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Hand Foot and Mouth Disease

Disease Pathophysiology Research Template

2026-03-09
Falcon MONDO:0005779 Model: Edison Scientific Literature 41 citations

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Pathophysiology Research Template

Target Disease

  • Disease Name: Hand Foot and Mouth Disease
  • MONDO ID: (if available)
  • Category: Infectious

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Hand Foot and Mouth Disease. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

  • What are the primary pathophysiological mechanisms?
  • What molecular pathways are dysregulated?
  • What cellular processes are affected?

2. Key Molecular Players

  • Genes/Proteins: Which genes are causally involved or implicated?
  • Chemical Entities: What metabolites, drugs, or small molecules are relevant?
  • Cell Types: Which cell types are primarily affected?
  • Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

  • What biological processes (GO terms) are disrupted?
  • Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

  • Where in the cell do key processes occur?
  • Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

  • What is the sequence of events from initial trigger to clinical manifestation?
  • Are there distinct stages or phases?

6. Phenotypic Manifestations

  • What are the key clinical phenotypes?
  • How do they relate to the underlying mechanisms?

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Comprehensive pathophysiology report: Hand, Foot and Mouth Disease (HFMD)

Disease overview and definitions

Hand, foot and mouth disease (HFMD) is an acute, highly contagious pediatric infection most commonly caused by Enterovirus A species, including Enterovirus A71 (EV‑A71), coxsackievirus A16 (CV‑A16), coxsackievirus A6 (CV‑A6), and coxsackievirus A10 (CV‑A10). Severe HFMD is classically associated with EV‑A71 and features neurologic involvement (e.g., brainstem encephalitis) and cardiopulmonary complications (notably pulmonary edema), whereas most infections are self-limited mucocutaneous disease. Recent surveillance has shown a post‑EV‑A71 vaccine shift toward CV‑A6/CV‑A10 as dominant causes of HFMD in multiple Chinese settings (yang2023molecularepidemiologyand pages 1-2, yuan2024epidemiologicalandetiological pages 1-2, xia2024clinicalaetiologicaland pages 1-2).

Current understanding (unifying concept). HFMD pathophysiology is best conceptualized as (i) mucosal entry and early replication, (ii) viremia and tissue dissemination, (iii) host innate and adaptive immune responses (and viral evasion), and (iv) in a subset, neuroinvasion with blood–brain barrier (BBB) dysfunction and brainstem injury leading to systemic inflammatory and neurogenic cardiopulmonary collapse (zhu2023currentstatusof pages 11-12, ji2024thekeymechanisms pages 7-8, ji2024thekeymechanisms pages 12-13).

Note on ontology identifiers. MONDO ID was not available in the retrieved sources; this report provides ontology-ready terms (GO/CL/UBERON/HP/CHEBI) where possible based on the cited mechanistic literature.

1) Core pathophysiology (molecular and cellular mechanisms)

1.1 Viral entry, receptors, and uncoating (EV‑A71 emphasized)

Receptor-mediated entry is multi-step and cell-type dependent. A key 2024 mechanistic advance is strong evidence that EV‑A71 uses distinct factors for (a) cell-surface attachment/internalization versus (b) intracellular uncoating.

This attachment–uncoating separation refines older “single receptor” models and implies that receptor expression and endolysosomal trafficking biology are central determinants of tissue tropism and severity (nishimura2024enterovirusa71does pages 1-2, nishimura2024enterovirusa71does pages 2-4).

A complementary 2024 pathogenesis study highlights host regulation of receptor availability: TRIB3 promotes EV‑A71 infection, in part by maintaining “the metabolic stability of…SCARB2…to enhance the infectious entry and spreading of the virus” (Emerging Microbes & Infections; Jan 2024; https://doi.org/10.1080/22221751.2024.2307514) (wang2024tribblespseudokinase3 pages 1-2).

Visual synthesis (authoritative review figure/table). Zhu et al. (J Biomed Sci; Feb 2023; https://doi.org/10.1186/s12929-023-00908-4) provide (i) a table of major enterovirus receptors (including SCARB2 and PSGL‑1) and (ii) a schematic of innate immune evasion mechanisms relevant to HFMD pathogenesis (zhu2023currentstatusof media ba7d7b3e, zhu2023currentstatusof media 86593dfb).

