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Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in health status, an inability to track individuals over time, and accurately measuring living standards and productivity in low-income settings. This study exploits a randomized school health intervention that provided deworming treatment to Kenyan children, and uses longitudinal data to estimate impacts on economic outcomes up to 20 y later. The effective respondent tracking rate was 84%. Individuals who received two to three additional years of childhood deworming experienced a 14% gain in consumption expenditures and 13% increase in hourly earnings. There are also shifts in sectors of residence and employment: treatment group individuals are 9% more likely to live in urban areas, and experience a 9% increase in nonagricultural work hours. Most effects are concentrated among males and older individuals. The observed consumption and earnings benefits, together with deworming’s low cost when distributed at scale, imply that a conservative estimate of its annualized social internal rate of return is 37%, a high return by any standard.

Helminth infections are ubiquitous in grazing ruminant production systems, and are responsible for significant costs and production losses. Anthelmintic Resistance (AR) in parasites is now widespread throughout Europe, although there are still gaps in our knowledge in some regions and countries. AR is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, and increased greenhouse gas emissions through increased parasitism and farm inputs. A better understanding of the extent of AR in Europe is needed to develop and advocate more sustainable parasite control approaches. A database of European published and unpublished AR research on gastrointestinal nematodes (GIN) and liver fluke (Fasciola hepatica) was collated by members of the European COST Action “COMBAR” (Combatting Anthelmintic Resistance in Ruminants), and combined with data from a previous systematic review of AR in GIN. A total of 197 publications on AR in GIN were available for analysis, representing 535 studies in 22 countries and spanning the period 1980–2020. Reports of AR were present throughout the European continent and some reports indicated high within-country prevalence. Heuristic sample size-weighted estimates of European AR prevalence over the whole study period, stratified by anthelmintic class, varied between 0 and 48%. Estimated regional (country) prevalence was highly heterogeneous, ranging between 0% and 100% depending on livestock sector and anthelmintic class, and generally increased with increasing research effort in a country. In the few countries with adequate longitudinal data, there was a tendency towards increasing AR over time for all anthelmintic classes in GIN: aggregated results in sheep and goats since 2010 reveal an average prevalence of resistance to benzimidazoles (BZ) of 86%, macrocyclic lactones except moxidectin (ML) 52%, levamisole (LEV) 48%, and moxidectin (MOX) 21%. All major GIN genera survived treatment in various studies. In cattle, prevalence of AR varied between anthelmintic classes from 0–100% (BZ and ML), 0–17% (LEV) and 0–73% (MOX), and both Cooperia and Ostertagia survived treatment. Suspected AR in F. hepatica was reported in 21 studies spanning 6 countries. For GIN and particularly F. hepatica, there was a bias towards preferential sampling of individual farms with suspected AR, and research effort was biased towards Western Europe and particularly the United Kingdom. Ongoing capture of future results in the live database, efforts to avoid bias in farm recruitment, more accurate tests for AR, and stronger appreciation of the importance of AR among the agricultural industry and policy makers, will support more sophisticated analyses of factors contributing to AR and effective strategies to slow its spread.

Infection with the soil-transmitted helminth Trichuris trichiura affects up to 300 million people globally, with children in rural areas in less economically developed countries being most at risk. If untreated, infection compromises physical and cognitive development and leads to long-lasting morbidity. We assessed whether moxidectin co-administered with albendazole is superior to the recommended albendazole monotherapy in treating trichuriasis in school-aged children. This randomised, double-blind, parallel-group, superiority, phase 3 trial took place between May 14 and Aug 5, 2024, in the Piki administrative district primary school in the Wete district, Pemba Island, Tanzania. Children aged between 6 and 11 years were screened for the presence of T trichiura eggs in their stool via quadruplicate Kato–Katz thick smears. Using computer-generated group allocation (block randomisation stratified by infection intensity and age), parasitologically and clinically eligible participants (two or more of four slides positive for eggs) were randomly assigned in a 3:2:1 ratio to receive single oral doses of either moxidectin (4 mg [aged 6–7 years] and 8 mg [aged 8–11 years]) plus 400 mg albendazole, moxidectin placebo plus 400 mg albendazole, or moxidectin placebo plus albendazole placebo. The primary endpoint was cure rate, assessed at 14–21 days post-treatment, using the full analysis set population. Safety was formally assessed at 3 h, 24 h, and 14–21 days post-treatment. This trial is registered at ClinicalTrials.gov (NCT06188715) and is complete. 272 participants were screened, and after 48 participants were excluded for not meeting eligibility criteria, 224 eligible participants were randomly assigned to moxidectin–albendazole (n=114 [51%]), albendazole (n=74 [33%]), or placebo (n=36 [16%]). Of the 224 participants, 129 (58%) were male and 95 (42%) were female, and the mean age was 8·0 years (SD 1·3). For the 213 participants with primary outcome data, we observed a cure rate of 69% (77 of 111) in the moxidectin–albendazole group, which was significantly higher than the cure rate of 16% (11 of 68) in the albendazole group (absolute difference 53·2 percentage points [95% CI 39·6–64·2]). The cure rate in the placebo group was 12% (four of 34). The most common treatment-emergent adverse events were abdominal pain (five [4%] of 114 with moxidectin–albendazole, two [3%] of 74 with albendazole, and one [3%] of 36 with placebo) and headache (two [2%] of 114, none, and one [3%] of 36, respectively), which were all mild and transient. Moxidectin-albendazole combination therapy was superior to albendazole monotherapy in terms of efficacy in the treatment of trichuriasis in school-aged children. Both treatments presented a similar safety profile to placebo. Our study paves the way for a much-needed well tolerated and effective alternative combination treatment for children with trichuriasis. Swiss National Science Foundation (reference 320030_175585).

