Rhombencephalitis and Coxsackievirus A16

Goto, Kazuna; Sanefuji, Masafumi; Kusuhara, Koichi; Nishimura, Yorihiro; Shimizu, Hiroyuki; Kira, Ryutaro; Torisu, Hiroyuki; Hara, Toshiro

doi:10.3201/eid1510.090594

Cited by 56 publications

(39 citation statements)

References 9 publications

(19 reference statements)

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“…Clinical symptoms and disease caused by CA16 infection are usually mild, such as HFMD, fever, and herpangina. However, some reports indicate that CA16 infection also can cause severe complications, such as aseptic meningitis, rhombencephalitis, pulmonary complications, cardiac and pericardial disease, and even fatal myocarditis and pneumonitis (14,21,34,40,(44)(45)(46)50). The disease process caused by the CA16 infection progressed very quickly when severe complications occurred.…”

Section: Discussionmentioning

confidence: 99%

“…While most CA16-associated HFMD infections present only mild symptoms, many recent reports show that CA16 infections might lead to severe health issues, such as aseptic meningitis, rhombencephalitis, cardiac and pericardial disease, pulmonary complications, spontaneous abortion, and even lethal myocarditis and pneumonia (14,21,23,40,(44)(45)(46)50). The coinfection of EV71 and CA16 makes it more complex and difficult to control epidemic HFMD (54).…”

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A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

Mao

Wang

Gao

et al. 2012

J Virol

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cTo evaluate vaccine efficacy in protecting against coxsackievirus A16 (CA16), which causes human hand, foot, and mouth disease (HFMD), we established the first neonatal mouse model. In this article, we report data concerning CA16-induced pathological changes, and we demonstrate that anti-CA16 antibody can protect mice against lethal challenge and that the neonatal mouse model could be used to evaluate vaccine efficacy. To establish a mouse model, a BJCA08/CA16 strain (at 260 50% lethal doses [LD 50 ]) was isolated from a patient and used to intracerebrally (i.c.) inoculate neonatal mice. The infection resulted in wasting, hind-limb paralysis, and even death. Pathological examination and immunohistochemistry (IHC) staining indicated that BJCA08 had a strong tropism to muscle and caused severe necrosis in skeletal and cardiac muscles. We then found that BJCA08 pretreated with goat anti-G10/CA16 serum could significantly lose its lethal effect in neonatal mice. When the anti-G10 serum was intraperitoneally (i.p.) injected into the neonatal mice and, within 1 h, the same mice were intracerebrally inoculated with BJCA08, there was significant passive immunization protection. In a separate experiment, female mice were immunized with formaldehyde-inactivated G10/CA16 and BJCA08/CA16 and then allowed to mate 1 h after the first immunization. We found that there was significant protection against BJCA08 for neonatal mice born to the immunized dams. These data demonstrated that anti-CA16 antibody may block virus invasion and protect mice against lethal challenge, and that the neonatal mouse model was a viable tool for evaluating vaccine efficacy. C oxsackievirus A16 (CA16) belongs to the Enterovirus genus of the Picornaviridae family and is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) (4,16,19). CA16 was first isolated in 1951 (43). It is a single positive-stranded RNA virus and has an icosahedral symmetry structure. Its genome has approximately 7,410 nucleotides with one predominant serotype. Based on the VP4 nucleotide sequences, CA16 is classified into three distinct genetic lineages: A, B, and C. Before the 1990s, lineages A and B were the major epidemic strains in Asia (predominantly the B strain). After that, the CA16 gene gradually mutated to form lineage C, which replaced the B strain as the predominant epidemic strain (22).Epidemics of HFMD have been reported in England, Australia, Japan, Germany, Malaysia, Singapore, mainland China, and Taiwan (2,4,11,19,23,27,32,38,41,48). Recently, HFMD was highly epidemical in the west Pacific region, resulting in severe illness and fatalities (15, 23). The HFMD epidemics were mainly caused by CA16 and human enterovirus 71 (EV71), which circulated alternatively or together in the epidemic area (19,22,23,25,37). Because the most severe or fatal cases were caused by EV71, studies have mainly focused on EV71 but not CA16. However, in England, the largest HFMD outbreak (in 1994) was caused by CA16 (2). Similarly, in Taiwan the leading cau...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

