Abstract:

Objective This study is to identify and analyze the risk factors of recurrence of pulmonary tuberculosis after successful completion of treatment of relapsed smear positive tuberculosis.Methods This was a multi-centered open-label randomized controlled prospective cohort study which recruited patients from 22 TB specialized clinical centers across China. From March 2013 to January 2019, 300 relapsed pulmonary TB patients after completion of anti-TB retreatment had been followed-up for 6 consecutive years. Twenty-three of those who had completed retreatment relapsed again formed the recurrent cohort, the rest 277 patients who remained clear of TB formed the control cohort. Indicators including past accumulated time of anti-TB medication including initial treatment and retreatment, the presence of drug resistance prior initiation of retreatment, retreatment chemo-regimens, dosages of rifampicin or rifapentine (in short rifamycins)of retreatment regimens as well as cavitation on chest X-ray after successful completion of retreatment were investigated and analyzed by using mono-factor or multi-factor analysis for further TB recurrence. SPSS 19.0 was used for statistical analysis, collected data were verified using χ² test; a logistical regression was utilized to analyze the correlation between clinical characteristics of both cohorts and TB recurrence, P<0.05 was considered statistically significant difference.Results 7.1%(1/14) of patient from recurrent cohort having his or hers lung cavity closed which was much lower than control with 49.2%(90/183)of patients having their lung cavities closed, the difference was statistically significant(χ²=9.246,P=0.002). Using mono-factor analysis, percentages of patients who received ≥7 months of past accumulated time of administration of first-line anti-TB drugs from both recurrent and control cohort were 60.9%(14/23)and 29.1% (80/275) respectively, difference between 2 cohorts was statistically significant (χ²=9.926, P=0.002). Presence of drug resistance prior to initiation of retreatment was found in 63.6% (14/22) of patients in the recurrent cohort and 35.8% (93/260) of patients in control, difference between 2 cohorts was statistically significant (χ²=6.690, P=0.010). Using multi-factor analysis, the odds ratios (OR) between further TB recurrence and past accumulated time of anti-TB medication as well as presence of drug resistance prior retreatment were 4.911 (95%CI, 1.885-12.792) and 3.085 (95%CI, 1.204-7.902) (P=0.001 and P=0.019) respectively. In the meantime, lower dosage of rifamycins in the retreatment regimen was found to be closely associated with further recurrence of TB after retreatment completion, OR was 3.499 (95%CI, 1.302-9.404) (P=0.013).Conclusion ≥7 months of past accumulated time of anti-TB medication, the presence of drug resistance prior to initiation of retreatment, lower dosage of rifamycins in the retreatment regimen as well as persistence of pulmonary cavitation on the chest X-ray at the end of retreatment have been identified as risk factors for further TB recurrence after completion of treatment of relapsed TB.

Key words: Tuberculosis, pulmonary, Retreatment, Recurrence, Risk factors, Factor analysis, statistical