Enterovirus epidemics and control

Molecular epidemiology of a variant of coxsackievirus A24 in Taiwan: two epidemics caused by phylogenetically distinct viruses from 1985 to 1989
(J Clin Microbiol 1993. 31: 1160-6)
Lin KH, Wang HL, Sheu MM, Huang WL, Chen CW, Yang CS, Takeda N, Kato N, Miyamura K, Yamazaki S.

Abstract
In order to know the phylogenetic relationship and the route of transmission of a variant of coxsackievirus A24 (CA24v), an agent that caused four sequential outbreaks of acute hemorrhagic conjunctivitis from 1985 to 1989 in Taiwan, the nucleotide sequence variations in the virus-encoded proteinase 3C region (549 nucleotides) were studied with 19 isolates. The prototype strain (EH24/70), four isolates from Japan, and two isolates from Hong Kong were used for comparison. The nucleotide sequences of the Taiwan strains from the 1985-1986 and 1988-1989 epidemics were closely related within each epidemic, while they were more distantly related between strains from two epidemics. Phylogenetic analysis by the unweighted pairwise grouping method of the arithmetic average revealed that the 19 Taiwan isolates had diverged into two groups, 1985-1986 and 1988-1989 groups. The time at which these two groups diverged was estimated to be around May 1982, more than 3 years prior to the first appearance of the CA24v epidemic in Taiwan. On each occasion, the viruses caused a 2-year epidemic and then disappeared. The Taiwan isolates from 1985 to 1986 were closely related to the Japan isolates from 1985 to 1986 and the Taiwan isolates from 1988 to 1989 were phylogenetically close to the 1989 Japan isolates, indicating that Taiwan and Japan had two common-source outbreaks. However, none of the 1988 Taiwan isolates were phylogenetically close to the 1988 Japan or Hong Kong isolates. The evidence revealed that Taiwan has had two repeated but discontinuous introductions of CA24v since its first appearance in Taiwan in 1985. None of the other CA24v strains have been detected so far.

************************************************************************

Outbreak of aseptic meningitis in Taipei in spring 1993
(J Formos Med Assoc 1995. 94: 14-8)
Hsu CM, Chen JM, Huang LM, Lee PI, Kao CL, Lee CY.

Abstract
An outbreak of aseptic meningitis in the Taipei area occurred from January to August 1993. A total of 114 cases were identified by cerebrospinal fluid (CSF) examination at National Taiwan University Hospital. Most of the cases were found from February to May 1993. The peak of age distribution was 3 to 11 years. The male-to-female ratio was 2.1 to 1. Most patients had fever, headache, and vomiting and nausea. On initial CSF examination, protein concentrations > 400 mg/L were noted in 38 of 93 CSF samples, while 19 of 70 initial samples had hypoglycorrhachia (CSF/serum glucose ratio < 0.5). CSF white cell counts of the initial lumbar puncture were 0-9 x 10(6) cells/L in 4 patients, 10-99 x 10(6) cells/L in 42 patients, 100-199 x 10(6) cells/L in 27 patients, 200-499 x 10(6) cells/L in 24 patients, 500-999 x 10(6) cells/L in 12 patients and > or = 1,000 x 10(6) cells/L in 5 patients. Polymorphonuclear cells predominated in 73 of 114 cases. Viral cultures from CSF, throat swabs and rectal swabs were done with a majority yielding nteroviruses. Enterovirus as a definite etiology was found in 58 of 114 cases and was the presumptive etiology in 15 of 114 cases. The serotypes of the enteroviruses isolated were mostly echovirus type 30. All patients recovered without obvious sequelae.

************************************************************************

Deaths among children during an outbreak of hand, foot, and mouth disease–Taiwan, Republic of China, April-July 1998
(MMWR Morb Mortal Wkly Rep 1998. 47: 629-32)
Centers for Disease C, Prevention.

