Peter Charles McMinn,1
Kwai Peng Chan2 & Mary Jane Cardosa3
1 Telethon Institute for Child Health
Research, Perth, Australia
2 Singapore
General Hospital, Singapore
3 Universiti Malaysia
Sarawak, Kuching, Sarawak,
Malaysia
Enterovirus 71 (EV71) is a frequent cause of hand, foot and
mouth disease (HFMD) epidemics associated with severe neurological sequelae in
a proportion of cases. There has been a significant increase in EV71 epidemic
activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics
in our region have been associated with a severe form of brainstem encephalitis
associated with pulmonary oedema ("neurogenic pulmonary oedema") and
high case-fatality rates. Six genetic lineages of EV71 have co-circulated since
1997, including four previously undescribed genogroups (B3, B4, B5, C3). Viruses belonging to genogroups B3, B4 and B5 have
circulated endemically in Southeast Asia during this
period and were the primary cause of several large HFMD/encephalitis epidemics
in Malaysia, Singapore
and Western Australia. Viruses
belonging to genogroup C1 underwent low-level endemic circulation in the
Asia-Pacific region prior to 2002 and emerged in epidemic form in Malaysia
during 2003. Viruses belonging to genogroup C2 were the primary cause of the
large Taiwanese EV71 epidemic in 1998, during which there were 78 fatal cases
of neurogenic pulmonary oedema. Viruses belonging to genogroup C3 were isolated
during a HFMD and meningitis outbreak in Korea
in 2001. In general, attempts to identify neurovirulence determinants in
circulating EV71 strains have been disappointing. However, we have recently
identified a single lineage of C2 genogroup viruses that was responsible for
all cases of severe neurological disease identified in Perth
during 1999. This lineage is characterized by a unique point mutation in the
VP1 gene that results in an amino acid change from alanine to valine at
position 170. VP1-170 is located at the rim of the receptor-binding canyon on
the virion surface and may thus affect neurovirulence through alteration of
receptor binding.