Hepatitis E virus (HEV) is one of the most frequent causes of acute viral hepatitis of enteric transmission worldwide. In South America the overall epidemiology has been little studied, and the burden of the disease remains largely unknown. A research of all scientific articles about HEV circulation in South America until November 2017 was carried out. Human seroprevalences of HEV varied according to the studied population: blood donors presented prevalence rates ranging from 1.8% to 9.8%, while reports from HIV-infected individuals, transplant recipients and patients on hemodialysis showed higher prevalence rates. Only 2 cases of chronic hepatitis in solid-organ transplant patients from Argentina and Brazil have been described. Detection of HEV in the swine population is widely prevalent in the region. Anti-HEV antibodies have also been recently documented in wild boars from Uruguay. Although scarce, studies focused on environmental and food HEV detection have shown viral presence in these kind of samples, highlighting possible transmission sources of HEV in the continent. HEV genotype 3 was the most frequently detected in the region, with HEV genotype 1 detected only in Venezuela and Uruguay. HEV is widely distributed throughout South America, producing sporadic cases of acute hepatitis, but as a possible agent of chronic hepatitis. Finding the virus in humans, animals, environmental samples and food, show that it can be transmitted through many sources, alerting local governments and health systems to improve diagnosis and for the implementation of preventive measures.

Abbreviations

ELISA: Enzyme-Linked Immunosorbent Assay
HBV: hepatitis B virus
HCV: hepatitis C virus
HEV: hepatitis E virus
HIV: human immunodeficiency virus
IgG: immunoglobulin G
IgM: immunoglobulin M
ORF: open reading frame
RNA: ribonucleic acid

Key points

HEV has been detected in humans, pigs, wild boars, environmental samples (water, sewage) and food in South America.
Seroprevalences vary according to the region and the population studied, ranging from 0.1% to 38%.
HIV positive patients, hemodialysis patients and solid-organ transplant patients present higher HEV seroprevalences.
HEV genotype 3 has been the most widely found in the continent.
Only 2 cases of chronic hepatitis E in transplant patients (liver and kidney) have been described; one from Brazil and the other from Argentina.

1 INTRODUCTION

The hepatitis E virus (HEV) is an emergent causative agent of enteric acute hepatitis worldwide. The World Health Organization estimates 20 million HEV infections occur every year all over the world, leading to an estimated 3.3 million symptomatic cases of viral hepatitis because of the virus.1 HEV (family Hepeviridae, genus Orthohepevirus, specie Orthohepevirus A) is a non-enveloped virus with a positive stranded RNA genome of 7.2 kb that encodes 3 partially overlapped open reading frames (ORFs): ORF1 encodes viral replication proteins, while ORF2 encodes the capsid protein and ORF3 a protein involved in particle secretion.2 Eight genotypes (1-8) with multiple subtypes have been described for this virus; only genotypes 1, 2, 3, 4 and 7 are known to infect humans.3, 4 Genotypes 1 (HEV-1) and 2 (HEV-2) produce epidemic outbreaks via faecal-oral transmission route in endemic developing countries in Asia and Africa, and have been detected sporadically in America.5 Genotypes 3 (HEV-3) and 4 (HEV-4) are zoonotic viruses that infect humans by ingestion of contaminated food or direct contact with infected animals. Importantly, infection by these genotypes has been shown to cause persistent infection in immunocompromised individuals.2, 5 HEV-3 has a worldwide distribution, while HEV-4 circulates in Asia and Europe.5 Genotype 7 (HEV-7) was detected in dromedaries and humans fed with camel milk in the Middle East and very little is known about it.6

Since HEV was first described in South America in 19947 many studies have reported its circulation in the continent, including molecular detection in a variety of sources (human sera, human and animal stool, water, sewage) and serological surveys in many populations (general population, blood donors, HIV+ individuals, paediatric population, dialyzed patients, solid organ transplant recipients, etc.). However, there are still several important questions that have not been answered or that have been only partially answered, such as the role of pigs in human-zoonotic transmission, food consumption as a risk factor, the importance of HEV in the progression to chronic hepatitis in certain regions, and the overall burden of chronic hepatitis E in the South American continent.

The aim of this review is to provide and discuss updated information about HEV in South America, which may lead to a better understanding of the dynamics of HEV, as well as to promote preventive measures in this part of the world. For that purpose, we searched published scientific articles regarding HEV in South America by assessment of Pubmed/NLM using the following keywords: HEV, South America, seroprevalence, genotypes, circulation. The search yielded 81 articles published until November 2017, and these were evaluated to address the seroprevalence of HEV in human and animal samples, acute and chronic cases, associated risk factors and viral environmental circulation in the region.

2 DETECTION OF HEV IN HUMANS IN SOUTH AMERICA

2.1 Seroprevalence of HEV in immunocompetent individuals

The updated prevalence of IgG anti-HEV antibodies among general populations and risk groups of South America is shown in Table 1.

Table 1. Prevalence of serum IgG anti-hepatitis E virus (HEV) in many populations in South America