Abstract
During April-July 1998, the Ministry of Health in Taiwan received approximately 90,000 reports of hand, foot, and mouth disease (HFMD) among young children based on passive surveillance from sentinel physicians. Approximately 320 children have been hospitalized with HFMD associated with suspected meningitis, encephalitis, or acute flaccid paralysis (AFP), and at least 55 have died. This report describes the clinical course of two fatal cases and presents summary findings from an ongoing clinical, epidemiologic, and laboratory investigation of the 55 deaths.

************************************************************************

Coxsackievirus B1 infection in infants less than 2 months of age
(Am J Perinatol 1998. 15: 155-9)
Chiou CC, Liu WT, Chen SJ, Soong WJ, Wu KG, Tang RB, Hwang B.

Abstract
Most of the neonatal enteroviral infections reported in the literature are associated with Coxsackievirus B2-B5 and echovirus 9 and 11. We report a
retrospective Coxsackievirus B1 (CB1) infection in infants less than 2 months of age. Seventeen patients had aseptic meningitis and 8 had systemic sepsis (multi-organ involvement including meningitis, impaired liver function, and abnormality in coagulation). The symptoms and signs were nonspecific and could not be distinguished with bacterial infection on clinical grounds. Virus isolation was mandatory for diagnosis. Impaired liver function and coagulation profiles were noted in patients with systemic sepsis, but not in patients with meningitis only. CSF examination showed some uncommon features of viral meningitis: predominance of polymorphonuclear cells (PMN) was noted in 62.5% of patients and hypoglycorrhachia in 64% of patients.
The patients with only meningitis recovered completely without any sequela. One of the eight patients with systemic sepsis died with case fatality rate 12.5%. Physicians should be aware of the possibility of CB1 virus infection in young infants during prevalent seasons. Specimens should be sent for viral culture in patients with meningitis and sepsis to make a definite diagnosis.

************************************************************************

Outbreaks of enterovirus 71 infection
(N Engl J Med 2000. 342: 355-6)
AbuBakar S, Chan YF, Lam SK.

Abstract
The outbreak of enterovirus 71 infection in Taiwan, reported by Ho et al. (Sept. 23 issue), 1 occurred almost a year after the outbreak in Malaysia. Though both outbreaks occurred in Asia and both involved large numbers of deaths, it was not known whether the two outbreaks were related. We studied the nucleotide sequence and secondary RNA structure of some of the isolates, using the sequence of the 5′ untranslated region (UTR). Enterovirus 71 isolates from patients in Singapore (seven isolates), Taiwan (two isolates), and Japan (one isolate) were examined and compared with those previously report ed in Malaysia at least two major clusters of enterovirus 71 isolates. 2, 3 or with sequences deposited in GenBank. A phylogenetic tree that we constructed using the aligned 5′ UTR sequences revealed at least two major clusters of enterovirus 71 isolates.

************************************************************************

Enterovirus 71: the virus, its infections and outbreaks
(J Microbiol Immunol Infect. 2000 Dec;33(4):205-16.)
Ho M.

Abstract
Enterovirus 71 (EV71) was first recognized in 1974. Since then it has been implicated in 13 small and large outbreaks world-wide. Large outbreaks of
hand, foot and mouth disease (HFMD), mostly benign, occurred in Japan in 1973 and 1978. Four outbreaks with brain stem encephalitis and significant
numbers of deaths occurred in Bulgaria and Hungary in the late 1970’s and in Malaysia and Taiwan in 1997 and 1998 respectively. During the latter two
epidemics, pulmonary edema and hemorrhage often leading to quick deaths in children aged from 0.5 to 3 years old was first recognized. In Taiwan 78 deaths and over 100,000 cases of HFMD occurred. Coxsackie A16 cocirculated with EV 71, without however, causing any severe illnesses. The
transmission of EV 71 was related to number of siblings in a household, rural residence and contact with cases of HFMD. Genotype analyses show that genotypes have changed with time in the United States and Japan. Recent isolates from Japan are similar to the isolates from Malaysia and Taiwan in 1997 and 1998, respectively. Even though genotype analysis has not identified specific sequences responsible for neurovirulence, the strains causing brain stem encephalitis and pulmonary edema in the Far East are similar and have arisen since 1997. Seroepidemiological studies in Taiwan suggest that children aged from 0.5 to 4 years old are most susceptible while the rest of the population are over 50% immune. Theoretically there is a pool of such susceptible subjects every few years. In prevention for another major outbreak, a simple, inactivated Salk type vaccine should be immediately prepared and made available.

