High seroprevalence of enterovirus infections in apes and old world monkeys.
ABSTRACT To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.
- SourceAvailable from: Tytti Vuorinen[show abstract] [hide abstract]
ABSTRACT: Human enteroviruses are currently grouped into five species Human enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D and Poliovirus. During surveillance for enteroviruses serologically non-typable enterovirus strains were found from acute flaccid paralysis patients and healthy individuals. In this study, we report isolates of recently described enterovirus types EV76 and EV90 of HEV-A species and characterize two new enterovirus type candidates, EV96 and EV97, to species HEV-C and HEV-B, respectively. Analysis of partial 3D regions of EV96 strains revealed sequence divergence consistent with several recombination events between EV96, other HEV-C viruses and polioviruses. Phylogenetic analysis of all available 5'-untranslated region sequences of human entero- and rhinovirus prototype strains and 10 simian enterovirus strains suggested interspecies recombination involving this region.Journal of General Virology 10/2007; 88(Pt 9):2520-6. · 3.13 Impact Factor
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ABSTRACT: Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools.American Journal of Epidemiology 03/1979; 109(2):103-23. · 4.78 Impact Factor
Article: Hybrid origin of SIV in chimpanzees.Science 07/2003; 300(5626):1713. · 31.20 Impact Factor
S eroprevalenc e
Infec tions in Apes
and Old World
Heli Harvala, Chloe L. McIntyre, Natsuko Imai,
Lucy Clasper, Cyrille F. Djoko, Matthew LeBreton,
Marion Vermeulen, Andrew Saville,
Francisca Mutapi, Ubald Tamoufé, John Kiyang,
Tafon G. Biblia, Nicholas Midzi, Takafi ra Mduluza,
Jacques Pépin, Richard Njoum, Teemu Smura,
Joseph N. Fair, Nathan D. Wolfe, Merja Roivainen,
and Peter Simmonds
To estimate population exposure of apes and Old World
monkeys in Africa to enteroviruses (EVs), we conducted a
seroepidemiologic study of serotype-specifi c neutralizing
antibodies against 3 EV types. Detection of species A, B,
and D EVs infecting wild chimpanzees demonstrates their
potential widespread circulation in primates.
divided genetically into 4 species (EV A–D), and each
contains numerous antigenically distinct serotypes (1).
Although EVs were originally classifi ed by serologic
analysis and pathogenic properties in laboratory animals,
sequences from the viral capsid region provide an
alternative method for classifi cation (2). More recently,
classifi ed variants have been assigned as chronologically
numbered EV types (currently to EV-C116).
nteroviruses (EVs) form a diverse genus in the virus
family Picornaviridae. EVs that infect humans are
EVs also naturally infect other mammalian species,
although most are in separate species from those that infect
humans. However, EVs isolated from Old World monkeys
(OWMs) (principally Asian macaques) are grouped into
species A and B; a separate simian species (SEV-A); or are
unassigned (EV-108, SV6, and EV-103) (3).
Although EV isolates from OWMs have been
extensively characterized, little attention has been paid
to EVs that circulate in apes. We recently detected EV-
A76 (species A) and a new EV type in species B and D
(EV-B110 and EV-D111) that infect a wild population
of chimpanzees (Pan troglodytes) in Cameroon (3).
Detection frequencies of 15% in fecal samples suggest that
EV infections are relatively common in this species. We
estimated population exposure of apes in Africa and OWM
species to EVs.
To estimate population exposure of apes and OWM
species in Africa to EVs, we conducted a seroepidemiologic
study of serotype-specifi c neutralizing antibodies against
3 EV types. These seroprevalences were compared with
seroprevalences in human populations in areas where
primates also lived (Cameroon, Zimbabwe, and South
Africa) and with those in control populations in Europe
(United Kingdom and Finland). Ethical approval for the
use of study samples was obtained from the University of
Zimbabwe Institutional Review Board and the Medical
Research Council of Zimbabwe; the Human Research
Ethics Committee, South African National Blood Service;
the ethics committees of the Cameroonian Ministry of
Health; the Centre Hospitalier Universitaire de Sherbrooke,
Canada; and Lothian Regional Ethics Committee,
EV-D94 (E210), EV-A76 (KAZ00–14550) (4,5), and
a clinical isolate of echovirus 11 from Edinburgh (E-11)
were used for seroprevalence studies. Neutralization assays
were performed in human rhabdomyosarcoma cells as
described (6) with 1 minor change (inactivation at 56°C for
45 min). Serum specimens at 2 dilutions (1:16 and 1:64)
were incubated with virus (one hundred 50% tissue culture
infectious doses) in 96-well plates. Rhabdomyosarcoma
cells were added to wells (≈2 × 105 cells/mL), and cultures
were incubated at 37°C for <6 days. The highest dilution
that completely inhibited viral replication was taken as the
endpoint titer for the sample.
