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The Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in Vietnamese School Children

Phase 4
Withdrawn
Conditions
Intestinal Helminthiasis
Diarrhea
Interventions
Drug: Placebo
Registration Number
NCT02597556
Lead Sponsor
Oxford University Clinical Research Unit, Vietnam
Brief Summary

Cheap and effective drugs called 'anthelmintics' are routinely administered to children in developing countries to eliminate infections by parasitic helminths. However, the effects of anthelmintic treatment on other pathogens (e.g., bacteria, viruses, protozoa) remain unknown. The aim of this study is to investigate the impact of anthelmintic treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam. Diarrheal disease remains a substantial cause of morbidity and mortality in children in Vietnam, and these children are typically co-infected with intestinal helminths. As helminths and diarrheal pathogens infect the same intestinal niche, anthelmintic treatments may alter host immune responses and the composition of the gut microbiota in ways that affect infection and disease risks caused by diarrheal pathogens.

This study will recruit 350 helminth-infected and 350 helminth-uninfected children aged 6-15 years. Recruited children will be randomized to receive either anthelmintic or placebo treatment once every three months and will be monitored for incidences of diarrheal disease for 12 months. At the 12-month time point, all children will receive anthelmintic treatment. Blood and stool samples will be collected throughout the study and used for evaluation of anemia and host immune responses, and for classification of gut microbes and parasite detection, respectively. The interventional study proposed here will provide an important first test of whether anthelmintic treatments have any indirect effects on infections caused by diarrheal pathogens.

Detailed Description

This study is a randomized, double-blind, placebo-controlled trial to evaluate the effects of 400 mg albendazole treatment against placebo on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Children will be enrolled from three primary schools in Cu Chi district in Ho Chi Minh City, Vietnam. Children will be screened for infections by the four most common soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale. Infected and uninfected individuals will be recruited into the study and randomized to either receive albendazole treatment once every three months for 12 months, or to placebo once every three months for 9 months, after which albendazole treatment will be given at month 12, in accordance with the current deworming schedule in Cu Chi district. A questionnaire regarding the participant's demographics, his/her daily habits, and potential sources of infection will be administered at baseline. Weekly active and passive surveillance of diarrheal cases will be conducted throughout the study, and a health questionnaire will be administered during all cases of diarrhea and at the end of the study.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Between 6-15 years of age
  • Written informed consent from a parent or guardian
  • Written assent from children >10 years of age
Exclusion Criteria
  • Subjects who do not fulfill any component of the inclusion criteria
  • Subjects that are both hookworm-positive and anemic, as defined by the WHO guidelines

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AlbendazoleAlbendazoleAlbendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months.
PlaceboPlaceboMatching Placebo will be administered as a single chewable tablet at 0, 3, 6, and 9 months. At month 12, all participants will receive a single 400mg Albendazole tablet.
Primary Outcome Measures
NameTimeMethod
Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance12 months

Incidence of diarrhea will be defined according to WHO guidelines as three or more loose stools in a 24-hour period or at least one bloody/mucoid stool. To be considered a new episode of diarrhea, at least three intervening days of normal stools without other gastrointestinal symptoms need to have passed between diarrhea occurrences.

Secondary Outcome Measures
NameTimeMethod
Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopyBaseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in blood cytokine (Th1, Th2, TH17, and Treg) levels by bead-based immunoassaysBaseline, 6, and 12 months of study
Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen PanelTime Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in fecal microbiota composition by Illumina sequencingBaseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Antibody isotype response to helminth and diarrheal antigens by ELISABaseline, 6, and 12 months
Mean z-scores (height-for-age, weight-for-age, weight-for-height)Baseline and 12 months

Trial Locations

Locations (1)

Cu Chi, Viet Nam

🇻🇳

Ho Chi Minh city, Vietnam

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