Supportive Pentoxifylline in Falciparum Malaria: No Effect on Tumor Necrosis Factor Alpha Levels or Clinical Outcome: A Prospective, Randomized, Placebo-Controlled Study

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  • Department of Medicine, Bernhard-Nocht-Institute for Tropical Medicine, Infectious Diseases and Clinical Immunology Section, University of Ulm, Department of Medicine, Hemostaseology Section, Philipps University, First Department of Medicine, University of Heidelberg, Department of Biometry and Medical Documentation, University of Ulm, Hamburg, Germany

Pentoxifylline (POF) may suppress overproduction of tumor necrosis factor alpha (TNFα), which is thought to contribute to complications of human falciparum malaria. However, POF is believed to improve impaired capillary blood flow, which can be impaired in falciparum malaria. To test whether POF affects TNFα serum levels or other variables in this disease, we administered POF (20 mg/kg/day intravenously in 150 ml of saline for five days) randomized versus placebo (150 ml of saline without POF) in addition to standard antimalarial therapy. After recruitment of 51 patients with Plasmodium falciparum malaria, those receiving POF had more nausea and abdominal discomfort than the placebo group, as expected. Eleven of 27 patients receiving POF and three of 24 patients receiving placebo requested termination of the study medication (P < 0.05). Pentoxifylline did not change the decrease of TNFα levels or affect the clinical course in a significant way. Since POF failed to improve the clinical situation or to impact numerous laboratory parameters (including TNFα, thrombin-antithrombin III, thrombomodulin, and human neutrophil elastase), the study was terminated earlier than planned. While this study does not specifically address cerebral complications of malaria, the results suggest that POF is not useful as a routine adjunct to the standard therapy of falciparum malaria.

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