Severe hand, foot, and mouth disease and coxsackievirus A6-Shenzhen, China.

TO THE EDITOR—Hand, foot, and mouth disease (HFMD) is a common children’s illness characterized by fever, sore throat, general malaise, and vesicular eruptions on the hands, feet, oral mucosa, and tongue. Severe cases can also involve serious complications, such as encephalitis, meningitis, acute flaccid paralysis, cardiorespiratory failure, or death. HFMD is predominately associated with enterovirus (EV) 71 and coxsackievirus (CV) A16, but has also been linked with human enterovirus types A and B, including CV-A6, which has caused outbreaks in Finland, Taiwan, the United States, Thailand, and Japan [1–5]. In China, HFMD afflicts millions of patients annually and is considered a substantial public health threat. In recent years, we have analyzed the etiology and symptoms of severe HFMD cases in the heavily endemic city of Shenzhen, China. In 2008 and 2009, the most prevalent serotype in Shenzhen was EV71, followed by CV-A16. In 2010–2012, EV71 remained the most common serotype, but CV-A6 became the second most common [6]. At the Third People’s Hospital of Shenzhen, throat swabs were collected from all patients with severe HFMD from 2012 (36 cases) and April to July 2013 (19 cases). Samples were analyzed by seminested reverse transcription polymerase chain reaction of the 5′ partial region of VP1 and sequencing as previously described [7]. Sequence alignment revealed EV71 in 31 of the 36 severe cases in 2012; CV-A16 was identified in 3 cases, and CVA10 and CV-A4 in 1 case each. In contrast, of the 19 cases from 2013, 11 involved EV71 and 8 involved CV-A6, indicating that CV-A6 and EV71 had become almost equally prevalent causes of severe HFMD. We compared the clinical features between CV-A6–associated and EV71– associated severe HFMD cases in 2013 (Table 1). EV71 has been associated with severe HFMD and death in young children. CV-A6 has recently emerged as a primary cause of HFMD, but very few CV-A6– associated severe cases were reported. Here we found that although CV-A6 was the second most common HEV in HFMD in Shenzhen in 2012, no CVA6–associated severe HFMD cases were observed in 2012. We observed a substantial increase of CV-A6–associated severe HFMD cases in 2013. Meningitis and encephalitis have been previously described in some severe HFMD cases [8, 9]. Here we found only meningitis in CV-A6–associated severe cases. Consistent with previous reports, most CV-A6 patients had herpangina. We also observed 2 cases of severe CVA6 with myocardial damage. Compared with the EV71 manifestation, the CVA6–associated severe cases showed higher fever and shorter fever duration. Clinicians should be aware of the recent substantial increase of CV-A6– associated severe HFMD cases. More detailed clinical and genetic analyses are required to characterize the role of CVA6 in severe cases of HFMD.