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J Infect Dis. 2015 Jan 15;211(2):290-7. doi: 10.1093/infdis/jiu427. Epub 2014 Sep 2.

Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria.

Author information

1
Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière Laboratory of Excellence GR-Ex.
2
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
3
Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odonto-stomatology, University of Bamako, Mali.
4
AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
5
Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255.
6
Centre National de Référence du Paludisme site Pitié-Salpêtrière AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
7
Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière.
8
Centre for Immunity, Infection and Evolution, University of Edinburgh, United Kingdom.
9
Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
10
Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière Laboratory of Excellence GR-Ex AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.

Abstract

BACKGROUND:

In Plasmodium falciparum-infected patients treated with artemisinins, parasitemia declines through so-called pitting, an innate splenic process that transforms infected red blood cells (iRBCs) into once-infected RBCs (O-iRBCs).

METHODS:

We measured pitting in 83 French travelers and 42 Malian children treated for malaria with artesunate.

RESULTS:

In travelers, O-iRBCs peaked at 107.7% initial parasitemia. In Malian children aged 1.5-4 years, O-iRBCs peaked at higher concentrations than in children aged 9-13 years (91.60% vs 31.95%; P = .0097). The parasite clearance time in older children was shorter than in younger children (P = .0001), and the decline in parasitemia in children aged 1.5-4 years often started 6 hours after treatment initiation, a lag phase generally absent in infants and older children. A 6-hour lag phase in artificial pitting of artesunate-exposed iRBCs was also observed in vitro. The proportion of iRBCs recognized by autologous immunoglobulin G (IgG) correlated with the parasite clearance time (r = -0.501; P = .0006) and peak O-iRBC concentration (r = -0.420; P = .0033).

CONCLUSIONS:

Antimalarial immunity correlates with fast artemisinin-induced parasite clearance and low pitting rates. In nonimmune populations, artemisinin-induced P. falciparum clearance is related to pitting and starts after a 6-hour lag phase. In immune populations, passively and naturally acquired immune mechanisms operating faster than pitting may exist. This mechanism may mitigate the emergence of artemisinin-resistant P. falciparum in Africa.

KEYWORDS:

Plasmodium falciparum; acquired immunity; artemisinin; malaria; parasite clearance; pitting; spleen

PMID:
25183768
PMCID:
PMC4334830
DOI:
10.1093/infdis/jiu427
[Indexed for MEDLINE]
Free PMC Article

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