Factors associated with month 2 smear non-conversion among category 1 tuberculosis patients in Karachi, Pakistan

Predictors of smear non-conversion at baseline can help identify cases at risk for failure of tuberculosis treatment. Retrospective data for smear-positive Category 1 patients in Karachi, Pakistan, was analyzed. Predictors of sputum conversion were determined using multiple logistic regression with sputum conversion as outcome variable and patient demographics, baseline weight, baseline sputum smear grade, case-finding approach as explanatory variables. Age ≥35 years, baseline sputum grade of 3+ were significantly associated with predicting sputum smear positivity at month 2 of treatment. Monitoring compliance to TB treatment should be considered amongst older patients and those with a high sputum grade at baseline

How the redox state regulates immunity

Oxidative stress is defined as an imbalance beween the levels of reactive oxygen species (ROS) and antioxidant defences. The view of oxidative stress as a cause of cell damage has evolved over the past few decades to a much more nuanced view of the role of oxidative changes in cell physiology. This is no more evident than in the field of immunity, where oxidative changes are now known to regulate many aspects of the immune response, and inflammatory pathways in particular. Our understanding of redox regulation of immunity now encompasses not only increases in reactive oxygen and nitrogen species, but also changes in the activities of oxidoreductase enzymes. These enzymes are important regulators of immune pathways both via changes in their redox activity, but also via other more recently identified cytokine-like functions. The emerging picture of redox regulation of immune pathways is one of increasing complexity and while therapeutic targeting of the redox environment to treat inflammatory disease is a possibility, any such strategy is likely to be more nuanced than simply inhibiting ROS production

Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi, Pakistan: A Mixed Methods Study

<div><p>Purpose</p><p>Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.</p><p>Methods</p><p>In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.</p><p>Results</p><p>Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default.</p><p>Conclusions</p><p>In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.</p></div

Multivariate analysis of sociodemographic and clinical variables associated with default.^*

<p>*1998 patients; excludes patients who died, transferred out, or had a change in diagnosis</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs</p><p>Multivariate analysis of sociodemographic and clinical variables associated with default.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142384#t005fn001" target="_blank">*</a>}</p

Themes with related categories and inductive codes.

<p>TB = tuberculosis</p><p>Themes with related categories and inductive codes.</p

Univariate analysis of sociodemographic and clinical variables associated with default.^*

<p>*1998 patients; excludes patients who died, transferred out, or had a change in diagnosis</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs</p><p>Univariate analysis of sociodemographic and clinical variables associated with default.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142384#t004fn001" target="_blank">*</a>}</p

Demographic and clinical characteristics of study population.

<p>*Smear status available for 951 patients with pulmonary TB</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs; Intensive phase = first 2 months of treatment; Continuation phase = 4–6 months of treatment following the first 2 months of treatment</p><p>Demographic and clinical characteristics of study population.</p

Examples of in-depth interview questions (English translations).

<p>TB = tuberculosis</p><p>Examples of in-depth interview questions (English translations).</p