Diagnosing tuberculosis (TB) relies primarily on two methods. One involves a process that’s more than 140 years old, and the other is a more recent technological advance. Both methods have their limitations.

The most prevalent method, smear microscopy, was developed in the early 1880s by German scientist Robert Koch. It involves collecting a sample from a patient, placing it on a glass slide and staining it with a dye, then examining the sample under a microscope. While the technique can be performed in low-resource settings, it’s time consuming and misses half or more of TB cases.

Rapid molecular TB diagnostic tests, like the Xpert Ultra MTB/RIF test, are quicker, far more accurate, and have been endorsed by the World Health Organization (WHO) as the recommended first-line test since 2011. But the equipment to run these tests is expensive and requires a stable power supply. More than half of TB units in high-burden countries don’t have access to this type of molecular testing, according to Adithya Cattamanchi, MD, MPH, a professor of medicine at the University of California, Irvine.

Furthermore, both methods are primarily performed on sputum, the mucus coughed up from deep within the lungs. The problem with that, said Cattamanchi, is that many patients coming to be tested, from babies to the elderly to people with HIV, can’t produce sputum.

“It’s been estimated that anywhere from a quarter to 40% of people who are coming in with TB symptoms or being evaluated for TB are unable to produce sputum,” Cattamanchi told CIDRAP News. “So that’s a big limitation.”

The limitations of current TB diagnostic tests partly explain why the estimated number of people infected with Mycobacterium tuberculosis each year is higher than the number of officially diagnosed and reported cases.

But if the findings published yesterday in the New England Journal of Medicine are any indication, a test that addresses these limitations has arrived.

Test meets WHO standards for accuracy, usability

The MiniDock MTB test platform, made by Chinese company Pluslife Biotech, is a battery-operated near point-of-care nucleic acid amplification test (NPOC-NAAT). Like the at-home COVID-19 tests many people used during the COVID pandemic, it includes a swab for collecting patient samples and a tube with a releasing agent that you swirl the swab in. 

The kit also includes a device that heats and spins the tube to inactivate and separate the TB DNA, a test card that collects the liquid sample from the tube, and a card reader that provides results. The whole process takes around 30 minutes to provide results and is “absolutely feasible to implement” in simpler laboratories, Cattamanchi said.

And it works. In the National Institutes of Health–funded study, conducted by Cattamanchi and an international team of TB researchers at outpatient centers in seven high TB-burden countries (India, Nigeria, the Philippines, South Africa, Uganda, Vietnam, and Zambia), MiniDock MTB met the WHO requirements for accuracy and usability for TB detection. 

Used on 1,380 patients, the test correctly detected TB from sputum samples in 85.7% of cases (sensitivity) and correctly identified people without TB (specificity) in 97.6% of cases. The WHO targets for near point-of-care diagnostic TB tests are 85% or greater sensitivity and 98% or greater specificity. The results matched those of the Xpert MTB/RIF Ultra test and far exceeded those of smear microscopy. 

More important, MiniDock MTB’s sensitivity and specificity on tongue swabs were 79.6% and 99.5%, respectively. The accuracy on tongue swabs was a little bit lower compared with Xpert Ultra sputum testing, “but far better than microscopy,” said Addithya, and met WHO requirements for non-sputum testing (75% or greater sensitivity and 98% or greater specificity).

I think what this means is that now we have a flexible specimen testing platform that enables, essentially, molecular testing for anyone coming in who needs TB evaluation, regardless of their ability to produce sputum.

In a usability evaluation involving 18 healthcare workers (clinicians, nurses, and lab technicians), the media usability score was 75%, and the test was consistently described as “easy to use.” When combined with the cost—the card reader and the thermolyze device each cost around $180, and the test cards cost roughly $4—the results of the study show MiniDock MTB “offers reasonable accuracy with practical advantages,” the study authors wrote.

“I think what this means is that now we have a flexible specimen testing platform that enables, essentially, molecular testing for anyone coming in who needs TB evaluation, regardless of their ability to produce sputum,” Cattamanchi said.

In addition, the low cost could give smaller, rural clinics access to molecular TB tests, which means that people with TB symptoms in low-resource countries would not have to travel long distances or take time off of work to get to the larger healthcare facilities where such tests have traditionally been available. It also might enable high-burden countries to do more active case-finding, Cattamanchi suggested.

“You can arm healthcare workers with this test to go out into communities and find cases,” he said. “We hope that this will enable much wider molecular testing.”

A ‘highly scalable’ test

Madhukar Pai, MD, PhD, a physician and TB researcher who chairs the department of global and public health at McGill University in Montreal and wasn’t involved in the study, said in an email that, in addition to providing a good option for people who can’t produce sputum, the simplicity of the MiniDock technology will allow molecular TB testing to be taken “closer to people and communities.” He also noted that the attractive pricing “makes it highly scalable for high TB burden countries that are reeling under the stress of all the aid cuts.”

MiniDock MTB does have some limitations. For one, the researchers observed that the sensitivity declined with tongue swabs from patients with a lower mycobacterial load. And the current version can’t detect drug-resistant TB, which is a growing problem. 

Still, the WHO, based on data provided by the researchers, recently recommended the testing platform and use of tongue swabs to simplify and expand access to TB testing. Guidance on how to implement MiniDock MTB and other NPOC-NAATs that meet WHO standards into national TB programs will be published by the agency later this year.

“WHO urges countries and partners to work together to roll out these guidelines to close persistent diagnostic gaps and ensure that everyone with TB can be diagnosed early and start life-saving treatment without delay,” said Tereza Kasaeva, MD, PhD, director of WHO’s Department for HIV, Tuberculosis, Hepatitis and Sexually Transmitted Infections.