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- Title
Rosetting in Plasmodium vivax: A Cytoadhesion Phenotype Associated with Anaemia.
- Authors
Marín-Menéndez, Alejandro; Bardají, Azucena; Martínez-Espinosa, Flor E.; Bôtto-Menezes, Camila; Lacerda, Marcus V.; Ortiz, Jon; Cisteró, Pau; Piqueras, Mireia; Felger, Ingrid; Müeller, Ivo; Ordi, Jaume; del Portillo, Hernando; Menéndez, Clara; Wahlgren, Mats; Mayor, Alfredo
- Abstract
Background: Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates. Methodology/Principal findings: Rosetting and adhesion to CSA, CD36, ICAM1, placental and brain cryosections were determined in P. vivax peripheral isolates from 12 pregnant women, 24 non-pregnant women and 23 men from Manaus (Brazil). P. falciparum co-infection was excluded by PCR and P. vivax isolates were genotyped by assessing the size polymorphism of microsatellites ms2, ms20 and msp1F3 through capillary electrophoresis of PCR products. P. vivax monoinfection was confirmed by PCR in 59 isolates, with 50 (85%) of them being single-clone infections. One P. vivax haplotype was more frequently found among pregnant women (33%) than in non-pregnant women (0%) and men (4%; p = 0.010). Rosetting was observed in 64% of the isolates, adhesion to CSA in 15%, to ICAM1 in 12% and to placental cryosections in 9%, being similar among pregnant and non-pregnant groups. Intensity of rosetting was higher among anaemic individuals compared to non-anaemic (p = 0.010) and decreased with increasing haematocrit (p = 0.033) and haemoglobin levels (p = 0.015). Conclusions/Significance: P. vivax peripheral isolates from pregnant women do not exhibit a prominent adhesion to CSA, although other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones observed among pregnant hosts. Rosetting is a frequent cytoadhesive phenotype in P. vivax infections that may contribute to the development of anaemia. Author Summary: Despite being considered a relatively benign disease, Plasmodium vivax infection has been recently associated with fatal outcomes. The mechanisms contributing to severe disease in P. vivax malaria remain largely unknown, although scarce evidences suggests that similarly to P. falciparum, P. vivax may also adhere to host receptors on the vascular endothelium or on uninfected erythrocytes to form 'rosettes'. Such cytoadhesion phenotypes might contribute to mild sequestration of P. vivax and poor clinical outcomes. The present study aimed to describe clinically relevant cytoadhesive phenotypes of P. vivax infected erythrocytes isolated from peripheral blood of pregnant and non-pregnant patients in the Brazilian Amazon. We did not observe any specific cytoadhesion phenotype associated to pregnancy, although a P. vivax haplotype was more frequent among pregnant women than in non-pregnant hosts. This finding suggests that other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones among pregnant hosts. In addition, we found that rosetting was a frequent cytoadhesive phenotype in P. vivax infections that was associated with an increased risk of anaemia. This study places cytoadhesion and specifically rosetting as a target for the development of new therapies to treat or prevent life-threatening P. vivax malaria.
- Subjects
MANAUS (Brazil); PLASMODIUM vivax; PHENOTYPES; ANEMIA; PREGNANT women; VASCULAR endothelium
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 4, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002155