Blood Test Predicts Future Disease in TB Patient Contacts -Results identified those at greatest risk to develop active TB

A whole blood test accurately predicted progression to tuberculosis in close contacts of TB patients up to two years before the disease was clinically evident, according to the international research consortium that developed the molecular test.

People living with tuberculosis patients are at risk for becoming infected with Mycobacterium tuberculosis, but only a small percentage (5% to 10%) will develop active disease. There is currently no highly accurate blood test to predict which infected close contacts of patients will develop clinical TB.

Identifying asymptomatic individuals at high risk to progressing to active TB following exposure to TB patients living in the same household would help to prioritize preventive treatments and lead to better TB control, noted senior author Gerhard Walzl, of Tygerberg, South Africa's Stellenbosch University Immunology Research Group, and colleagues.
 

TB

In their study, published online ahead of print April 6 in the American Journal of Respiratory and Critical Care Medicine, Walzl and colleagues reported findings from a study conducted to examine the efficacy of their predictive blood test in multiple populations of HIV-negative people living in sub-Saharan Africa.

The polymerase chain reaction (PCR) test analyzes a four-gene transcript signature associated with inflammatory response, known as RISK4.

Walzl and colleagues included 4,466 HIV-negative, healthy participants living with 1,098 TB patients in South Africa, Gambia and Ethiopia. Blood samples were taken and stored from all study participants.

Follow-up included 79 participants who progressed to active TB 3 to 24 months following exposure and 328 who remained healthy during the two years of follow-up.

The four-transcript RISK4 signature predicted progression up to two years before onset of disease in blinded test samples from all three countries with little population-associated variability. The test was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection.

Area under the receiver-operating characteristic curve ranged from 0.59 to 0.86, depending on the specific patient cohort and analytical algorithm employed. While far from perfect, the results suggested such an approach could at least identify individuals who could benefit from close monitoring.

In contrast, previously published diagnostic or prognostic tuberculosis signatures were predictive on samples from some, but not all three, countries, the researchers wrote.

Post-hoc meta-analysis identified a single gene pair -- C1QC/TRAV27 -- that consistently predicted TB progression in household contacts from multiple sites, but was not predictive in adolescents without recent exposure events.

"Our study identifies and validates a simple PCR-based test from accessible blood samples that predicts TB in heterogeneous African populations with intermediate to high TB burdens," the researchers wrote. "Such a test can potentially be developed into a screening test for risk of progression during TB contact investigation, implemented by national public health structures."

The next step, the researchers noted, involves assessment of the performance of RISK4 and the 2-transcript C1QC/TRAV27 signature in other settings, including non-African populations.

They also hope to further research the feasibility of developing a near-patient test for targeted intervention.

Walzl and colleagues noted that while there are already tests on the market that predict progression to TB, they are not specific to high-risk household contacts.

Study limitations included the relatively small sample size (100 of the 4,466 participants progressed to active TB), and the fact that the sample was limited to just three countries. Samples from Uganda were initially included in the study design, but they were not available in large enough quantities to be included in the analysis.

It is also not yet clear if the test is easily reproducible in clinically meaningful settings, the researcher wrote.

"Encouragingly, recent advances in point-of-care PCR technologies offer promise for developing rapid diagnostics," they wrote. "We envision platforms where blood from a finger prick can be translated through field-friendly, handheld PCR instruments to interpret able scores. Field staff would then triage near-patient contacts into low-risk and higher-risk groups for further assessment and potential treatment for subclinical or active TB disease."

Source : www.medpagetoday.com      2018/4/8 13:19

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