Both Mishra and Mohapatra1 and Harries et al.2 raise important concerns about the implementation of Xpert® MTB/RIF (Cepheid, Sunnyvale, CA, USA) testing in high-burden countries. Mishra et al. point out that undue reliance on Xpert as a sole diagnostic test for multidrug-resistant (MDR-TB) can result in missed outbreaks of drug-resistant TB with tragic outcomes for affected patients and communities. Harries et al. highlight the tremendous challenges of implementing Xpert in real-world settings, in which well over half of individuals who deserve Xpert testing currently derive no benefit from this expensive assay. Many other examples—from inappropriate sample processing, inadequate power supply, and module failure,3 to losses to follow-up resulting in no improvement in treatment outcomes4—could be given as well. The assertion that ‘successful implementation of Xpert in most resource-constrained settings is a challenge’ is a tremendous understatement, to say the least.
It is important, however, to maintain a degree of optimism as we face these very real challenges of implementing Xpert. As both Mishra and Mohapatra and Harries et al. point out, some of these obstacles can be overcome with technical solutions, from expanding the rifampicin-resistance determining region of Xpert to the use of systems such as GxAlert (SystemOne, Northampton, MA, USA) that provide automated results to patients. Xpert is now also available in the GeneXpert I and GeneXpert Edge platforms, which address some of the problems related to portability and power supply. There is strong reason to believe that other technological innovations, including Xpert fast-followers and add-on systems, will reduce the number of implementation hurdles still further.5 Systems-based innovations, including stronger referral networks for specimen transport and integration of diagnostic capacity with other disease entities (e.g., use of Xpert for HIV viral load testing), can also make an important impact. Ultimately, while no technical or systemic improvement is likely to be a ‘silver bullet,’ solving all problems across the diverse array of existing health systems, important progress can—and will—still be made.
Arguably, we have made as much progress in improving the diagnosis of TB over the past 10 years as in any decade since the advent of fluorescence microscopy in the 1930s. This progress has been fueled in large part by the development and implementation of Xpert. As we look forward to the next 10 years, we must acknowledge that the challenges of implementing Xpert in current health systems are very real. But we must also not underestimate the ability of human innovation to transform our ability to detect and treat a pathogen that has plagued our species since antiquity.
Footnotes
Conflicts of interest: none declared.
References
- 1.Mishra B, Mohapatra P. Expand the hotspot to improve GeneXpert outcome. Int J Tuberc Lung Dis 2019; 23: 1043. [DOI] [PubMed] [Google Scholar]
- 2.Harries AD, Timire C, Takarinda KC, Sandy C. Ensuring that Xpert MTB/RIF is used to its maximum potential. Int J Tuberc Lung Dis 2019; 23: 1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Agizew T, Boyd R, Ndwapi N, et al. Peripheral clinic versus centralized laboratory-based Xpert MTB/RIF performance: experience gained from a pragmatic, stepped-wedge trial in Botswana. PLOS ONE 2017; 12(8): e0183237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Evans D, Sineke T, Schnippel K, et al. Impact of Xpert MTB/RIF and decentralized care on linkage to care and drug-resistant tuberculosis treatment outcomes in Johannesburg, South Africa. BMC Health Serv Res 2018; 18(1): 973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Denkinger CM, Pai M. Diagnosis of tuberculosis: current pipeline, unmet needs, and new developments In: Lu Y, Wang L, Duanmu H, Chanyasulkit C, Strong AJ, Zhang H, eds. Handbook of global tuberculosis control. Boston, MA, USA: Springer, 2017: pp 77–98. [Google Scholar]