Evaluation of the Genotype® MTBDRplus assay as a tool for drug resistance surveys.

SETTING: A national tuberculosis (TB) drug resistance survey in Tanzania. OBJECTIVE: To compare the performance of the Genotype® MTBDRplus line-probe assay (LPA) on smear-positive sputum specimens with conventional culture and isoniazid (INH) plus rifampicin (RMP) drug susceptibility testing (DST). DESIGN: Mycobacterium tuberculosis isolates tested at the Tanzanian Central TB Reference Laboratory (CTRL) were submitted for quality assurance of phenotypic DST to its supranational reference laboratory (SRL), together with ethanol-preserved sputum specimens for LPA DST. RESULTS: Only 321 samples could be tested using LPA; of these, three were identified as being non-tuberculous mycobacteria using CTRL DST. Both tests had 269 sets with interpretable results. CTRL DST yielded almost the same number of interpretable results as LPA, with 90% concordance (κ = 0.612, P < 0.001). Five (1.9%) multidrug-resistant (MDR) strains, 46 (17.1%) resistant to INH only and 0 RMP only, were found by CTRL DST. For the LPA, these results were respectively 5 (1.9%), 26 (9.7%) and 2 (0.7%). With SRL DST as the gold standard, LPA was more accurate than CTRL DST for RMP, but missed almost half the INH-resistant samples. CONCLUSION: LPA applied directly on ethanol-preserved sputum specimens was similar to phenotypic DST in terms of yield of interpretable results. Although probably more accurate for RMP and MDR-TB, it appears to seriously underestimate INH resistance. Considering speed, easy and safe specimen transportation and low infrastructure requirements, LPA DST from sputum can be recommended for surveys in resource-poor settings.

National anti-tuberculosis drug resistance study in Tanzania.

OBJECTIVE: To assess the prevalence of anti-tuberculosis drug resistance in a national representative sample of tuberculosis (TB) patients in Tanzania according to recommended methodology. DESIGN: Cluster survey, with 40 clusters sampled proportional to size, of notified TB patients from all diagnostic centres in the country. RESULTS: The survey enrolled 1019 new and 148 retreatment patients. The adjusted prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line drugs in new patients was 8.3%, while the prevalence of multidrug-resistant TB (MDR-TB) was 1.1%. In retreatment patients, the crude prevalence for any resistance and for MDR-TB was respectively 20.6% and 3.9%. The prevalence of drug resistance did not differ in relapse patients compared to failure patients. These estimates are among the lowest in those African countries with an estimated level of drug resistance in the last 5 years. CONCLUSION: The low levels of drug resistance in Tanzania are likely due to a well performing TB control programme and the absence of noticeable involvement of the private sector in TB treatment.

Trend in HIV prevalence among tuberculosis patients in Tanzania, 1991-1998.

OBJECTIVE: To determine the trend in human immunodeficiency virus (HIV) prevalence among tuberculosis patients in Tanzania and estimate what proportion of the increase in notification rates between the surveys was directly attributable to HIV infection. METHODS: Consecutive tuberculosis patients were enrolled over 6-month periods in most regions. Demographic and clinical data were collected on standard forms and a single HIV ELISA test performed. Trends in tuberculosis incidence were estimated from regional notification data. RESULTS: Of 10612 eligible tuberculosis patients, 44% had HIV infection, compared with 32% in the previous survey. The largest increase was observed in the youngest birth cohorts, suggesting active HIV transmission. Approximately 60% of the increase in notification rates of smear-positive tuberculosis between surveys was directly attributable to HIV infection. CONCLUSION: The HIV epidemic has had a strong influence on tuberculosis incidence. However, since 1995, tuberculosis notification data have increased less steeply, AIDS notifications have gone down, and HIV prevalence in blood donors has not increased a great deal. Another survey among tuberculosis patients in 5 years' time may show whether the HIV epidemic in Tanzania has reached a maximum or steady state.

Density of tuberculin skin reaction and its association with tuberculosis infection as defined by dual tuberculin testing.

OBJECTIVE: To determine whether the density of tuberculin skin reactions is associated with tuberculosis infection. METHODS: In a national tuberculin survey in Tanzania, 1983-1987, all eligible children in a random sub-sample of schools underwent dual tuberculin skin testing with PPD-RT23 and PPD-scrofulaceum. The density of reactions to RT23 was classified as proposed by Palmer. A larger reaction to PPD-scrofulaceum than to PPD-RT23 is suggestive of infection with environmental mycobacteria. Tuberculosis infection was defined based on dual skin test results applying a range of possible definitions. RESULTS: A total of 10,782 children aged 5-14 years and without BCG scar were included in the analysis. Large skin reactions to RT23 were generally firmer than small ones. After taking the size of the skin reaction to RT23 into account, its density was not associated with the size of the skin reaction against PPD-scrofulaceum. In particular, the density of reactions in the range 6-11 mm was not associated with tuberculosis infection according to any of the definitions used. CONCLUSION: This study suggests that the density of reaction was not associated with tuberculosis infection in Tanzanian school children after taking the size of the induration into account.