Mao

Wang

Gao

et al. 2012

J Virol

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“…Compared with EV71, another major causative agent of HFMD, the patients infected with CVA16 usually showed relatively mild symptoms followed by fever, maculopapular rashes on the skin of the hands, feet, and oral cavity, with a certain self-limiting trend [5,10]. However, severe complications occasionally occurred in individuals infected with CVA16, such as encephalitis [11,12], myocarditis and intractable shock [13], fatal pneumonitis [14], severe rhabdomyolysis, renal failure [15], and even death [13][14][15]. Apparently, CVA16 infection is not always a benign one, but so far, the molecular evolution and pathogenesis of CVA16 have not been fully described.…”

Section: Introductionmentioning

confidence: 99%

Genetic characteristics of coxsackievirus A16 associated with hand, foot, and mouth disease in Nanjing, China

Wei

Qiao

Shi

et al. 2016

J Infect Dev Ctries

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Introduction: Coxsackievirus A16 (CVA16) is a main pathogen in hand, foot, and mouth disease (HFMD) worldwide. This study intended to clarify the genetic characteristics of CVA16 associated with HFMD in a defined area in Nanjing, China. Methodology: A total of 175 CVA16 strains isolated from throat swabs between 2011 and 2013 were obtained through sentinel hospitals in Nanjing. Multiplex polymerase chain reaction (PCR) was used to amplify the VP1 sequence of local CVA16 strains, and their genetic relationship with 138 CVA16 strains isolated in China and other countries of the world was compared. Results: Phylogenetic analysis based on complete VP1 sequences revealed that subgenotype B1a and B1b were predominantly circulating in Nanjing and B1b strains were spread more widely. The evolution of CVA16 strains is very conservative, with a mean distance of less than 9%. Moreover, six reported conservative regions in VP1 protein were examined, and three of them exhibited high conservation in all CVA16 genotypes except the G-10 prototype and may serve for further vaccine research. Conclusions: The CVA16 strains circulating in Nanjing, China, in 2011 to 2013 belonged to different genotypes and evolved in a conservative way. To provide further evidence for epidemiological linkage and evolutionary recombination events in CVA16, persistent surveillance of HFMD-associated pathogens is required.

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“…The presence of enterovirus-RNA is not always possible, and, for example, some cases of enterovirus brainstem encephalitis have already been described without any CSF positive enterovirus detection [3,15,18,19]. The detection of the virus in the nasopharyngeal and stool specimen and the absence of such detection in CSF confirm the necessity of peripheral sampling in order to extend the virological diagnosis.…”

Section: Discussionmentioning

confidence: 99%

A Non-Human Enterovirus A71 Brainstem Encephalitis in France In 2016

Voinçon¹,

Mansuy²,

Mirand³

et al. 2017

Clin Microbiol Infect Dis

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Brainstem encephalitis may be a serious complication of enteroviral infection. Mainly due to human enterovirus A71, it has become a real health issue in Asia Oceania. In Europe, infection remains sporadic or causes small epidemics. Here we report an original case of Coxsackie B3 brainstem encephalitis, the first one to the best of our knowledge. A healthy five years old girl developed brainstem involvement signs. Clinical examination showed no fever, normal heart frequency and normal blood pressure. She presented a self-limited divergent squint which lasted 2 hours followed by oculomotor troubles and a right facial palsy. Biological tests performed on cerebrospinal fluid were not informative. The cerebral Magnetic Resonance Imaging was compatible with a rhombencephalitis. She totally recovered one month after this episode.Enterovirus was detected by real-time PCR on the nasopharyngeal and the stool sample collected on day of admission but was not detected on the cerebrospinal fluid. Coxsackie B3 was genotyped by sequencing of VP1 protein coding sequence. Despite the absence of enterovirus detection on the cerebrospinal fluid, the diagnosis of enterovirus rhombencephalitis was classified as probable by the French National Reference Centre for enterovirus. Our description highlights the necessity of nasopharyngeal and stool sampling in order to extend the diagnosis with the aim of learning about enterovirus circulation in Europe as well.

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Rhombencephalitis and Coxsackievirus A16

Cited by 56 publications

References 9 publications

A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

Genetic characteristics of coxsackievirus A16 associated with hand, foot, and mouth disease in Nanjing, China

A Non-Human Enterovirus A71 Brainstem Encephalitis in France In 2016

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