Tuberculosis Assays: Past, Present and Future

Novel N Chegou; Kim GP Hoek; Magdalena Kriel; Robin M Warren; Thomas C Victor; Gerhard Walzl

Disclosures

Expert Rev Anti Infect Ther. 2011;9(4):457-469. 

In This Article

Abstract and Introduction

Abstract

Recent developments in the field of TB diagnostics, including the introduction of the Xpert MTB/RIF assay in field testing, raise the hope for faster and more accurate identification of active TB patients. However, there are still many issues that need to be addressed as no point-of-care tests are yet available. Furthermore, no tests are available which are universally applicable to all patients. Improvements in the microbiological and molecular-based approaches are promising and the diagnostic pipeline is encouraging. Host markers associated with active disease may hold promise, especially in situations where sputum diagnostics are problematic, including in children, HIV-infected individuals and in the case of extrapulmonary TB.

Introduction

TB remains a pervasive, morbid and lethal disease that thrives on neglect. It has been studied for decades and boasts curative treatment, yet to this day, its spread, associated mortality and burden of suffering impacts patients of all ages and races, on all continents.[1] Despite global attempts at TB control, the worldwide disease incidence rate was 139 per 100,000 population in 2008, with the incidence rate in Africa reaching 350 per 100,000 in the same year. This corresponds with the staggering estimate of 9.4 million incident cases of TB worldwide in 2008. Only 61% of these cases were reported and of the 440,000 estimated total number of multidrug resistant (MDR) cases in 2008, only 11% were notified and treated according to international guidelines.[2] If infectious cases are quickly identified and treated, TB control improves, as patients' infectivity decreases rapidly on appropriate treatment. Indeed, the dynamics of the TB epidemic are greatly determined by how soon cases are diagnosed, impacting the duration of infectiousness.[3]

In line with the objectives of the WHO Stop TB Strategy and the Global Plan to stop TB, TB diagnostics should lead our endeavor to control the epidemic. These two international programs aim for universal access to quality diagnostics and the detection of 84% of global cases by 2015.[2] Furthermore, the updated goals for the new diagnostics component of the Global Plan to Stop TB 2011–2015 include increased diagnosis of active TB at point-of-care level and screening for MDR and extensively drug resistant (XDR) TB.[4]

A recent prospective study in South Africa showed that 17% of 367 TB cases diagnosed on smear results never started treatment owing to incomplete sputum sample collection, problems with sample transport and poor record-keeping of the samples taken and their subsequent results.[5] This illustrates that the key to effectively combat TB remains comprehensive case finding and reporting. It has become clear that a rapid, simple and reliable method of diagnosis at the point of care could mean the end of missed opportunities – lowering the incidence of delayed treatment, nosocomial infections, drug resistance and treatment failure. Figure 1 presents the current pipeline of diagnostic tests.[4] This article addresses the advances and challenges in the search for effective diagnostics.

Figure 1.

10-year diagnostic pipeline. Timeline of diagnostic tests currently endorsed by the WHO, as well as those that are under development and review.
CRI: Colorimetric redox assay; DST: Drug-susceptibility testing; IGRA: IFN-γ release assay; LED: Light-emitting diode; LPA: Line-probe assay; LTBI: Latent TB infection; MDR-TB; Multidrug-resistant TB; MODS: Microscopic observation of drug susceptibility; NAAT: Nucleic acid amplification test; NRA: Nitrate reductase assay; POC: Point of care; SS+: Sputum smear positive; STAG: Strategic and Technical Advisory Group; XDR-TB: Extensively drug-resistant TB.
Figure provided by Richard O'Brien (Foundation for Innovative New Diagnostics). Reproduced with permission from [4].

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