A prospective, comparative study of severe neurological and uncomplicated hand, foot and mouth forms of paediatric enterovirus 71 infections

Crabol, Yoann; Pean, Polidy; Mey, Channa; Duong, Veasna; Richner, Beat; Laurent, Denis; Santy, Ky; Sothy, Heng; Dussart, Philippe; Tarantola, Arnaud; Buchy, Philippe; Horwood, Paul F.

doi:10.1016/j.ijid.2017.04.005

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…HFMDs caused by enteroviruses, such as CVA16 and EV71, are a group of infectious disease that affects millions of people globally, especially children under the age of 5 25 . Severe HFMDs are often associated with aseptic meningitis, brain stem encephalitis, and acute flaccid paralysis and can be fatal 26,27 .…”

Section: Resultsmentioning

confidence: 99%

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1

et al. 2019

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Excessive or uncontrolled release of proinflammatory cytokines caused by severe viral infections often results in host tissue injury or even death. Phospholipase C (PLC)s degrade phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) lipids and regulate multiple cellular events. Here, we report that PLCβ2 inhibits the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-β-activated kinase 1 (TAK1) activation. Mechanistically, PI(4,5)P2 lipids directly interact with TAK1 at W241 and N245, and promote its activation. Impairing of PI(4,5)P2’s binding affinity or mutation of PIP2-binding sites on TAK1 abolish its activation and the subsequent production of pro-inflammatory cytokines. Moreover, PLCβ2-deficient mice exhibit increased expression of proinflammatory cytokines and a higher frequency of death in response to virus infection, while the PLCβ2 activator, m-3M3FBS, protects mice from severe Coxsackie virus A 16 (CVA16) infection. Thus, our findings suggest that PLCβ2 negatively regulates virus-induced pro-inflammatory responses by inhibiting phosphoinositide-mediated activation of TAK1.

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Section: Resultsmentioning

confidence: 99%

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1

et al. 2019

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“…In contrast, our study found that some clinical features, such as rash, mouth ulcers, and fever, are related to coxsackieviruses. A prospective cohort study conducted in Cambodia reported that EV-A71 was associated with severe clinical signs and symptoms among HFMD-infected children, particularly those with nervous system complications [ 51 ]. EV-A71 is a predominant serotype of an HFMD outbreak in Spain and is associated with severe clinical signs such as brainstem symptoms [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology and clinical features of hand, foot and mouth disease in northern Thailand in 2016: a prospective cohort study

et al. 2018

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BackgroundHand, foot and mouth disease (HFMD) is a major communicable disease in children ≤6 years old, particularly in several countries in the Asia-Pacific Region, including Thailand. HFMD impacts public health and the economy, especially in northern Thailand.MethodsA prospective cohort study was conducted to estimate the incidence rate and to identify the serotype and clinical features of HFMD among children in northern Thailand. A validated questionnaire and throat swab were used for data collection. Polymerase chain reaction (PCR) was used to detect human enterovirus and identify its serotypes. Participants were recruited from 14 hospitals in two provinces in northern Thailand, specifically, Chiang Rai and Pha Yao Province, between January 1, 2016, and December 31, 2016. Chi-square or Fisher’s exact test was used to detect the associations of signs and symptoms with HFMD serotype. Logistic regression was used to detect the associations of variables with a positive enterovirus at alpha = 0.05.ResultIn total, 612 children aged ≤6 years from Chiang Rai and Pha Yao Province who were diagnosed with HFMD by a throat swab were recruited for the analysis. Approximately half of the cohort was male (57.2%), 57.5% was aged < 2 years, and 57.5% lived in rural areas. The incidence rate was 279.72/100,000 person-years in Chiang Rai Province and 321.24 per 100,000 person-years in Pha Yao Province. Additionally, 42.5% of children were positive for human enterovirus; among these children, 56.1% were positive for enterovirus-A (EV-A), 17.7% were positive for coxsackievirus (CV), and 26.2% were positive for other human RNA enteroviruses. During the study period, 21 distinct outbreaks of HFMD were recognized. Four to five patients (total 92 patients) were selected from each outbreak for identifying its serotype; enterovirus-A71 (EV-A71) was detected in 34.8% of HFMD cases, coxsackievirus-A16 (CV-A16) in 26.1%, coxsackivirus-A6 (CV-A6) in 15.2%, coxsackievirus-A10 (CV-A10) in 10.9%, coxsackievirus-A4 (CV-A4) in 2.2%, coxsackievirus-B2 (CV-B2) in 2.2%, human rhinovirus in 2.2%, and unknown serotype in 6.4%. Multivariable analysis demonstrated that a history of breastfeeding for ≤6 months was associated with a higher chance of enterovirus infection than a history of breastfeeding > 6 months, and children who had mother who worked as farmers, daily wage employees, and unprofessional skilled jobs had a greater chance of enterovirus infection than those who had unemployed mothers. Coxsackievirus-infected children had a higher rate of rashes on the buttocks, knee, and elbow and fever but a lower rate of lethargy and malaise than EV-A71-infected children.ConclusionsEV-A71 is a major cause of HFMD in children < 6 years old in northern Thailand, but rash, fever, and mouth ulcers are mostly found in participants with coxsackievirus infection. Breastfeeding should be promoted during early childhood for at least 6 months to prevent HFMD particularly those mother who are working in unprofessional skill jobs.Electronic supplementary materialT...

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“…Although HFMD is typically a mild illness, severe complications can sometimes occur. These include encephalitis, meningitis, acute flaccid paralysis, cardiorespiratory failure and can be fatal ( Figure 1 ; Crabol et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

et al. 2017

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Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host–viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions.

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A prospective, comparative study of severe neurological and uncomplicated hand, foot and mouth forms of paediatric enterovirus 71 infections

Abstract: EV-A71 is an important cause of encephalitis in the Asia-Pacific region. Further studies to determine the risk factors associated with severe EV-A71 disease are needed.

Cited by 14 publications

References 31 publications

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1

Molecular epidemiology and clinical features of hand, foot and mouth disease in northern Thailand in 2016: a prospective cohort study

Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

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