Optimizing treatment for soil-transmitted helminthiasis

Soil-transmitted helminths (STHs), namely Ascaris lumbricoides ̧ Trichuris trichiura and hookworms, are intestinal parasites infecting a quarter of the people living in the world today. Highest at risk for infection are children in subtropical and tropical climates with limited access to improved drinking water sources, inadequate sanitation and living in poverty. Infections with helminths tend to be asymptomatic, though more intense infections can cause abdominal discomfort, anemia and wasting. Preventive chemotherapy, or treatment without diagnosis, to at-risk populations is the current recommendation by the World Health Organization (WHO) for the control of STHs. The strategy of preventive chemotherapy is carried out through mass drug administration of either single dose albendazole or mebendazole to reduce the morbidity of infections in the target population. Though there has been a reduction in the prevalence of STHs in the last 15 years, the low efficacy of both treatment options against T. trichiura, and to a lesser extent hookworm infections, is a drawback to control strategies. Optimized therapies for STH control are needed if elimination is to be reached and maintained.
The objectives of this thesis are to assess regimens and dosages of current available treatment options that are potentially available for mass drug administration. The first and second objectives of this thesis are to identify an optimal dose of the currently used albendazole in preschool-aged children (PSAC), school-aged children (SAC) and adults infected with either T. trichiura or hookworms in Côte d'Ivoire. In the first objective of this PhD thesis, results show albendazole, regardless of dose, has low efficacy against T. trichiura, though findings need to be interpreted carefully as recruitment goals were not met for PSAC and adults. In the second objective, moderate efficacy of albendazole was shown against hookworm; specifically, an 800 mg dose (twice the current standard dose) provides superior efficacy in adults.
The third objective of this PhD research was to design and conduct a multi-country trial assessing the efficacy of combination therapy of albendazole and ivermectin against T. trichiura. The trial was conducted in three settings: Pemba Island, Tanzania, Lao PDR and Côte d'Ivoire using the same standardized protocol. Though the combination therapy was proved to be efficacious in Pemba Island, Tanzania and Lao PDR, albendazole combined with ivermectin was not found to be superior than monotherapy of albendazole in Côte d'Ivoire. Potential reasons for this discrepancy range from emerging resistance to population-based differences, which are being further investigated.
The last objective of this thesis aimed to identify potential gut morbidity markers in participants included in the efficacy trial of the third objective. Identifying two potential morbidity markers: fecal calprotectin and fecal occult blood, the study assessed the correlation between the markers and STH infection. No association was found between either marker and STH infection, making them poor markers for STH gut morbidity.
Based on the findings of the research conducted, it is recommended that alternative combination therapies be used for the control of STHs. Drugs such as oxantel pamoate or moxidectin combined with a higher dose of albendazole could be highly efficacious against all three STHs, especially in settings such as Côte d'Ivoire. Furthermore, a thorough evaluation of control programs are needed to assess the benefits and costs of mass drug administration in reducing the burden of disease. Finally, research in the fields of STH and neglected tropical diseases need to expand and diversify the study designs used in assessing drug efficacy and effectiveness.