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Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150–200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment. We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18–50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs ≥21 kg/m2; women: <23 vs ≥23 kg/m2), with permuted blocks of three, to receive 3 days of ivermectin 300 μg/kg per day, ivermectin 600 μg/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353. Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 μg/kg per day (n=47), ivermectin 300 μg/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 μg/kg per day risk ratio [RR] 2·26, 95% CI 1·93–2·65, p<0·0001; hazard ratio [HR] 6·32, 4·61–8·67, p<0·0001; ivermectin 300 μg/kg per day RR 2·18, 1·86–2·57, p<0·0001; HR 4·21, 3·06–5·79, p<0·0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 μg/kg per day RR 1·23, 1·01–1·50, p=0·0374; and ivermectin 300 μg/kg per day 1·21, 1·01–1·44, p=0·0337). Five (11%) of 45 patients receiving ivermectin 600 μg/kg per day, two (4%) of 48 patients receiving ivermectin 300 μg/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events. Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 μg/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination. Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC).

The success of crucial vector control efforts in Africa (eg, long-lasting insecticide-treated nets [ITNs] and indoor residual spraying) are threatened by widespread insecticide resistance and insufficient effect on outdoor mosquito biting. Studies have shown that ivermectin, used for the treatment of parasitic diseases, can kill malaria vectors that feed on the blood of treated people and thus might be an effective complementary vector control tool if administered widely to communities in malaria endemic regions. We aimed to test the safety of repeated, high-dose ivermectin mass drug administration (MDA) and its efficacy for reducing malaria incidence among children when integrated with seasonal malaria chemoprevention (SMC) delivery. We conducted a phase 3, double-blind, placebo-controlled, cluster-randomised, parallel-group trial in southwest Burkina Faso over two consecutive rainy seasons (2019–20). 14 villages or village sectors (clusters) were randomly assigned (1:1) to ivermectin or placebo MDA by random draw, and study-eligible participants (those who regularly lived in the cluster and provided written informed consent) from all households were enrolled in July, 2019 and July, 2020. Participants were eligible for MDA if they were 90 cm in height or taller and not excluded for other safety reasons (eg, pregnancy or taking SMC drugs). There were no age restrictions for participants. Each rainy season (July to October), eligible participants from the intervention group clusters received monthly high-dose oral ivermectin MDA (three daily doses, approximately 300 μg/kg dosed by height bands) and those from the control group received monthly oral placebo MDA for up to eight treatment rounds. MDA was performed by study staff alongside community health worker administration of monthly SMC to children aged 3–59 months in both groups. All participants and study personnel, apart from the pharmacist, were masked to group assignment. The primary outcome was weekly malaria incidence in children aged 10 years and younger, as assessed by weekly active case detection until week 16 of year 2, by intention to treat. Adverse events were monitored in all MDA participants through active and passive surveillance. Blood was sampled for secondary parasitological outcomes, including analysis of parasite species distribution among malaria cases. Mosquitoes were sampled from pre-selected households in three clusters per group for secondary entomological outcomes, including analysis of blood-fed mosquito survivorship, mosquito biting rates, and entomological inoculation rates. Changes in haemoglobin pre-intervention and post-intervention in children aged 10 years and younger were assessed in 2020. The trial is registered with ClinicalTrials.gov (NCT03967054) and the Pan African Clinical Trials Registry (PACT201907479787308) and is completed. The study took place from July 13, 2019, to Nov 8, 2020, with seven villages assigned to the control group and seven to the intervention group. Participants were enrolled from households in both groups in July, 2019, and July, 2020. In the intervention group, 1928 participants in 2019 and 2163 participants in 2020 were followed up, and 703 children in 2019 and 686 children in 2020 were analysed. In the control group, 1604 participants in 2019 and 1921 participants in 2020 were followed up, and 605 children in 2019 and 641 children in 2020 were analysed. MDA coverage (receiving ≥1 dose) in the enrolled population (including those who were ineligible) varied over the intervention period (68–74%), with 86–95% of participants who were eligible receiving ivermectin or placebo over the study period. 288 (47·2%) of 610 children in the control group and 312 (44·2%) of 706 children in the ivermectin group received SMC, and all clusters received new dual-chemistry Interceptor G2 ITNs containing chlorfenapyr and α-cypermethrin by government authorities in October, 2019. The average estimated weekly malaria incidence rate per 100 person-weeks among children in the intervention group was 1·78 (95% CI 1·24–2·53) and 1·84 (1·29–2·64) in the control group, and the incidence rate ratio was 0·96 (95% CI 0·58–1·59; p=0·8723). The risk of adverse events among eligible participants in the intervention group was lower than in the control group (risk ratio 0·63, 95% CI 0·46–0·87; p=0·0049). The distribution of Plasmodium spp detected in children with clinical malaria was unexpectedly diverse with non-Plasmodium falciparum species detected in 56 (11%) of 505 symptomatic children; however, species distribution did not differ between groups (p=0·15). Blood-fed Anopheles gambiae species complex mosquitoes captured in intervention group clusters the week after MDA in 2019 had decreased survival relative to those captured from control group clusters (p<0·0001), but this effect was not seen in mosquitoes captured 3 weeks after MDA. Overall entomological inoculation rates (EIRs; infectious bites per person per night) did not differ between groups (intervention EIR 0·010; control EIR 0·011; between-group ratio 0·91, 95% CI 0·56–1·30; p=0·45). In 2020, children aged 10 years and younger in the intervention group had a significantly higher increase in haemoglobin pre-intervention versus post-intervention than children in the control group (p=0·007). Repeated high-dose ivermectin MDA integrated with SMC distributions at the study site did not reduce malaria incidence among children relative to placebo MDA, despite evidence that, compared with the control group, mosquito survivorship in the first year was reduced in the intervention group the week following MDA and overall improvements in haemoglobin were greater in children in the intervention group. Confounding factors, including unexpectedly low malaria incidence over the trial period, possibly due to government distribution of dual-chemistry ITNs to all trial clusters in the middle of the intervention period, overdispersion of the primary incidence outcome between clusters, and high parasite and mosquito species diversity, might have influenced the primary outcome. National Institute of Allergy and Infectious Diseases.