1.2 Tissue tropism, dissemination, and neuroinvasion

Entry sites and early replication. EV‑A71 infection begins at mucosal epithelial surfaces of the gastrointestinal and respiratory tracts in the early phase of infection (wei2024recentprogressin pages 2-4).

Progression to systemic disease. Severe HFMD is linked to CNS involvement—particularly brainstem structures—and downstream dysautonomia and inflammation (ji2024thekeymechanisms pages 7-8, zhu2023currentstatusof pages 11-12). Ji et al. (Infectious Medicine; Sep 2024; https://doi.org/10.1016/j.imj.2024.100124) describe clinical progression consistent with a systemic dissemination step: “primary and a secondary viremia after ~4–5 days enabling systemic/CNS spread” (ji2024thekeymechanisms pages 7-8).

BBB disruption as a gateway to CNS disease. Multiple mechanisms converge on BBB compromise:

  • In CV‑A16, IP‑10/CXCL10 rises early and is mechanistically linked to BBB junctional loss via TNF‑α. Hu et al. (Frontiers in Immunology; Nov 2024; https://doi.org/10.3389/fimmu.2024.1374447) report elevation of “TLR3‑TRIF‑TRAF3‑TBK1‑NF‑κB and RIG‑I/MDA5‑MAVS‑…‑TBK1‑NF‑κB pathways” and show that IP‑10/TNF‑α reduce junctional proteins (Claudin5, Occludin, ZO‑1, VE‑cadherin) in infected endothelial cells, “enhanc[ing] virus entry into the CNS” (hu2024ip10actsearly pages 1-2).
  • Ji et al. (2024) summarize BBB disruption routes that include “MMP‑9–mediated disruption of junctional complexes” in CV‑A16 and other BBB‑integrity mechanisms (ji2024thekeymechanisms pages 7-8, ji2024thekeymechanisms pages 12-13).

Neural routes and extracellular vesicles. Ji et al. further summarize evidence for neural spread (e.g., retrograde axonal transport) and non-lytic dissemination via exosomes/small extracellular vesicles that can enable CNS entry without overt BBB destruction (ji2024thekeymechanisms pages 7-8, ji2024thekeymechanisms pages 12-13).

1.3 Innate immune sensing and viral immune evasion (dysregulated pathways)

Mechanistically, severe disease reflects both antiviral responses and viral suppression of those responses.

Key innate-sensing nodes. A 2024 review of EV‑A71 innate immunity (International Journal of Molecular Sciences; May 2024; https://doi.org/10.3390/ijms25115688) summarizes canonical sensing and signaling engaged by EV‑A71, including endosomal TLR3/TLR7 and cytosolic RIG‑I/MDA5→MAVS leading to IRF3/IRF7 and NF‑κB activation and downstream type I interferon signaling via IFNAR→JAK/STAT (wei2024recentprogressin pages 2-4).

Viral antagonism of interferon and inflammasome. Zhu et al. (J Biomed Sci; Feb 2023; https://doi.org/10.1186/s12929-023-00908-4) provide multiple examples of EV‑A71 immune evasion/rewiring:

  • Inflammasome manipulation: EV‑A71 3D polymerase binds NLRP3 to form a complex promoting IL‑1β secretion, whereas viral proteases can cleave NLRP3 to inhibit activation (zhu2023currentstatusof pages 11-12).
  • Type I IFN pathway interference: EV proteases can impair type I IFN signaling (e.g., targeting IFNAR and suppressing STAT1/STAT2 nuclear translocation) and cleave RIG‑I (zhu2023currentstatusof pages 11-12).

These observations map HFMD severity to dysregulation of innate antiviral and inflammatory cascades (type I IFN signaling, NF‑κB activation, inflammasome activation) rather than viral cytopathicity alone (zhu2023currentstatusof pages 11-12, wei2024recentprogressin pages 2-4).

1.4 Metabolic reprogramming as a host-dependency mechanism

A 2023 proteomics+metabolomics study provides direct evidence that EV‑A71 reprograms glycolysis:

This supports a host-directed therapeutic concept (metabolic intervention) in addition to antiviral approaches (shi2023proteomicandmetabonomic pages 12-13).

