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PubMed2002

Treatment of childhood tuberculosis with a six month directly observed regimen of only two weeks of daily therapy.

BACKGROUND: Recommended treatment of childhood tuberculosis is 6 months in duration with at least 3 drugs. We studied a regimen requiring as few as 58 doses, given entirely by directly observed therapy (DOT), under program conditions. METHODS: An observational trial was conducted to determine the effectiveness of a completely DOT 6-month regimen for pulmonary, pleural and lymph node tuberculosis in children with the use of 2 weeks of daily isoniazid, rifampin and pyrazinamide therapy; then 6 weeks of twice weekly isoniazid, rifampin and pyrazinamide therapy; followed by 16 weeks of twice weekly isoniazid and rifampin. All therapy was given by workers from the health department, and patients were followed by the Children's Tuberculosis Clinic in Houston, TX. Patients were evaluated for changes in symptoms, weight, clinical or radiographic findings and adherence to therapy. RESULTS: Of the 175 evaluable children (159 pulmonary/thoracic node, 4 pleural, 12 cervical lymph node), 81% of children completed treatment in 6 months. Of the 33 patients who received extended treatment, 3 did so because of physician choice, 17 had an inadequate response to initial therapy, 2 had significant adverse reactions to drugs and 16 had poor adherence to the DOT. Only 37% of patients had complete resolution of disease at the end of treatment, but all continued to improve after therapy was stopped. There was only 1 patient who relapsed after 4 years. CONCLUSION: This regimen had results comparable with those of 6-month regimens with longer durations of daily therapy. Determining treatment response in pediatric tuberculosis is difficult because of the slow resolution of chest radiograph abnormalities. DOT is an important aspect of treatment but does not solve all problems with treatment adherence.

Adolescent↗
PubMed2004

Airways infection with virulent Mycobacterium tuberculosis delays the influx of dendritic cells and the expression of costimulatory molecules in mediastinal lymph nodes.

Despite tuberculosis resurgence and extensive dendritic cell (DC) research, there are no in vivo studies evaluating DC within regional lymphoid tissue during airways infection with virulent Mycobacterium tuberculosis (Mtb) H37Rv. Using DC-specific antibodies, immunocytochemistry, flow cytometry and Ziehl-Neelsen (ZN) for bacilli staining, we searched for Mtb and DC changes within mediastinal lymph nodes, after intratracheal (ITT) inoculation of virulent Mtb. ZN and immunocytochemistry in frozen and paraffin sections of mediastinal lymph nodes identified Mtb until day 14 after ITT inoculation, associated with CD11c(+) and Dec205(+) DC. Analysing CD11c, MHC-CII, and Dec205 combinations by flow cytometry in MLN suspensions revealed that CD11c(+)/MHC-CII(+) and CD11c(+)/Dec205(+) DC did not increase until day 14, peaked on day 21, and sharply declined by day 28. No changes were seen in control, saline-inoculated animals. The costimulatory molecules evaluated in CD11c(+) DCs followed a similar trend; the CD80 increase was negligible, slightly surpassed by CD40. CD86 increased earlier and the three markers peaked at day 21, declining by day 28. While antigen-specific proliferation was not evident for MLN CD4(+) T cells at 2 weeks postinfection, delayed-type hypersensitivity responses upon ITT inoculation revealed that, as early as day 3 and 7, both the priming and peripheral systemic immune responses were clearly established, persisting until days 14-21. While airways infection with virulent Mtb triggers an early, systemic peripheral response maintained for three weeks, this seems dissociated from regional events within mediastinal lymph nodes, such as antigen-specific T-cell reactivity and a delay in the influx and local activation of DC.

Animals↗