Hand, foot, and mouth disease associated with coxsackievirus A10: more serious than it seems

ABSTRACT

Introduction: Hand, foot, and mouth disease (HFMD) is a common viral childhood illness, that has been a severe public health concern worldwide, particularly in the Asia-Pacific region. According to epidemiological data of HFMD during the past decade, the most prevalent causal viruses were enterovirus (EV)-A71, coxsackievirus (CV)-A16, CV-A6, and CV-A10. The public health burden of CV-A10-related diseases has been underestimated as their incidence was lower than that of EV-A71 and CV-A16 in most HFMD outbreaks. However, cases of CV-A10 infection are more severe, and its genome is more variable, which has alerted the research community worldwide.

Areas covered: In this paper, studies on the epidemiology, laboratory diagnosis, clinical manifestations, molecular epidemiology, seroepidemiology, animal models of CV-A10, and vaccines and antiviral strategies against this genotype are reviewed. In addition, the genetic evolution of circulating strains was analyzed.

Expert opinion: Multivalent vaccines against EV-A71, CV-A16, CV-A6, and CV-A10 should be a next-step HFMD vaccine strategy.

KEYWORDS:

• Coxsackievirus A10 (CV-A10)
• enterovirus 71 (EV-A71)
• epidemiology
• hand
• foot and mouth disease (HFMD)
• vaccine

Article highlights

• Coxsackievirus A10 (CV-A10), a member of enterovirus (EV)-A–D, is most commonly associated with severe hand, foot, and mouth disease (HFMD) and central nervous system disease, and, similar to CV-A6, can cause onychomadesis. The incidence of CV-A10 infection seems higher in younger children.

• CV-A10 has caused a series of HFMD outbreaks worldwide, especially several severe HFMD outbreaks in mainland China. CV-A10-associated diseases have become a significant challenge for the prevention and control of HFMD.

• CV-A10 strains are clustered into six phylogenetic branches, named lineages A–F. Sub-lineage F2 and F3 strains are the predominant pathogens responsible for a series of HFMD outbreaks worldwide since 2008, including strains causing severe HFMD in mainland China.

• The public health burden of diseases caused by CV-A10 infections has been underestimated. An enhanced worldwide epidemiological and laboratory-based surveillance is useful to predict CV-A10 outbreaks.

• The development of multivalent HFMD vaccines target EV-A71, CV-A16, CV-A6, and CV-A10 could be an efficient and economical opportunity for the prevention of HFMD, and some other EV-A–D-related diseases.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they serve on the scientific advisory board of Provention Bio Inc., which is developing an enterovirus vaccine. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was funded by Major Special Projects Funding Program (No. 2018ZX09737-011) from the Ministry of Science and Technology of the People’s Republic of China.