Soil-transmitted Helminth Control Programs Research Articles

SOSIALISASI PENINGKATAN DETEKSI SOIL TRANSMITTED HELMINTH (STH) MELALUI MODIFIKASI PADA LARUTAN ZnS (SULFIDA SENG) DAN NaCl (NATRIUM KLORIDA) 0,9%

Public health is a crucial aspect of disease prevention efforts. One significant health issue in many countries, including Indonesia, is Soil Transmitted Helminth (STH) infection, often caused by poor sanitation and lack of environmental cleanliness awareness. STH, typically caused by Ascaris lumbricoides, Trichuris trichiura, and hookworm, can have severe health impacts, particularly on children. Fecal examination methods, especially flotation techniques using ZnS (zinc sulfide) and 0.9% NaCl (sodium chloride) solutions, are commonly employed for STH detection. However, optimizing flotation methods in the field is essential to enhance STH detection sensitivity. This study focuses on the modification of ZnS and 0.9% NaCl solutions to improve the effectiveness of detecting STH eggs. By disseminating information on these modifications to public health practitioners, this socialization aims to enhance detection and prevention efforts for STH infections. The evaluation results show significant improvements in participants' knowledge, skills, attitudes, understanding, method application, and satisfaction, indicating the effectiveness of this socialization in promoting better STH control and prevention programs.

A Comparison of Markov and Mechanistic Models for Soil-Transmitted Helminth Prevalence Projections in the Context of Survey Design.

Globally, there are over 1 billion people infected with soil-transmitted helminths (STHs), mostly living in marginalized settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The World Health Organization recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education and the delivery of preventive chemotherapy (PC) to school-age children delivered through schools. Progress of STH control programs is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these 2 methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that, although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not decrease despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other neglected tropical diseases.

Effectiveness of one and two doses of ivermectin mass drug administration in reducing the prevalence and intensity of soil-transmitted helminth (STH) infections in Western Province, Solomon Islands: a cluster-randomised, before-after analysis

Ivermectin mass drug administration (MDA) is effective for controlling onchocerciasis and scabies, with evidence supporting its role in some species of soil-transmitted helminth (STH) infections. In the context of RISE, a cluster-randomised trial for scabies, this study evaluated the effectiveness of ivermectin MDA in reducing STH burden in the Western Province of Solomon Islands. Twenty villages were randomised 1:1 to receive ivermectin MDA as one dose (IVM-1) or two doses (IVM-2) for scabies. The effectiveness of one and two doses in reducing STH prevalence and intensity was evaluated before (May 2019) and 21 months after (February 2021) MDA in May 2019. All residents aged 12 months or older in the study villages were eligible to participate and provide stool specimens. Species-specific STH infection and intensity were assessed using quantitative PCR. We compared prevalence and intensity of infection between baseline and 21 months in each intervention arm individually using cluster-level analysis (adjusted for clustering) and individual-level analysis (adjusted for sex, age, and clustering). The primary outcomes were the prevalence risk difference (RD) from the cluster-level analysis, and the change in adjusted odds of infection from the individual-level analysis. Secondary outcomes included change in incident rates of mean eggs per gram (epg) of stool from baseline to 21 months, relative risk difference in prevalence and relative change in odds of infection between arms at 21 months. Sex data (male/female) were self-reported. Overall, STH infection was assessed in 830 participants from 18 villages at baseline and 1172 from 20 villages at follow-up. Females represented 58% (n=478) of the sample at baseline and 59% (n=690) at follow-up. We observed a reduction in Strongyloides spp. prevalence following two doses of ivermectin MDA in the cluster-level analysis from 7.0% (32/458 participants) to 1.2% (8/674 participants), corresponding to a RD of-0.07 (95% CI-0.14 to-0.01, p=0.036), and in the individual-level analysis (OR 0.11, 95% CI 0.04-0.33, p<0.001). T.trichiura prevalence decreased following one dose from 19.4% (74/372 participants) to 11.7% (56/505 participants) (OR 0.44, 95% CI 0.26-0.73, p=0.0040), while egg count reduced in both arms (IVM-1: IRR 0.28, 95% CI 0.11-0.70, p=0.0070; IVM-2: IRR 0.18, 95% CI 0.08-0.40, p<0.001), in the individual-level analysis. We did not detect a significant difference in effect measures between the one- and two-dose arms for any species after 21 months. Our study highlights the long-term benefits of ivermectin MDA in reducing the burden of Strongyloides spp. and T.trichiura. STH control programs should leverage the geographical overlap of NTDs, existing drug distribution channels, and broad-spectrum agents. The National Health and Medical Research Council of Australia.

