Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients.

BACKGROUND: Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies have been conducted to date in an African population. OBJECTIVES: To compare exposure to TB drugs in Tanzanian TB patients with and without DM. PATIENTS AND METHODS: A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs. RESULTS: A trend was shown for 25% lower total exposure (AUC0-24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0-24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0-24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid. CONCLUSIONS: There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM.

Childhood tuberculosis in the Kilimanjaro region: lessons from and for the TB programme.

OBJECTIVE: To determine the magnitude of childhood TB and treatment outcome in Kilimanjaro region. METHODS: Retrospective review of registration-based data on TB notifications in Kilimanjaro region for the period 2002-2006. RESULTS: Between 2002 and 2006, there were 1615 patients of childhood TB in Kilimanjaro region constituting 13% of total TB burden and the average case detection rate was 147/100 000 for urban and 41.8/100 000 for rural populations. Of them, 54.2% were men and 75.2% had pulmonary TB (PTB); 24.9% were tested for acid-fast bacilli (AFB) by Ziehl-Neelsen staining showing that 5.8% of all patients with TB were AFB smear positive. The remaining 94.2% were presumptively treated for TB. Treatment success rate was 79.9%, mortality 10.9% and default rate was 7%. Unfavourable outcome was more common among unconfirmed TB patients. HIV testing was very rare but increased after 2004 (<2% before 2005, 11-16% afterwards.) CONCLUSION: The rate of childhood TB in Kilimanjaro region is among the highest in the world. Microbiological diagnosis for TB and AFB smear positivity is very low. Treatment outcome in this region is poor. These findings argue for specific TB control strategies to be designed for children such as more AFB testing using new tools such as induced sputum and laryngeal swabs, active case finding, HIV testing of all suspected TB children, promoting and monitoring adherence. Regular epidemiological studies are also needed.