Accuracy of Diagnostic Methods and Surveillance Sensitivity for Human Enterovirus, South Korea, 1999–2011 - Vol. 19 No. 8 - August 2013 - Emerging Infectious Disease journal - CDC
Table of Contents
Volume 19, Number 8–August 2013
Volume 19, Number 8—August 2013
Accuracy of Diagnostic Methods and Surveillance Sensitivity for Human Enterovirus, South Korea, 1999–2011
Human enteroviruses (EVs) belong to the family Picornaviridae, genus Enterovirus, and are classified into 4 species, EV-A, B, C, and D (1–3). More than 90 serotypes are currently recognized by the International Committee on Taxonomy of Virus Classifications. EV-A (17 serotypes), EV-B (56 serotypes), EV-C (16 serotypes), and EV–D (3 serotypes) species classifications are based on similarities in virus capsid protein (VP) genes (4–6). Among them, 65 serotypes are known to cause infections in humans, including polioviruses, echoviruses (E), coxsackieviruses A (CA) and B (CB), and EV types 68–71 (7,8).
AbstractThe epidemiology of enteroviral infection in South Korea during 1999–2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. Of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human EV); as diagnostic methods improved, the rate of positive results increased. A seasonal trend of outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes identified. Accurate test results correlated clinical syndromes to enterovirus genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth disease with neurologic complications to enterovirus 71. There are currently no treatments specific to human EV infections; surveillance of enterovirus infections such as this study provides may assist with evaluating the need to research and develop treatments for infections caused by virulent human EV genotypes.
Most EV infections (hand, foot and mouth disease [HFMD]; gastroenteritis; and acute hemorrhagic conjunctivitis) are asymptomatic or mild, and infected persons can recover without specific medication (5,8–10). However, the neurotropism of some EVs can cause serious central nervous system complications such as aseptic meningitis, encephalitis, and flaccid paralysis (9,11, 12). Although some EVs cause severe and potentially life-threatening illness, there is currently no antiviral treatment available for EV infection (9).
Laboratory diagnosis of EV infection is based on detection of the virus in clinical specimens such as fecal or rectal swab samples, cerebrospinal fluid (CSF), nasopharyngeal secretions collected by throat swab, and blood (11,13). Detection of EV is usually performed by isolation of the virus in cell culture, reverse transcription PCR (RT-PCR), or real-time RT-PCR (11,14–16). Currently, RT-PCR is used routinely worldwide to diagnose EV infection because of its sensitivity, specificity, and ability to detect highly conserved 5′ noncoding regions of the human EV genome (15,17,18). For determining subtype, the neutralization test is the standard diagnostic tool and is generally reliable, but it is also labor-intensive, time-consuming, and may fail to identify an isolate (16,19). Therefore, RT-PCR amplification of the VP1 coding region, then amplicon sequencing, is a sufficient mechanism for molecular typing of EVs (20).
Since 1993, the national enterovirus surveillance system of the Korea Centers for Disease Control and Prevention (KCDC) has monitored and characterized human EV infection in patients with EV-related diseases. Three basic detection methods for diagnosis have been used in this system since surveillance began. During 1993–2004 (phase I), cell culture methods were used; during 2005–2007, RT-PCR was used (phase II); and from 2008–2011 (phase III), real-time RT-PCR was the standard detection method used. Before 2005, genotyping was performed by using the neutralization test, but since then, as documented for phases II and III of this study, VP1 sequencing was used to genotype EV. In this study, we obtained the clinical and epidemiologic data regarding enterovirus infections, including outbreaks and sporadic cases, during 1999–2011 in South Korea, and focused on the improvement of surveillance sensitivity as diagnostic methods developed.