Background
Methods
Patients’ selection and study design
Eligibility, inclusion and exclusion criteria
Treatment regimens for MDR-TB in Brazil
Outcomes, exposure and statistical analysis
Variable | Included in study (1972) | Excluded from study (2057) |
P- value |
---|---|---|---|
Sex | 0.06 | ||
Female | 662 (34%) | 749 (36%) | |
Male | 1310 (66%) | 1308 (64%) | |
Age (mean) | 39.5 (SD 13.5) | 39.6 (SD 13.4) | 0.89 |
Regimen | <0.01 | ||
Individualized | 448 (23%) | 562 (27%) | |
Standardized | 1524 (77%) | 1466 (72%) | |
Unknown | 0 (0%) | 29 (1%) | |
Ethnical group | |||
Afro-Brazilian | 1213 (61%) | 1217 (59%) | 0.04 |
Indigenous | 10 (1%) | 6 (1%) | |
Caucasian | 728 (37%) | 795 (39%) | |
Other | 21 (1%) | 39 (1%) | |
TB Site | 0.80 | ||
Pulmonary | 1916 (97%) | 1994 (97%) | |
Extra-pulmonary | 21 (1%) | 21 (1%) | |
Both | 35 (2%) | 42 (2%) | |
AFB at baseline | |||
Negative | 273 (14%) | 293 (14%) | <0.01 |
Positive | 1650 (84%) | 1647 (80%) | |
Unknown | 49 (2%) | 117 (6%) | |
HIV | <0.01 | ||
Positive | 180 (9%) | 201 (10%) | |
Negative | 1721 (87%) | 1697 (83%) | |
Unknown | 71 (4%) | 159 (7%) | |
Cavity | 0.20 | ||
Yes | 1554 (79%) | 1665 (81%) | |
No | 396 (20%) | 371 (18%) | |
Unknown | 22 (1%) | 21 (1%) | |
Bilateral disease | <0.01 | ||
Yes | 1283 (65%) | 1456 (70%) | |
No | 667 (34%) | 580 (29%) | |
Unknown | 22 (1%) | 21 (1%) | |
Smoking | <0.01 | ||
Yes | 156 (8%) | 231 (11%) | |
No/unknown | 1816 (92%) | 1826 (89%) | |
Alcohol use | 0.02 | ||
Yes | 350 (18%) | 424 (21%) | |
No/unknown | 1622 (82%) | 1633 (79%) | |
Diabetes | 0.40 | ||
Yes | 227 (12%) | 218 (11%) | |
No/unknown | 1745 (88%) | 1839 (89%) | |
DOT | <0.01 | ||
Yes | 1558 (79%) | 1472 (72%) | |
No/unknown | 414 (21%) | 585 (28%) | |
Macro-region | 0.08 | ||
North | 223 (11%) | 204 (9%) | |
North-eastern | 580 (29%) | 560 (28%) | |
Centre-west | 51 (3%) | 45 (2%) | |
South-eastern | 856 (44%) | 981 (48%) | |
South | 262 (13%) | 267 (13%) | |
First DR-TB episode | <0.01 | ||
Yes | 1643 (84%) | 1510 (73%) | |
No | 284 (14%) | 456 (23%) | |
Unknown | 45 (2%) | 91 (4%) | |
Outcome | <0.01 | ||
Cure* | 686 (35%) | 444 (22%) | |
Complete treatment* | 489 (25%) | 430 (21%) | |
Failure | 183 (9%) | 215 (10%) | |
Loss to follow-up | 389 (20%) | 344 (17%) | |
Death | 211 (9%) | 261 (13%) | |
Unknown | 7 (1%) | 30 (1%) | |
Transfer | 0 (0%) | 1 (0%) | |
On treatment | 7 (1%) | 332 (16%) | |
Six month culture conversion | <0.01 | ||
Yes | 879 (45%) | 795 (39%) | |
No | 206 (10%) | 210 (10%) | |
Unknown | 887 (45%) | 1052 (51%) |
Ethical approval
Results
Odds of treatment success (cure/completed) vs. failure/relapse
N = 1358 | Odds of treatment success (cure/completed) vs. failure/relapse/death
N = 1569 | Odds of treatment success (cure/completed) vs. failure/death/loss to follow-up N = 1972 | ||||