************************************************************************

Enterovirus infections with special reference to enterovirus 71
(J Microbiol Immunol Infect. 2000 Mar;33(1):1-8.)
Hsiung GD, Wang JR.

Abstract
The enteroviruses comprise a large group of immunologically distinct serotypes of viruses belonging to the family of Picornaviridae. Many enteroviruses cause diseases in human, but the infections are generally mild as asymptomatic, therefore, enteroviruses are considered to be unimportant as human pathogens. However, enteroviruses may also result in serious or even fatal disease (as shown in the enterovirus 71 (EV71) epidemic in Taiwan in 1998). There are three types of polioviruses, Coxsackievirus group A and group B viruses, and echoviruses group. All together a total of 67 types are available. Starting from enterovirus type 68 to 71, they are named as enterovirus types. Enterovirus type 72 is hepatitis A virus. Paralytic disease of poliomyelitis was recorded in ancient time but characterization of poliovirus was not reported until the turn of the 19th century that poliomyelitis was a viral disease. The major breakthrough for diagnosing and controlling of poliomyelitis was the discovery that poliovirus can be propagated in human embryonic tissues in cultures. As soon as cultures of human and monkey cells began to use for isolating polioviruses in stool specimen of patients, more unknown viruses were isolated which unlike polioviruses nor Coxsackie viruses; they were called “orphan” viruses or human enteric viruses, name later simplified to
“echoviruses”. Morphologically all enteroviruses are alike. They are small, ether insensitive viruses with an RNA genome. Their nucleic acid is single
stranded, and the nucleocapsid has a cubic (icosahedral) symmetry, and is naked. The host ranges of enteroviruses vary greatly from one type to the
next and even among strains of the same type. Polioviruses have a very restricted host range among laboratory animals. Virus isolation is the best
method for diagnosis of enterovirus infection, but infection in the central nervous system (CNS) may be detected by polymerase chain reaction (PCR).
Currently final identification and serotyping of enteroviruses are by indirect immunofluorescent tests using monoclonal antibody or by neutralization test using antiserum pools described by Lim and Benyesh-Melnick. The incidence and prevalence of diseases associated with the enterovirus infections are varied. The circulation of enteroviruses recently in Tainan and the epidemic of EV71 in Taiwan in 1998 are described in this review. Although poliovirus infection may be eradicated from the world due to the efficient vaccination program, there is no specific antiviral agents for either treatment or prevention for other enterovirus infections. In 1991, a new antiviral “pleconaril” which is a novel orally bioavailable and systematically acting small molecule inhibitor for picornaviruses. “Pleconaril” is currently in clinical trials for treatment of enterovirus meningitis and respiratory infections.

************************************************************************

Duration of enterovirus shedding in stool
(J Microbiol Immunol Infect 2001. 34: 167-70)
Chung PW, Huang YC, Chang LY, Lin TY, Ning HC.

Abstract
Excretion of enterovirus (EV) may persist for months after an EV infection; the exact duration of excretion, however, is not yet known. Twelve children
who were infected with EV between September 1998 and June 1999 were enrolled into this study. The patients included 4 boys and 8 girls, aged from
1 month to 5 years. Six patients were asked to join this virus isolation program, and the other 6 were followed-up regularly. Only 2 of the patients were infected with EV 71. To delineate the duration of EV shedding in each case, throat swabs for virus isolation were performed every 1 or 2 weeks for at least 1 month, and stools were analyzed for at least 2 months following the same schedule. After the infection, EV was identifiable in the throat in 4 patients for 1 to 2 weeks. Excretion of EV through stool was evidenced for up to 7 weeks in 6 patients, 8 weeks in 3, and 11 weeks in 1. In the 2 patients who failed to show up for follow-up visits from the 7th week, excretion of EV through stool was recorded for at least 7 weeks. Different serotypes of EV could be isolated from the same patient who was not experiencing febrile illness in 2 instances in a series of virus cultures. Coexistence of vaccine poliovirus and non-polio EV, both isolated from stool, was evidenced in 2 patients. Results from this study suggest that EV may not be identified from the throat 2 weeks after the infection, but its excretion through stool can persist for up to 11 weeks. This study also demonstrated that subclinical EV coinfection could occur, and that live vaccine poliovirus did not interfere with the invasion of other non-polio EV.

