Abstract
Tuberculosis (TB) remains the leading cause of death from a curable infectious disease1 , despite the availability of short-course therapy that can be both inexpensive and effective.
Clinical management of cases in developing countries is hampered by the lack of a simple and effective diagnostic test. Correct diagnosis of TB is needed to improve treatment, reduce transmission, and control development of drug resistance.
In patients with active pulmonary TB, only an estimated 45% of infections are detected by sputum microscopy2 . This test, first developed in the 1880s and basically unchanged today, has the advantage of being simple, but is hampered by very low sensitivity: it may only detect half of all cases with active infection. It is also very dependent on the skill of the technician, and a single technician can only process a relatively small number of slides per day3 . Furthermore, a staggering three million people who present annually with suspected TB may not be properly diagnosed, because their infection (so-called smear-negative disease) cannot be detected by sputum microscopy4 .
There are specific epidemiological factors that present additional challenges to TB diagnosis. HIV infection is thought to be a major contributor to the increase in TB incidence across the world2 . An estimated 9% of adults globally with newly diagnosed TB are HIV positive, but this rate is 31% in Africa5 . HIV co-infection with TB presents challenges to effective diagnosis of TB and diagnosis can also be more difficult in children.
The rapid rise of drug-resistant (DR) TB has further complicated TB diagnosis6 . Tests that measure drug susceptibility are essential to monitor the spread of resistant TB strains, and ensure that patients are given effective treatment. The recent cluster of so-called extensively drug resistant (XDR) TB cases in South Africa were untreatable by any available drugs, and had a devastating mortality rate: 52 of 53 patients died7 .
New diagnostic tests that are simple and robust enough to be used in the field, accurate enough to diagnose all infected individuals, and able to identify drug resistance are desperately needed, and represent an essential complement to new drug development efforts and to effective control and treatment programmes.
