Innovative tablet combination shows promise in combating Trichuris Trichiura and other helminths

Innovative tablet combination shows promise in combating Trichuris Trichiura and other helminths

A new tablet that combines albendazole and ivermectin is safe and more effective than albendazole alone in treatmentTrichuris Trichiuraand other soil-transmitted helminths (STH), according to a clinical trial carried out by the Stop Consortium and led by the Barcelona Institute of Global Health (ISGlobal), a center supported by the “La Caixa” Foundation. The results, published inThe Lancet Infectious Diseasesopen opportunities to improve control of these neglected tropical infections, which affect around 1.5 billion people worldwide.

Soil-transmitted helminthia (STH) are caused by four species of parasitic worms (STH) (Ascaris Lumbricoides, Trichuris Trichiuraand the hookwormsAncylostoma DuodenaleAndNecator Americanus)which are transmitted through contact with contaminated soil or water. They have a significant impact on nutrition and health, particularly among children and women of reproductive age living in endemic areas of Latin America, Asia and sub-Saharan Africa.

The current STH control strategy relies on regular deworming treatments with albendazole for at-risk populations, as well as water, sanitation and sanitation improvements. Albendazole is very effective againstAscarisbut its effectiveness againstT. Trichiurahas declined, likely due to emerging drug resistance. In addition, albendazole is not effective againstStrongyloides stercoralisanother helminth added to the list of intestinal parasites requiring control measures.

A new tablet

To address these gaps, the EDCTP-funded Stop consortium tested an innovative tablet that combines a fixed dose of albazol and ivermectin. Ivermectin has been shown to be more effective against thisT. TrichiuraIn combination with albendazole and is the drug of choice to treatS. Stercoralisand other parasitic infections.

This fixed dose co-formulation (FDC) has several advantages. It is easy to administer because it is a single pill and does not require dosage adjustments based on the child's weight. “

Jose Muñoz, project leader, ISGlobal researcher and head of the International Health Service at the Barcelona Hospital Clinic

“We also hope that combining two drugs with different mechanisms of action will reduce the risk of the parasites becoming drug-resistant,” he adds.

A clinical trial in three African countries

The living clinical trial conducted in Ethiopia, Kenya and MozambiqueT. Trichiurahookworms,S. Stercoralisor a combination. The children were randomly divided into three treatment groups: group 1 received a single dose of albendazole; Group 2 received one dose of the FDC (FDCX1); and Group 3 received three doses of the FDC (FDCX3) on three consecutive days.

Safety first

Phase 2 of the trial focused on safety. A small number of participants were recruited and treated sequentially by weight to monitor adverse effects caused by higher than usual doses of ivermectin (above 200 mcg/ml). No serious side effects were observed, and the side effects were similar to those of the albendazole group. This allowed the trial to move into Phase 3, where effectiveness was assessed in a much larger number of participants alongside continued safety monitoring.

A total of 4,353 children were screened for STH infections and 1,001 were randomized to treatment. Of those infected, 63% were positive forT. Trichiura36% for hookworms and 10% forS. Stercoralis.

Greater effectiveness againstT. Trichiura and hookworms

The effectiveness of the treatment was evaluated on the basis of cure rates (absence of eggs in stool samples after treatment) and a reduction in the number of eggs in stool compared to before treatment. ForT. TrichiuraThe FDC achieved higher cure rates with both regimens (97% for FDCX3, 83% for FDCX1) compared to albendazole alone (36%). In hookworms, the FDCX3 regimen showed a higher cure rate (95%), while the FDCX1 regimen was similar to albendazole (79% and 65%, respectively). ForS. StercoralisThe sample size was too small to assess effectiveness, but existing evidence suggests that FDC would also be more effective, as ivermectin is far more effective against this parasite than albendazole.

Although most infections were classified as mild, both FDC regimens achieved higher egg reduction rates than albendazole alone.

Public health implications

“This is a pivotal effort that opens up the possibility of controlling all STH species, includingStrongyloidesand may lead to re-examination of elimination targets that were considered unattainable with albendazole alone,” says Alejandro Krolewiecki, clinical trials coordinator of the FDC in the context of mass deworming campaigns.

Defining optimal implementation strategies is also essential if FDC is to be adopted by national programs. The trial results suggest that a single dosing regimen of the FDC can be easily applied in mass defeuherming activities, while the three-day regimen, which provides superior efficacy, may be better for individual treatment decisions or for programs aimed at completely eliminating Sth from the population.

“With its child-friendly formulation-orodspermersable and mango flavor-and its high acceptance, this tablet has great potential to improve the regions affected by these diseases,” says Stella Kepha, researcher at the Kenya Medical Research Institute (KEMRI).

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