2) Key molecular players (genes/proteins, chemicals, cell types, anatomy)

2.1 Gene/protein players (HGNC-level; key mechanisms)

Primary mechanistic nodes supported by the retrieved evidence include:

2.2 Chemical entities (CHEBI-level)

2.3 Cell types (CL-level; evidence-based involvement)

2.4 Anatomical locations (UBERON-level)

3) Biological processes (GO-ready) disrupted in HFMD

Representative processes supported in the retrieved sources include:

4) Cellular components (GO-CC-ready)

Key subcellular sites implicated include:

5) Disease progression: trigger-to-phenotype sequence (integrated model)

Stage 1: Exposure and mucosal replication

Exposure typically occurs through fecal–oral and/or respiratory routes, with early replication at GI/respiratory mucosa (wei2024recentprogressin pages 2-4).

Stage 2: Viremia and dissemination

A subset of cases progress beyond localized mucocutaneous disease, with systemic dissemination enabling access to secondary tissues including muscle and CNS; Ji et al. summarize a clinical timeline including a secondary viremia around 4–5 days (ji2024thekeymechanisms pages 7-8).

Stage 3: Innate immune activation and viral evasion (determinant of viral load/inflammation)

Host PRR signaling (TLRs and RIG‑I/MDA5) drives IFN and cytokine responses, while EV‑A71 employs multiple evasion strategies (IFNAR/STAT interference; RIG‑I cleavage; inflammasome modulation) (wei2024recentprogressin pages 2-4, zhu2023currentstatusof pages 11-12).

Stage 4 (severe subset): BBB dysfunction and neuroinvasion

In CV‑A16, IP‑10 (CXCL10) is induced early and promotes TNF‑α, which reduces junctional proteins and facilitates virus entry into the CNS (hu2024ip10actsearly pages 1-2). Broader HFMD literature synthesis implicates additional BBB-disruptive pathways (e.g., MMP‑9) (ji2024thekeymechanisms pages 7-8, ji2024thekeymechanisms pages 12-13).

Stage 5: CNS/brainstem injury → systemic collapse

Brainstem infection/damage is linked to sympathetic hyperactivation and a catecholamine “storm,” driving pulmonary microvascular leakage and cardiopulmonary failure. Ji et al. report marked catecholamine elevation in severe cases and mechanistic links to pulmonary edema: excessive catecholamines increase pulmonary permeability and can induce cardiomyocyte injury (ji2024thekeymechanisms pages 7-8). Zhu et al. similarly connect cardiopulmonary failure to brainstem-mediated hypercatecholaminemia (zhu2023currentstatusof pages 11-12).

6) Phenotypic manifestations and mechanistic links (HP-ready)

Recent developments (2023–2024 prioritized)

A) Refined receptor/uncoating model (2024)

The most concrete 2024 mechanistic advance in this corpus is the demonstration that EV‑A71 does not rely on cell-surface SCARB2 for attachment; instead, SCARB2 acts intracellularly in endolysosomes for uncoating. Key quotes include SCARB2 being “within the cytoplasm, but not on the cell surface” and “highly concentrated in lysosomes and late endosomes…likely to trigger acid-dependent uncoating” (Nishimura et al., Feb 2024, PLOS Pathogens; https://doi.org/10.1371/journal.ppat.1012022) (nishimura2024enterovirusa71does pages 1-2, nishimura2024enterovirusa71does pages 2-4).

B) Chemokine-driven BBB disruption pathway for CV‑A16 (2024)

Hu et al. (Nov 2024; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2024.1374447) provide direct mechanistic evidence that the IP‑10/TNF‑α axis reduces BBB junctional proteins and increases CNS entry during CV‑A16 infection, with anti‑IP‑10 or anti‑TNF‑α improving outcomes in a suckling mouse model (hu2024ip10actsearly pages 1-2).

C) Host metabolic dependency and potential host-directed therapy (2023)

Shi et al. (Nov 2023; PROTEOMICS; https://doi.org/10.1002/pmic.202200362) show glycolysis activation during EV‑A71 infection and that DCA or ENO1 knockdown suppresses infection (shi2023proteomicandmetabonomic pages 12-13).

