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Strain variation in tumor necrosis factor induction by parasites from children with acute falciparum malaria
1Department of Paediatrics, John Radcliffe Hospital, Oxford, United Kingdom.
Abstract:
A small proportion of individuals infected with Plasmodium falciparum develop cerebral malaria. Why it affects some infected individuals but not others is poorly understood. Since tumor necrosis factor (TNF) has been implicated strongly in the pathogenesis of cerebral malaria, here we have compared different parasite isolates for their ability to induce TNF production by human mononuclear cells in vitro. Wild isolates were collected from 34 Gambian children with cerebral malaria and 66 children with uncomplicated malaria fever. Cerebral malaria isolates tended to stimulate more TNF production than mild malaria isolates, but there was considerable overlap between the two groups, and the present data provide only limited support for the hypothesis that cerebral malaria is caused by strains of P. falciparum inducing high levels of TNF. However, it is notable that the amounts of TNF induced by different wild isolates from a single locality differed by over 100-fold. The biological significance of this polymorphism deserves further scrutiny in view of the central role that TNF is believed to play in host defense and in the clinical symptomatology of human malaria.
Insights
Tumor necrosis factor (TNF) may play a role in cerebral malaria. This study found varying TNF production levels in response to different Plasmodium falciparum parasite isolates, suggesting complex interactions in disease development.
Area of Science:
- Infectious Diseases
- Immunology
- Malariology
Background:
- Cerebral malaria affects a subset of Plasmodium falciparum-infected individuals.
- Tumor necrosis factor (TNF) is a key factor in cerebral malaria pathogenesis.
- The reasons for differential susceptibility to cerebral malaria remain unclear.
Purpose of the Study:
- To investigate the capacity of different Plasmodium falciparum isolates to induce TNF production.
- To explore the relationship between parasite strain variation and cerebral malaria development.
Main Methods:
- Collected wild Plasmodium falciparum isolates from Gambian children with cerebral malaria and uncomplicated malaria.
- Assessed the ability of these isolates to stimulate TNF production by human mononuclear cells in vitro.
Main Results:
- Cerebral malaria isolates showed a tendency to stimulate higher TNF production compared to mild malaria isolates.
- Significant overlap in TNF induction levels was observed between isolates from both groups.
- TNF induction varied over 100-fold among isolates from the same locality.
Conclusions:
- The data provide limited support for the hypothesis that high TNF-inducing Plasmodium falciparum strains cause cerebral malaria.
- The significant polymorphism in TNF induction by different parasite isolates warrants further investigation.
- Understanding this polymorphism is crucial given TNF's role in host defense and malaria symptomatology.