TAG 2010 Pipeline Report
Ten years later, the low-hanging fruit has yielded a small but flavorful harvest. Many advanced technologies are now ready to launch or are in place in central reference laboratories and in some referral laboratories in tertiary (usually major city hospital) settings. Both “rapid� (2–4 week) liquid culture techniques and nucleic acid amplification tests (which detect Mycobacterium tuberculosis, or MTB, DNA sequences) are available if the proper financial and technical support is provided. However, there has as yet been no breakthrough diagnostic test to revolutionize TB diagnostics in peripheral health post or community point-of-care settings. These peripheral health post settings are the most decentralized health care facilities that have inconsistent access to running water, electricity, trained laboratory workers, or any laboratory equipment and yet provide care for the largest number of people with TB. To date, TB is most commonly diagnosed with a 125-year-old sputum-smear microscopy test despite the fact that it has low sensitivity, is unable to diagnose TB disease if the bacterial load in the sputum is low (smear-negative TB), is unable to diagnose TB that is not in the lungs (extrapulmonary TB), can pick up acidfast bacilli that are not TB, and cannot distinguish between drug-sensitive and drug-resistant TB. FIND estimates that only about 20% of TB cases worldwide are detected with sputum-smear microscopy (World Health Organization 2006). The failure of the most common diagnostic test to pick up more than half of TB cases, and the lack of facilities, meant that in 2008 only 61% of all forms of TB (smear-negative, smear-positive, and extrapulmonary) were reported by national TB programs to the World Health Organization (World Health Organization 2009b). Where programs do not exist no one will receive care, and even when programs do exist, if they rely on sputum-smear microscopy they will miss half the cases overall and much more among children and people with HIV who have higher levels of smear-negative and extrapulmonary TB. Cultivating the TB bacillus on solid or liquid growth media, or TB culture, is still considered the gold standard for diagnosis. Though the culture method is very sensitive, it too can be nonspecific, as nontuberculous mycobacteria will also be detected in culture, and subsequent speciation tests using a lateral flow (dipstick) TB antibody test such as the Tauns test are required to definitively identify the growing organisms as MTB. Culture does detect smear-negative and drugresistant strains, and can even detect extrapulmonary TB if the right sample is drawn, but it is still far from ideal as it takes an average of up to two weeks to become detectable with rapid liquid culture and four weeks to grow to visible levels on solid media (Dorman 2010). Culture also requires skilled laboratory staff, electricity, and biosafety infrastructure in order to be performed safely and accurately. TB culture testing is not available or accessible for most people with TB who live in low-income countries and access care at health posts. To address these challenges, from 2007 to 2009, the Strategic and Technical Advisory Group for TB (STAG-TB), the group that advises the World Health Organization 108