Diagnosis of drug-resistant tuberculosis: reliability and rapidity of detection

Abstract

With the emergence of multidrug-resistant tuberculosis (MDR-TB), the need for rapid drug susceptibility testing (DST) is felt globally. National tuberculosis control programmes (NTPs) may find it hard to choose from the bewildering variety of rapid tests. We give an overview of the most important methods, discussing their merits and shortcomings, emphasising techniques that offer an alternative to the commercial systems and genotypic tests. Correlation between phenotypic and genotypic DST remains problematic due to our insufficient knowledge of the mutations underlying drug resistance, besides the past standardisation of phenotypic DST. Rapid growth-based DST tends to be less accurate due to growth retardation of some resistant strains. To arrive at optimal resistance monitoring and management of MDR-TB without overloading the laboratories, the test indications and definition of a suspect need careful consideration, while excellent microscopy remains crucial but challenging. The hitherto little-studied fluorescein diacetate vital staining technique may offer the solution, reconciling earlier detection and appropriate pre-selection for rapid DST. For the choice of methods, appropriateness and sustainability should be considered in conjunction with the prospects for complete population coverage. Excellent coverage will only be feasible through decentralisation of simple, low-requirement methods or alternatively by centralised genotypic DST with, in principle, easy specimen referral. The small differences in DST turnover time are relatively unimportant, provided primary culture isolation is not required. No test is fully accurate, and proper pre-selection may allow the use of less accurate but simple screening methods. Conventional slow DST will still be needed for confirmation and for epidemiological monitoring.