Plasma samples were collected from chimpanzees
(P. troglodytes), gorillas (Gorilla gorilla gorilla), and
several OWMs (Table 1). Sample shipments complied
with the Convention on International Trade in Endangered
Species of Wild Fauna and Flora. Samples were collected
for veterinary welfare purposes from animals in 2 wildlife
sanctuaries in Yaoundé and Limbe, Cameroon. Animals
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012 283
Author affi liations: Royal Infi rmary of Edinburgh, Edinburgh,
Scotland (H. Harvala); University of Edinburgh, Edinburgh (H.
Harvala, C.L. McIntyre, N. Imai, L. Clasper, F. Mutapi, P. Simmonds);
Global Viral Forecasting Initiative, Yaoundé, Cameroon (C.F. Djoko,
M. LeBreton, U. Tamoufé, J.N. Fair, N.D. Wolfe) Global Forcasting
Initiatve, San Francisco, California, USA (C.F. Djoko, M. LeBreton,
N.D. Wolfe); South African National Blood Service, Weltevreden
Park, South Africa (M. Vermeulen, A. Saville); Limbe Wildlife Centre,
Limbe, Cameroon (J. Kiyang); Ape Action Africa, Yaoundé, (T.G.
Biblia); National Institute of Health Research, Harare, Zimbabwe
(N. Midzi); University of Zimbabwe, Harare (T. Mduluza); Université
de Sherbrooke, Sherbrooke, Quebec, Canada (J. Pepin); Centre
Pasteur du Cameroun, Yaoundé (R. Njoum); and National Institute
for Health and Welfare, Helsinki, Finland (T. Smura, M. Roivainen)
were primarily wild born and brought to sanctuaries after
confi scation by authorities or abandonment by owners.
Human samples were obtained from 3 sub-Saharan African
populations and control groups in the United Kingdom and
Finland (Table 2). None had identifi able compounding risk
factors that infl uenced their exposure to EVs. Plasma was
separated from anticoagulated blood by centrifugation and
stored at −70°C until testing.
The study was designed to determine the extent to which
a human EV serotype (E-11) could spread into nonhuman
populations, and conversely, the extent to which EV-A76
(previously recovered from chimpanzees) circulated in
human populations in areas where chimpanzees also lived
(Cameroon), elsewhere in Africa in regions without apes,
and in nonprimate-exposed control populations in Europe.
Species D viruses are frequently isolated from chimpanzees
and gorillas (3), and we selected EV-D94, isolated from
populations in central Africa, as a representative of this
Chimpanzees and gorillas showed evidence (Figure)
of extensive previous exposure to E-11 (58% and 72%)
and EV-A76 (40% and 11%). Lower levels of antibodies
were detected against EV-D94 (13% and 0%). Conversely,
OWMs showed higher seroreactivity with EV-A76
(37%) than with E-11 (15%) and EV-D94 (2%), which
demonstrated wide circulation of this virus among OWM
species. Seven samples from mona monkeys accounted
for half of E-11–positive samples, and EV-A76 antibodies
were widely distributed in baboons, mandrills, and other
Contrasting patterns of EV exposure to the 3 EV types
were observed in humans (Figure). High seroprevalences of
E-11 and EV-D94 were observed in all human populations
(53%–95% and 63%–85%), whereas seroreactivity to
EV-A76 was largely confi ned to Cameroon (55%) and
Zimbabwe (35%), and uniformly <6% elsewhere.
Serologic testing of nonhuman primate samples
provided unequivocal evidence of exposure to all 3
serotypes. Although primate sampling was restricted to
animals held in sanctuaries under veterinary supervision
and infections may have been acquired in captivity from
human or dietary sources, epidemiologic observations
support the hypothesis that EV infections may also be
acquired in the wild. Many sampled animals were adults on
entry to sanctuaries, while analogous to human infections,
and EV exposure is frequent during infancy or childhood.
Also, EV infections in apes are widespread in the wild,
and active infections are found in more than one sixth of
animals screened (3).
