Moving An Exciting New TB Diagnostic from Policy to Practice

by Javid Syed

On December 8, 2010 the World Health Organization (WHO) endorsed the use of the new Xpert® MTB/RIF test as the initial test offered to people suspected of having HIV-associated TB or multidrug-resistant (MDR) TB. The test, developed by Cepheid Inc., Foundation for Innovative and New Diagnostics (FIND), and University of Dentistry and Medicine New Jersey (UNDMJ), is highly accurate and can diagnose TB and MDR-TB in two hours. It represents a major advance over microscopy, which has been the primary method of diagnosing TB for the last 125 years. In 2010, by using microscopy, the world was only able to detect 63% of TB cases. The rate of MDR-TB case detection was far worse: an abysmally low 12%[1]. The WHO has also recommended that the Xpert MTB/RIF might be used as a follow up test to microscopy where TB/HIV and MDR-TB are less prevalent. Through these bold recommendations, the WHO has initiated a change in TB diagnostics that–if fully implemented–can address some of the major challenges in the care of TB, which is the leading cause of death among people with HIV globally.

The Xpert MTB/RIF is a fully automated nucleic acid amplification test that can accurately identify 92% of patients with TB while the commonly used sputum smear microscopy test routinely misses nearly 50% of TB cases. The Xpert MTB/RIF is also able to identify 72.5% of those TB cases that the smear test is unable to diagnose because there are too few bacteria in the sputum sample, a condition called smear-negative TB, which is more common in people with HIV. To detect smear-negative TB, the TB has be grown or cultured over four weeks in a laboratory equipped with special safety equipment and skilled staff, making culture relatively inaccessible and time consuming. Besides the advantage of accuracy and speed over currently available smear and culture tests, the Xpert MTB/RIF also detects 98% of rifampicin resistant TB cases within 2 hours[2]. In addition, because it is fully automated and does not need a special laboratory equipped with protective gear or highly trained staff, this test can potentially be used in district level health centers, bringing it closer to where patients access services.

Despite the significant improvements the test offers over current TB diagnostics, the path to the scale up of Xpert MTB/RIF still faces challenges. The biggest barriers to the roll out of the test are cost, its need for uninterrupted power supply and annual calibration to ensure its accuracy.  FIND has negotiated a price that is 70% lower than the commercial price for the public sector in low- and middle-income countries, but the machine and accompanying test cartridge are still expensive at $17,000 and nearly $17, respectively. Although modeling studies suggest the test is cost-effective at these prices, there is need to continue advocacy to further drive down the cost and ensure that funds are available to support its roll out. FIND and Cepheid are developing methods of training laboratory staff to enable them to do the annual calibration, thereby keeping these auxiliary expenses low. The need for uninterrupted power cannot be circumvented, and this will place some limits on where the test can be used.

These limitations not withstanding, if rolled out as widely as possible the test can significantly increase TB case detection rates (especially smear-negative and MDR-TB) and thereby pave the way to greatly reducing death and disease.  For this reason the test has generated a lot of excitement in the public health community. The momentum it has generated can be judged by the reaction of the WHO, which moved Xpert MTB/RIF with uncharacteristic efficiency through its approval process (from examining data at its expert committee to recommending the use of the test within three months). In response to the WHO announcement, for the first time in history the three leading US government agencies that contribute to global TB control — U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), U.S. Agency for International Development, and U.S. Department of Health and Human Services—put out a joint statement in support of the urgent need to make the test available.  TAG also contributed by pushing for bold recommendations at the WHO expert committee meetings and global consultations, putting out our own press release, and holding a conference call with the test developers along with other advocates—all aimed at reducing the test cost and facilitating access to Xpert MTB/RIF for those most at risk of disease or death due to TB.

In addition to these developments at the global level, there has been swift uptake at the national level as well. By March 2011, 17 countries had placed firm orders for the test and India and South Africa, among others, have ambitious plans for making it widely available. There remains a need for the WHO’s Global Laboratory Initiative, FIND, and Cepheid to work with national partners implementing Xpert MTB/RIF to ensure that funds are used efficiently and minimize overlap of efforts. Part of this coordination should include gathering evidence to show the impact the test, not just on diagnosis but on treatment outcomes as well. It will be important to find out how far the test can be decentralized in order to make it as accessible to TB patients as possible. All this evidence will strengthen advocacy to expedite global access—advocacy that in turn will lead to price reductions as the volume of the tests being used increases. Only through such coordinated efforts and continued advocacy can we ensure that Xpert MTB/RIF will lead to the ultimate goal of increasing access to appropriate TB care, ultimately preventing illness and saving lives.