Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.

Dengue: a continuing global threat

Summary: Much remains to be learned about the pathogenesis of the different manifestations of dengue virus (DENV) infections in humans. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever (DHF), and eventually dengue shock syndrome (DSS). As both cell tropism and tissue tropism of DENV are considered major determinants in the pathogenesis of dengue, there is a critical need for adequate tropism assays, animal models, and human autopsy data. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of DHF and DSS involves viral virulence factors and detrimental host responses, collectively resulting in abnormal hemostasis and increased vascular permeability. Differential targeting of specific vascular beds is likely to trigger the localized vascular hyperpermeability underlying DSS. A personalized approach to the study of pathogenesis will elucidate the basis of individual risk for development of DHF and DSS as well as identify the genetic and environmental bases for differences in risk for development of severe disease.

Dengue Virus Pathogenesis: an Integrated View

Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

https://www.omicsonline.org/conference-proceedings/2332-0877.C1.020_003.pdf

Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis.

Despite considerable advances in our understanding of myocarditis pathogenesis, the clinical management of myocarditis has changed relatively little in the last few years. This review aims to help bridge the widening gap between recent mechanistic insights, which are largely derived from animal models, and their potential impact on disease burden. We illustrate the pathogenetic mechanisms that are prime targets for novel therapeutic interventions. Pathway and pathogen-specific molecular diagnostic tests have expanded the role for endomyocardial biopsy. State of the art cardiac magnetic resonance imaging can now provide non-invasive tissue characterization and localize inflammatory infiltrates but imaging techniques are misleading if infectious agents are involved. We emphasize the gaps in our current clinical knowledge, particularly with respect to aetiology-based therapy, and suggest opportunities for high impact, translational investigations.

The management of myocarditis

Apoptosis in tissues from fatal dengue shock syndrome.

A myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005.

Fatal severe dengue and cell death in sickle cell disease during the 2001–2002 Havana dengue epidemic

Diabetes mellitus (DM) is reported to be a risk factor for increased dengue severity in dengue epidemics both in Cuba and elsewhere. Dengue is a major cause of morbidity and mortality throughout tropical and subtropical regions of the world. Four distinct dengue viral serotypes (DENV1–4), transmitted principally by Aedes aegypti mosquitoes, cause dengue fever (DF) and dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). DF is a self-limited febrile disease. However, the most severe clinical form of dengue (DHF) is defined mostly by the hallmark pathological characteristic of vascular leakage, represented by ascites and hydrothorax. Some severe DHF cases progress to the life-threatening disease, DSS, which is associated with hypovolaemic shock. The pathogenesis of DHF/DSS involves viral, immunological and host factors. Sequential DENV infections by distinct serotypes constitute the most important risk factor for DHF/DSS. It is possible that interactions between high viral load and altered immune response, including cytokine overproduction, might trigger vascular leakage. Individuals with chronic diseases such as DM are at high risk of severe dengue. Very recently, in vivo apoptosis in cerebral cells, leukocytes and microvascular endothelial cells (MECs) has been demonstrated for the first time in tissues from fatal cases of DHF/DSS. Apoptotic cells were detected in five out of six individuals studied. These subjects died during the DENV-2 epidemic in Santiago de Cuba in 1997. One of them suffered from type 2 DM. Apoptosis of MECs was demonstrated in the intestinal serosa of this individual. Thus, the serosal oedema and ascites described in the post-mortem study were associated with apoptosis in the serosal MECs. Prior studies have shown endothelial dysfunction and increased production of cytokines in patients with type 2 DM. In vitro induction of apoptosis in endothelial cells by serum tumour necrosis factor (TNF)-α was observed. Additionally, high levels of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) have been reported in type 2 DM patients. Similarly, in vitro induction of apoptosis in endothelial cells associated with a high level of TNF-α in dengue patients’ serum has been reported. Very recently, high expressed levels of MCP-1 have been found in DHF/DSS patients, which were also related to the in vitro increase of vascular endothelial cell permeability, probably an effect on the endothelial cell tight junctions. Also VEGF, a cytokine that enhances permeability, has been linked to vascular permeability regulation in DHF/DSS. These data together suggest cytokines present in sera from type 2 DM patients might predispose them to vascular leakage and consequently to severe dengue and death during DENV infection. To our knowledge, this is the first post-mortem study to report apoptosis findings in a type 2 DM case dying of DHF/DSS. Notably, apoptosis in intestinal MECs was found in this fatal case in which the presence of ascites was described at autopsy. It is very likely that pathophysiological features and increased risk of severe dengue in type 2 DM patients may be related to microvascular endothelium abnormalities and cytokine overproduction. Further studies are required to address the high risk of severe dengue in diabetic patients and the plausible immunopathological links between dengue and diabetes.

Apoptosis, vascular leakage and increased risk of severe dengue in a type 2 diabetes mellitus patient

https://tspace.library.utoronto.ca/bitstream/1807/8475/1/oc97006.pdf

Virginia Capó

Papers

Apoptosis in tissues from fatal dengue shock syndrome.

A myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005.

Fatal severe dengue and cell death in sickle cell disease during the 2001–2002 Havana dengue epidemic

Apoptosis, vascular leakage and increased risk of severe dengue in a type 2 diabetes mellitus patient

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