Can we predict tuberculosis cure? What tools are available?

Abstract

Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerantMycobacterium tuberculosisbacilli. However, the majority of patients treated for only 2–3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of “cure”. Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests.

Latent tuberculosis infection screening in persons newly-diagnosed with HIV infection in Italy: A multicentre study promoted by the Italian Society of Infectious and Tropical Diseases

“…This is a very interesting issue; however this parameter was not evaluated in our survey. The low implementation of LTBI screening is likely due to the low perception of TB risk in PLWH (Evenblij et al, 2016), and to the awareness of the inaccuracy of LTBI tests, which can give falsenegative results in immunosuppressed persons (Goletti et al, 2014;Goletti et al, 2007;Vincenti et al, 2007) and are inadequate to predict progression to disease (Diel et al, 2011;Petruccioli et al, 2016a;Goletti et al, 2018a;Goletti et al, 2018b). The accuracy of LTBI tests improves if a selected population known to have a higher probability to progress to active disease is identified, as recommended in the recent guidelines of the British HIV Association (BHIVA) (BHIVA, 2018).…”

“…In spite of the existing recommendations, there is evidence that even in resource-rich countries, a significant proportion of PLWH are not screened for LTBI diagnosis (WHO, 2019;Evenblij et al, 2016;Wyndham-Thomas et al, 2016). This may be due to the low accuracy of LTBI tests to predict the development of active TB (Diel et al, 2011;Petruccioli et al, 2016a;Goletti et al, 2018a;Goletti et al, 2018b), to the awareness of the reduction in TB risk in those on combined antiretroviral therapy (cART) (Girardi et al, 2004;Girardi et al, 2012), and to the lack of availability of LTBI tests in clinical centres (CDC, 2011;Web site, 2018).…”

Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate ofMycobacterium tuberculosisin patients with multidrug-resistant tuberculosis in Tanzania

“…Limitations of the study include the endpoints, which were limited to 4 months such that predicting long-term treatment success was beyond the scope of this study. Nevertheless, modelling M. tuberculosis elimination for 4 months as we accomplished here has been used as marker for treatment failure and relapse in several observational studies [18,30] , and exceeds the duration of monitoring used in other trials of R/MDR-TB regimens that have employed conventional culture based techniques. [20] Additionally, this study had no control over the treatment regimens prescribed.…”

“…The overall mean Mtb load log10 eCFU/mL at baseline was 5.19 (95% CI; 4.40 -5.78), and was similar in all patients treated with any of the regimens (Table 3, decades, culture has been used as a routine microbiological tool for monitoring drug-resistant TB treatment response [17,18] , but in many TB endemic settings, culture is unavailable or limited to specialized centres. Importantly, culture results can take up to 8 weeks from the time of sputum collection, which when making treatment decisions based on a result from a two-months old specimen, is akin to driving a car while only looking in the rear-view mirror.…”

Towards individualised treatment of tuberculosis

“…Studies on different biomarkers has increased our understanding of the pathogenesis of TB and the continuum between latent and active TB. Nevertheless, a single biomarker that is indicative for treatment response and long-term outcome remains to be identified (229). Optimising the host response, both innate and adaptive immunity, by nutritional supplementation and adjuvant immunotherapy may be potential interventions to prevent TB activation or improve TB cure rates (8).…”