Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China

Abstract

Coxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.

Figure 1

Monthly distribution of total and severe HFMD cases Total number of HFMD cases caused by EV-A71, other HEVs and non-HEV (HEV negative) were 4415 and were confirmed using Real Time PCR Kits, specific EV-A71 and pan-HEVs.

Figure 2

Proportion of the untypeable and typeable enteroviruses identified in HFMD patients. The total numbers of 3703 specimens were used for serotyping with combination of real time RT-PCR, conventional RT-PCR and cell cultures.

Figure 3

Proportion of the confirmed enterovirus serotypes identified in HFMD patients. The total case numbers of confirmed serotypes were 3201 performed with combination of Real Time RT-PCR, conventional RT-PCR and cell cultures.

Figure 4

Monthly distribution of HFMD cases caused by the six major serotypes. A total number of HFMD cases caused by the six major serotypes is 3130, confirmed with combination of Real Time RT-PCR, conventional RT-PCR and cell cultures.

Figure 5

Phylogenetic dendrograms based on the partial VP1 nucleotide sequences of EV-A71 (a), CV-A16 (b), CV-A6 (c), CV-A5 (d), CV-A10 (e), CV-A2 (f). The dendrograms were constructed using the neighbor-joining method based on the alignment of the partial VP1-region sequences of Xiangyang strains and other strains downloaded from GenBank. Bootstrap values (%) for 1000 replicates were calculated, and only values > 70% are shown at the nodes. Red dots indicate Xiangyang strains, and black square indicate prototype strains.