Retrospective evaluation of routine whole genome sequencing of Mycobacterium tuberculosis at the Belgian National Reference Center, 2019

Figures & data

Figure 1. Comparison of the old (using conventional methods) and new (using WGS) diagnostic/surveillance strategies used in the Belgian NRC for M. tuberculosis complex. Turnaround time for the different steps is given. In case of urgent analysis, a GeneXpert® MTB/RIF assay can be performed

Tuberculosis PCR: Polymerase Chain reaction specific for Mycobacterium tuberculosis complex based on the detection of the 12.7-kb fragment [16] MTB: Mycobacterium tuberculosis complex DST: Drug susceptibility Testing MIRU-VNTR: Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat

Table 1. Description of the phenotypic and genotypic drug resistance profiles obtained on the M. tuberculosis complex strains analysed in 2019 at the Belgian National Reference Center

Phenotypic (MGIT)	Genotypic (WGS)	Number of strains
Drug resistance profile	Drug resistance profile
INH-RIF-EMB-PZA	INH-RIF-EMB-PZA
S-S-S-S	S-S-S-S	233
S-S-S-R	S-S-S-R	12
	S-R-S-S	1
	S-S-S-S	12
S-S-S-NI	S-S-S-S	4
S-S-NI-S	S-S-S-S	1
S-R-S-S	S-R-S-S	1
R-S-S-S	S-S-S-S	4
	R-S-S-S	20
	R-S-R-S	2
R-S-S-R	R-S-S-R	2
R-R-S-S	R-R-S-S	4
	R-R-R-S	1
R-S-R-R	R-R-R-S	1
	R-R-R-R	1
R-R-S-R	R-R-S-R	1
	R-R-R-R	3
R-R-R-R	R-R-R-R	3
Total		306

INH: Isoniazid – RIF: Rifampicin – EMB: Ethambutol – PZA: Pyrazinamide

R: resistant; S: Susceptible; NI: Not interpretable

Bold: fully concordant between phenotypic and genotypic drug resistance profiles (for the 4 first line drugs)

Table 2. Performance of whole-genome sequencing compared to phenotypic drug susceptibility testing (MGIT) for first-line drugs on the M. tuberculosis complex strains analysed in 2019 at the Belgian National Reference Center

Drug	Phenotype resistant		Phenotype Susceptible		Sensitivity	Specificity	PPV	NPV
	Genotype resistant	Genotype susceptible	Genotype resistant	Genotype susceptible
INH	38	4	0	264	90.5	100.0	100.0	98.5
RIF	12	0	3*	290	100.0	99.0	80.0	100.0
EMB	5	0	6^#	294	100.0	98.0	45.4	100.0
PZA	22	14	0	266	61.1	100.0	100.0	95.0

INH: Isoniazid – RIF: Rifampicin – EMB: Ethambutol – PZA: Pyrazinamide

PPV: Positive Predictive Value

NPV: Negative Predictive Value

*rpoB: Leu452Pro, Leu452Pro and Asp435Tyr

^#embB: Met306Ile (n = 2), Gly406Ser, Gly406Ala, Gln497Lys, Asp328Tyr

Bakshi CS, Shah DH, Verma R, et al. Rapid differentiation of Mycobacterium bovis and Mycobacterium tuberculosis based on a 12.7-kb fragment by a single tube multiplex-PCR. Vet Microbiol. 2005;109(3–4):211–216.

 Google Scholar