interventions, such as cost-effectiveness and cost-benefit analyses. No date or language stipulations were applied to the searches. Results: We identified 53 relevant health economic analyses of schistosomiasis interventions. Most studies related to Schistosoma japonicum followed by S. haematobium. Several studies also included other NTDs. In Africa, most studies evaluated preventive chemotherapy, whereas in China they mostly evaluated programmes using a combination of interventions (such as chemotherapy, snail control and health education). There was wide variation in the methodology and epidemiological settings investigated. A range of effectiveness metrics were used by the different studies. Conclusions: Due to the variation across the identified studies, it was not possible to make definitive policy recommendations. Although, in general, the current WHO recommended preventive chemotherapy approach to control schistosomiasis was found to be cost-effective. This finding has important implications for policymakers, advocacy groups and potential funders. However, there are several important inconsistencies and research gaps (such as how the health benefits of interventions are quantified) that need to be addressed to identify the resources required to achieve schistosomiasis control and elimination.

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.

Background: Schistosomiasis is one of the most prevalent neglected tropical diseases (NTDs) with an estimated 229 million people requiring preventive treatment worldwide. Recommendations for preventive chemotherapy strategies have been made by the World Health Organization (WHO) whereby the frequency of treatment is determined by the settings prevalence. Despite recent progress, many countries still need to scale up treatment and important questions remain regarding optimal control strategies. This paper presents a systematic review of the economic evaluations of human schistosomiasis interventions. Methods: A systematic review of the literature was conducted on 22nd August 2019 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. The focus was economic evaluations of schistosomiasis interventions, such as cost-effectiveness and cost-benefit analyses. No date or language stipulations were applied to the searches. Results: We identified 53 relevant health economic analyses of schistosomiasis interventions. Most studies related to Schistosoma japonicum followed by S. haematobium. Several studies also included other NTDs. In Africa, most studies evaluated preventive chemotherapy, whereas in China they mostly evaluated programmes using a combination of interventions (such as chemotherapy, snail control and health education). There was wide variation in the methodology and epidemiological settings investigated. A range of effectiveness metrics were used by the different studies. Conclusions: Due to the variation across the identified studies, it was not possible to make definitive policy recommendations. Although, in general, the current WHO recommended preventive chemotherapy approach to control schistosomiasis was found to be cost-effective. This finding has important implications for policymakers, advocacy groups and potential funders. However, there are several important inconsistencies and research gaps (such as how the health benefits of interventions are quantified) that need to be addressed to identify the resources required to achieve schistosomiasis control and elimination.

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

Soil Transmitted Helminth (STH) infections affect over 1.5 billion people worldwide. Although prevalent in all age groups, school aged children are a high-risk groups for STH infections. In Bhutan, epidemiological data on STH were collected from western Bhutan in 2003, which found a prevalence of 16.5%. However, little evidence is available on the prevalence of infection at national level. Therefore, this study was conducted with the aim to assess the prevalence and intensity of STH infections, and identify significant correlates of STH among students. A school-based survey was conducted in three regions of Bhutan. Two-stage cluster sampling was adopted to select a sample of 1500 students from 24 schools, in equal proportion from three regions of the country. A total of 1456 (97%) students were interviewed and their stool sample examined for the presence of parasites. Mini-FLOTAC technique was used to detect the parasite eggs/ova. The prevalence of any STH infection was 1.4%, with 0.8% Ascaris lumbricoides, 0.5% Trichuris trichiura and 0.2% hookworms. The eastern region had the highest prevalence at 2.3%. Except for one student who had moderate intensity of A. lumbricoides, the rest had light infection. Any STH presence was significantly associated with father's occupation, father's education level, type of house and the flooring of the house in which students reported to live. No significant associations were observed between water, sanitation and hygiene (WASH) variables measured and presence of any STH infection. The prevalence of STH was found to be very low with primarily light intensity in this study. Nonetheless, it was also found that the sanitation situation is not ideal in the country, with several students reporting constant or partial open defecation leading to environmental contamination. Based on this prevalence and in line with the WHO guideline, it is recommended that deworming be reduced to once a year in combination with concerted health education on proper hygiene and sanitation practice.

