High Mycobacterium tuberculosis Bacillary Loads Detected by Tuberculosis Molecular Bacterial Load Assay in Patient Stool: a Potential Alternative for Nonsputum Diagnosis and Treatment Response Monitoring of Tuberculosis.

Not all patients produce sputum, yet most available TB tests use sputum. We investigated the utility of a novel RNA-based quantitative test, the tuberculosis molecular bacterial load assay (TB-MBLA), for the detection and quantification of Mycobacterium tuberculosis in stool. Stools from 100 adult individuals were treated with OMNIgene-sputum reagent and tested using Xpert MTB/RIF ultra (Xpert ultra), auramine O smear microscopy (smear), mycobacterial growth indicator tube (MGIT), and Lowenstein-Jensen (LJ) cultures. The remaining portions were frozen at -20°C and later tested by TB-MBLA. MGIT sputum culture was used as a TB confirmatory test and reference for stool tests. Sixty-one of 100 participants were already confirmed TB positive by MGIT sputum culture, 20 (33%) of whom were HIV coinfected. TB-MBLA detected M. tuberculosis in 57/100 stool samples, including 49 already confirmed for TB. The mean bacterial load measured by stool TB-MBLA was 5.67 ± 1.7 log10 estimated CFU (eCFU) per mL in HIV-coinfected participants, which was higher than the 4.83 ± 1.59 log10 eCFU per mL among the HIV-negative participants (P = 0.04). The sensitivities (95% confidence intervals [CI]) of stool assays were 80% (68 to 89) and 90% (79 to 98) for TB-MBLA and Xpert ultra, which were both higher than the 44% (32 to 58), 64% (51 to 76), and 62% (45 to 77) for smear, MGIT, and Lowenstein-Jensen (LJ) stool cultures, respectively. The specificity (95% CI) of stool assays was highest for smear, at 97% (87 to 100), followed by Xpert ultra at 91% (76 to 98), TB-MBLA at 79% (63 to 90), LJ at 80% (64 to 91), and MGIT at 62% (45 to 77). Twenty-six percent of MGIT and 21% of LJ stool cultures were indeterminate due to contamination. Detection and quantification of viable M. tuberculosis bacilli in stool raises its utility as an alternative to sputum as a sample type for TB diagnosis. IMPORTANCE This paper highlights the value of stool as a sample type for diagnosis of tuberculosis. While other studies have used DNA-based assays like the Xpert MTB/RIF and culture to detect Mycobacterium tuberculosis in stool, this is the first study that has applied TB-MBLA, an RNA-based assay, to quantify TB bacteria in stool. The high microbial density and diversity in stool compromises the specificity and sensitivity of culture-based tests due to overgrowth of non-M. tuberculosis flora. Consequently, TB-MBLA becomes the most sensitive and specific test for the detection and quantification of viable TB bacteria in stool. Most crucially, this study raises the possibility of a nonsputum alternative sample type for diagnosis of TB among people who have difficulty in producing sputum.

Genetic factors associated with tuberculosis-related clinical outcomes in HIV-infected Black African patients: a systematic review and meta-analysis.

Aim: To evaluate the genetic factors influencing tuberculosis (TB) clinical outcomes in HIV-infected Black African patients. Materials & methods: We systematically searched and identified eligible publications from >550 databases indexed through February 2021. Results: Eighteen studies were included in the qualitative synthesis. Only two cohorts from one study were included in quantitative synthesis of which the low expression MIF-794 CATT5,6 (5/5 + 5/6 + 6/6) genotypes were not associated with TB infectivity in HIV-infected patients (OR: 1.31, 95% CI: 0.46-3.79). Other TB clinical outcomes observed in HIV/TB co-infected patients included: drug-induced liver injury, peripheral neuropathy, mortality, lung function and TB cure. Conclusion: This review finds inconclusive evidence that genetic factors are associated with TB clinical outcomes among HIV-infected patients in sub-Saharan Africa.