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This retrospective review of clinical records and chest radiographs (CR) of adolescents aged 10-18 years was designed to determine age and sex differences in the clinical and radiological features of adolescent tuberculosis (TB). Records of adolescents who were admitted to Brooklyn Hospital for Chest Diseases (BCH) or who were treated at local authority health clinics were screened. Data from 324 adolescents (male:female ratio 1:1.2) were studied. Intra-thoracic lesions were present on CR in 306 (94%). Primary TB with mediastinal adenopathy was present in 32 (10%). Cavitation was present in 180 (56%), 16% at 10 and 73% at 18 years of age. Cavitation occurred in 55% of males and in 56% of females with increasing frequency from 15 years of age in the former and from age 14 in the latter. Microbiological confirmation of diagnosis was obtained in 254 (78%) cases, 52% in those aged 10-13 years and 86% in those > or = 14 years. Pleural effusion was present in 42 (13%), 26 males and 16 females (p < 0.05). Thirteen (7%) of the 182 hospitalized adolescents and 27 (19%) of the ambulant group did not complete therapy. The nature of tuberculous disease in adolescents changed dramatically with increasing age.

The impact of changing environmental factors--disease, nutrition and a high-dose multi-drug treatment regimen--on isoniazid (INH) elimination kinetics in children of both sexes and various ages was investigated. Thirteen children (mean age 2.3 years), hospitalized for the treatment of tuberculous meningitis, participated in the trial. Although all the children had protein-energy malnutrition, none had marasmus or kwashiorkor. After an oral dose of 20 mg/kg of INH, the concentrations in plasma were determined by the liquid chromatographic method of Lacroix et al. The 2-hour post-dose isoniazid concentration, the apparent first-order elimination rate constant and the corresponding INH half-life were determined in each child on two occasions 6 months apart. All comparisons were tested for significance using the Wilcoxon matched-pair signed-ranks test. There was no significant difference in any of the pharmacokinetic parameters of INH in our patients evaluated at the extremes of the 6-month term of treatment. It was apparent that changing conditions of disease and nutrition and a high-dosage, multi-component antimicrobial agent regimen over a 6-month period of treatment did not significantly influence INH elimination parameters. The trend evident in the pharmacokinetic profile of isoniazid in our children supports a trimodal distribution of acetylator phenotypes.

Many factors can influence the dynamic balance that exists between the host and the pathogen (M. tuberculosis), but the host immune response seems to be the most important. This is illustrated by the vulnerability of immune-compromised individuals to develop tuberculosis and by the age-related spectrum of disease witnessed in immune-competent children. This age-related spectrum of disease reflects the ontogeny of the host immune response towards M. tuberculosis. Renewing our focus on the ontogeny of the immune response in children might provide valuable insights to direct future research regarding tuberculosis prevention, vaccine development and treatment.

The impact of HIV infection on clinical presentation and outcome of tuberculosis (TB) was studied in children hospitalised at the Brooklyn Hospital for Chest Diseases (BCH), Cape Town over the 2-year period January 1998 to December 1999. Clinical data were extracted from a prospectively compiled patient register. Of 261 children with TB, 114 (median age 24 mths) were not HIV-infected and 36 (median age 23 mths) were HIV-infected. The HIV status of 111 children (median age 37 mths) was not determined. Pulmonary TB with or without extrapulmonary TB occurred in 97 (85%) children who were not HIV-infected, 35 (97%) HIV-infected children and 87 (78%) of those not tested (p = 0.025). A tuberculin reactionor = 15 mm was elicited in ten (31%) of 32 HIV-infected children, 76 (72%) of 106 non-HIV-infected and 62 (71%) of those not tested (p0.001). Mycobacterium tuberculosis was cultured from 116 (49%) of 238 children and drug sensitivity was evaluated in 79. Nine isolates (11%) were resistant to isoniazid (INH) and 11 (14%) to INH and rifampicin (RMP). Two HIV-infected children treated previously in BCH for drug-sensitive TB were re-admitted with INH and RMP resistance. Two (2%) non-HIV-infected children, six (17%) HIV-infected children and one (1%) child with undetermined HIV status died (p0.001).

Three recent studies found that corticosteroids improve clinical outcome and mortality in tuberculous meningitis (TBM), although the exact mechanism of action of the drug remains speculative. A number of reports on the effect of corticosteroids on cerebrospinal fluid (CSF) findings in TBM have been published, often with conflicting results regarding serial cell counts and protein levels. As part of a controlled, randomized trial on the effect of oral prednisone on outcome in childhood TBM at our institution, CSF was collected and analysed weekly during the 1st month of treatment. We found no significant difference in serial CSF cell counts between the steroid and non-steroid groups in the study. However, the steroid group had significantly lower CSF protein and globulin levels after the 1st month of treatment, and a more steady rise in CSF glucose levels than the non-steroid group. Knowledge of the different CSF responses during the course of anti-tuberculosis therapy is important in clinical decision-making.

The pharmacokinetics of intravenous amikacin, administered as a mean (SD) bolus dose of 5.5 (1.2) mg/kg to children between the ages of 1 and 4 years with kwashiorkor, was studied. Although there was a tendency for the average volume of distribution to increase to the upper limit of normal, plasma elimination half-life, first order elimination-phase rate constant and clearance remained close to the reference values for adults. Despite marginal elevation of the average t1/2 beta-value, reflecting a general trend, renal impairment in respect of amikacin clearance could not be demonstrated. It was concluded that the changes in pharmacokinetic parameters found in kwashiorkor are not large enough to amend the current therapeutic regimens for amikacin in this condition.