Molecular bacterial load assay versus culture for monitoring treatment response in adults with tuberculosis

Abstract

The lack of rapid, sensitive, and deployable tuberculosis diagnostic tools is hampering the early diagnosis of tuberculosis and early detection of treatment failures. The conventional sputum smear microscopy or Xpert MTB/RIF assay cannot distinguish between alive and dead bacilli and the culture method delays providing results. Tuberculosis molecular bacterial load assay is a reverse transcriptase real-time quantitative polymerase chain reaction that quantifies viable tuberculosis bacillary load as a marker of treatment response for patients on anti-tuberculosis therapy. However, results are not synthesized enough to inform its comparative advantage to tuberculosis culture technique which is yet the gold standard of care. With this review, we searched electronic databases, including PubMed, Embase, and Web of Science, from March 2011 up to February 2021 for clinical trials or prospective cohort studies that compared tuberculosis molecular bacterial load assay with tuberculosis culture in adults. We included eight studies that meet the inclusion criteria. Tuberculosis molecular bacterial load assay surpasses culture in monitoring patients with tuberculosis during the first few weeks of anti-tuberculosis treatment. It is more desirable over culture for its shorter time to results, almost zero rates of contamination, need for less expertise on the method, early rate of decline, lower running cost, and reproducibility. Its rapid and specific tuberculosis treatment monitoring competency benefits patients and healthcare providers to monitor changes of bacillary load among isolates with drug-susceptible or resistance to anti-tuberculosis regimens. Despite of the high installing cost of the tuberculosis molecular bacterial load assay method, molecular expertise, and a well-equipped laboratory, tuberculosis molecular bacterial load assay is a cost-effective method with comparison to culture in operational running. To achieve maximum utility in high tuberculosis burden settings, an intensive initial investment in nucleic acid extraction and polymerase chain reaction equipment, training in procedures, and streamlining laboratory supply procurement systems are crucial. More evidence is needed to demonstrate the potential large-scale and sustainable use of tuberculosis molecular bacterial load assay over culture in resource-constrained settings.

Five-year trend analysis of tuberculosis in Bahir Dar, Northwest Ethiopia, 2015–2019

“…There were an estimated 1.2 million TB deaths among HIV-negative people in 2019 (a reduction from 1.7 million in 2000), and an additional 208,000 deaths among HIV-positive people (a reduction from 678,000 in 2000). [ 1 ] Efforts are underway to provide equitable access to quality and timely diagnosis, treatment, and prevention of TB, particularly in resource-constrained settings, [ 2 – 5 ] and TB incidence and deaths are falling. [ 1 ]…”

Validity of InterVA model versus physician review of verbal autopsy for tracking tuberculosis-related mortality in Ethiopia

“…Hospital diagnoses, on the other hand, have limitations as a gold standard since the composition and distribution of hospital CODs may not be indicative of community mortality. Furthermore, in resource-constrained healthcare settings, when hospital diagnoses are available, they are of poor quality and are limited by insufficient clinical data and record keeping [ 31 – 33 ]. Moreover, hospital users and residential users may have varied abilities to notice, recall, and report indicators of sickness.…”