Background. Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. Methods. We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. Results. Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. Conclusions. Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. Clinical Trials Registration. NCT01975441.

This trial of strategies for scabies control in Fiji compared administration of permethrin to affected persons and their contacts with mass administration of either permethrin or ivermectin. The prevalence of scabies declined in all groups, with the greatest decline in the ivermectin group. Scabies, a skin condition that is recognized by the World Health Organization as a disease of public health importance, 1 is a substantial contributor to global morbidity and mortality. Scabies is caused by a microscopic mite ( Sarcoptes scabiei var. hominis ) and is transmitted primarily through person-to-person contact. Infestation can result in debilitating itchiness, with associated sleep disturbance, reduced ability to concentrate, 2 social stigmatization, 3 and ongoing health care expenses. 4 , 5 In many developing countries, scabies-related scratching is an important cause of impetigo, 6 – 10 which is most often due to Streptococcus pyogenes or Staphylococcus aureus infection and can lead to septicemia, . . .

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.

Ivermectin is widely used in mass drug administrations for controlling neglected parasitic diseases, and can be lethal to malaria vectors that bite treated humans. Therefore, it could be a new tool to reduce plasmodium transmission. We tested the hypothesis that frequently repeated mass administrations of ivermectin to village residents would reduce clinical malaria episodes in children and would be well tolerated with minimal harms. We invited villages (clusters) in Burkina Faso to participate in a single-blind (outcomes assessor), parallel-assignment, two-arm, cluster-randomised trial over the 2015 rainy season. Villages were assigned (1:1) by random draw to either the intervention group or the control group. In both groups, all eligible participants who consented to the treatment and were at least 90 cm in height received single oral doses of ivermectin (150–200 μg/kg) and albendazole (400 mg), and those in the intervention group received five further doses of ivermectin alone at 3-week intervals thereafter over the 18-week treatment phase. The primary outcome was cumulative incidence of uncomplicated malaria episodes over 18 weeks (analysed on a cluster intention-to-treat basis) in an active case detection cohort of children aged 5 years or younger living in the study villages. This trial is registered with ClinicalTrials.gov, number NCT02509481. Eight villages agreed to participate, and four were randomly assigned to each group. 2712 participants (1333 [49%] males and 1379 [51%] females; median age 15 years [IQR 6–34]), including 590 children aged 5 years or younger, provided consent and were enrolled between May 22 and July 20, 2015 (except for 77 participants enrolled after these dates because of unavailability before the first mass drug administration, travel into the village during the trial, or birth), with 1447 enrolled into the intervention group and 1265 into the control group. 330 (23%) participants in the intervention group and 233 (18%) in the control group met the exclusion criteria for mass drug administration. Most children in the active case detection cohort were not treated because of height restrictions. 14 (4%) children in the intervention group and 10 (4%) in the control group were lost to follow-up. Cumulative malaria incidence was reduced in the intervention group (648 episodes among 327 children; estimated mean 2·00 episodes per child) compared with the control group (647 episodes among 263 children; 2·49 episodes per child; risk difference −0·49 [95% CI −0·79 to −0·21], p=0·0009, adjusted for sex and clustering). The risk of adverse events among all participants did not differ between groups (45 events [3%] among 1447 participants in the intervention group vs 24 events [2%] among 1265 in the control group; risk ratio 1·63 [1·01 to 2·67]; risk difference 1·21 [0·04 to 2·38], p=0·060), and no adverse reactions were reported. Frequently repeated mass administrations of ivermectin during the malaria transmission season can reduce malaria episodes among children without significantly increasing harms in the populace. Bill & Melinda Gates Foundation.

In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7–14 days apart using weight-based bands, or 5% permethrin cream 7–14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505). During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5–99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4–84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7–37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6–53·1). Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies. International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.

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.

Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication . We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin–piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions. This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7–46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin–piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300–400 μg/kg per day for 3 consecutive days] and dihydroartemisinin–piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin–piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313. Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin–piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16–0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66–1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention. The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin–piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed. Joint Global Health Trials Scheme. For the French translation of the abstract see Supplementary Materials section.