D) Pathogen landscape shift post EV‑A71 vaccination (2023–2024)

Multiple surveillance studies show EV‑A71 reductions and increasing dominance of CV‑A6/CV‑A10:

These epidemiologic shifts are critical to “real-world implementation” because they create vaccine/therapeutic pressure toward multivalent approaches beyond EV‑A71-only strategies (yang2023molecularepidemiologyand pages 1-2, yuan2024epidemiologicalandetiological pages 1-2).

Current applications and real-world implementations

1) Vaccination impact (population-level)

Real-world surveillance supports a sharp decrease in EV‑A71 detections and severe HFMD after EV‑A71 vaccine rollout (e.g., post‑2016 trends in multiple Chinese datasets) (yang2023molecularepidemiologyand pages 1-2, dai2024epidemiologyandetiology pages 4-6). However, non‑EV‑A71 serotypes now dominate detected cases in many settings, implying that single-serotype vaccination is insufficient to fully control HFMD burden (yang2023molecularepidemiologyand pages 1-2, yuan2024epidemiologicalandetiological pages 1-2, dai2024epidemiologyandetiology pages 4-6).

2) Translational targets and therapeutic concepts

  • Host-directed metabolic inhibition: DCA and ENO1 perturbation suppress EV‑A71 infection in vitro, supporting exploration of metabolic pathway modulation as adjunct therapy (shi2023proteomicandmetabonomic pages 12-13).
  • Anti-chemokine/cytokine strategies for severe disease: Anti‑IP‑10 (Eldelumab in vitro) and anti‑TNF‑α reduced severity in CV‑A16 models, indicating a plausible immunomodulatory strategy for neuroinvasive HFMD phenotypes (hu2024ip10actsearly pages 1-2).

These are not established clinical standards of care in the retrieved sources, but represent mechanistically grounded directions.

Expert interpretation (authoritative synthesis)

Mechanistic convergence. Across pathogens, severe HFMD appears to converge on BBB compromise, neuroinflammation, and autonomic dysregulation rather than only higher peripheral viral replication. The IP‑10/TNF‑α → tight junction loss mechanism (CV‑A16) provides a testable causal chain from innate immune signaling to BBB dysfunction and neuroinvasion (hu2024ip10actsearly pages 1-2). The catecholamine-storm mechanism provides a plausible bridge from brainstem injury to pulmonary edema and rapid deterioration (ji2024thekeymechanisms pages 7-8, zhu2023currentstatusof pages 11-12).

Host genetics as an outcome modifier. Case-control genetic studies support the concept that host receptor variants influence severity (SCARB2 SNPs protective; PSGL‑1 VNTR modest risk) (duan2023theeffectsof pages 1-2, wang2024correlationsofpsgl1 pages 2-4).

Implication for future countermeasures. The consistent shift to CV‑A6/CV‑A10 dominance (while EV‑A71 remains a key severe pathogen) suggests that multivalent vaccines and broad-spectrum antivirals/host-directed therapies are likely necessary for durable control (yang2023molecularepidemiologyand pages 1-2, yuan2024epidemiologicalandetiological pages 1-2, dai2024epidemiologyandetiology pages 4-6).

Relevant statistics and data (recent studies)

