Correlation Analysis of EV71 Detection and Case Severity in Hand, Foot, and Mouth Disease in the Hunan Province of China

Gao, Lidong; Hu, Shixiong; Zhang, Hong; Luo, Kaiwei; Liu, Yunzhi; Xu, Qi; Huang, Wei E.; Deng, Zhihong; Zhou, Shuaifeng; Liu, Fuqiang; Zhang, Fan; Chen, Yu

doi:10.1371/journal.pone.0100003

Cited by 25 publications

(26 citation statements)

References 8 publications

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“…52, 64, 65 Subgenotype C4a, which was detected in most Cambodian cases, was already suspected to both cause more severe disease (CPF) and be associated with higher lethality. 50, 52, 66, 67, 68 We did not find any significant molecular difference, however, between EV-A71 subgenotype C4a sequences isolated from mild HFMD and severe (CNSI and CPF) cases. Similar observations were also reported by other authors.…”

Section: Discussioncontrasting

confidence: 58%

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

Duong

Mey

Éloit

et al. 2016

Emerging Microbes & Infections

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Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.

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Section: Discussioncontrasting

confidence: 58%

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

Duong

Mey

Éloit

et al. 2016

Emerging Microbes & Infections

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“…A laboratory-confirmed case was defined as a suspected case with laboratory evidence of enterovirus infection (EV-A71, CV-A16, or other EV detected by RT-PCR, real-time PCR or virus isolation) [12, 13]. …”

Section: Methodsmentioning

confidence: 99%

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

Luo

Gao

et al. 2016

PLoS ONE

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Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1–3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0–1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1–3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0–1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5–2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions.

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“…Severe cardiopulmonary and neurological complications are seen mainly in children <6 years, with a mean age of <2 years, and the risk falls with increasing age . The rate of severe EV‐A71 cases is between 0.1% and 1.1%, and the case‐fatality rate is between 0.01% and 0.03% . In a recent systematic review, the hospitalization rate of HFMD in East and Southeast Asia was about 6%, of which 20% develop CNS complications and 5% die …”

Section: What Is Known About Enterovirus A71mentioning

confidence: 99%

Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong

NikNadia

Tan

et al. 2019

Reviews in Medical Virology

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Summary Enterovirus A71 (EV‐A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV‐A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV‐A71 infection is very common. Children of very young age are particularly vulnerable. Large‐scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B‐ and T‐cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T‐cell epitopes that induce cross‐reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL‐6, IL‐10, IL‐17A, MCP‐1, IL‐8, MIG, IP‐10, IFN‐γ, and G‐CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV‐A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV‐A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross‐protection and memory T‐cell responses among enteroviruses.

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Correlation Analysis of EV71 Detection and Case Severity in Hand, Foot, and Mouth Disease in the Hunan Province of China

Cited by 25 publications

References 8 publications

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

Immune responses against enterovirus A71 infection: Implications for vaccine success

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