Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: Results from randomized controlled trials in Lao PDR and Pemba Island, Tanzania

Abstract

Background Preventive chemotherapy is the cornerstone of soil-transmitted helminth (STH) control. Long-term outcomes and adequate treatment frequency of the recently recommended albendazole-ivermectin have not been studied to date. Methodology/principal findings Double-blind randomized controlled trials were conducted in Lao PDR, Pemba Island, Tanzania and Côte d’Ivoire between 2018 and 2020 to evaluate the efficacy and safety of ivermectin-albendazole versus albendazole-placebo in Trichuris trichiura-infected individuals aged 6 to 60. In the framework of this study, in Lao PDR 466 and 413 participants and on Pemba Island, 558 and 515 participants were followed-up six and 12 months post-treatment, respectively. From each participant at least one stool sample was processed for Kato-Katz diagnosis and cure rates (CRs), egg reduction rates (ERRs) and apparent reinfection rates were calculated. If found helminth-positive at 6-months, participants were re-treated according to their allocated treatment. Long-term outcomes against T. trichiura based on CRs and ERRs of ivermectin-albendazole compared to albendazole were significantly higher at six months in Lao PDR (CR, 65.8% vs 13.4%, difference; 52.4; 95% CI 45.0–60.0; ERRs: 99.0% vs 79.6, difference 19.4; 95% CI 14.4–24.4) and Pemba Island (CR: 17.8 vs 1.4%, difference; 16.4%; 95% CI 11.6–21.0; ERRs: 84.9 vs 21.2, difference 63.8; 95% CI 50.6–76.9) and also at 12 months in Lao PDR (CR, 74.0 vs 23.4%, difference; 50.6; 95% CI 42.6–61.0; ERRs: 99.6 vs 91.3, difference 8.3; 95% CI 5.7–10.8) and Pemba Island (CR, 19.5 vs 3.4%, difference; 16.1; 95% CI 10.7–21.5; ERRs: 92.9 vs 53.6, difference 39.3; 95% CI 31.2–47.4) respectively. Apparent reinfection rates with T. trichiura were considerably higher on Pemba Island (100.0%, 95% CI, 29.2–100.0) than in Lao PDR (10.0%, 95% CI, 0.2–44.5) at 12 months post-treatment for participants treated with albendazole alone. Conclusions/significance The long-term outcomes against T. trichiura of ivermectin-albendazole are superior to albendazole in terms of CRs and ERRs and in reducing infection intensities. Our results will help to guide decisions on how to best use ivermectin-albendazole in the context of large-scale PC programs tailored to the local context to sustainably control STH infections. Trial registration ClinicalTrials.gov registered with clinicaltrials.gov, reference: NCT03527732, date assigned: 17 May 2018.

Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases

“…Between January and May 2019, people from ten villages in Nambak, Luang Prabang district in Laos were tested for T. trichiura . 549 people were included and randomly assigned to either monotherapy (albendazole) or combination therapy (albendazole-ivermectin) 21 . Daily post-treatment stool samples were collected from a subset of 88 patients up to 28 days after first administration, among which 80 were included for microbiome assessment (Fig.…”

Efficacy and safety of moxidectin and albendazole compared with ivermectin and albendazole coadministration in adolescents infected with Trichuris trichiura in Tanzania: an open-label, non-inferiority, randomised, controlled, phase 2/3 trial

“…Additionally, the combination also improved infection status and intensity 12 months after treatment with intermediate retreatment after 6 months. 13 Ivermectin is widely used for veterinary deworming and against human lymphatic filariasis and onchocerciasis in control programmes. 14 , 15 Since usage across various fields and infections is often associated with an increased risk for the development of resistance, concerns have been voiced on the possible emergence of ivermectin resistance.…”

Impact of preventive chemotherapy on transmission of soil-transmitted helminth infections in Pemba Island, United Republic of Tanzania, 1994–2021

“…On the one hand, further studies to elucidate the existence of mutations in the STH genome leading to resistance to benzimidazole derivatives are under way. On the other hand, a recent study from Keiser and collaborators [ 22 ] found that the egg reduction rate obtained with albendazole for trichuriasis in Pemba was of 57%, which is within the range of efficacy indicated by WHO as normal [ 23 ].…”