Diagnostic Capacities for Multidrug-Resistant Tuberculosis in the World Health Organization European Region: Action is Needed by all Member States

Abstract

The World Health Organization (WHO) recently revised its guidelines for rapid diagnosis of drug-resistant tuberculosis (TB). This study aimed to investigate if TB reference diagnostic services are prepared to support these revisions. An online survey was performed among 44 TB National Reference Laboratories (NRLs) in the WHO European Region. Questions addressed the use of WHO-recommended molecular techniques for the diagnosis of drug-resistant TB, the techniques applied to investigate antimicrobial resistance, and questions on quality assurance. Among 35 of 44 (80%) participating NRLs, 29 of 35 (83%) reported using the GeneXpert platform as the initial test to detect Mycobacterium tuberculosis complex and rifampicin resistance. Five laboratories reported using another WHO-recommended, moderate-complexity, automated nucleic acid amplification test for detection of Mycobacterium tuberculosis complex and resistance to rifampicin and isoniazid. Most (32 of 35; 91%) NRLs reported the capacity to test second-line drugs that have been in clinical use for many years (fluoroquinolones, linezolid, and injectable agents). Only 23 of 35 (66%) and 21 of 35 (60%) NRLs reported the capacity to test bedaquiline and clofazimine. Further efforts will be needed to improve the availability of quality-controlled testing against WHO Group A and Group B drugs. Earlier considerations on the scale-up of diagnostic capacities should be enforced as part of future approval processes for new antimycobacterial agents.

Figure 1

Survey questions and responses. ∗Multiple answers possible. ^†Other answers included Becton Dickinson BD Max (n = 2), Hain Lifescience FluoroType (n = 1), Bioneer real-time PCR (Daejeon, Republic of Korea) (n = 1), unspecified real-time PCR (n = 2), BIOCHIP-IMB TB-Test (Moscow, Russia) (n = 1), Sanger sequencing of rpoB and pncA genes (n = 2), targeted next-generation sequencing (n = 1), whole-genome sequencing (n = 2). Three laboratories reported more than one other test. ^‡Other answers included unspecified real-time PCRs (n = 4), BIOCHIP-IMB TB-Test (n = 1), targeted next generation sequencing (n = 1), whole genome sequencing (n = 5); 2 laboratories reported more than one other test. ^§Amikacin, kanamycin, and capreomycin. ^¶Mostly relating to bedaquiline and delamanid. ^||Implementation and interpretation of second-line line probe assay (LPA) (n = 2), interpretation of whole-genome sequencing data (n = 1). ∗∗Decisions on standardization such as whether the broth microdilution method can be used for routine phenotypic drug susceptibility testing (pDST) (n = 1), support with regard to cost reductions (n = 1), and educational support for clinicians on how to interpret laboratory data (n = 1). DR-TB, drug-resistant tuberculosis; DST, drug susceptibility testing; EQA, external quality assessment; MDR-TB, multidrug-resistant tuberculosis; RR-TB, rifampicin-resistant tuberculosis; TB, tuberculosis; WHO, World Health Organization.