Clinical trial to evaluate intermittent screening and treatment with high sensitivity rapid diagnostic tests and intermittent preventive treatment of malaria in asymptomatic school children to decrease P. falciparum infection and transmission
Abstract
Type of research study: Randomized clinical trial
Problem: How should school-based malaria preventive treatment programs be designed to improve
the health and educational achievement of children and decrease malaria transmission?
Objectives:
Obj 1: Evaluate the efficacy of intermittent screening and treatment (IST) and intermittent preventive
treatment (IPT) to improve student health and education.
Obj 2: Assess the impact of IST and IPT on P. falciparum (Pf) transmission.
Obj 3: Compare the sensitivity of currently used (conventional) and high sensitivity rapid diagnostic
tests (hs-RDT) to detect Pf infections that impact health and transmission to evaluate their use as a
screening test for IST.
Methodology:
All objectives will be addressed in the context of a randomized controlled clinical trial in one school in
Machinga District comparing the efficacy of school-based hsRDT-IST and IPT to standard care (control).
Outcomes include Pf infection, clinical malaria disease, anemia, school attendance, test scores, as well
as predicted infectiousness and household infection prevalence in a subsample of participants’s
households. Students in all grades in a single primary school in an area of moderate transmission of
malaria will be offered enrollment (total target sample size 750 students). Students will be randomized
to receive either hsRDT-IST, IPT, or standard care (control). Students in the IPT arm and students with
positive hsRDT on screening in the IST arm will be treated. Girls less than 10 years old and all boys will
be treated with dihydroartemisinin-piperaquine. Girls 10 years old and older will be treated with
chloroquine. The intervention will be conducted three times total during school terms which coincide
with peak malaria transmission (January-June). Outcomes will be measured at each intervention visit
and 6-8 weeks after the final intervention. At each visit, students will be interviewed about symptoms
and treatment history and a fingerprick blood sample will be obtained to detect and characterize
infection. At baseline and final visits, hemoglobin will be measured. At the baseline visit for students
in the IST arm and the final visit for students in the control arm will be tested for infection with both a
conventional RDT and hsRDT. Treatment will be based on hsRDT results, but conventional RDT results
will provide further comparisons of the need for the increased sensitivity of hsRDTs. Symptomatic
malaria is defined as objective fever and a positive conventional RDT. Pf infection is defined as parasite
DNA detected by qPCR amplification of the 18SrRNA gene. Detection, quantification, and assessment
of gametocyte sex ratio will be conducted using RT-qPCR amplification of CCp4 (female gametocyte
marker) and PfMGET (male gametocyte marker). A subsample of households of students in each arm
will be visited and household members who chose to participate will be tested for Pf infection to
determine if treatment of schoolchildren decreases transmission of infection to their household
members.
Expected findings and dissemination: We hypothesize that both approaches to preventive treatment
(IST and IPT) will be effective in improving health and education outcomes when compared to control.
However, IPT will be more effective in reducing transmission as measured by predicted infectiousness
and household infection prevalence. We will discuss our findings with national and district-level
leaders. Results will be disseminated in peer-reviewed journals, international conferences, KUHeS
Research Day, as well as provided to community leaders. The findings will be useful for policymakers and program managers for both national and international malaria control programs. We anticipate that results will directly inform the design of programmatic implementation of school-based malaria chemoprevention programs.
Description
Keywords
Clinical trial testing and treating malaria in children using rapid diagnostic test