Country	Population	No of cases	IgG anti-HEV % of positivity	Test utilized	Reference
Argentina	Paediatrics	1304	0.15	Abbot GmbH Diagnostika, Germany	10
	Previous surgery	1735	3.1	Abbot GmbH Diagnostika, Germany	10
	Blood donors	2157	1.8	Abbot GmbH Diagnostika, Germany	18
	HIV +	484	6.6	Abbot GmbH Diagnostika, Germany	18
	General population	433	4.4	Diapro, Italy	37
	Volunteers	95	9.5	Diapro, Italy	38
	Volunteers	28	14.3	Wantai, China	38
	Blood donors	24	16.7	Wantai, China	38
	Healthcare workers	27	14.8	Wantai, China	38
	HIV +	28	35.7	Wantai, China	38
	HIV +	204	7.3	Diapro, Italy	40
	Solid organ transplant recipients	120	5.8	Diapro, Italy	45
	Dialysis patients	88	10.2	Diapro, Italy	45
Brazil	Gold miners	97	6.1	Genelabs Inc., Redwood City, CA	9
	Blood donors	200	2.0	Abbott Lab., Chicago	12
	Acute NANBNC hepatitis relatives	66	10.6	Abbott Lab., Chicago	24
	Acute NANBNC hepatitis	16	12.2	Abbott Lab., Chicago	24
	Schistosomiasis carriers	30	10.0	Abbott Lab., Chicago	12
	Acute Hepatitis C	12	0.0	Abbott Lab., Chicago	12
	Dialysis patients	392	0.0	Abbott Lab., Chicago	12
	General population	1059	1.7	NA	15
	General population	97	6.1	NA	16
	Acute NANBNC hepatitis	17	29.0	NA	23
	Cleaning service workers	53	13.2	Abbot GmbH Diagnostika, Germany	19
	Women at risk of HIV infection	214	17.7	Abbot GmbH Diagnostika, Germany	19
	Healthcare workers	170	2.6	Abbot GmbH Diagnostika, Germany	19
	Blood donors (ALT>2UNL)	40	7.5	Abbot GmbH Diagnostika, Germany.	19
	Pregnant women	304	1.0	Abbott Lab., Chicago	20
	Individuals from rural area	145	2.1	Abbott Lab., Chicago	20
	Individuals from urban area	260	0.0	Abbott Lab., Chicago	20
	IDVU	102	11.8	Abbott Lab., Chicago, USA	20
	Individuals living in low socioeconomic community	260	2.4	Abbott Lab., Chicago, USA	21
	Blood donors (ALT<2UNL)	165	3.0	Abbott Lab., Chicago, USA	22
	Pediatrics	487	4.5	Abbott Lab., Chicago, USA	22
	Acute NANBNC hepatitis	12	17.0	NA	25
	Acute hepatitis A	50	38.0	NA	25
	Acute hepatitis B	42	10.0	NA	25
	Blood donors	996	2.3	Abbott Lab., IL, USA	97
	Individuals from rural área	310	8.4	MP Biomedicals Asia Pacific Pte Ltd, Singapore	31
	Blood donors	110	4.0	MP Biomedicals Asia Pacific Pte Ltd, Singapore	31
	Individuals from rural área	388	12.9	Biokit, Spain	35
	Recyclable waste pickers	431	5.1	Mikrogen GmBH, Germany	36
	Renal transplant patients	192	15.0	Mikrogen, Neuried, Germany	33
	Acute NANBNC hepatitis	379	5.3	Mikrogen GmBH, Germany	41
	Schitosomiasis carriers	80	18.8	Wantai, China	42
	Blood donors	300	10.0	Wantai, China	47
	Blood donors	500	9.8	Wantai, China	43
	Blood donors	780	30.3	In house	44
	HIV+	354	10.7	Mikrogen GmBH, Germany	46
Bolivia	Individuals from rural area	490	7.3	Mikrogen GmBH, Germany	17
	General population	236	6.3	Diapro, Italy	30
Chile	Blood donors	1360	8.0	Abbott Lab	11
	Healthcare workers	72	12.5	Abbott Lab	11
	Prisoners	241	7.5	Abbott Lab.	11
	Indigenous community	100	17.0	Abbott Lab	11
	Acute NANBNC hepatitis	59	7.0	Abbott Lab	26
	Pedriatics living in low socieconomic community	168	1.2	Abbott Lab	29
Colombia	Individuals from rural area with occupational exposure to pigs	98	11.2	Diapro, Italy	32
	Acute NANBNC hepatitis	344	8.7	Diapro, Italy	34
	Individuals from rural area with occupational exposure to pigs	159	15.7	Diapro, Italy	39
	Individuals from rural area without occupational exposure to pigs	34	5.9	Diapro, Italy	39
	Individuals from urban area	983	7.2	Diapro, Italy	39
French Guiana	General population	996	6.4	NA	14
Peru	Healthy sewage workers	191	10.5	Abbot GmbH Diagnostika, Germany	27
Uruguay	General population	214	2.8	Abbot GmbH Diagnostika, Germany	13
	Blood donors	252	1.2	Abbot GmbH Diagnostika, Germany	13
Venezuela	Pregnant women	184	1.6	NA	7
	Prisoners	204	3.9	NA	7
	Indigenous community	223	5.4	NA	7
	Pregnant women from low income population	106	1.9	NA	8
	Pregnant women from medium-high economic class population	105	1.3	NA	8
	Indigenous community	463	9.7	NA	28

NA, not available.

The first serological studies of HEV infection in the continent date from the 1990s and the beginnings of 2000s, when several reports were published with prevalence rates ranging between 0.1% to 8% among either rural or urban populations,7-22 and between 3% and 29% within groups with risk factors or with hepatitis of unknown source.10, 12, 18-21, 23-29

A 10-year gap in knowledge followed, until 2011, when studies from Argentina, Bolivia, Brazil and Colombia, reported respective HEV prevalences.30-47 This wave of studies followed the global reports of chronic hepatitis E virus infection by HEV-3 in immunosuppressed individuals, especially those with solid organ transplantation as well as the reports of extra-hepatic manifestations of HEV. Studies performed in blood donors show current prevalence rates between 1.8% and 9.8%, showing moderate circulation. The only longitudinal study found, reports a significant linear trend of IgG anti-HEV positivity with years in Brazilian blood donors, showing that the prevalence of IgG anti-HEV antibodies varied between 0% to 4.3% from 1997 to 2006, with the highest frequencies observed from 2011 to 2013: 5.9% (2/34), 8.6% (12/139) and 6.1% (9/148) respectively.48 In general, HEV positivity trended to increase with age.15, 17, 31, 35, 37, 43, 47, 48 There is only 1 study that reported new HEV infections in a 7 years period, carried out in Brazil, although it did not involve the follow-up of a group of patients. Five hundred and fifty-two IgM tests were performed from 2006 to 2013, and the IgM anti-HEV positivity rate ranged from 0.0% to 8.8% annually, showing a linear trend over time.48 Despite these studies, the data from the region is still limited and incomplete.

Some of the main barriers to a proper understanding about HEV include: (i) discrepancy in the sampling criteria of the studies (sample sizes, study periods, study populations); (ii) use of different commercial diagnostic kits, which can yield different results in the same population; (iii) different diagnostic criteria, as some authors report confirmation based on western blot or immunoblot after a positive ELISA result, which make comparisons difficult. Regarding the use of different commercial diagnostic kits, studies performed using Wantai ELISA kits show higher prevalence rates than those in which other ELISA kits are used (Table 1). In this sense, a study that compared 8 different commercial kits coated with HEV genotypes 1 and 2 antigens, demonstrated that the Mikrogen and the Wantai assays had greater sensitivity and specificity than the rest, although all current commercial HEV ELISAs can be used to diagnose HEV infection adequately.49 A recent study with a new “in house” immunoassay developed in Brazil using a recombinant HEV-3 capsid protein revealed a high prevalence of antibodies (30%),44 suggesting, for the first time, that the Southern region of Brazil might be endemic to HEV-3. This finding raises new challenges in the evaluation of the circulation of the virus in the region, which should be explored in a consensual way in the near future, extending the range of study with this new configuration of immunoassays.

2.2 Seroprevalence of HEV in immunosuppressed individuals

Multiple studies from our group and others worldwide have reported that immunosuppressed individuals could present higher HEV prevalences, compared to general population.45, 50, 51

Brazil and Argentina are the only countries in South America which have reported studies about HEV circulation in immunocompromised populations (Table 1).33, 38, 40, 45, 46 In Argentina higher circulation of HEV was registered in HIV+ individuals, compared to blood donors (6.6% vs 1.8%),18 volunteers (35.7% vs 14.3% or 9.5%, depending on the kit used)38 and general population (7.3% vs 4.4%).40 A study from our group found that HIV+ individuals with severe immunosuppression (CD4 cell count < 200/mm³) presented significantly higher prevalence for HEV (16%) than those with CD4 cell count > 200/mm³ (4.5%), suggesting a correlation between T-cell immunity and risk for HEV infection.40 However, during this study patients were not divided by age, place of living or socio-economic groups, so it was not possible to elucidate if these variables influenced the prevalence results. The only study conducted in Brazil in this population (prevalence of 10.7% for IgG anti-HEV) found no correlation between serological status with sex, age, CD4 T cell count, HIV viral load, antiretroviral therapy, liver enzyme levels or co-infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).46

Among transplant recipients, prevalences found are between 5.8% and 15% (Table 1). Most studies performed in Brazil were conducted among renal transplant patients compared to blood donors, while those in Argentina were among kidney and liver transplant recipients compared to the general population.33, 45

In patients undergoing dialysis, the only South American reported study was conducted in the central region of Argentina, showing a significantly higher prevalence than the registered for general population (10.2% vs 4.4%).45

The higher values of prevalence reported in immunosuppressed populations in South America would be owing to several factors not fully elucidated. The low CD4 cell count (in HIV+ patients),40 the exposure to parenteral route, which increases the chances of infection (particularly during the hemodialysis period in dialysis and renal transplant patients), and blood transfusions33 seem to be some of them. In the case of hemodialysis patients, a positive correlation between IgG anti-HEV prevalence and fish consumption was observed.45

As we described above, most reports come from a limited number of studies from few countries in South America. It is critical to expand the knowledge of the epidemiological distribution of HEV among immune-compromised individuals.

