Comparing Chemoprevention Approaches for School-based Malaria Control

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

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.

Study Overview

• Status: Completed
• Conditions: Malaria,Falciparum; Anemia in Children
• Intervention / Treatment: Drug: Dihydroartemisinin-Piperaquine; Drug: Chloroquine

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 746
• Phase: Phase 4

Contacts and Locations

Study Locations

• Malawi
  • Blantyre, Malawi
    • Kamuzu University of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intermittent Screening and Treatment (IST); 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; Treatment of females less than 10 years old and all males in Arm 2 and those who test positive in Arm 1.; Other Names: Eurartesim; Artekin; Ridmal; DP; DuoCotecxin; Drug: Chloroquine; Treatment of females 10 years old and older in Arm 2 and those who test positive in Arm 1.; Other Names: Aralen
Experimental: Intermittent Preventive Treatment (IPT); 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; Treatment of females less than 10 years old and all males in Arm 2 and those who test positive in Arm 1.; Other Names: Eurartesim; Artekin; Ridmal; DP; DuoCotecxin; Drug: Chloroquine; Treatment of females 10 years old and older in Arm 2 and those who test positive in Arm 1.; Other Names: Aralen
No Intervention: Control; Students will not receive preventive treatment.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function test scores	standardized scores	6-8 weeks after the last intervention
Reading test scores	standardized scores	6-8 weeks after the last intervention
Math test scores	standardized scores	6-8 weeks after the last intervention
School attendance	number of days missed based on registers and spot checks	from the first intervention to 6-8 weeks after the last intervention
Mean infectiousness	regression modeled infectiousness based on gametocyte density, gametocyte sex ratio, symptom status, and other predictors of infectiousness	from the first intervention to 6-8 weeks after the last intervention
Performance characteristics of conventional RDT	compared to PCR to detect: P. falciparum infection, P. falciparum parasite density, anemia, hemoglobin, gametocytemia, gametocyte density, and potential infectiousness score	through study completion, on average 6 months
Performance characteristics of high-sensitivity RDT	compared to PCR to detect: P. falciparum infection, P. falciparum parasite density, anemia, hemoglobin, gametocytemia, gametocyte density, and potential infectiousness score	through study completion, on average 6 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Kamuzu University of Health Sciences; Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Lauren Cohee, MD MS, University of Maryland School of Medicine

Publications and helpful links

General Publications

• Cohee LM, Valim C, Coalson JE, Nyambalo A, Chilombe M, Ngwira A, Bauleni A, Seydel KB, Wilson ML, Taylor TE, Mathanga DP, Laufer MK. School-based screening and treatment may reduce P. falciparum transmission. Sci Rep. 2021 Mar 25;11(1):6905. doi: 10.1038/s41598-021-86450-5.
• Cohee LM, Opondo C, Clarke SE, Halliday KE, Cano J, Shipper AG, Barger-Kamate B, Djimde A, Diarra S, Dokras A, Kamya MR, Lutumba P, Ly AB, Nankabirwa JI, Njagi JK, Maiga H, Maiteki-Sebuguzi C, Matangila J, Okello G, Rohner F, Roschnik N, Rouhani S, Sissoko MS, Staedke SG, Thera MA, Turner EL, Van Geertruyden JP, Zimmerman MB, Jukes MCH, Brooker SJ, Allen E, Laufer MK, Chico RM. Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses. Lancet Glob Health. 2020 Dec;8(12):e1499-e1511. doi: 10.1016/S2214-109X(20)30325-9. Epub 2020 Oct 22.
• Halliday KE, Okello G, Turner EL, Njagi K, Mcharo C, Kengo J, Allen E, Dubeck MM, Jukes MC, Brooker SJ. Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomised trial. PLoS Med. 2014 Jan 28;11(1):e1001594. doi: 10.1371/journal.pmed.1001594. eCollection 2014 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): August 26, 2022

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: hemoglobin; adolescent; cognitive function; education; malaria; chemoprevention; school; preventive treatment; screening and treatment
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine; Piperaquine; Artenimol
• Other Study ID Numbers: HP-00098250

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all individual participant data that underlie results in a publication
• IPD Sharing Time Frame: After results publication
• IPD Sharing Access Criteria: Public access with registration to allow tracking
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No