Global Tuberculosis Report -- 2012.pdf

FIGURE 8.1 The development pipeline for new TB diagnostics, July 2012Liquid culture and DSTRapid speciationLPA for MDR-TBNon-commercial culture and DST(MODS, NRA, CRI)LPA for XDR-TBLPA for MDR-TB 2nd generation10–40Distance from patientsREFERENCE LEVELNew SS+ case definition Xpert MTB/RIF2-specimen approachesLED microscopySame-day diagnosisManual NAATRapid colorimetric DSTXpert 2ndgeneration70Access after 5 years (%)INTERMEDIATE LEVELVOC detectionEnzymatic detectionAg and Ab detectionNAAT 2nd generationPERIPHERAL LEVEL952007 2008 2009 2010 2011 2012 2013 2014 2015 2016Technologies or methods endorsed by WHOTechnologies at feasability stageTechnologies commercialized, not yet endorsed by WHOTechnologies at early stages of developmentAbbreviations: DST Drug susceptibility test; NAAT Nucleic acid amplifi cation test; LTBI Latent TB infection; Ag Antigen; Ab Antibody; MODS Microscopic observation drugsusceptibility;NRA Nitrate reductase assay; CRI Colorimetric redox indicator assay; LED Light-emitting diode; LPA Line probe assay; VOC Volatile organic compound.several other national, bilateral and multilateral agencies,private companies and philanthropic organizations. Tohighlight the need for and catalyse further efforts in TBresearch, a roadmap outlining critical priority areas forfuture scientific investment across the research spectrumwas published in 2011. 1In 2011, a chapter on the latest status of progress in TBresearch and development was introduced in the series ofWHO global reports on TB for the first time. In this 2012report, the status of progress as of July 2012 is summarized,drawing primarily on information provided by thesecretariats of the relevant working groups of the Stop TBPartnership.8.1 New diagnostics for TBSputum-smear microscopy – the most commonly useddiagnostic test for TB – is more than 100 years old. Thistest is relatively insensitive and it cannot be used to identifypaucibacillary or extrapulmonary TB. Diagnosisusing culture methods – the current reference standard– requires laboratory infrastructure that is not widelyavailable in countries with a high burden of TB (Chapter6), and results are only available after a few weeks. Con-1An international roadmap for tuberculosis research. Geneva, WorldHealth Organization, 2011 (also available at:www.stoptb.org/assets/documents/resources/publications/technical/tbresearchroadmap.pdf;accessed July 2012).ventional methods used to diagnose multidrug-resistantTB (MDR-TB) also rely on culturing of specimens followedby drug susceptibility testing (DST); results takeweeks to obtain and not all laboratories with the capacityto perform DST of first-line drugs have the capability toperform DST of second-line drugs.The status of the pipeline for new TB diagnostics inJuly 2012 is shown in Figure 8.1. After decades of stagnation,accelerated development of new TB diagnostics inthe past decade presents real hope that rapid diagnosisof TB and MDR-TB can become a reality, thus removinglongstanding barriers to TB care and control.In the past 5 years, WHO has endorsed several newtests and diagnostic approaches. These include:● liquid culture with rapid speciation as the referencestandards for bacteriological confirmation;● molecular line probe assays for rapid detection ofMDR-TB;● non-commercial culture and DST methods;● light-emitting diode fluorescence microscopes forimproved smear microscopy; and● Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) forthe rapid diagnosis of TB and rifampicin-resistant TB.Following WHO’s endorsement of Xpert MTB/RIF inDecember 2010, research on its use has proliferated. ByJuly 2012, more than 65 peer-reviewed publications hadbeen published, covering the full spectrum of researchand confirming initial findings on the test’s performance.GLOBAL TUBERCULOSIS REPORT 2012 83