2.3 Acute hepatitis E

Despite high documented seroprevalences of HEV in South America, reports of clinically significant cases are low or infrequent, similar to the observed in developed countries.52 This fact likely reflects a high rate of asymptomatic cases associated with HEV-3 (the most frequent genotype in South America), and unrecognized symptomatic cases secondary to limited access to diagnostic tests and awareness of the virus.

Table 2 summarizes the acute cases of HEV infection reported in the last 17 years in South America, diagnosed by the presence of serological or molecular specific markers (anti-HEV IgM and/or HEV RNA). HEV-3 was the most frequent: subgenotype 3a was detected in Argentina and subgenotypes 3b and 3i in Argentina and Brazil.48, 53 Recently in Colombia, symptomatic acute hepatitis E was reported for the first time in 22% (9/40) of the cases analyzed.54

Table 2. Cases of acute hepatitis E determined in South America by IgM anti-HEV and/or RNA-HEV detection

Country	Studied patients	IgM anti-HEV	HEV RNA	HEV genotype (N)	References
Argentina	Not given	Nd	2	3i (2)	91
	35	3	3	3i (3)	92
	231	6	9	1a (1)a	53
				3a (5)
				3b (1)
	143	4	9	3a (7)	38
	143	4	9	3i (2)	38
Brazil	17	5	Nd	Nd	98
	64	1	1	3b (1)	76
	96b	0	3	3 (2)	96
	96b	0	3	3i (1)	96
	552	6c	6	3b (1)	48
Chile	59	1	Nd	Nd	26
Chile	35	12	Nd	Nd	99
Colombia	40	Nd	9 stool	3	54
Peru	747	4	Nd	Nd	100
Peru	2	Nd	2	Nd	101
Uruguay	Not given	9	9	3 (9)	93
Uruguay	1	1	1	1	56
Venezuela	74	22	3	1 (2)	55
Venezuela	74	22	3	3 (1)	55

Nd, not determined.
^a Imported case from India.
^b Renal transplant recipients.
^c Two liver transplant recipients.

In the last 5 years, 2 cases of autochthonous hepatitis E by HEV-1 were reported in Venezuela and one in Uruguay.55, 56 An imported case by this genotype was registered in Argentina in an international traveller.53

2.4 Hepatitis E associated to extra hepatic manifestations and chronicity: Case reports

Autochthonous hepatitis E has a wide spectrum of reported complications, including “acute-on-chronic” liver failure, neurological disorders, pancreatitis and development of chronic hepatitis.57

Chronic infections by HEV-3 and HEV-4 have been identified among immunocompromised persons worldwide, including organ transplant recipients, patients receiving cancer chemotherapy and HIV-infected persons.50, 51, 58

In South America, there are few reported cases of chronic hepatitis E or HEV infection with extra hepatic complications. Argentina is the only South American country where 2 cases of acute HEV associated to extra hepatic manifestations had been reported, both in immunocompetent adult patients with confirmed HEV-3a infection. One of the cases corresponded to a 45 year old male health worker who developed subacute thyroiditis,59 and the other, to a 59–year-old alcoholic female patient who developed aplastic anaemia.60

One case of “acute-on-chronic” liver failure was reported in an individual from Peru who developed autoimmune hepatitis and severe hepatic decompensation associated to HEV infection.61

Two cases of chronic hepatitis E have been reported in transplant patients: an adult kidney transplant recipient in Argentina and a paediatric liver transplant recipient in Brazil.62, 63 These cases highlight the need to increase the search of this virus in susceptible populations and to increase awareness to clinicians to develop a higher sense of suspicion of HEV when addressing complex clinical cases.

3 DETECTION OF HEV IN DOMESTIC AND WILD ANIMALS IN SOUTH AMERICA

Hepatitis E virus is the only known hepatitis virus with an animal reservoir,57 and accumulating lines of evidence has suggested that HEV is a zoonosis.64 Pigs are the main reservoirs and other animals have also been shown to be susceptible to HEV. These include wild boars, deers, cows, sheeps, goats, camels, horses, dogs, cats, rats and mongooses worldwide.65-67

Data regarding HEV prevalence and molecular epidemiology in animal reservoirs in South America is still scant. Most of the serological surveys reported from Brazil, show similar average seroprevalence rates ranging from 88.4% to 97.3% in animals between 22 and 25 weeks respectively,68, 69 suggesting that HEV is widely distributed among swine herds. By contrast, low antibody rates have been described in swine herds from the Brazilian Amazonia.70

Domestic pigs are also highly exposed to HEV in Colombia, with seroprevalence rates of 100% in slaughter-aged pigs from the Antioquia region.71

In Chile, Argentina and Uruguay, by contrast, antibody prevalences among swine herds seem to be lower and exhibit a significant variability among different geographical regions, ranging from 0.6% to 58%, depending on the study.72-74

Molecular epidemiology of swine HEV has been studied in many South American countries. In 2006, Munné et al73 reported for the first time in the region, the detection and molecular characterization of swine strains of HEV isolated from faecal samples in a herd located in Buenos Aires province. In Brazil, Paiva et al75 (2007) described the first HEV strain isolated from pigs in 2007, even when no autochthonous cases of HEV infection in humans had yet been reported in this country. Later, subtype 3b strains of HEV-3 isolated from swine and effluent samples from slaughterhouses, were found to be closely related to the sample obtained from the first reported autochthonous human case in Brazil.76-79 Furthermore, co-circulation of subtypes 3c and 3f has been reported.70

A study from Bolivia also reported the circulation of HEV-3 among domestic pigs, but a different genetic variant was found from that recovered from humans in the same rural community, suggesting no zoonotic transmission in that region.79, 80

As in the rest of the South American countries, HEV seems to be widely spread among swine herds from Colombia. Very recent studies have reported high infection rates of HEV subtype 3a in pigs from Antioquia.81 Interestingly, HEV RNA had been previously detected in 25% of pig livers from grocery stores in the same geographical region.82

In Uruguay, Mirazo et al74 (2018) have recently documented the detection of HEV-3 RNA in liver samples from slaughter-age pigs (16.6% of positivity), indicating a wide circulation of the virus and a potential risk for zoonotic transmission.

