Clinicopathologic features and molecular analysis of enterovirus 71 infection: Report of an autopsy case from the epidemic of hand, foot and mouth disease in China

Abstract

A 15‐month boy with fatal hand, foot, and mouth disease (HFMD) exhibited atypical symptoms and progressed rapidly to death. An autopsy was performed the next day and tissue sections were stained for histopathological examination. His intestinal samples were tested for enterovirus 71 (EV71), and the whole‐genome sequence of EV71 was analyzed. An autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, edema, moderate inflammatory infiltration, and hemorrhage as well as intestinal mucosal congestion, epithelial necrosis, thinning intestinal wall, and submucosal lymphoid follicular hyperplasia. The heart showed myocardial interstitial congestion, myocardial edema, and some inflammatory infiltrates. There were no significant alterations in the architecture of other organs. EV71 antigen and apoptotic cells were detected in brain, lung and intestine by immunohistochemical staining and TUNEL (TdT‐mediated dUTP nick‐end labeling) respectively. Intestinal contents and intestinal autopsy samples of this case were positive for EV71, and the EV71 strain was classified as subgenogroup C4. In China, the severe forms of HFMD were mostly caused by EV71 subgenogroup C4 infection. Severe intestinal damages may relate to EV71 subgenogroup C4 infection. Thus, children with severe EV71 HFMD may have serious pathological changes in their central nervous system, lungs, and gut. Physicians should pay special attention to infants with atypical symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.

Pyrrolidine dithiocarbamate inhibits enterovirus 71 replication by down-regulating ubiquitin–proteasome system

“…However, acute EV71 infection can also lead to severe neurological complications and significant mortality, especially in children under 5 years old. The neurological complications associated with EV71 infection may rang form aseptic meningitis to brainstem or cerebellar encephalitis (Badran et al, 2011;Ooi et al, 2010;Zhang et al, 2012b). Infants and young children are often susceptible to severe EV71 infection which may lead to delayed neurodevelopment and reduced cognitive functions (Chang et al, 2007).…”

Analysis of miRNAs Involved in Mouse Brain Damage upon Enterovirus 71 Infection

“…In addition, complications arising from CNS inflammation, like pulmonary oedema and myocarditis are the main causes of death (Ye et al, 2015). Post-mortem histopathological examination of EV71 infected individuals has shown a high degree of inflammation, oedema, and necrosis in the brainstem and spinal cord, accompanied by lymphocyte and macrophage infiltration (Zhang et al, 2012). These observations indicate that inflammatory damage in the brain plays a crucial role in the pathogenesis of EV71 infection.…”

“…However, the CNS possesses a unique blood-brain barrier (BBB) that serves to protect the CNS from invasion by pathogens, inflammatory cells, or other deleterious molecules (Spindler and Hsu, 2012). Vascular dilatation and infiltration of inflammatory cells such as lymphocytes and macrophages that have been observed in the brainstem of EV71-infected patients (Zhang et al, 2012) likely arose because of a complicated interaction between the virus, lymphocytes/macrophages, the BBB, and the host immune system. To date, all the research examining EV71 related miRNAs have been performed using human cell lines.…”

Necrotizing myositis causes restrictive hypoventilation in a mouse model for human enterovirus 71 infection

“…Although many infected patients have died from a pulmonary edema or hemorrhage, results from autopsy studies suggest that the cardiopulmonary disease is neurogenic [15,16]. Pathologic analysis of several EV71-infected patients has shown that inflammation occurs in different regions of the central nervous system (CNS), including the cerebral cortex, brain stem, and all levels of the spinal cord [17].…”