Pathogen shift and burden

Hospitalization and severity signals

Host genetic associations

Ontology-ready annotation table

Table (click to expand)
Category Entity Role in HFMD Pathophysiology Key Evidence
Gene/Protein SCARB2 (HGNC:1664) Primary intracellular receptor facilitating viral uncoating in acidic endosomes/lysosomes; SNPs associated with reduced severity. (wei2024recentprogressin pages 2-4, nishimura2024enterovirusa71does pages 6-9, nishimura2024enterovirusa71does pages 1-2, duan2023theeffectsof pages 1-2, duan2023theeffectsof pages 6-7)
Gene/Protein SELPLG / PSGL-1 (HGNC:10720) Major attachment receptor on leukocytes directing viral tropism; VNTR polymorphisms linked to severe disease susceptibility. (wei2024recentprogressin pages 2-4, nishimura2024enterovirusa71does pages 6-9, nishimura2024enterovirusa71does pages 2-4, wang2024correlationsofpsgl1 pages 2-4, wang2024correlationsofpsgl1 pages 1-2)
Gene/Protein CXCL10 / IP-10 (HGNC:10636) Pro-inflammatory chemokine elevated early in infection that drives TNF-alpha production and blood-brain barrier disruption. (ji2024thekeymechanisms pages 12-13, zhu2023currentstatusof pages 11-12, hu2024ip10actsearly pages 1-2)
Gene/Protein TNF / TNF-alpha (HGNC:11892) Cytokine induced by IP-10 that reduces endothelial tight junction proteins (Claudin5, Occludin), promoting neuroinvasion. (hu2024ip10actsearly pages 1-2, zhu2023currentstatusof pages 11-12)
Gene/Protein NLRP3 (HGNC:16400) Inflammasome component bounded by viral 3D polymerase to form a complex promoting IL-1beta secretion. (zhu2023currentstatusof pages 11-12, wei2024recentprogressin pages 2-4, zhu2023currentstatusof media ba7d7b3e)
Gene/Protein ENO1 (HGNC:3350) Glycolytic enzyme upregulated by EV-A71 to reprogram host metabolism and support viral replication. (shi2023proteomicandmetabonomic pages 1-2, shi2023proteomicandmetabonomic pages 12-13)
Gene/Protein TRIB3 (HGNC:16228) Host pseudokinase that maintains SCARB2 metabolic stability, enhancing viral entry and spread. (wang2024tribblespseudokinase3 pages 1-2)
Gene/Protein MMP9 (HGNC:7176) Matrix metalloproteinase implicated in disrupting junctional complexes at the blood-brain barrier. (ji2024thekeymechanisms pages 12-13, ji2024thekeymechanisms pages 7-8)
Gene/Protein IFNAR1 / IFNAR2 Type I interferon receptor subunits targeted by viral proteases to evade innate immune signaling. (wei2024recentprogressin pages 2-4)
Gene/Protein VIM / Vimentin (HGNC:12692) Cell surface attachment receptor upregulated by viral VP1, facilitating BBB penetration. (ji2024thekeymechanisms pages 7-8, hu2024ip10actsearly pages 1-2)
Pathway (GO) Type I interferon signaling pathway (GO:0060337) Antiviral response pathway suppressed by viral cleavage of RIG-I, MAVS, and inhibition of STAT nuclear translocation. (zhu2023currentstatusof pages 11-12, wei2024recentprogressin pages 2-4, zhu2023currentstatusof media ba7d7b3e)
Pathway (GO) Glycolytic process (GO:0006096) Metabolic pathway activated/reprogrammed by virus via ENO1 upregulation to support replication. (shi2023proteomicandmetabonomic pages 1-2, shi2023proteomicandmetabonomic pages 12-13)
Cellular Component Lysosome (GO:0005764) / Late Endosome (GO:0005770) Acidic compartments where SCARB2 resides and triggers the critical viral uncoating step. (nishimura2024enterovirusa71does pages 6-9, nishimura2024enterovirusa71does pages 1-2, nishimura2024enterovirusa71does pages 13-15, nishimura2024enterovirusa71does pages 10-13)
Cellular Component Inflammasome complex (GO:0061702) Multiprotein complex (3D-NLRP3-ASC) engaged to drive cytokine storm and inflammation. (zhu2023currentstatusof pages 11-12, wei2024recentprogressin pages 2-4)
Cellular Component Tight junction (GO:0005923) Endothelial barrier structure degraded by IP-10/TNF-alpha-mediated downregulation of ZO-1/Occludin. (hu2024ip10actsearly pages 1-2)
Chemical Entity Norepinephrine (CHEBI:18357) Major mediator of the "catecholamine storm" causing neurogenic pulmonary edema and cardiac failure. (ji2024thekeymechanisms pages 7-8, zhu2023currentstatusof pages 11-12)
Chemical Entity Dichloroacetic acid (CHEBI:41879) Glycolysis inhibitor shown to suppress EV-A71 infection in vitro. (shi2023proteomicandmetabonomic pages 1-2, shi2023proteomicandmetabonomic pages 12-13)
Anatomy Blood-brain barrier (UBERON:0000202) Physical barrier compromised by viral proteins (VP1) and host cytokines, facilitating neuroinvasion. (ji2024thekeymechanisms pages 12-13, ji2024thekeymechanisms pages 7-8, hu2024ip10actsearly pages 1-2)
Anatomy Brainstem (UBERON:0002298) Critical CNS region infected via neural routes, triggering autonomic dysfunction and catecholamine surge. (ji2024thekeymechanisms pages 7-8, zhu2023currentstatusof pages 11-12)
Phenotype Pulmonary edema (HP:0002104) Severe complication resulting from brainstem damage and subsequent sympathetic hyperactivation. (ji2024thekeymechanisms pages 12-13, ji2024thekeymechanisms pages 7-8)

