Introduction
Methods
Patient enrollment
Detection methods
Smear microscopy
Isolation of M. tuberculosis and drug susceptibility testing (DST)
The GenoType MTBDRplus test for detecting drug resistance
Entry of results
Statistical analysis
Results
Characteristics of the screened subjects
N= 3,308 cases | ||
---|---|---|
Subject characteristics | ||
Age (years)* | 61.5 ± 17.3 | |
Gender | Male | 2,545 (76.9%) |
Female | 763 (23.1%) | |
Reason for screening | Relapse | 1,552 (46.9%) |
Treatment failure | 1,166 (35.2%) | |
Aboriginal inhabitants | 379 (11.5%) | |
Individual from high MDR-TB burden countries | 76 (2.3%) | |
Default (loss to follow-up) | 69 (2.1%) | |
MDR-TB contacts | 66 (2.0%) | |
AFB Smear titer | Negative | 762 (23.0%) |
Scanty | 326 (9.9%) | |
1+ | 1,147 (34.7%) | |
2+ | 513 (15.5%) | |
3+ | 255 (7.7%) | |
4+ | 305 (9.2%) | |
M. tuberculosis isolation† | 827 (25%) |
M. tuberculosis isolation among the screened populations
Year | Total | Relapse | Treatment failure | Aboriginal inhabitants | Individual from high MDR-TB burden countries | Default (Loss to follow-up) | MDR-TB contacts |
---|---|---|---|---|---|---|---|
Total | 25% (827/3,308) | 29.4% (456/1,552) | 7.3% (85/1,166) | 41.7% (158/379) | – | 34.2% (13/38) | 57.6% (38/66) |
Year 2012 (March to Dec.) | 18.9% (242/1,278) | 20.8% (129/620) | 8.1% (30/370) | 25.7% (56/218) | 43.8% (14/32) | ||
Year 2013 | 28.8% (302/1,047) | 33.1% (164/496) | 9.3% (36/389) | 57.3% (55/96) | 83.9% (26/31) | 44.4% (8/18) | 76.5% (13/17) |
Year 2014 | 28.8% (283/983) | 37.4% (163/436) | 4.7% (19/407) | 72.3% (47/65) | 75.6%(34/45) | 69.2% (9/13) | 64.7% (11/17) |
Comparison of GenoType MTBDRplus test results with conventional mycobacterial DST results
GenoType MTBDRplus
|
M. tuberculosis isolation | Sen. | Spe. | PPV | NPV | Accuracy | ||
---|---|---|---|---|---|---|---|---|
Yes | No | |||||||
TB | Yes | 710 | 851 | 85.9% | 65.7% | 45.5% | 93.3% | 70.7% |
No | 117 | 1,630 |
GenoType MTBDRplus
| Corresponding DST results† | Sen. | Spe. | PPV | NPV | Accuracy | ||
---|---|---|---|---|---|---|---|---|
R | S | |||||||
RIF resistance | R | 93 | 16 | 92.1% | 97.3% | 85.3% | 98.6% | 96.5% |
S | 8 | 567 | ||||||
INH resistance | R | 109 | 1 | 77.9% | 99.8% | 99.1% | 94.6% | 95.2% |
S | 31 | 543 | ||||||
MDR | R | 67 | 2 | 82.7% | 99.7% | 97.1% | 97.7% | 97.7% |
S | 14 | 601 |
Associations of rpoB mutations with reason for screening and geographic area
Reason for screening (n, %) | Geographic area (n, %) | (n, %) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Recurrent | Failed (treatment failure) | Aboriginal inhabitants | High MDR-TB burden countries | Default (lost to follow-up) | MDR-TB contacts | North | Central | South | East | Outlying islands | ||
