OBJECTIVETo compare the differences of epidemiological and clinical characteristics in children with hand-foot-mouth disease (HFMD) caused by Coxsackievirus A16 (CA16) and Enterovirus 71 (EV71).

METHODSThe samples of vesicle fluid and throat swabs of 108 children with HFMD were collected and detected for enterovirus by RT-PCR. The clinical data of children with EV71 and CA16 infection were retrospectively reviewed and compared.

RESULTSThe total positive rate of enterovirus was 97.2% (105/108). Of the 105 cases, 56 cases were positive for EV71 (51.9%), 39 cases were positive for CA16 (36.1%), 2 cases were positive for other enterovirus (1.9%), and 8 cases were co-infected by EV71 and CA16 (7.4%). There were no significant differences in age and sex between EV71 and CV16 infected cases. The univariate analysis showed that the incidences of herpes of mouth, erythra of knees, and nose running in children infected by CA16 were higher than in those infected by EV71. The multivariate logistic regression analysis showed that the HFMD children who had erythra of knees had higher probability of CA16 infection.

CONCLUSIONSEV71 should be considered as the pathogen in children with HFMD who have no herpes of mouth, erythra of knees, and nose running.

Child ; Child, Preschool ; Coxsackievirus Infections ; epidemiology ; Enterovirus A, Human ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; Humans ; Infant ; Logistic Models ; Male

OBJECTIVETo analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) in Ningbo.

METHODSA descriptive analysis was conducted through the surveillance data of HFMD in Ningbo, Zhejiang province, from 2008 to 2011. Genes on EV71 and Cox A16 were amplified with RT-PCT from the stool samples of HFMD patients. Sequences were analyzed by bioinformatics software.

RESULTS37 524 cases of HFMD were reported from 2008 to 2011, including 196 severe cases and 12 deaths. The reported incidence was 145.26 per 100 000 and the case fatality was 0.03%. Cases in children aged 5 or younger accounted for 95.89%, and the scattered cases accounted for 64.10%. Xiangshan and Ninghai counties had the highest incidence rates in Ningbo. The peak of incidence was from April to July. The number of male patients was obviously higher than females. 2394 cases of HFMD were laboratory confirmed and EV71 with the predominant epidemic strain. Data from phylogenetic analysis revealed that EV71 isolated from HFMD patients in Ningbo belonged to C4a evolution branch of C4 sub-genotype, with several transmission chains. Cox A16 belonged to B1 evolution branch. 53.48% of the healthy children in Ningbo showed EV71 antibody positive. The geometric mean of the antibody titer (GMT) was 11.23 (8.33 - 14.98) in healthy children. Cox A16 antibody was detected at 63.18% of the healthy children in Ningbo. GMT in healthy children was 12.61 (6.70 - 16.52).

CONCLUSIONHFMD was highly endemic in Ningbo, with children under 5 years old were at high-risk. The major etiologic agent was EV71 which belonged to C4a in the C4 sub-genotypes. Cox A16 belonged to the B1 evolution branch, which were in line with the predominant virus circulating in the mainland of China.

Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; Enterovirus ; isolation & purification ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male

OBJECTIVETo investigate the epidemic characteristics of etiological agents in children with hand, foot and mouth disease (HFMD) and analyze the differences between the severe and mild cases with HFMD seen from 2008 to 2009 in the Children's Hospital.

METHODSA total of 154 patients with HFMD were enrolled from May 2008 to September 2008 and from May 2009 to September 2009, including 28 severe HFMD patients. Data from 80 cases with suspected herpangina were collected as control. Enterovirus universal type, enterovirus type 71 (EV71) and coxsackie virus group A 16 (CA16) were detected by real-time RT-PCR respectively.

