NCT01240603

Plasmodium Falciparum Clearance Rates in Response to Artesunate in Eastern Cambodia

Completed Last updated 5 April 2018

What this trial tests

trial in Malaria in 415 participants. Completed in 11 September 2013.

Timeline

24 October 2010

11 September 2013

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Status	Completed
Study type	OBSERVATIONAL
Enrollment	415
Start date	24 October 2010
Estimated completion	11 September 2013
Sites	1 location across Cambodia

Conditions studied

• Malaria — all drugs for Malaria →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

1 and older, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Plasmodium falciparum parasite clearance rates (PCRs) after oral artesunate treatment of patients with uncomplicated malaria were recently found to be significantly slower in Pailin (Western Cambodia) compared to Wang Pha (Eastern Thailand). This difference in PCRs has been attributed to different histories of artesunate drug pressure in the two areas. In Pailin, artesunate monotherapy has been used inappropriately for 30 years and is hypothesized to have selected for artemisinin-resistant parasites (slow PCRs). To investigate the potential contribution of human factors to the artemisinin resistance phenotype, we have identified a study site in Eastern Cambodia where artemisinin-resistant parasites are not believed to be present. The main aims of this study are to 1) determine whether the artemisinin resistance phenotype (i.e., a half-life longer than the 2-hour half-life observed in Wang Pha) is present in Eastern Cambodia, 2) determine whether hemoglobin E affects parasite clearance rates in vivo, 3) determine whether age-associated acquired immunity affects parasite clearance rates in vivo, and 4) identify parasite-heritable traits that are associated with slow parasite clearance rates in vivo. To meet these aims, we are conducting a prospective, longitudinal study to recruit Cambodian residents of Lumphat District in Ratanakiri Province who complain of fever and/or symptoms of malaria. Patients diagnosed with uncomplicated malaria will be treated with weight-based doses of artesunate given orally each day for 3 days followed by mefloquine given orally for 2 days. During this time, finger prick blood smears will be obtained every 6 hours until parasite density is zero. From these data, we will estimate parasite clearance rates using a half-life parameter. We will also collect parasitized red blood cell samples from malaria patients prior to antimalarial drug administration. These parasites will be tested in short-term in vitro culture experiments to determine their susceptibility to artemisinins and other antimalarial drugs.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Genetic architecture of artemisinin-resistant Plasmodium falciparum.
   Miotto O, Amato R, Ashley EA, MacInnis B, et al · · 2015 · cited 526× · PMID 25599401 · DOI 10.1038/ng.3189
2. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.
   Miotto O, Almagro-Garcia J, Manske M, Macinnis B, et al · · 2013 · cited 385× · PMID 23624527 · DOI 10.1038/ng.2624
3. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study.
   Amato R, Lim P, Miotto O, Amaratunga C, et al · · 2017 · cited 328× · PMID 27818095 · DOI 10.1016/s1473-3099(16)30409-1
4. Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples.
   Venkatesan M, Amaratunga C, Campino S, Auburn S, et al · · 2012 · cited 80× · PMID 22321373 · DOI 10.1186/1475-2875-11-41
5. Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in western, northern, and eastern Cambodia, 2011-2012: association with molecular markers.
   Lim P, Dek D, Try V, Eastman RT, et al · · 2013 · cited 33× · PMID 23939897 · DOI 10.1128/aac.00687-13
6. Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.
   Srimuang K, Miotto O, Lim P, Fairhurst RM, et al · · 2016 · cited 24× · PMID 27825353 · DOI 10.1186/s12936-016-1598-6
7. High-efficiency enrichment enables identification of aptamers to circulating Plasmodium falciparum-infected erythrocytes.
   Oteng EK, Gu W, McKeague M. · · 2020 · cited 9× · PMID 32546848 · DOI 10.1038/s41598-020-66537-1