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Abstract: Infection with soil-transmitted helminths (STH) is a major public health problem in many developing countries, with pregnant women and children particularly at risk. Preventive chemotherapy, which is the intervention currently recommended by the WHO against the main helminth infections including those caused by STHs, aims at reducing morbidity through periodical administration of anthelminthic drugs either alone or in combination. The Expanded Programme on Immunization is one of the most widely implemented health programmes in the world and has well established access to children and women. The present study investigated the cost of the provision of anthelminthic drugs during existing immunisation campaigns. In Lao PDR, use of this integrated approach compared with implementation of the vertical deworming campaign alone allowed a reduction of the individual cost of deworming by 10 times (from US$0.23 in the vertical deworming campaign to US$0.03 in the integrated campaign). When drug cost was excluded, the cost of deworming an individual was US$0.007, implying that deworming 100 children would cost less than US$1 if drug donation was in place. The burden posed on health workers by the integration process was perceived as minimal and manageable. Moreover, delivery of anthelminthic drugs during immunisation campaigns enabled campaign teams to observe drug intake directly, which assured safety. These findings prove that integration is an opportunity to maximise health benefits through the delivery of multiple health products and the attainment of high coverage. [Copyright &y& Elsevier]

Summary: Infections with soil-transmitted helminths (STHs) are among the commonest infections in Lao PDR. Recent investigation in this country showed that intestinal helminths currently infect the majority of school-aged children. The Lao Government has addressed the problem by organizing regular anthelminthic chemotherapy with mebendazole 500mg for school and pre-school children in conjunction with health education activities incorporated into the national school curriculum. The school deworming campaign in Lao PDR reached a national coverage rate of 95% at a cost of US$0.124/head for two rounds of deworming per year. The programme operates under the umbrella of the national school health programme. After 1 year (two rounds of deworming) the intervention reduced the prevalence of Ascaris lumbricoides from 60% to 20% and of Trichuris trichiura from 42% to 31%. Although infection was not eliminated by the deworming interventions, over 90% of those children who remain infected had a ‘light’ infection. The virtual absence of high and moderate intensity infection demonstrates the effectiveness of periodical deworming in reducing morbidity due to STHs. We expect that additional rounds of deworming will further reduce the STH prevalence in Lao PDR. [Copyright &y& Elsevier]

Background: Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment., Methodology/principal Findings: We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People's Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites., Conclusions/significance: We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB., Trial Registration: The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018., Competing Interests: The authors have declared that no competing interests exist.

Background: Efforts 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., Methodology: During 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., Results: Across 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/significance: In 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., Competing Interests: The authors have declared that no competing interests exist.

Background: Preventive 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., Methods: An 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 Conclusions: The 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 Registration: ClinicalTrials.gov NCT03465488., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

Background: Because 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)., Methodology: We 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 Findings: All 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/significance: Our 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 Registration: ClinicalTrials.gov NCT03465488., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, the affiliations of ET, GM, GC, LR and MPM did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

In 2001, Urbani and Palmer published a review of the epidemiological situation of helminthiases in the countries of the Western Pacific Region of the World Health Organization indicating the control needs in the region. Six years after this inspiring article, large-scale preventive chemotherapy for the control of helminthiasis has scaled up dramatically in the region. This paper analyzes the most recent published and unpublished country information on large-scale preventive chemotherapy and summarizes the progress made since 2000. Almost 39 million treatments were provided in 2006 in the region for the control of helminthiasis: nearly 14 million for the control of lymphatic filariasis, more than 22 million for the control of soil-transmitted helminthiasis, and over 2 million for the control of schistosomiasis. In general, control of these helminthiases is progressing well in the Mekong countries and Pacific Islands. In China, despite harboring the majority of the helminth infections of the region, the control activities have not reached the level of coverage of countries with much more limited financial resources. The control of food-borne trematodes is still limited, but pilot activities have been initiated in China, Lao People's Democratic Republic, and Vietnam.