Timing of treatment interruption among latently infected tuberculosis cases treated with a nine-month course of daily isoniazid: findings from a time to event analysis

Abstract

Background Treatment of latent tuberculosis infection (LTBI) in high-risk groups is an effective strategy for TB control and elimination in low incidence settings. A nine-month course of daily isoniazid (INH) has been the longest prescribed therapy; however, completion rates are suboptimal. We need data to guide TB program outreach efforts to optimize LTBI treatment completion rates. Methods We pooled seven (2009–2015) years of LTBI treatment outcome data. We computed the probability of INH treatment disruption over time by patient demographic and clinical risk factors. We used log-rank tests and Cox proportional hazards models to assess the risk factors for treatment disruption. Results We analyzed data from 12,495 persons with complete data on INH treatment initiation. Pediatric cases (0–17 years), recent contacts of active TB patients, and non-U.S.-born adults living in the United States ≤5 years represented 25.2, 13.0, and 59.2% of the study population, respectively. Overall, 48.4% failed to complete therapy. The median treatment duration was 306 days (95% CI: 297, 315). A significant drop in adherence could be observed around day 30 of treatment initiation. Indeed, by day 30 of treatment, 17.0% (95% CI: 16.4, 17.7) of patients had defaulted on therapy. Pediatric patients (HR = 0.83, 95% CI: 0.78, 0.89), recent contacts (HR = 0.74, 95% CI: 0.68, 0.81), patients with diabetes (HR = 0.77, 95% CI: 0.60, 0.98), and patients with HIV (HR = 0.39, 95% CI: 0.30, 0.51) had a lower risk of treatment default. However, black patients (HR = 1.57, 95% CI: 1.44, 1.70), Hispanic patients (HR = 1.54, 95% CI: 1.43, 1.66), and non-U.S.-born persons living in the United States ≤5 years (HR = 1.25, 95% CI: 1.18, 1.32) were significantly more likely to default on therapy. Conclusions In this analysis of INH treatment outcome, we see high levels of treatment discontinuation. On average, patients defaulted on their prescribed nine-month daily INH therapy within 30 days of initiating treatment, and those at increased risk of progression to active disease were most likely to do so. We highlight the need to introduce patient-centered programs to increase treatment adherence in this population. Electronic supplementary material The online version of this article (10.1186/s12889-019-7524-4) contains supplementary material, which is available to authorized users.

The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism

“…Decreased serum calcium amount in the LEV-treated groups induces the secretion of PTH in elevated levels. 23 Moreover, the elevated amount of PTH induces the production of 1,25(OH) 2 D. 24 Furthermore, the transcription of the PTH gene can be inhibited independently by 1,25(OH) 2 D. 25 In the present study, besides the reduced calcium and increased PTH level in LEVtreated rats, serum levels of both vitamin D molecules were decreased. Therefore, it was indicated that LEV induces reduced vitamin D amounts by affecting vitamin D metabolism.…”

A scoping review of paediatric latent tuberculosis infection care cascades: initial steps are lacking

“…In analyses that included adults with HIV, people living with HIV have been found to have higher rates of treatment completion than comparison groups. 19 20 32 …”

“…In analyses that included adults with HIV, people living with HIV have been found to have higher rates of treatment completion than comparison groups. 19 20 32 Children and adolescents in LMIC face unique barriers to retention in the care cascade. There remains a wide policy-practice gap in identifying those at high risk for TB disease and with TB infection, and active contact tracing and case finding in LMIC remain critical areas for improvement.…”

“…3 Several studies have found that children face different barriers and complete one or more cascade steps at different rates than adults. [12][13][14][15][16][17][18][19][20] Yet two prior systematic reviews of the TB infection care cascade have either excluded children or did not distinguish the unique challenges paediatric patients face. 3 21 The full TB infection cascade is not always needed-existing guidance recommends that child contacts <5 years old and people living with HIV exposed to infectious TB can be started on TPT following a clinical exam without preceding TB infection testing.…”

The Treatment of Latent Tuberculosis Infection: Province Based Practice and Problems

“…24 In a USA study focused on the treatment outcomes of LTBI (n=12.495) between the years 2009 and 2015, 48.4% of the patients were unable to complete the treatment. 25 In a Japanese study, the rate for treatment completion was 71.9%, and also the treatment duration was shorter than 180 days in 20% of the patients. 26 In a study performed in Porto ve Lisbon-Portugal between the years 2013 and 2017, 13.8% of the patients were unable to complete the LTBI treatment.…”