---|---|---|---|---|---|---|
Success (%) | OR (95% CI) | Success (%) | OR (95% CI) | Success (%) | OR (95% CI) | |
Regimen | ||||||
Standardized | 922 (89%) |
2.8 (2.0; 3.8)
| 922 (77%) |
1.7 (1.3; 2.2)
| 922 (61%) | 1.3 (1.0; 1.6)† |
Individualized | 243 (76%) | Reference | 243 (66%) | Reference | 243 (54%) | Reference |
HIV co-infection* | ||||||
No | 1053 (86%) | 1.1 (0.6; 2.1) | 1089 (75%) |
1.7 (1.2; 2.6)
| 1089 (61%) |
2.2 (1.6; 3.0)
|
Yes | 76 (86%) | Reference | 76 (64%) | Reference | 76 (42%) | |
Sex | ||||||
Female | 402 (84%) | 0.8 (0.6; 1.1)† | 402 (74%) | 0.9 (0.7; 1.2) | 402 (61%) | 1.1 (0.9; 1.4) |
Male | 763 (87%) | Reference | 763 (75%) | Reference | 763 (58%) | Reference |
Age | – | 1.0 (1.0; 1.1) | – | 1.1 (1.0; 1.1) | – | 1.1 (1.0; 1.1) |
Macro-region | ||||||
North | 153 (92%) | 0.9 (0.4; 2.1) | 153 (79%) | 1.0 (0.6; 1.6) | 153 (69%) |
1.6 (1.1; 2.3)
|
Northeastern | 309 (82%) |
0.3 (0.2; 0.6)
| 309 (67%) |
0.5 (0.4; 0.8)
| 309 (54%) | 0.8 (0.6; 1.1)† |
Centre-West | 31 (86%) | 0.6 (0.2; 2.0) | 31 (82%) | 1.2 (0.4; 2.8) | 31 (61%) | 1.1 (0.6; 2.0)† |
Southeastern | 519 (86%) |
0.5 (0.3; 0.9)
| 519 (76%) | 0.9 (0.6; 1.3) | 519 (61%) | 1.1 (0.8; 1.5) |
South | 153 (92%) | Reference | 153 (80%) | Reference | 153 (58%) | Reference |
Smoking | ||||||
No/unknown | 1087 (86%) |
1.7 (1.1; 2.9)
| 1087 (75%) | 1.5 (1.0; 2.2)† | 1087 (60%) |
1.5 (1.1; 2.1)
|
Yes | 78 (79%) | Reference | 78 (68%) | Reference | 78 (50%) | Reference |
Ethnical Group | ||||||
Afro-Brazilian | 687 (86%) | 1.0 (0.7; 1.3) | 687 (73%) | 0.9 (0.7; 1.1) | 687 (57%) |
0.8 (0.6; 0.9)
|
Indigenous | 7 (88%) | 1.1 (0.1; 8.9) | 7 (88%) | 2.1 (0.3; 17.6) | 7 (70%) | 1.4 (0.4; 5.5) |
Other/unknown | 15 (83%) | 0.8 (0.2; 2.7) | 15 (79%) | 1.2 (0.4; 3.5) | 15 (75%) | 1.8 (0.6; 5.0) |
Caucasian | 455 (86%) | Reference | 455 (76%) | Reference | 455 (63%) | Reference |
Alcohol use | ||||||
No/unknown | 978 (86%) | 1.1 (0.7; 1.6) | 978 (75%) | 1.2 (0.8; 1.6) | 978 (60%) | 1.3 (1.0; 1.6)† |
Yes | 187 (85%) | Reference | 187 (72%) | Reference | 187 (53%) | Reference |
Diabetes | ||||||
No/unknown | 1006 (85%) | 0.7 (0.4; 1.2)† | 1006 (74%) | 0.8 (0.5; 1.1)† | 1006 (57%) |
0.6 (0.4; 0.8)
|
Yes | 159 (90%) | Reference | 159 (79%) | Reference | 159 (70%) | Reference |
Cavity‡ | ||||||
No | 241 (89%) | 1.3 (0.8; 2.0)† | 241(76%) | 1.1 (0.9; 1.4) | 241(61%) | 1.1 (0.9; 1.4) |
Yes | 907 (85%) | Reference | 907 (74%) | Reference | 907 (58%) | Reference |
Bilateral disease‡ | ||||||
No | 432 (88%) |
1.4 (1.1; 2.1)
| 432 (80%) |
1.7 (1.3; 2.2)
| 432(65%) |
1.5 (1.2; 1.8)
|
Yes | 716 (84%) | Reference | 716 (71%) | Reference | 716 (56%) | Reference |
AFB positive§ | ||||||
No | 190 (93%) |
2.3 (1.3;4.1)
| 190 (83%) |
