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| Name | Class |
|---|---|
| National Center for Parasitology, Entomology, and Malaria Control (CNM) | UNKNOWN |
| Ministry of National Defense, Royal Cambodian Armed Forces Department of Health | UNKNOWN |
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Antimalarial drug resistance has reached critical levels on the Thai-Cambodian border. Many have begun advocating for concerted malaria elimination efforts in Cambodia. However, there is currently no consensus on how malaria elimination is to be achieved with the tools available.
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.
This is a cluster-randomized, open label interventional study to determine the feasibility of achieving significant reduction in malaria cases in military encampments on the Thai-Cambodian border. The study will compare the effectiveness, safety, and tolerability of monthly malaria prophylaxis (MMP) to monthly focused screening and treatment (FSAT). This study will thus investigate the effectiveness of two potential interventions for malaria elimination. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Focused Screening and Treatment + ITU | Active Comparator | Approved antimalarial based on the malaria species identified on the monthly follow ups, following national treatment guidelines in Cambodia AND Insecticide Treated Uniform with 40% Permethrin; DHA-PIP or Artesunate + Mefloquine based on the malaria species, single dose Primaquine 15 mg in subjects with P.f uncomplicated malaria or Primaquine 45 mg weekly x 8 weeks in G6PD-deficient volunteers, or Primaquine 15 mg daily for 14 days in G6PD-normal volunteers. |
|
| Focused Screening and Treatment + sITU | Active Comparator | Approved antimalarial based on the malaria species identified at the monthly follow up and following national treatment guidelines in Cambodia AND sham treated uniform. DHA-PIP or Artesunate + Mefloquine based on the malaria species, single dose Primaquine 15 mg in subjects with P.f uncomplicated malaria or Primaquine 45 mg weekly x 8 weeks in G6PD-deficient volunteers, or Primaquine 15 mg daily for 14 days in G6PD-normal volunteers. |
|
| Monthly Malaria Prophylaxis + ITU | Active Comparator | Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive insecticide treated uniforms with 40% Permethrin |
|
| Monthly Malaria Prophylaxis + sITU |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DHA-PIP | Drug | Administered monthly (weight-based) on days 1-3, during months 1, 2, and 3 in the MMP arm and also as a first line agent for P.v malaria recurrence in both MMP and FSAT treatment arms |
| Measure | Description | Time Frame |
|---|---|---|
| The 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 | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 months | |
| Number of participants with abnormal lab values and/or Adverse Events that are related to the treatments in each arm |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chanthap Lon, MD | Armed Forces Research Institute of Medical Sciences, Thailand | Principal Investigator |
| Mariusz Wojnarski, MD | Armed Forces Research Institute of Medical Sciences, Thailand | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RCAF treatment facilities | Anlong Veaeng | Oddar Meancheay | Cambodia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41382293 | Derived | Wojnarski M, Chaudhury S, Boonchan T, Bun R, Chann S, Gosi P, Soveasna K, Song S, Buathong N, Ittiverakul M, Sriwichai S, Arsanok M, Kuntawunginn W, Saingam P, Chaisatit C, Ponlawat A, Fansiri T, Vanachayangkul P, Jaichapor B, Sinoun M, Chuor CM, Kheangheng T, So M, Wanja E, Davidson S, Spring M, Rekol H, Dysoley L, Saly K, Livezey JR, Lin JT, Smith PL, Satharath P, Manning JE, Sok S, Saunders DL. Evaluating malaria elimination strategies among military forces in Cambodia: a multi-arm clinical trial comparing monthly prophylaxis and focused screening and treatment. BMC Infect Dis. 2025 Dec 12;26(1):84. doi: 10.1186/s12879-025-12207-4. | |
| 30326952 |
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The preliminary results, final report and key data will be shared with a broad array of stakeholders from Cambodia, the region, bilateral and multilateral implementing partners, and donor organizations.
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| ID | Term |
|---|---|
| D008288 | Malaria |
| D010272 | Parasitic Diseases |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| D011319 | Primaquine |
| D000077332 | Artesunate |
| D015767 | Mefloquine |
| D026023 | Permethrin |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive sham treated uniforms |
|
|
| Primaquine | Drug | 22.5 mg weekly for 12 weeks in the MMP arm; low dose primaquine (15mg) for transmission blocking of P. falciparum or 14 days of primaquine (15mg) in G6PD normal volunteers or 8 weeks of low dose primaquine (45mg) in G6PD-deficient volunteers for radical cure of P. vivax |
|
| Artesunate + Mefloquine | Drug | Weight based; first line agent for P.f malaria infection diagnosed at monthly follow ups, administered on days 1-3 in subjects with malaria recurrence |
|
|
| Permethrin (Insecticide treated uniform) | Drug | 40% Permethrin IDA kit, applied once to the uniforms for volunteers assigned to ITU arm |
|
| 6 months |
| Kaplan-Meier survival analysis of asexual and sexual blood stage at 28-day intervals after treatment or prophylaxis up to 180 days | 6 months |
| Comparison of all-species and species-specific malaria incidence density in each arm over 180-day period | 6 months |
| Comparative incidence of malaria detected by RDT versus RT-PCR versus microscopy | 6 months |
| Comparative incidence of G6PD deficiency in the study population as determined by RDT, quantitative, and qualitative tests | At the time of enrollment |
| Estimate of apparent rates of preexisting immunity to malaria based on medical history, days of fever prior to presentation, and preexisting parasitological parameters (gametocytemia, low asexual stage parasitemias) | 6 months |
| 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 | At the time of enrollment |
| Odds ratio for P.v recurrence for each CYP2D6 phenotype | 6 months |
| Rate of cytochrome P450 2D6 genotypes/phenotypes in the population at risk | 6 months |
| Percent reduction in hemoglobin and HTC for each 2D6 haplotype in subjects with available CBC following PQ dosing | Day 3 (and day 7 in those volunteers with Hgb or HCT drop of at least 10% from baseline on Day 3) |
| Percentage of subjects with malaria recurrence for each CYP2D6 phenotype | 6 months |
| Derived |
| Manning J, Lon C, Spring M, Wojnarski M, Somethy S, Chann S, Gosi P, Soveasna K, Sriwichai S, Kuntawunginn W, Fukuda MM, Smith PL, Rekol H, Sinoun M, So M, Lin J, Satharath P, Saunders D. Cluster-randomized trial of monthly malaria prophylaxis versus focused screening and treatment: a study protocol to define malaria elimination strategies in Cambodia. Trials. 2018 Oct 16;19(1):558. doi: 10.1186/s13063-018-2931-x. |
| D006571 | Heterocyclic Compounds |
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D010647 | Phenyl Ethers |
| D004987 | Ethers |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011722 | Pyrethrins |
| D000081004 | Cyclopentane Monoterpenes |
| D039821 | Monoterpenes |