Journal of Medical Virology 85:10371045 (2013)
Hepatitis E Virus Infection in Latin America:
A Review
J.M. Echevarra,1* J.E. Gonzalez,2 L.L. Lewis-Ximenez,3 D.R. Lopes dos Santos,4 M.S. Munne,2
M.A. Pinto,3 F.H. Pujol,5 and L.A. Rodrguez-Lay6
1
Carlos III Health Institute, Madrid, Spain
2
National Institute of Infectious Diseases, Buenos Aires, Argentina
3
Instituto Oswaldo Cruz, FioCruz, Rio de Janeiro, Brazil
4
Institute of Veterinary, Rural Federal University of Rio de Janeiro, Seropedica, Brazil
5
Venezuelan Institute of Scientic Research, Caracas, Venezuela
6
Institute of Tropical Medicine Pedro Kour, La Habana, Cuba
Data reported during recent years reveal the
complex picture of the epidemiology of hepati-
tis E virus (HEV) infection in Latin America.
Whereas in countries like Argentina and Brazil
is almost identical to the characteristic of most
countries from North America and Europe, HEV
in the Caribbean and Mexico involves the wa-
ter-borne, non-zoonotic viral genotypes respon-
sible for epidemics in Asia and Africa.
Nevertheless, Latin America has been consid-
ered a highly endemic region for hepatitis E in
the scientic literature, a generalization that
ignores the above complexity. In addition,
reports from isolated Amerindian communities,
which display well known, important and very
specic epidemiological features for hepatitis B
and D virus infections are neither taken into ac-
count when considering the epidemiology of
hepatitis E in the region. This review updates
compilation of the available information for the
HEV infection, both among humans and other
mammals, in Latin America, discusses the
strengths and the weaknesses of our current
knowledge, and identies future areas of re-
search. J. Med. Virol. 85:10371045,
2013. 2013 Wiley Periodicals, Inc.
KEY WORDS: hepatitis E; hepatitis E virus;
hepatitis E virus genotypes;
Latin America; epidemiology
INTRODUCTION
Hepatitis E virus (HEV) causes enterically trans-
mitted non-A, non-B hepatitis with a worldwide distri-
bution, and is responsible for both sporadic cases and
large hepatitis epidemics in developing countries
[Khuroo, 2011; Meng, 2011]. HEV is classied as a
2013 WILEY PERIODICALS, INC.
member of the Hepevirus genus in the Hepeviridae
family, containing a single-stranded RNA genome of
approximately 7.3 kb [Reyes et al., 1990]. The genome
contains three partially overlapped open reading
frames (ORFs) and two short 50 and 30 non-translated
regions [Purcell and Emerson, 2008; Xing et al., 2010;
Ahmad et al., 2011] (Fig. 1). Two species have been
identied: the mammalian HEV, reported from
humans, primates [Huang et al., 2011; Nakamura et
al., 2012; Yamamoto et al., 2012], pigs, and several
other domestic (cattle, lamb, rabbit) or wild (wild
boar, mouon, deer, ferret, mouse, rat) mammals [Hu
and Ma, 2010; Wang and Ma, 2010; Cossaboom et al.,
2012; Raj et al., 2012; Vasickova et al., 2012]; and the
avian HEV [Marek et al., 2010].
Mammalian HEV is classied into four distinct gen-
otypes (14) and 24 subtypes (1a1e, 2a, 2b, 3a3j,
4a4g) [Meng, 2011]. Genotypes 1 and 2 are restricted
to primate animals, are transmitted predominantly by
the fecaloral route and are limited geographically
to tropical regions [Purdy and Khudyakov, 2011].
Genotype 3 infects numerous mammalian species, can
be transmitted to humans through ingestion of raw or
undercooked meat from infected animals (pig, deer,
wild boar), and is distributed worldwide [Meng, 2011].
Genotype 4 behaves like genotype 3, and was thought
to be restricted to Asia until its recent identication
in European human and swine isolates [Nishizawa
et al., 2003; Wichmann et al., 2008; Hakze-van der
Honing et al., 2011; Tesse et al., 2012]. Swine seem to
Grant sponsor: Oswaldo Cruz Institute Foundation, Rio de
Janeiro.
