Monitoring Drug Efficacy and Anthelmintic Resistance in Soil-transmitted Helminth Programs

NCT04177654 | Completed FDA Drug

• 1 other identifier: OPP1120972_WP2
• Study Type: observational
• Target: 9,457
• Locations: 8 countries
• Sites: 8

Brief 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 overall aim of this study is to pilot a surveillance system to assess anthelmintic drug efficacy and the emergence of AR in 9 countries were drug pressure has been high over a long period of time. The specific objectives are to:

1. 1.Assess the prevalence of moderate/heavy intensity infections of the different STH
2. 2.Assess the drug efficacy of a single dose of BZ drugs against STH infections in these countries
3. 3.Assess the frequency of the ß-tubulin SNPs linked to BZ resistance
4. 4.Identify implementation-related barriers and opportunities for monitoring drug efficacy and AR in national PC programs for STH.
5. 5.Expand the Starworms repository of STH field samples

Conditions

Soil-transmitted Helminth Infections

Keywords

parasitology; helminth infections; Ascaris; Trichuris; hookworm; qPCR; microscopy; drug resistance; diagnosis; drug efficacy

Outcome Measures

Primary Outcomes (3)

• moderate/heavy intensity infections of the different STH

  The data collected at baseline (prior to treatment) will provide valuable information on the infection intensities and prevalence of the different STH in that population.

  up to 12 months

• drug efficacy of a single dose of BZ drugs against STH infections in these countries

  The reduction in egg output of the cohort of infected school aged children will inform us on the efficacy of the administered drug.

  up to 12 months

• frequency of the ß-tubulin SNPs linked to BZ resistance

  The collected stool samples will be analyzed and SNPs linked to benzimidazole drug resistance in STH will be quantified using molucular techniques like pyrosequencing, whole gene sequencing and LAMP.

  up to 12 months

Secondary Outcomes (2)

• costs related to monitoring drug efficacy and AR in national PC programs for STH.

  up to 12 months

• Expand the Starworms repository of STH field samples

  up to 12 months

Study Arms (8)

Cambodia

The group of school-aged children from Cambodia who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Bangladesh

The group of school-aged children from Cambodia who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Vietnam

The group of school-aged children from Vietnam who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Lao PDR

The group of school-aged children from Lao PDR who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Ghana

The group of school-aged children from Ghana who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Senegal

The group of school-aged children from Senegal who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Rwanda

The group of school-aged children from Rwanda who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Haiti

The group of school-aged children from Haiti who are being screened. Children will receive a single standard dose of benzimidazole drug (either 400mg of Albendazole or 500mg of Mebendazole) and stool samples will be collected prior to and 2-3 weeks following treatment.

Drug: Benzimidazoles

Interventions

Benzimidazoles DRUG

A single dose of benzimidazole drug (400mg Albendazole or 500mg Mebendazole) will be administered as part of routine deworming services.

Also known as: Albendazole, Mebendazole

Bangladesh; Cambodia; Ghana; Haiti; Lao PDR; Rwanda; Senegal; Vietnam

Eligibility Criteria

• Age: 5 Years - 14 Years
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Healthy school-aged children aged 5-14.

You may qualify if:

• Subject, male or female, is 5-14 years of age
• Subject is otherwise in healthy condition (based on medical history and physical examination)
• Parent(s)/guardians of subject signed an informed consent document indicating that they understand the purpose of and procedures required for the study and that they are willing to have their child participate in the study
• Subject of ≥6 years has assented to participate in the study
• Subject of ≥12 years has signed an informed consent document indicating that they understand the purpose of the study and procedures required for the study and are willing to participate in the study
• Subject has provided a stool sample of at least 5 grams.

You may not qualify if:

• Subject has active diarrhoea (defined as the passage of 3 or more loose or liquid stools per day) at baseline or follow-up.
• Subject has an acute medical condition or is experiencing a severe concurrent medical condition
• Subject has a known hypersensitivity to ALB or MEB
• Subject has received anthelmintic treatment within 90 days prior to the start of the treatment
• Subject vomited within 4 hours following drug ingestion.
• Subject is not able to provide a stool sample of minimum 5 grams at baseline or follow-up.
• Subject has not swallowed the entire tablet.

Sponsors & Collaborators

• University Ghent: lead

Study Sites (8)

Filariasis Elimination, STH Control and Little Doctor Program, Communicable Disease Control (CDC),Directorate General of Health Services (DGHS), MOHFW

Dhaka, Bangladesh

Location

Ministry of Health, Cambodia

Phnom Penh, Cambodia

Location

Centre for Science and Industrial Research

Accra, Ghana

Location

PAHO

Port-au-Prince, Haiti

Location

Centre for Malariology, Parasitology and Entomology Lao PDR

Vientiane, Laos

Location

Rwanda Biomedical Center/Ministry of Health of Rwanda - NTD&OPD Unit

Kigali, Rwanda

Location

NTD Programme, Ministry of Health

Dakar, Senegal

Location

Institute of Malariology Parasitology and Entomology (Nimpe),

Hanoi, Vietnam

Location

Related Links

• Project homepage

Biospecimen

Retention: SAMPLES WITH DNA

stool samples preserved in Ethanol

MeSH Terms

Conditions

Trematode Infections; Ancylostomiasis; Disease

Interventions

Benzimidazoles; Albendazole; Mebendazole

Condition Hierarchy (Ancestors)

Helminthiasis; Parasitic Diseases; Infections; Hookworm Infections; Strongylida Infections; Secernentea Infections; Nematode Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Bruno Levecke, PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 26, 2019
• Study Start: May 15, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: No specific time-frame will be applied.
• Access Criteria: Free access for all

Locations

BA (1); VN (1); SE (1); CA (1); GH (1); HA (1); LA (1); RW (1)