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1 February 2005

Volume 191, Number 3
The Journal of Infectious Diseases 2005;191:410–421
© 2004 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19103-0013$15.00
DOI: 10.1086/426871
MAJOR ARTICLE

Malaria‐Filaria Coinfection in Mice Makes Malarial Disease More Severe unless Filarial Infection Achieves Patency

Andrea L. Graham,

Tracey J. Lamb,a

Andrew F. Read, and

Judith E. Allen

Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland

Coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. For example, type 1–dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. Alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. Using rodent models of lymphatic filariasis (Litomosoides sigmodontis) and noncerebral malaria (clone AS Plasmodium chabaudi chabaudi), we quantified disease severity, parasitemia, and polyclonal splenic immune responses in BALB/c mice. We found that coinfected mice, particularly those that did not have microfilaremia (Mf−), had more severe anemia and loss of body mass than did mice with malaria alone. Even when controlling for parasitemia, malaria was most severe in Mf− coinfected mice, and this was associated with increased interferon‐γ responsiveness. Thus, in Mf− mice, filariasis upset a delicate immunological balance in malaria infection and exacerbated malaria‐induced immunopathology.

Received 29 June 2004; accepted 18 August 2004; electronically published 21 December 2004.

Reprints or correspondence: Dr. Andrea L. Graham, Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King’s Bldgs., Ashworth Laboratories, Edinburgh, Scotland EH9 3JT ().

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  • Financial support: Wellcome Trust (grant 064121/Z/01/Z); Medical Research Council; European Commission (grant ICA4‐CT1999‐10002).

  • Present affiliation: Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, England.

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