Host Transcriptional Signatures Predict Etiology in Community-Acquired Pneumonia: Potential Antibiotic Stewardship Tools.

Background: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. Methods: In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA). Results: In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98). Conclusion: Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.

How participatory is parental consent in low literacy rural settings in low income countries? Lessons learned from a community based study of infants in South India.

BACKGROUND: A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed. AIMS: The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation. METHODS: In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process. RESULTS: In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location. CONCLUSIONS: The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease.

The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial.

BACKGROUND: Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain. OBJECTIVE: The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear-positive pulmonary tuberculosis. DESIGN: Participants attending a primary care tuberculosis clinic in Cape Town, South Africa, were randomly assigned to receive micronutrients (single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk) or matching placebo. Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media (BACTEC MGIT 960; Becton Dickinson, Sparks, MD). Performance status, chest radiographs, and anthropometric measures were assessed at baseline and again at 8 wk. RESULTS: The participants (n = 154) were randomly assigned to the micronutrient (n = 77) or placebo (n = 77) group. Twenty participants were HIV infected (13%), and 12 participants had an unknown HIV status (8%). No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis (P = 0.15 and P = 0.38, respectively; log-rank test). Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period (P = 0.32). No significant differences in weight gain (2.3 ± 3.5 compared with 2.2 ± 2.4 kg, P = 0.68) or radiologic resolution were observed between the treatment groups. CONCLUSION: Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk. This trial was registered at controlled-trials.com as ISRCTN80852505.