Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

BACKGROUND: Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. OBJECTIVES: To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. STUDY DESIGN: Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. RESULTS: A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. CONCLUSIONS: Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

Non-polio enteroviruses from acute flaccid paralysis surveillance in Shandong Province, China, 1988-2013.

Enteroviruses (EVs) are important human pathogens associated with various clinical syndromes. This study represents an overview of non-polio enteroviruses (NPEVs) isolated from acute flaccid paralysis (AFP) surveillance in Shandong Province, China from 1988 to 2013. Altogether 792 and 170 NPEV isolates were isolated from stool specimens of 9263 AFP cases and 1059 contacts, respectively. Complete VP1 sequencing and typing on all 962 isolates revealed 53 NPEV types in which echovirus (E) 6 (7.6%), E14 (7.6%), E11 (7.4%), coxsackievirus (CV) B3 (7.4%), E25 (5.6%), CVB5 (4.9%), E7 (4.5%) and EV-A71 (4.4%) were the eight most commonly reported serotypes. Distinct summer-fall seasonality was observed, with June-October accounting for 79.3% of isolation from AFP cases with known month of specimen collection. Increase of isolation of EV-A71 and CVA--the predominant pathogens for the hand, foot, and mouth disease--was observed in recent years. Sequence analysis on VP1 coding region of EV-A71 and E6 suggested Shandong strains had great genetic divergence with isolates from other countries. The results described in this study provide valuable information on the circulation and emergence of different EV types in the context of limited EV surveillance in China.

[Identification and genetic characterization of coxsackieviruses A2, 6, 8 and 12 isolated in Shandong Province].

In previous study, molecular typing method was performed to identify human enteroviruses (HEVs) isolates collected from acute flaccid paralysis (AFP) cases from 1989 to 2011 and hand, foot and mouth disease (HFMD) patients, and 8 HEV-A serotypes were identified. In order to explore the genotypes and molecular evolution characteristics of HEV-A in Shandong province, viral RNA of the remaining isolates was extracted and entire VP1 coding region was amplified, sequenced and identified with HEV-A primers. Another 7 HEV-A Shandong isolates were obtained, and identified as Coxsackievirus A (CVA) 2, 6, 8 and 12 by molecular typing method. Homologous comparison showed that the nucleotide acid identities of Shandong strains ranged from 80.8% to 85.0% with prototype strains. Phylogenetic analysis based on VP1 sequences indicated that CVA8 and CVA12 strains were genetically related with domestic strains. However, CVA2 and CVA6 strains were distinct from both domestic and foreign strains. In addition, multiple transmission chains of CVA2 and CVA6 existed within Shandong province. So far, a total of 12 HEV-A serotypes were identified in Shandong province. This study enriched the distribution of serotypes and genetic evolution characteristics of HEV-A isolates in Shandong, and revealed different transmission chains of CVA2, 6, 8, 12 serotypes co-circulated in Shandong province or in China.