Increased Levels of Inflammatory Mediators in Children with Severe Plasmodium falciparum Malaria with Respiratory Distress
1Immunology Department, Noguchi Memorial Institute for Medical Research, and 2Department of Child Health, University of Ghana Medical School, College of Health Sciences, and 3Department of Biochemistry, University of Ghana, Legon, Accra; 4Unité d’Immunologie Moléculaire des Parasites, Institut Pasteur, Paris, France; 5Centre for Medical Parasitology, Department of Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark
Background.
Respiratory distress (RD), a symptom of underlying metabolic acidosis, has been identified as a major risk factor for mortality in children with severe malaria in Africa, yet the molecular mediators involved in the pathogenesis of RD have not been identified.
Methods.We studied circulating levels of mediators of inflammation—including the cytokines tumor necrosis factor (TNF)–α and interleukin (IL)–10; the chemokines macrophage inflammatory protein (MIP)–1α, MIP‐1β, and IL‐8; and the immune activation marker neopterin—in children with RD, severe malarial anemia (SMA), cerebral malaria (CM), and uncomplicated malaria (UM).
Results.Children with RD had significantly higher plasma levels of TNF‐α, IL‐10, and neopterin and a significantly higher TNF‐α:IL‐10 ratio than those without RD. In addition, the results demonstrated that, relative to UM, CM was associated with increased levels of TNF‐α and decreased levels of MIP‐1α, whereas SMA was associated with decreased levels of IL‐10. Circulating levels of neopterin were inversely correlated with hemoglobin, whereas levels of MIP‐1β were positively correlated with parasitemia.
Conclusions.We conclude that distinct clinical presentations of severe malaria are associated with specific patterns of inflammatory mediators. In particular, we show, to our knowledge for the first time, that patients with malaria and RD have a strong and unbalanced proinflammatory response that may be involved in the pathogenesis of the underlying metabolic acidosis.
Received 23 May 2006; accepted 22 July 2006; electronically published 10 October 2006.
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Online publication date: 1-Aug-2008.
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Online publication date: 14-May-2008.
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Financial support: United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases (TDR) (Multilateral Initiative on Malaria/TDR grant 980037); International Cooperation Program of the European Commission with Developing Countries (project IC18CT980370); Programme for Enhancement of Research Capacity in Developing Countries, Danish International Development Assistance.
Potential conflicts of interest: none reported.