Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia

Abstract

Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia.

Dynamic Constitution of the Pathogens Inducing Encephalitis in Hand, Foot and Mouth Disease in Kunming, 2009–2011

“…In recent years, hand, foot and mouth disease (HFMD) has emerged as one of the major epidemic communicable diseases in children in Asian-Pacific countries (1)(2)(3)(4)(5). It manifests as vesicles on the hands, feet, and mouth; herpangina and other cold-like symptoms, and it is occasionally associated with severe encephalitis and cerebromeningitis, which pose a major threat to patients (6)(7)(8)(9).…”

Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review

“…[5][6][7] Outbreaks of EV71 in the region have been identified in 41% of HFMD cases, 81% of severe cases, and 93% of deaths, resulting in higher rates of complications, neurological disease, and fatalities compared with other causative agents such as CA16. 6,[8][9][10][11][12] It is therefore important to distinguish EV71 from other HFMD strains during the outbreak. 13 In 2011, following the emergence of HFMD outbreaks throughout the Western Pacific Region, the HKSAR Government announced EV71 infection as one of the 47 statutorily notifiable communicable diseases under the Prevention and Control of Disease Ordinance (Central Notification Office).…”

Molecular Analysis of Enteroviruses

“…The Ala to Val substitution at VP1 position 170 appears to be associated with increased neurovirulence [69]. Additionally, the nucleotide mutation (A→G) at position 485 in the 5' UTR may be one of the molecular determinants of EV-A71 attenuation of neurovirulence in cynomolgus monkeys [111].…”

“…To understand the molecular epidemiology and evolution of EV-A71, whole-genome sequences [1] and several distinct regions of the EV-A71 genome have been employed for analysis, such as 5' UTR [19,66], 3D polymerase region [67], VP4 region [68], and VP1 region [19,49,61,69,70]. However, the VP1 gene is considered to be the most informative and robust region for evolutionary study due to a high degree of diversity and lack of involvement in recombination [71].…”