Molecular Epidemiology of Human Enterovirus Associated with Aseptic Meningitis in Shandong Province, China, 2006–2012

Abstract

BackgroundHuman 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.ObjectivesTo characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features.Study DesignCerebrospinal 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.ResultsA 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.ConclusionsMultiple 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.

Molecular epidemiology of coxsackievirus type B1

“…The population model chosen did not significantly affect the calculated substitution rates, which ranged from 6.95 9 10 -3 to 7.37 9 10 -3 substitutions per site per year. Despite the obvious increase in the incidence of infections with CVB1 in humans, its recent emergence as the predominant enterovirus genotype in many countries, its association with several human diseases with significant morbidity, and its involvement in extensive outbreaks throughout the world [4][5][6][7][8]30], little is known about the molecular epidemiology of this virus. Recent studies have attempted to determine the clinical and molecular characteristics of CVB1 viruses involved in symptomatic infection in Korea [4] and to investigate the genetic relatedness of CVB1 strains isolated in India [31].…”

Infectious Meningitis

“…Additionally, they solve the discrepancy problems in suspected patients who show culture-negative results. These combined characteristics provide advantages for PCR over any other laboratory test (10,23). Reverse transcription (RT)-PCR targeting the 5' non-translated region (NTR) of the enteroviral genome, which is the most conserved genomic region, is essential for enteroviral-meningitis diagnosis and delivers results in as little as 5 hours, thereby shortening inpatient hospital stays and minimizing the unnecessary use of empirical antimicrobial agents.…”

“…Recently, molecular typing approaches to enteroviruses targeting the VP1 region of the enteroviral genome that encodes serotypespecific neutralization epitopes have been successfully applied during enteroviral-meningitis outbreak investigations in many countries worldwide (18,23,24,25,27,33,34,44,47). They have provided details of enteroviral molecular phylogeny that help us to understand its association with specific disease manifestations and possible clonal geographical clustering (34) ( Table 2).…”

Detection and identification of coxsackievirus B3 from sera of an Indonesian patient with undifferentiated febrile illness

“…CVB3 is an important human pathogen, and has been reported to be associated with type 1 diabetes mellitus, myopericarditis, aseptic meningitis, herpangina, pancreatitis and hand, foot, and mouth diseases (HFMD) [2][3][4][5][6][7]. Infection can be fatal, especially among infants younger than three months of age and pregnant women, whose infection may also lead to fetal growth retardation and miscarriage [6,8]. During an outbreak of HFMD in China and France, CVB3 was reported to be co-circulating with other enteroviruses [9][10][11][12].…”