*Correspondence to: J.M. Echevarra, Department of Virology,
Centro Nacional de Microbiologa, Instituto de Salud Carlos III,
Majadahonda, Madrid 28220, Spain. E-mail: jmecheva@isciii.es
Accepted 18 December 2012
DOI 10.1002/jmv.23526
Published online in Wiley Online Library
(wileyonlinelibrary.com).
1038
Fig. 1. HEV genome organization. The viral genome is capped at
the 50 end and polyadenylated at the 30 end, and displays three open
reading frames (ORFs): ORF1, encoding a non-structural polyprotein
with various functional units (methyltransferase, MeT, papain-like
cysteine protease, PCP, RNA helicase, Hel, and RNA dependent
RNA polymerase, RdRp; ORF2, encoding the viral core protein; and
ORF3, encoding a small, regulatory phosphoprotein.
be a natural reservoir for HEV, corroborated by the
genetic similarity between swine and human strains,
with swine genotype 3 being the main cause for spo-
radic human infections in America and Europe
[Meng, 2010].
The course of HEV infection in humans is usually
benign. However, association with severe fulminant
hepatitis has been observed in pregnant women [Khu-
roo and Kamili, 2003] and among patients with un-
derlying liver disease [Aggarwal, 2011]. Chronic
infection by HEV genotype 3 has been identied in
immunocompromised individuals, such as transplant
recipients and patients undergoing chemotherapy,
who progress rapidly to advanced liver disease
[Haagsma et al., 2008; Kamar et al., 2008a, 2008b;
Tavitian et al., 2010].
It is nearly 30 years since the discovery of HEV,
and yet the literature testies to the vast inconsisten-
cy between assays for HEV-specic immunoglobulin
M and G antibody detection (anti-HEV IgG, IgM)
[Drobeniuc et al., 2010; Khudyakov and Kamili,
2011]. The duration of anti-HEV IgG and IgM in en-
demic areas following HEV acute infection is widely
discrepant [Goldsmith et al., 1992; Khuroo et al.,
1993; Bryan et al., 1994; Koshy et al., 1996]; more-
over, high prevalence of anti-HEV in non-endemic
areas is sometimes reported [Thomas et al., 1997;
Bendall et al., 2010]. These inconsistent results may
be due to the diversity of the HEV recombinant anti-
gens used by the different assays to detect anti-HEV
and to the genetic variations between the different
HEV strains [Khudyakov and Kamili, 2011]. Further-
more, false-positive anti-HEV IgM testing has been
reported by several researchers [Meky et al., 2006;
Fogeda et al., 2009a; Kim et al., 2011] and observed
also by the Brazilian National Reference Laboratory-
IOC/Fiocruz among patients infected with other viral
acute infections who never seroconverted to anti-HEV
IgG during follow-up [Lewis-Ximenez, unpublished
observations].
National surveillance programs utilize serologic
results (anti-HEV IgM) from available but inconsistent
commercial assays, and based on these results Brazil,
for example, which rarely identies true HEV
J. Med. Virol. DOI 10.1002/jmv
Echevarra et al.
infection, was recently qualied as a hyperendemic re-
gion for HEV [Khuroo, 2011]. Detection of the viral ge-
nome in serum or stool samples is limited in the
region to specic laboratories.
The present review aims to bring together and dis-
cuss relevant information on the characteristics of the
HEV infection in Latin America, which may add to a
better understanding of the global distribution of this
virus.
HUMAN HEV PREVALENCE IN LATIN
AMERICA
The rst serological evidence of HEV infection in
South America was found in Venezuela in 1994 [Pujol
et al., 1994]. Table I summarizes the results from se-
rological surveys of HEV exposure performed in Latin
America since this date. Outbreaks of HEV infection
have been reported from Mexico, but the prevalence of
anti-HEV is only slightly higher in that country than
the one observed in other countries of the region, as
for example Chile.
Comparison of data presented in Table I is im-
paired, however, by the diversity of the methodology
used in these studies. Although all were performed by
well-established immunoassays, technical perfor-
mance may vary from assay to assay [Bendall et al.,
2010]. Sequence diversity of the antigens used and
differences in sampling criteria might also affect the
results and impair the comparisons.
