Molecular diagnostics for TB: we need solutions across the value chain
In a recent paper, we argued that we need affordable and point-of-care TB diagnostics at lower tiers of healthcare, while planning for specialized solutions at the referral level, with efficient systems for sample referral.
By Emily MacLean, Sophie Huddart, and Madhukar Pai
Without early and accurate diagnosis, TB is impossible to control. Historically, TB control programs have relied on sputum smear microscopy as the main diagnostic tool for active TB. More recently, molecular TB diagnostics are starting to get rolled out, even in low and middle income countries (LMICs). WHO has endorsed 3 rapid nucleic acid amplification tests (NAATs) since 2008: line probe assays for detection of resistance to first and second line TB drugs, Xpert MTB/RIF, an automated, cartridge-based assay, and a manual TB-LAMP assay, based on isothermal amplification process.
In a recent paper, published in Expert Review of Molecular Diagnostics, we made a case for ensuring molecular solutions across the healthcare delivery value chain, from primary care, to reference laboratories. In the short term (the next 5 years), we need to expand the range of molecular technologies that can replace sputum smear microscopy at the primary care level, where most patients with suspected TB seek medical care. Since most LMICs have only microscopy to offer at the primary care level, we must find ways to move high sensitivity molecular technologies down the value chain to the primary care (L1) level, in order to diagnose TB early in the patient pathway. And there are products that are now available for such decentralized testing (Figure).
At the same time, we also need specialized solutions at the district and referral level, with efficient systems for patient and sample referral. While it would be ideal for drug-susceptibility testing (DST) to be available as close as possible to where patients first seek care, it must at least be available in reference centers. Since expanded DST options are likely to be deployable (or necessary) only at the reference (L3) laboratory level, it is clear that we need to invest in systems for rapid, reliable transport of samples up the referral chain, enabled by digital tracking technologies; ideally, these could also deliver results to patients and care providers. Thus, there is a role for centralized TB testing models, although these would need to be optimized to reduce long turn-around times, and minimize the proportion of patients who are lost to follow-up.
In sum, we need to take TB tests lower, while ensuring that we have systems to move samples to reference labs.
Sophie Huddart and Emily MacLean are doctoral candidates in epidemiology at McGill University, Montreal, Canada. Madhukar Pai is a professor of epidemiology, and Director of McGill Global Health Programs.