An Investigation of Epidemic Enterovirus 71 Infection in Taiwan, 2008

Min-Shi Lee, Tzou-Yien Lin, Pai-Shan Chiang, Wen-Chen Li, Shu-Ting Luo, Kuo-Chien Tsao, Guan-Yuan Liou, Mei-Liang Huang, Shao-Hsuan Hsia, Yhu-Chering Huang, and Shih-Cheng Chang

Article Published by the Pediatric Infectious Disease Journal on November 2010

Background: Enterovirus 71 (EV71) is causing life-threatening hand-foot- mouth disease in Asia. In Taiwan, EV71 epidemics with different predom- inant genotypes occurred in 1998 (C2), 2000 –2001 (B4), and 2004 –2005 (C4). This genotype replacement may have important implications for vaccine development and prediction of epidemics. A nationwide EV71 outbreak occurred again in 2008, which provided a unique opportunity to characterize clinical, virologic, and serologic features of this epidemic. Methods: We analyzed clinical and virologic data of 111 EV71 patients hospitalized in 2008 and prospectively conducted follow-ups of healthy children from June 2006 to December 2008.

Results: Among the 111 EV71 inpatients, 21 (19%) developed complica- tions. Among the 21 complicated cases, 15 had central nervous system complication only, 2 had acute heart failure, and 4 had central nervous system and pulmonary complications. In the prospective study, 11 symp- tomatic infections and 4 asymptomatic infections were detected. Twenty- two EV71 isolates were genotyped, and 21 of them belong to genotype B5, which is phylogenetically close to B5 viruses circulating in Southeast Asia. Serologic tests show that children infected with B5 viruses have lower geometric mean titers of neutralizing antibody against genotype C4 than those against genotype B5 (P 􏰁 0.004, t test).

Conclusions: The 2008 nationwide EV71 epidemic was caused by geno- type B5 that was likely introduced to Taiwan from Southeast Asia. Clinical features of the 2008 epidemic were not different from those observed before in Taiwan. Potential antigenic variations between genotype C4 and B5 viruses could be detected and its long-term epidemiologic significance needs further investigation to clarify.

7An Investigation of Epidemic Enterovirus 71 Infection in Taiwan,2010

Incidence Rates of Enterovirus 71 Infections in Young Children during a Nationwide Epidemic in Taiwan, 2008–09

      Comments Off on Incidence Rates of Enterovirus 71 Infections in Young Children during a Nationwide Epidemic in Taiwan, 2008–09

Min-Shi Lee1, Pai-Shan Chiang, Shu-Ting Luo, Mei-Liang Huang, Guan-Yuan Liou, Kuo-Chien Tsao, Tzou-Yien Lin

Article Published by POLS Neglected Tropical Disease on February 14, 2012

Objective: Enterovirus 71 (EV71) is causing life-threatening outbreaks in tropical Asia. In Taiwan and other tropical Asian countries, although nationwide EV71 epidemics occur cyclically, age-specific incidence rates of EV71 infections that are critical to estimate disease burden and design vaccine trials are not clear. A nationwide EV71 epidemic occurred in 2008–09 in Taiwan, which provided a unique opportunity to estimate age-specific incidence rates of EV71 infections.

Study Design: We prospectively recruited 749 healthy neonates and conducted follow-ups from June 2006 to December 2009. Sera were obtained from participants at 0, 6, 12, 24, and 36 months of age for measuring EV71 neutralizing antibody titers. If the participants developed suspected enterovirus illnesses, throat swabs were collected for virus isolation.

Results: We detected 28 EV71 infections including 20 symptomatic and 8 asymptomatic infections. Age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0–6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7–12, 13–24, and 25–36 months of age, respectively. Cumulative incidence rate was 15.15 per 100 persons by 36 months of age, respectively.

Conclusions: Risk of EV71 infections in Taiwan increased after 6 months of age during EV71 epidemics. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children.

