Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity.

Abstract

BACKGROUND:

Artemisinin resistance, a long parasite clearance half-life in response to artemisinin, has been described in patients with Plasmodium falciparum malaria in southeast Asia. Few baseline half-lives have been reported from Africa, where artemisinins were recently introduced.

METHODS:

We treated P. falciparum malaria in 215 Malian children aged 0.5-15 years with artesunate (0, 24, 48 hours) and amodiaquine (72, 96, 120 hours). We estimated half-life by measuring parasite density every 6 hours until undetectable and evaluated the effects of age, sex, ethnicity, and red blood cell (RBC) polymorphisms on half-life. We quantified the proportion of parasitized RBCs recognized by autologous immunoglobulin G (IgG).

RESULTS:

The geometric mean half-life was 1.9 hours (95% confidence interval, 1.8-2.0) and did not correlate with parasite ex vivo susceptibility to artemisinins. In a linear model accounting for host factors, half-life decreased by 4.1 minutes for every 1-year increase in age. The proportion of parasitized RBCs recognized by IgG correlated inversely with half-life (r = -0.475; P = .0006).

CONCLUSIONS:

Parasite clearance in response to artesunate is faster in Mali than in southeast Asia. IgG responses to parasitized RBCs shorten half-life and may influence this parameter in areas where age is not an adequate surrogate of immunity and correlates of parasite-clearing immunity have not been identified.

CLINICAL TRIALS REGISTRATION:

NCT00669084.

• Authors: Tatiana M Lopera-Mesa, Saibou Doumbia, Serena Chiang, Amir E Zeituni, Drissa S Konate, Mory Doumbouya, Abdoul S Keita, Kasia Stepniewska, Karim Traore, Seidina A S Diakite, Daouda Ndiaye, Juliana M Sa, Jennifer M Anderson, Michael P Fay, Carole A Long, Mahamadou Diakite, Rick M Fairhurst
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 11 Pg. 1655-63 (Jun 01 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23448727 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Protozoan
• Antimalarials
• Artemisinins
• Immunoglobulin G
• Amodiaquine
• Artesunate

Topics

• Adaptive Immunity
• Adolescent
• Amodiaquine (administration & dosage)
• Antibodies, Protozoan (blood)
• Antimalarials (administration & dosage)
• Artemisinins (administration & dosage)
• Artesunate
• Child
• Child, Preschool
• Cohort Studies
• Erythrocytes (parasitology)
• Female
• Humans
• Immunoglobulin G (blood)
• Infant
• Malaria, Falciparum (drug therapy, immunology)
• Male
• Mali
• Parasite Load
• Parasitemia (drug therapy, immunology)
• Plasmodium falciparum (immunology, isolation & purification)