Association Between Tuberculosis and Depression on Negative Outcomes of Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Ruíz-Grosso, Paulo; Cachay, Rodrigo; Flor, Adriana de la; Schwalb, Alvaro; Ugarte-Gil, César

doi:10.1101/19010538

Cited by 5 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data strongly indicated potential activation of the host cell inflammasome by SRT. With several studies supporting inverse regulation of type I IFN and inflammasome activation (58, 59), we tested the efficacy of SRT to potentiate antibiotic mediated killing in the presence of inflammasome inhibitors. Again, while SRT enhanced the ability of HR to control Mtb in macrophages, pretreatment of cells with the inflammasome inhibitor, isoliquiritigenin (I), completely nullified the boosting effect of SRT on antibiotic efficacy (Fig.…”

Section: Resultsmentioning

confidence: 99%

The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy

Shankaran

Singh

Dawa

et al. 2020

Preprint

View full text Add to dashboard Cite

12A prolonged therapy regimen, primarily responsible for development of drug resistance by 13Mycobacterium tuberculosis (Mtb), the causative agent of human TB, obligates any new regimen 14 to not only reduce treatment duration but also escape pathogen resistance mechanisms. With 15 the aim of harnessing the host response in providing additional support to existing regimens (host 16 directed therapy-HDT), we established the ability of a well-tolerated anti-depressant (sertraline -17 SRT) to modulate the pro-pathogenic type I IFN response of macrophages to Mtb infection. More 18 importantly, while SRT alone could only arrest bacterial growth, it could effectively escalate the 19 bactericidal activities of Isoniazid (H) and Rifampicin (R) in macrophages. This strengthening of 20 antibiotic potencies by SRT was more evident in conditions of ineffective control by these frontline 21 TB drugs: against HR tolerant strains or dormant Mtb. SRT, could significantly combine with 22 standard TB drugs to enhance early pathogen clearance from tissues of mice infected with either 23 drug sensitive/ tolerant strains of Mtb. Further, we demonstrate an enhanced protection of the 24 highly susceptible C3HeB/FeJ mice in an acute model of TB infection with the combination 25 therapy signifying the use of SRT as a potent adjunct to standard TB therapeutic regimens against 26 Abbreviations: IFN-Interferon, SRT-sertraline hydrochloride, Mtb-Mycobacterium tuberculosis, 30HDT-host directed therapy 31 Introduction: 32The current TB therapy regimen ranging between 6 months for pulmonary and 1-2 years for 33 extrapulmonary infections, is often associated with severe drug induced toxicity in patients. 34Moreover, its failure to completely eradicate the pathogen from the host forms an ideal platform 35 for the emergence of drug resistant strains 1,2 . It is not surprising that these strains have emerged 36 at an alarming rate in the population and are imposing serious impediments to TB control 37 programs globally 3,4 . Introduction of newer modalities like Host directed therapies (HDT) with the 38 potential to reduce duration of therapy and not be affected by pathogen resistance mechanisms 39 offer significant advantages in this scenario 5,6 . Several strategies for HDT with diverse modes of 40 action-boosting immune response 7,8,9 , targeting virulence mechanisms 10-12 , augmenting host 41 metabolism 13 and host nutrition 14 have been identified in recent times. Effective molecular entities 42 like antibodies 15,16 , cytokines 17,18 , cell based therapies 19 , drugs used for other human non-43 infectious diseases and recombinant proteins 20 have been tested against bacterial infections like 44 Streptococcus pneumoniae 16 , Bordetella pertussis 21,22 , Helicobacter pylori 23 and against viral 45 infections like HIV 24 , CMV 25 , Hepatitis C 18 , influenza 26 and Ebola viruses 27 . 46 Mtb infection invokes several mechanisms of pathogen clearance in host cells like induction of 47A prominent response of Mtb infected macrophages is the early an...

show abstract

Section: Resultsmentioning

confidence: 99%

The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy

Shankaran

Singh

Dawa

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…While we did not formally measure depression, more than one-fifth of patients who reported missing doses described feeling depressed as a major reason. A recent systematic review found that depression is associated with increased loss to follow-up and death—but not medication non-adherence—during TB treatment; however, the included studies had suboptimal measures of adherence [36]. Future studies using rigorous measures of both depression and adherence, such as the urine testing we used here, may help to understand whether non-adherence mediates the association between depression and treatment outcomes.…”

Section: Discussionmentioning

confidence: 99%

Understanding non-adherence to tuberculosis medications in India using urine drug metabolite testing: a cohort study

Subbaraman

Thomas

Kumar

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundSuboptimal adherence to tuberculosis (TB) treatment is associated with increased disease recurrence and death. Little research has been conducted in India to understand TB medication non-adherence.MethodsWe enrolled adult drug-susceptible TB patients, about half of whom were people living with HIV (PLHIV), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for non-adherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for non-adherence and identified factors associated with non-adherence (negative urine test) using multivariable logistic regression. We also assessed the association between non-adherence and unfavorable treatment outcomes.ResultsOf 650 patients in the cohort, 77 (11.8%) had a negative urine test result. Non-adherence was independently associated with daily wage labor (aOR 3.1, CI: 1.3—7.7), smear-positive pulmonary disease (aOR 2.1, CI: 1.1—4.1), alcohol use (aOR 2.3, CI: 1.1—4.8), and spending 60 minutes or more picking up medication refills (aOR 9.1, CI: 1.8—45.4). PLHIV reported greater barriers to picking up medications than non-PLHIV. Among 167 patients who reported missing doses, common reasons reported included traveling away from home, forgetting, feeling depressed, and running out of pills. The odds of non-adherence was 3.8 (CI: 2.1—6.9) times higher among patients with unfavorable treatment outcomes compared to those with favorable outcomes.ConclusionAddressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify non-adherent patients to facilitate early intervention during treatment.Key pointsWe evaluated adherence to tuberculosis medications in 650 Indian patients by conducting urine isoniazid tests collected during unannounced home visits. Structural barriers to collecting medication refills and psychosocial barriers emerged as the most important factors contributing to medication non-adherence.

show abstract

“…These results are similar to but weaker than associations reported in another recent systematic review focused only on depression. 28 This difference may be partially due to variations in outcome definitions and statistical approaches between studies. The strong link between mental disorders and non-adherence to TB treatment is consistent with studies examining medication adherence in patients with mental disorders comorbid with HIV and non-communicable diseases.…”

Section: Discussionmentioning

confidence: 99%

Impact of mental disorders on active tuberculosis treatment outcomes: a systematic review and meta-analysis

Lee

Scuffell

Galea

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Comorbid mental disorders in patients with tuberculosis (TB) may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes. Methods: We searched eight databases for studies published from 1990-2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (OR) with 95% confidence intervals (CI). Findings: Of 7,687 studies identified, ten were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95% CI: 0.85-5.37), 1.90 (0.33-10.91), and 1.60 (0.81-3.02), respectively. High statistical heterogeneity was present. Interpretation: Our review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

show abstract

Association Between Tuberculosis and Depression on Negative Outcomes of Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Cited by 5 publications

References 27 publications

The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy

The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy

Understanding non-adherence to tuberculosis medications in India using urine drug metabolite testing: a cohort study

Impact of mental disorders on active tuberculosis treatment outcomes: a systematic review and meta-analysis

Contact Info

Product

Resources

About