With such limitations in mind, the region exhibits a
moderate endemicity to HEV. Most prevalence rates
reported among either urban or rural populations
ranged from 1% to 10%, and none reached 20%. There
are no evident differences in prevalence between the
different regions (Central America and the Caribbean,
the Amazon Basin, the Northern Andes, and the
Southern Cone). Isolated Amerindian communities
have been sampled and studied just in Venezuela
[Pujol et al., 1994; Blitz-Dorfman et al., 1996], Chile
[Ibarra et al., 1997], and Bolivia [Leon et al., 1999],
with prevalence ranging from 5% to 17%. One study
performed in the Bolivian Amazon recorded, however,
prevalence ranging from 20% to 41% in most commu-
nities sampled. HEV strains responsible for infections
among Amerindians in these isolated communities
have not yet been described, and the sources of virus
and the mechanisms of transmission operating these
infections remain unknown.
ACUTE HEPATITIS E IN LATIN AMERICA
Acute hepatitis E cannot be distinguished by symp-
toms from other viral hepatitides. Infection by geno-
type 1 may be severe during pregnancy [Aggarwal,
2011], but fulminant hepatitis has never been
reported among pregnant women in Latin America.
The infection is often subclinical when the patient is
exposed to a small inoculum of virus, thus remaining
unrecognized. Such subclinical human infections may
Hepatitis E in Latin America 1039
TABLE I. Prevalence of Anti-HEV in Latin America

Anti-HEV prevalence
Country Population (%) (positive/tested) Refs.
Argentina Pediatrics 0.15 (2/1,304) Rey et al. [1997]a
Previous surgery 3.1 (54/1,735)
Blood donors 1.8 (39/2,157) Fainboim et al. [1999]a
Adults HIV 6.6 (32/484)
Brazil Blood donors 2.0 (04/200) Parana et al. [1997]
Acute viral hepatitis 17.7 (14/79) Goncales et al. [2000]a
Haemodialyzed patients (0/392)
Schistosomiasis carriers 10.0 (03/30)
Blood donors 3.0 (5/165)
Women at risk of HIV infection 17.7 (38/214)
Hospital employees 5.9 (10/170) Trinta et al. [2001]a
Acute non-A, non-B, and non-C hepatitis 2.1 (03/146)
Haemodialyzed patients 6.2 (04/65)
Blood donors 4.3 (04/93)
IVDUs 11.8 (12/102)
Pregnant women 1.0 (03/304) Assis et al. [2002]a
Rural area population 2.1 (03/145)
Urban area population 0.0 (0/260)
School children 4.5 (22/487)
Laboratory patients (pediatric and adults) 2.4 (17/699) Santos et al. [2002]a
Gold miners 6.1 Carrilho et al. [2005]
General population 3.3
Blood donors 2.07.5
Pregnant women 1.0
Children 4.5 Vitral et al. [2005]
Prostitutes in risk of HIV 1418
Intravenous drug users 12
Pig handlers 6.3 (2/32)
Blood donors 2.3 (23/996) Bortoliero et al. [2006]a
Bolivia Rural (pediatric and adults) 7.3 (36/490) Bartoloni et al. [1999]a
Blood donors 16.2 (93/574) Konomi et al. [1999]
Amerindian 20,1 (64/318) Leon et al. [1999]a
Rural (pediatric and adults) 6.3 (15/236) DellAmico et al. [2011]
Chile Blood donors 8.0 (109/1,360) Ibarra et al. [1997]
Health Care Workers 12.5 (9/72)
Inmates state jails 7.5 (18/241)
Amerindians 17.0 (17/100)
Cuba Blood donors 1.4 (16/1,149) Lemos et al. [2000]
HBsAg 0.4 (1/251)
antiHCV 2.4 (5/210)
Elevated ALT 3.2 (4/124) Quintana et al. [2005]
Plasmaphaeresis 1.7 (2/118)
Healthy adults 5.3 (11/209)
Healthy adults 10 (47/469) Villalba et al. [2010]
Guatemala Peacekeepers UN 5.0 (5/100) Gambel et al. [1998]
Haiti Peacekeepers UN 3.0 (3/100) Gambel et al. [1998]
Honduras Peacekeepers UN 6.0 (6/100) Gambel et al. [1998]