Another factor determining whether EVs can be
indigenous to a species or originate from repeated
external (cross-species) transmission is host population
size. Perpetuation of nonpersistent viruses requires
minimum population sizes large enough to sustain
chains of transmission, which is dependent on duration
of infectivity, seasonality of infections, duration of
284 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012
Table 1. Seroprevalence of echovirus and enterovirus among apes and Old World monkeys, sub-Saharan Africa and Europe
Taxonomic name (common name)
Pan troglodytes (chimpanzee)
Gorilla gorilla gorilla (gorilla)
Old World Monkeys
C. erythrotis (red-eared monkey)
C. preussi (Preussi’s monkey)
C. pogonias (crowned monkey)
C. mona (mona monkey)
C. nictitans (spot-nosed monkey)
M. sphinx (mandrill)
M. leucophaeus (drill)
C. tantalus (tantalus monkey)
E. patas (patas monkey)
P. anubis (olive baboon)
No. (%) positive
Table 2. Human samples from sub-Saharan Africa and Europe
tested for echovirus and enterovirus antibodies*
Cameroon General population
Zimbabwe General population
South Africa Blood donors
Finland Pregnant women
UK General population
*Forty samples from each country were used.
Mean age, y
Enterovirus in Apes and Old World Monkeys
immunity, generation time of the virus and host, rate of
population turnover (7,8), and degree of fragmentation
of populations. These parameters are diffi cult to estimate
in nonhuman primates, although studies of isolated
human communities show that population size needed
for maintaining transmission of EVs may be large, e.g.,
poliovirus infections were not sustained among an Eskimo
community of 450 persons (9). Therefore, chimpanzee
and gorilla populations may be too small and fragmented
to sustain EV infections. However, relatively long-term
fecal excretion of EVs, the environmental stability of
shed EVs, and contamination of nest sites may perpetuate
infections within an established group.
In contrast to apes, the population size of several OWM
species is large and with higher population connectivity,
turnover, and supply of susceptible animals, may support
indigenous circulation of EVs. Supporting this suggestion
is genetic evidence that EVs isolated from OWMs in
southern Asia and Africa group separately from most
variants identifi ed in humans elsewhere by phylogenetic
analysis (10). EV variants in chimpanzees that matched
OWM serotypes (e.g., EV-B110 most closely related to
SA5, and EV-A76, EV-A89, and EV-A90 in the OWM
species A group) (3; unpub. data) suggest that OWMs
are a potential source of infection. Predation of the red
colobus monkey by chimpanzees (11,12) may favor such
cross-species transmissions, as documented in the genesis
of simian immunodefi ciency virusCPZ from OWM simian
immunodefi ciency viruses (13). Cross-species transmission
from OWMs to apes is consistent with high seroprevalences
of EV-A76 antibodies in apes, baboons, and other OWMs.
Overall, our serologic survey data and previous
fecal sampling data (3) provide evidence for extensive
circulation of EVs between primates and existence of
human and OWM reservoirs of infection that may spill
over into ape populations too small to maintain indigenous
EV variants. Whether OWMs or apes represent a potential
source of new EVs in humans (that may become pandemic
in the absence of prior population exposure) is uncertain.
However, the global outbreak of EV-D70 that originally
centered on a cluster of human infections in central Africa
(14,15) provides a potential example of this occurrence.
Extensive past infection of a variety of EVs in apes and
OWMs should lead to a reappraisal of the host range of
what have been considered to be primarily human viruses
and a potential source for the periodic emergence of new
EV types into immunologically naive human populations.
We thank the Cameroon Ministry of Forestry and Fauna,
Limbe Wildlife Centre, Ape Action Africa, and the US Embassy in
Cameroon for support; the Ministry of Health and Child Welfare
in Zimbabwe; the Provincial Medical Director of Mashonaland
East; and the environmental health workers, residents, teachers,
and school children in Mutoko and Rusike for their cooperation;
and members of the National Institutes for Health Research
(Zimbabwe) for technical support.
This study was supported by the Wellcome Trust, UK (grant
no. WT082028MA), and the Thrasher Foundation. Global viral
forecasting is supported by Google.org, the Skoll Foundation,
the Henry M. Jackson Foundation for the Advancement of
Military Medicine, the US Armed Forces Health Surveillance
Center Division of Global Emerging Infections Surveillance
Operations, and the US Agency for International Development
Emerging Pandemics Threat Program (PREDICT Project) under
Cooperative Agreement no. GHN-A-OO-09-00010-00. F.M. was
supported by Medical Research Council UK (grant no G81/538).
N.D.W. was supported by the National Institutes of Health
Director’s Pioneer Award (DP1-OD000370),
Dr Harvala is a specialist registrar at the Royal Infi rmary of
Edinburgh. Her research interest is enterovirus pathogenesis.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012 285
Figure. Seroprevalence of neutralizing antibody (titers >16) to
echovirus 11 (E-11) and enteroviruses A76 (EV-A76) and D94 (EV-
D94) in A) human populations and B) nonhuman primates.
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Address for correspondence: Heli Harvala, Virology Laboratory, Royal
Infi rmary of Edinburgh, Little France Crescent, Edinburgh, EH16 4SU,
Scotland; email: firstname.lastname@example.org
286 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012