title: New and improved diagnostics for detection of drug-resistant pulmonary tuberculosis.
abstract: OBJECTIVE
  Tuberculosis (TB) remains a global emergency and continues to kill 1.7 million people globally each year. Drug-resistant TB is now well established throughout the world and most TB patients are not being screened for drug resistance due to lack of laboratory resources and rapid accurate point-of-care tests. Accurate and rapid diagnosis of TB and drug-resistant TB is of paramount importance in establishing appropriate clinical management and infection control measures. During the past decade, there have been significant advances in diagnostic technologies for TB and drug-resistant TB. The purpose of this article is to review the current data, recommendations and evidence base for these tests.
  
  
  RESULTS
  Second-line drug susceptibility testing (DST) is complex and expensive. Automated liquid culture systems and molecular line probe assays are recommended by the WHO as the current 'gold standard' for first-line DST. Liquid culture DST for aminoglycosides, polypeptides and fluoroquinolones has been shown to have relatively good reliability and reproducibility for diagnosis of extensively drug-resistant TB; however, DST for other second-line drugs (ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, clofazimine, amoxicillin-clavulanate, clarithromycin, linezolid) is not recommended. Automated liquid culture systems are currently recommended by the WHO as the 'gold standard' for second-line DST.
  
  
  CONCLUSIONS
  In this review, we describe the phenotypic and genotypic methods currently available for the diagnosis of TB and drug-resistant forms of Mycobacterium tuberculosis and discuss future prospects for TB diagnostics. Current technologies for the detection of drug resistant M. tuberculosis vary greatly in terms of turnaround time, cost and complexity. Ultimately, the 'holy grail' diagnostic for TB must fulfil all technical specifications for a good point-of-care test, screen for drug resistance concurrently and be adaptable to the various health system levels and to countries with diverse economic status and TB burden.
authors.affiliation: Department of Infection, University College London Medical School, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London, UK. j.ogrady@ucl.ac.uk
authors.forename: Justin
authors.initials: J
authors.lastname: O'Grady
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.forename: Nathan
authors.initials: N
authors.lastname: Kapata
authors.forename: Matthew
authors.initials: M
authors.lastname: Bates
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D003955:Diagnostic Tests, Routine / Q000379:methods* / Q000639:trends*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics; D010641:Phenotype; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents