Plasmodium falciparum Clearance Rates in Response to Artesunate in Malian Children With Malaria: Effect of Acquired Immunity
| Autor: | Seidina A. S. Diakite, Mory Doumbouya, Michael P. Fay, Saibou Doumbia, Tatiana M. Lopera-Mesa, Serena Chiang, Karim Traore, Daouda Ndiaye, Drissa Konaté, Abdoul S. Keita, Mahamadou Diakite, Kasia Stepniewska, Rick M. Fairhurst, Juliana M. Sá, Carole A. Long, Jennifer M. Anderson, Amir E. Zeituni |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Erythrocytes Adolescent medicine.medical_treatment Plasmodium falciparum antimalarial immunity malaria Antibodies Protozoan Artesunate Dihydroartemisinin Parasitemia Adaptive Immunity Biology Mali Parasite load Parasite Load Cohort Studies Antimalarials Major Articles and Brief Reports chemistry.chemical_compound parasitic diseases medicine Humans Immunology and Allergy Parasites Artemether Malaria Falciparum Artemisinin Child parasite clearance Amodiaquine Infant biology.organism_classification medicine.disease Virology Artemisinins Infectious Diseases artemisinin chemistry Child Preschool Immunoglobulin G Immunology Female Malaria medicine.drug |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Artemisinins rapidly kill all asexual blood stages of Plasmodium falciparum [1], including young ring forms before they sequester in the microvessels of vital organs, and are thus more effective than quinolines in reducing malaria morbidity and mortality [2, 3]. For this reason, artemisinin-based combination therapies (ACTs) are first-line treatments for P. falciparum malaria worldwide [4]. ACTs are the use of artemisinin or one of its derivatives—artesunate, artemether, dihydroartemisinin (DHA)—in combination with a partner drug. DHA, the active metabolite of all artemisinins, has a short half-life (approximately 1–3 hours) in plasma; therefore, partner drugs with longer half-lives (ie, approximately 7–21 days) are needed to eliminate residual parasites [5, 6]. Parasite resistance to nearly every commonly used partner drug is entrenched or emerging in western Cambodia [7]. Reports of artemisinin resistance in western Cambodia [8, 9] and western Thailand [10]—where antimalarial-resistant parasites have previously emerged and spread to Africa [11–13]—are thus extremely worrisome. This phenotype manifests as a slow parasite clearance rate in response to an artemisinin taken orally to treat uncomplicated malaria [14]. Unlike quinoline resistance, artemisinin resistance does not associate with known molecular markers of drug resistance or reduced parasite drug susceptibility in vitro [8, 9, 15]. Slow parasite clearance may be partly defined as a parasite-heritable trait [9, 10, 16] and was recently associated with a major region of the parasite genome [17]. Microsatellite-defined parasite genetics, however, has not been able to account for all the variation in parasite clearance rates in Cambodia and Thailand [9, 10, 16]. Few studies have explored how host factors, such as naturally acquired immunity and red blood cell (RBC) polymorphisms, influence parasite clearance rates in response to artemisinins. A retrospective analysis of 18 699 patients with P. falciparum malaria treated with artemisinins found that parasite clearance was slowest in low-transmission settings and relatively fast in high-transmission settings, suggesting that acquired immunity accelerates parasite clearance [18]. A recent prospective study suggested that hemoglobin (Hb) E is associated with slow parasite clearance rate in Pursat, western Cambodia [9], but the effect of acquired immunity on this parameter is not well defined. This is because, in southeast Asia, age is an inadequate surrogate of immunity to malaria and no in vitro correlate of parasite-clearing immunity has been identified. Few parasite clearance rates have been reported from Africa [19], where ACTs were recently introduced and artemisinin monotherapies have been used for 15 years in some areas [20]. The proposed mechanism of action of artemisinins involves endoperoxide-derived, free radicals that alkylate and oxidize the proteins and lipids of intraerythrocytic parasites [21]. Artemisinin-treated parasites undergo pyknosis rapidly in vivo and are cleared from the bloodstream by “pitting” in the spleen, which returns previously infected, intact RBCs back into circulation (Figure (Figure11A) [22–25]. Although largely determined by the rates of pyknosis and pitting, the parasite clearance rate is nonetheless a complex phenotype produced by a combination of parasite and host factors. Parasite expression of cytoadherence ligands, for example, can determine when late ring-stage parasites sequester in microvessels and disappear from peripheral blood (Figure (Figure11C) [26]. If parasites sequester en masse [26] while parasite clearance is being monitored, parasite densities may decrease markedly by an artemisinin-independent mechanism. Host antibody responses that prevent sequestration and opsonize parasitized RBCs may also accelerate parasite clearance (Figure (Figure11B). Figure 1. Clearance of ring-stage Plasmodium falciparum parasites from peripheral blood during a parasite clearance rate study. Dihydroartemisinin, the active metabolite of all artemisinins, causes ring-stage parasites to undergo pyknosis (A). These circulating ... To obtain baseline surveillance data for the emergence or spread of artemisinin resistance in Africa and to investigate the role of acquired immunity in parasite clearance, we measured parasite clearance rates in response to artesunate in a high transmission area of Mali, where ACTs were introduced only 2 years previously and where children rapidly acquire antimalarial immunity with age. |
| Databáze: | OpenAIRE |
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