Trends in Parasitology
Volume 19, Issue 4, April 2003, Pages 188-193
Journal home page for Trends in Parasitology

Vivax series:
The paroxysm of Plasmodium vivax malaria

https://doi.org/10.1016/S1471-4922(03)00036-9Get rights and content

Abstract

The paroxysms of Plasmodium vivax malaria are antiparasite responses that, although distressing to the human host, almost never impart serious acute pathology. Using plasma and blood cells from P. vivax patients, the cellular and noncellular mediators of these events have been studied ex vivo. The host response during a P. vivax paroxysm was found to involve T cells, monocytes and neutrophils, and the activity, among others, of the pyrogenic cytokines tumor necrosis factor α and interleukin 2 in addition to granulocyte macrophage–colony stimulating factor. However, interferon γ activity, associated with serious acute pathogenesis in other studies on malaria, was absent. Induction of the cytokines active during a P. vivax paroxysm depends upon the presence of parasite products, which are released into the plasma before the paroxysm. Chemical identification of these natural parasite products will be important for our understanding of pathogenesis and protection in malaria.

Section snippets

In vivo studies on the paroxysm of P. vivax malaria

As was first demonstrated by Golgi in 1889 [1], a malarial paroxysm is preceded by the synchronous rupture of schizont-infected red blood cells. This observation led to the idea that malarial fever is the product of fever-inducing toxins (pyrogens) released by the parasites during schizont rupture. In 1904, in Vera Cruz, Mexico, an observation was made which seemed to confirm this view. Five ml of serum from blood collected from a P. vivax malaria patient at the height of a paroxysm was passed

Ex vivo studies on P. vivax paroxysm

The following sections discuss the observations made upon blood plasma or whole blood cells collected from P. vivax patients at or around the time of a paroxysm.

Conclusions

The mediators and mechanisms of P. vivax paroxysm have been discussed here based on observation and experiment on P. vivax patients, and on material collected directly from them. The event of P. vivax paroxysm and the mediators and processes that we have identified in association with it all lack acute serious pathogenic features. In particular, the activity of one specific host mediator, IFN-γ, and of one class of parasite products, GPI, have not registered prominently in any of our analyses

Acknowledgements

We thank Dominic Kwiatkowski, George E. Grau, Giuseppe Del Giudice, Ian A. Clark, Louis H. Miller and Lakshmi Kumaratilate for discussions and/or collaboration in the development of these investigations. The work has been supported at various times by grants from the Rockefeller Foundation, the TDR/UNDP/World Bank/WHO, the European Union and the Wellcome Trust, to whom we express our gratitude. K.N.M. is formerly of the University of Colombo, Department of Parasitology, Faculty of Medicine,

References (47)

  • R. Carter

    Cellular mechanisms and soluble mediators in the paroxysm of Plasmodium vivax malaria

    J. Pharm. Pharmacol.

    (1997)
  • T.S. Naotunne

    Malaria parasites (sexual stages) are killed by cytokines produced during blood infection

    J. Exp. Med.

    (1991)
  • J. Lou

    Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans

    Clin. Microbiol. Rev.

    (2001)
  • A.E. Brown

    Macrophage activation in vivax malaria: fever is associated with increased levels of neopterin and interferon-gamma

    Parasite Immunol.

    (1991)
  • T.S. Naotunne

    Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white cells

    Immunology

    (1993)
  • C.A. Bate

    Malaria parasites induce tumour necrosis factor production by macrophages

    Immunology

    (1988)
  • D. Kwiatkowski

    Tumour necrosis factor production in falciparum malaria and its association with schizont rupture

    Clin. Exp. Immunol.

    (1989)
  • P.H. Jakobsen

    Isolation and characterisation of a soluble antigen complex of Plasmodium falciparum with pyrogenic properties

    Acta Path. Microbiol. Immunol. Scand.

    (1991)
  • C.A.W. Bate

    Tumour necrosis factor induction by malaria exoantigens depends upon phospholipid

    Immunology

    (1992)
  • L. Schofield et al.

    Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites

    J. Exp. Med.

    (1993)
  • S. Pichyangkul

    Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor alpha and interleukin-1 beta

    Am. J. Trop. Med. Hyg.

    (1994)
  • B.A. Sherry

    Malaria-specific metabolite haemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro and altered thermoregulation in vivo

    J. Inflamm.

    (1995)
  • C.A.W. Bate

    Serological relationship of TNF-inducing exoantigens of P. falciparum and P. vivax

    Infect. Immun.

    (1992)
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