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. 2021 Apr 26:8:656699.
doi: 10.3389/fmed.2021.656699. eCollection 2021.

Molecular Epidemiology and Clinical Features of Enteroviruses-Associated Hand, Foot, and Mouth Disease and Herpangina Outbreak in Zunyi, China, 2019

Yuanhang Ai  1 , Weiwei Zhang  2 , Jie Wu  3 , Jingzhi Zhang  1 , Meijing Shen  1 , Shifei Yao  1 , Chengmin Deng  3 , Xiaoqian Li  3 , Dejing Wu  3 , Peng Tian  3 , Xiaoju Cheng  3 , He Zha  1 , Kaifeng Wu  1   3
Affiliations

Molecular Epidemiology and Clinical Features of Enteroviruses-Associated Hand, Foot, and Mouth Disease and Herpangina Outbreak in Zunyi, China, 2019

Yuanhang Ai et al. Front Med (Lausanne). .

Abstract

Background: Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases. Methods: We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types. Results: From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher. Conclusions: The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.

Keywords: clinical features; enterovirus types; hand foot and mouth disease; herpangina; molecular epidemiology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Distribution of EV types causing HFMD/HA in the year of 2019.
Figure 2
Figure 2
Percentage of non-EV-A71/CVA16 serotypes in HFMD/HA patients. Left: HFMD (166 cases in total); Right: HA (107 cases in total).
Figure 3
Figure 3
Levels of C-reactive protein (CRP) in cases with CVA6, CVA2, CVA5, and CVA16 (*P < 0.05; **P < 0.01; ***P < 0.001).
Figure 4
Figure 4
Phylogenetic analysis of CVA6 based on partial VP1 gene sequence. Strains identified from HFMD are marked by circle, and those identified from HA are marked by triangle.
Figure 5
Figure 5
Phylogenetic analysis of CVA5 based on partial VP1 gene sequence. Strains identified from HFMD are marked by circle, and those identified from HA are marked by triangle.
Figure 6
Figure 6
Phylogenetic analysis of CVA2 based on partial VP1 gene sequence. Strains identified from HFMD are marked by circle, and those identified from HA are marked by triangle.
See this image and copyright information in PMC

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