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Molecular epidemiology of enterovirus 71 in peninsular Malaysia, 1997-2000

Herrero LJ, Lee CS, Hurrelbrink RJ, Chua BH, Chua KB, McMinn PC

Arch Virol, 2003 Jul;148(7):1369-85.
PMID: 12827466

Human enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae) has been responsible for sporadic cases and outbreaks of hand-foot-and-mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like disease in Europe, the U.S.A., Australia and Asia. Recently, there has been an increase in EV71 activity in the Asia-Pacific region, with many outbreaks of HFMD associated with brainstem encephalitis manifesting as neurogenic pulmonary oedema with a high case fatality rate. In 1997, and again in 2000, EV71 outbreaks occurred in peninsular Malaysia. Variations in VP1 gene sequences have been shown to divide all known EV71 field isolates into three distinct genogroups (A, B and C). Consequently we examined the VP1 gene sequences of 43 EV71 strains isolated in peninsular Malaysia between 1997 and 2000 in order to determine the genogroup prevalence over the period. In this study we show that four subgenogroups (B3, B4, C1 and C2) of EV71 circulated in peninsular Malaysia between 1997 and 2000. Subgenogroups B3, B4 and C1 have been identified as the primary cause of the outbreaks of EV71 in peninsular Malaysia. Subgenogroup C1 also displayed endemic circulation from 1997 to 2000 and subgenogroup C2 was present at a low level during the 1997 outbreak.

Matched MeSH terms: Enterovirus/classification
Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998

Brown BA, Oberste MS, Alexander JP, Kennett ML, Pallansch MA

J Virol, 1999 Dec;73(12):9969-75.
PMID: 10559310

Enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 x 10(-2) substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.

Matched MeSH terms: Enterovirus/classification
Sentinel surveillance for human enterovirus 71 in Sarawak, Malaysia: lessons from the first 7 years

Podin Y, Gias EL, Ong F, Leong YW, Yee SF, Yusof MA, et al.

BMC Public Health, 2006 Jul 07;6:180.
PMID: 16827926

BACKGROUND: A major outbreak of human enterovirus 71-associated hand, foot and mouth disease in Sarawak in 1997 marked the beginning of a series of outbreaks in the Asia Pacific region. Some of these outbreaks had unusually high numbers of fatalities and this generated much fear and anxiety in the region.
METHODS: We established a sentinel surveillance programme for hand, foot and mouth disease in Sarawak, Malaysia, in March 1998, and the observations of the first 7 years are described here. Virus isolation, serotyping and genotyping were performed on throat, rectal, vesicle and other swabs.
RESULTS: During this period Sarawak had two outbreaks of human enterovirus 71, in 2000 and 2003. The predominant strains circulating in the outbreaks of 1997, 2000 and 2003 were all from genogroup B, but the strains isolated during each outbreak were genetically distinct from each other. Human enterovirus 71 outbreaks occurred in a cyclical pattern every three years and Coxsackievirus A16 co-circulated with human enterovirus 71. Although vesicles were most likely to yield an isolate, this sample was not generally available from most cases and obtaining throat swabs was thus found to be the most efficient way to obtain virological information.
CONCLUSION: Knowledge of the epidemiology of human enterovirus 71 transmission will allow public health personnel to predict when outbreaks might occur and to plan interventions in an effective manner in order to reduce the burden of disease.

Matched MeSH terms: Enterovirus/classification
Fulltext Genetic diversity of Coxsackievirus A21 associated with sporadic cases of acute respiratory infections in Malaysia

Supian NI, Ng KT, Chook JB, Takebe Y, Chan KG, Tee KK

BMC Infect Dis, 2021 May 17;21(1):446.
PMID: 34001016 DOI: 10.1186/s12879-021-06148-x

BACKGROUND: Coxsackievirus A21 (CVA21), a member of Enterovirus C from the Picornaviridae family, has been associated with respiratory illnesses in humans.
METHODS: A molecular epidemiological investigation of CVA21 was conducted among patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014 in Kuala Lumpur, Malaysia.
RESULTS: Epidemiological surveillance of acute respiratory infections (n = 3935) showed low-level detection of CVA21 (0.08%, 1.4 cases/year) in Kuala Lumpur, with no clear seasonal distribution. Phylogenetic analysis of the new complete genomes showed close relationship with CVA21 strains from China and the United States. Spatio-temporal mapping of the VP1 gene determined 2 major clusters circulating worldwide, with inter-country lineage migration and strain replacement occurring over time.
CONCLUSIONS: The study highlights the emerging role of CVA21 in causing sporadic acute respiratory outbreaks.

Matched MeSH terms: Enterovirus/classification
Fulltext Detection and characterization of viruses causing hand, foot and mouth disease from children in Seri Kembangan, Malaysia

Ling BP, Jalilian FA, Harmal NS, Yubbu P, Sekawi Z

Trop Biomed, 2014 Dec;31(4):654-62.
PMID: 25776590 MyJurnal

Hand, foot and mouth disease (HFMD) is a common viral infection among infants and children. The major causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were reported in neighboring countries. Infected infants and children may present with fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71 infections might cause fatal neurological complications. Since 1997, EV71 caused fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to identify and classify the viruses which detected from the patients who presenting clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December 2012 until July 2013, a total of 28 specimens were collected from patients with clinical case definitions of HFMD. The HFMD viruses were detected by using semi-nested reverse transcription polymerase chain reaction (snRT-PCR). The positive snRT-PCR products were sequenced and phylogenetic analyses of the viruses were performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6 (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis studies, EV71 strains were identified as sub-genotype B5; CVA16 strains classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by different types of Enterovirus, which were EV71, CVA6 and CVA16.

Matched MeSH terms: Enterovirus/classification*
Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease

Ooi MH, Solomon T, Podin Y, Mohan A, Akin W, Yusuf MA, et al.

J Clin Microbiol, 2007 Jun;45(6):1858-66.
PMID: 17446325

Human enterovirus 71 and coxsackievirus A16 are important causes of hand-foot-and-mouth disease (HFMD). Like other enteroviruses, they can be isolated from a range of sterile and nonsterile sites, but which clinical sample, or combination of samples, is the most useful for laboratory diagnosis of HFMD is not clear. We attempted virus culture for 2,916 samples from 628 of 725 children with HFMD studied over a 3 1/2-year period, which included two large outbreaks. Overall, throat swabs were the single most useful specimen, being positive for any enterovirus for 288 (49%) of 592 patients with a full set of samples. Vesicle swabs were positive for 169 (48%) of 333 patients with vesicles, the yield being greater if two or more vesicles were swabbed. The combination of throat plus vesicle swabs enabled the identification of virus for 224 (67%) of the 333 patients with vesicles; for this patient group, just 27 (8%) extra patients were diagnosed when rectal and ulcer swabs were added. Of 259 patients without vesicles, use of the combination of throat plus rectal swab identified virus for 138 (53%). For 60 patients, virus was isolated from both vesicle and rectal swabs, but for 12 (20%) of these, the isolates differed. Such discordance occurred for just 11 (10%) of 112 patients with virus isolated from vesicle and throat swabs. During large HFMD outbreaks, we suggest collecting swabs from the throat plus one other site: vesicles, if these are present (at least two should be swabbed), or the rectum if there are no vesicles. Vesicle swabs give a high diagnostic yield, with the added advantage of being from a sterile site.

Matched MeSH terms: Enterovirus/classification*