Recurrence after Successful Treatment of Multidrug-Resistant Tuberculosis in Taiwan.

Recurrence after successful treatment for multidrug-resistant tuberculosis (MDR-TB) is challenging because of limited retreatment options. This study aimed to determine rates and predictors of MDR-TB recurrence after successful treatment in Taiwan. Recurrence rates were analyzed by time from treatment completion in 295 M DR-TB patients in a national cohort. Factors associated with MDR-TB recurrence were examined using a multivariate Cox regression analysis. Ten (3%) patients experienced MDR-TB recurrence during a median follow-up of 4.8 years. The overall recurrence rate was 0.6 cases per 1000 person-months. Cavitation on chest radiography was an independent predictor of recurrence (adjusted hazard ratio [aHR] = 6.3; 95% CI, 1.2-34). When the analysis was restricted to 215 patients (73%) tested for second-line drug susceptibility, cavitation (aHR = 10.2; 95% CI, 1.2-89) and resistance patterns of extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (aHR = 7.3; 95% CI, 1.2-44) were associated with increased risk of MDR-TB recurrence. In Taiwan, MDR-TB patients with cavitary lesions and resistance patterns of XDR-TB or pre-XDR-TB are at the highest risk of recurrence. These have important implications for MDR-TB programs aiming to optimize post-treatment follow-up and early detection of recurrent MDR-TB.

The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study.

BACKGROUND: Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan. METHODS: A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test. RESULTS: There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06-0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16-30 days and at 31-60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01). CONCLUSION: The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31-60 days of TB treatment might be optimal after considering the risks and benefits.

Risk for tuberculosis in child contacts. Development and validation of a predictive score.

RATIONALE: Contact investigation of persons exposed to tuberculosis (TB) is resource intensive. To date, no clinical prediction rule for TB risk exists for use as a guide during contact investigation. OBJECTIVES: We sought to develop and validate a simple and easy-to-use predictive score for TB risk, using data routinely available during contact investigation. METHODS: The derivation cohort consisted of 9,411 children aged 0 to 12 years from 2008 to 2009 national contacts cohort. We used a multivariate Cox proportional hazards model to predict the risk of developing active TB. The validation cohort consisted of 2,405 children from the 2005 national contacts cohort. We calculated area under the receiver operating characteristic curves of the model as well as the predicted risk of TB for contacts with different scores. MEASUREMENTS AND MAIN RESULTS: An 8-point scoring system was developed, including reaction to tuberculin skin test of the contacts, as well as smear-positivity, residence in high-incidence areas, and sex of the index cases. Area under the receiver operating characteristic curve was 0.872 (95% confidence interval, 0.810-0.935) for the derivation cohort and 0.900 (95% confidence interval, 0.830-0.969) for the validation cohort. The risk of developing active TB within 3 years is 100, 7.8, 4.3, 1.0, 0.7, and 0.2% for contacts with risk scores of 7, 6, 5, 4, 3, and 2, respectively. CONCLUSIONS: A risk predictive score was developed and validated to identify child contacts aged 0 to 12 years at increased risk for active TB. This predictive score can help to prioritize active case finding or isoniazid preventive therapy among children exposed to TB.

Lower prevalence of tuberculosis infection in BCG vaccinees: a cross-sectional study in adult prison inmates.

OBJECTIVES: To address whether the effect of BCG vaccination against tuberculosis (TB) infection lasts to adulthood. METHODS: A cross-sectional study on the prevalence of latent TB infection (LTBI) among HIV-negative men, using QuantiFERON-TB Gold In-tube (QFT-IT), was conducted at a prison in northern Taiwan with >3000 inmates. A QFT-IT ≥0.35 IU/ml was defined as LTBI. A QFT-IT ≥0.7 IU/ml was defined as recent LTBI. The association between the number of BCG scars and LTBI stratified by age was analysed. The study procedure was approved by the institutional review board, and all participants gave written informed consent before receiving screening tests. RESULTS: Among the 2385 participants, 25% had a QFT-IT ≥0.35 IU/ml. Increasing LTBI (14%, 32% and 50%) was observed with increased age (18-34 years, 35-54 years and ≥55 years) (p<0.001 by the Cochran-Armitage Trend Test). The number of BCG scars were found to be inversely correlated with QFT-IT results for both LTBI and recent LTBI in all three age groups (p<0.001 by Cochran-Mantel-Haenszel statistics). CONCLUSIONS: Our results suggest that BCG vaccine seems to have a protective effect in adults decades after vaccination according to the number of recent infections (QFT-IT ≥0.7 IU/ml). This finding has important implications for national policy of BCG vaccination. Further prospective cohort studies on the protective effect of BCG vaccination against TB infection in adults are warranted.