************************************************************************

Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan
(J Med Virol 2002. 67: 217-23)
Lu CY, Lee CY, Kao CL, Shao WY, Lee PI, Twu SJ, Yeh CC, Lin SC, Shih WY, Wu SI, Huang LM.

Abstract
In 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by enterovirus 71 occurred in Taiwan, leaving many fatalities and
severely handicapped survivors in its wake. The reasons this rather common pathogen would cause such a large-scale epidemic remain unknown. A seroepidemiological survey to elucidate the epidemiological characteristics of this outbreak, including its incidence and case-fatality rates was undertaken. Microneutralization tests for antibodies against enterovirus 71 were used to screen four collections of serum samples: 1) 202 specimens taken from individuals > or = 4 years old in 1994; 2) 245 specimens collected from individuals of all ages in 1997; 3) 1,258 specimens collected from individuals of all ages in 1999; and 4) sera samples from a birth cohort of 81 children who had yearly blood samples taken from 1988-98. After the maternal antibody had declined, the seropositive rates began to increase with age. Approximately half of all children aged 6 years or older were enterovirus 71 seropositive. Significantly higher seropositive rates were noted in 1999 than in 1997, in children aged 0.5-3 years. The incidence of enterovirus 71 infection during the epidemic was estimated to be 13-22%, with the higher rates in younger children. The case-fatality rate was highest (96.96 per 100,000) in infants aged 6-11 months, and declined in older children. The results showed that enterovirus 71 is endemic in Taiwan. The apparent lack of large-scale enterovirus 71 activity in the 3 years before 1998 might have been the prelude to the epidemic’s appearance in 1998, and might suggest that enterovirus 71 infection
will reappear every few years. The lack of a protective antibody in younger children may account for the high incidence and case-fatality rate in this age group.

************************************************************************

Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections
(Pediatr Infect Dis J 2003. 22: 889-94)
Lin TY, Kao HT, Hsieh SH, Huang YC, Chiu CH, Chou YH, Yang PH, Lin RI, Tsao KC, Hsu KH, Chang LY.

Abstract
OBJECTIVES: Neonatal enterovirus infections have diverse manifestations, from asymptomatic to fatal. An understanding of the risk factors associated
with severe cases might help to reduce enterovirus-related morbidity and mortality. METHODS: From July 1989 through June 1998, neonates with virus culture-confirmed nonpolio enterovirus infection at Chang Gung Children’s Hospital were enrolled in the study and divided into three groups: nonspecific febrile illness; aseptic meningitis; and hepatic necrosis with coagulopathy (HNC). Demographic factors, clinical manifestations, laboratory data and outcome were analyzed to reveal factors associated with clinical severity and fatality. RESULTS: There were 146 cases including 43 neonates with nonspecific febrile illness, 61 with aseptic meningitis and 42 with HNC. By multiple logistic regression analysis, the most significant factors associated with HNC were prematurity, maternal history of illness, earlier age of onset (< or =7 days), higher white blood cell count (WBC > or =15 000/mm3) and lower hemoglobin (< or =10.7 g/dl). In 10 (24%) of 42 cases, HNC was fatal. In comparison with nonfatal cases of HNC, fatal cases had higher WBC, lower hemoglobin, higher bilirubin and higher incidence of concurrent myocarditis. Multivariate analysis showed the most significant factors associated with fatality from HNC to be total bilirubin >14.3 mg/dl (adjusted odds ratio, 29.1; 95% confidence interval, 2.5 to 355.5; P = 0.007) and concurrent myocarditis (adjusted odds ratio, 13.7; 95% confidence interval, 1.1 to 177.2; P = 0.04). Intravenous immunoglobulin did not correlate with clinical outcomes in cases with HNC. CONCLUSIONS: Prematurity, maternal history of illness, earlier age of onset, higher WBC and lower hemoglobin are significant factors associated with HNC; higher total bilirubin and concurrent myocarditis were most significantly associated with fatality from HNC.

