On cytoadhesion of Plasmodium vivax: raison d'être?

Costa, Fabio T. M.; Lopes, Stefanie CP; Ferrer, M. Carmen Olivé; Leite, Juliana Almeida; Martín-Jaular, Lorena; Bernabeu, Maria; Nogueira, Paulo Afonso; Mourão, Maria Paula Gomes; Fernández-Becerra, Carmen; Lacerda, Marcus Vinícius Guimarães; Portillo, Hernando del

doi:10.1590/s0074-02762011000900010

Cited by 32 publications

(24 citation statements)

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“…Regardless its former association with benign malaria [3, 22], complications of P. vivax malaria have been reported in adult patients living in Amazon Basin endemic areas [11, 12]. It has been proposed that a balance between the pro- and anti-inflammatory responses can account for the control against the development of the severe malaria episodes [54].…”

Section: Discussionmentioning

confidence: 99%

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Immune response pattern in recurrent Plasmodium vivax malaria

Chaves

Costa

Pereira

et al. 2016

Malar J

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BackgroundPlasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually. In Brazil, it is the most prevalent species, being responsible by around 70 % of the malaria cases.MethodsA cross-sectional study was performed in Manaus (Amazonas, Brazil), including 36 adult patients with primary malaria, 19 with recurrent malaria, and 20 endemic controls. The ex vivo phenotypic features of circulating leukocyte subsets (CD4+ T-cells, CD8+ T-cells, NK, NKT, B, B1 and Treg cells) as well as the plasmatic cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ) were assessed, aiming at establishing patterns of immune response characteristic of primary malaria vs recurrent malaria as compared to endemic controls.ResultsThe proportion of subjects with high levels of WBC was reduced in malaria patients as compared to the endemic control. Monocytes were diminished particularly in patients with primary malaria. The proportion of subjects with high levels of all lymphocyte subsets was decreased in all malaria groups, regardless their clinical status. Decreased proportion of subjects with high levels of CD4+ and CD8+ T-cells was found especially in the group of patients with recurrent malaria. Data analysis indicated significant increase in the proportion of the subjects with high plasmatic cytokine levels in both malaria groups, characterizing a typical cytokine storm. Recurrent malaria patients displayed the highest plasmatic IL-10 levels, that correlated directly with the CD4+/CD8+ T-cells ratio and the number of malaria episodes.ConclusionThe findings confirm that the infection by the P. vivax causes a decrease in peripheral blood lymphocyte subsets, which is intensified in the cases of “recurrent malaria”. The unbalanced CD4+/CD8+ T-cells ratio, as well as increased IL-10 levels were correlated with the number of recurrent malaria episodes. These results suggest that the gradual remodelling of the immune response is dependent on the repeated exposure to the parasite, which involves a strict control of the immune response mediated by the CD4+/CD8+ T-cell unbalance and exacerbated IL-10 secretion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1501-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Although the Amazon region has low transmission levels as compared to other regions in sub-Saharan Africa, the most affected population in the Amazon Basin are adults and the incidence of complications has been already reported [11, 12]. …”

Section: Introductionmentioning

confidence: 99%

Immune response pattern in recurrent Plasmodium vivax malaria

Chaves

Costa

Pereira

et al. 2016

Malar J

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“…Kirchgatter and del Portillo (159) explain this complexity in P. falciparum and cite the 3 parasite phenotypes likely to mediate virulence in that infection: cyto-adherence, rosetting, and antigenic variation. Although apparently important differences between P. falciparum and P. vivax occur among these phenotypes (160,161), none gets to the heart of the primary question-how do such low-grade parasitemias cause such severe disease states in vivax malaria? The quantitative threat of parasite biomass, regardless of precise phenotypes at work within it, is the primary problem to reconcile in severe vivax malaria.…”

Section: A Plausible and Testable Hypothesis On Pathogenesismentioning

confidence: 99%

Evidence and Implications of Mortality Associated with Acute Plasmodium vivax Malaria

2013

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SUMMARYVivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of “perniciousness” historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite—it is a complex problem for the entire endemic world, and both species are of fundamental importance. Humanity must rally substantial resources, intellect, and energy to counter this daunting but profound threat.

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“…Although P. vivax is known to adhere to vascular endothelium, its capacity to do so is relatively limited compared with P. falciparum ,19 and little is known regarding the mechanisms of P. vivax cythoadherence to those and other human tissues. There is a need to better understand the role, magnitude, and reversibility of such processes in P. vivax , both in (severe) pathology and in the maintenance of chronic P. vivax infections.…”

Section: Biology Culture and Drug Screeningmentioning

confidence: 99%

Key Knowledge Gaps for Plasmodium vivax Control and Elimination

Bassat¹,

Velarde²,

Müeller³

et al. 2016

Am J Trop Med Hyg

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There is inadequate understanding of the biology, pathology, transmission, and control of Plasmodium vivax, the geographically most widespread cause of human malaria. During the last decades, study of this species was neglected, in part due to the erroneous belief that it is intrinsically benign. In addition, many technical challenges in culturing the parasite also hampered understanding its fundamental biology and molecular and cellular responses to chemotherapeutics. Research on vivax malaria needs to be substantially expanded over the next decade to accelerate its elimination and eradication. This article summarizes key knowledge gaps identified by researchers, national malaria control programs, and other stakeholders assembled by the World Health Organization to develop strategies for controlling and eliminating vivax malaria. The priorities presented in this article emerged in these technical discussions, and were adopted by expert consensus of the authors. All involved understood the priority placed upon pragmatism in this research agenda, that is, focus upon tools delivering better prevention, diagnosis, treatment, and surveillance of P. vivax.

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On cytoadhesion of Plasmodium vivax: raison d'être?

Cited by 32 publications

References 56 publications

Immune response pattern in recurrent Plasmodium vivax malaria

Immune response pattern in recurrent Plasmodium vivax malaria

Evidence and Implications of Mortality Associated with Acute Plasmodium vivax Malaria

Key Knowledge Gaps for Plasmodium vivax Control and Elimination

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