Strongyloidiasis is a pernicious, sometimes fatal, infectious disease caused by the parasitic nematode Strongyloides stercoralis and infects millions of people worldwide. Ivermectin is the only recommended single-dose treatment option available, but concerns of drug resistance are rightly founded, therefore driving the demand for efficacious alternatives. Emodepside, an anthelmintic recently repurposed from the veterinary field, is currently under clinical development for the treatment of onchocerciasis and soil-transmitted helminthiasis. We aimed to identify the most efficacious and safe dose of emodepside against S stercoralis infections. We conducted a phase 2a, dose-ranging, randomised, parallel-group, placebo-controlled, single-blind clinical trial. Recruitment took place in 17 endemic villages in the Champhone district of Laos. Adults aged 18–60 years who provided three stool samples with a mean number of S stercoralis larvae per g of at least 0·75, as assessed by sextuplicate Baermann assays, were invited to participate. Clinically eligible participants were randomly assigned (1:1:1:1:1:1:1:1) to receive a single oral dose of placebo, ivermectin (200 μg/kg), or emodepside at doses 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg. The participants, laboratory technicians, study nurses, and physicians were masked to the treatment assignments; study investigators were not masked. Participants providing at least one sample during follow-up were included in the primary outcome analysis, whereby efficacy was estimated by cure rate (defined as the proportion of participants who became S stercoralis negative 14–21 days after treatment). Treated patients were assessed for adverse events at 3-h, 24-h, 72-h, and 14 days post-treatment. This trial is registered at ClinicalTrials.gov (NCT06373835) and is completed. Between May 20, 2024, and Aug 14, 2024, 820 individuals were screened for S stercoralis infection and, of these, 202 individuals (108 male and 94 female) were randomly allocated to treatment groups and treated. 25 participants were treated with ivermectin, 25 with placebo, 25 participants with emodepside at 5 mg, 15 mg, 25 mg, or 30 mg dose, and 26 participants with emodepside at 10 mg or 20 mg dose. 5 mg emodepside had a predicted cure rate of 78·3% (95% CI 59·4–89·9), which was higher than the observed cure rate in the placebo treatment group (0%; 0·0–13·7; 0 of 25 participants). The dose–response curve plateaued at 15 mg, with a predicted cure rate of 89·1% (81·6–93·7). The observed cure rate in the ivermectin treatment group was 88·0% (68·8–97·5; 22 of 25 participants). The most common adverse event in all treatment groups was somnolence at 3-h post-treatment (ranging from nine [36%] of 25 participants in the emodepside 15 mg group to 17 [68%] of 25 in the 30 mg group). Other common adverse events included vision blur (two [8%] of 25 participants in the ivermectin group to 11 [44%] of 25 in the emodepside 30 mg group at 3-h post-treatment), vision impairment (three [4%] of 26 in the 10 mg group to eight [32%] of 25 in the emodepside 30 mg group), and dizziness (two [8%] of 25 participants in the emodepside 5 mg group to seven [28%] of 25 in the emodepside 30 mg group) at 3-h post-treatment. Adverse events were predominantly mild in nature and no serious adverse events occurred. At all doses tested, emodepside was efficacious and well tolerated in individuals infected with S stercoralis. The broad-spectrum weight-independent dose and robust safety profile positions emodepside as a promising new candidate for strongyloidiasis treatment. European Research Council and the Uniscientia Foundation.

