title: Pulmonary and central nervous system pathology in fatal cases of hand foot and mouth disease caused by enterovirus A71 infection.
abstract: In the past 17 years, neurological disease associated with enterovirus A71 (EV-A71) has increased dramatically in the Asia-Pacific region with a high fatality rate in young infants, often due to pulmonary oedema, however the mechanism of this oedema remains obscure. We analysed the brainstem, heart and lungs of 15 fatal cases of confirmed EV-A71 infection in order to understand the pathophysiological mechanism of death and pulmonary oedema. In keeping with other case studies, the main cause of death was neurogenic pulmonary oedema. In the brainstem, 11 cases showed inflammation and all cases showed parenchymal inflammation with seven cases showing moderate or severe clasmatodendrosis. No viral antigen was detected in sections of the brainstem in any of the cases. All fatal cases showed evidence of pulmonary oedema; however, there was absence of direct pulmonary viral damage or myocarditis-induced damage and EV-A71 viral antigen staining was negative. Though there was no increase in staining for Na/K-ATPase, 11 of the 15 cases showed a marked reduction in aquaporin-4 staining in the lung, and this reduction may contribute to the development of fatal pulmonary oedema.
authors.affiliation: Division of Laboratory Management, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hong Kong University, Hong Kong Special Administrative Region, China.
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hong Kong University, Hong Kong Special Administrative Region, China.
authors.forename: Joshua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Office of the Director, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Pathology Department, Beijing Hospital, Beijing, China.
authors.forename: Dongge
authors.initials: D
authors.lastname: Liu
authors.affiliation: Pathology Department, Beijing Capital Medical University Affiliated Xuanwu Hospital, Beijing, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Beijing IPE Center for Clinical Laboratory, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Pathology Department, Affiliated Hospital of Guilin Medical University, China.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institution for Infectious Disease Control and Prevention, Guangxi Provincial Centre for Disease Control and Prevention, Nanning, Guangxi, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.affiliation: Institution for Infectious Disease Control and Prevention, Hebei Provincial Centre for Disease Control and Prevention, Shijiazhuang, Hebei, China.
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Qi
authors.affiliation: Institution for Infectious Disease Control and Prevention, Henan Provincial Centre for Disease Control and Prevention, Zhengzhou, Henan, China.
authors.forename: Xueyong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Infectious Disease Control and Prevention, Changping District Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Jilin
authors.initials: J
authors.lastname: Sui
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Liao
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Malik
authors.initials: M
authors.lastname: Peiris
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Office of the Director, Chinese Centre for Disease Control and Prevention, Beijing, China. Electronic address: wangyu@chinacdc.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000821:virology; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000821:virology; D006321:Heart / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007249:Inflammation; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D009206:Myocardium / Q000473:pathology; D014709:Vero Cells
chemical_list: D020346:Aquaporins
keywords: Hand, foot and mouth disease; central nervous system; fatal cases; human enterovirus A71; pathology; pulmonary