A general framework to support cost-efficient survey design choices for the control of soil-transmitted helminths when deploying Kato-Katz thick smear.

To monitor and evaluate soil-transmitted helminth (STH) control programs, the World Health Organization (WHO) recommends screening stools from 250 children, deploying Kato-Katz thick smear (KK). However, it remains unclear whether these recommendations are sufficient to make adequate decisions about stopping preventive chemotherapy (PC) (prevalence of infection <2%) or declaring elimination of STHs as a public health problem (prevalence of moderate-to-heavy intensity (MHI) infections <2%). We developed a simulation framework to determine the effectiveness and cost of survey designs for decision-making in STH control programs, capturing the operational resources to perform surveys, the variation in egg counts across STH species, across schools, between and within individuals, and between repeated smears. Using this framework and a lot quality assurance sampling approach, we determined the most cost-efficient survey designs (number of schools, subjects, stool samples per subject, and smears per stool sample) for decision-making. For all species, employing duplicate KK (sampling 4 to 6 schools and 64 to 70 subjects per school) was the most cost-efficient survey design to assess whether prevalence of any infection intensity was above or under 2%. For prevalence of MHI infections, single KK was the most cost-efficient (sampling 11 to 25 schools and 52 to 84 children per school). KK is valuable for monitoring and evaluation of STH control programs, though we recommend deploying a duplicate KK on a single stool sample to stop PC, and a single KK to declare the elimination of STHs as a public health problem.

A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

Soil-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. We 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. Kato-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. We 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. ClinicalTrials.gov NCT03465488.

Model validation for a knowledge and practices survey towards prevention of soil-transmitted helminth infections in rural villages in Indonesia

The rate of soil-transmitted helminth (STH) infection is estimated to be around 20% in Indonesia. Health promotion and health education are cost-effective strategies to supplement STH prevention and control programs. Existing studies suggest that quantitative tools for knowledge, attitudes and practices (KAP) are important to monitor effective community-based STH interventions. However, evidence is limited regarding the applicability of such tools. This study aims to identify the socio-demographic predictors for STH-related knowledge and practices and validate the quantitative tools in population use. A cross-sectional study design was conducted among residents of 16 villages in Central Java, Indonesia. Adult and child respondents were interviewed to assess general knowledge and practices in relation to STH. Two mixed effects models identified the significant factors in predicting knowledge and practice scores. The model predicted knowledge and practice scores were compared with the observed scores to validate the quantitative measurements developed in this study. Participants’ socio-demographic variables were significant in predicting an individual’s STH-related knowledge level and their hand washing and hygiene practices, taking into account household-level variability. Model validation results confirmed that the quantitative measurement tools were suitable for assessing STH associated knowledge and behaviour. The questionnaire developed in this study can be used to support school- and community-based health education interventions to maximize the effect of STH prevention and control programs.

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

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

Comparison of coproprevalence and seroprevalence to guide decision-making in national soil-transmitted helminthiasis control programs: Ethiopia as a case study.

BackgroundWHO recommends periodical assessment of the prevalence of any soil-transmitted helminth (STH) infections to adapt the frequency of mass drug administration targeting STHs. Today, detection of eggs in stool smears (Kato-Katz thick smear) remains the diagnostic standard. However, stool examination (coprology) has important operational drawbacks and impedes integrated surveys of multiple neglected tropical diseases. Therefore, the aim of the present study was to assess the potential of applying serology instead of coprology in STH control program decision-making.MethodologyAn antibody-ELISA based on extract of Ascaris lung stage larvae (AsLungL3-ELISA) was applied in ongoing monitoring activities of the Ethiopian national control program against schistosomiasis and soil-transmitted helminthiasis. Blood and stool samples were collected from over 6,700 students (median age: 11) from 63 schools in 33 woredas (districts) across the country. Stool samples of two consecutive days were analyzed applying duplicate Kato-Katz thick smear.Principal findingsOn woreda level, qualitative (seroprevalence) and quantitative (mean optical density ratio) serology results were highly correlated, and hence seroprevalence was chosen as parameter. For 85% of the woredas, prevalence based on serology was higher than those based on coprology. The results suggested cross-reactivity of the AsLungL3-ELISA with Trichuris. When extrapolating the WHO coproprevalence thresholds, there was a moderate agreement (weighted κ = 0.43) in program decision-making. Using the same threshold values would predominantly lead to a higher frequency of drug administration.SignificanceThis is the first time that serology for soil-transmitted helminthiasis is applied on such large scale, thereby embedded in a control program context. The results underscore that serology holds promise as a tool to monitor STH control programs. Further research should focus on the optimization of the diagnostic assay and the refinement of serology-specific program decision-making thresholds.

