TB Serology: A boon or BAN?

Tuberculosis (TB) remains a major global healthcare issue with around 1.7 million deaths in 2009 due to TB and rising absolute number of cases each year due to the increasing global population, the emergence of drug resistance, and the detrimental effects of HIV coinfection.

The diagnosis of active TB is traditionally made using direct identification of the bacillus by smear microscopy or subsequent culture of Mycobacterium tuberculosis (M Tb). This requires appropriate specimens to examine, and time for the bacillus to grow. This can cause considerable difficulty if the infection is non-pulmonary, or if the patient does not expectorate sputum. Thus, invasive tests like surgical biopsy or bronchoscopy may have to be resorted to. Unlike in many other infections, culture of M Tb may be prolonged or difficult, hence numerous kits for the detection of antibodies to the pathogen have been marketed, as a means for rapid identification.


Serological testing can detect various classes of antibodies to the infective pathogen in the patients' serum (IgG, IgM, IgA). These antibodies are produced in response to antigenic substances or proteins on the surface of the bacterium.

Pulmonary Tuberculosis

Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI). They are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis. IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used for diagnosis of active TB, which is a microbiological diagnosis. Clinical evaluation and additional tests (such as a chest radiograph, sputum smear, and culture) are needed to differentiate between a diagnosis of latent TB or active TB.
A positive IGRA result may not necessarily indicate active TB, and a negative IGRA result may not rule out active TB.

Because IGRAs are not affected by Bacille Calmette-Guérin (BCG) vaccination status, IGRAs are useful for evaluation of LTBI in BCG-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple (booster) BCG vaccinations are given.

QuantiFERON GOLD or TB-Gold also known as QFT-G is an interferon-γ release assay (IGRA) used in tuberculosis diagnosis. For QFT-G, the antigens include mixtures of synthetic peptides representing two M. tuberculosis proteins, ESAT-6 and CFP-10.


Findings from several systematic reviews and an independent evaluation of rapid tests suggest that serological tests for both pulmonary and extra- pulmonary TB are inaccurate. No test performs well enough to replace smear microscopy. Currently available commercial serological TB tests appear to do more harm than good because of the harm caused to patients through false-positive or false-negative tests results. Furthermore, these tests prove to be an economic burden to the country as well.

Echoing these concerns, in a recent editorial Singh and Katoch wrote, ‘Unfortunately, unethical medical practices provided major boost to these kits in recent years, without bothering much on quality of tests and implications of false-positive and false negative results...

In July 2011, WHO issued a policy stating that commercial serological tests provide inconsistent and imprecise estimates of sensitivity and specificity. There is no evidence that existing commercial serological assays improve patient outcomes, and high proportions of false-positive and false-negative results adversely impact patient safety. Overall data quality was graded as very low, with harms/risks far outweighing any potential benefits. It is, therefore, recommended that these tests should not be used in individuals suspected of active pulmonary or extra- pulmonary TB, irrespective of their HIV status.
Immediately following the WHO policy, the RNTCP published an advisory statement against the use of TB serological tests in India. More recently, an expert committee convened by the Drug Controller General of India has recommended a ban on import and sale of TB serological tests in India and this ban has been endorsed by the Indian health ministry.

Thus, the void in the diagnostics of tuberculosis which was to be filled up by these serology tests, has still remained a void. We hope that scientific research comes up soon with more reliable aids in the diagnosis of TB.