************************************************************************

Enterovirus 71 outbreaks, Taiwan: occurrence and recognition
(Emerg Infect Dis 2003. 9: 291-3)
Lin TY, Twu SJ, Ho MS, Chang LY, Lee CY.

Abstract
Enterovirus 71 (EV71) caused a large outbreak in Taiwan in 1998 with 78 deaths, and smaller outbreaks recurred in 2000 and 2001. The outbreak was
recognized because of a large number of hand, foot, and mouth disease cases and the rapid deaths of children with the disease. Virologic and pathologic studies indicated that EV71 was the most important agent related to severe and fatal cases and that a neurogenic inflammatory response was involved in the pathogenesis of cardiopulmonary collapse resulting from fulminant EV71 infection. Seroepidemiologic study suggested that EV71 had circulated for at least 16 years and that the accumulation of susceptible hosts might have triggered the 1998 outbreak. However, a change in EV71 neurovirulence and host genetic susceptibility may also have affected the clinical outcome. The Taiwan outbreak shows that worldwide attention should be paid to such outbreaks, new antiviral drugs should be developed, and that vaccination of children under 5 years of age may be warranted.

************************************************************************

Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region
(Pediatr Int 2004. 46: 231-5)
Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, Pongsuwanna Y, Miyamura T.

Abstract
BACKGROUND: Recently, there have been large outbreaks of hand, foot and mouth disease (HFMD) mainly caused by enterovirus 71 (EV71) associated
with severe neurological diseases in the Western Pacific Region (WPR). To monitor the realtime trend of EV71 transmission throughout the WPR, the
authors conducted a molecular epidemiological analysis of EV71 infection. METHODS: Viruses were isolated from clinical samples from patients with
HFMD or those with neurological complications. The EV71 isolates were identified by microneutralization assay. The VP4 and/or VP1 regions of recent EV71 isolates were sequenced and subjected to phylogenetic analysis using reference EV71 strains. RESULTS: The phylogenetic analysis of EV71
isolates from the WPR revealed two major genogroups, B and C, based on the nucleotide sequence alignment of the VP1 or VP4 region. These two
major genogroups were further divided into subgenogroups, B1, B2, B3, and B4 and C1, C2, C3 and C4, respectively. CONCLUSIONS: The molecular
epidemiological analyses of recent and previous EV71 isolates in the WPR indicated that two major genogroups of EV71 are co-circulating in Australia,
Malaysia, Singapore, Taiwan and Japan. Recent EV71 isolates in Mainland China constitute a new distinct genetic cluster, subgenogroup C4. Two major lineages of EV71 are the major causative agents of the present HFMD epidemics in the WPR and both are considered to be neurovirulent.

************************************************************************

Appearance of intratypic recombination of enterovirus 71 in Taiwan from 2002 to 2005
(Virus Res 2008. 131: 250-9)
Huang SC, Hsu YW, Wang HC, Huang SW, Kiang D, Tsai HP, Wang SM, Liu CC, Lin KH, Su IJ, Wang JR.

Abstract
Genetic recombination is a well-known phenomenon for enteroviruses. In this study, we determined the phylogenetic relationships of five distinct regions of the EV71 genome for 73 EV71 isolates from 1986 and from 1998 to 2005 in Taiwan. Phylogenetic analyses showed that the 5′-UTR, VP4-VP2, VP1, and 3D regions of EV71 isolated in 2004 and 2005 were grouped into genotype C. However, the 2B region of these isolates differed in that it grouped with genotype B, indicating recombination within EV71 had occurred. This intratypic recombination was first seen in 2002 and became predominant in 2004 and 2005. The simplot and bootscan analyses identified two recombination points located at the 3′-termini of the 2A and 3C regions. This intratypic recombination was identified among naturally circulating EV71 isolates in Taiwan, therefore, it suggests that nonstructural genes may recombine to produce new EV71 variants.