rpoB MUT1 | + | 1 (2.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (2.7) | 0 (0) | 0 (0) |
− | 39 (97.5) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 3 (100.0) | 21 (100.0) | 32 (100.0) | 22 (100.0) | 36 (97.3) | 9 (100.0) | 1 (100.0) | |
rpoB MUT2A | + | 2 (5.0) | 2 (9.1) | 0 (0) | 1 (16.7) | 0 (0) | 0 (0) | 2 (6.3) | 1 (4.5) | 1 (2.7) | 1 (11.1) | 0 (0) |
− | 38 (95.0) | 20 (90.9) | 9 (100.0) | 5 (83.3) | 3 (100.0) | 21 (100.0) | 30 (93.7) | 21 (95.5) | 36 (97.3) | 8 (88.9) | 1 (100.0) | |
rpoB MUT2B | + | 3 (7.5) | 2 (9.1) | 0 (0) | 0 (0) | 1 (33.3) | 1 (4.8) | 1 (3.1) | 1 (4.5) | 5 (13.5) | 0 (0) | 0 (0) |
− | 37 (92.5) | 20 (90.9) | 9 (100.0) | 6 (100.0) | 2 (66.7) | 20 (95.2) | 31 (96.9) | 21 (95.5) | 32 (86.5) | 9 (100.0) | 1 (100.0) | |
rpoB MUT3 | + | 22 (55.0) | 8 (36.4) | 7 (77.8) | 4 (66.7) | 1 (33.3) | 11 (52.4) | 22 (68.8) | 11 (50.0) | 13 (35.1)* | 7 (77.8) | 0 (0) |
− | 18(45.0) | 14 (63.6) | 2 (22.2) | 2 (33.3) | 2 (66.7) | 10 (47.6) | 10 (31.2) | 11 (50.0) | 24 (64.9) | 2 (22.2) | 1 (100.0) | |
rpoB WT1 | + | 39 (97.5) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 3 (100.0) | 21 (100.0) | 32 (100.0) | 22 (100.0) | 36 (97.3) | 9 (100.0) | 1 (100.0) |
− | 1 (2.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (2.7) | 0 (0) | 0 (0) | |
rpoB WT2 | + | 37 (92.5) | 19 (86.4) | 9 (100.0) | 5 (83.3) | 3 (100.0) | 20 (95.2) | 31 (96.9) | 22 (100.0) | 31 (83.8) | 8 (88.9) | 1 (100.0) |
− | 3 (7.5) | 3 (13.6) | 0 (0) | 1 (16.7) | 0 (0) | 1 (4.8) | 1 (3.1) | 0 (0) | 6 (16.2) | 1 (11.1) | 0 (0) | |
rpoB WT3 | + | 33 (82.5) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 2 (66.7) | 14 (66.7) | 30 (93.7) | 17 (77.3) | 30 (81.1) | 8 (88.9) | 1 (100.0) |
− | 7 (17.5) | 0 (0) | 0 (0) | 0 (0) | 1 (33.3) | 7 (33.3)† | 2 (6.3) | 5 (22.7) | 7 (18.9) | 1 (11.1) | 0 (0) | |
rpoB WT4 | + | 35 (87.5) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 2 (66.7) | 15 (71.4) | 30 (93.7) | 18 (81.8) | 32 (86.5) | 8 (88.9) | 1 (100.0) |
− | 5 (12.5) | 0 (0) | 0 (0) | 0 (0) | 1 (33.3) | 6 (28.6)† | 2 (6.3) | 4 (18.2) | 5 (13.5) | 1 (11.1) | 0 (0) | |
rpoB WT5 | + | 38 (95.0) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 3 (100.0) | 21 (100.0) | 32 (100.0) | 21 (95.5) | 36 (97.3) | 9 (100.0) | 1 (100.0) |
− | 2 (5.0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (4.5) | 1 (2.7) | 0 (0) | 0 (0) | |
rpoB WT6 | + | 38 (95.0) | 22 (100.0) | 9 (100.0) | 6 (100.0) | 3 (100.0) | 21 (100.0) | 32 (100.0) | 21 (95.5) | 36 (97.3) | 9 (100.0) | 1 (100.0) |
− | 2 (5.0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (4.5) | 1 (2.7) | 0 (0) | 0 (0) | |
rpoB WT7 | + | 34 (85.0) | 14 (63.6) | 9 (100.0) | 5 (83.3) | 2 (66.7) | 19 (90.5) | 28 (87.5) | 20 (90.9) | 26 (70.3) | 8 (88.9) | 1 (100.0) |
