Comparing Chemoprevention Approaches for School-based Malaria Control

Study Overview
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Brief Summary
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This is an individually randomized, controlled, single blind three arm clinical trial of malaria chemoprevention strategies Arm 1: Intermittent screening and treatment (IST) - students will receive treatment if they have a positive high sensitivity rapid diagnostic test (RDT). Arm 2: Intermittent preventive treatment (IPT) - all students will receive treatment. Arm 3: Control - students will receive standard of care (no preventive treatment). Outcomes include P. falciparum infection and parasite density, gametocyte carriage and gametocyte density, anemia, cognitive function and educational testing, as well as infection prevalence in student's households to assess the impact on transmission.

Detailed Description
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Students will be enrolled in a single primary school in Machinga District, Malawi. The intervention will be conducted every 6-weeks during the two school terms which coincide with peak malaria transmission. Students in the IPT are and those that test positive in the IST arm will be treatment with dihydroartemisinin-piperaquine (DP) (females less than 10 years old and all males) or chloroquine (females 10 years old or older).

Official Title
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Clinical Trial to Evaluate Intermittent Screening and Treatment and Intermittent Preventive Treatment of Malaria in Asymptomatic Schoolchildren to Decrease P. Falciparum Infection and Transmission

Conditions
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Malaria,Falciparum, Anemia in Children

Intervention / Treatment
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* Drug: Dihydroartemisinin-Piperaquine
* Drug: Chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Students (enrolled in the primary intervention) Currently enrolled in the study school Plan to attend the study school for the remainder of the school year Parent/guardian available to provide written informed consent Household members (enrolled in the Household Prevalence survey) Slept in the household for most nights in the last month Age 6 months or older For minors, parent/guardian available to provide written informed consent Exclusion Criteria: Students (enrolled in the primary intervention) Current evidence of severe malaria or danger signs Known adverse reaction to the study drugs History of cardiac problems or fainting Taking medications known to prolong QT Family history of prolonged QT Girls 10 years old and older with epilepsy or psoriasis Household members (enrolled in the Household Prevalence survey) Household with more than one school-age child enrolled in the study Current evidence of severe malaria or danger signs

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Students will be randomized to intermittent screening-and-treatment (IST - Arm 1), intermittent preventive treatment (IPT - Arm 2), or control with no preventive treatment (Arm 3). Females less that 10 years of age (pre-menarche) and all males will be treated with DP if they are in Arm 2 or test positive in Arm 1. Females 10 years and older will be treated with chloroquine if they are in Arm 2 or test positive in Arm 1.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent Screening and Treatment (IST)<br>Students will be screened for infection using a higher sensitivity malaria rapid diagnostic test and treated if positive. Treatment will be with DP (females less than 10 years old and all males) or chloroquine (females 10 years old or older). | Drug: Dihydroartemisinin-Piperaquine<br>* Treatment of females less than 10 years old and all males in Arm 2 and those who test positive in Arm 1.<br>* Other names: Ridmal;Drug: Chloroquine<br>* Treatment of females 10 years old and older in Arm 2 and those who test positive in Arm 1.<br>* Other names: Aralen;|
| Experimental: Intermittent Preventive Treatment (IPT)<br>All students are treated at each intervention. Treatment will be with DP (females less than 10 years old and all males) or chloroquine (females 10 years old or older). | Drug: Dihydroartemisinin-Piperaquine<br>* Treatment of females less than 10 years old and all males in Arm 2 and those who test positive in Arm 1.<br>* Other names: Ridmal;Drug: Chloroquine<br>* Treatment of females 10 years old and older in Arm 2 and those who test positive in Arm 1.<br>* Other names: Aralen;|
| No Intervention: Control<br>Students will not receive preventive treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P. falciparum infection | detected by polymerase chain reaction (PCR, binary) | 6-8 weeks after the last intervention | 
| P. falciparum gametocyte carriage | detected by q-rtPCR (binary) | 6-8 weeks after the last intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participant with anemia | World Health Organization age-sex definitions (binary) | 6-8 weeks after the last intervention | 
| Mean hemoglobin concentration | g/dL (continuous) | 6-8 weeks after the last intervention | 
| Total parasite density | log transformed (continuous) | 6-8 weeks after the last intervention | 
| Gametocyte density | log transformed (continuous) | 6-8 weeks after the last intervention | 
| Rate of clinical malaria | cumulative incidence | from the first intervention to 6-8 weeks after the last intervention | 
| P. falciparum prevalence among household members | detected by PCR | 6-8 weeks after the last intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, school, chemoprevention, preventive treatment, screening and treatment, education, cognitive function, adolescent, hemoglobin