6Incidence Rates of Enterovirus 71 Infections in Young Children During a Nationwide Epidemic in Taiwan, 2008-09

Comparing Molecular Methods for Early Detection and Serotyping of Enteroviruses in Throat Swabs of Pediatric Patients

Article published by POLS ONE on October 25,2012

ABSTRACT

Background: Enteroviruses include over 100 serotypes and usually cause self-limited infections with non-specific symptoms in children, with the exceptions of polioviruses and enterovirus 71 which frequently cause neurologic complications. Therefore, early detection and serotyping of enteroviruses are critical in clinical management and disease surveillance. Traditional methods for detection and serotyping of enteroviruses are virus isolation and immunofluorescence assay, which are time-consuming. In this study, we compare virus isolation and two molecular tests for detection and serotyping of enteroviruses in clinical samples.

Methods: One hundred and ten throat swabs were collected from pediatric outpatients with enterovirus-like illnesses (hand-foot-mouth disease, herpangina, and non-specific febrile illness). Virus isolation was conducted using multiple cell lines and isolated viruses were serotyped using immunofluorescent assay. In the molecular tests, a semi-nested RT-PCR and a novel CODEHOP platform were used to detect the 59UTR and VP1 genes of enteroviruses, respectively. Amplified nucleotides were sequenced and genotyped.

Results: Among the 110 cases, 39(35%), 52(47%), and 46(42%) were tested positive with these three tests, respectively. Using the consensus results of these three tests as the gold standard, agreement of the VP1 CODEHOP test was 96%, which is higher than those of the virus isolation (89%) and the 59-UTR test (88%). The VP1 CODEHOP test also has the best performance on serotyping confirmed with serum neutralization tests.

Conclusions: The VP1 CODEHOP test performed well for detection and serotyping of enteroviruses in clinical specimens and could reduce unnecessary hospitalization cares during enterovirus seasons.

5Comparing molecular methods for early detection and serotyping of enteroviruses in throat swabs of pediatric patients_

Cross-reactive Neutralizing Antibody Responses to Enterovirus 71 Infections in Young Children: Implications for Vaccine Development

Article published by POLS ONE on February 14, 2013

Background: Recently, enterovirus 71 (EV71) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C) and 11 genotypes (A, B1,B5 and C1,C5). In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2), 2000–2001 (B4), 2004–2005 (C4), and 2008 (B5). In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes.

Methods: We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses.

Results: Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (.4-fold difference). The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1) are specific for genogroup A and may be related to the observed antigenic variations.

Conclusions: This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions.

4Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young childrenImplications for vaccine development2013

Genetic and Antigenic Characterization of Enterovirus 71 in Ho Chi Minh City, Vietnam, 2011

      Comments Off on Genetic and Antigenic Characterization of Enterovirus 71 in Ho Chi Minh City, Vietnam, 2011

Le Phan Kim Thoa, Pai-Shan Chiang, Truong Huu Khanh, Shu-Ting Luo, Tran Ngoc Hanh Dan, YaFang Wang, Tang Chi Thuong, Wan-Yu Chung, Nguyen Thanh Hung, Jen-Ren Wang, Le Nguyen Thanh Nhan, Le Quoc Thinh, Ih-Jen Su, Than Duc Dung, Min-Shi Lee

Article Published by POLS ONE on July 19, 2013

Enterovirus 71 (EV71) frequently causes fatal infections in young children in Asia. In 2011, EV71 epidemics occurred in southern Vietnam. We conducted genetic and antigenic analysis of the EV71 isolates and found that 94% of them were genotype C4a related to two lineages circulating in China and 6% were genotype C5 which have circulated in Vietnam since 2003. Antigenic variants were not detected. EV71 vaccines are being developed. Longitudinal enterovirus surveillance data are critical to formulate vaccination policy in Vietnam.