All these data strongly suggest that HEV is highly disseminated in the swine population of South America. In fact, both swine and human strains isolated in most regions seem to be phylogenetically related, suggesting that the high prevalence of HEV in domestic pigs might present an important risk for human infection.

In addition to pigs, specific anti-HEV antibodies and HEV RNA have been recently detected, for the first time in South America, in wild boars from Uruguay (22.1% and 9.3% respectively).74 The potential role of these animals as zoonotic sources of infection remains unknown.

4 DETECTION OF HEV IN ENVIRONMENTAL MATRICES AND FOOD IN SOUTH AMERICA

Since HEV is an enteric virus whose main transmission route is faecal-oral, aqueous matrices are postulated to have an important role in the transmission and maintenance of the virus.83, 84

Drinking water as well as irrigation water can be contaminated with HEV via animal stool, with concomitant contamination of vegetables, fruits and fish, leading to food safety risk.77, 83 In addition, the presence of the virus in surface waters (rivers, dams), constitutes a potential risk of infection for susceptible persons who are in contact with them, since some of these watercourses are usually used with recreational purpose (for swimming, sailing, kayaking, surfing and more).

Studies about environmental HEV detection in South America are scarce. Only 4 studies, performed in Argentina, Brazil and Colombia, have searched the virus on environmental samples (Table 3).37, 77, 84-86 In all studies HEV-3 was found and the subtypes described belonged to clade 3abchij. Most of the sequences were closely related to human and/or swine strains, showing that the environment could play an important role in the maintenance of the virus in many regions of South America, possibly being the source of infection for exposed human and animal populations, but also as receptor for viral discharge from these same populations. That is the case of environments close to places where pigs are present, which have very high HEV detection rates (50%-100%, Table 3),77, 87 emphasizing the participation of these animals in the transmission of HEV. Also the presence of virus in sewage, which is assumed to have human origin,37, 84 which could be discharged to recreational waters.

Table 3. Environmental RNA-HEV detections in South America performed by molecular assays

Country	Source	% of HEV detection (positive/n)	HEV genotype and subtype	Amplified genomic region	Year of detection	Reference
Argentina	River water	3.2% (1/32)	3c	ORF2a	2010	37
	Dam water	2.1% (1/48)	3	ORF2a	2013	86
	Dam water	7.57% (5/66)	3	ORF2a	2015	86
	Sewage	6.3% (3/48)	3a, 3b, 3c	ORF2a	2007, 2010, 2011	37
Brazil	Slautherhouses effluent	50% (3/6)	3b	ORF1 and ORF2a^,b	2008	77
	Effluents from slurry lagoons (near pig farms)	100% (8/8)	3b	ORF1a		87
	River water	0% (0/250)	-	ORF1a	From 2012 to 2014	85
	River sediment	0% (0/68)	-	ORF1a	2014	85
Colombia	Water from a drinking water plant or a creek	23.3% (7/30)	3	ORF2/3a	From 2012 to 2014	84
Colombia	Sewage	16.7% (5/30)	3	ORF2/3a	From 2012 to 2014	84

^a Nested PCR;
^b Real time PCR.

One particularly concerning point is the presence of HEV in water samples for consumption.84 This constitutes a risk for human populations that directly consume these waters or use them for animal consumption or irrigation of crops. There is evidence of HEV outbreaks in other parts of the world where drinking water was pointed to be the source of infection,88 so this possibility should not be discarded in our region.

Foodborne transmission of HEV by consumption of raw or undercooked liver, meat or sausages prepared from infected animals (swine, deer, wild board) has been documented in North America, Europe and Asia, but only few studies have been published on the detection of HEV in pork products so far.89 South America is not the exception, and, although the virus has been described to circulate in swines in this region, there is only 1 study performed in Brazil, in which viral presence in pork products was investigated. During this study, 50 samples of pate and blood sausage marketed in the Sinos River region were tested for the presence of HEV genome, resulting in 36% of positivity; all samples belonged to HEV-3.85 Although studies about HEV in food are scarce, these results show the potential for zoonotic transmission of HEV infection through foods of porcine origin in places where pig infection has been demonstrated in our continent. Besides, they emphasize the need to deepen research of HEV in food matrices, as well as to promote implementation of preventive measures.

5 HEV IN BLOOD PRODUCTS IN SOUTH AMERICA

HEV has also been transmitted by blood transfusion from asymptomatic viremic donors, and has been detected in blood components in other parts of the world.90 In South America, there are no studies about molecular detection of HEV in blood products, which constitutes a gap in the knowledge of HEV in the continent. This could be critical, since blood recipients are usually people with some disease or immunosuppressed individuals, and HEV infection could be a serious additional problem. Studies focusing the search of RNA HEV in blood products and/or blood donors are needed to determine the impact of HEV in local blood banks.

6 MOLECULAR EPIDEMIOLOGY OF HEV IN SOUTH AMERICA

Eight HEV genotypes have been described4 from these, HEV-1, HEV-2, HEV-3, HEV-4 and HEV-7 can infect humans and produce disease, and have a particular geographical distribution.3 In South America, only HEV-1 and HEV-3 have been detected. HEV-3 is the most frequent genotype found in this region, isolated from humans, pigs and environmental samples (as described above) in Argentina, Brazil, Bolivia, Colombia, Uruguay and Venezuela (Figure 1). This genotype presents a high heterogeneity, reflected by the large number of subtypes described worldwide,3 which is also evidenced in South America, where several subtypes have been reported: 3a, 3b, 3c, 3h, 3i, 3e, 3f.37, 38, 53, 60, 69, 70, 73-75, 77, 78, 80, 91-96 In some regions of the continent, the same subtypes (or subtypes belonging to the same clade) have been reported in humans, pigs and environmental samples,37, 38, 53, 69, 73, 74, 76 showing that these hosts and matrices could be involved in the HEV life cycle, and confirming the zoonotic transmission of this virus. On the other hand, in Bolivia, the subtype detected in humans and swines differed, suggesting host-specific infection without zoonotic-transmission.80

Details are in the caption following the image — **Figure 1**
Open in figure viewer PowerPoint

HEV genotype and subtype distribution in South America and sources of isolation. Countries in grey correspond to those from which there is no data of molecular HEV detection

Hepatitis E virus-1 in South America was only detected in Venezuela and Uruguay (Figure 1), isolated from acute human hepatitis cases, although no large outbreaks have been reported in the continent.55, 56

A limitation for the study of molecular epidemiology in South America is the existence of short genomic fragments of different genomic regions (of all genotypes and subtypes), which makes comparisons and molecular analyses difficult to perform. Sequencing of larger genomic regions and/or complete genomes is needed to continue studying the phylogenetic and evolutionary relationships of the strains in the continent.

7 CONCLUSIONS

Hepatitis E is a global infection with an estimated incidence of millions of cases per year worldwide. In South America, there is sufficient evidence of its circulation in humans, animals and environmental matrices, although no large HEV outbreaks have been reported, showing a similar behaviour to other regions considered of low endemicity, such as Europe. The epidemiology of HEV in this continent displays some regional variations, which may impact in the public health in each country. Prospective studies aimed to investigate the clinical impact (presence of acute and chronic infections in populations not studied yet), genetic variations, life cycle and other aspects of this virus in our continent, would be suitable.

