RESUMO
Background: Clinical symptoms are the benchmark of tuberculosis (TB) diagnosis and monitoring of treatment response but are not clear how they relate to TB bacteriology, particularly the novel tuberculosis-molecular bacterial load assay (TB-MBLA). Methods: Presumptive cases were bacteriologically confirmed for TB and assessed for symptoms and bacteriological resolution using smear microscopy (SM), culture, and TB-MBLA over 6-month treatment course. Kaplan-Meier and Kappa statistics were used to test the relationship between symptoms and bacteriological positivity. Results: A cohort of 46 bacteriologically confirmed TB cases were analyzed for treatment response over a 6-month treatment course. Pre-treatment symptoms and bacteriological positivity concurred in over 70% of the cases. This agreement was lost in over 50% of cases whose chest pain, night sweat, and loss of appetite had resolved by week 2 of treatment. Cough resolved at a 3.2% rate weekly and was 0.3% slower than the combined bacteriological (average of MGIT and TB-MBLA positivity) resolution rate, 3.5% per week. A decrease in TB-MBLA positivity reflected a fall in bacillary load, 5.7 ± 1.3- at baseline to 0.30 ± 1.0- log10 eCFU/ml at month 6, and closer to cough resolution than other bacteriological measures, accounting for the only one bacteriologically positive case out of seven still coughing at month 6. Low baseline bacillary load patients were more likely to be bacteriologically negative, HR 5.6, p = 0.003 and HR 3.2, p = 0.014 by months 2 and 6 of treatment, respectively. Conclusion: The probability of clinical symptoms reflecting bacteriological positivity weakens as the patient progresses on anti-TB therapy, making the symptom-based diagnosis a less reliable marker of treatment response.
RESUMO
BACKGROUND: The diagnosis of paediatric tuberculosis is complicated by non-specific symptoms, difficult specimen collection, and the paucibacillary nature of the disease. We assessed the accuracy of a novel immunodiagnostic T-cell activation marker-tuberculosis (TAM-TB) assay in a proof-of-concept study to identify children with active tuberculosis. METHODS: Children with symptoms that suggested tuberculosis were prospectively recruited at the NIMR-Mbeya Medical Research Center in Mbeya, and the Ifakara Health Institute in Bagamoyo, Tanzania, between May 10, 2011, and Sept 4, 2012. Sputum and peripheral blood mononuclear cells were obtained for Mycobacterium tuberculosis culture and performance assessment of the TAM-TB assay. The children were assigned to standardised clinical case classifications based on microbiological and clinical findings. FINDINGS: Among 290 children screened, we selected a subgroup of 130 to ensure testing of at least 20 with culture-confirmed tuberculosis. 17 of 130 children were excluded because of inconclusive TAM-TB assay results. The TAM-TB assay enabled detection of 15 of 18 culture-confirmed cases (sensitivity 83·3%, 95% CI 58·6-96·4). Specificity was 96·8% (95% CI 89·0-99·6) in the cases that were classified as not tuberculosis (n=63), with little effect from latent tuberculosis infection. The TAM-TB assay identified five additional patients with highly probable or probable tuberculosis, in whom M tuberculosis was not isolated. The median time to diagnosis was 19·5 days (IQR 14-45) for culture. INTERPRETATION: The sputum-independent TAM-TB assay is a rapid and accurate blood test that has the potential to improve the diagnosis of active tuberculosis in children. FUNDING: European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.