In the summer after my second year of medical school, I found myself in a hospital clinic in Swaziland with what was quickly becoming a familiar scenario: An unwell-looking woman from a remote village had traveled for many hours to seek our opinion on her cough and night sweats. Was it tuberculosis?
It was a frustratingly difficult question to answer with any certainty using the cumbersome combination of smear microscopy and sputum culture. Smear negative? We’d still have to wait weeks for culture results to reassure her that it definitely wasn’t TB. Smear positive? We’d start first-line antibiotics – and then wait weeks to see if she grew a resistant strain. In either scenario, she’d bear the expense and difficulty of a repeat trip to the clinic, and she looked like she could easily get much worse in the interim. The need for a reliable point-of-care test for TB was distressingly obvious, but such a test simply wasn’t available.
As reported in this week’s NEJM, automated nucleic acid amplification tests might fill that void. One such test, the Xpert MTB/RIF assay, allows a relatively unskilled healthcare worker to diagnose tuberculosis and detect rifampin resistance within 90 minutes. Boehme et al examined the diagnostic performance of the MTB/RIF assay in four resource-poor countries, comparing the results of the automated molecular test to a reference standard of smear microscopy and sputum culture in more than seventeen hundred patients with suspected pulmonary TB.
Among all culture-positive subjects, the MTB/RIF assay demonstrated excellent diagnostic accuracy, with a 97% sensitivity and a 99% specificity for the diagnosis of TB. Among the smear-negative/culture-positive subgroup, a single MTB/RIF test had a modest sensitivity, but substantial improvement was obtained by testing three sequential sputum samples. The test was also sensitive for rifampin resistance, a crucial consideration when prescribing a long course of therapy that may be ineffective if resistance is present.
“The global burden of TB is tremendous, and rapid, accurate, and cost-effective diagnostic tests are needed,” says NEJM deputy editor and infectious-disease specialist Dr. Lindsey Baden. “This trial rigorously evaluates the diagnostic characteristics of the MTB/RIF test, and sets the stage for other studies to evaluate its utility once operationalized in a developing-world setting.”
Will this test transform care for patients such as those I saw over a decade ago? It’s hard to imagine it doing so single-handedly. In my brief time in Swaziland, the importance of context became clear: Difficulties retaining trained laboratory staff, unpredictable shortages of laboratory reagents, and the daunting poverty of patients and health care system alike all hindered the daily task of diagnosis. Such system-level limitations are key barriers to a global scale-up of point-of-care testing, according to editorialists Small and Pai. Despite these challenges, the editorialists are optimistic that further innovation and leadership may originate from within emerging economies themselves.
With luck, ongoing innovation in point-of-care diagnostics will help answer the age-old question “TB, or not TB?” with greater speed. And if global TB elimination is a success, it might even help render its very asking a thing of the past.