Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules) This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic

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Host-directed therapies for bacterial and viral infections

Dengue is one of the most important emerging viral diseases globally. The majority of symptomatic infections result in a relatively benign disease course. However, a small proportion of patients develop severe clinical manifestations, including bleeding, organ impairment, and endothelial dysfunction with increased capillary permeability causing hypovolaemic shock that can lead to cardiovascular collapse. Evidence is increasing that dengue can also cause myocardial impairment, arrhythmias and, occasionally, fulminant myocarditis. No antiviral agents or vaccines are licensed for dengue, and treatment remains supportive with judicious fluid replacement for patients with severe disease. Defining the role of cardiac dysfunction in the haemodynamic compromise of severe dengue has potentially important management implications. In this Review, we will outline the current understanding of the cardiovascular manifestations of dengue, including myocardial and vascular involvement, and conclude with a discussion of the available therapeutic options and potential future research directions.

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Cardiovascular manifestations of the emerging dengue pandemic

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/144361/Recent advances in dengue pathogenesis and clinical management.pdf

Recent advances in dengue pathogenesis and clinical management

Dengue is the most common arboviral disease of humans. There is an unmet need for a therapeutic intervention that reduces the duration and severity of dengue symptoms and diminishes the likelihood of severe complications. To this end, there are active discovery efforts in industry and academia to develop interventions, with a focus on small molecule inhibitors of dengue virus replication that are suitable for therapy or chemoprophylaxis. Advancements in animal models of dengue virus infection together with the possibility of a dengue human infection model have further enhanced the platform for dengue drug discovery. Whilst drug discovery efforts gestate, there are ongoing clinical research designed to benefit today's patients, including trials of supportive care interventions, and descriptive studies that should improve the ability of clinicians to make an accurate diagnosis early in the illness course and to identify patients most at risk of progression to severe disease. This review provides a state of the art summary of dengue drug discovery, clinical trials, and supportive allied research and reflects discussions at the 2nd International Dengue Therapeutics Workshop held in Ho Chi Minh City, Vietnam, in December 2013.

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Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions.

Towards antiviral therapies for treating dengue virus infections

BACKGROUND Dysregulated immune responses may contribute to the clinical complications that occur in some patients with dengue. 

FINDINGS In Vietnamese pediatric dengue cases randomized to early prednisolone therapy, 81 gene-transcripts (0.2% of the 47,231 evaluated) were differentially abundant in whole-blood between high-dose (2 mg/kg) prednisolone and placebo-treated patients two days after commencing therapy. Prominent among the 81 transcripts were those associated with T and NK cell cytolytic functions. Additionally, prednisolone therapy was not associated with changes in plasma cytokine levels. 

CONCLUSION The inability of prednisolone treatment to markedly attenuate the host immune response is instructive for planning future therapeutic strategies for dengue.

/pdf/corticosteroids-for-dengue-why-don-t-they-work-3hjtiun2p0.pdf

Corticosteroids for dengue - why don't they work?

Purpose. On the basis of analysis and assessment of geological conditions, technological parameters and support methods of a longwall, the author has pointed out the causes and rules of the phenomenon of face spall and roof falling in fully mechanized longwall. From there, the author proposes some solutions to prevent this phenomenon to ensure the safety of the longwall. Methods. The statistical, survey and analysis methods of actual field data are used to achieve research results. Findings. The results of applying solutions to prevent the phenomenon of face spall and roof falling are relatively good. There are some effective solutions such as the technique of force-pumping chemicals directly into the coal seam to increase the connection among the coal masses, the solution of force-pumping water into the seam combined with enhanced support at the place of face spall and roof falling on a small scale. Originality. There are many reasons and factors that cause the phenomenon of face spall and roof falling in the longwalls. In the present paper, the author focuses on 5 main causes and factors ruling face spall and roof falling in longwalls. On that basis, the author proposes 5 solutions that can be applied to prevent the face spall and roof falling in geological conditions of longwalls in Quang Ninh coalfield, Vietnam. Practical implications. The research results presented in the article will help mines be proactive in production. These technical solutions, after being applied in actual production, allowed to achieve quite good results, and effectively handled the phenomenon of face spall and roof falling in the longwall according to each specific geological condition. Thus, it is possible to develop technical and technological solutions for troubleshooting in fully mechanized longwall at some current underground mines of Quang Ninh coalfield, Vietnam.

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Tuan Trung Vu

Papers

Corticosteroids for dengue - why don't they work?

Solutions to prevent face spall and roof falling in fully mechanized longwall at underground mines, Vietnam