BackgroundLarge-scale deworming programs have, to date, mostly targeted preschool- and school-age children. As community-based deworming programs become more common, deworming will be offered to women of reproductive age. The World Health Organization recommends preventive chemotherapy be administered to pregnant women only after the first trimester. It is therefore important for deworming programs to be able to identify women in early pregnancy. Our objective was to validate a short questionnaire which could be used by deworming program managers to identify and screen out women in early pregnancy.Methodology/principal findingsIn May and June 2018, interviewers administered a questionnaire, followed by a pregnancy test, to 1,203 adult women living in the Peruvian Amazon. Regression analyses were performed to identify questions with high predictive properties (using the pregnancy test as the gold standard). Test parameters were computed at different decision tree nodes (where nodes represented questions). With 106 women confirmed to be pregnant, the positive predictive value of asking the single question 'Are you pregnant?' was 100%, at a 'cost' of a false negative rate of 1.9% (i.e. 21 women were incorrectly identified as not pregnant when they were truly pregnant). Additional questions reduced the false negative rate, but increased the false positive rate. Rates were dependent on both the combination and the order of questions.Conclusions/significanceTo identify women in early pregnancy when deworming programs are community-based, both the number and order of questions are important. The local context and cultural acceptability of different questions should inform this decision. When numbers are manageable and resources are available, pregnancy tests can be considered at different decision tree nodes to confirm pregnancy status. Trade-offs in terms of efficiency and misclassification rates will need to be considered to optimize deworming coverage in women of reproductive age.

The egg reduction rate (ERR) is the current standard mean to assess the efficacy of drugs against human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura and hookworm). Although the timing of post-treatment sampling is pivotal for a readily interpretation of drug efficacy, there is lack empirical data that allows recommending the optimal time point for a follow-up egg counting. In the present study, we re-analyzed both the kinetics of worm expulsion and egg output for Ascaris lumbricoides following a single oral dose of albendazole in a series of studies previously conducted in Kenyan communities. The results indicate that it takes up to 10 days post-treatment before the expulsion of both adult male and female Ascaris worms is completed, approximately 20% of the worms being expelled between day 7 and 10 post-treatment. The sequential analysis of the egg out put, indicated a poor ERR (89.4%) at day 7 post-treatment, but a 100% ERR at day 14 and 21 post-treatment. Based on our findings we recommend to wait at least 14 days after an albendazole treatment before conducting the follow-up egg count. Any sampling before this time point may result in biased ERR estimates, due the release of residual eggs from moribund or degenerating worms. Keywords: Ascaris lumbricoides, Worm expulsion, Egg reduction rate, Anthelmintic resistance, Albendazole

BackgroundIn South Asia, hundreds of millions of people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura). However, high-resolution risk profiles and the estimated number of people infected have yet to be determined. In turn, such information will assist control programs to identify priority areas for allocation of scarce resource for the control of soil-transmitted helminth infection.MethodologyWe pursued a systematic review to identify prevalence surveys pertaining to soil-transmitted helminth infections in four mainland countries (i.e., Bangladesh, India, Nepal, and Pakistan) of South Asia. PubMed and ISI Web of Science were searched from inception to April 25, 2019, without restriction of language, study design, and survey date. We utilized Bayesian geostatistical models to identify environmental and socioeconomic predictors, and to estimate infection risk at high spatial resolution across the study region.Principal findingsA total of 536, 490, and 410 georeferenced surveys were identified for A. lumbricoides, hookworm, and T. trichiura, respectively. We estimate that 361 million people (95% Bayesian credible interval (BCI) 331-395 million), approximately one-quarter of the South Asia population, was infected with at least one soil-transmitted helminth species in 2015. A. lumbricoides was the predominant species. Moderate to high prevalence (>20%) of any soil-transmitted helminth infection was predicted in the northeastern part and some northern areas of the study region, as well as the southern coastal areas of India. The annual treatment needs for the school-age population requiring preventive chemotherapy was estimated at 165 million doses (95% BCI: 146-185 million).Conclusions/significanceOur risk maps provide an overview of the geographic distribution of soil-transmitted helminth infection in four mainland countries of South Asia and highlight the need for up-to-date surveys to accurately evaluate the disease burden in the region.

BackgroundBecause the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs).MethodologyWe compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs.Principal findingsAll diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration.Conclusions/significanceOur results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program.Trial registrationClinicalTrials.gov NCT03465488.

BackgroundPreventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz.MethodsAn ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy.Principal findings and conclusionsThe results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance.Trial registrationClinicalTrials.gov NCT03465488.

BackgroundThe World Health Organization has recently reemphasized the importance of providing preventive chemotherapy to women of reproductive age in countries endemic for soil-transmitted helminthiasis as they are at heightened risk of associated morbidity. The Demographic and Health Surveys (DHS) Program is responsible for collecting and disseminating accurate, nationally representative data on health and population in developing countries. Our study aims to estimate the number of pregnant women at risk of soil-transmitted helminthiasis that self-reported deworming by antenatal services in endemic countries that conducted Demographic and Health Surveys.Methodology/principal findingsThe number of pregnant women living in endemic countries was extrapolated from the United Nations World Population Prospects 2015. National deworming coverage among pregnant women were extracted from Demographic and Health Surveys and applied to total numbers of pregnant women in the country. Sub-national DHS with data on self-reported deworming were available from 49 of the 102 endemic countries. In some regions more than 73% of STH endemic countries had a DHS. The DHS report an average deworming coverage of 23% (CI 19-28), ranging from 2% (CI 1-3) to 35% (CI 29-40) in the different regions, meaning more than 16 million pregnant women were dewormed in countries surveyed by DHS. The deworming rates amongst the 43 million pregnant women in STH endemic countries not surveyed by DHS remains unknown.Conclusions/significanceThese estimates will serve to establish baseline numbers of deworming coverage among pregnant women, monitor progress, and urge endemic countries to continue working toward reducing the burden of soil-transmitted helminthiasis. The DHS program should be extended to STH-endemic countries currently not covering the topic of deworming during pregnancy.

[This corrects the article DOI: 10.1371/journal.pntd.0006655.].

BACKGROUND:To work towards reaching the WHO goal of eliminating soil-transmitted helminth (STH) infections as a public health problem, the total number of children receiving anthelmintic drugs has strongly increased over the past few years. However, as drug pressure levels rise, the development of anthelmintic drug resistance (AR) is more and more likely to appear. Currently, any global surveillance system to monitor drug efficacy and the emergence of possible AR is lacking. Consequently, it remains unclear to what extent the efficacy of drugs may have dropped and whether AR is already present. The overall aim of this study is to recommend the best diagnostic methods to monitor drug efficacy and molecular markers to assess the emergence of AR in STH control programs. METHODS:A series of drug efficacy trials will be performed in four STH endemic countries with varying drug pressure (Ethiopia and Brazil: low drug pressure, Lao PDR: moderate drug pressure and Tanzania: high drug pressure). These trials are designed to assess the efficacy of a single oral dose of 400 mg albendazole (ALB) against STH infections in school-aged children (SAC) by microscopic (duplicate Kato-Katz thick smear, Mini-FLOTAC and FECPAKG2) and molecular stool-based diagnostic methods (quantitative PCR (qPCR)). Data will be collected on the cost of the materials used, as well as the time required to prepare and examine stool samples for the different diagnostic methods. Following qPCR, DNA samples will also be submitted for pyrosequencing to assess the presence and prevalence of single nucleotide polymorphisms (SNPs) in the β-tubulin gene. These SNPs are known to be linked to AR in animal STHs. DISCUSSION:The results obtained by these trials will provide robust evidence regarding the cost-efficiency and diagnostic performance of the different stool-based diagnostic methods for the assessment of drug efficacy in control programs. The assessment of associations between the frequency of SNPs in the β-tubulin gene and the history of drug pressure and drug efficacy will allow the validation of these SNPs as a marker for AR in human STHs. TRIAL REGISTRATION:The trial was retrospectively registered the 7th of March 2018 on Clinicaltrials.gov (ID: NCT03465488).

