ArticlesArtemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study
Introduction
Artemisinin resistance in Plasmodium falciparum has not yet been fully defined. In Pailin, western Cambodia, it has been described as a slower parasite clearance rate after artesunate treatment than in Wang Pha, western Thailand.1 A 2012 report2 showed that artemisinin resistance is emerging in western Thailand, and predicts that in 2–6 years it will reach levels reported in Pailin. In Cambodia, the provinces of Pailin, Battambang, Pursat, and Kampot constitute zone 1—a region where the global plan for artemisinin resistance containment focuses its parasite elimination efforts because persistent parasitaemia has been reported more than 72 h after artemisinin-based combination therapy.3 However, parasite clearance rates in zone 1 provinces other than Pailin (population 70 482 in 2008;4 area 803 km2) have not been reported.
In Pailin and western Thailand, the finding that genetically related P falciparum clones are cleared at similar rates in different patients suggests that parasite genetics has a role.2, 5 However, much variation in parasite clearance rates remains unexplained, implying that host factors affect this phenotype. Erythrocyte polymorphisms are common in western Cambodia, where greater than 40% of individuals carry at least the haemoglobin E (HbE) polymorphism.6, 7
Erythrocyte polymorphisms and acquired immunity could account for some variation in parasite clearance rates, thus affecting association analyses between these rates and parasite genotypes. One possibility is that oxidative stress exerted by HbE,8 α-thalassaemia,9 and erythrocytes deficient in glucose-6-phosphate dehydrogenase (G6PD)10 stimulates ring-stage parasites to upregulate their antioxidant defences, thereby antagonising the pro-oxidant activity of artemisinins11 and delaying parasite clearance by the spleen.12, 13, 14 Another possibility is that effectors of acquired immunity (eg, immune IgG) remove parasites from the circulation,15 thereby accelerating parasite clearance. To assess the effects of parasite genetics and host factors on the artemisinin-resistance phenotype in western Cambodia, we studied parasite clearance rates in response to artesunate in Pursat province (population 397 107 in 2008;4 area 12 692 km2; 146 km south of Pailin).
Section snippets
Study design and participants
During the 2009 and 2010 malaria seasons (June 19 to Nov 28, 2009; June 26 to Dec 6, 2010) we did a study at the Sampov Meas Referral Hospital in Pursat, Cambodia. We enrolled patients from all six districts of Pursat province. Patients were referred to our study clinic from Sampov Meas, Krakor, Bakan, and Kandieng districts. Our study team recruited patients from Kravanh and Veal Veng districts by travelling daily through these westernmost regions to assess patients presenting at the side of
Results
We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. 712 people (20·3%) were diagnosed with falciparum malaria, but 544 (76·4%) of these patients were not enrolled because of low parasite densities or other exclusion criteria (appendix). The remaining 168 patients were predominantly men with a median age of 24 years (table), which is consistent with our previous findings (unpublished). 103 patients (61·3%) had at least one erythrocyte
Discussion
The time taken to clear P falciparum parasites in patients from Pursat is lengthy, with half-life as long as 11·28 h, suggesting that the artemisinin-resistance phenotype is well established outside Pailin (panel; appendix). We have identified a genetically defined cluster of parasites (PG1) that is significantly associated with increased half-life; a heritability analysis suggested that roughly 40% of half-life variation can be attributed to parasite genetics. Additionally, some host factors
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Dr Lindegardh died in January, 2012