A case presentation of a fatal dengue myocarditis showing evidence for dengue virus-induced lesion.

Dengue is a prevalent arthropod-borne viral disease in tropical and subtropical areas of the globe. Dengue clinical manifestations include asymptomatic infections; undifferentiated fever; dengue fever, which is characterized by fever, headache, retroorbital pain, myalgia, and arthralgia; and a severe form of the disease denominated dengue haemorrhagic fever/dengue shock syndrome, characterized by haemoconcentration, thrombocytopenia, and bleeding tendency. However, atypical manifestations, such as liver, central nervous system, and cardiac involvement, have been increasingly reported. We report an atypical and rare presentation of dengue disease marked by a dramatic and fatal cardiogenic shock due to acute myocarditis. Histopathological analysis of heart tissue showed several multifocal areas of muscle necrosis and intense interstitial oedema associated with clusters of virus particles inside the cardiomyocytes and in the interstitial space, providing evidence of a possible direct action of dengue virus on myocardium.

Evaluation of cardiac involvement during dengue viral infection.

BACKGROUND: Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established. METHODS: From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging. RESULTS: Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients. CONCLUSIONS: Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago.

First report on fatal myocarditis associated with adenovirus infection in Cuba.

Myocarditis is caused frequently by viral infections of the myocardium. In the past, enteroviruses (EV) were considered the most common cause of myocarditis in all age groups. Other viruses that cause myocarditis are adenovirus and influenza viruses. Parvovirus B19 infection is associated sometimes with myocarditis. Members of the Herpesviridae family, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) have been associated occasionally with myocarditis. During an atypical outbreak of acute febrile syndrome, eight children, with ages from 5 months to 15 years, died in cardiogenic shock due to myocarditis in July-August 2005, in the city of Havana, Cuba. Nested polymerase chain reaction (nPCR) and nested reverse transcription-PCR (nRT-PCR) were carried out on fresh heart muscle and lung tissue to analyze the genomic sequences of adenovirus, CMV, HHV-6, herpes simplex virus, Epstein-Barr virus (EBV), varizella zoster virus, influenza virus A, B, C, respiratory syncytial virus (RSV) A and B, parainfluenza viruses, rhinoviruses, coronavirus, flaviruses and enteroviruses. Evidence was for the presence of the adenovirus genome in 6 (75%) of the children. Phylogenetic analyses of a conserved hexon gene fragment in four cases showed serotype 5 as the causal agent. No others viruses were detected. Histological examination was undertaken to detect myocardial inflammation. After exclusion of other possible causes of death, the results indicated that viral myocarditis was the cause of death in patients with adenovirus infection.

Mechanisms of shock in hantavirus pulmonary syndrome.

PURPOSE OF REVIEW: Despite abundant literature on hantavirus, few reports have focused on the shock in hantavirus pulmonary syndrome. This review approaches recent advances that allow us to better understand the pathogenesis of hantavirus pulmonary syndrome shock. RECENT FINDINGS: Hantavirus pulmonary syndrome has been studied in a hamster model that mimics human shock and respiratory failure. In-vitro experiments show that pathogenic hantaviruses are able to inhibit antiviral responses, and that cytotoxicity of hantavirus-specific T cells enhances the permeability of infected endothelial cells. The idea that the primary cardiac lesion of shock is mostly functional has been shaken by the report of a typical myocarditis in hearts from human hantavirus pulmonary syndrome fatal cases. The involvement of regulatory T cells on hantavirus persistence in its rodent reservoir suggests that these cells could protect from severe hantavirus pulmonary syndrome and shock. SUMMARY: Hantavirus pulmonary syndrome shock is probably related to an exacerbated immune response of CD8+ T cells producing cytotoxicity on infected endothelial cells, presence of myocarditis and myocardial depression induced by nitric oxide. The virulence elements in G1 glycoprotein could also contribute to shock. Active suppression of immune T regulatory cells is probably involved in hantavirus pulmonary syndrome pathogenesis. These are all new aspects of hantavirus pulmonary syndrome pathogenesis that stimulate further studies to elucidate mechanisms of shock and to develop effective treatment strategies.