- New blood test that measures levels
of expression of combination of four-genes can predict development of
tuberculosis two years before onset in contacts who are at high risk
- Currently there is no test that can
predict development of TB without putting large numbers of people who are
at low risk to undergo unnecessary preventive anti-tuberculous treatment.
A newly developed blood test has been
shown to more accurately predict the development of tuberculosis in persons
living in close contact with someone suffering from active TB, according to
research that appears online in the American Journal of Respiratory and
Critical Care Medicine, an American Thoracic Society journal.
Although those living with someone having
active TB infection are at greatest risk for developing the disease, only about 5-20 percent of people exposed
to tuberculosis infection
go on to develop active TB.
Currently there is no test that can
distinguish between low risk and high risk (of developing disease) contacts exposed
to active TB infection.
‘The four gene combination blood test overcomes the need for healthy contacts to undergo unnecessary TB preventive treatment with possibility of serious side effects
Levels of four-gene signature combination blood test
identify persons at
risk upto two years before onset
disease, overcoming the need for persons at low risk to go through preventive
anti-tuberculous therapy with known side effects.
"We found that this prediction [up
to two years before the onset of the disease] is possible through measurements
of a combination of a four-gene signature in the blood," said Professor
Gerhard Walzl, MMed, PhD, lead study author and leader of the Stellenbosch
University Immunology Research Group, Tygerberg, South Africa.
The Four Gene Combination Blood Test
- The research team developed and
validated a blood test that measures the expression levels of four genes
to precisely predict the development of TB in high-risk contacts in
- The "four gene combination or
signature", referred to as 'RISK4,' was found to be present in all
participants included in the study drawn from South Africa, Gambia and
Ethiopia." The RISK4 combination of four genes has been associated
with inflammatory responses.
- The scientists used a training-test
set approach described below to ensure quality control.
- The sample data was divided blindly
into two parts namely a discovery (training) set on which the signature
was developed; the developed signature was then tested on the remaining
samples (test set).
- Initially persons from Uganda were
included in the study design but were not tested as they were not
available in large enough quantities to be properly analyzed.
Details of the Study
- The team enrolled 4,466
HIV-negative, healthy participants from households of 1,098 index cases
(patients with active TB, who consented to the scientists enlisting
members of their family who did not have active TB infection).
- Blood samples of all the 4466
participants were collected and stored.
- At the finish of the two year study
period, it was evident that 79 participants had progressed to active
tuberculosis between three to 24 months after exposure.
- Blood test was carried out on the 79
cases of active infection as well as 328 individuals who remained healthy;
the remaining samples were not analyzed due to the high cost of the test.
- The different bio signatures -
(combinations of gene expression or protein measurements that when taken
together reflect current or future risk for developing TB) - were
"The individual components of this
signature may not be sufficient to deliver an accurate diagnosis of prediction,
but a combination of these markers improves
," said Prof. Walzl.
Four Gene Blood Test Versus Other Available Tests
- Although there are tests available
on the market predict risk of progression to TB, the latest test developed by Prof. Walzl and his team is able to
predict development of active TB in a smaller percentage of high risk
household contacts compared to currently available tests. This means fewer
people getting treated unnecessarily to prevent TB.
"Preventative treatment is several
weeks long and has potential side effects," explained Prof. Walzl.
"One wants to limit the number of people who have to undergo such
treatment to those most likely to be at risk for developing active TB."
- According to Prof Walzl, the
efficacy of this test in preventing tuberculosis needs to be further assessed in multicenter trials
and additionally the validity of this test should be assessed in other high risk regions of the world
including Asia and South America.
is a bacterial infection caused by
and is the world's leading cause of death due
to a single pathogen. It spreads from one person to another by inhaling
droplets released into the atmosphere when a person with active TB speaks,
coughs, or sneezes.
More than 10 million new cases of TB are
diagnosed annually, and nearly two million people die due to this disease.
Globally, 1.7 billion people are estimated to have tuberculosis infection
In conclusion it is hoped that sometime
soon tests to measure theRISK4 gene combination will become widely
available for use in primary health centers and small clinics in the developing
world where tuberculosis is still common.
- Tuberculosis (TB) - (https://www.cdc.gov/tb/publications/faqs/qa_introduction.htm)