Individual-level analysis of the efficacy of albendazole and albendazole-ivermectin fixed-dose coformulation (FDC) against Trichuris trichiura and hookworms

Background

Anthelmintic drugs are vital for controlling soil-transmitted helminths (STH), but treatment failures remain common. The egg reduction rate (ERR) is a key metric for assessing anthelmintic efficacy. This study calculated individual ERRs (ERRi) to evaluate a new anthelmintic drug and identify factors associated with treatment failure.

Methodology

Data were collected from 369 children infected with T. trichiura and 226 infected with hookworms, who participated in a Phase II/III clinical trial. Participants received a single dose of ivermectin/albendazole 9/400 mg or 18/400 mg fixed-dose coformulation (FDC) or albendazole 400 mg (ALB). Egg counts were measured pre- and post-treatment using the Kato-Katz test. A Bayesian mixed model was used to calculate ERRi and assess covariates influencing treatment response.

Results

In T. trichiura-infected participants (n = 369), complete therapeutic failure (uncured and lacking significant ERRi) occurred in 54 % of the albendazole group compared to 7 % in the FDC group. Notably, 59 % of uncured participants in the FDC arm achieved significant ERRi, versus only 16 % in the albendazole arm. Co-infections influenced outcomes: A. lumbricoides co-infection improved response in the albendazole group, while S. stercoralis co-infection reduced efficacy in the FDC arm. Among hookworm-infected participants (n = 226), complete failure was observed in 15 % (albendazole) and 10 % (FDC). Both arms showed 56 % of uncured participants achieving significant ERRi. S. stercoralis co-infection was linked to poorer response in the FDC arm, while no covariates influenced albendazole response.ERRi modeling demonstrated the superior efficacy of FDC over albendazole in T. trichiura treatment, with comparable efficacy for hookworms.