Here we demonstrate that aerosols of host directed therapies [HDT] administered during a chronic Mycobacterium tuberculosis (Mtb) infection have bactericidal effect. The pulmonary bacterial load of C57BL/6 mice chronically infected with Mtb was reduced by 1.7 and 0.6 log10CFU after two weeks of treatment via aerosol delivery with ST3-H2A2, [a selective peptide inhibitor of the STAT3 N-terminal domain] or IL10R1-7 [selective peptide inhibitor for the IL-10Ra] respectively and when compared to control mice treated with IL10R1-14 [peptide inhibitor used as negative control] or untreated mice infected with Mtb. Accordingly, when compared to control mice, the bactericidal capacity in mice was enhanced upon treatment with peptide inhibitors ST3-H2A2 and IL10R1-7 as evidenced by higher pulmonary activities of nitric oxide synthase, NADPH oxidase and lysozyme enzymes and decreased arginase enzyme activity. This therapy also modulated important checkpoints [Bcl2, Beclin-1, Atg 5, bax] in the apoptosis-autophagy pathways. Thus, even in the absence of antibiotics, targeting of the host pulmonary IL-10-STAT3 pathway can significantly reduce the Mtb bacilli load in the lungs, modulate the host own bactericidal capacity and apoptosis and autophagy pathways. Our approach here also allows targeting checkpoints of the lungs to determine their specific contribution in pulmonary immunity or pathogenesis.
13th International Congress on Infectious Diseases Abstracts, Poster Presentations e459 (PCT) and its effects and important for quickly distinguishing between bacterial and viral infections in children and infantsResults: We found that the procalcitonin (PCT) concentrations increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and molecule is stable, making it as potentially useful marker for distinguishing between bacterial and viral infections.Discussion: Its advantages over CRP, IL-6 and INF alpha are clear but it doesn't mean that those methods, despite some disadvantages earlier explained, should be rejected.Comclusions: PCT may be useful in an emergency room for differentiation of bacterial from viral infections in children and for making decisions about antibiotic treatments. The change is rapid and the molecule is stable, making it a potentially useful marker for distinguishing between bacterial and viral infections. Comparing PCT with CRP (C reactive protein), interleukin 6, and interferon alpha demonstrates increased values for PCT than for the others for and thus may be better for differentiation between bacterial and viral infections.
Background: Hydroxychloroquine (HCQ) has been extensively used during COVID-19 pandemic both as a therapeutic and prophylactic drug. HCQ is generally well tolerated; however, adverse drug reactions (ADRs) in COVID-19 need further exploration. In this study, we have determined the type and pattern of ADRs of HCQ as a prophylactic and therapeutic drug in COVID-19. Methods: All spontaneous suspected ADR reports due to HCQ in COVID-19 patients submitted to the ADR monitoring of a tertiary care hospital were included. Additionally, a survey was designed for active surveillance of ADRs among healthcare professionals (HCPs) who were on prophylaxis with HCQ. The ADRs were analyzed to determine severity, causality and preventability using Hartwig Scale, WHO-UMC scale and modified Schumock and Thornton criterion respectively. Results: Sixty-four ADR reports were received from COVID-19 patients. A total of 78 ADRs were reported by 49 HCPs who were on HCQ prophylaxis. The majority of the patients had ADRs related to skin and soft tissues (37.5 %) whereas the HCPs on prophylaxis mostly had gastrointestinal complaints (42.3%). ADRs observed in HCPs on prophylaxis were mild, not requiring any intervention. However, 50% ADRs in patients were of “moderate” category. Conclusion: Undiscerning and unsupervised use of HCQ can expose the general population as well as patients to serious adverse drug effects. Utmost care is necessary before using HCQ prophylactically or for treatment in COVID-19.
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