CONFLICT OF INTEREST

The authors do not have any disclosures to report.

REFERENCES

1 World Health Organization (WHO). Fact sheet HEV, July 2017.
Google Scholar
2Debing Y, Moradpour D, Neyts J, Gouttenoire J. Update on hepatitis E virology: implications for clinical practice. J Hepatol. 2016; 65: 200-212.
10.1016/j.jhep.2016.02.045
PubMed Web of Science® Google Scholar
3Smith DB, Simmonds P, Izopet J, et al. Proposed reference sequences for hepatitis E virus subtypes. J Gen Virol. 2016; 97: 537-542.
10.1099/jgv.0.000393
CAS PubMed Web of Science® Google Scholar
4Sridhar S, Teng JLL, Chiu TH, Lau SKP, Woo PCY. Hepatitis E virus genotypes and evolution: emergence of camel hepatitis E variants. Int J Mol Sci. 2017; 18: 1-19.
10.3390/ijms18040869
Web of Science® Google Scholar
5Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: discovery, global impact, control and cure. World J Gastroenterol. 2016; 22: 7030-7045.
10.3748/wjg.v22.i31.7030
CAS PubMed Web of Science® Google Scholar
6Woo PC, Lau SK, Teng JL, et al. New hepatitis E virus genotype in camels, the Middle East. Emerg Infect Dis. 2014; 20: 1044-1048.
10.3201/eid2006.140140
PubMed Web of Science® Google Scholar
7Pujol FH, Favorov MO, Marcano T, et al. Prevalence of antibodies against hepatitis E virus among urban and rural populations in Venezuela. J Med Virol. 1994; 42: 234-236.
10.1002/jmv.1890420305
CAS PubMed Web of Science® Google Scholar
8Pujol FH, Rodríguez I, Martínez N, et al. Viral hepatitis serological markers among pregnant women in Caracas, Venezuela: implication for perinatal transmission of hepatitis B and C. G E N. 1994; 48: 25-28.
CAS PubMed Google Scholar
9Pang L, Alencar FE, Cerutti C Jr, et al. Short report: hepatitis E infection in the Brazilian Amazon. Am J Trop Med Hyg. 1995; 52: 347-348.
10.4269/ajtmh.1995.52.347
CAS PubMed Web of Science® Google Scholar
10Rey JA, Findor JA, Daruich JR, et al. Prevalence og IgG anti-HEV in Buenos Aires, a non-endemic area for hepatitis E. J Travel Med. 1997; 4: 100-101.
10.1111/j.1708-8305.1997.tb00788.x
CAS PubMed Google Scholar
11Ibarra H, Riedemann S, Reinhardt G, et al. Prevalence of hepatitis E virus antibody in blood donors and other population groups in Southern Chile. Rev Med Chil. 1997; 125: 257-258.
Google Scholar
12Parana R, Cotrim HP, Cortey-Boennec ML, Trepo C, Lyra L. Prevalence of hepatitis E virus IgG antibodies in patients from a referral unit of liver diseases in Salvador, Bahia, Brazil. Am J Trop Med Hyg. 1997; 57: 60-61.
10.4269/ajtmh.1997.57.60
CAS PubMed Web of Science® Google Scholar
13Cruells MR, Mescia G, Gaibisso R, et al. Epidemiological study of hepatitis A and E viruses in different populations in Uruguay. Gastroenterol Hepatol. 1997; 20: 295-298.
CAS PubMed Google Scholar
14Talarmin A, Kazanji M, Cardoso T, Pouliquen JF, Sankale-Suzanon J, Sarthou JL. Prevalence of antibodies to hepatitis A, C, and E viruses in different ethnic groups in French Guiana. J Med Virol. 1997; 52: 430-435.
10.1002/(SICI)1096-9071(199708)52:4<430::AID-JMV15>3.0.CO;2-K
CAS PubMed Web of Science® Google Scholar
15Focaccia R, Conceição OJG, Sette H Jr, et al. Estimated prevalence of viral hepatitis in the general population of the municipality of São Paulo, measured by a serologic survey of a stratified, randomized and residence-based population. Braz J Infect Dis. 1998; 2: 269-284.
CAS PubMed Google Scholar
16Souto FJ, Fontes CJ. Prevalence of IgG-class antibodies against hepatitis E virus in a community of the southern Amazon: a randomized survey. Ann Trop Med Parasitol. 1998; 92: 623-625.
10.1080/00034983.1998.11813321
CAS PubMed Google Scholar
17Bartoloni A, Bartalesi F, Roselli M, et al. Prevalence of antibodies against hepatitis A and E viruses among rural populations of the Chaco region, south-eastern Bolivia. Trop Med Int Health. 1999; 4: 596-601.
10.1046/j.1365-3156.1999.00457.x
CAS PubMed Web of Science® Google Scholar
18Fainboim H, González J, Fassio E, et al. Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat. 1999; 6: 53-57.
10.1046/j.1365-2893.1999.t01-1-6120135.x
CAS PubMed Web of Science® Google Scholar
19Gonçales NSL, Pinho JRR, Moreira RC, et al. Hepatitis E virus immunoglobulin G antibodies in different populations in Campinas, Brazil. Clin Diagn Lab Immunol. 2000; 7: 813-816.
CAS PubMed Web of Science® Google Scholar
20Trinta KS, Liberto MIM, De Paula VS, Yoshida CFT, Gaspar AMC. Hepatitis E virus infection in selected Brazilian populations. Mem Inst Oswaldo Cruz. 2001; 96: 25-29.
10.1590/S0074-02762001000100004
CAS PubMed Web of Science® Google Scholar
21Santos DC, Souto FJ, Lopes dos Santos DR, Vitral CL, Gaspar AM. Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro, RJ, Brazil. Mem Inst Oswaldo Cruz. 2002; 97: 637-640.
10.1590/S0074-02762002000500007
PubMed Web of Science® Google Scholar
22Assis SB, Souto FJ, Fontes CJ, Gaspar AM. Prevalence of hepatitis A and E virus infection in school children of an Amazonian municipality in Mato Grosso State. Rev Soc Bras Med Trop. 2002; 35: 155-158.
10.1590/S0037-86822002000200005
PubMed Google Scholar
23Parana R, Vitviski L, Andrade Z, et al. Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history. Hepatology. 1999; 30: 289-293.
10.1002/hep.510300143
CAS PubMed Web of Science® Google Scholar
24Souto FJ, Fontes CJ, Parana R, Lyra LG. Short report: further evidence for hepatitis E in the Brazilian Amazon. Am J Trop Med Hyg. 1997; 57: 149-150.
10.4269/ajtmh.1997.57.149
CAS PubMed Web of Science® Google Scholar
25Lyra AC. Aspectos Virológicos Associados a Pacientes Com Hepatite Aguda Viral [Tese Doutorado]. São Paulo, Brazil: Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo; 2003.
Google Scholar
26Ibarra H, Riedemann S, Siegel F, Toledo C, Reinhardt G. Acute hepatitis caused by virus A, E and non A-E in Chilean adults. Rev Med Chil. 2001; 129: 523-530.
10.4067/S0034-98872001000500008
CAS PubMed Web of Science® Google Scholar