Mexico Volunteers 6.3 (23/363) Bernal and Licona [1996]a
Low income pregnant women 1.6 (5/307) Redlinger et al. [1998]
Young adults and children 10.4 (374/3,549) Alvarez-Munoz et al. [1999]
Nicaragua Healthy population 4.68 (25/399) Perez et al. [1996]
Peru Healthy sewage workers 10.5 (20/191) Vildosola et al. [2000]a
Uruguay Clinic outpatients 2.8 (6/214) Cruells et al. [1997]a
Blood donors 1.2 (3/252)
Venezuela Urban pregnant woman 1.6 (3/184) Pujol et al. [1994]
Rural populations 3.9 (8/204)
Amerindians 5.4 (12/223)
Amerindians 9.7 (45/463) Blitz-Dorfman et al. [1996]
a
Studies performed with the test commercialized by Abbott GmbH Diagnostika, Wiesbaden, Germany. The test used two recombinant anti-
gens (SG-3 and 85) derived from ORFs 1 and 2 of a HEV genotype 1 genome (Burma strain) expressed as a CMP-2-keto-3-deoxyoctulosonic
acid synthetase fusion protein in Escherichia coli.

induce a limited immune response but, nevertheless,
might result in viremia and fecal shedding [Purdy
and Khudyakov, 2011].
Two outbreaks of hepatitis E took place in two Mex-
ican villages in 19861987. In the village of Huitzilla,
94 icteric cases were found among their 1,157 resi-
dents; of these, two patients died. In Telixtac, 129
icteric cases were recorded among their 2,194 inhabi-
tants, with death reported in one patient. Three of the
16 stool specimens obtained from these outbreaks

J. Med. Virol. DOI 10.1002/jmv

1040 Echevarra et al.

tested positive by immune electron microscopy for 32
34 nm virus-like particles similar to the particles seen
in HEV outbreaks from Asia [Velazquez et al., 1990].
Molecular characterization studies identied the pro-
totype strain for genotype 2a (M74506) on the basis of
a single strain characterized, but subsequent studies
found genotype 3 strains in one of the two villages
[Drobeniuc et al., 2009]. Hepatitis E has not been
reported since from Mexico, but nevertheless the
country is considered hyperendemic for HEV [Khuroo,
2011].
Epidemic outbreaks and sporadic cases of hepatitis
E were reported also from Cuba. Most patients were
children, and the HEV infection was often associated
with concomitant acute HAV infection [Montalvo
et al., 2005; Rodrguez-Lay et al., 2008]. Involvement
of HEV was found in 21 of 33 outbreaks investigated,
and in 18 of 39 sporadic cases studied. Dual involve-
ment of HAV and HEV was implicated in 14 of these
outbreaks and in ve sporadic cases. Twenty-three
HEV strains recovered from two outbreaks and from
12 sporadic cases were genotyped, and all of them
clustered within genotype 1 in phylogenetic trees
[Montalvo et al., 2008]. Therefore, genotypes 13
could circulate among the human population of
Mexico and the Caribbean region, but reports conrm-
ing some of these ndings were absent until very
recently.
In a recent study performed in Venezuela, anti-
HEV IgM was found in 22 of 74 (30%) cases of acute
hepatitis studied, 16/22 (73%) among patients younger
than 20 years [Gutierrez et al., 2012]. Dual infection
by HEV and hepatitis A virus (HAV) was detected in
12 cases, as described in Cuba. HEV RNA detected in
serum was sequenced in three cases. Two sequences
clustered within genotype 1 and the third one clus-
tered within genotype 3. These data conrm the co-
circulation of HEV genotypes 1 and 3 in the Caribbe-
an region, whereas the presence of genotype 2a in
Mexico still remains unconrmed by additional
ndings.
