The resurfacing of hand, foot, and mouth disease: Are we on the verge of another epidemic?

India has reported 26 cases of children up to 9 years old with Hand, foot, and mouth disease (HFMD) in Bhubaneswar, as of May 28th, 2022 [1]. This has alerted the world regarding a possible new outbreak in India. HFMD is a contagious viral disease, caused by coxsackievirus A16 (CV-A16), enterovirus 71 (EV-71), or coxsackievirus A6 (CV-A6). They are non-enveloped single-stranded RNA viruses from Enterovirus species under the umbrella of the Picornaviridae family. The CV-A16 genome has a single open reading frame (ORF) encoding 4 structural (VP1, 2, 3, and VP4) and 7 non-structural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D). VP1 is the most important protein, always exposed to the immune system, and used for serotyping and target genes in experimental studies. The CV-A16 genome is divided into the genotypes B1 (B1a, B1b, and B1c), B2 and A. HFMD has spread worldwide since its first identification in 1957 [2].

It mostly infects infants and children younger than 5 years old but rarely infects older children or adults. It usually occurs in early summer and autumn and has an incubation period of 7–10 days [3]. HFMD is not a zoonotic disease, but it spreads through human-to-human transmission by direct contact through contaminated objects or discharge, stool or blisters of infected cases, respiratory droplets, and saliva. It is also transmitted to children in preschools and kindergartens [3].

HFMD symptoms are fever, sore throat, appetite loss, malaise, rash on hands, feet, knees, elbow, and buttocks, and vesicles on the mouth and tongue. Vesicles have a pathognomonic football shape and usually fall off in 1–3 weeks after the disease incidence. These symptoms can progress into onychomadesis. CV-A 16 is self-limiting but may lead to a rare complication of aseptic meningoencephalitis [3].

HFMD outbreaks can be triggered by viruses [4]. Thus, the Covid-19 pandemic may be contributing to the recurrence of a large outbreak of HFM. Thus, COVID-19 could introduce genetic changes to the CV-A 16 circulating strains. Doctors have seen cases of children up to 14 years old, which is unusual to see. Hence, we need to perform genome sequencing for the current virus to what occurred exactly.

HFMD has a substantial impact on young children. In the early stages of the COVID-19 outbreak, SARS-CoV-2 infections among children were considered rare due to lower exposure [5]. However, children are at increased risk of infection due to the recent new virus variation [5].

There was a strong association between the non-pharmaceutical interventions against COVID-19 and the decrease in HFMD incidence. As a result, the peak of the HFMD epidemic either did not occur or was delayed [5].

Researchers in China have developed a vaccine against hand, foot, and mouth disease. The Lancet reported a trial involving 10,000 children that showed 90% effectiveness of the vaccine against EV-71. However, the vaccine does not protect against other viruses that cause the disease [4]. HFMD outbreaks can be prevented by closing kindergartens [5]. Surveillance programs are needed to identify the causes behind this surge. Furthermore, researchers, healthcare providers, and the medical community should play a vital role in enhancing public awareness, especially among mothers about HFMD to decrease or even prevent the incidence of future HFMD outbreaks.

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Author contribution

RAF: designed the study. RAF, MK, and NS: made the first draft. RAF and MK: updated the manuscript. RAF, MK, AS and AA: reviewed the final draft and edited final. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.

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Declaration of competing interest

None declared.