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Ndour P.A.,CNRS Immunology and Infectious Disease Center | Ndour P.A.,Center National Of Reference Du Paludisme Site Pitie Salpetriere | Ndour P.A.,Laboratory of Excellence GR Ex | Lopera-Mesa T.M.,National Institute of Allergy and Infectious Diseases | And 21 more authors.
Journal of Infectious Diseases | Year: 2015

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. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.


Jaureguiberry S.,Assistance Publique Hopitaux de Paris | Jaureguiberry S.,CNRS Immunology and Infectious Disease Center | Jaureguiberry S.,Center National Of Reference Du Paludisme Site Pitie Salpetriere | Ndour P.A.,CNRS Immunology and Infectious Disease Center | And 23 more authors.
Blood | Year: 2014

Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected area, an alteration likely contributing to their shorter lifespan. Delayed clearance of infected erythrocytes spared by pitting during AS treatment is an original mechanism of hemolytic anemia. Our findings consolidate a disease framework for posttreatment anemia in malaria in which delayed hemolysis is a new entity. The early concentration of once-infected erythrocytes is a solid candidate marker to predict post-AS delayed hemolysis © 2014 by The American Society of Hematology.

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