Are oral swabs the future of TB testing?

Are oral swabs the future of TB testing?A recent study published in the journal Clinical Infectious Diseases found that there was an association between healthcare workers’ exposure to high levels of carbon dioxide (CO2) and their risk of being exposed to tuberculosis (TB). IMAGE:
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The World Health Organization (WHO) estimates that every year 40% of people who fall ill with tuberculosis (TB) globally are not diagnosed. There is thus an urgent need for faster, safe, and more convenient TB tests. The current gold standard of testing still requires people to cough up sputum, something that some people and children, in particular, struggle with. The coughing up of sputum also poses an infection risk to healthcare workers collecting sputum samples.

An alternative that will not require the coughing up of sputum is to perform an oral swab, which in current research means collecting a sample by scraping the tongue. Several studies exploring how well such oral swab TB tests perform at detecting TB are now underway in South Africa and elsewhere. If oral swab tests turn out to be accurate enough, they may revolutionise TB testing. Not only do they promise to be quick and easy to collect, but they may also open the door to people collecting their own samples for testing – something that is not possible with the current tests.

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How it works

Professor Grant Theron, head of the Clinical Mycobacteriology and Epidemiology (CLIME) Research group at Stellenbosch University’s Molecular Biology and Human Genetics Unit says swab-based testing involves the use of a swab with a tip (Flock, foam, or cotton) designed to scrape the upper surface of the tongue. Theron and his team use Flocked swabs (a type of swab with fibres of variable lengths that helps better absorb and release samples than other types of swabs).

“Scientific evidence suggested that Mycobacterium tuberculosis (Mtb) DNA is deposited on the oral epithelium during active TB disease,” he says.

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Dr Angelique Luabeya, Chief Research Officer at the South African Tuberculosis Vaccine Initiative (SATVI), explains that healthcare workers gently brush a person’s tongue with a sterile swab for about 10 seconds (seven to eight times) to collect cells and saliva. The head of each swab is then ejected or broken off in a tube containing buffer.

“The procedure is non-invasive and does not put the subject at risk for physical injury,” says Luabeya.

As Luabeya and colleagues previously reported, the tongue is a better site for sample collection, with higher positivity for TB DNA, than the cheek or gums. “One explanation might be that the tongue has more biomaterial than other sites in the mouth,” she says.

“How these samples are transported is a crucial process,” says Theron. “The swabs need to be transported under the correct conditions and temperature to ensure the DNA is preserved and intact.” Samples have to be stored at -20 or -80 degrees Celsius (depending on how long they have to be stored). After collection, samples are typically transported in special cooler boxes to laboratories.

The samples are then analysed with a brand of Polymerase Chain Reaction (PCR) test called GeneXpert MTB/RIF Ultra, a test that is already widely used in South Africa to test for TB in sputum samples. GeneXpert machines have also been used for some SARS-CoV-2 testing.

“At this stage of research, we are batching the samples before performing the PCR testing,” says Luabeya. “We would like to have the Oral Swab Analysis methods as point-of-care testing in clinics. The aim is to have results available within a few hours.”

In the 2019 study by Luabeya and colleagues, two tongue swabs were found to have a sensitivity of 92.8% compared to sputum-based GeneXpert testing – results were less impressive when only one tongue swab was done. Doing two tongue swabs, however, also detected some cases of TB missed by sputum-based testing so that the overall yield from the two methods was similar.

Several further research projects are now underway in South Africa and elsewhere. Among others, these are exploring the use of oral swabs in children and adolescents, and people living with HIV. Research is also being conducted on how oral swabs can be rolled out in diverse settings and how they might be used as a point of care test (where analysis is done at the healthcare facility rather than at a lab). Details on how to optimally take, store, and analyse samples at scale are also ongoing.

Potential for self-testing

Luabeya says healthcare workers find it easier and less time-consuming to collect oral swabs compared to sputum, especially in patients who struggle to provide sputum. One potential advantage of tongue swabs is that people can do the swabbing themselves, thus reducing the potential exposure of healthcare workers even further.

“We have trained patients and provided videos to demonstrate how to collect the sample. They find it easy. Healthcare workers were also trained and could perform the sample collection without difficulty,” says Luabeya.

Theron echoes this. “As tongue swab collection is a non-invasive procedure, it is easy to collect and poses no to minimal risks to patients. Anyone can have it done. This is especially useful in children, people living with HIV, and those at the early stages of the disease who are diagnostically more challenging and often cannot produce sputum,” he says.

“Self-collection of the tongue swabs is already underway in our clinical studies,” Theron tells Spotlight. “The patients collect the tongue swabs themselves under the supervision of a research nurse or healthcare worker. The nurse or healthcare workers will demonstrate and explain to the patient how the collection is done prior to sampling. Minimal training is required, and a video is also made available on the collection procedure. Overall, the patients have been receptive to the procedure and no problems have been anticipated,” says Theron.

Professor and pulmonologist, Keertan Dheda at Groote Schuur Hospital. PHOTO: Supplied
Professor and pulmonologist, Keertan Dheda at Groote Schuur Hospital. PHOTO: Supplied

Promising method

“The results from the tongue swab studies are very encouraging,” says Professor Keertan Dheda, a general physician, pulmonologist, and critical care specialist who heads up the Division of Pulmonology at Groote Schuur Hospital and the University of Cape Town.

“In individuals who could produce sputum, swabbing the tongue had almost the same diagnostic yield as detecting DNA in the sputum using the conventional PCR test that is being used throughout South Africa (Gene Xpert). Patients with TB may not always be able to produce good quality sputum samples [and] often instructions on how to produce sputum are not made clear to patients. Using a simple swab on the tongue would be much more convenient for patients,” he says.

Other advantages, Dheda says, would include creating a safer environment for healthcare workers, who already have high rates of TB infection.

“However, although these preliminary studies are encouraging, we need larger studies in different settings to confirm these findings, and also to see whether the tongue swabbing method would work on an automated detection platform. The major unanswered question is whether the yield of the tongue swabbing method would be as good as conventional methods in people who have smear-negative TB (low concentration of TB bugs in the sputum) and in individuals who are sputum-scarce (unable to produce adequate quantities of sputum),” he says.

He also points out that tongue swabs will specifically have to be studied in children and in people living with HIV – both groups in which sputum sampling is challenging. It will also be important to establish whether one could determine drug resistance from samples taken with tongue swabs, as is the case with sputum samples.