RESULTSThe positive rate of enterovirus universal type in the 154 patients with HFMD was 81.82%(126/154). EV71 positive rate in these 126 patients with enterovirus universal type infection was 57.14%(72/126). The positive rate of enterovirus universal type in the 80 cases with suspected herpangina was 68.75%(55/80). There was no EV71 infection in these 80 cases with suspected herpangina. EV71 infection was mainly popular in 2008. Both EV71 and CA16 were prevalent in 2009. The epidemic characteristics of enterovirus infection with HFMD between 2008 and 2009 had significant differences (χ(2) = 23.50, P = 0.000) (P < 0.01). The epidemic characteristics of enterovirus infection between severe and mild HFMD patients also had significant differences (χ(2) = 29.85, P < 0.01). There were 28 cases with severe HFMD, in whom the EV71 positive rate was 92.86% (26/28). EV71 positive rate in the mild HFMD was 36.51% (46/126) (χ(2) = 29.22, P < 0.01). There was no significant difference in the gender (χ(2) = 0.135, P = 0.714) and virus load (t = 0.141, P = 0.889) between the mild and severe HFMD cases. But the age of mild and severe HFMD showed a significant difference (t = 2.926, P = 0.009). Patients who were less than 2 years of age had a proportion of 88.89% (8/9) with severe HFMD. The mean age of mild HFMD patients was 3.19 years.

CONCLUSIONHFMD showed different epidemic characteristics at different times of enterovirus infection. There was no significant difference in the gender and virus load between the mild and severe cases with HFMD. Children under 3 years of age with EV71 infection were at high risk for severe HFMD.

Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; Enterovirus ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; Viral Load

Objective: To analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) cases caused by Coxsackie virus A16 (Cox A16) in Guangdong province from 2012 to 2016. Methods: The data of mild HFMD cases caused by Cox A16 were collected from 8 sentinel hospitals in 8 prefecture-level cities in Guangdong to estimate Cox A16 infection status and its population and time distribution characteristics. Results: (1) The highest estimated incidence of Cox A16 infection was in 2014 (113.0/100 000), followed by 2016 (86.4/100 000) and 2012 (79.1/100 000), while the estimated incidence was lower in 2015 (29.0/100 000) and 2013 (28.8/100 000). (2) Cox A16 was confirmed to be the predominant pathogen causing HFMD outbreaks (54.6%, 89/163). The number of outbreaks in the year with high incidence (28 outbreaks) was 11.2 times higher than that in the year with low incidence (2.5 outbreaks). (3) Across all age groups, the annual estimated incidence of Cox A16 infection decreased with age (trend χ(2)=853 905.63, P<0.01). The incidence was highest in age group 1 year (1 449.2/100 000), followed by that in age group 3 years (1 097.0/100 000), in age group 2 years (1 083.5/100 000), in age group 4 years (687.8/100 000) and in age group 0 year (604.9/100 000). Among the age groups <12 months, the estimated incidence increased with age (trend χ(2)=5 541.77, P<0.01), which was highest in age group 11-months (2 105.1/100 000), followed by that in age groups 10-months (1 448.6/100 000), 9-months (938.3/100 000), 8-months (703.3/100 000) and 6-months (664.6/100 000). (4) The annual incidence peak was during May (143.9/100 000)-June (131.5/100 000). Conclusion: The prevalence of Cox A16 infection differed with year in Guangdong during 2012-2016. When the incidence of Cox A16 infection was high, more outbreaks occurred. The prevalence occurred mainly in nurseries and kindergartens from May to June each year. Children aged 0-4 years were the high risk group for Cox A16 infection, children aged 6-11 months were at high risk for Cox A16 infection.
Animals ; Child ; Child, Preschool ; China/epidemiology* ; Cities ; Coxsackievirus Infections/epidemiology* ; Disease Outbreaks ; Enterovirus A, Human/isolation & purification* ; Hand, Foot and Mouth Disease/epidemiology* ; Hospitals ; Humans ; Incidence ; Infant ; Schools

Amino Acid Sequence ; China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; Enterovirus A, Human ; genetics ; isolation & purification ; Genes, Viral ; genetics ; Hand, Foot and Mouth Disease ; virology ; Humans ; Phylogeny

