title: Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible anti-inflammatory role.
abstract: 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-alpha 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.
authors.affiliation: Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, South Africa. jfs@gerga.sun.ac.za
authors.forename: J F
authors.initials: JF
authors.lastname: Schoeman
authors.forename: P
authors.initials: P
authors.lastname: Springer
authors.forename: A
authors.initials: A
authors.lastname: Ravenscroft
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.forename: L G
authors.initials: LG
authors.lastname: Bekker
authors.forename: A J
authors.initials: AJ
authors.lastname: van Rensburg
authors.forename: W A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: P A
authors.initials: PA
authors.lastname: Haslett
authors.forename: G
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000134:cerebrospinal fluid; D007427:Intracranial Pressure; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D010865:Pilot Projects; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*
chemical_list: D000276:Adjuvants, Immunologic; D000995:Antitubercular Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide