Seroprevalence and molecular epidemiology of enterovirus 71
Sabine Diedrich Æ Anna Weinbrecht Æ
Received: 5 February 2009 / Accepted: 25 May 2009 / Published online: 9 June 2009
Ó Springer-Verlag 2009
Abstract Enterovirus 71 (EV71) has emerged as a sig-
niﬁcant pathogen with potential to cause large outbreaks.
Because little is known about its seroprevalence and
molecular epidemiology in Germany, data for 1997–2007
are presented. Four hundred thirty-six sera from persons
aging 10 months to 75 years were tested in a neutralisation
test; 63.4% of pre-school children were seronegative,
whereas about 75% of adults had antibodies to EV71.
Phylogenetic analysis of 28 isolates associated with neu-
rological or cutaneous manifestations showed that isolates
belonging to genogroup C1 predominated in 2000–2005,
followed by a change to genogroup C2 in 2006 and 2007.
This shows the importance of monitoring the diversity of
one of the most relevant neurotropic enteroviruses.
EV71 is one of the more than 100 human enterovirus
(HEV) types that have been identiﬁed to date. It belongs to
the family Picornaviridae, genus Enterovirus, species
Human enterovirus A. By molecular typing, EV71 can be
divided into three genogroups (A, B, C), the last two being
further subdivided into B1–B5 and C1–C5 . Currently,
genogroups B and C are co-circulating worldwide.
EV71 is transmitted through the faecal-oral route and
direct contact with throat discharges or ﬂuid from blisters.
EV71 infections manifest most frequently as a mild exan-
thema known as hand, foot and mouth disease (HFMD). A
small proportion of EV71 infections are associated with
severe complications, including aseptic meningitis, pul-
monary oedema and acute ﬂaccid paralysis.
Since the initial description of EV71 40 years ago, many
outbreaks of infection with this virus have been reported.
Three separate waves of E71 activity occurred in the world
between 1970 and 2000, one in each decade . The most
severe EV71 epidemic occurred in Taiwan in 1998, where
at least 130,000 cases of HFMD were reported . In
China, a lasting HFMD outbreak has affected more than
30,000 children . Although most cases occur in South
East Asia, E71 activity is not conﬁned to this part of the
world. In Europe, severe E71 outbreaks with poliomyelitis-
like symptoms have been reported from Bulgaria in 1975
and Hungary in 1978 [5, 6]. Sporadic cases with EV71
detection have been reported from several other European
Because little is known about the seroprevalence and
occurrence of E71 in Germany, seroepidemiological and
molecular data from 1997 to 2007 are presented in this
Neutralising antibodies to EV71 were tested on 436
randomly selected stored serum samples from healthy
children and adults who participated in the German Health
Examination Survey organised at the Robert Koch Institute
in 1997/1998 .
The neutralising antibody test of EV71 followed the
standard protocol of a microneutralisation test using the
prototype strain BrCr and RD cells. It is known that anti-
bodies raised in rabbits or collected from infected patients
are able to neutralise EV71 virus stocks, regardless of the
genogroup of the virus used for challenge (antigenic cross-
Overall, 60.3% of tested samples had neutralising anti-
bodies to EV71 (Fig. 1). The seroprevalence increased with
age, but there was a signiﬁcant gap of antibodies in young
S. Diedrich (&) Á A. Weinbrecht Á E. Schreier
Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany
Arch Virol (2009) 154:1139–1142