Patients with enterovirus infections may present with symptoms varying from an uncomplicated common cold to life-threatening conditions such as encephalitis, myocarditis, and neonatal sepsis [4
]. Most manifestations of enterovirus infections are mild and more than 90% are either asymptomatic or cause a nonspecific febrile illness. The most common presentation on the skin was HFMD. HFMD is a vesicular eruption in the oropharynx, palms, soles, and interdigits of toddlers and school-aged children. Patients often present oral ulcers after 1–2 days of fever and have a characteristic viral exanthem. Lesions are more common on the dorsal surfaces of the hands and feet than in other locations. The most common causative agent is coxsackievirus group A, serotype 16, but strains of enterovirus 71 circulating in East Asia are currently causing outbreaks of HFMD that are associated with a serious rhombencephalitis, with significant mortality [10
In a previous study, CA9 infection was not in the top five enterovirus infections in Taiwan from 1998 to 2006 [10
]. In contrast with previous years, the second most common serotype from August 2010 to August 2011 was CA9. In 2011, sixty one (61%) from 100 children infected with CA9 had skin rashes observed during physical examination. The most common rash pattern (56%) was generalized maculopapular rash (size from 1 to 3 mm). Only 4 patients had the rash pattern with papulovesicles with or without petechiae. Of the CA9-infected patients with skin rashes, distribution was mainly seen over the trunk, extremities, face (70%, 70%, and 61%, respectively), while hands and/or feet only 10%; 23% of patients with skin rashes had pruritus. Only 19 patients (19%) had oral ulcers. Our study found that the patients with CA9 infections presented with more widespread skin lesions. Extensive skin involvement in our study indicated a broad spectrum of direct cell infection by the CA9 virus. This finding is consistent with previous studies [3
]. In 51% of rash cases, the exanthem was reported to appear after the first fever episode.
Ninety six percent of the CA9-infected patients were reported to experience fever for a mean duration of 5.9 days and the longest fever duration in the present study was 16 days. In a previous study, the patients with enteroviral infections who had a fever lasting more than three days usually had complications, especially central nervous system involvement [12
]. The longer duration of fever may reflect that the CA9 is a more virulent virus associated with more widespread of skin invasion.
CA9 is one of the enteroviruses which may be associated with aseptic meningitis [13
]. Most enteroviruses infections are asymptomatic, but they can cause a wide variety of clinical diseases, the most common complicated enteroviral infection in pediatric patients remains aseptic meningitis. Serotypes of the HEV-B species, including coxsackievirus B and echovirus, accounted for more than 90% of aseptic meningitis, while coxsackievirus A accounted for less than 5% [15
]. That could cause sporadic cases, outbreaks, or epidemics of aseptic meningitis worldwide. In the present study, the majority of CA9-infected patients recovered completely. Several complicated cases were seen including aseptic meningitis (n=8), bronchopneumonia (n=6), acute cerebellitis (n=1), and -polio-like syndrome (n=1). As previous studies reported, the most common etiology of aseptic meningitis is enterovirus and the clinical course is benign and self-limited and resolves in 1–2 weeks [20
]. All our aseptic meningitis patients recovered from the acute illnesses with had no need for intensive care and no long-term sequelae.
HEV-B frequently causes nonspecific illness, including fever, viral exanthem, upper respiratory tract infections, and lower respiratory tract infections (LRI). Bronchopneumonia and bronchiolitis were the most common diagnoses in LRI. Echovirus 4, coxsackievirus B4, and CA9 are the most common serotypes related to LRI [22
]. In our 6 CA9-infected patients complicated with bronchopneumonia, they all presented with nonproductive cough and bilateral rales on auscultation. They recovered completely under symptomatic treatment and did not have long-term sequelae.
The genetic heterogeneity of enteroviruses makes it difficult to develop molecular typing that is both reliable and easy to perform. The genome of enteroviruses encodes 11 proteins, including VP1 to VP4, 2A to 2C, and 3A to 3D. Among these genes, VP1 is the one that can induce a human neutralizing antibody response and correlates well with serotypes. The genomic sequence encoding the VP1 capsid protein gives excellent results because of the high correlation between serotype and genetic information, and the availability of a complete database of reference strains isolated in the 1950’s and 1960’s [15
]. In this study, the pathogen was identified as CA9 based on the VP1 gene. The CA9 strain circulating in 2011 is most close to the CA9 isolate 27-YN-2008 which was isolated from one healthy child near the border of Yunnan province of Mainland China with Myanmar in 2008.
There are several limitations in this study. The data was obtained retrospectively from northern Taiwan which limits the patient number and the results might not be representative for CA9 infection for all of Taiwan. Further island-wide studies will be conducted until the virus detection method becomes more uniform and accurate. In addition, the CA9 isolated in northern Taiwan is genetically similar to that detected near the Mainland China and Myanmar border. This could be due to close geographic relationship and frequent transportation between the two areas. However, the true transmission route had not been clarified and we did not have clear evidence of that the current strains were imported from Mainland China or Myanmar.