Sputum smear negative TB: validity of complementary laboratory tests and effectiveness of alternative diagnostic strategies.

There is evidently an urgent need for TB diagnostic tests which are cost-effective, simple enough to be used under limited resource settings and allowing sensitive, specific and timely detection of TB cases. Recently, WHO recommends the use of culture techniques in liquid medium (WHO 2008). The Mycobacteria Growth Indicator Tube (MGIT, Becton Dickinson, Sparks, MD, USA) culture technique has some advantages, but its relatively high contamination rate and its considerable cost raises questions with regard to its appropriateness for routine programme use in developing countries (Apers et al., 2003). Thin Layer Agar (TLA) - an easily implemented technique of culturing and identifying mycobacteriae that does not require special laboratory equipment - has recently been shown to provide rapid results with have at least the same sensitivity in detecting Mycobacterium tuberculosis as conventional culture methods (Robledo et al., 2006). Those rapid culture methods and PCR tests have however never been tested under real programme conditions in resource poor settings with high TB incidence. This study wants to evaluate which of the above tests, MGIT, TLA or PCR is the most accurate, rapid and economic alternative diagnostic method for TB detection in resource-constrained settings.
The specific objectives of this study are to
(1) Validate the accuracy of TLA, MGIT and Automated-PCR for TB diagnosis against results in conventional culture using Löwenstein-Jensen medium as the gold standard
(2) Determine the impact of the use of TLA or MGIT or automated-PCR on the rate of TB detection in a population with high TB incidence
(3) Evaluate the acceptability and costs of employing those tests under routine programme condition in a high burden setting.