The Pediatric Infectious Disease Journal • Volume 33, Number 12, December 2014
Hongyan et al
HAND, FOOT AND MOUTH DISEASE CAUSED BY COXSACKIEVIRUS A6, BEIJING, 2013 Gu Hongyan, MD,* Ma Chengjie, PhD,† Yang Qiaozhi, MD,‡ Hua Wenhao, MD,† Li Juan, MD,† Pang Lin, PhD,† Xu Yanli, MD,† Wei Hongshan, PhD,† and Li Xingwang, MD*† Abstract: Specimens and clinical data were collected from 243 hand, foot and mouth disease patients in Beijing in 2013. In total, 130 stool specimens were genotyped for enterovirus. Hand, foot and mouth disease was mainly detected in suburban areas and at the edges of urban areas between May and August. Coxsackievirus (CV) A6 replaced enterovirus (EV) 71 and CVA16, becoming the main causative agent of hand, foot and mouth disease. CVA6 infection led to significantly reduced fever duration and glucose levels compared with EV71 infection. Key Words: hand, foot and mouth disease, enterovirus, coxsackievirus A6, enterovirus 71 Accepted for publication June 20, 2014.
From the *Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China; †Beijing Ditan Hospital, Capital Medical University, Beijing, China; and ‡Liaocheng City Hospital, Liaocheng, Shandong, China. All authors declare that they have no conflict of interest. This work was supported by project—Comparison and Selection of Rapid Molecular Detection Methods of New Emergent Respiratory Infectious Disease, from Collaborative Innovation Center of Major Infectious Diseases from Beijing Municipal Education Commission. Address for correspondence: Li Xingwang, MD, Beijing Ditan Hospital, Peking University Teaching Hospital, No. 8 East Jingshun Street, Chaoyang District, Beijing 100015, China. E-mail: [email protected]. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000467
H
and, foot and mouth disease (HFMD) is a common disease that mainly infects infants and children.1 On May 2, 2008, the Ministry of Health of the People’s Republic of China listed HFMD as a category C infectious disease. Since then, the number of cases and deaths due to HFMD has ranked first among category C infectious diseases. HFMD can be caused by various enteroviruses. Since the 1970s, enterovirus (EV) 71 and coxsackievirus (CV) A16, which alternately circulate, have served as the major etiologic agents of HFMD.2 However, in recent years, HFMD outbreaks caused by other enteroviruses have been increasingly reported in the USA and several countries in Europe and Asia.3–7 As a result, we analyzed specimens from patients to investigate the pattern, etiologic agents and clinical manifestations of HFMD in Beijing, China during 2013.
MATERIALS AND METHODS Patients clinically diagnosed with HFMD in Beijing at the Beijing Ditan Hospital, the fixed-point hospital for HFMD treatment, in 2013 were included in the study. Each patient had at least 1 specimen, such as a throat swab or stool specimen, collected within 3 days of diagnosis. Medical records were reviewed retrospectively. Selected patients or their caregivers were interviewed by telephone to collect information about the presence of onychomadesis (nail separation starting at the matrix).4 Informed consent was obtained from the patients or their parents. Viral RNA was extracted using the QIAamp viral RNA mini kit (Qiagen, Hilden, Germany). Real-time reverse transcription polymerase chain reaction was performed according to the
1302 | www.pidj.com
method developed by the Shanghai Kehua Bio-engineering Co., Ltd (KHB), China. To genotype the viruses, one-step reverse transcription polymerase chain reaction (TaKaRa) was performed with primers 486/488, 292/222 or 490/492.8 PCR products were examined by gel electrophoresis, purified using a commercial procedure (Beijing Dingguochangsheng Biotechnology Co., Ltd, China) and subjected to nucleotide sequencing. The sequences were compared with known genotypes in the GenBank database using the BLAST search tool. SPSS 16.0 software was used for the statistical analyses. Categorical variables were tested using the χ2 or Fisher’s exact test. Continuous variables were tested using the independent-samples t test. A P value of less than 0.05 was considered significant.
