Impact of Repeated Anthelmintic Treatment on the Risk of Malaria in Kenyan School Children

Sponsor

London School of Hygiene and Tropical Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT01658774

Collaborator

European Union (Other), Wellcome Trust (Other)

2,377

Enrollment

Location

Arms

Duration (Months)

99.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Many school children in Kenya are infected with plasmodia and helminth species and are at risk of coinfection. It has been suggested that the immune response evoked by helminth infections may modify immune responses to plasmodia species and consequently alter infection and disease risks. However, studies conducted to date have been typically cross-sectional and produced conflicting results, and there is a need for longitudinal studies to better understand the clinical consequences for individuals harbouring coinfection. This study aims to investigate the impact of intensive (once every 3 months) anthelminthic treatment versus annual treatment on the risk of clinical malaria and on immune responses among school children aged 5-14 years in Western Province. Specifically, this study aims to investigate the impact of intensive anthelminthic treatment on (i) the incidence of clinical malaria in school children, assessed using active case detection; (ii) the prevalence and density of Plasmodium spp. infection, using repeat cross-sectional surveys; and (iii) malaria and helminth specific immune responses. The study hypothesis is that intensive anthelminthic treatment among children infected with either Ascaris lumbricoides or hookworm modifies human host immune responses to plasmodia and helminth infections, and therefore alters the risk of Plasmodium infection and clinical disease.

This individually randomised trial will recruit 1,450 children aged 5-14 years found to be infected with either Ascaris lumbricoides or hookworm species. Recruited children will be randomized to receive albendazole treatment either every three months or annually and monitored through periodic surveillance for clinical malaria episodes over 18 months. In addition, blood samples will be collected from sub-sample of children and screened for malaria specific immunoglobulin (Ig)G1 and IgG3 and helminth specific IgE, IgG2, IgG4 and IgM. Cell culture supernatants will be assayed for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-5, IL-4 and IL-2.

Condition or Disease	Intervention/Treatment	Phase
Intestinal Helminthiasis Ascariasis Hookworm Malaria	Drug: Albendazole Dietary Supplement: Vitamin C	N/A

Detailed Description

This will be an individual randomized, single-blind trial to evaluate the impact of intensive versus annual anthelminthic treatment on the incidence of clinical malaria in healthy school children.

The target population includes children attending primary school in western Kenya. The accessible population includes children attending the participating primary schools in standards 1-7 in western Kenya. The unit of analysis is the individual child. Children with informed consent and assent will be screened for helminth infections and those children found to be infected with either Ascaris lumbricoides or hookworm species will be recruited into the study. These children will be randomized to one or two groups, receiving either albendazole treatment every three months or albendazole at the start of the study and placebo every three months thereafter. Cross-sectional health surveys will be conducted before the intervention and at 6, 12 and 18 months follow-up. Weekly active case detection during school visits will be undertaken.

Study Design

Study Type:

Interventional

Actual Enrollment :

2377 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Impact of Repeated Anthelminthic Treatment on Malaria in School Children: an Individual Randomized, Double-blind, Placebo-controlled Trial in Western Kenya

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Albendazole & Vitamin C Anthelmintics. A single dose of Albendazole (400mg) at month 0 and single dose of Vitamin C (500 mg) at 3, 6, 9 and 12 months.	Drug: Albendazole Single 400mg dose Other Names: Zentel Dietary Supplement: Vitamin C 500 mg Vitamin C
Experimental: Albendazole Anthelmintics. A single does of Albendazole (400mg) every three months for 12 months	Drug: Albendazole Single 400mg dose Other Names: Zentel

Arm

Intervention/Treatment

Active Comparator: Albendazole & Vitamin C

Anthelmintics. A single dose of Albendazole (400mg) at month 0 and single dose of Vitamin C (500 mg) at 3, 6, 9 and 12 months.

Drug: Albendazole

Single 400mg dose

Other Names:

Zentel

Dietary Supplement: Vitamin C

500 mg Vitamin C

Experimental: Albendazole

Anthelmintics. A single does of Albendazole (400mg) every three months for 12 months

Drug: Albendazole

Single 400mg dose

Other Names:

Zentel

Outcome Measures

Primary Outcome Measures

Incidence of clinical malaria [18 months]
Incidence of clinical malaria, defined as fever (axillary temperature > 37.5 °C) or a reported history of fever within the preceding 24 hours in conjunction with a slide positive for Plasmodium spp. parasites at any density during 18 months of follow-up.

Secondary Outcome Measures

Prevalence and density of Plasmodium spp. infection. [18 months]
Antibody isotype response to Plasmodium antigens. [18 months]
ELISA analysis will be carried out to determine IgG1and IgG3 antibody response to Plasmodium antigens (schizont extract and Merozoite Surface Proteins (MSP)
Antibody isotype response to helminth antigens. [18 months]
ELISA analysis will be carried out to determine and IgE, IgG2, IgG4 and IgM responses to hookworm and Ascaris lumbricoides.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Pupils enrolled at participating schools in classes 1-7.
Provision of informed consent from parent or legal guardian.
Provision of assent by student.
Detectable infection with A.lumbricoides, T. trichiura and/or hookworm species.

Exclusion Criteria:

Pupils unwilling to participate in the study.
Pupils who are infected with S. haematobium or S. mansoni. These children will be treated with praziquantel.
Known or suspected sickle-cell trait.