3Genetic and Antigenic Characterization of Enterovirus 71 in Ho Chi Minh City, Vietnam, 2011

Epidemiology of Enterovirus 71 Infections in Taiwan

Min-Yuan Chia, Pai-Shan Chiang, Wan-Yu Chung, Shu-Ting Luo, Min-Shi Lee

Article Accepted by ELSEVIER on July 17, 2013

Enterovirus 71 (EV71) was first described in USA in 1969 but retrospective studies in The Netherlands further detected EV71 in the clinical specimens collected in 1963. EV71 has one single serotype measured by using hyperimmune animal antisera but can be phylogenetically classified into three genogroups (A, B, and C) including 11 genotypes (A, B1eB5, C1eC5). In Taiwan, EV71 caused a large-scale nationwide epidemic in 1998. Retrospective studies further detected EV71 in clinical specimens collected from handefootemouth disease patients in 1980 and 1986. Therefore, EV71 may have circulated in Taiwan prior to 1980. Since 1998, EV71 has cyclically caused nationwide epidemics with different predominant genotypes in 1998 (geno- type C2), 2000e2001 (B4), 2005 (C4), 2008 (B5), and 2012 (B5). Phylogenetic analysis revealed that C4 viruses isolated in 2005 were probably from China, B5 viruses isolated in 2008 were probably from South Eastern Asia, and B5 viruses isolated in 2012 were probably from Xiamen, China. Several studies have collected postinfection sera from children to measure cross- reactive neutralizing antibody titers against different EV71 genotypes and found that antigenic differences between genogroup B and C viruses did not have a clear pattern but that genotype A virus was antigenically different from genogroup B and C viruses. In conclusion, EV71 cycli- cally caused nationwide epidemics through international importations. EV71 surveillance in Taiwan should combine genetic and serological methods.

2.Epidemiology of Enterovirus 71 Infections in Taiwan

CODEHOP-based RT-PCR (VP1- CODEHOP) for enterovirus infections detection and serotyping

      Comments Off on CODEHOP-based RT-PCR (VP1- CODEHOP) for enterovirus infections detection and serotyping

Article Published by POLS ONE on December 1, 2016

ABSTRACT

Traditional methods for detection and serotyping of enterovirus infections are virus isolation and immunofluorescence assay (VI-IFA), which are labor-intensive and time-consuming. Recently, VP1 gene has been targeted to develop a CODEHOP-based RT-PCR (VP1- CODEHOP) for the same purpose. In this study, we conducted a 5-year enterovirus surveil- lance comparing the VI-IFA and VP1-CODEHOP tests. Throat swabs were collected from 431 pediatric patients and 208(48%) and 250(58%) were tested positive by the VI-IFA and VP1-CODEHOP tests, respectively. Among the 47 cases who had inconsistent results between the VI-IFA and VP1-CODEHOP tests and provided paired sera for serological verifications, correct diagnosis for the VI-IFA and VP1-CODEHOP were 5(11%) and 40(85%) cases, respectively. Therefore, the VP1-CODEHOP is more reliable for detection of human enteroviruses than the VI-IFA. Based on serological verifications for the eight cases who had inconsistent serotypes between the two tests and provided paired sera, five and two showed consistent serotypes with the VP1-CODEHOP and VI-IFA tests, respec- tively. CVA16, CVA6 and EV71 were the most prevalent serotypes in northern Taiwan, 2008~2012. Moreover, variant CVA2, CVA6 and EV71 viruses were further identified based on phylogenetic analysis of partial VP1 sequences. In conclusion, the VP1-CODEHOP test could be used as the primary method for enterovirus surveillance to support decision-mak- ing for outbreak control.

A Molecular Approach Applied to EV Surveillance in Northern Taiwan 2008-2012

As enterovirus activity peaks, public advised to wash hands with soap and water frequently and watch for prodromal signs of complications in children with enterovirus infection

Press released by CDC, Taiwan

Date: July 25, 2017

As enterovirus activity in Taiwan gradually peaks, during July 16 and 22,2017, the number of visits to outpatient services and ER for enterovirus infection in the nation exceeded the epidemic threshold, indicating enterovirus activity has reached its peak. In addition, one new case of enterovirus infection with severe complications was confirmed. Currently, coxsackie A virus is the dominant strain circulating in the community, while enterovirus 71 continues to circulate. Taiwan CDC stresses that enterovirus is highly contagious, especially among family members. Therefore, the public is urged to heighten vigilance, wash hands with soap and water frequently, and practice good personal hygiene. Adults returning home from work are advised to change clothes and wash hands with soap and water before coming into contact with children to lower the risk of infection and transmission. Continue reading