Elsevier

Forensic Science International

Volume 268, November 2016, Pages 73-80
Forensic Science International

Coxsackievirus B heart infections and their putative contribution to sudden unexpected death: An 8-year review of patients and victims in the coastal region of Tunisia

https://doi.org/10.1016/j.forsciint.2016.09.014Get rights and content

Highlights

Abstract

Coxsackieviruses B (CV B) are known as the most common viral cause of human heart infections. Cardiac inflammations contribute to sudden unexpected death (SUD) significantly. The diagnosis remains difficult with the traditional diagnostic tests and must be substantially improved. This has prompted health professionals to seek new diagnostic procedures which may provide important clues regarding underlying etiology.

The present study is based on patients with infectious heart diseases and SUD victims with no relevant pathologies. They were investigated for possible CV-B infection. Patients with coronary artery diseases and unnatural road and domestic accident victims served as controls. The samples were studied for CV-B applying PCR. Histopathology for inflammatory markers, immunohistochemistry (IHC) for immune inflammatory cells and the enteroviral VP1-capsid protein were performed. Overall, 102 patients and 87 SUD victims were studied. As controls, 100 patients and 54 SUD unnatural accident victims were enrolled.

CV-B were detected in 28 patients and 15 SUD victims. The control group samples were completely virus negative. Compared to controls, IHC revealed a significant presence of T and B lymphocytes within the myocardium. Furthermore, enteroviral VP1-capsid protein were detected from samples by IHC.

Applying a comprehensive combination of methods, our results demonstrate the involvement of CV-B in cases of heart infection suggesting they play a significant role in SUD. Our results emphasize the importance of opting for a combination of methods.

Introduction

Infectious heart diseases include a group of entities involving the heart wall, mainly myocarditis and dilated cardiomyopathy. Myocarditis is clinically and pathologically defined as an inflammatory myocardial disease [1]. A number of patients with acute myocarditis may develop dilated cardiomyopathy as a complication [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Although it is rare, pericarditis represents one of the main pericardial syndromes that are encountered in clinical practice. Pericarditis is a swelling and irritation of the pericardium, the thin sac-like membrane that surrounds the heart [17]. Pericarditis and myocarditis share common aetiologies, and overlapping forms may be encountered in clinical practice. Pericarditis with known or clinically suspected concomitant myocardial involvement should be referred to as ‘myopericarditis’ according to Task Force Consensus [18], [19].

Recent clinical studies and anecdotal communications reported on different viruses. Among them, CV-B, a small nonenveloped single-stranded and positive-sense RNA virus of the Picornaviridae family and Enterovirus genus, has been implicated in 25–40% of acute myocarditis and dilated cardiomyopathy cases in infants, young adolescents and adults [20]. These processes are most commonly associated with SUD. From a forensic point of view, SUD is defined mainly as rapid, unexpected and natural death [21]. Most often, SUD due to natural causes results from previously unknown cardiovascular diseases though extra cardiac causes should not be ruled out [21], [22]. SUD of infants, youngsters and adults has received increasing attention over the past decades. In the current study, we provide an overview of this problem while considering mass screening and intensive heart care strategies for newly diagnosed patients with heart infections and adopting medicolegal investigations complemented with developed laboratory tests to elucidate the underlying cause of SUD. Finally, we present an alternative approache based on a comprehensive combination of methods: conventional histopathology for the detection of inflammatory infiltrates and necrosis sites, molecular pathology for the investigation of the enteroviral genomic RNA (conserved sequences and VP1-capsid-protein coding region) and modern IHC to reveal the enteroviral VP1-capsid-protein and immune inflammatory markers (CD3-T and CD19-B-lymphocytes).

Section snippets

Populations study

In this prospective study, the sampling was performed at three university hospitals located on the coast of Tunisia: Fattouma Bourguiba (Monastir), Farhat Hached (Sousse) and Sahloul (Sousse) from 2006 to 2014. Initially, 102 patients with infectious heart disease, and aged 17–46 years (mean age 30.8 years) were studied. Subsequently, 87 SUD victims without any relevant pathological finding n = (48)-aged 18–42-years-old and n = (39)-aged 3–9-months were enrolled (Table 1). Blood samples were

Results

Of the 102 evaluated affected individuals, Myocardium and/or pericardium inflammation was presumed to be due to a typical history of viral infection at the time of cardiac disease onset. The 48 sudden unexpected death cases included in this study were clinically suspected with inflammatory heart disease.

Discussion

The present study conducted for the first time in Tunisia provides evidence of a high incidence of virus-induced heart affections significantly contributing to SUD. More importantly, the combined investigation methods suggested herein would enable pathologists to diagnose viral heart infections in a rapid and specific way and to better understand and elucidate the cause of death [31], [32], [33].

Based on clinical data and using histological as well as histopathological findings, PCR and IHC,

Acknowledgments

The present study was partially supported by the National Institute of Health grant (HL108371).

The authors are grateful to Mr. Adel Rdissi for proof-reading the paper.

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