Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

Song, Ci; Liu, Yu; Zhou, Yonghong; Liang, Lu; Turtle, Lance; Wang, Fang; Wu, Peng; Qiu, Qi; Yang, Junmei; Wang, Kai; Cui, Peng; Cheng, Yibing; Zhang, Tianchen; Guo, Chun; Zeng, Mengyao; Lü, Long; Peiris, Malik; Zhou, Chunmei; Cowling, Benjamin J.; Yu, Hongjie

doi:10.1016/j.ebiom.2020.103078

Cited by 18 publications

(17 citation statements)

References 23 publications

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“…Based on our study, 56.7% of the specimens were positive for anti-EV-A71 antibodies, which means that EV-A71 has had a circulation in our society. Our finding is consistent with few reports of EV-A71 in neurological diseases and no reports of HFMD cases with EV-A71 ( 30 , 31 ).…”

Section: Discussionsupporting

confidence: 93%

First seroepidemiological investigation of human enterovirus 71 in Iran

Javadi¹,

Nejati²,

Yousefi³

et al. 2021

IJM

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Background and Objectives: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neu- tralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). Materials and Methods: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. Results: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody in- creased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). Conclusion: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.

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Section: Discussionsupporting

confidence: 93%

First seroepidemiological investigation of human enterovirus 71 in Iran

Javadi¹,

Nejati²,

Yousefi³

et al. 2021

IJM

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“…However, due to the characteristic of low viral loads in CSF, the detection rate of pathogens is underestimated and the definite pathogen diagnoses are insufficient [ 2 ]. Moreover, it’s reported that the viral loads can assess disease severity and predict clinical outcomes [ 9 ]. Thus, a highly sensitive approach with strong quantitative ability is needed.…”

Section: Discussionmentioning

confidence: 99%

“…In Australia, parechovirus makes almost equal contributions to CNS infection compared with EV [ 8 ]. The CNS of children is susceptible to EV and HPeV, and HSV encephalitis is common in both children and the elderly [ 9 – 11 ]. As these infections may lead to serious sequelae, prompt recognition and treatment are crucial for patients [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a multiplex droplet digital PCR assay for detection of enterovirus, parechovirus, herpes simplex virus 1 and 2 simultaneously for diagnosis of viral CNS infections

Zhu

Liu

et al. 2022

Virol J

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Background Enterovirus (EV), parechovirus (HPeV), herpes simplex virus 1 and 2 (HSV1/2) are common viruses leading to viral central nervous system (CNS) infections which are increasingly predominant but exhibit deficiency in definite pathogen diagnosis with gold-standard quantitative PCR method. Previous studies have shown that droplet digital PCR (ddPCR) has great potential in pathogen detection and quantification, especially in low concentration samples. Methods Targeting four common viruses of EV, HPeV, HSV1, and HSV2 in cerebrospinal fluid (CSF), we developed a multiplex ddPCR assay using probe ratio-based multiplexing strategy, analyzed the performance, and evaluated it in 97 CSF samples collected from patients with suspected viral CNS infections on a two-channel ddPCR detection system. Results The four viruses were clearly distinguished by their corresponding fluorescence amplitude. The limits of detection for EV, HPeV, HSV1, and HSV2 were 5, 10, 5, and 10 copies per reaction, respectively. The dynamic range was at least four orders of magnitude spanning from 2000 to 2 copies per reaction. The results of 97 tested clinical CSF specimens were identical to those deduced from qPCR/qRT-PCR assays using commercial kits. Conclusion The multiplex ddPCR assay was demonstrated to be an accurate and robust method which could detect EV, HPeV, HSV1, and HSV2 simultaneously. It provides a useful tool for clinical diagnosis and disease monitoring of viral CNS infections.

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“…Enteroviruses are known to have vast variations in their genomes ( Simmonds et al. 2006 ) and are prone to recombination events, which have been suggested to be a driving force for evolution ( Song et al. 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

Cassidy¹,

Schuele

Lizarazo-Forero

et al. 2022

Virus Evolution

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Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10−3 substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient.

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Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

Cited by 18 publications

References 23 publications

First seroepidemiological investigation of human enterovirus 71 in Iran

First seroepidemiological investigation of human enterovirus 71 in Iran

Development of a multiplex droplet digital PCR assay for detection of enterovirus, parechovirus, herpes simplex virus 1 and 2 simultaneously for diagnosis of viral CNS infections

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

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