BACKGROUND:Standard diagnosis of human soil-transmitted helminth (STH) infections is based on the microscopic detection of helminth eggs in stool and supports programmatic decision making in control programs. However, the current standard diagnostic techniques still show a number of limitations. Recently, the FECPAKG2 method was developed to detect helminth infections and asses drug efficacy in sheep or cattle. It includes a device that takes digital images of helminth eggs that have been concentrated into one microscopic field of view and stores these images online for future evaluation. The goal of this study was to introduce a standard operating procedure (SOP) for the detection and quantification of human STH eggs using the FECPAKG2 and to optimize 2 crucial steps of the protocol, namely the sedimentation step (aimed at separating sinking eggs from floating debris) and the accumulation step (aimed at concentrating the eggs by flotation). METHODOLOGY/PRINCIPAL FINDINGS:A total of 55 stool samples from naturally infected children were used from 4 different geographical areas (Ethiopia, Laos, Tanzania and Brazil). The results showed that Trichuris eggs generally moved slower than eggs of the other two STH species during both sedimentation in water in the FECPAKG2 sedimenter as during accumulation in flotation solution in the FECPAKG2 cassettes. The highest number of eggs were present in the slurry of the sedimenter after overnight sedimentation (Ascaris: 95.7%, Trichuris: 89.8% and hookworm: 94.2% of the eggs). A minimum of 24 minutes were needed to ensure the accumulation of at least 80% of the eggs from all three STH species in the FECPAKG2 cassette (Ascaris: 96.1%; Trichuris: 88.2% and hookworm: 87.6%). CONCLUSIONS/SIGNIFICANCE:This study introduces for the first time a SOP for the FECPAKG2 method. Different aspects of the method for diagnosing human STH infections were optimized. Our study forms the basis for a thorough and objective evaluation of the system as a diagnostic tool that could be implemented in STH control programs.

Abstract Background Globally, hookworms infect 440 million people in developing countries. Especially children and women of childbearing age are at risk of developing anaemia as a result of infection. To control hookworm infection and disease (i.e. reduce the prevalence of medium and heavy infection to

Strongyloidiasis is a common neglected tropical disease in tropical and sub-tropical climatic zones. At the worldwide level, there is high uncertainty about the strongyloidiasis burden. This uncertainty represents an important knowledge gap since it affects the planning of interventions to reduce the burden of strongyloidiasis in endemic countries. This study aimed to estimate the global strongyloidiasis prevalence. A literature review was performed to obtain prevalence data from endemic countries at a worldwide level from 1990 to 2016. For each study, the true population prevalence was calculated by accounting for the specificity and the sensitivity of testing and age of tested individuals. Prediction of strongyloidiasis prevalence for each country was performed using a spatiotemporal statistical modeling approach. The country prevalence obtained from the model was used to estimate the number of infected people per country. We estimate the global prevalence of strongyloidiasis in 2017 to be 8.1% (95% CI: 4.2–12.4%), corresponding to 613.9 (95% CI: 313.1–910.1) million people infected. The South-East Asia, African, and Western Pacific Regions accounted for 76.1% of the global infections. Our results could be used to identify those countries in which strongyloidiasis prevalence is highest and where mass drug administration (MDA) should be deployed for its prevention and control.

BACKGROUND:Soil-transmitted helminth infections are among the most common infections in developing countries. Globally, as many as 2 billion people are considered to be at risk for soil-transmitted-helminth (STH) infections. Preschool children (PSAC), school-age children (SAC) and women of reproductive age (WRA) are at high risk of STH-attributable morbidity and preventive chemotherapy (PC) for STH is recommended by the World health Organization (WHO). METHODOLOGY/PRINCIPAL FINDINGS:Over the last five years, PC coverage in PSAC and SAC has gradually increased, while coverage in WRA has lagged. Estimating the numbers of WRA in each endemic country would inform scale-up in this group. A two-step process was used: 1) total numbers of girls and women between 15 and 49 years of age were obtained from the United Nations World Population Prospects 2015 database; and 2) the proportion in need of PC was obtained primarily from extrapolation from the WHO PC Databank. WRA were divided into four sub-groups reflecting different reproductive life stages, each having a potentially different interface with the health care system and, consequently, presenting different opportunities for intervention strategies. Worldwide, we estimated that 688 million WRA in 102 countries were in need of PC for STH in 2015. The South-East Asia (49%) and Africa regions (26%) had the highest numbers. Adolescent girls accounted for 16%, while pregnant and lactating women each represented 10%. Over 25 million pregnant women alone were estimated living in areas where the prevalence of hookworm and T. trichiura infection was ≥ 20%. Approximately 20% of at-risk WRA had received deworming with albendazole through the Global Programme to Eliminate Filariasis. CONCLUSIONS/SIGNIFICANCE:To close current gaps in coverage, numbers of WRA in need of PC for STH are essential for operational strategies to control STH infection.