Bottlenecks and recent advancements in detecting Mycobacterium tuberculosis in patients with HIV

Tuberculosis (TB) remains a leading cause of deaths among patients with acquired immunodeficiency syndrome patients. Early diagnosis of TB is essential for administering timely anti-TB therapy and improving health outcomes, particularly in the people living with HIV. However, conventional techniques used to detect Mycobacterium tuberculosis have significant drawbacks: for example, sputum smear microscopy has low sensitivity, and liquid culture is time-consuming in patients with HIV-TB co-infection due to low sputum production. In addition, while immunological-based methods involving tuberculin skin testing and interferon gamma release assays are commonly used for auxiliary TB diagnosis, they are often inaccurate in immunodeficient patients. Molecular techniques such as line probe assays, Xpert MTB, and lipoarabinomannan assay are recommended for early diagnosis by World Health Organization. However, no single technique is sufficicent for diagnosing HIV/TB co-infection, suggesting that multiple diagnostic tests should be used to detect TB. Here, we summarize the drawbacks and advantages of existing TB-diagnostic methods, as well as their applications to diagnosing HIV/TB co-infection. We describe newly emerging technologies such as whole genome sequencing and mass spectrometry, with the aim of providing updated guidelines and alternative strategies for TB diagnosis, and particularly HIV/TB diagnosis.