TB testing in HIV-positive patients prior to antiretroviral treatment.

BACKGROUND: TB diagnosis in patients with HIV is challenging due to the lower sensitivities across tests. Molecular tests are preferred and the Xpert® MTB/RIF assay has limitations in lower-income settings. We evaluated the performance of loop-mediated isothermal amplification (LAMP) and the lipoarabinomannan (LAM) test in HIV-positive, ART-naïve clinic patients.METHODS: A total of 783 eligible patients were enrolled; three spot sputum samples of 646 patients were tested using TB-LAMP, Xpert, smear microscopy and culture, while 649 patients had TB-LAM testing. Sensitivity, specificity, and negative and positive predictive values were estimated with 95% confidence intervals.RESULTS: Sensitivities for smear microscopy, TB-LAMP and Xpert were respectively 50%, 63% and 74% compared to culture, with specificities of respectively 99.2%, 98.5% and 97.5%. An additional eight were positive on TB-LAM alone. Seventy TB patients (9%) were detected using standard-of-care testing, an additional 27 (3%) were detected using study testing. Treatment was initiated in 57/70 (81%) clinic patients, but only in 56% (57/97) of all those with positive TB tests; 4/8 multidrug-resistant samples were detected using Xpert.CONCLUSION: TB diagnostics continue to miss cases in this high-burden setting. TB-LAMP was more sensitive than smear microscopy, and if followed by culture and drug susceptibility testing as required, can diagnose TB in HIV-positive patients. TB-LAM is a useful add-in test and both tests at the point-of-care would maximise yield.

Detecting Mycobacterium tuberculosis using the loop-mediated isothermal amplification test in South Africa.

SETTING: In South Africa, KwaZulu-Natal is the epicentre of the human immunodeficiency virus (HIV) epidemic, where approximately 70% of people with tuberculosis (TB) are co-infected with HIV. Undiagnosed TB contributes to high mortality in HIV-infected patients. Delays in diagnosing TB and treatment initiation result in prolonged transmission and increased infectiousness. OBJECTIVE: To evaluate the LoopampTM MTBC Detection kit (TB-LAMP; based on the loop-mediated isothermal amplification assay), smear microscopy and Xpert test with the gold standard of mycobacterial culture. METHODS: Sputum samples were collected from 705 patients with symptoms of pulmonary TB attending a primary health care clinic. RESULTS: The TB-LAMP assay had significantly higher sensitivity than smear microscopy (72.6% vs. 45.4%, P < 0.001), whereas specificity was slightly lower (99% vs. 96.8%, P = 0.05), but significantly higher than Xpert (92.9%, P = 0.004). There was no significant difference in sensitivity of smear-positive, culture-positive and smear-negative, culture-positive sputum samples using TB-LAMP vs. Xpert (respectively 95.9%/55.9% vs. 97.6%/66.1%; P =0.65, P = 0.27). The positive predictive value of TB-LAMP was significantly higher than that of Xpert (87.5% vs. 77.0%; P = 0.02), but similar to that of smear microscopy (94.2%; P = 0.18). The negative predictive value was respectively 91.9%, 92.5% (P = 0.73) and 83.1% (P = 0.0001). CONCLUSION: Given its ease of operability, the TB-LAMP assay could be implemented as a point-of-care test in primary health care settings, and contribute to reducing treatment waiting times and TB prevalence.