− | 6 (15.0) | 8 (36.4) | 0 (0) | 1 (16.7) | 1 (33.3) | 2 (9.5) | 4 (12.5) | 2 (9.1) | 11 (29.7) | 1 (11.1) | 0 (0) | |
rpoB WT8 | + | 14 (35.0) | 12 (54.5) | 0 (0) | 2 (33.3) | 1 (33.3) | 9 (42.9) | 7 (21.9) | 8 (36.4) | 21 (56.8)¶ | 2 (22.2) | 0 (0) |
− | 26 (65.0) | 10 (45.5) | 9 (100.0)† | 4 (66.7) | 2 (66.7) | 12 (57.1) | 25 (78.1) | 14 (63.6) | 16 (43.2) | 7 (77.8) | 1 (100.0) |
Associations of inhA/katG mutations with reason for screening and gengraphic area
Reason for screening (n, %) | Gengraphic area (n, %) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Recurrent | Failed (treatment failure) | Aboriginal inhabitants | High MDR-TB burden countries | Default (lost to follow-up) | MDR-TB contacts | North | Central | South | East | ||
inhA MUT1 | + | 10 (18.2) | 9 (28.1) | 7 (35) | 3 (42.9) | 0(0) | 11 (47.8)* | 11 (23.4) | 11 (33.3) | 13 (29.5) | 5 (31.3) |
− | 45 (81.8) | 23 (71.9) | 13 (65) | 4 (57.1) | 3 (100.0) | 12 (52.2) | 36 (76.6) | 22 (66.7) | 31 (70.5) | 11 (68.7) | |
inhA MUT2 | + | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
− | 55 (100.0) | 32 (100.0) | 20 (100.0) | 7 (100.0) | 3 (100.0) | 23 (100.0) | 47 (100.0) | 33 (100.0) | 44 (100.0) | 16 (100.0) | |
inhA MUT3A | + | 3 (5.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 3 (6) | 0 (0) | 0 (0) | 0 (0) |
− | 52 (94.5) | 32 (100.0) | 20 (100.0) | 7 (100.0) | 3 (100.0) | 23 (100.0) | 44 (94) | 33 (100.0) | 44 (100.0) | 16 (100.0) | |
inhA MUT3B | + | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
− | 55 (100.0) | 32 (100.0) | 20 (100.0) | 7 (100.0) | 3 (100.0) | 23 (100.0) | 47 (100.0) | 33 (100.0) | 44 (100.0) | 16 (100.0) | |
inhA WT1 | + | 46 (83.6) | 23 (71.9) | 13 (65) | 4 (57.1) | 3 (100.0) | 11 (47.8)* | 35 (74.5) | 22 (66.7) | 32 (72.7) | 11 (68.8) |
− | 9 (16.4) | 9 (28.1) | 7 (35) | 3 (42.9) | 0 (0) | 12 (52.2) | 12 (25.5) | 11 (33.3) | 12 (27.3) | 5 (31.2) | |
inhA WT2 | + | 51 (92.7) | 32 (100.0) | 20 (100.0) | 7 (100.0) | 3 (100.0) | 23 (100.0) | 43 (91.5) | 33 (97.6) | 44 (94.7) | 16 (97.7) |
− | 4 (7.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 4 (8.5) | 0 (0) | 0 (0) | 0 (0) | |
katG MUT1 | + | 24 (43.6) | 20 (62.5) | 11 (55) | 4 (57.1) | 3 (100.0) | 12 (52.2) | 27 (57.4) | 13 (39.4) | 23 (52.3) | 11 (68.8) |
− | 31 (56.4) | 12 (37.5) | 9 (45) | 3 (42.9) | 0 (0) | 11 (47.8) | 20 (42.6) | 20 (60.6) | 21 (47.7) | 5 (31.2) | |
katG MUT2 | + | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
− | 55 (100.0) | 32 (100.0) | 20 (100.0) | 7 (100.0) | 3 (100.0) | 23 (100.0) | 47 (100.0) | 33 (100.0) | 44 (100.0) | 16 (100.0) | |
katG WT | + | 34 (61.8) | 14 (43.8) | 8 (40) | 3 (42.9) | 0 (0) | 11 (47.8) | 22 (46.8) | 20 (60.6) | 24 (54.5) | 4 (25) |
− | 21 (38.2) | 18 (56.2) | 12 (60) | 4 (57.1) | 3 (100.0) | 12 (52.2) | 25 (53.2) | 13 (39.4) | 20 (45.5) | 12 (75) |