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Adjunctive Thalidomide Therapy of Childhood Tuberculous Meningitis: Possible Anti-Inflammatory Role

Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, Tygerberg, jfs{at}gerga.sun.ac.za

Priscilla Springer, MB, ChB, FCP

Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, Tygerberg

Alice Ravenscroft, MB, ChB, MMed

Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, Tygerberg

Peter R. Donald, MB, ChB, MD

Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, Tygerberg

Linda-Gail Bekker, MB, ChB, FCP

Department of Medical Microbiology, University of Cape Town, Cape Town, South Africa

Anita Janse van Rensburg

Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, Tygerberg

Willem A. Hanekom, MB, ChB, FCP

Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY

Patrick A. J. Haslett, MB, MRCP

Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY

Gilla Kaplan, Ph.D.

Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY

The objective of this study was to determine the safety and tolerability of the immunomodulatory agent thalidomide as adjunct therapy in children with tuberculous meningitis. Children with stage 2 tuberculous meningitis received oral thalidomide for 28 days in a dose-escalating study, in addition to standard four-drug antituberculosis therapy, corticosteroids, and specific treatment of complications such as raised intracranial pressure. Clinical and laboratory evaluations were carried out. Fifteen patients (median age, 34 months) were enrolled. Thalidomide was administered via nasogastric tube in a dosage of 6 mg/kg/day, 12 mg/kg/day, or 24 mg/kg/day. The only adverse events possibly related to the study drug were transient skin rashes in two patients. Levels of tumor necrosis factor- in the cerebrospinal fluid decreased markedly during thalidomide therapy. Clinical outcome and neurologic imaging showed greater improvement than that experienced with historical controls. Thalidomide appeared safe and well tolerated in children with stage 2 tuberculous meningitis and could have important anti-inflammatory effects. These promising results have led us to embark on a randomized, double-blind, placebo-controlled trial of the efficacy of thalidomide in tuberculous meningitis. (J Child Neurol 2000;15:497-503).

Journal of Child Neurology, Vol. 15, No. 8, 497-503 (2000)
DOI: 10.1177/088307380001500801


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