Validating Egg-based Diagnostics and Molecular Markers for the Spread of Anthelmintic Resistance

• Status: Completed
• Trial end date: 2019-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Soil-transmitted helminths (STHs) are a group of parasitic worms that infect millions of children in sub-tropical and tropical countries, resulting in malnutrition, growth stunting, intellectual retardation and cognitive deficits. To control the morbidity due to these worms, school-based deworming programs are implemented, in which anthelminthic drugs are administered to children without prior diagnosis. The continued fight against these worms is aided by the London declaration on neglected tropical diseases, which helps sustain and expand global drug donation program, resulting in an unprecedented growth of deworming programs. However, the high degree of drug pressure makes deworming programs vulnerable to the development of anthelmintic resistance because they only rely on one drug with sometimes suboptimal efficacy and there is no availability of alternative drugs. Moreover, at present, there is no surveillance system to monitor the emergence and spread of anthelmintic resistance. It remains unclear to what extent the efficacy of drugs may have dropped and whether anthelmintic resistance is already present.

This project aims to strengthen the monitoring and surveillance of drug efficacy and anthelmintic resistance in STH programs. As such, it will support deworming programs in their quest to eliminate STHs as a public health problem.

The specific objectives of the first work package are to validate diagnostic tools to monitor drug efficacy and the spread of anthelmintic resistance, and to validate molecular markers for benzimidazole resistance.

This study will be conducted at four different sites (Ethiopia, Tanzania, Lao PDR and Brazil) and will focus on school-aged children (age 5-14). At baseline subjects will be asked to provide a recent stool sample which will be processed using 3 different microscopic techniques (KK, Mini-Flotac and FECPAKG2). All children will be treated with a single-oral dose of albendazole (ALB) 400 mg and 14-21 days after treatment, a second stool sample will be collected from all children to again determine the fecal egg counts. At each sampling, stool is stored in preservative. Stored stool will be shipped to Belgium for DNA extraction and quantitative PCR (qPCR) analysis. A subset of the samples will be analysed by pyrosequencing to evaluate the single nucleotide polymorphisms in the b-tubulin gene. Pooling of the stored samples will also be performed to compare with the values obtained from analysing individual samples.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Ghent
• Collaborator: Swiss Tropical & Public Health Institute
• Treatments: Albendazole; Anthelmintics

Criteria

Inclusion Criteria:

• Subject, male or female, is 5-14 years of age

• Subject is otherwise in an healthy condition (medical history and physical examination)

• Parent(s)/guardians of subjects (or their legally-accepted representatives) signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to have their child participate in the study.

• Subject of ≥6 years has assented (agreed) to participate in the study.

• Subject of ≥12 has signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

• The subject swallowed the entire drug (ALB 400 mg) under supervision

• Subject provides a stool sample of at least 9 grams

Exclusion Criteria:

• Subject has active diarrhea (defined as the passage of 3 or more loose or liquid stools per day) at baseline or follow-up

• Subject has any acute medical condition or is experiencing a severe concurrent medical condition

• Subject has a known hypersensitivity to benzimidazole drugs

• Subject has received an anthelminthic treatment within 90 of the start of the treatment.

• Subject vomited within 4 hours after drug administration

• Subject is unable to provide a stool sample at follow-up