The Impact of HIV Infection and CD4 Cell Count on the Performance of an Interferon Gamma Release Assay in Patients with Pulmonary Tuberculosis

BACKGROUND:The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance. METHODOLOGY/PRINCIPAL FINDINGS:161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39). CONCLUSIONS/SIGNIFICANCE:Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent

Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison

BACKGROUND: The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains. METHODS: Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups. RESULTS: Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) γ and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression (p = 0.018) and lower IFN-γ : IL-4 cDNA copy number ratios (p = 0.01). CONCLUSION: Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression

Sensing and Adaptation to Low pH Mediated by Inducible Amino Acid Decarboxylases in Salmonella

During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i) to survive an extreme acid shock, (ii) to grow at mild acidic pH and (iii) to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection

The Role of Health Literacy, Depression, Disease Knowledge, and Self-Efficacy in Self-Care Among Adults with Heart Failure: An Updated Model

BACKGROUND: Patients with inadequate health literacy and heart failure face high healthcare costs, more hospitalizations, and greater mortality. To address these negative consequences, patients need to improve heart failure self-care. Multiple factors may influence self-care, but the exact model by which they do so is not fully understood. OBJECTIVES: The objective of this study was to examine a model exploring the contribution of health literacy, depression, disease knowledge, and self-efficacy to the performance of heart failure self-care. METHODS: Using a cross-sectional design, patients were recruited from a heart failure clinic and completed validated assessments of their cognition, health literacy, depression, knowledge, self-efficacy and self-care. Patients were separated into two groups according to their health literacy level: inadequate/marginal and adequate. Differences between groups were assessed with an independent t-test. Hypothesized paths and mediated relationships were estimated and tested using observed variable path analysis. RESULTS: Participants (n = 100) were mainly male (67%), white (93%), and at least had a high school education (85%). Health literacy was associated with disease knowledge (path coefficient=0.346, p = 0.002), depression was negatively associated with self-efficacy (path coefficient=-0.211, p = 0.037), self-efficacy was positively associated with self-care (path coefficient=0.402, p CONCLUSIONS: Self-efficacy and depression are associated with heart failure self-care. Data generated from the model suggest that healthcare professionals should actively engage all patients to gain self-efficacy and address depression to positively affect heart failure self-care