Table: A structured mapping of key molecular entities, biological processes, and anatomical sites involved in Hand, Foot, and Mouth Disease pathophysiology, linked to ontology categories and recent supporting evidence.

Evidence items (PMID-focused) and links

The retrieved evidence set includes several high-quality mechanistic papers with DOI links and publication dates; however, PMIDs were not present in the provided tool outputs for many items. Below are the URL/DOI and publication month/year as provided by the tool results:

1) Nishimura et al. “Enterovirus A71 does not meet the uncoating receptor SCARB2 at the cell surface.” PLOS Pathogens, Feb 2024. https://doi.org/10.1371/journal.ppat.1012022 (nishimura2024enterovirusa71does pages 1-2)

2) Hu et al. “IP‑10 acts early in CV‑A16 infection to induce BBB destruction…” Frontiers in Immunology, Nov 2024. https://doi.org/10.3389/fimmu.2024.1374447 (hu2024ip10actsearly pages 1-2)

3) Wei et al. “Recent Progress in Innate Immune Responses to Enterovirus A71 and Viral Evasion Strategies.” Int J Mol Sci, May 2024. https://doi.org/10.3390/ijms25115688 (wei2024recentprogressin pages 2-4)

4) Zhu et al. “Current status of hand-foot-and-mouth disease.” Journal of Biomedical Science, Feb 2023. https://doi.org/10.1186/s12929-023-00908-4 (zhu2023currentstatusof pages 11-12)

5) Shi et al. “Proteomic and metabonomic analysis uncovering EV‑A71 reprogramming host cell metabolic pathway.” PROTEOMICS, Nov 2023. https://doi.org/10.1002/pmic.202200362 (shi2023proteomicandmetabonomic pages 1-2)

6) Duan et al. “The effects of SCARB2 and SELPLG gene polymorphisms on EV71 infection…” Biomolecules and Biomedicine, Apr 2023. https://doi.org/10.17305/bb.2023.8948 (duan2023theeffectsof pages 1-2)

7) Wang et al. “Correlations of PSGL‑1 VNTR polymorphism with susceptibility to severe HFMD…” Virology Journal, Aug 2024. https://doi.org/10.1186/s12985-024-02461-4 (wang2024correlationsofpsgl1 pages 2-4)

8) Yang et al. “Molecular epidemiology…HFMD in Chengdu, 2013–2022.” Virology Journal, Sep 2023. https://doi.org/10.1186/s12985-023-02169-x (yang2023molecularepidemiologyand pages 1-2)

9) Xia et al. “Outpatient HFMD in Chengdu, 2019–2022.” BMC Public Health, Dec 2024. https://doi.org/10.1186/s12889-024-20909-8 (xia2024clinicalaetiologicaland pages 1-2)

Limitations of this synthesis (evidence coverage)

1) While EV‑A71 and CV‑A16 mechanisms are richly supported in the retrieved full-text evidence, CV‑A6/CV‑A10 molecular receptor usage and CNS mechanisms were not deeply extracted from the available full texts in this run; the report therefore emphasizes shared enterovirus mechanisms and EV‑A71/CV‑A16 exemplars. 2) PMIDs were not surfaced by the tools for many included items; DOIs/URLs and publication dates are provided as substitutes.

References

  1. (yang2023molecularepidemiologyand pages 1-2): Qiuxia Yang, Fang Liu, Li Chang, Shuyu Lai, Jie Teng, Jiaxin Duan, Hui Jian, Ting Liu, and Guanglu Che. Molecular epidemiology and clinical characteristics of enteroviruses associated hfmd in chengdu, china, 2013–2022. Virology Journal, Sep 2023. URL: https://doi.org/10.1186/s12985-023-02169-x, doi:10.1186/s12985-023-02169-x. This article has 43 citations and is from a peer-reviewed journal.

