Last Updated: 14/01/2015
Defining effective, appropriate, implementable strategies for malaria elimination in military forces in Cambodia as a model for mobile migrant populations within the Greater Mekong Subregion (GMS)
Objectives
In this study, the investigators will conduct operational research with the Royal Cambodian Armed Forces (RCAF) and National Malaria Center (CNM) to quantify the relative effectiveness of the two major interventional approaches – monthly malaria prophylaxis (MMP) or focused screening and treatment (FSAT) – in a head-to-head comparison.
In addition, the investigators will quantify the relative contribution of a recently advocated vector intervention for military personnel – the insecticide-treated uniform (ITU) – in addition to other vector control measures currently employed by the RCAF. The investigators will employ the same permethrin insecticide self-application kits currently used by the US military.
The investigators will estimate the cost effectiveness of each approach and attempt to define the best way forward for malaria elimination efforts in a critically important malaria reservoir in military population (and their dependents) who reside on the Thai-Cambodian border.
The aim of the study is not only to conduct research to better define the best way forward in malaria elimination efforts in the high risk military populations, but to also build capacity within the RCAF to support and lead future elimination efforts in the most difficult-to-reach mobile populations.
Armed Forces Research Institute of Medical Sciences (AFRIMS), United States
Subjects in the monthly malaria prophylaxis (MMP) arm will receive a standard 3-day treatment course of dihydroartemisinin-piperaquine on months 1, 2 and 3 and weekly low-dose primaquine (22.5mg for 12 weeks). Volunteers in the focused screening and treatment (FSAT) arm will be screened monthly and then treated for malaria following national treatment guidelines. For G6PD-deficient volunteers in the FSAT arm, primaquine will be administered weekly (45mg for 8 weeks) as radical curative and/or presumptive anti-relapse therapy. For G6PD normal volunteers with vivax infection, primaquine will be administered daily (15mg for 14 days). All FSAT volunteers with confirmed P. falciparum infection will receive a single, low dose (15mg) Primaquine as a P. falciparum transmission-blocking agent. The incremental benefit of an insecticide-treated uniform (ITU) will also be assessed as a single-blind sham-controlled intervention in addition to personal protective measures currently employed by the RCAF. Volunteers will be followed monthly for a total of 6 months, to determine the proportion remaining malaria-free on day 180 following enrollment.
The concomitant interventions deployed are self-protective measures, such as LLINs under normal field use.
Outcome measures:
- Primary:
- Absolute risk reduction based on the proportion of subjects remaining malaria-free at the end of 6 months between the study arms as diagnosed by PCR-corrected malaria microscopy
- Secondary:
- Overall rate of sexual stage infections at Months 1 through 6 in each arm based on a combined endpoint of light microscopy and PCR analysis for detection of gametocyte maturity
- Number of participants with abnormal lab values and/or Adverse Events that are related to the treatments in each arm
- Kaplan-Meier survival analysis of asexual and sexual blood stage at 28-day intervals after treatment or prophylaxis up to 180 days
- Comparison of all-species and species-specific malaria incidence density in each arm over 180-day period
- Comparative incidence of malaria detected by RDT versus RT-PCR versus microscopy
- Comparative incidence of G6PD deficiency in the study population as determined by RDT, quantitative, and qualitative tests
- Estimate of apparent rates of pre-existing immunity to malaria based on medical history, days of fever prior to presentation, and pre-existing parasitological parameters
- Sensitivity and specificity assessment of the currently recommended rapid diagnostic test in Cambodia to detect moderate to severe G6PD deficiency using quantitative G6PD testing as the reference standard
- Odds ratio for P.v recurrence for each CYP2D6 phenotype
- Rate of cytochrome P450 2D6 genotypes/phenotypes in the population at risk
- Percent reduction in hemoglobin and HTC for each 2D6 haplotype in subjects with available CBC following PQ dosing
- Percentage of subjects with malaria recurrence for each CYP2D6 phenotype
Clinicaltrials.gov ID: NCT02653898
Type: Interventional
Allocation: Cluster Randomized
Intervention model: Parallel assignment
Masking: open-label for study drug interventions but volunteers were blinded to ITU vs sITU
Primary purpose: Prevention, reduction of malaria transmission/incidence
Jan 2016 — Dec 2021
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