Epidemics of hand, foot and mouth disease (HFMD) have mainly been caused by Coxsackievirus A16 (CVA16) and Enterovirus A 71 (EV-A71), which circulated alternatively or together in the affected area. CVA16 has caused numerous outbreaks and epidemics in multiple countries and geographical regions, and has become an important public health problem. Based on an analysis of the complete VP1 coding region, all CVA16 strains can be divided into genotypes A, B1, and B2. Furthermore, genotype B1 can be divided into subgenotypes B1a, B1b, and B1c. After 2000, no reports of genotype B2 virus strains have been reported. All of the CVA16 strains reported in mainland China have belonged to subgenotypes B1a and B1b. Most CVA16-associated infections cause only mild symptoms; however, some CVA16 infections can lead to severe complications and even death. Vaccination is considered to be the most effective method to control the transmission and infection rate of this virus. A number of research groups are studying various vaccine types, including inactivated vaccines, genetic engineering vaccines, and DNA vaccines, amongst others. In this review, an overview is provided of the research advances in molecular epidemiology and vaccines of CVA16.
Animals ; China ; Coxsackievirus Infections ; epidemiology ; immunology ; prevention & control ; virology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Humans ; Molecular Epidemiology ; Viral Vaccines ; administration & dosage ; genetics ; immunology

To identify and trace the pathogen of acute hemorrhagic conjunctivitis (AHC) epidemic in Zhejiang Province in 2010. Viral nucleic acid of Enterovirus (EV) and Coxsackievirus A24 variant (CA24v) were directly detected by real-time RT-PCR from the conjunctival swab collected from suspected patients. The virus was isolated from the swab samples using Hep-2 cell. The viral RNAs were extracted from the isolated viruses and followed by RT-PCR to amplify VP1 gene and 3C protease region(3C). The amplified fragments were sequenced and phylogenetic trees were also constructed. Eight out of 13 swab samples from suspected patients were both positive for EV and CA24v RNA (61.5%), 6 CA24v strains were isolated (46.2%). The complete VP1 genes of CA24v in 4 sequenced virus strains were 915 nt in length and the complete 3C genes were 549 nt in length. All VP1 and 3C genes were confirmed without any insertion or deletion. The identity of nucleotide and amino acid in 3C between the 2010 isolated strains and the prototype strain EH24/70 were 85.2%-85.8% and 96.2%-96.7%, and that between the 2010 Zhejiang strains and the Zhejiang,Yunnan and Guangdong CA24v strains isolated between 2007-2008 were 93.4%-93.8% and 96.7%-97.3%, respectively. The phylogenetic tree of 3C indicated that the isolated CA24v viruses of Zhejiang in 2010 located in the CA24v IV genotype cluster 4 (GIV-C4) and all the VP1 genes located in the human Enterovirus C (EV-C) CA24v. These findings indicated that AHC epidemic in Zhejiang Province in 2010 was caused by CA24v GIV-C4 viruses and they most likely evolved from CA24v viruses circulating locally in external environment from 2002.
Amino Acid Sequence ; China ; epidemiology ; Conjunctivitis, Acute Hemorrhagic ; epidemiology ; virology ; Coxsackievirus Infections ; epidemiology ; virology ; Disease Outbreaks ; Enterovirus ; classification ; genetics ; isolation & purification ; Enterovirus Infections ; epidemiology ; virology ; Genes, Viral ; genetics ; Humans ; Molecular Sequence Data ; Phylogeny ; RNA, Viral ; genetics ; Sequence Alignment ; Sequence Homology

OBJECTIVETo understand the etiology of hand, foot and mouth disease (HFMD) in Guangzhou area in 2008.

METHODTotally 1023 clinical specimens were collected from pediatric patients suspected of HFMD in 2008. TaqMan real-time RT-PCR were used for detection of enterovirus 71 (EV71), Coxsackievirus A16 (CA16) and other enteroviruses. The specimens which were enterovirus positive by RT-PCR method with universal primer but EV71 and CA16 negative, were amplified and sequenced for 5'untranslated region.

RESULTEnterovirus was identified from 434 of 1023 samples and detection rate of enterovirus was 42.42%; of the 434 samples, 276 were positive for EV71 (63.6%), 126 for CA16 (29%), 4 samples for enterovirus 84, 3 for Echovirus 11, 2 for Echovirus 9, 3 for Coxsackievirus B3, 4 for Coxsackievirus A10, 3 for Coxsackievirus A6, 6 for Coxsackievirus A12 or A5, and for 7 samples typing was difficult.

