Clinical trial NCT01658774: Impact of Repeated Anthelmintic Treatment on the Risk of Malaria in Kenyan School Children
Official title: Impact of Repeated Anthelminthic Treatment on Malaria in School Children: an Individual Randomized, Double-blind, Placebo-controlled Trial in Western Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intestinal Helminthiasis
Ascariasis
Hookworm
Malaria
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: European Union
name: Wellcome Trust
First posted: 2012-08-07
Enrollment: 2377
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of clinical malaria
timeFrame: 18 months
Secondary outcomes:
measure: Prevalence and density of Plasmodium spp. infection.
timeFrame: 18 months
measure: Antibody isotype response to Plasmodium antigens.
timeFrame: 18 months
measure: Antibody isotype response to helminth antigens.
timeFrame: 18 months
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: KEMRI-Wellcome Trust Programme
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Simon J Brooker, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kepha S, Nuwaha F, Nikolay B, Gichuki P, Mwandawiro CS, Mwinzi PN, Odiere MR, Edwards T, Allen E, Brooker SJ. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial. J Infect Dis. 2016 Jan 15;213(2):266-75. doi: 10.1093/infdis/jiv382. Epub 2015 Jul 13.