  2. (yuan2024epidemiologicalandetiological pages 1-2): Yongjuan Yuan, Yun Chen, Jian Huang, Xiaoxia Bao, Wei Shen, Yi Sun, and Haiyan Mao. Epidemiological and etiological investigations of hand, foot, and mouth disease in jiashan, northeastern zhejiang province, china, during 2016 to 2022. Frontiers in Public Health, May 2024. URL: https://doi.org/10.3389/fpubh.2024.1377861, doi:10.3389/fpubh.2024.1377861. This article has 12 citations.

  3. (xia2024clinicalaetiologicaland pages 1-2): Maoyao Xia, Yu Zhu, Juan Liao, Shirong Zhang, Denghui Yang, Peng Gong, Shihang Zhang, Guiyu Jiang, Yue Cheng, Jiantong Meng, Zhenhua Chen, Ye Liao, Xiaojing Li, Yilan Zeng, Chaoyong Zhang, and Lu Long. Clinical, aetiological, and epidemiological studies of outpatient cases of hand, foot, and mouth disease in chengdu, china, from 2019 to 2022: a retrospective study. BMC Public Health, Dec 2024. URL: https://doi.org/10.1186/s12889-024-20909-8, doi:10.1186/s12889-024-20909-8. This article has 5 citations and is from a peer-reviewed journal.

  4. (zhu2023currentstatusof pages 11-12): P. Zhu, W. Ji, Dong Li, Zijie Li, Yu Chen, B. Dai, Shujie Han, Shuaiyin Chen, Yuefei Jin, and G. Duan. Current status of hand-foot-and-mouth disease. Journal of Biomedical Science, Feb 2023. URL: https://doi.org/10.1186/s12929-023-00908-4, doi:10.1186/s12929-023-00908-4. This article has 243 citations and is from a domain leading peer-reviewed journal.

  5. (ji2024thekeymechanisms pages 7-8): Wangquan Ji, Peiyu Zhu, Yuexia Wang, Yu Zhang, Zijie Li, Haiyan Yang, Shuaiyin Chen, Yuefei Jin, and Guangcai Duan. The key mechanisms of multi-system responses triggered by central nervous system damage in hand, foot, and mouth disease severity. Infectious Medicine, 3:100124, Sep 2024. URL: https://doi.org/10.1016/j.imj.2024.100124, doi:10.1016/j.imj.2024.100124. This article has 8 citations.

  6. (ji2024thekeymechanisms pages 12-13): Wangquan Ji, Peiyu Zhu, Yuexia Wang, Yu Zhang, Zijie Li, Haiyan Yang, Shuaiyin Chen, Yuefei Jin, and Guangcai Duan. The key mechanisms of multi-system responses triggered by central nervous system damage in hand, foot, and mouth disease severity. Infectious Medicine, 3:100124, Sep 2024. URL: https://doi.org/10.1016/j.imj.2024.100124, doi:10.1016/j.imj.2024.100124. This article has 8 citations.

  7. (nishimura2024enterovirusa71does pages 1-2): Yorihiro Nishimura, Kei Sato, Yoshio Koyanagi, Takaji Wakita, Masamichi Muramatsu, Hiroyuki Shimizu, Jeffrey M. Bergelson, and Minetaro Arita. Enterovirus a71 does not meet the uncoating receptor scarb2 at the cell surface. PLOS Pathogens, 20:e1012022, Feb 2024. URL: https://doi.org/10.1371/journal.ppat.1012022, doi:10.1371/journal.ppat.1012022. This article has 8 citations and is from a highest quality peer-reviewed journal.

  8. (nishimura2024enterovirusa71does pages 2-4): Yorihiro Nishimura, Kei Sato, Yoshio Koyanagi, Takaji Wakita, Masamichi Muramatsu, Hiroyuki Shimizu, Jeffrey M. Bergelson, and Minetaro Arita. Enterovirus a71 does not meet the uncoating receptor scarb2 at the cell surface. PLOS Pathogens, 20:e1012022, Feb 2024. URL: https://doi.org/10.1371/journal.ppat.1012022, doi:10.1371/journal.ppat.1012022. This article has 8 citations and is from a highest quality peer-reviewed journal.

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