Background The increasing difficulties in combating anthelmintic resistance in gastrointestinal nematodes (GINs) of sheep worldwide, and the residues of chemical drugs in animal products and the environment, necessitate the search for alternatives. Previous studies have shown that plant essential oils (EOs) could be valuable anthelmintic agents, due to their numerous advantages. The present study aimed to evaluate the possibility of using winter savory ( Satureja montana L.) EO against sheep GINs. The chemical composition of the tested oil was determined by gas chromatography-mass spectrometry (GC–MS). The efficacy of the tested oil was determined in vitro using the egg hatch test (EHT), and in vivo using the faecal egg count reduction test (FECRT) performed in two farms. Preliminary toxicity studies including clinical observation, haematological and biochemical blood analysis were also performed to evaluate the safety of the tested oil to the hosts. In addition, a coproculture study was carried out in the tested farms using the appropriate morphological keys. Results Main compounds of the S. montana oil identified by GC–MS analysis were p -cymene (42.8%), carvacrol (28.1%) and y-terpinene (14.6%). The in vitro EHT showed a dose-dependent (R 2  = 0.94) anthelmintic potential of the tested oil, with ovicidal activity varying from 17.0–83.3% and determined IC 50 value of 0.59 mg/ml. The field efficacy reached 33% (at group level) and 50% (at individual level) at D14 after treatment. In vivo efficacy was significantly higher in farm 2 (FEC above 65% at group level, p  < 0.05) where sheep were kept in pens during treatment. No toxic effects were observed, either in the physical observation of the test animals or in their liver and kidney function. No significant changes ( p  > 0.05) in the percentage representation of GIN genera were observed in the coproculture study, indicating that the treatment agent was not specific to a single genus. Conclusion The anthelmintic potential showed on EHT and FECRT, without adverse effects on the sheep, suggests that S. montana EO is suitable for the control of sheep GINs as part of an integrated parasite management. However, further studies should be conducted to increase efficacy in field conditions.

The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin. This double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998. Between April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment. Skin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination. UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis. There was no funding source for this study.

Trichuris trichiura , a soil-transmitted helminth (STH), often persists after a single dose of anthelminthic treatment. To overcome limited efficacy against T . trichiura of benzimidazoles (albendazole or mebendazole), the primary drugs used in mass drug administration (MDA) campaigns, the World Health Organization endorses the use of a combination of ivermectin and albendazole as a more effective treatment to be used for preventive chemotherapy. Given observed considerable differences in efficacy of the combination therapy over albendazole monotherapy between different settings, it is necessary to evaluate the performance of the combination before introducing it on a larger scale. This open-label, randomized controlled superiority trial in two Ugandan primary schools enrolled eligible 6- to 12-year-olds positive for T . trichiura . Participants were randomized 1:1 to receive either a single dose of albendazole alone or co-administered albendazole and ivermectin. Adverse events were monitored at three and 24h post-treatment. Follow-up samples were collected 14 to 21 days post-treatment for efficacy assessment. The combination of albendazole with ivermectin showed superior efficacy against T . trichiura compared to albendazole alone, both in terms of cure rates (31.3% versus 12.3%, difference 18.9%-points, 95% CI 6.2–31.2, p < 0.004) and in terms of egg reduction rates (ERRs; 91.4% versus 52.7%). A higher cure rate against co-infecting Ascaris lumbricoides was observed in the combination compared to the albendazole monotherapy arm (100% versus 83.9%). Both therapies showed an excellent safety profile with few and only mild and transient treatment emergent adverse events observed in the albendazole monotherapy and albendazole plus ivermectin arm (total of 22 and 19 events, respectively). In conclusion, the efficacy of the combination therapy against T . trichiura in Uganda is superior to that of albendazole alone. Given the high ERRs observed, albendazole-ivermectin might aid in eliminating morbidity, an important target of STH control programs. Trial registration (clinicaltrials.gov): NCT06037876 .

The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals provides comprehensive awareness and potential solutions for issues relating to the health of people, animals, and the environment. This approach has increasingly gained appeal as the standard strategy for tackling emerging infectious diseases, most of which are zoonoses. Treatment with anthelmintics (AHs) without a doubt minimizes the severe consequences of soil-transmitted helminths (STHs); however, evidence of anthelmintic resistance (AR) development to different helminths of practically every animal species and the distinct groups of AHs is overwhelming globally. In this regard, the correlation between the application of anthelmintic drugs in both human and animal populations and the consequent development of anthelmintic resistance in STHs within the context of a One-Health framework is explored. This review provides an overview of the major human and animal STHs, treatment of the STHs, AR development and drug-related factors contributing towards AR, One-Health and STHs, and an outline of some One-Health strategies that may be used in combating AR.

Nematode infections impose a significant health and economic burden, particularly as parasites develop resistance to existing treatments and evade host defenses. This study explores the efficacy of 48 paraherquamide analogs, a class of polycyclic spiro-oxindole alkaloids with unique structural features, as potential anthelmintic agents. Employing advanced computational methods, including molecular docking, MM-GBSA, and molecular dynamics simulations, we assessed the interaction of these analogs with the Ls-AchBP receptor, a model for nematode neurotransmission. Among the analogs studied, Paraherquamide K, Mangrovamide A, and Chrysogenamide A showed comparable docking and MM-GBSA scores to the native antagonist. Notably, their binding interactions exhibited slight distinction attributed to structural differences, such as the absence of a di-oxygenated 7-membered ring. Additionally, these analogs demonstrated robust binding stability in the molecular dynamic simulation studies and favorable pharmacokinetic properties in our in-silico ADME assessment. The insights gained from the study highlight the potential of these analogs as a basis for developing new therapeutics for nematode infections. The promising results from this computational analysis set the stage for subsequent in-vivo validations and pre-clinical studies, contributing to the arsenal against parasitic resistance.