Using Routinely Collected Health Records to Identify the Fine-Resolution Spatial Patterns of Soil-Transmitted Helminth Infections in Rwanda.

Background. Soil-transmitted helminths (STH) are parasitic diseases with significant public health impact. Analysis is generally based on cross-sectional prevalence surveys; outcomes are mostly aggregated to larger spatial units. However, recent research demonstrates that infection levels and spatial patterns differ between STH species and tend to be localized. Methods. Incidence data of STHs including roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura) and hookworms per primary health facility for 2008 were linked to spatially delineated primary health center service areas. Prevalence data per district for individual and combined STH infections from the 2008 nationwide survey in Rwanda were also obtained. Results. A comparison of reported prevalence and incidence data indicated significant positive correlations for roundworm (R2 = 0.63) and hookworm (R2 = 0.27). Weak positive correlations were observed for whipworm (R2 = 0.02) and the three STHs combined (R2 = 0.10). Incidence of roundworm and whipworm were found to be focalized with significant spatial autocorrelation (Moran’s I > 0: 0.05–0.38 and p ≤ 0.03), with (very) high incidence rates in some focal areas. In contrast, hookworm incidence is ubiquitous and randomly distributed (Moran’s I > 0: 0.006 and p = 0.74) with very low incidence rates. Furthermore, an exploratory regression analysis identified relationships between helminth infection cases and potential environmental and socio-economic risk factors. Conclusions. Findings show that the spatial distribution of STH incidence is significantly associated with soil properties (sand proportion and pH), rainfall, wetlands and their uses, population density and proportion of rural residents. Identified spatial patterns are important for guiding STH prevention and control programs.

Using quantitative PCR to identify opportunities to strengthen soil-transmitted helminth control in Solomon Islands: A cross-sectional epidemiological survey

BackgroundThe Kato-Katz microscopy technique is the global standard for assessment of soil-transmitted helminth (STH) burden. However, major limitations include its poor sensitivity, requirement for rapid sample processing, and inability to differentiate hookworm species nor detect Strongyloides spp. infections. We assessed the prevalence and intensity of STH species in Solomon Islands by conducting a province-wide survey using quantitative PCR (qPCR) for diagnosis, which can provide much better characterisation of STH burden than microscopy.Methodology/Principal findingsWe conducted a cross-sectional survey in 18 villages in Western Province to detect infections with six STH species and quantify intensity with three. We used linear mixed model regression to identify potential water, sanitation, and hygiene (WASH) and environmental risk factors for infection. We collected stool specimens from 830 village residents. Overall STH prevalence was 63.3% (range 27.5 to 91.5% across villages), led by Necator americanus (54.5% [range 17.5–89.4%]), followed by Ancylostoma ceylanicum (15.5% [range 2.8–45.8%]), Trichuris trichiura (9.1% [range 0–79.2%]), and Strongyloides spp. (3.2% [range 0–29.2%]). Most infections were of light intensity for N. americanus (85.7%) and T. trichiura (90.7%). Owning a household latrine was associated with a lower risk of N. americanus infection (AOR 0.41, 95% CI 0.24–0.68) while greater precipitation was linked to more common T. trichiura infection (AOR 1.14, 95% CI 1.04–1.25).Conclusion/SignificanceIn this first large-scale population survey of STH in the Pacific using qPCR, we found evidence that ivermectin should be incorporated into STH control programmes because of the presence of T. trichiura and Strongyloides spp., both of which are poorly responsive to albendazole. Furthermore, One Health strategies are needed for improved A. ceylanicum and Strongyloides spp. control, WASH access and use should be improved to complement deworming programmes, and control efforts should ideally be expanded to entire communities.Trial registrationClinicalTrials.gov Australian and New Zealand Clinical Trials Registry ACTRN12618001086257.

Two-stage lot quality assurance sampling framework for monitoring and evaluation of neglected tropical diseases, allowing for imperfect diagnostics and spatial heterogeneity.