In addition to Venezuela, other South American
countries, including Argentina, Brazil, Chile, Peru,
and Uruguay, have diagnosed patients with acute
hepatitis E by anti-HEV IgM and/or HEV RNA detec-
tion (Table II). HEV RNA was amplied from patients
diagnosed in Argentina, Brazil and Uruguay, and
some strains were genotyped. Imported cases due to
HEV genotype 1 were detected among international
travelers in Argentina [Munne et al., 2011], and
autochthonous cases due to genotype 3 were also
found in all three countries [Lopes dos Santos et al.,
2010a; Mirazo et al., 2011]. Subgenotype 3b was
recorded in Argentina and Brazil, and subgenotypes
3a and 3i were also found in the former country. Pres-
ence of HEV RNA from genotype 3 was, in addition,
reported in four of 236 stool specimens collected from
healthy people in the Southwest of Bolivia [DellAmico
et al., 2011; Purdy and Khudyakov, 2011; Purdy
et al., 2011], but anti-HEV IgG and IgM were
negative in the sera of these four persons. The lack of
antibody response impairs the interpretation of
the ndings, but suggests true HEV infection without
detectable humoral immune response.
HEV INFECTION IN DOMESTIC AND WILD
ANIMALS
Only in the last 10 years has hepatitis E been stud-
ied as a potential zoonotic disease in Latin America.
The lack of reports on water-borne hepatitis E out-
breaks in areas other than the Caribbean, and the ac-
cumulated evidence of HEV circulation among
humans and among the swine livestock, reinforce the
consideration of hepatitis E as a zoonosis in most
countries of the region, and contradict the consider-
ation of some of them as hyperendemic for this agent
[Khuroo, 2011].

TABLE II. Diagnosis of Sporadic Cases of Acute Hepatitis E in South America by Anti-HEV IgM and/or HEV RNA
Detection

Positive for HEV markers of acute infection

Country Patients studied Anti-HEV IgM HEV RNA HEV genotype (N) Refs.
Venezuela 74 22 3 1 (2) Gutierrez et al. [2012]
3 (1)
Peru 747 4 Nd Not known Hyams et al. [1996]
Brazil 17 5 Nd Not known Lyra et al. [2005]
64 1 1 3b (1) Lopes dos Santos et al. [2010a]
Chile 59 1 Nd Not known Ibarra et al. [2001]
35 12 Nd Not known Hurtado et al. [2005]
Argentina Not given Nd 2 3i (2) Schlauder et al. [2000]
35 3 3 3i (3) Munne et al. [2006a]
231 6 9 1a (1)a Munne et al. [2011]
3a (5)
3b (1)
Uruguay Not given 9 9 3 (9) Mirazo et al. [2011]
Nd, not done.
a
International traveller returning from India.

J. Med. Virol. DOI 10.1002/jmv

Hepatitis E in Latin America 1041

Despite their scarcity, the reports available consis-

tently conrm hepatitis E virus circulation among
pigs from Argentina [Munne et al., 2006b], Bolivia
[DellAmico et al., 2011], Brazil [Vitral et al., 2005;
Paiva et al., 2007; De Souza et al., 2012], Chile [Ibarra
et al., 2007], Costa Rica [Kase et al., 2008], and
Mexico [Cooper et al., 2005]. Studies in other animal
species performed in Brazil found anti-HEV IgG also
among cattle, dogs, chicken, and wild rodents, with
prevalence rates ranging from 1.4% to 50%, but not in
sera from New World primates, sheep or goat [Vitral
et al., 2005]. Serological evidence of HEV circulation
has been obtained recently among cynomolgus mon-
keys designated to biomedical research in the
Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
HEV genome from genotype 3 was formerly
detected in piglets from pig farms in ve provinces of
Argentina, from Santa Fe to Ro Negro, with frequen-
cy ranging from 4% to 98% [Munne et al., 2006a].
This study provided the rst evidence of the circula-
tion of HEV in commercial pig farms in South Amer-
ica. The Argentinean strains were closely related to
genotype 3 human strains isolated from sporadic
cases recorded in the country [Munne et al., 2006b],
but also in this case to a HEV strain isolated from a
sporadic case in Brazil [Lopes dos Santos et al.,
2010a]. In Costa Rica, 19 of 52 stool specimens
collected at seven swine farms tested positive for
HEV RNA. Viral shedding occurred mainly among
piglets 1.54 months old, and strains were closely
related to HEV genotype 3 strains reported among
humans and animals from other countries [Kase
et al., 2008].
