A new treatment of albendazole and ivermectin shows higher efficacy against Trichuris trichiura and hookworm infections, offering a new treatment approach for soil-transmitted worms.
Alejandro Krolewiecki, PhD
Image credits: Children With Worms
Soil-transmitted helminths (STHs) like Trichuris trichiura, hookworms, and Strongyloides stercoralis continue to pose a significant health threat, particularly in sub-Saharan Africa. These infections cause debilitating conditions, especially in tropical and subtropical regions. Existing treatments, such as albendazole, have shown limited effectiveness, particularly against T trichiura. Recent studies show that combining albendazole with ivermectin, widely used for other parasitic infections, may offer more effective treatment. A study published in The Lancet Infectious Diseases investigates the safety, efficacy, and palatability of a fixed-dose combination (FDC) of these two drugs in school-aged children from Ethiopia, Kenya, and Mozambique, regions heavily impacted by STHs.
The Phase 2/3 adaptive, randomized trial, conducted between January 2022 and March 2023, involved 1,001 children aged five to 18 years. These participants were diagnosed with T trichiura, hookworm, or S stercoralis. They were randomly assigned to one of three treatment arms: albendazole alone, a single dose of the FDC (albendazole 400 mg plus ivermectin 9 or 18 mg), or the FDC administered over three consecutive days. The trial measured safety and efficacy, with the primary outcomes being safety within 3 hours and 7 days (Phase 2, conducted in Kenya) and efficacy at day 21 (Phase 3), specifically the proportion of participants cured of T trichiura.
In an exclusive email interview, Alejandro Krolewiecki, director of innovation at Mundo Sano and principal investigator of the STOP2030 project, shared insights from the trial and its implications for global efforts to eliminate STH by 2030, as outlined by the WHO roadmap.
A Powerful Duo Against Soil-Transmitted Helminths
Krolewiecki explained the rationale behind combining albendazole and ivermectin, "Albendazole/mebendazole is very effective against hookworms (Ancylostoma duodenale and Necator americanus) and Ascaris lumbricoides. Ivermectin is very effective against Strongyloides stercoralis. While neither drug is very effective against Trichuris trichiura on its own, treating with both at the same time delivers a much greater efficacy against this species."
Regarding the trial’s results Krolewiecki added, "We believe it is safe to assume the FDC can target the four species considered in WHO’s 2021-2030 Roadmap for STH (ie, hookworms, A lumbricoides, T trichiura, S stercoralis). Meanwhile, the most used anthelmintic drugs in high-prevalence areas, albendazole and mebendazole monotherapies, only control two of the four species."
Among the 1,001 participants, 465 (46%) were female, and 536 (54%) were male. The majority of participants were infected with T trichiura (636, or 64%), followed by hookworm (360, or 36%) and S stercoralis (104, or 10%). Approximately 9% had co-infections. The FDC demonstrated significantly higher cure rates compared to albendazole alone. For T trichiura, the cure rate in the FDC×3 group (three daily doses) was 97.2%, compared to 35.9% in the albendazole-only group. The FDC×1 group (single dose) showed a cure rate of 82.9%, still higher than albendazole alone. For hookworm infections, the FDC×3 group had a cure rate of 95%, compared to 65.1% in the albendazole group, while the FDC×1 group had a cure rate of 79.8%. Although, the efficacy of the FDC against S stercoralis could not be fully evaluated due to an insufficient sample size.
In terms of safety, the most common side effects were mild gastrointestinal symptoms, including nausea and abdominal discomfort, which resolved within 48 hours without medical intervention. Treatment-related adverse events were reported in 14% of participants in the albendazole group, 20% in the FDC×1 group, and 23% in the FDC×3 group. There were no serious adverse events during the trial.
Krolewiecki emphasized the importance of these findings, "The FDC of albendazole and ivermectin has superior efficacy in treating T trichiura and hookworm infections compared to albendazole alone. This combination therapy could significantly improve treatment outcomes for children in areas where STH infections are endemic. Importantly, the safety profile of the FDC is comparable to that of albendazole monotherapy, which is important for widespread adoption."
Streamlined Treatment Logistics with the FDC
One of the key advantages of the FDC is its simplicity in administration. Albendazole and ivermectin are typically administered separately, with ivermectin doses adjusted according to the individual's weight or height. This can complicate distribution, as each person needs a different number of pills. Krolewiecki noted, "If you want to target all four STH species you need to provide both albendazole and ivermectin, but the latter drug is dosed individually by weight or height. So you need to measure every person and deliver a different amount of tablets—anywhere from 2 to 5. The FDC has simpler logistic needs: one person gets one pill, no measurements needed, while maintaining the superior efficacy of the combination strategy."
Addressing the Challenge of Trichuris trichiura
The FDC of albendazole and ivermectin shows significantly higher cure rates for Trichuris trichiura and hookworm infections compared to albendazole alone.
The FDC simplifies treatment by combining two drugs into a single pill, eliminating the need for individual weight-based dosing.
This combination therapy has the potential to improve outcomes for multiple soil-transmitted helminths and contribute to the global STH elimination goals by 2030.
T trichiura, or whipworm, has long been one of the most difficult STHs to treat with albendazole alone. Previous studies have shown that albendazole monotherapy achieves only a 30-35% cure rate for this species. However, combining albendazole with ivermectin has significantly improved treatment outcomes, with cure rates now exceeding 80%. Krolewiecki explained the impact of the FDC, "Albendazole monotherapy has been shown to be only partially effective against T trichiura. The cure rate hovers around 30-35%. Complementing it with ivermectin delivers a much stronger cure rate, above 80%. The FDC combines both drugs into a single, fixed-dose pill and provides this superior efficacy."
The results of this clinical trial suggest that combining albendazole with ivermectin could be a key tool in the fight against soil-transmitted helminths. This combination therapy has shown superior efficacy, particularly for T trichiura and hookworms, and has been well-tolerated by participants. The simplicity of the FDC also makes it a practical choice for deworming programs in high-prevalence areas, where logistic challenges often hinder treatment delivery.
While further research is needed to evaluate the FDC’s efficacy against S stercoralis and its long-term impact on STH control, the results from this trial offer strong evidence that the FDC could play an important role in global efforts to reduce the burden of STH by 2030.