27Vildosola H, Colichón A, Barreda M, Piscoya J, Palacios O. Hepatitis E IgG antibodies seroprevalence in a Peruvian risk group. Rev Gastroenterol Peru. 2000; 20: 111-116.
PubMed Google Scholar
28Blitz-Dorfman L, Monsalve F, Atencio R, et al. Serological survey of viral hepatitis infection markers among the Yukpa Amerindians from Western Venezuela: lack of antibody to hepatitis C virus. Ann Trop Med Parasitol. 1996; 90: 655-657.
10.1080/00034983.1996.11813098
CAS PubMed Web of Science® Google Scholar
29Ibarra H, Riedemann S, Toledo C. Hepatitis A and E virus antibodies in Chilean children of low socioeconomic status: a 1 year follow-up study. Rev Med Chil. 2006; 134: 139-144.
PubMed Web of Science® Google Scholar
30Dell'Amico MC, Cavallo A, Gonzales JL, et al. Hepatitis E virus genotype 3 in humans and Swine, Bolivia. Emerg Infect Dis. 2011; 17: 1488-1490.
PubMed Web of Science® Google Scholar
31Silva SM, Oliveira JM, Vitral CL, Vieira Kde A, Pinto MA, Souto FJ. Prevalence of hepatitis E virus antibodies in individuals exposed to swine in Mato Grosso, Brazil. Mem Inst Oswaldo Cruz. 2012; 107: 338-341.
10.1590/S0074-02762012000300007
PubMed Web of Science® Google Scholar
32Betancur CA, Mejía MV, Portillo S. Seroprevalencia de hepatitis E en trabajadores de fincas porcícolas del Valle de Aburrá 2011–2012. Acta Méd Colomb. 2013; 38: 68-70.
Google Scholar
33Hering T, Passos AM, Perez RM, et al. Past and current hepatitis E virus infection in renal transplant patients. J Med Virol. 2014; 86: 948-953.
10.1002/jmv.23915
CAS PubMed Web of Science® Google Scholar
34Peláez D, Hoyos MC, Rendón JC, et al. Infección por el virus de la hepatitis E en pacientes con diagnóstico clínico de hepatitis viral en Colombia. Biomedica. 2014; 34: 354-365.
10.7705/biomedica.v34i3.2236
PubMed Web of Science® Google Scholar
35Vitral CL, da Silva-Nunes M, Pinto MA, et al. Hepatitis A and E seroprevalence and associated risk factors: a community-based cross-sectional survey in rural Amazonia. BMC Infect Dis. 2014; 14: 458.
10.1186/1471-2334-14-458
PubMed Web of Science® Google Scholar
36Martins RM, Freitas NR, Kozlowski A, et al. Seroprevalence of hepatitis E antibodies in a population of recyclable waste pickers in Brazil. J Clin Virol. 2014; 59: 188-191.
10.1016/j.jcv.2014.01.002
CAS PubMed Web of Science® Google Scholar
37Martínez Wassaf MG, Pisano MB, Barril PA, et al. First detection of hepatitis E virus in central Argentina: environmental and serological survey. J Clin Virol. 2014; 61: 334-339.
10.1016/j.jcv.2014.08.016
PubMed Web of Science® Google Scholar
38Munné MS, Altabert NR, Otegui MLO, et al. Updating the knowledge of hepatitis E: new variants and higher prevalence of anti-HEV in Argentina. Ann Hepatol. 2014; 13: 496-502.
10.1016/S1665-2681(19)31248-7
PubMed Web of Science® Google Scholar
39Gutiérrez-Vergara CC, Rodríguez B, Parra-Suescún J, et al. Determinación de anticuerpos totales (IgG/IgM) y específicos (IgM) para el virus de la hepatitis E y detección molecular del virus en heces de humanos con o sin exposición ocupacional a porcinos en 10 municipios de Antioquia. Iatreia. 2015; 28: 248-258.
10.17533/udea.iatreia.v28n3a03
Web of Science® Google Scholar
40Debes JD, Martínez Wassaf M, Pisano MB, et al. Increased hepatitis E virus seroprevalence correlates with lower CD4 + cell counts in HIV-infected persons in Argentina. PLoS ONE. 2016; 11: e0160082.
10.1371/journal.pone.0160082
PubMed Web of Science® Google Scholar
41Freitas NR, Santana EB, Silva ÁM, et al. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. Mem Inst Oswaldo Cruz. 2016; 111: 692-696.
10.1590/0074-02760160256
PubMed Web of Science® Google Scholar
42Passos-Castilho AM, de Sena A, Domingues AL, et al. Hepatitis E virus seroprevalence among schistosomiasis patients in Northeastern Brazil. Braz J Infect Dis. 2016; 20: 262-266.
10.1016/j.bjid.2016.03.001
PubMed Web of Science® Google Scholar
43Passos-Castilho AM, Reinaldo MR, Sena A, Granato CFH. High prevalence of hepatitis E virus antibodies in Sao Paulo, Southeastern Brazil: analysis of a group of blood donors representative of the general population. Braz J Infect Dis. 2017; 21: 535-539.
10.1016/j.bjid.2017.05.004
PubMed Web of Science® Google Scholar
44Pandolfi R, Ramos de Almeida D, Alves Pinto M, Kreutz LC, Frandoloso R. In house ELISA based on recombinant ORF2 protein underline high prevalence of IgG anti-hepatitis E virus amongst blood donors in south Brazil. PLoS ONE. 2017; 12: e0176409.
10.1371/journal.pone.0176409
PubMed Web of Science® Google Scholar
45Pisano MB, Balderramo D, Wassaf MM, et al. Hepatitis E virus infection in patients on dialysis and in solid organ transplant recipients in Argentina: exploring associated risk factors. Arch Virol. 2017; 162: 787-792.
10.1007/s00705-016-3171-6
CAS PubMed Web of Science® Google Scholar
46Ferreira AC, Gomes-Gouvêa MS, Lisboa-Neto G, et al. Serological and molecular markers of hepatitis E virus infection in HIV-infected patients in Brazil. Arch Virol. 2018; 163: 43-49.
10.1007/s00705-017-3562-3
CAS PubMed Web of Science® Google Scholar
47Passos-Castilho AM, de Sena A, Geraldo A, Spada C, Granato CF. High prevalence of hepatitis E virus antibodies among blood donors in Southern Brazil. J Med Virol. 2016; 88: 361-364.
10.1002/jmv.24336
CAS PubMed Web of Science® Google Scholar
48Passos-Castilho AM, de Sena A, Reinaldo MR, Hernandes Granato CF. Hepatitis E virus infection in Brazil: results of laboratory-based surveillance from 1998 to 2013. Rev Soc Bras Med Trop. 2015; 48: 468-470.
10.1590/0037-8682-0036-2015
PubMed Web of Science® Google Scholar
49Pas SD, Streefkerk RH, Pronk M, et al. Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients. J Clin Virol. 2013; 58: 629-634.
10.1016/j.jcv.2013.10.010
CAS PubMed Web of Science® Google Scholar
50Murali AR, Kotwal V, Chawla S. Chronic hepatitis E: a brief review. World J Hepatol. 2015; 7: 2194-2201.