HEV genome was detected in six of eight stool
pools from piglets 40 to 60 days old sampled from
the Brazilian state of Sao Paulo [Paiva et al., 2007],
and in South Brazil, HEV RNA was detected in
62.5% of the pig farms and 15.3% of fecal samples
studied [Gardinali et al., 2012a]. Detection in swine
bile and liver tissue was also achieved [Gardinali Fig. 2. A: Passive transfer of HEV IgG to piglets from sow by co-
lostrum conferring a protection against HEV infection during the
et al., 2012b]. HEV strains isolated were always rst 8 weeks of age. B: Natural course of HEV infection in piglets
from genotype 3, as observed for swine livestock in born from anti-HEV IgG-positive sow. Seroconversion occurred after
Europe and in the USA. Further studies performed active exposition to hepatitis E virus genotype 3. Data were obtained
from commercial herds located in Rio de Janeiro, Brazil [Lopes dos
among swine herds in the state of Rio de Janeiro Santos et al., 2009].
showed that new born piglets became susceptible to
HEV between weeks seven to nine, when the serum
levels of maternal antibodies acquired from colos-
trum declined (Fig. 2A). Anti-HEV IgG detection Despite outbreaks of hepatitis E being reported in
increased thereafter to 95.5% at week 20 because of South America exclusively from Venezuela, the risk of
natural infections attributed to HEV genotype 3 environmental virus contamination by sewage from
(Fig. 2B). At that point, signicant liver necro- slaughterhouses has been taken into consideration in
inammatory activity was observed in 26.6% of the Brazil. In a recent study, HEV RNA was detected in
piglets sampled [Lopes dos Santos et al., 2009]. sewage samples from a slaughterhouse in Rio de
Another study performed among Mexican pig herds Janeiro, the mean viral load being of about 102 genome
showed similar results, including detection of geno- copies/ml [Lopes dos Santos et al., 2010b]. Sequencing
type 3 strains [Cooper et al., 2005]. More recently, and phylogenetic analysis classied the strains within
co-circulation of HEV strains from two different sub- subgenotype 3b, and found them closely related to the
genotypes, with dual infection occurring in swine strains responsible for human and swine infections
from the Eastern Brazilian Amazon region in Brazil, recorded in the state [Lopes dos Santos et al., 2009;
was reported [De Souza et al., 2012]. 2010a].
J. Med. Virol. DOI 10.1002/jmv
1042
HEV-infected swine is considered a main source for
zoonotic virus transmission. However, in the South-
east of Bolivia genotype 3 strains belonged to different
subgenotypes depending on the host species, 3e for
humans and 3i for pigs [DellAmico et al., 2011]. Anal-
ysis of these viruses showed that human and swine
genotype 3 strains from that region shared their most
recent common ancestor no less than 275 years ago
[Purdy et al., 2012]. More investigations are needed to
elucidate non-zoonotic, human-to-human transmission
of HEV genotype 3 in Latin America.
CONCLUSIONS AND PERSPECTIVES
The epidemiology of hepatitis E displays signicant
regional variations in Latin America, and these differ-
ences may inform strongly the impact of HEV on the
public health in each country. Prospective studies
aimed to evaluate better the spread of HEV genotype
1 in the Caribbean, and to conrm the involvement of
HEV genotype 2 among patients with hepatitis E in
Mexico, would be suitable.
As already shown for hepatitis B and D virus infec-
tions, scant data available from isolated Amerindian
communities [Pujol et al., 1994; Blitz-Dorfman et al.,
1996; Leon et al., 1999] suggest that HEV infection
might display distinctive characteristics in these pop-
ulations. Further investigation of such behavior might
elucidate the complex epidemiology of the HEV infec-
tion in the region. Specic studies on hepatitis E in
these communities would, therefore, merit the support
of the health authorities holding responsibility of
ensuring the present and the future of these unique
human populations.
