Chen-Yuan Chiang

Background: Economic burdens of tuberculosis (TB) in high-income settings remain overlooked. None of the 40 countries reporting TB cost surveys to the World Health Organization (WHO) were high-income. We conducted the first such survey in a high-income country, Taiwan, to assess WHO End TB Strategy’s zero catastrophic total cost target.Methods: Nationwide cross-sectional survey data were collected from households sampled from 2018 National TB Registry. Following WHO’s protocol, we extrapolated costs throughout the TB episode. Catastrophic total cost was defined as total costs, consisting of direct medical and direct non-medical and indirect costs, exceeding 20% of annual household income. Predictors of catastrophic total cost were assessed using multivariable logistic regression.Findings: Of 481 people with drug-susceptible TB (DS‑TB) and 64 with multidrug-resistant TB (MDR‑TB), 72% were male; mean age was 65. Mean total costs (95% Confidence Interval, CI) were US$2,316 (US$2,083-2,550) for DS‑TB and US$6,665 (US$4,460-8,869) for MDR‑TB. For DS‑TB, indirect, non‑medical, and medical costs comprised 57%, 29%, and 14%; for MDR‑TB, 67%, 29%, and 4%. Catastrophic total cost affected 23% (95% CI: 19-27%) of DS‑TB households and 52% (39-64%) of MDR‑TB households. Household income below the minimum cost of living, diagnosis of MDR-TB, and lack of private health insurance were the predictors of catastrophic total costs.Interpretation: Despite the well-functioning national TB program and national health insurance, a subset of TB-affected households in Taiwan faced substantial financial burdens. Integrated strategies tailored to different cost components are essential to achieve the End TB goal.

Nucleic acid amplification tests (NAATs) were performed selectively as an initial diagnostic test for pulmonary tuberculosis (TB) in Taiwan. We assessed whether expanded use of Xpert MTB/RIF assay as an initial diagnostic test made positive contribution to the management of TB. Patients who had NAATs as an initial diagnostic test requested by clinician were classified as group A. Those who did not were randomized in a 1:1 ratio into group B who had an immediate Xpert test by intervention and group C who had usual care. 6835 patients were enrolled. Comparing group B and group C, the proportion of patients diagnosed with active TB (3.1% vs 2.7%, p = 0.336), the proportion of patients died before anti-TB treatment (2.3% vs 5.1%. p = 0.318), the median interval between submitting sputum and initiation of anti-TB treatment (7.0 days, interquartile range 3.0–25.0 vs 6.0 days, interquartile range 2.0–23.0, p = 0.589), and the proportion of TB patients with treatment success (73.8% vs 81.8%, p = 0.657) were not significantly different. There is no evidence that expanded use of Xpert MTB/RIF test as an initial diagnostic test for pulmonary TB among cases with a relatively low pretest probability of TB has positive influence on TB control in Taiwan. Trial Registration: ClinicalTrials.gov. Number NCT04433195 (date: 16/06/2020).

Treatment of rifampicin-resistant tuberculosis (RR-TB) involves drugs that can prolong the QT interval. There is limited data on risk factors and the level of cardiac monitoring required. We analysed STREAM Stage 2 data to address these issues. A post-hoc analysis was undertaken of data from participants allocated to 3 regimens: 9-month control (n = 202), 9-month oral (n = 211) and 6-month (n = 143). Risk factors for development of a QT or QTcF (corrected QT interval [Fredericia’s formula]) interval ≥500ms were assessed. The diagnostic accuracy of a monitoring strategy for QT/QTcF prolongation was tested. QT/QTcF ≥ 500ms occurred on all regimens: 9-month control (n = 14 (6.9%)), 9-month oral (n = 8 (3.8%)) and 6-month (n = 6 (4.2%)). The participating country with the highest number of QT/QTcF interval ≥500ms events was Mongolia (18 events [64%]). A higher baseline QTcF was significantly associated with development of QT/QTcF ≥ 500ms (OR 1.05; 95% CI 1.03 to 1.07, p < 0.001). There was a suggested association between moxifloxacin (compared to levofloxacin, OR 2.49; 95% CI 0.92 to 6.71, p = 0.07) and a higher baseline TSH (OR 3.52; 95% CI 0.84 to 14.73, p = 0.08) and increased odds of QT/QTcF ≥ 500ms. The monitoring strategy performed well in the control (sensitivity 100%; specificity 62%; positive predictive value (PPV) 13% and negative predictive value (NPV) 100%) and oral (sensitivity 100%, specificity 59%, PPV 6% and NPV 100%) regimen groups. Baseline QTcF and geographical region were associated with increased odds of QT/QTcF prolongation. The monitoring strategy performed well in the identification of participants at higher risk of QT/QTcF prolongation.

(1) Background: The World Health Organisation (WHO) categorises moxifloxacin and levofloxacin as Group A drugs, which should be prioritised in the treatment of rifampicin-resistant tuberculosis. We compare their relative efficacy and safety using data from the STREAM trial; (2) Methods: Marginal structural models were used to balance differences in the baseline characteristics of participants receiving the STREAM control regimen containing either moxifloxacin or levofloxacin as this was not a randomised comparison. The difference in proportions between regimens was estimated for favourable outcome, any grade 3/4 adverse event, QTcF increase to ≥500 ms, QTcF increase from baseline by at least 60 ms, and any grade 3/4 adverse event excluding QT events, using weighted analyses; (3) Results: In efficacy analyses (n = 123), the weighted risk difference (moxifloxacin—levofloxacin, wRD) for a favourable outcome was −0.045 (−0.213, 0.123), p = 0.60. Similarly, estimates from the safety analyses (n = 127) showed no evidence of a difference between the fluoroquinolones, other than a suggestion of fewer QTcF increases from baseline on levofloxacin (wRD 0.160 (−0.026, 0.346), p = 0.091); (4) Conclusions: In this small dataset, we found no statistically significant difference in key efficacy or safety outcomes between the moxifloxacin- and levofloxacin-containing regimens; there was a suggestion that QTcF increases from baseline were fewer on levofloxacin.