A newly discovered way of testing people for tuberculosis (TB) dramatically cuts the time it takes for a diagnosis to under an hour. The development by chemist Jianghong Rao of Stanford and microbiologist Jeffrey Cirillo of Texas A&M Health Science Center could not only make TB diagnosis faster, but prevent new infections by confirming someone has it before they are contagious. All that for a test that will cost roughly $5.
Initial human trial results are in, showing that the new diagnostic test has an 86% sensitivity, far better than the 50% to 60% sensitivity for the commonly used smear microscopy method. The findings were published earlier this month in the journal Angewandte Chemie. The results come from a test of 50 sputum samples. The test was able to detect 80% of samples that contained Mycobacterium tuberculosis that were not detected by a microscope. It is a major improvement over traditional methods.
The innovation is in the discovery of a unique enzyme present in TB. A substance developed by Rao and Cirillo reacts with the enzyme create a fluorescent hue that can be read by a battery-powered device. Efforts are underway to develop a paper-based test, making it easier for the test to be used.
The WHO issued its endorsement of the Xpert MTB/RIF test for TB. The device under went rigorous testing to show that it is far and away the best way to determine whether or not a person has TB. More than three years later, the device has rolled out to more than 88 countries who are eligible for concessional pricing. Despite its significant advance, the Xpert is still expensive, making it unavailable in every part of high TB-burden countries. This new test seeks to fill the gap.
“This will probably be used as a triage test prior to GeneXpert,” said Cirillo to Humanosphere.
Current testing methods require 10,000 bacteria in a sputum sample to detect TB. The problem is that it can take up to six months to reach the point where there is enough bacteria, which is generally after a person starts transmitting the infection to others. The new test can detect as little as 10 bacteria, says Cirillo. Symptoms start showing up after two months of infection.
“Transmission is thought to occur 3 to 4 months after infection,” explained Cirillo. “This could probably help prevent the spread of TB.”
The potential impact is significant. A triaging strategy of TB testing reduces diagnostic costs by more than 30% in Uganda, India and South Africa, found a study published in December. As a result, the money saved could help countries to afford buy Xpert machines for more precise testing.
“The affordability gain of a triage test with high sensitivity and modest specificity is particularly large with enhanced case finding,” said the study authors.
The motivation for creating a new test was fueled by a disappointment at what was already available. Most notable was the need to modify the TB in current tests. Cirillo says he wanted to develop something that was simple and did not require a modification. Discovering the enzyme opened the door for a new way.
“It turned out that this enzyme in TB is unique, that allows us to develop a substrate that is for it,” said Cirillo.
Some changes have made the test improve in its ability to detect the TB. There is still more work to be done. All of the research is being done in discussion with the WHO, TB Alliance, Doctors Without Borders and other partners. Cirillo hopes that doing so will help to speed up the process so that the new test is under use in as soon as 18 months. Before that, the test will have to withstand the conditions of the real world, not a well ordered and sterile laboratory.
“The conditions for TB are so diverse,” said Cirillo. “I expect there to be some challenges with temperature, implementation and even dust!”