10.4254/wjh.v7.i19.2194
PubMed Web of Science® Google Scholar
51Debes JD, Pisano MB, Lotto M, Re V. Hepatitis E virus infection in the HIV-positive patient. J Clin Virol. 2016; 80: 102-106.
10.1016/j.jcv.2016.05.006
PubMed Web of Science® Google Scholar
52Kumar S, Subhadra S, Singh B, Panda BK. Hepatitis E virus: the current scenario. Int J Infect Dis. 2013; 17: e228-e233.
10.1016/j.ijid.2012.11.026
PubMed Web of Science® Google Scholar
53Munné MS, Altabert NR, Vladimirsky SN, et al. Identifications of polyphyletic variants in acute hepatitis suggest an underdiagnosed circulation of hepatitis E virus in Argentina. J Clin Virol. 2011; 52: 138-141.
10.1016/j.jcv.2011.06.015
PubMed Web of Science® Google Scholar
54Rendon J, Hoyos MC, di Filippo D, et al. Hepatitis E Virus genotype 3 in Colombia: survey in patients with clinical diagnosis of viral hepatitis. PLoS ONE. 2016; 11: e0148417.
10.1371/journal.pone.0148417
PubMed Web of Science® Google Scholar
55García CG, Sánchez D, Villalba MC, et al. Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela. J Med Virol. 2012; 84: 1025-1029.
10.1002/jmv.23277
CAS PubMed Web of Science® Google Scholar
56Mirazo S, Mainardi V, Ramos N, Gerona S, Rocca A, Arbiza J. Indigenous hepatitis E virus genotype 1 infection, Uruguay. Emerg Infect Dis. 2014; 20: 171-173.
10.3201/eid2001.131471
PubMed Web of Science® Google Scholar
57Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012; 367: 1237-1244.
10.1056/NEJMra1204512
CAS PubMed Web of Science® Google Scholar
58Sridhar S, Chan JFW, Yap DYH, et al. Genotype 4 hepatitis E virus is a cause of chronic hepatitis in renal transplant recipients in Hong Kong. J Viral Hepat. 2018; 25: 209-213.
10.1111/jvh.12799
CAS PubMed Web of Science® Google Scholar
59Martínez-Artola Y, Poncino D, García ML, Munné MS, González J, García DS. Acute hepatitis E virus infection and association with a subacute thyroiditis. Ann Hepatol. 2015; 14: 141-142.
10.1016/S1665-2681(19)30813-0
CAS PubMed Web of Science® Google Scholar
60Zylberman M, Turdó K, Odzak A, Arcondo F, Altabert N, Munné S. Hepatitis E virus-associated aplastic anemia. Report of a case. Medicina (B Aires). 2015; 75: 175-177.
PubMed Web of Science® Google Scholar
61Valenzuela V, Pinto J, Padilla M, et al. Severe decompensation of hepatitis e in a patient with autoimmune hepatitis: a case report. Rev Gastroenterol Peru. 2012; 32: 187-191.
CAS PubMed Google Scholar
62Passos-Castilho AM, Porta G, Miura IK, et al. Chronic hepatitis E virus infection in a pediatric female liver transplant recipient. J Clin Microbiol. 2014; 52: 4425-4427.
10.1128/JCM.02286-14
PubMed Web of Science® Google Scholar
63Gruz F, Munné MS, González J, et al. Ribavirin treatment of patient with chronic hepatitis E. First case reported in Latin America. Acta Gastroenterol Latinoam. 2016; 46: 122-125.
PubMed Google Scholar
64Balayan MS, Usmanov RK, Zamyatina NA, Djumalieva DI, Karas FR. Experimental hepatitis E infection in domestic pigs. J Med Virol. 1990; 32: 58-59.
10.1002/jmv.1890320110
CAS PubMed Web of Science® Google Scholar
65Meng XJ. Hepatitis E virus: animal reservoirs and zoonotic risk. Vet Microbiol. 2009; 140: 256-265.
10.1016/j.vetmic.2009.03.017
PubMed Web of Science® Google Scholar
66Pavio N, Meng XJ, Doceul V. Zoonotic origin of hepatitis E. Curr Opin Virol. 2015; 10: 34-41.
10.1016/j.coviro.2014.12.006
PubMed Web of Science® Google Scholar
67Doceul V, Bagdassarian E, Demange A, Pavio N. Zoonotic hepatitis E virus: classification. Animal Reservoirs and Transmission Routes. Viruses. 2016; 8: 270-278.
10.3390/v8100270
PubMed Web of Science® Google Scholar
68Vitral CL, Pinto MA, Lewis-Ximenez LL, Khudyakov YE, dos Santos DR, Gaspar AM. Serological evidence of hepatitis E virus infection in different animal species from the Southeast of Brazil. Mem Inst Oswaldo Cruz. 2005; 100: 117-122.
10.1590/S0074-02762005000200003
PubMed Web of Science® Google Scholar
69Dos Santos DR, Vitral CL, de Paula VS, et al. Serological and molecular evidence of hepatitis E virus in swine in Brazil. Vet J. 2009; 182: 474-480.
10.1016/j.tvjl.2008.08.001
CAS PubMed Web of Science® Google Scholar
70De Souza AJ, Gomes-Gouvêa MS, Soares Mdo C, et al. HEV infection in swine from Eastern Brazilian Amazon: evidence of co-infection by different subtypes. Comp Immunol Microbiol Infect Dis. 2012; 35: 477-485.
10.1016/j.cimid.2012.04.004
PubMed Web of Science® Google Scholar
71Forero J, Gutiérrez-Vergara C, Parra J, et al. Serological evidence of Hepatitis E Virus infection in Antioquia, Colombia slaughtered pigs. Rev MVZ Córdoba. 2015; 20: 4602-4613.
10.21897/rmvz.63
Web of Science® Google Scholar
72Reinhardt G, Ibarra H, Riedemann S, Vega I. Swine hepatitis E preliminary serological study in Chile. Arch Med Vet. 2003; 35: 233-236.
10.4067/S0301-732X2003000200011
Web of Science® Google Scholar
73Munné MS, Vladimirsky S, Otegui L, et al. Identification of the first strain of swine hepatitis E virus in South America and prevalence of anti-HEV antibodies in swine in Argentina. J Med Virol. 2006; 78: 1579-1583.
10.1002/jmv.20741
PubMed Web of Science® Google Scholar
74Mirazo S, Gardinali NR, D'Albora C, et al. Serological and virological survey of hepatitis E virus (HEV) in animal reservoirs from Uruguay reveals elevated prevalences and a very close phylogenetic relationship between swine and human strains. Vet Microbiol. 2018; 213: 21-27.
10.1016/j.vetmic.2017.11.013
CAS PubMed Web of Science® Google Scholar
75Paiva H, Tzaneva V, Haddad R, Yokosawa J. Molecular characterization of swine hepatitis E virus from southeastern Brazil. Braz J Microbiol. 2007; 38: 693-698.
10.1590/S1517-83822007000400020
Web of Science® Google Scholar
76Lopes dos Santos DR, Lewis-Ximenez L, da Silva MF, de Sousa PS, Gaspar AM, Pinto MA. First report of a human autochthonous hepatitis E virus infection in Brazil. J Clin Virol. 2010; 47: 276-279.
10.1016/j.jcv.2009.12.021
