Preventing Malaria in School Children to Protect the Whole Community in Rural Blantyre District, Malawi

Study Overview
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Brief Summary
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This is an individually randomized, controlled, single blind four arm clinical trial of malaria chemoprevention strategies Arm 1: Intermittent preventive treatment with dihydroartemisinin-piperaquine (IPT-DP). Arm 2: Intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) plus chloroquine (CQ) (IPT-SPCQ). Arm 3: Intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) (IPT-SPAQ).Arm 4: Control - students will receive standard of care (no preventive treatment). Outcomes include P. falciparum infection and parasite density, anemia, cognitive function and educational testing, as well as infection prevalence and disease incidence in young children sleeping student's households to assess the impact on transmission.

Detailed Description
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Students attending primary school in rural Blantyre District, Malawi will be offered enrollment in this study. The intervention will be conducted every 6-weeks during the two school terms which coincide with peak malaria transmission. Students in the IPT-DP arm will be treated with with dihydroartemisinin-piperaquine (DP) (females less than 13 years old and all males) or chloroquine (females 13 years old or older). Students in the IPT-SPCQ arm will be treated with sulfadoxine-pyrimethamine plus chloroquine (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older). Students in the IPT-SPAQ arm will be treated with sulfadoxine-pyrimethamine plus amodiaquine (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older). Students in the all arms will receive routine malaria education.

Official Title
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Preventing Malaria in School Children to Protect the Whole Community in Rural Blantyre District, Malawi

Conditions
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Malaria,Falciparum, Anemia in Children

Intervention / Treatment
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* Drug: Dihydroartemisinin-Piperaquine
* Drug: Chloroquine
* Drug: Sulfadoxine pyrimethamine
* Drug: Sulfadoxine-pyrimethamine-amodiaquine


Participation Criteria
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Eligibility Criteria
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Student Inclusion Criteria: 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 Student Exclusion Criteria: 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 History of epilepsy or psoriasis Taking cotrimoxazole for long-term prophylaxis Younger child Inclusion Criteria Slept in the household for most nights in the last month Age 6-59 months Parent/guardian available to provide written informed consent Younger child Exclusion Criteria - 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 four arms Arm 1: intermittent preventive treatment with dihydroartemisinin-piperaquine (IPTsc-DP); Arm 2: intermittent preventive treatment with sulfadoxine-pyrimethamine plus chloroquine (IPTsc-SPCQ). Arm 3: intermittent preventive treatment with sulfadoxine-pyrimethamine plus amodiaquine (IPTsc-SPAQ); Arm 4 the control arm. Females 13 years and older (likely post-menarche) in Arms 1, 2 and 3 will receive chloroquine alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent Preventive Treatment with dihydroartemisinin-piperaquine (IPT-DP)<br>All students are treated at each intervention. Treatment will be with DP (females less than 13 years old and all males) or chloroquine (females 13 years old or older). | Drug: Dihydroartemisinin-Piperaquine<br>* Treatment will be with DP (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older).<br>* Other names: Ridmal;Drug: Chloroquine<br>* Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).<br>* Other names: Lariago;|
| Experimental: Intermittent Preventive Treatment with sulfadoxine-pyrimethamine plus chloroquine (IPT-SPCQ)<br>All students are treated at each intervention. Treatment will be with SP and CQ (females less than 13 years old and all males) or chloroquine (females 13 years old or older). | Drug: Chloroquine<br>* Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).<br>* Other names: Lariago;Drug: Sulfadoxine pyrimethamine<br>* Treatment in combination with CQ in Arm 2 (females less than 13 years old and all males). Treatment in combination with AQ in Arm 3 (females less than 13 years old and all males).<br>* Other names: SP;|
| Experimental: Intermittent Preventive Treatment with sulfadoxine-pyrimethamine plus amodiaquine (IPT-SPAQ)<br>All students are treated at each intervention. Treatment will be with SP and AQ (females less than 13 years old and all males) or chloroquine (females 13 years old or older). | Drug: Chloroquine<br>* Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).<br>* Other names: Lariago;Drug: Sulfadoxine-pyrimethamine-amodiaquine<br>* Treatment in Arm 3 (females less than 13 years old and all males).<br>* Other names: SPAQ-Co;|
| 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 |
| --- | --- | --- |
| Number of participants with P. falciparum infection | detected by polymerase chain reaction (PCR, binary) | 6-8 weeks after the last intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants 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 | 
| Rate of clinical malaria | cumulative incidence | through study completion (approximately 6 months), and 6 months following the intervention | 
| sustained attention | code transmission test score (continuous) | 6-8 weeks after the last intervention | 
| Literacy skills | Early grade reading assessment | 6-8 weeks after the last intervention | 
| Math skills | Early grade math assessment | 6-8 weeks after the last intervention | 
| P. falciparum prevalence among children less than 5 years old living in households with study participants | detected by PCR | 6-8 weeks after the last intervention | 
| Rate of clinical malaria among children less than 5 years old living in households with study participants | cumulative incidence | through study completion (approximately 6 months) |