First Report of Sudden Death Due to Myocarditis Caused by Adenovirus Serotype 3

Abstract

Myocarditis is a rare cause of sudden death in childhood. We describe the sudden death of a child from viral myocarditis, which we demonstrate was likely caused by an uncontrolled inflammatory response to a disseminated adenovirus serotype 3 infection originating in the tonsil. CASE REPORTAn 11-year old boy collapsed suddenly at home. He was transferred to a hospital by ambulance. Cardiopulmonary resuscitation was unsuccessful, and he was pronounced dead. He had visited his general practitioner (GP) 1 day earlier with a sore throat and was treated with antibiotics for tonsillitis. No investigations were carried out by his GP or on arrival at the hospital due to his sudden death. He had no past medical history of note, and there was no family history of cardiac illness or sudden death. No recent foreign travel was reported, nor was there contact with persons from abroad. A postmortem was carried out at the direction of the coroner.Much of the postmortem examination was normal. His tonsils were mildly enlarged and showed a surface purulent exudate. However, on postmortem examination, his heart was enlarged (weight, 214.2 g; expected weight, 124 g). On sectioning, the myocardium appeared diffusely abnormal with areas of petechiae and pallor. There was no evidence of myocardial hypertrophy. Microscopically, there was a severe myocardial infiltrate diffusely present composed of lymphocytes, histiocytes, and plasma cells with occasional eosinophils and neutrophils (Fig. 1). There were admixed areas of necrosis and hemorrhage. There was no evidence of fibrosis or myofiber hypertrophy. Immunohistochemical staining revealed that the infiltrate was predominantly lymphohistiocytic (CD45 positive). CD3 staining confirmed that this was a T-lymphocytemediated response (Fig. 2).All routine investigations, including swabs for bacterial culture, blood cultures, meningococcal PCR, and pneumococcal PCR, were negative. Toxicology testing for alcohol and drugs was negative. Target-specific immunoglobulin M assays were performed for Mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, parvovirus B19, and rubella virus, along with complement fixation testing for total antibodies to Mycoplasma pneumoniae, Chlamydia group, and adenovirus and latex agglutination testing for Toxoplasma gondii. All serological investigations were negative. In addition, no viruses were observed in the lung or myocardial tissue by electron microscopy. Cerebrospinal fluid Gram staining and culture were negative.The most common viral etiologies of myocarditis are Coxsackie group B viruses and members of the adenovirus genus (3, 5). Therefore, molecular methods were employed to investigate the presence of these viruses. Total viral RNA/DNA was extracted from serum using the Qiagen QIAmp viral RNA mini kit, and total viral DNA was extracted from myocardial and pulmonary tissue using the QIAamp DNA mini kit (Qiagen) in accordance with the manufacturer's instructions. Enterovirus RNA was not detected in lung or myocardial tissue using a nested reverse trans...

Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

“…CD3 ϩ T cells and F4/80 ϩ macrophages were recruited to the hearts of neonatal mice after MAV-1 infection. This is consistent with observations that hearts of patients with HAdV myocarditis are infiltrated with T cells and macrophages (34,37). The T cell infiltrates following MAV-1 infection were mainly CD8 ϩ T cells, although CD4 ϩ T cells were also present.…”

Genotyping of human adenoviruses circulating in Southwest India

“…Several studies showed that types 1, 2, 3, 5 and 21 are associated with myocarditis in children [16]. Fatal cases of HAdV-3 myocarditis have been reported by Treacy et al [15]. Adenovirus type-3 was identified as the causative agent of LRTI and suspected myocarditis in the current study.…”

Molecular epidemiology and clinical presentation of human adenovirus infections in Kansas City children

“…Several earlier reports have documented the association of HAdV-3 with conjunctivitis, pharyngitis and gastrointestinal symptoms in children and adolescents and also with fatal pneumonia and myocarditis. 10,31,32 The frequency of detection of HAdV-7 increased to 25% from 5.6% in the previous two years of surveillance efforts in Kansas City. HAdV-7 infections in children were associated with severe illness such as acute bronchiolitis (54.4%) and pneumonia (44.4%).…”

“…9 Recently, a sudden death of a child from myocarditis was reported due to an uncontrolled inflammatory response to a disseminated adenovirus serotype 3 infection in the UK. 10 Sequences of hypervariable regions of hexon gene provide excellent correlation for identification of adenoviruses at the serotype level. [11][12][13][14] Each adenovirus serotype can be further discriminated into genome types on the basis of distinct DNA fragment patterns generated with restriction enzymes, and this type of analysis has been widely used in molecular epidemiologic studies.…”