Table 2.
WHO recommended DOTS (directly observed treatment, short course) six months’ treatment regimens for patients newly diagnosed with tuberculosis and data abstracted from included studies of disease recurrence after successful treatment
| DOTS regimen, study | Description of patients* | No of patients | Reasons for exclusion from recurrence analysis | No (%) of patients assessed for recurrence | No, % (95% CI) of patients with recurrent tuberculosis) | Assessment and definition of recurrence | Duration of follow-up after treatment (range) | Quality rating (follow-up) |
|---|---|---|---|---|---|---|---|---|
| Daily regimen with ethambutol†: | ||||||||
| British Thoracic Societyw1-w3 | New, negative culture at treatment end; not tested for HIV; not tested for drug susceptibility | 141 | Death, prolonged treatment, and lost to follow-up | 127 (90) | 4, 3.1 (0.9 to 7.9) | Patients seen at 2 month intervals in first year and every 3 months thereafter; <1 positive culture within 4 months at least 2 weeks apart or diagnosed on radiography | 36 months | Average |
| Gonzalez-Montaner et alw4 | New, negative bacteriology at treatment end; HIV negative; not tested for drug susceptibility | 153 | Death and lost to follow-up | 119 (78) | 1, 0.8 (0.0 to 4.6) | Patients seen every 6 months; 2 successive positive cultures | 24 months | Poor |
| Sonnenberg et al,w5 Murray et alw6 | New and previously treated patients; negative culture or unable to produce sputum at treatment end; HIV negative; not tested for drug susceptibility | 175 | Lost to follow-up | 169 (97) | 24, 14.2 (9.0 to 19.7) | Patients seen at 3 and 6 months, thereafter monitored by routine tuberculosis surveillance; positive culture and symptomatic for tuberculosis; deaths not considered recurrence | Mean 29.5 months (17.8-35.2) | High |
| Intermittent continuation phase regimen with ethambutol‡: | ||||||||
| Cox et alw7 | New, DOTS treatment success; cases of multidrug resistant tuberculosis excluded; not tested for HIV | 71 | Lost to follow-up | 67 (94) | 9, 13.4 (6.3 to 24.0) | Retrospective review of tuberculosis registers and clinical records; positive sputum smear; deaths without positive smear not considered recurrence | Median 16 months (13-21) | Average |
| Intermittent regimen with ethambutol§: | ||||||||
| Chaisson et alw8 | New, DOTS treatment success; HIV negative; data not given by drug susceptibility | 212 | None | 212 (100) | 6, 2.8 (1.0 to 6.1) | Monthly contact by outreach workers and clinical assessment every 6 months; clinical diagnosis of tuberculosis with or without bacteriology; deaths not considered recurrence | Median 29 months | High |
| Dholakia et alw9 | New, DOTS treatment success; HIV not reported; not tested for drug susceptibility | 1483 | None | 1483 (100) | 63, 4.3 (3.3 to 5.4) | Current and previous health status assessed at single patient interview (or family); stated as relapse, exact definition not given; deaths attributed to tuberculosis counted as recurrence | 12-36 months | Average |
| Vijay et alw10 | New and previously treated, DOTS cured; HIV not reported; tested for drug susceptibility, but recurrence not given by drug resistance | 178 | Death and lost to follow-up | 132 (74) | 15, 11.4 (6.5 to 18.0) | Current and previous health status assessed at single patient interview (or family); positive bacteriology | Mean 24 months (14-37) | Poor |
| Thomas et alw11 | New, DOTS cured; HIV not reported; tested for drug susceptibility among subset; data inadequately reported | 534 | Death and lost to follow-up | 503 (94) | 62, 12.3 (9.6 to 15.5) | Patients seen at 6 month intervals; positive smear or culture | 18 months | High |
| Daily regimen with streptomycin¶: | ||||||||
| Singapore Tuberculosis Service/British Medical Research Councilw12-w14 | New, fully susceptible, negative bacteriology at treatment end; excludes patients who missed >14 days treatment in intensive phase or 4 weeks overall; not tested for HIV | 80 | None | 80 (100) | 2, 2.5 (0.3 to 8.7) | Patients seen monthly in first year and every 3 months thereafter; >1 positive culture obtained at monthly intervals within 3 months | 24 months | High |
