Simple Blood-Based PCR Test Can Predict Progression to Tuberculosis

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Factors associated with elevated risk for progression to TB include age, sex, HIV, and especially being in recent contact with a patient with active pulmonary TB.
Factors associated with elevated risk for progression to TB include age, sex, HIV, and especially being in recent contact with a patient with active pulmonary TB.

A simple blood-based polymerase chain reaction (PCR) test can predict the risk for infection and progression to active tuberculosis (TB), according to new findings published in the American Journal of Respiratory and Critical Care Medicine.1

Most individuals infected with Mycobacterium tuberculosis will not have progression to active disease during their lifetime, but even so, more than 10 million cases of TB are diagnosed each year.2 Persons who are in direct contact with people with TB are an important target population for preventive measures, as they are at high risk for both infection and development of active disease.

In this study, the authors investigated their hypothesis that gene expression signatures can predict incident TB in recent household contacts of people with active TB. The cohort included 4466 HIV-negative healthy household contacts of 1098 index TB cases, who were enrolled between 2006 and 2010 into the Grand Challenges 6-74 study that was conducted across 4 African sites.

A multisite PCR-based signature of risk (RISK4) was developed and was validated by blind prediction of TB progression in test sets from South Africa, The Gambia, and Ethiopia. The RISK4 signature predicted progression in the entire combined test set (area under the curve =0.67 [0.57-0.77], P =2.6X10-4) and for each individual site. The robustness of RISK4 was then evaluated with blinded predictions performed on samples from an external cohort of individuals, where the time of TB exposure was unknown. RISK4 also significantly predicted risk for TB progression in this population (area under the curve =0.69 [0.62-0.76], P =3.4X10-7).

This type of test “can potentially be developed into a screening test for risk of progression during TB contact investigation, implemented by national public health structures,” wrote the authors.

References

  1. Suliman S, Thompson E, Sutherland J, et al; GC6-74 and ACS cohort study groups. Four-gene pan-African blood signature predicts progression to tuberculosis [published online April 6, 2018]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201711-2340OC
  2. World Health Organization. Global Tuberculosis Report 2017. Published 2017. Accessed May 14, 2018.
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