RESULTS A total of 243 HFMD patients, including 22 outpatients and 221 inpatients, were enrolled in this study. The patients included 152 boys and 91 girls, with a sex ratio of 1.7:1. The cases occurred in patients ranging from 2 months to 20 years of age (mean 1.8 years); the cases primarily occurred in children
Hongyan et al
HAND, FOOT AND MOUTH DISEASE CAUSED BY COXSACKIEVIRUS A6, BEIJING, 2013 Gu Hongyan, MD,* Ma Chengjie, PhD,† Yang Qiaozhi, MD,‡ Hua Wenhao, MD,† Li Juan, MD,† Pang Lin, PhD,† Xu Yanli, MD,† Wei Hongshan, PhD,† and Li Xingwang, MD*† Abstract: Specimens and clinical data were collected from 243 hand, foot and mouth disease patients in Beijing in 2013. In total, 130 stool specimens were genotyped for enterovirus. Hand, foot and mouth disease was mainly detected in suburban areas and at the edges of urban areas between May and August. Coxsackievirus (CV) A6 replaced enterovirus (EV) 71 and CVA16, becoming the main causative agent of hand, foot and mouth disease. CVA6 infection led to significantly reduced fever duration and glucose levels compared with EV71 infection. Key Words: hand, foot and mouth disease, enterovirus, coxsackievirus A6, enterovirus 71 Accepted for publication June 20, 2014.
From the *Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China; †Beijing Ditan Hospital, Capital Medical University, Beijing, China; and ‡Liaocheng City Hospital, Liaocheng, Shandong, China. All authors declare that they have no conflict of interest. This work was supported by project—Comparison and Selection of Rapid Molecular Detection Methods of New Emergent Respiratory Infectious Disease, from Collaborative Innovation Center of Major Infectious Diseases from Beijing Municipal Education Commission. Address for correspondence: Li Xingwang, MD, Beijing Ditan Hospital, Peking University Teaching Hospital, No. 8 East Jingshun Street, Chaoyang District, Beijing 100015, China. E-mail: [email protected]. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000467
H
and, foot and mouth disease (HFMD) is a common disease that mainly infects infants and children.1 On May 2, 2008, the Ministry of Health of the People’s Republic of China listed HFMD as a category C infectious disease. Since then, the number of cases and deaths due to HFMD has ranked first among category C infectious diseases. HFMD can be caused by various enteroviruses. Since the 1970s, enterovirus (EV) 71 and coxsackievirus (CV) A16, which alternately circulate, have served as the major etiologic agents of HFMD.2 However, in recent years, HFMD outbreaks caused by other enteroviruses have been increasingly reported in the USA and several countries in Europe and Asia.3–7 As a result, we analyzed specimens from patients to investigate the pattern, etiologic agents and clinical manifestations of HFMD in Beijing, China during 2013.
MATERIALS AND METHODS Patients clinically diagnosed with HFMD in Beijing at the Beijing Ditan Hospital, the fixed-point hospital for HFMD treatment, in 2013 were included in the study. Each patient had at least 1 specimen, such as a throat swab or stool specimen, collected within 3 days of diagnosis. Medical records were reviewed retrospectively. Selected patients or their caregivers were interviewed by telephone to collect information about the presence of onychomadesis (nail separation starting at the matrix).4 Informed consent was obtained from the patients or their parents. Viral RNA was extracted using the QIAamp viral RNA mini kit (Qiagen, Hilden, Germany). Real-time reverse transcription polymerase chain reaction was performed according to the
1302 | www.pidj.com
method developed by the Shanghai Kehua Bio-engineering Co., Ltd (KHB), China. To genotype the viruses, one-step reverse transcription polymerase chain reaction (TaKaRa) was performed with primers 486/488, 292/222 or 490/492.8 PCR products were examined by gel electrophoresis, purified using a commercial procedure (Beijing Dingguochangsheng Biotechnology Co., Ltd, China) and subjected to nucleotide sequencing. The sequences were compared with known genotypes in the GenBank database using the BLAST search tool. SPSS 16.0 software was used for the statistical analyses. Categorical variables were tested using the χ2 or Fisher’s exact test. Continuous variables were tested using the independent-samples t test. A P value of less than 0.05 was considered significant.
RESULTS A total of 243 HFMD patients, including 22 outpatients and 221 inpatients, were enrolled in this study. The patients included 152 boys and 91 girls, with a sex ratio of 1.7:1. The cases occurred in patients ranging from 2 months to 20 years of age (mean 1.8 years); the cases primarily occurred in children