PubMed Web of Science® Google Scholar
77Dos Santos DR, de Paula VS, de Oliveira JM, Marchevsky RS, Pinto MA. Hepatitis E virus in swine and effluent samples from slaughterhouses in Brazil. Vet Microbiol. 2011; 149: 236-241.
10.1016/j.vetmic.2010.10.024
PubMed Web of Science® Google Scholar
78Gardinali NR, Barry AF, Otonel RA, Alfieri AF, Alfieri AA. Hepatitis E virus in liver and bile samples from slaughtered pigs of Brazil. Mem Inst Oswaldo Cruz. 2012; 107: 935-939.
10.1590/S0074-02762012000700016
PubMed Web of Science® Google Scholar
79Passos-Castilho AM, Granato CFH. High frequency of hepatitis E virus infection in swine from South Brazil and close similarity to human HEV isolates. Braz J Microbiol. 2017; 48: 373-379.
10.1016/j.bjm.2016.10.022
CAS PubMed Web of Science® Google Scholar
80Purdy MA, Dell'Amico MC, Gonzales JL, et al. Human and porcine hepatitis E viruses, southeastern Bolivia. Emerg Infect Dis. 2012; 18: 339-340.
10.3201/eid1802.111453
PubMed Web of Science® Google Scholar
81Forero J, Gutiérrez-Vergara C, Parra J, et al. Phylogenetic analysis of Hepatitis E virus strains isolated from slaughter-age pigs in Colombia. Infect Genet Evol. 2017; 49: 138-145.
10.1016/j.meegid.2017.01.005
CAS PubMed Web of Science® Google Scholar
82Gutiérrez-Vergara C, Quintero J, Duarte JF, Suescún JP, López-Herrera A. Detection of hepatitis E virus genome in pig livers in Antioquia, Colombia. Genet Mol Res. 2015; 14: 2890-2899.
10.4238/2015.March.31.20
CAS PubMed Web of Science® Google Scholar
83Van der Poel WH. Food and environmental routes of Hepatitis E virus transmission. Curr Opin Virol. 2014; 4: 91-96.
10.1016/j.coviro.2014.01.006
PubMed Web of Science® Google Scholar
84Baez PA, Lopez MC, Duque-Jaramillo A, Pelaez D, Molina F, Navas MC. First evidence of the Hepatitis E virus in environmental waters in Colombia. PLoS ONE. 2017; 12: e0177525.
10.1371/journal.pone.0177525
PubMed Web of Science® Google Scholar
85Heldt FH, Staggmeier R, Gularte JS, Demoliner M, Henzel A, Spilki FR. Hepatitis E virus in surface water, sediments, and pork products marketed in Southern Brazil. Food Environ Virol. 2016; 8: 200-205.
10.1007/s12560-016-9243-7
CAS PubMed Web of Science® Google Scholar
86Masachessi G, Pisano MB, Prez VE, et al. Enteric viruses in surface waters from Argentina: molecular and viable-virus detection. Appl Environ Microbiol. 2018; 84: e02327–17.
10.1128/AEM.02327-17
PubMed Web of Science® Google Scholar
87Vasconcelos J, Soliman MC, Staggemeier R, et al. Molecular detection of hepatitis E virus in feaces and slurry from swine farms, Rio Grande do Sul, Southern Brazil. Arq Bras Med Vet Zootec. 2015; 67: 777-782.
10.1590/1678-4162-7733
Google Scholar
88Chen YJ, Cao NX, Xie RH, et al. Epidemiological investigation of a tap water-mediated hepatitis E virus genotype 4 outbreak in Zhejiang Province, China. Epidemiol Infect. 2016; 22: 1-13.
CAS Google Scholar
89Szabo K, Trojnar E, Anheyer-Behmenburg H, et al. Detection of hepatitis E virus RNA in raw sausages and liver sausages from retail in Germany using an optimized method. Int J Food Microbiol. 2015; 215: 149-156.
10.1016/j.ijfoodmicro.2015.09.013
CAS PubMed Web of Science® Google Scholar
90Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014; 384: 1766-1773.
10.1016/S0140-6736(14)61034-5
PubMed Web of Science® Google Scholar
91Schlauder GG, Frider B, Sookoian S, Castaño GC, Mushahwar IK. Identification of 2 novel isolates of hepatitis E virus in Argentina. J Infect Dis. 2000; 182: 294-297.
10.1086/315651
CAS PubMed Web of Science® Google Scholar
92Munné MS, Vladimirsky S, Otegui L, et al. Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina. Acta Gastroenterol Latinoam. 2006; 36: 125-130.
PubMed Google Scholar
93Mirazo S, Ramos N, Russi JC, Gagliano G, Arbiza J. Detection and molecular characterization of sporadic cases of acute human hepatitis E virus infection in Uruguay. Arch Virol. 2011; 156: 1451-1454.
10.1007/s00705-011-0991-2
CAS PubMed Web of Science® Google Scholar
94Mirazo S, Ramos N, Russi JC, Arbiza J. Genetic heterogeneity and subtyping of human Hepatitis E virus isolates from Uruguay. Virus Res. 2013; 173: 364-370.
10.1016/j.virusres.2013.01.005
CAS PubMed Web of Science® Google Scholar
95Da Costa Lana MV, Gardinali NR, da Cruz RA, et al. Evaluation of hepatitis E virus infection between different production systems of pigs in Brazil. Trop Anim Health Prod. 2014; 46: 399-404.
10.1007/s11250-013-0503-3
PubMed Web of Science® Google Scholar
96Passos AM, Heringer TP, Medina-Pestana JO, Ferraz ML, Granato CF. First report and molecular characterization of hepatitis E virus infection in renal transplant recipients in Brazil. J Med Virol. 2013; 85: 615-619.
10.1002/jmv.23494
CAS PubMed Web of Science® Google Scholar
97Bortoliero AL, Bonametti AM, Morimoto HK, Matsuo T, Reiche EMV. Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the regional blood bank of Londrina, State of Paraná, Brazil. Rev Inst Med Trop Sao Paulo. 2006; 48: 87-92.
10.1590/S0036-46652006000200006
PubMed Google Scholar
98Lyra AC, Pinho JR, Silva LK, et al. HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis. Braz J Med Biol Res. 2005; 38: 767-775.
10.1590/S0100-879X2005000500015
CAS PubMed Web of Science® Google Scholar
99Hurtado C, Muñoz G, Brahm J. Detection of IgM antibodies against hepatitis E virus. Rev Med Chil. 2005; 133: 645-647.
PubMed Web of Science® Google Scholar
100Hyams KC, Yarbough PO, Gray S, et al. Hepatitis E virus infection in Peru. Clin Infect Dis. 1996; 22: 719-720.
10.1093/clinids/22.4.719
CAS PubMed Web of Science® Google Scholar
101Rivero JDM, Manrique RJB, Arróspide MT. Acute hepatitis secondary to Hepatitis E. Report of two cases from a population of high socioeconomic level Lima. Rev Gastroenterol Peru. 2010; 30: 357-362.
PubMed Google Scholar

Citing Literature

Volume38, Issue9

September 2018

Pages 1536-1546

Hepatitis E virus in South America: The current scenario