The pulmonary complications associated with EV71-infected hand–foot–mouth disease

Li, Huanguo; Lao, Qun

doi:10.1016/j.jrid.2017.01.001

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…This coincides with the study of Li and Lao et al [15] which found that some HFMD patients had a complication of encephalitis and pulmonary edema. The complication of HFMD was related to the genotype of virus and had been detected and confirmed in South East Asia including Thailand [16][17][18][19].…”

Section: Discussionsupporting

confidence: 92%

Epidemiology of hand foot mouth disease in Northern Thailand in 2016: A prospective cohort study

Upala¹,

Apidechkul²,

Suttana³

et al. 2017

APJTD

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Section: Discussionsupporting

confidence: 92%

Epidemiology of hand foot mouth disease in Northern Thailand in 2016: A prospective cohort study

Upala¹,

Apidechkul²,

Suttana³

et al. 2017

APJTD

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“…For example, hypoxia is one of the factors correlated with long term sequelae in Taiwanese pateints [48, 49]. In addition, both hypoxia ischemia of grey nuclei and acute progressive hypoxia were observed in clinical manifestations [50, 51]. In our EV-A71 infected wt-129 mice, hypoxia occurred locally and directly in the white-jade patches of the hindlimb skeletal muscle, without involving any malfunction in the lung or respiration.…”

Section: Discussionmentioning

confidence: 91%

“…In this mouse model, the systemic hypoxia is caused indirectly by the failure in the smooth muscle involved in lung respiration. In human clinical studies, hypoxia has been noted by different research groups [48–51]. For example, hypoxia is one of the factors correlated with long term sequelae in Taiwanese pateints [48, 49].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia and therapeutic treatment of EV-A71 with an immune modulator TLR7 agonist in a new immunocompetent mouse model

et al. 2019

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BackgroundEnterovirus 71 (EV71 or EV-A71) was first identified in California about half a century ago. In recent years, outbreaks of EV-A71 were prevalent worldwide, including Taiwan, Malaysia, Singapore, Japan, and China. Between 2008 and 2011, China alone reported 1894 deaths associated with EV-A71 infection. In mild cases, EV-A71 can cause herpangina and hand-foot-and-mouth disease (HFMD). However, in severe cases, it could cause neurological disorders, including meningitis and encephalitis. Cardiopulmonary failure is common among hospitalized children with EV-A71 infection. No effective FDA-approved therapeutics against EV-A71 are clinically available.MethodsWe report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.ResultsOne intriguing disease phenotype of this new model is the development of characteristic “White-Jade” patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host’s immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.ConclusionsIn this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.

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“…EV-A71 and CV-A16 are the most important causative agents of hand, foot, and mouth disease, however, EV-A71 can also cause a diverse range of neurological diseases, including brainstem encephalitis and neurogenic pulmonary edema and is now considered as the primary etiological agent for acute flaccid paralysis [52]. Compared to the previous studies conducted in Cyprus [17,29] there was a significant increase in EV-A71, which was detected in 7 out of the 10 years investigated.…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of enteroviruses in Cyprus 2008-2017

Richter¹,

Tryfonos²,

Christodoulou³

2019

PLoS ONE

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Enteroviruses (EVs) are associated with a broad spectrum of disease manifestations, including aseptic meningitis, encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis with outbreaks being reported frequently world-wide. The aim of this study was the molecular characterization of all enteroviruses detected in Cyprus in the ten-year period from January 2008 and December 2017 as well as a description of the circulation patterns associated with the most frequently encountered genotypes. For this purpose, serum, cerebrospinal fluid, nasal swab, skin swab and/or stool samples from 2666 patients with a suspected EV infection were analysed between January 2008 and December 2017. Enteroviruses were detected in 295 (11.1%) patients, which were then investigated further for epidemiological analysis by VP1 genotyping. Overall, 24 different enterovirus types belonging to three different species were identified. The predominant species was EV-B (209/295, 71%), followed by species EV-A (77/295, 26.1%). Only one virus belonged to species EV-D, whereas EV-C enteroviruses were not identified at all. The most frequent genotypes identified were echovirus 30 (26.1%), echovirus 6 (14.2%) and coxsackievirus A6 (10.9%). While Echovirus 30 and echovirus 6 frequency was significantly higher in patients older than 3 years of age, the opposite was observed for CV-A16 and EV-A71, which dominated in young children less than 3 years. Importantly, for the current study period a significant increase of previously only sporadically observed EV-A types, such as EV-A71 and CV-A16 was noted. A phylogenetic analysis of EV-A71 showed that the majority of the EV-A71 strains from Cyprus belonged to sub-genogroup C1 and C2, with the exception of one C4 strain that was observed in 2011. The data presented provide a comprehensive picture of enteroviruses circulating in Cyprus over the last decade and will be helpful to clinicians and researchers involved in the treatment, prevention and control of enteroviral infections by helping interpret trends in enteroviral diseases by associating them with circulating serotypes, for studying the association of enteroviruses with clinical manifestations and develop strategies for designing future EV vaccines.

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The pulmonary complications associated with EV71-infected hand–foot–mouth disease

Cited by 11 publications

References 26 publications

Epidemiology of hand foot mouth disease in Northern Thailand in 2016: A prospective cohort study

Epidemiology of hand foot mouth disease in Northern Thailand in 2016: A prospective cohort study

Hypoxia and therapeutic treatment of EV-A71 with an immune modulator TLR7 agonist in a new immunocompetent mouse model

Molecular epidemiology of enteroviruses in Cyprus 2008-2017

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