BackgroundMonitoring and evaluation (M&E) is a key component of large-scale neglected tropical diseases (NTD) control programs. Diagnostic tests deployed in these M&E surveys are often imperfect, and it remains unclear how this affects the population-based program decision-making.MethodologyWe developed a 2-stage lot quality assurance sampling (LQAS) framework for decision-making that allows for both imperfect diagnostics and spatial heterogeneity of infections. We applied the framework to M&E of soil-transmitted helminth control programs as a case study. For this, we explored the impact of the diagnostic performance (sensitivity and specificity), spatial heterogeneity (intra-cluster correlation), and survey design on program decision-making around the prevalence decisions thresholds recommended by WHO (2%, 10%, 20% and 50%) and the associated total survey costs.Principal findingsThe survey design currently recommended by WHO (5 clusters and 50 subjects per cluster) may lead to incorrect program decisions around the 2% and 10% prevalence thresholds, even when perfect diagnostic tests are deployed. To reduce the risk of incorrect decisions around the 2% prevalence threshold, including more clusters (≥10) and deploying highly specific diagnostic methods (≥98%) are the most-cost saving strategies when spatial heterogeneity is moderate-to-high (intra-cluster correlation >0.017). The higher cost and lower throughput of improved diagnostic tests are compensated by lower required sample sizes, though only when the cost per test is <6.50 US$ and sample throughput is ≥3 per hour.Conclusion/SignificanceOur framework provides a means to assess and update M&E guidelines and guide product development choices for NTD. Using soil-transmitted helminths as a case study, we show that current M&E guidelines may severely fall short, particularly in low-endemic and post-control settings. Furthermore, specificity rather than sensitivity is a critical parameter to consider. When the geographical distribution of an NTD within a district is highly heterogeneous, sampling more clusters (≥10) may be required.

Diagnostic Techniques for Soil-Transmitted Helminths - Recent Advances.

Soil-transmitted helminth (STH) infections (hookworms, Trichuris, Ascaris) and Strongyloides spp. are associated with a substantial global burden and high morbidity. Sensitive and specific methods for diagnosis of these infections are essential for mapping the burden in communities, accurate assessment of infection levels, to guide interventions and monitoring the success of STH control programs. Despite considerable progress to control STH over several decades, we are still far from identifying a fully adequate diagnostic test. Conventional microscopy-based methods such as direct Kato–Katz smear or mounts after stool centrifugation/flotation-based concentration techniques have been the mainstay of diagnosis, especially in resource-poor countries where these infections abound. However, recently, these are being adapted to closed, easy to perform, digital formats, thereby improving the sensitivity as well as applicability in a remote, resource-limited setting. The use of image analysis systems to identify and quantify helminth eggs, with potential adaptation to smartphones, is also promising. Antibody detection tests have a limited role mostly in the case of Strongyloides hyperinfection. Coproantigen detection tests have been developed and used in veterinary practice for detection of STH, but these have not been evaluated for use in humans. More sensitive molecular diagnostics, including assays developed with new bioinformatic tools and techniques such as polymerase chain reaction (PCR), quantitative PCR (qPCR) and loop-mediated amplification assay, can help in the clear and precise assessment of STH burden during elimination phase and are of immense value for diagnosis in areas with low endemicity and in travelers to endemic regions. Moreover, the molecular techniques will help detect new species that may emerge. Sample preservation and efficient DNA extraction are critical and significantly affect the efficiency of molecular diagnostic tests. In addition to the diagnosis of clinical or asymptomatic infection in humans, detection of STH eggs in environmental samples is imperative to boost STH control efforts. Overall the diagnostic performance, cost-effectiveness, ease of performance, rapidity and in-field applicability of any test should be considered when choosing from the various diagnostic assays in areas with different endemicity, in addition to striving towards the development of novel technologies and optimization of existing methods.

Prevalence and Correlation Analysis of Soil-Transmitted Helminths Infections and Treatment Coverage for Preschool and School Aged Children in Kenya: Secondary Analysis of the National School Based Deworming Program Data.

