Dilemma in TB diagnostic testing; phenotypic or genotypic testing

International Journal of Mycobacteriology

H O S T E D BY

4 (2015) 74

Available at www.sciencedirect.com

ScienceDirect journal homepage: www.elsevier.com/locate/IJMYCO

Dilemma in TB diagnostic testing; phenotypic or genotypic testing Salman H. Siddiqi Sparks, MD, USA

A R T I C L E I N F O

A B S T R A C T

Article history:

Testing for tuberculosis (TB) is difficult because there are so many tests available. Except for

Received 26 November 2014

the culture-based tests, all others are for screening or add-on tests. On the other hand,

Accepted 30 November 2014

there is an urgent need to develop a rapid TB diagnostic test with good sensitivity and spec-

Available online 7 January 2015

ificity.

Keywords:

MGIT was a great improvement in a definitive diagnosis, but still results are not as fast

Tuberculosis

as needed. After the discovery of IS6110 sequence and the whole genome sequence of Myco-

Phenotypic

bacterium tuberculosis (MTB) many rapid diagnostic tests have been developed based on the

Genotypic testing

molecular platform. This brought hope that these molecular tests will be the answer to the

The introduction of liquid culture medium in 1980 (BACTEC 460 radiometric) and later

need for an ideal rapid test for diagnosis and drug susceptibility testing (DST). Among these notable molecular tests are Hain’s LPA and Cepheid’s GeneXpert–GeneXpert being the leading one. Time to results for detection and DST, which used to take 6–8 weeks with solid media, was reduced to 4 weeks by the BACTEC method and now to 2 h by the GeneXpert. Despite significant improvement in the time to report, molecular-based tests still face many challenges. Sensitivity and specificity of a diagnostic test is critical in infectious diseases. For molecular tests lack of sensitivity in smear-negative TB cases is a great concern. In case of DST it is important to have a test which can detect resistance to first-line and most of the second-line drugs with high sensitivity and specificity. At present the genotypic tests are applicable for only a few drugs, while GeneXpert detects only Rifampicin resistance. Because of these limitations, genotypic tests are considered as good screening tests. Until the molecular tests are made more sensitive for the detection of TB and more knowledge is acquired on molecular mechanisms of drug resistance, these tests will remain as screening tools. Sustainability is another issue. Presently, funding agencies are supporting the high cost of the genotypic tests, but what if these funds dry out? This overall situation has created a dilemma of what should be the right option in choosing a TB diagnostic test. Efforts are being made to improve the sensitivity and specificity of molecular tests. Until then, it appears that phenotypic tests, especially using liquid medium, still remain as the only one offering a comprehensive solution in TB diagnosis and DST. There is still a need for a diagnostic test which is simple, rapid and affordable for the low-income, high-TB prevalence countries, and as comprehensive, sensitive and specific as the liquid culture for TB diagnosis and DST. Ó 2015 Published by Elsevier Ltd. on behalf of Asian-African Society for Mycobacteriology.

http://dx.doi.org/10.1016/j.ijmyco.2014.11.022 2212-5531/Ó 2015 Published by Elsevier Ltd. on behalf of Asian-African Society for Mycobacteriology.