1.7 (1.2; 2.5)
| 190 (69%) |
1.7 (1.3; 2.2)
|
Yes | 960 (86%) | Reference | 960 (74%) | Reference | 960 (58%) | Reference |
First DR-TB episode†† | ||||||
Yes | 1083 (91%) |
8.7 (5.9; 12.8)
| 1083 (81%) |
5.6 (4.2; 7.8)
| 1083 (66%) |
5.6 (4.2; 7.4)
|
No | 73 (52%) | Reference | 73 (41%) | Reference | 73 (26%) | Reference |
Number of previous treatment
| – |
0.2 (0.15; 0.26)
| – |
0.30 (0.20; 0.33)
| – |
0.26 (0.2; 0.33)
|
DOT | ||||||
No/unknown | 233 (83%) | 0.6 (0.5; 1.0)† | 233 (73%) | 0.9 (0.7; 1.2) | 233 (56%) | 0.9 (0.7; 1.1)† |
Yes | 932 (87%) | Reference | 932 (75%) | Reference | 932 (59%) | Reference |
Six month culture conversion ** | ||||||
No | 181 (95%) | 1.0 (0.5; 2.1) | 181 (93%) | 1.0 (0.5; 1.9) | 181 (87%) | 1.3 (0.9;2.1) |
Yes | 741 (95%) | Reference | 741 (93%) | Reference | 741 (84%) | Reference |
Quinolone used‡‡ | ||||||
Levofloxacin | 799 (90%) | 1.5 (0.9; 2.5)† | 799 (78%) |
1.6 (1.1; 2.3)
| 799 (62%) |
1.5 (1.1; 1.9)
|
Ofloxacin | 123(86%) | Reference | 123 (69%) | Reference | 123 (53%) | Reference |
Injectable used‡‡ | ||||||
Streptomycin | 503 (92%) |
1.7 (1.2; 2.6)
| 503 (82%) |
1.8 (1.4; 2.4)
| 503 (64%) |
1.4 (1.2; 1.7)
|
Amikacin | 419 (87%) | Reference | 419 (77%) | Reference | 419 (57%) | Reference |
Pyrazinamide used‡‡ | ||||||
No | 147 (92%) | 1.5 (0.8; 2.6) | 147 (74%) | 0.8 (0.6;1.1)† | 147 (74%) | 1.0 (0.8; 1.3) |
Yes | 775 (89%) | Reference | 775 (78%) | Reference | 775 (78%) | Reference |
Adjusted odds of treatment success (cure/completed) vs. failure/relapse (N = 1,302) OR (95% CI) | Adjusted odds of treatment success (cure/completed) vs. failure/relapse/death (N = 1,483) OR (95% CI) | Adjusted odds of treatment success (cure/completed) vs. failure/relapse/death/lost to follow-up (N = 1,864) OR (95% CI) | |
---|---|---|---|
HIV | |||
No | 1.7 (0.9; 3.4) |
2.7 (1.7; 4.2)
|
2.3 (1.6; 3.4)
|
Yes | Reference | Reference | Reference |
Regimen | |||
Standardized |
2.7 (1.8; 3.9)
|
1.4 (1.1; 1.9)
| 1.0 (0.8; 1.3) |
Individualized | Reference | Reference | Reference |
First DR-TB episode | |||
Yes |
8.8 (5.7; 13.5)
|
5.4 (3.8; 7.7)
|
2.1 (1.1; 4.1)
|
No | Reference | Reference | Reference |
AFB positive | |||
No |
4.2 (2.1; 8.2)
|
2.1 (1.4; 3.1)
|
2.1 (1.5; 2.8)
|
Yes | Reference | Reference | Reference |
Bilateral disease | – | ||
No |
1.4 (1.1.; 1.9)
|
1.3 (1.1; 1.6)
| |
Yes | Reference | Reference | |
Number of previous regimens | – | – |
0.4 (0.2; 0.7)
|
Diabetes | – | – | |
No/Unknown |
0.7 (0.5; 0.9)
| ||
Yes | Reference | ||
Macro-region | – | ||
North | 0.9 (0.3; 2.2) | 0.9 (0.5; 1.5) | – |
Northeastern |
0.2 (0.1; 0.5)
|
0.4 (0.4; 0.7)
| |
Centre-West | 0.4 (0.1; 1.8) | 1.0 (0.4; 2.6) | |
Southeastern |
0.4 (0.2; 0.8)
| 0.7 (0.5; 1.1) | |
South | Reference | Reference |