Background: Soil-transmitted helminths (STH) are among the most common parasitic infections globally, disproportionately affecting children. Treatment of STH in Kenya is often targeted at preschool (PSAC) and school aged (SAC) children delivered through annual mass drug administration (MDA) in primary schools. Understanding group-specific prevalence and dynamics between treatment and coverage is critical for continued treatment success. This study aims to provide detailed information on group-specific infection prevalence and relative reductions (RR), and their relationships with treatment coverage over time. Additionally, it aims to quantify the correlation between the observed school level infection prevalence and treatment coverage.Methods: Secondary analysis of existing data collected between 2012 and 2018 by the monitoring and evaluation (M&E) program of the National School-Based Deworming (NSBD) program was used. The M&E program conducted surveys utilizing cross-sectional study design, at four survey time points, in a nationally-representative sample of schoolchildren across counties in Kenya. In each participating school, the program randomly sampled 108 children per school, of both groups. Infection prevalence was estimated using binomial regression, RR in prevalence using multivariable mixed effects model, statistical correlations using structural equation modeling, and change-point-analysis using the binary segmentation algorithm.Results: Overall, STH prevalence for PSAC was 33.7, 20.2, 19.0, and 17.9% during Year 1 (Y1), Year 3 (Y3), Year 5 (Y5), and Year 6 (Y6) surveys, respectively with an overall RR of 46.9% (p = 0.001) from Y1 to Y6. Similarly, overall STH prevalence for SAC was 33.6, 18.4, 14.7, and 12.5% during Y1, Y3, Y5, and Y6 surveys, respectively with an overall RR of 62.6% (p < 0.001). An overall (all time points) significant but very weak negative correlation was found between treatment coverage and undifferentiated STH prevalence (r = −0.144, p = 0.002) among PSAC but not in SAC. Further, we observed inter-county heterogeneity variation in infection prevalence, RR, as well as correlations.Conclusion: The analysis showed that after six rounds of MDA, prevalence of STH has significantly declined among both groups of children, however not to a point where it is not a public health problem (below 1%). The analysis, additionally established an overall significant but weak negative correlation between treatment coverage and prevalence, indicating that the current treatment coverage might not be sufficient to drive the overall STH prevalence to below 1%. These findings will allow STH control programs in Kenya to make decisions that will accelerate the attainment of STH elimination as a public health problem.

Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity.

The design and evaluation of control programs for soil-transmitted helminths (STHs) is based on surveillance data recording measurements of egg counts in the stool of infected individuals, which underpin estimates of the prevalence and average intensity of infection. There is considerable uncertainty around these measurements and their interpretation. The uncertainty is composed of several sources of measurement error and the limit of detection of fecal smear tests on the one hand, and key assumptions on STH biology on the other hand, including assumptions on the aggregation of worms within hosts and on the impact of density-dependent influences on worm reproduction. Using 2 independently developed models of STH transmission we show how different aspects of STH biology and human behavior impact on STH surveillance and control programs and how accounting for uncertainty can help to develop optimal and sustainable control strategies to meet the World Health Organization (WHO) morbidity target for STHs.

The role of diagnostic technologies to measure progress toward WHO 2030 targets for soil-transmitted helminth control programs.

The role of diagnostic technologies to measure progress toward WHO 2030 targets for soil-transmitted helminth control programs.

Baseline patterns of infection in regions of Benin, Malawi and India seeking to interrupt transmission of soil transmitted helminths (STH) in the DeWorm3 trial.

Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was divided into 40 clusters of at least 1,650 individuals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible individuals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 individuals per cluster (6,000 total per site) was selected from the baseline census using stratified random sampling, and each individual provided a single stool sample for analysis of STH infection using the Kato-Katz technique. Study site, household and individual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4-22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1-8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1-6.2%) and Ascaris (2.0%, 95% CI: 1.6-2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03014167).

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

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

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

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

Diagnosis and drug resistance of human soil-transmitted helminth infections: A public health perspective.

Soil-transmitted helminth (STH) infections represent a major public health problem globally, particularly among socio-economically disadvantaged populations. Detection of STH infections is often challenging, requiring a combination of diagnostic techniques to achieve acceptable sensitivity and specificity, particularly in low infection-intensity situations. The microscopy-based Kato-Katz remains the most widely used method but has low sensitivity in the detection of, for instance, Strongyloides spp. infections, among others. Antigen/antibody assays can be more sensitive but are parasite species-specific. Highly sensitive PCR methods have been developed to be multiplexed to allow multi-species detection. Novel diagnostic tests for all STH species are needed for effective monitoring, evaluation of chemotherapy programmes, and to assess the potential emergence of parasite resistance. This review discusses available diagnostic methods for the different stages of STH control programmes, which vary in sensitivity and spectrum of detection requirements, and tools to evaluate drug efficacy and resistance.

Modification and optimization of the FECPAKG2 protocol for the detection and quantification of soil-transmitted helminth eggs in human stool.

BackgroundStandard 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 findingsA 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/SignificanceThis 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.