CONCLUSIONThe major causative agents of HFMD in Guangzhou were EV71 and CA16 in 2008, and EV84, CA10, CA12, CA6, COSB3, ECHV11, ECHV9 were also the pathogens for smaller proportions of patients.

Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; DNA Primers ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; RNA, Viral ; Reverse Transcriptase Polymerase Chain Reaction

To identify the cause of an outbreak of acute hemorrhagic conjunctivitis (AHC) in Jiangxi (China) in 2010, 20 eye conjunctival swabs were first collected from AHC patients. Then, viruses were isola- ted and tested for human enterovirus 70, coxsackievirus A24 variant (CV-A24v) and adenovirus using the polymerase chain reaction. All CV-A24v isolates underwent sequencing of 3C and VP1 coding regions. Then, a phylogenetic tree was constructed for Jiangxi CV-A24v and worldwide CV-A24v based on,3C and VP1 regions, respectively. Ten out of 20 specimens were positive for CV-A24v, implying that the outbreak was caused by CV-A24v. The phylogenetic tree based on the 3C region showed that Jiangxi CV- A24v belonged to cluster 5 in genotype IV (GIV-C5) with strains isolated throughout the world after 2010, and were divided further into A and B lineages. Phylogenetic analyses of the VP1 region showed that all of the worldwide CV-A24v strains isolated after 2000 could be divided into five groups (1-5). Jiangxi CV-A24v was classified into group 5 and also divided further into A and B lineages upon analyses of the 3C region. These data suggested that CV-A24v causing AHC outbreaks in China in 2010 belonged to GIV-C3 and GIV-C5. At least two transmission lineages were circulated in Jiangxi in 2010. The classification of CV-A24v isolated after 2010 worldwide using the phylogenetic tree based on the VP1 region was almost consistent with that based on the 3C region and also had significant chronological clustering.
China ; epidemiology ; Conjunctivitis, Acute Hemorrhagic ; epidemiology ; virology ; Coxsackievirus Infections ; epidemiology ; virology ; Disease Outbreaks ; Enterovirus C, Human ; classification ; genetics ; isolation & purification ; Genotype ; Humans ; Molecular Sequence Data ; Phylogeny ; Viral Proteins ; genetics

OBJECTIVETo identify the pathogen caused an outbreak of aseptic meningitis in Tancheng county of Shandong province in 2008, and to analyze the molecular characterization of VP1 gene of the Coxsackievirus B3(CVB3) isolates.

METHODSStool and cerebrospinal fluid(CSF) specimens were collected from this outbreak for virus isolation with RD and Hep-2 cell. After typing by neutralization test, the VP1 gene of the isolates were amplified by RT-PCR and sequenced. Homologous comparison and phylogenetic analysis were performed.

RESULTS35 strains of enteviruse were isolated from 22 stools and 120 CSFs(7 from stools and 28 from CSFs), 34 strains identified as CVB3 and 1 as Echovirus 30(ECHO30) by neutralization test. The nucleotide homologies were 90.5%-100.0% in the partial VP1 gene (381 bp) among 34 CVB3 isolates. Homology comparisons indicated that Shandong strains have the identity of 79.5%-81.6% with the CVB3 prototype strain Nancy. 012/2008TC/SD/CHN and 177/2008TC/SD/CHN showed the highest nucleotides homologies (98.2% and 91.0% respectively) with Fuyang19 strain of Anhui province in 2008 in complete VP1 gene. The phylogenetic tree based on complete VP1 genes showed that all the CVB3 correlated with aseptic meningitis in China recently came from the same evolution linkage and formed a monophyletic cluster.

CONCLUSIONThe causative agent of this outbreak of aseptic meningitis was CVB3. CVB3 circulated in China was genetically different from other countries.

China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; virology ; Disease Outbreaks ; Enterovirus B, Human ; classification ; genetics ; isolation & purification ; Feces ; virology ; Female ; Humans ; Male ; Meningitis, Aseptic ; epidemiology ; virology ; Molecular Sequence Data ; Phylogeny ; Viral Proteins ; genetics