| British Medical Research Councilw15 w16 | New, negative culture at treatment end; susceptible to all drugs; not tested for HIV | 197 | Death, prolonged treatment, and lost to follow-up | 166 (84) | 4, 2.4 (0.7 to 6.1) | Patients seen monthly in first year and every 3 months thereafter; ≥2 positive cultures obtained at monthly intervals within 3 months | 24 months | Poor |
| British Thoracic Societyw1-w3 | New, negative culture at treatment end; not tested for HIV; not tested for drug susceptibility | 146 | Death, prolonged treatment, and lost to follow-up | 119 (82) | 2, 1.7 (0.2 to 5.9) | Patients seen at 2 month intervals in first year and every 3 months thereafter; >1 positive culture within 4 months at least 2 weeks apart or diagnosed on radiography | 36 months | Poor |
| Malkin et alw17 | New and previously treated, treatment success (not defined); HIV negative; not tested for drug susceptibility | NA | Death and lost to follow-up | 232 (NA) | 13, 5.6 (3.0 to 9.4) | Patients evaluated 12 months after treatment; positive sputum smear | 12 months | Poor |
| Mohanty and Dhamgayew18 | New, smear negative at treatment end; HIV negative; not tested for drug susceptibility | 17 | None (no deaths reported) | 17 (100) | 1, 5.9 (0.2 to 28.7) | Patients seen at 3 and 12 months after treatment; positive sputum smear | 24 months | High |
| Intermittent continuation phase regimen with streptomycin**: | ||||||||
| Singapore Tuberculosis Service/British Medical Research Councilw19 w20 | New, drug susceptible, negative culture at treatment end; excludes patients who missed ≥1 drugs for 2 weeks of intensive phase or 6 weeks overall or otherwise had treatment regimen changed; not tested for HIV | 102 | Death and lost to follow-up | 96 (94) | 2, 2.1 (0.3 to 7.3) | Patients seen at 3 month intervals in first year, every 3 months to 30 months and every 6 months thereafter; ≥2 positive cultures obtained at monthly intervals within 3 months | 60 months | High |
| Singapore Tuberculosis Service,w21 Teow22 | New, drug susceptible, negative bacteriology at treatment end, and receiving treatment regimen as separate drugs; excludes patients who missed >1 week in first month, >2 weeks in 2 months, or 6 weeks overall; not tested for HIV | 47 | None (no deaths reported) | 47 (100) | 0, 0 (0.0 to 7.5) | Patients seen monthly in first year and every 3 months thereafter; ≥2 positive cultures obtained at monthly intervals within 3 months | 18 months | High |
| Intermittent regimen with streptomycin††: | ||||||||
| Cao et alw23 | New, two negative smears at or near end of treatment; HIV not reported; not tested for drug susceptibility | 306 | None | 306 (100) | 10, 3.3 (1.6 to 5.9) | Patients seen every 6 months after treatment end; positive sputum smear; deaths without positive smear not considered recurrence | 24 months | High |
| Tam et alw24-w26 | New, completed trial treatment excludes rifampicin resistant cases; not tested for HIV | NA | Death and lost to follow-up | 172 (NA) | 7, 4.1 (1.7 to 8.2) | Patients seen every 6 months after treatment end; positive culture or diagnosed on radiography | Median 31 months (6-48) | Poor |
NA=not available.
*DOTS cured refers to patients with negative sputum bacteriology (either smear or culture) at or near end of treatment and on one previous occasion. DOTS treatment completed refers to patients that have completed treatment without bacteriology results and without evidence of treatment failure. DOTS treatment success is defined as categories of cured and treatment completed combined.
†Isoniazid, rifampicin, pyrazinamide, and ethambutol daily for two months followed by isoniazid and rifampicin daily for four months.
‡Isoniazid, rifampicin, pyrazinamide, and ethambutol daily for two months followed by three doses of isoniazid and rifampicin weekly for four months.
§Three doses of isoniazid, rifampicin, pyrazinamide, and ethambutol weekly for two months followed by three doses of isoniazid and rifampicin weekly for four months.
¶Isoniazid, rifampicin, pyrazinamide, and streptomycin daily for two months followed by isoniazid and rifampicin daily for four months.
**Isoniazid, rifampicin, pyrazinamide, and streptomycin daily for two months followed by three doses of isoniazid and rifampicin weekly for four months.
††Three doses of isoniazid, rifampicin, pyrazinamide, and streptomycin weekly for two months followed by three doses of isoniazid and rifampicin weekly for four months.