Cluster-randomized trial of monthly malaria prophylaxis versus focused screening and treatment: A study protocol to define malaria elimination strategies in Cambodia

Jessica Manning*, Chanthap Lon, Michele Spring, Mariusz Wojnarski, Sok Somethy, Soklyda Chann, Panita Gosi, Kin Soveasna, Sabaithip Sriwichai, Worachet Kuntawunginn, Mark M. Fukuda, Philip L. Smith, Huy Rekol, Muth Sinoun, Mary So, Jessica Lin, Prom Satharath, David Saunders

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Malaria remains a critical public health problem in Southeast Asia despite intensive containment efforts. The continued spread of multi-drug-resistant Plasmodium falciparum has led to calls for malaria elimination on the Thai-Cambodian border. However, the optimal approach to elimination in difficult-to-reach border populations, such as the Military, remains unclear. Methods/design: A two-arm, cluster-randomized controlled, open-label pilot study is being conducted in military personnel and their families at focal endemic areas on the Thai-Cambodian border. The primary objective is to compare the effectiveness of monthly malaria prophylaxis (MMP) with dihydroartemisinin-piperaquine and weekly primaquine for 12 weeks compared with focused screening and treating (FSAT) following current Cambodian national treatment guidelines. Eight separate military encampments, making up approximately 1000 military personnel and their families, undergo randomization to the MMP or FSAT intervention for 3 months, with an additional 3 months' follow-up. In addition, each treatment cluster of military personnel and civilians is also randomly assigned to receive either permethrin- or sham (water)-treated clothing in single-blind fashion. The primary endpoint is risk reduction for malaria infection in geographically distinct military encampments based on their treatment strategy. Monthly malaria screening in both arms is done via microscopy, PCR, and rapid diagnostic testing to compare both the accuracy and cost-effectiveness of diagnostic modalities to detect asymptomatic infection. Universal glucose-6-phosphate dehydrogenase (G6PD) deficiency screening is done at entry, comparing the results from a commercially available rapid diagnostic test, the fluorescence spot test, and quantitative testing for accuracy and cost-effectiveness. The comparative safety of the interventions chosen is also being evaluated. Discussion: Despite the apparent urgency, the key operational elements of proposed malaria elimination strategies in Southeast Asian mobile and migrant populations, including the Military, have yet to be rigorously tested in a well-controlled clinical study. Here, we present a protocol for the primary evaluation of two treatment paradigms - monthly malaria prophylaxis and focused screening and treatment - to achieve malaria elimination in a Cambodian military population. We will also assess the feasibility and incremental benefit of outdoor-biting vector intervention - permethrin-treated clothing. In the process, we aim to define the cost-effectiveness of the inputs required for success including a responsive information system, skilled human resource and laboratory infrastructure requirements, and quality management. Despite being a relatively low transmission area, the complexities of multi-drug-resistant malaria and the movement of vulnerable populations require an approach that is not only technically sound, but simple enough to be achievable. Trial registration:, ID: NCT02653898. Registered on 13 January 2016.

Original languageEnglish
Article number558
Issue number1
StatePublished - 16 Oct 2018
Externally publishedYes


  • Cambodia
  • Dihydroartemisinin-piperaquine
  • Elimination
  • Malaria
  • Mass drug administration
  • Permethrin
  • Primaquine


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