Impact of molecular diagnostic tests on diagnostic and treatment delays in tuberculosis: a systematic review and meta-analysis

Abstract

Background: Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB).

Methods: We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays.

Results: A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods.

Conclusions: Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.

Keywords: Communicable diseases; Global Health; Nucleic acid amplification tests; Point-of-Care Systems.

Fig. 1

Conceptual framework of time delay components in diagnosis and treatment of tuberculosis. The illustrations depicted here are our own

Fig. 2

PRISMA diagram. DS-TB drug-sensitive tuberculosis, DR-TB drug-resistant tuberculosis. *One study [30] reported data for both DS-TB and DR-TB

Fig. 3

Forest plots of raw median difference in diagnostic delay for Xpert and smear for drug-sensitive TB

Fig. 4

Forest plots of raw median difference in treatment initiation delay for Xpert and smear for drug-sensitive TB

Fig. 5

Forest plots of raw median difference in diagnostic delay for LPA and culture DST for drug-resistant TB

Fig. 6

Forest plots of raw median difference in treatment initiation delay LPA and culture DST for drug-resistant TB