scholarly journals Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia

2016 ◽  
Vol 10 (3) ◽  
pp. e0004562 ◽  
Author(s):  
NMN NikNadia ◽  
I-Ching Sam ◽  
Sanjay Rampal ◽  
WMZ WanNorAmalina ◽  
Ghazali NurAtifah ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Enterovirus A71 ◽  
Foot And Mouth

Virulence of enterovirus-A71 fluctuates depending on the phylogenetic clade formed in the epidemic year and epidemic region

2021 ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Hidekazu Nishimura ◽  
Katsumi Mizuta ◽  
Tomoha Nishizawa ◽  
Son T. Chu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Foot And Mouth Disease ◽  
Virus Genome ◽  
Mouth Disease ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Viral Virulence ◽  
Foot And Mouth ◽  
Potential Risks ◽  
A Minor

Although epidemics of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) have occurred worldwide, the Asia-Pacific region has seen large sporadic outbreaks with many severe neurological cases. This suggests that the virulence of the circulating viruses fluctuates in each epidemic and that HFMD outbreaks with many severe cases occur when highly virulent viruses are circulating predominantly, which has not been experimentally verified. Here, we analyzed 32 clinically isolated strains obtained in Japan from 2002 to 2013, along with 27 Vietnamese strains obtained from 2015 to 2016 that we characterized previously using human SCARB2 transgenic mice. Phylogenetic analysis of the P1 region classified them into five clades belonging to subgenogroup B5 (B5-I to B5-V) and five clades belonging to subgenogroup C4 (C4-I to C4-V) according to the epidemic year and region. Interestingly, the clade B5-I and B5-II were very virulent, while clades B5-III, B5-IV, and B5-V were less virulent. Clades C4-II, C4-III, C4-IV, and C4-V were virulent, while clade C4-I was not. The result experimentally showed for the first time that several clades with different virulence levels emerged one after another. The experimental virulence evaluation of circulating viruses using SCARB2 transgenic mice is helpful to assess potential risks of circulating viruses. These results also suggest that a minor nucleotide or amino acid substitution in the EV-A71 genome during circulation may cause fluctuations in virulence. The data presented herein may increase our understanding of the dynamics of viral virulence during epidemics. IMPORTANCE Outbreaks of hand, foot, and mouth disease (HFMD) with severe enterovirus A71 (EV-A71) cases have occurred repeatedly, mainly in Asia. In severe cases, central nervous system complications can lead to death, making it an infectious disease of importance to public health. An unanswered question about this disease is why outbreaks of HFMD with many severe cases sometimes occur. Here, we collected EV-A71 strains that were prevalent in Japan and Vietnam over the past 20 years and evaluated their virulence in a mouse model of EV-A71 infection. This method clearly revealed that viruses belonging to different clades have different virulence, indicating that the method is powerful to assess the potential risks of the circulating viruses. The results also suggested that factors in the virus genome may potentially cause an outbreak with many severe cases and that further studies may facilitate the prediction of large epidemics of EV-A71 in the future.

scholarly journals Epidemiological study on hand, foot and mouth disease in Tongzhou District, Beijing, 2013–2017

2019 ◽  
Vol 47 (6) ◽  
pp. 2615-2625 ◽  
Author(s):  
Xiao-Feng Liu ◽  
Xiu-Mei Sun ◽  
Xiao-Wei Sun ◽  
Yu-Qing Yang ◽  
Cong-Hui Huang ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Local Population ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Migrant Population ◽  
Enterovirus A71 ◽  
Tongzhou District ◽  
Foot And Mouth ◽  
Polymerase Chain ◽  
Epidemiological Characteristics

Objective To study the epidemiological characteristics of hand, foot and mouth disease (HFMD) in Tongzhou District, Beijing between 2013 and 2017. Methods Data on HFMD infections from 1 January 2013 to 31 December 2017 were collected from the Notifiable Infectious Diseases Reporting Information System and analysed. Serotyping of enteroviruses from samples from patients with HFMD was undertaken using reverse transcription–polymerase chain reaction. Results A total of 15 341 patients with HFMD were reported and 32 patients (0.2%) were classified as having severe HFMD. The annual mean incidence rate of HFMD was 219.3/100 000 of the general population. The incidence and case-severity rates of HFMD generally decreased between 2013 and 2017. In the floating migrant population, the incidence and cases-severity rates of HFMD were significantly higher than in the local population. The peak incidence and severity-case rates were at 2 years of age and > 90% of patients were ≤5 years. Enterovirus A71 and Coxsackievirus A16 were the predominant pathogens in 2013–2017. Conclusions During the 5-year period 2013–2017, the incidence rate and case-severity rate of HFMD generally decreased in Tongzhou District, Beijing. The floating migrant population and children ≤5 years of age were at the highest risk of HFMD.

scholarly journals RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5′ Nontranslated Regions

2017 ◽  
Vol 92 (6) ◽  
Author(s):  
Thinesshwary Yogarajah ◽  
Kien Chai Ong ◽  
David Perera ◽  
Kum Thong Wong
Keyword(s):  
Viral Replication ◽  
Neuronal Cells ◽  
Neuroblastoma Cells ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Mouth Disease ◽  
Host Responses ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Foot And Mouth

ABSTRACT Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical S -adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5′ nontranslated regions (5′ NTRs) showed that RSAD2 expression/viral replication and AIM2 expression/viral replication patterns may be linked to the 5′ NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5′ NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection. IMPORTANCE Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5′ NTRs may play significant roles in eliciting different host response mechanisms.

scholarly journals Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0165659 ◽  
Author(s):  
Kam Leng Aw-Yong ◽  
I-Ching Sam ◽  
Mia Tuang Koh ◽  
Yoke Fun Chan
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Enterovirus A71 ◽  
Foot And Mouth

scholarly journals Severe enterovirus A71 associated hand, foot and mouth disease, Vietnam, 2018: preliminary report of an impending outbreak

2018 ◽  
Vol 23 (46) ◽  
Author(s):  
Le Nguyen Thanh Nhan ◽  
Nguyen Thi Thu Hong ◽  
Le Nguyen Truc Nhu ◽  
Lam Anh Nguyet ◽  
Nguyen Thi Han Ny ◽  
...  
Keyword(s):  
Young Children ◽  
Preliminary Report ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Referral Hospital ◽  
Ho Chi Minh City ◽  
Tertiary Referral ◽  
Tertiary Referral Hospital ◽  
Enterovirus A71 ◽  
Foot And Mouth

Since January 2018, over 53,000 hospitalisations and six deaths due to hand, foot and mouth disease (HFMD) have occurred across Vietnam with most cases from September onward. In a large tertiary referral hospital, Ho Chi Minh City, enterovirus A71 subgenogroup C4 was predominant, while B5 was only sporadically detected. The re-emergence of C4 after causing a severe HFMD outbreak with > 200 deaths in 2011–12 among susceptible young children raises concern of another impending severe outbreak.

scholarly journals Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Shao-Hua Wang ◽  
Ao Wang ◽  
Pan-Pan Liu ◽  
Wen-Yan Zhang ◽  
Juan Du ◽  
...  
Keyword(s):  
Mouse Model ◽  
Viral Protein ◽  
Northeast China ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Promising Target ◽  
Enterovirus A71 ◽  
Coxsackievirus A6 ◽  
Foot And Mouth ◽  
Cultured Human Cells

ABSTRACTCoxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCEHand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

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