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

NCT02597556 | Withdrawn Phase 4 DMC

• 1 other identifier: 16EN
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Intestinal Helminthiasis; Diarrhea

Keywords

Albendazole; Ancylostoma duodenale; Ascariasis lumbricoides; Coinfection; Diarrhea; Helminths; Necator americanus; Microbiota; Trichuris trichiura

Outcome Measures

Primary Outcomes (1)

• Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance

  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.

  12 months

Secondary Outcomes (6)

• Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy

  Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases

• Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen Panel

  Time Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases

• Changes in fecal microbiota composition by Illumina sequencing

  Baseline, 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 immunoassays

  Baseline, 6, and 12 months of study

• Antibody isotype response to helminth and diarrheal antigens by ELISA

  Baseline, 6, and 12 months

Study Arms (2)

Albendazole

ACTIVE COMPARATOR

Albendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months.

Drug: Albendazole

Placebo

PLACEBO COMPARATOR

Matching 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.

Drug: Placebo

Interventions

Albendazole DRUG

A single 400mg dose of Albendazole administered at 0, 3, 6, 9, and 12 months.

Albendazole

Placebo DRUG

Matching placebo tablet administered at 0, 3, 6, and 9 months. At month 12, all participants will receive a single dose of 400mg Albendazole.

Placebo

Eligibility Criteria

• Age: 6 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Between 6-15 years of age
• Written informed consent from a parent or guardian
• Written assent from children \>10 years of age

You may not qualify if:

• Subjects that are both hookworm-positive and anemic, as defined by the WHO guidelines

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• Ho Chi Minh Preventive Medicine Centre, Vietnam: collaborator
• Princeton University: collaborator
• Cu Chi Health Department: collaborator
• Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam: collaborator

Study Sites (1)

Cu Chi, Viet Nam

Ho Chi Minh City, 700000, Vietnam

Location

Related Publications (9)

• Blackwell AD, Martin M, Kaplan H, Gurven M. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics. Proc Biol Sci. 2013 Aug 28;280(1769):20131671. doi: 10.1098/rspb.2013.1671. Print 2013 Oct 22.

  PMID: 23986108 BACKGROUND

• Ezenwa VO, Jolles AE. Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales. Science. 2015 Jan 9;347(6218):175-7. doi: 10.1126/science.1261714.

  PMID: 25574023 BACKGROUND

• Ferrari N, Cattadori IM, Rizzoli A, Hudson PJ. Heligmosomoides polygyrus reduces infestation of Ixodes ricinus in free-living yellow-necked mice, Apodemus flavicollis. Parasitology. 2009 Mar;136(3):305-16. doi: 10.1017/S0031182008005404. Epub 2009 Jan 21.

  PMID: 19154651 BACKGROUND

• Knowles SC, Fenton A, Petchey OL, Jones TR, Barber R, Pedersen AB. Stability of within-host-parasite communities in a wild mammal system. Proc Biol Sci. 2013 May 15;280(1762):20130598. doi: 10.1098/rspb.2013.0598. Print 2013 Jul 7.

  PMID: 23677343 BACKGROUND

• Pedersen AB, Antonovics J. Anthelmintic treatment alters the parasite community in a wild mouse host. Biol Lett. 2013 May 8;9(4):20130205. doi: 10.1098/rsbl.2013.0205. Print 2013 Aug 23.

  PMID: 23658004 BACKGROUND

• Nacher M. Worms and malaria: resisting the temptation to generalize. Trends Parasitol. 2006 Aug;22(8):350-1; author reply 351-2. doi: 10.1016/j.pt.2006.06.003. Epub 2006 Jun 23. No abstract available.

  PMID: 16798090 BACKGROUND

• Rousham EK. An increase in Giardia duodenalis infection among children receiving periodic Anthelmintic treatment in Bangladesh. J Trop Pediatr. 1994 Dec;40(6):329-33. doi: 10.1093/tropej/40.6.329.

  PMID: 7853436 BACKGROUND

• Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database Syst Rev. 2015 Jul 23;2015(7):CD000371. doi: 10.1002/14651858.CD000371.pub6.

  PMID: 26202783 BACKGROUND

• Leung JM, Hong CT, Trung NH, Thi HN, Minh CN, Thi TV, Hong DT, Man DN, Knowles SC, Wolbers M, Hoang Nle T, Thwaites G, Graham AL, Baker S. The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial. Trials. 2016 Jun 6;17(1):279. doi: 10.1186/s13063-016-1406-1.

  PMID: 27266697 DERIVED

Related Links

• Oxford University Clinical research Unit

MeSH Terms

Conditions

Intestinal helminthiasis; Diarrhea; Coinfection; Trichuriasis

Interventions

Albendazole

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections; Enoplida Infections; Adenophorea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stephen Baker, PhD

  Oxford University Clinical Research Unit

  PRINCIPAL INVESTIGATOR

• Nghia Ho Dang Trung, PhD, MD

  Pham Ngoc Thach University of Medicine

  PRINCIPAL INVESTIGATOR

• Andrea Graham, PhD

  Princeton University, USA

  PRINCIPAL INVESTIGATOR

• Jacqueline Leung, MA

  Princeton University, USA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 5, 2015
• Study Start: February 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

VN (1)