Treatment outcomes and tolerability of the revised WHO anti-tuberculosis drug dosages for children.

BACKGROUND: In 2010, the World Health Organization (WHO) revised the paediatric dosages of anti-tuberculosis drugs, increasing rifampicin to 15 mg/kg, isoniazid to 10 mg/kg and pyrazinamide to 35 mg/kg. We assessed treatment outcomes, safety and adherence among children treated with the new recommended dosages. METHODS: Prospective cohort of children started on anti-tuberculosis treatment in Uganda with 12 months of follow-up, including alanine aminotransferase (ALT) monitoring. Treatment intake was observed. RESULTS: Of 144 treated children, 81 were male (56.3%), 106 (73.6%) were aged <5 years, 30 (22%) had moderate to severe malnutrition and 48 (33.3%) had human immunodeficiency virus infection. Treatment outcomes were as follows: 117 (81.3%) successes, 3 (2.1%) failures, 4 (2.8%) lost to follow-up, 19 (13.2%) deaths and 1 (0.7%) transferred out. There was no relapse. Severe malnutrition (adjusted hazard ratio 8.76, 95% confidence interval [CI] 1.59-48.25) was the only predictor of death. Two serious adverse events were attributed to treatment: one case of increased ALT and one with peripheral neuropathy. Median ALT values at baseline and at weeks 2, 4 and 8 were respectively 24 (interquartile range [IQR] 16-39), 26 (IQR 18-38), 28 (IQR 21-40) and 27 (IQR 19-38) international units/l. Treatment adherence was above 85% on all visits. CONCLUSION: We confirm the good tolerability of and adherence to the new treatment recommendations. The increased risk of fatal outcome among severely malnourished children requires attention.

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF.

SETTING: In early studies, Xpert® MTB/RIF accurately detected culture-proven pulmonary tuberculosis (TB). Recent reports have, however, found a lower than expected specificity in previously treated TB patients. OBJECTIVE: To investigate the diagnostic accuracy of Xpert in presumptive pulmonary TB patients in Southwestern Uganda. DESIGN: We obtained demographic and clinical information and collected three sputum samples from each patient for smear microscopy, Xpert and culture. We estimated Xpert sensitivity and specificity against culture, and stratified the analysis by previous treatment and sputum quality status. RESULTS: We analyzed results from 860 presumptive TB patients, including 109 (13%) with a previous history of anti-tuberculosis treatment; 205 (24%) were culture-positive. Xpert specificity was lower (91.8%, 95%CI 84.9-96.2) in previously treated than in new TB patients (97.5%, 95%CI 96.1-98.5; P = 0.01). In an adjusted analysis, patients with culture-, Xpert+ results were more likely to have been previously treated for TB (OR 8.3, 95%CI 2.1-32.0; P = 0.002), and to have mucosalivary sputum (OR 4.1, 95%CI 1.1-14.6; P = 0.03), but were less likely to self-report fever (OR 0.23, 95%CI 0.1-0.7; P = 0.008) than patients with concordant positive results. CONCLUSION: Xpert specificity was lower in previously treated patients with suspected TB. The clinical and programmatic impact of culture-, Xpert+ results requires evaluation in future studies.

Xpert(®) MTB/RIF for detection of Mycobacterium tuberculosis from frozen string and induced sputum sediments.

SETTING: Although it is now widely used for tuberculosis (TB) diagnosis, Xpert(®) MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated. OBJECTIVE: To assess the performance of Xpert in frozen samples of induced sputum (IS) and sputum from string test (ST) from non-expectorating individuals with presumed TB. DESIGN: This was a laboratory-based study of 377 ST and IS samples collected between March 2010 and March 2013 at a referral hospital in Uganda. Samples were decontaminated, centrifuged and cultured, and the resultant samples were frozen at -20°C before Xpert evaluation. RESULTS: TB was detected in ST and IS samples from 19/163 (11.7%) children and 63/201 (29.4%) adults using culture. Xpert sensitivity in frozen sediments from children was 37.5% (95%CI 8.5-75.5) in ST and 41.7% (95%CI 15.2-72.3) in IS samples, with specificities of respectively 100% (95%CI 94.9-100) and 98.6% (95%CI 92.7-100). In adults, sensitivity was respectively 50% (95%CI 31.3-68.7) and 48.5% (95%CI 30.8-66.4) in ST and IS samples, with specificities of respectively 100% (95%CI 95.5-100) and 98.6% (95%CI 92.4-100). CONCLUSION: Given these results, and particularly the high specificity, the use of Xpert on frozen ST and IS sediment samples from both children and adults is promising.

Intra-gastric string test: an effective tool for diagnosing tuberculosis in adults unable to produce sputum.

SETTING: Tuberculosis (TB) diagnosis is challenging in patients who are unable to produce sputum. The string test, a method for retrieving enteropathogens, is a potential alternative diagnostic tool. OBJECTIVES: To compare the TB detection yield and tolerability of the string test and that of sputum induction in adults with presumed TB in Uganda. DESIGN: Cross-sectional study. String test and sputum induction were performed consecutively in patients unable to produce sputum. The string was removed after a 2-h intra-gastric downtime. Sputum induction used nebulised 5% saline for 20 min. Light-emitting diode fluorescence microscopy, Löwenstein-Jensen and MGIT culture were performed on all specimens, and the Xpert(®) MTB/RIF assay on a subset. Tolerability questionnaires were administered. RESULTS: Of 210 patients included in the study, 59% were human immunodeficiency virus (HIV) positive and 50 (23.8%) were diagnosed with TB. Of these, 48 (96.0%) were detected with the string test and 46 (92.0%) with sputum induction. In patients with specimens collected using both methods for paired analysis, the yield of microscopy detection with the string test was 13.8% (26/188) vs. 13.3% (25/188) with sputum induction (P = 1.0). The yield increased to 22.9% (42/183) using culture for string test vs. 24.6% (45/183) for sputum induction (P = 0.37). Xpert detected TB in 15/96 (15.6%) patients with the string test vs. 17/96 (17.7%) with sputum induction (P = 0.62). Tolerability was comparable. CONCLUSION: The string test was well tolerated and provided similar yields to sputum induction, offering a viable alternative in resource-limited settings with minimal risk of transmission.