Annually, the World Health Organization (WHO) commemorates March 24 as World Tuberculosis Day in recognition of the continued impact of tuberculosis (TB), a widespread, and in many cases, fatal disease. By their estimate, more than 9 million people worldwide fell ill with TB in 2013 and 1.5 million died.

“The human impact of the disease is very much in our minds right now,” Gerard (Jerry) Cangelosi, an infectious disease researcher at the UW, said on World TB Day 2015. “In our field, numbers mean a lot. And for TB, the numbers are staggering.”

Cangelosi is one of many researchers worldwide working on ways to reduce TB’s health impacts. In collaboration with other researchers at the UW and the South African TB Vaccine Initiative (SATVI), Cangelosi hopes to develop an alternative method to diagnose TB. 

The oral swab PCR (OSP) test aims to directly detect the disease-causing agent rather than the body’s response to it, like in current TB tests.

In OSP, samples taken with a swab from the inside of the cheek is analyzed for the presence of Mycobacterium tuberculosis DNA. This is thought to be indicative of infection.

Currently, TB is generally diagnosed by obtaining and testing sputum, a thick mucus coughed up from the lungs of sick individuals. However, researchers say sputum testing is not optimal for detecting individuals with TB early. Not everybody infected with M. tuberculosis becomes sick. In most cases, the bacteria is latent in infected individuals.

“The only time that transmission takes place is between when the TB becomes active and when it is diagnosed,” Cangelosi said. “If the case-finding can be done earlier in the process, we can more readily prevent transmission and the disease.”

Collecting and testing sputum presents other problems too. Apart from being difficult to work with, obtaining sputum can be potentially hazardous for health workers. The test is also ineffective for young children and individuals whose immune system is compromised.

“[The bacteria is] more [spread out], not focused on the lungs,” he said. “Most of these people can’t even produce sputum and so diagnosing in these populations is very challenging with the current tests.”

So far, the collaborative effort has completed an early step in the process of determining the OSP’s effectiveness as a diagnostic tool for TB in humans. A study published in March 2015 by “Scientific Reports” compared results from OSP in two different groups of people located in different locations. The first consists of 20 individuals enrolled by SATVI which had recently been diagnosed with TB in Worcester, South Africa. 

Twenty individuals who are very unlikely to be TB positive were also enrolled in Seattle. This served as the control group.

The results from the study supported the validity of OSP as a diagnostic tool. While more studies are necessary to develop the testing method, the researchers concluded that OSP shows promise.

“I don’t think this technique that we’ve developed will completely replace sputum testing but it has the potential to help fill in the gaps where sputum testing falls short,” Cangelosi said.

In the mouth of the monkey

Considering the promise of OSP, Lisa Jones-Engel, an adviser on the project and a researcher at the Washington National Primate Research Center, is very surprised it took so long to be rigorously investigated. For her, the concept of OSP is not new. She first stumbled across it during graduate school at the University of New Mexico in 1998.

“Jerry is making it big now but [my colleagues and I have] been at this for a long time,” Jones-Engel said.

Her colleague at the time, Alicia Wilbur, was using OSP in conjunction with two standard TB tests while researching TB’s effects on two indigenous Paraguayan population, the Aché and the Avá. Despite the novelty of OSP as a diagnostic tool, which had yet to be rigorously tested, both Wilbur and Jones-Engel saw potential. 

“It just seemed very logical, especially to us as biological anthropologists,” Jones-Engel said. 

Due to the relative simplicity of OSP, Jones-Engel considered it a better fit for her own work on monkeys in the field than more established diagnostic tests. With Wilbur’s help, she adapted the procedure for use on monkeys.

“I needed an alternative test because of logistical problems,” Jones-Engel said. “You can’t get a sputum sample from monkeys. They don’t spit. And TB skin tests required an amount of time that I simply didn’t have.”

After seeing promising results in the field, Jones-Engel and Wilbur approached scientists that studied TB in humans and non-human primates about OSP. The response was almost universally dismissive. 

“They all said, ‘you’re out of your mind,’” Jones-Engel recalled. “We got horrendous pushback. Partly because, as biological anthropologists, we were outsiders in the field.”

While aware of the need for further experimental study, Jones-Engel was shocked by the strongly negative response to OSP. She believes that an outside perspective can sometimes be beneficial.

“We look at the problem differently and don’t get as bogged down by convention and dogma,” she said. 

Even with Cangelosi, who Jones-Engel met following a talk she gave on OSP, there was an initial period of hesitation. Despite some reservations, Cangelosi found the idea intriguing.

“As a bacteriologist, the concept seemed feasible to me,” Cangelosi said. “Lisa was sampling a biological surface (the inner cheek), and all bacteria like to stick to surfaces. I thought the concept needed a bit more validation in a case-control study, so we set out to do that.”

Future directions

With the encouraging results from this study, more collaborative studies on OSP are in the works. Among them are expansions and variations on the study already conducted to more rigorously test OSP and to specifically test its capabilities in immunocompromised populations.

For now, Jones-Engel is optimistic about the future of OSP in humans.

“Jerry has the TB world credibility behind him and he will be really good at moving the human side of the research forward,” Jones-Engel said.

Reach reporter Kevin Kwong at science@dailyuw.comTwitter: @DKdonkeykwong

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