Latin America is often considered highly endemic
for hepatitis E, but outside of the Caribbean region,
the information collected in the present review does
not support this. In Brazil and Argentina, countries
where the disease has been thoroughly investigated,
HEV seems to behave similarly to other regions con-
sidered of low endemicity. Spain has been for years a
main choice for immigrants from several Latin Ameri-
can countries, and the region is a preferred destina-
tion for many Spanish tourists. However, HEV strains
are imported into Spain mainly from Asia and Africa,
and rarely from Latin American countries [Echevarra
et al., 2011]. In addition, the single HEV strain
imported to Spain from the Dominican Republic was
from the genotype 3, and local acquisition of the infec-
tion could not be excluded [Fogeda et al., 2009b].
These ndings argue against the consideration of Lat-
in America as a highly endemic region for hepatitis E.
Although out-of-date and likely inadequate [Bendall
et al., 2010] laboratory assays generated most data re-
garding anti-HEV prevalence in Latin America, their
use does not fully explain the inconsistency between
studies. Actually, the identical test was used in studies
performed in Mexico [Bernal and Licona, 1996] and
Brazil [Assis et al., 2002] (see Table I), and the preva-
lence rates obtained were not signicantly different
(23/363, 6.3% vs. 22/487, 4.5%; x2 1.37, P < 0.1). In
J. Med. Virol. DOI 10.1002/jmv
Echevarra et al.
addition, prevalence rates were not higher in countries
such as Cuba and Venezuela, where epidemic out-
breaks due to genotype 1 have been demonstrated
[Montalvo et al., 2008; Gutierrez et al., 2012].
Besides the current efforts for standardization of
anti-HEV testing [Bendall et al., 2008, 2010], evalua-
tion of sensitivity and specicity of anti-HEV tests, and
interpretation of the differences for anti-HEV preva-
lence found in a given population after testing samples
by different assays remain still controversial issues.
Some reports suggested that the prevalence rates could
have been underestimated in most studies because of
the insensitivity of the methods used [Bendall et al.,
2010; Mansuy et al., 2011], but such interpretation
was not supported by studies using conrmatory re-
combinant immunoblot testing [Fogeda et al., 2012].
Whether estimation of the burden of HEV reported
from Latin America is impaired by the poor sensitivity,
or specicity, of the assays is a critical issue. Studies
utilizing standardized anti-HEV serology and molecu-
lar epidemiology approaches that target important pop-
ulations would help determine the true burden of HEV
and inform public health approaches.
ACKNOWLEDGMENTS
We thank Dr. Arthur Y Kim, Massachussets General
Hospital and Harvard Medical School, Boston, for
meaningful revision of the manuscript; and hosting
meetings held by RIHEPE where updated information
could be shared and discussed by participants.
Authors of this article are members of the Iberian-
American Network for the Research of Hepatitis E (Red
Iberoamericana para la Investigacion de la Hepatitis E,
RIHEPE). RIHEPE is constituted by researchers from
the following countries and institutions:
Argentina: Instituto Nacional de Enfermedades
Infecciosas, Buenos Aires (Jorge E Gonzalez, Silvina
Munne); Bolivia: Centro Nacional de Enfermedades
Tropicales, Santa Cruz de la Sierra (Jorge H Vargas,
Yeln Roca); Brazil: Instituto Oswaldo Cruz/FioCruz
and Universidade Federal Rural do Rio de Janeiro,
Rio de Janeiro (Marcelo Alves Pinto, Debora Regina
Lopes dos Santos, Lia Laura Lewis-Ximenez); Cuba:
Instituto de Medicina Tropical Pedro Kour, La
Habana (Licel Rodrguez-Lay, Caridad Montalvo,
Marite Bello); Spain: Instituto de Salud Carlos III,
Majadahonda (Jose M. Echevarra, Marta Fogeda,
Ana Avellon); Venezuela: Instituto Nacional de
Higiene Rafael Rangel, Caracas (Cristina Gutierrez,
Doneyla Sanchez), Instituto Venezolano de Investiga-
ciones Cientcas, Caracas (Flor Pujol, Carmen Lour-
eiro) and Universidad del Zulia, Maracaibo (Francisca
Monsalve, Diana Callejas).
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