Rosetting in Plasmodium vivax: A Cytoadhesion Phenotype Associated with Anaemia

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 findingsRosetting 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.

Glycophorin C (CD236R) mediates vivax malaria parasite rosetting to normocytes

“…[11][12][13][14][15][16][17] A renewed interest in vivax malaria and a better appreciation of its importance to public health has led to an increased number of studies examining particular aspects of P vivax pathogenesis. [18][19][20][21][22][23][24][25] Certainly in the case of P vivax, apart from some initial descriptions on P vivax rosetting 8,10 and its association with anemia, 26 little has been done to investigate the importance of rosetting to the survival of P vivax within the human host and the molecular mechanisms associated with the formation of rosettes in this species.…”

Plasmodium vivax Chloroquine Resistance and Anemia in the Western Brazilian Amazon

“…Moreover, both phenomena still have unclear pathogenesis. Anemia, for instance, seems to present multifactor determinants (40), with rosetting being one of the recently described mechanisms (41). Further studies from other areas of endemicity in which other causes of anemia are well characterized may contribute to the better understanding of the association between P. vivax CR and anemia.…”

The immunological balance between host and parasite in malaria

“…Plasmodium vivax-iRBCs are observed in spleen biopsies taken from splenectomized patients with acute P. vivax infections (Lubitz 1949;Machado et al 2012), and possibly also on lung autopsies from deceased P. vivax patients from the Brazilian Amazon region (Lacerda et al 2012;Machado et al 2012). Furthermore, in vitro experiments demonstrated cytoadherence of asexual P. vivax isolates, although to a variable degree, to microvascular ECs derived from human lungs, simian brains, and to placental cryosections, whereas conflicting data are found with human umbilical vein ECs (Udomsanpetch et al 1995;Carvalho et al 2010;Chotivanich et al 2012;De las Salas et al 2013;Marin-Menendez et al 2013). Several host receptors were identified, such as CSA and hyaluronic acid (HA), but not CD36 or thrombospondin.…”