Two new studies on TB diagnostics tests

Global and Indian data

TDR news item
9 August 2011

Two new studies on tuberculosis (TB) blood tests published in PLoS Medicine provide some of the data and methodology utilized for the recent World Health Organization (WHO) policy statement recommending against the use of serology (blood) tests for TB. The studies were supported by TDR and WHO's New Diagnostics Working Group.

Undiagnosed and misdiagnosed tuberculosis drives the tuberculosis epidemic by increasing the transmission of this disease spread by cough or sneeze, infecting the lungs.

Unfortunately, sputum smear microscopy, the current mainstay of tuberculosis diagnosis worldwide, detects only half of tuberculosis cases, mycobacterial culture can take weeks to provide a diagnosis, and rapid techniques such as nucleic acid amplification require infrastructure that is often not available in developing countries. Consequently, in India and other developing countries, serological tests are widely used for the diagnosis of tuberculosis. These blood tests detect antibodies against M. tuberculosis in the blood (antibodies are proteins made by the immune system in response to infections).

Although these tests have not been recommended by WHO, they are widely available in high-burden TB countries like India, where every year about 2 million people develop the disease – a fifth of the global incidence of this highly contagious bacterial infection. It is conservatively estimated that over 1.5 million serological tests for tuberculosis are conducted every year in India at a cost of more than US $15 million.

One of the PLoS articles provides an updated systematic review and meta-analysis on commercial blood tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis. It shows that these tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity.

The other study on sputum smear microscopy used in India shows that this method remains the most cost-effective diagnostic test available for active TB, and efforts to increase access to quality-assured microscopy should take priority. This study modelled the cost and effectiveness of blood testing for active TB in India and compared this with the cost and effectiveness of other diagnostics for TB. Although sputum smear microscopy misses 50% of cases and is often performed under suboptimal laboratory conditions, it remains the most cost-effective initial diagnostic test for active TB. The authors recognize the need to address the poor sensitivity of smear microscopy. Their study indicates that in areas where quality-assured smear microscopy is already available and where adequate resources exist, liquid TB culture is a more effective and less costly addition to smear microscopy than serological testing. It was estimated that for every new case of smear-negative TB diagnosed correctly by serological testing, 6 patients without TB would be incorrectly diagnosed with TB. The costs to patients and the health care sector are considerable.

The research has led to WHO issuing a policy statement advising against the use of these tests, which an editorial in PLoS Medicine calls for now being implemented in India.

For more information, contact Dr Andy Ramsay