Enteroviruses (EVs) are small, positive, single-stranded, non-enveloped RNA viruses belonging to the family
Picornaviridae, which are further classified into fifteen species: enterovirus (EV)-A, EV-B, EV-C, EV-D, EV-E, EV-F, EV-G, EV-H, EV-I, EV-J, EV-K, and EV-L and rhinovirus (RV)-A, RV-B, and RV-C [
1]. EVs cause a wide range of human diseases worldwide, including cutaneous, visceral, and neurological disorders. Among these diseases, hand, foot, and mouth disease (HFMD) is a common childhood disorder which typically presents as a brief, febrile illness characterized by the association of oral ulcerations (enanthema) and vesicular rash (exanthema) on the palms, soles, and buttocks [
2]. EV-A71 and CV-A16 are the major etiological agents of HFMD [
3,
4]. Serotypes of EV-B (Es) have been mainly related to herpangina and seasonal outbreaks of mild viral meningitis, but have recently been associated with epidemics of HFMD. Echovirus (E) belongs to species EV-B. And multiple E serotypes are detected in sporadic cases or outbreaks of HFMD, and frequently co-circulated with EV-A71 and CV-A16 in large epidemics, including E-3, E-4, E-5, E-6, E-7, E-9, E-11, E-16, E-17, E-18, E-24, E-25, and E-30 [
5‐
22].
In 1959, echovirus 33 (E-33) was isolated, and was identified as the last Enteric Cytopathic Human Orphan (ECHO) virus belonging to the species enterovirus B in 1963 [
23]. Since then, E-33 has been detected in several outbreaks and sporadic cases around the world, associated with rashes, diarrhea, fever, aseptic meningitis, encephalitis, acute flaccid paralysis (AFP), and influenza-like illness [
24‐
29]. The prototype strain (Toluca-3) of E-33 was isolated in 1959 [
23]. To date, there are only two full-length genome sequences in the GenBank database, including the prototype strain and another E-33 strain isolated in 2014, and clinical information on E-33 has not been reported. During HFMD surveillance, two E-33 viruses were isolated, from stool and CSF, and identified in two sporadic cases of HFMD complicated by meningitis. To our knowledge, this was the first study to report severe HFMD caused by E-33 in Yunnan China.