Two Coxsackievirus B3 outbreaks associated with hand, foot, and mouth disease in China and the evolutionary history worldwide

Abstract

Background Coxsackievirus B3 (CV-B3) is usually associated with aseptic meningitis and myocarditis; however, the association between CV-B3 and hand, foot, and mouth disease (HFMD) has not been clearly demonstrated, and the phylogenetic dynamics and transmission history of CV-B3 have not been well summarized. Method Two HFMD outbreaks caused by CV-B3 were described in Hebei Province in 2012 and in Shandong Province in 2016 in China. To analyze the epidemiological features of two CV-B3 outbreaks, a retrospective analysis was conducted. All clinical specimens from CV-B3 outbreaks were collected and disposed according to the standard procedures supported by the WHO Global Poliovirus Specialized Laboratory. EV genotyping and phylogenetic analysis were performed to illustrate the genetic characteristics of CV-B3 in China and worldwide. Results Two transmissible lineages (lineage 2 and 3) were observed in Northern China, which acted as an important “reservoir” for the transmission of CV-B3. Sporadic exporting and importing of cases were observed in almost all regions. In addition, the global sequences of CV-B3 showed a tendency of geographic-specific clustering, indicating that geographic-driven adaptation plays a major role in the diversification and evolution of CV-B3. Conclusions Overall, our study indicated that CV-B3 is a causative agent of HFMD outbreak and revealed the phylogenetic dynamics of CV-B3 worldwide, as well as provided an insight on CV-B3 outbreaks for effective intervention and countermeasures. Electronic supplementary material The online version of this article (10.1186/s12879-019-4107-z) contains supplementary material, which is available to authorized users.

A Large-Scale Outbreak of Echovirus 30 in Gansu Province of China in 2015 and Its Phylodynamic Characterization

“…Sporadic importing and exporting of cases among provinces of China were monitored, showing a certain level of genetic flow of E-30 among different regions. The clades of MCC phylogenetic tree, covering several provinces, showed a more complex distribution phenomenon compared with CV-B3 geographical distribution reported before (Han et al, 2019). For example, the strains isolated from Yunnan province almost located at each clade of MCC phylogenetic tree, indicating that the E-30 spread widely in China (Figure 5B, colored in light green).…”

“…Sporadic importing and exporting of cases were observed in several provinces of China, indicating that E-30 transmitted through different regions and that the gene flow of E-30 among different provinces was apparent. The substitution rate of VP1 coding region of E-30 is higher than that of CV-B3, indicating the relatively faster evolution extent of E-30 as compared to CV-B3 (Han et al, 2019). The low substitution rate, compared with EV-A71 and CV-A6, revealed relatively slower evolutionary levels, implying less possibility of outbreaks (McWilliam Leitch et al, 2012;Geoghegan et al, 2015;Anh et al, 2018).…”

“…values of CV-B3 cover the threshold value of E-30 (Han et al, 2019). According to the estimated molecular clock, the common ancestor of lineage 1 was dated to about July of 1986(95% HPD, November 1985-February 1987, whereas the strains of E-30 were isolated first in Taiwan of China in 1988.…”

“…These serotypes of enteroviruses are usually associated with a series of diseases, such as encephalitis; myocarditis; hand, foot, and mouth disease (HFMD); acute flaccid paralysis (AFP); and other diseases. For example, CV-B3 has been linked to myocarditis and encephalitis, whereas it could also cause outbreaks of HFMD as reported recently (Tao et al, 2012;Wu et al, 2013;Han et al, 2019). CV-B5 is an important pathogen that caused the outbreaks of encephalitis and HFMD (Han et al, 2012;Chen et al, 2013).…”

Molecular typing and characterization of a novel genotype of EV-B93 isolated from Tibet, China

“…Enteroviruses have complex pathogenesis and can cause a wide spectrum of diseases, but most people get a silent infection. Clinical symptoms of various severities may occur in cases of depressed immunity and recurrent exposure to viruses, such as acute flaccid paralysis (AFP); hand, foot, and mouth disease; aseptic meningitis; acute pulmonary oedema; myocarditis [12][13][14][15][16][17]. Some critically ill patients may die quickly.…”