Enterovirus coinfection during an outbreak of hand, foot, and mouth disease in Shandong, China.

During an Outbreak of Hand, Foot, and Mouth Disease in Shandong, China To the Editor—Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, most frequently human enterovirus 71 (HEV-71) and coxsackievirus A16 (CV-A16). Other viruses (CV-A4 to A7, A9, A10, A24, and B2 to B5; echoviruses 1, 4, 11, and 18; and HEV-18) may also be associated with HFMD outbreaks or sporadic cases. HFMD is generally a benign febrile exanthematous childhood disease, excluding a small proportion of HEV-71 infections associated with severe complications, including encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, and acute flaccid paralysis. CV-B5 has been reported to cause more serious neurologic symptoms such as encephalitis [1–3]. Currently, HEV-71 and CV-A16 can be routinely detected from throat swab or stool samples in hospitalized cases in China, allowing physicians to make a diagnosis and predict disease progression and prognosis. In China, a rapid expansion of HFMD outbreaks has occurred since 2004 [4]. From April to May 2009, a total of 110 HFMD children were brought to Linyi Hospital in Shandong, China; all patients were identified according to Ministry of Health diagnostic criteria (http://www.moh.gov.cn/publicfiles/ business/htmlfiles/mohyzs/s3586/201004/ 46884.htm). We collected clinical throat swabs and serum from patients and found that 97/110 (88.2%) swab samples were positive for HEV by seminested reverse-transcription polymerase chain reaction (RT-PCR) with general enterovirus primers. HEV-71 constituted 60/97 (61.9%) of positive cases, and CV-A16 constituted 16/97 (16.5%) of typed strains. We simultaneously detected four other HEVs: CV-B5 (14.4%), CV-A6 (3.1%), CV-A10 (1%), and CVA12 (3.1%). Following further cloning and sequencing of RT-PCR products of the CV-A16–positive swabs, 4 cases (Table 1) also carried another 1–2 types of enterovirus (CV-B5 and -A6). Although