************************************************************************

Evolution of re-emergent virus and its impact on enterovirus 71 epidemics
(Exp Biol Med (Maywood) 2011. 236: 899-908)
Huang SW, Kiang D, Smith DJ, Wang JR.

Abstract
Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, has become an emergent infectious disease worldwide, most notably in Asia. As a neurotropic virus, EV71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. In this review, we examine the epidemiology of EV71, with three waves of increased EV71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. Genetic changes including mutations and recombinations as well as the diversity of antigenic properties among EV71 strains in various outbreaks are described. Furthermore, the impact of genetic changes on viral pathogenesis and vaccine candidate selection are addressed. In conclusion, these genetic and antigenic investigations of EV71 evolution have provided us with new insight into the trend of EV71 epidemiology, which may contribute to a better understanding of the viral pathogenesis and vaccine development.

************************************************************************

Incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in Taiwan, 2008-09
(PLoS Negl Trop Dis 2012. 6: e1476)
Lee MS, Chiang PS, Luo ST, Huang ML, Liou GY, Tsao KC, Lin TY.

Abstract
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.

************************************************************************

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity
(Eur J Clin Microbiol Infect Dis 2012. 31: 1219-24)
Wang SM, Ho TS, Lin HC, Lei HY, Wang JR, Liu CC.

Abstract
Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 +/- 14.7 months) were younger than patients with herpangina/HFMD (35.8 +/- 26.4 months) or ANS dysregulation (33.9 +/- 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71.

************************************************************************

Update on enterovirus 71 infection
(Curr Opin Virol 2014. 5: 98-104)
Huang PN, Shih SR.

Abstract
Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis in children worldwide. The identified EV71 receptors provide useful information for understanding EV71replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the EV71 genome that determine virulence remain unclear. The EV71 capsid protein VP1 region might contribute to virulence and neurotropism. Transgenic mice expressing the EV71 receptor that were infected with the virus exhibited a disease similar to that observed in infected humans. Antiviral drug and vaccine development is urgently required to prevent EV71 epidemics. Delineating viral host interactions and identifying specific mechanisms that might control the neural tropism of EV71 pathogenesis would be substantial advances.

************************************************************************

Molecular and epidemiological study of enterovirus D68 in Taiwan
(J Microbiol Immunol Infect 2017. 50: 411-7)
Huang YP, Lin TL, Lin TH, Wu HS.

Abstract
BACKGROUND/PURPOSE: As an immunofluorescence assay for enterovirus D68 (EV-D68) is not available in the enteroviruses surveillance network in
Taiwan, EV-D68 may be the actual pathogen of untypeable enterovirus-suspected isolates. METHODS: The untypeable isolates collected from 2007
through 2014 were identified by nucleic acid amplification-based methods and sequencing of the VP1 region to analyze the phylogeny and epidemiology of EV-D68 in Taiwan. RESULTS: Twenty-nine EV-D68 isolates were sequenced, including 15 Cluster 3 and 14 Cluster 1 viruses. Approximately 41% of the patients were children under 5 years of age and their infections peaked in August. The ratio of male to female patients was 1.5 and 3.67 for Cluster 3 and Cluster 1, respectively. Fever and respiratory symptoms were commonly reported in EV-D68-infected patients. The results of phylogenetic analyses showed that EV-D68 isolates between 2007 and 2014 belonged to different clusters and existed for years, indicating that endemic circulation of EV-D68 existed in Taiwan. CONCLUSION: This study showed that EV-D68 has been endemic in Taiwan for some years despite a small number of positive cases. The continuous monitoring and efforts towards the improvement of diagnostic techniques are required to complete the surveillance system. This study provided the genetic and epidemiological information which could contribute to understanding the etiology and epidemiology of EV-D68.