Hepatitis E virus in animals, food and where else? Nicole Pavio Anses Laboratoire de santé animale, UMR 1161 INRA,ENVA, Anses, France nicole.pavio@anses.fr
Hepatitis E virus infection in human HEV1 to HEV4 Every year : 20 million hepatitis E infections 3 million symptomatic cases 56 600 hepatitis E-related deaths. • Incubation time 40 days (2-9 weeks) • Acute Hepatitis enteric transmission (similar to hepatitis A) • Fulminate Hepatitis 1%-4%. Pregnant women: 15%-25% • Chronic Hepatitis Immuno-suppression (solid organ transplant recipient) RNA+> 6 Mo • Neurologic syndroms Guillain-Barré, Parsonage-Turner (CSF+ chronic infection) • Extra-hepatic Kidney dysfunction, pancreatisis Liver enzyme X 10 • Hepatocellular carcinoma (Amougou Atsama, 2017; Borentain P et al 2017) Anti-HEV IgM + HEV RNA + IAFP Europe April 24-26 2019
Virale hepatitis E epidemiology Endemic Regions Authochtonous sporadic or grouped cases Tropical, subtropical Europe, Japan HEV Genotypes 3, 4 Water, spoiled foods Food Animal reservoirs HEV Genotypes 1, 2 IAFP Europe April 24-26 2019 HEV Genotypes 3, 4
HEV Phylogeny: HEPEVIRIDAE family Zoonotic transmissions Orthohepevirus 1 4 HEV-3 -4 2 3ra 7 5-6 3 4 A 1 3 B 2 D C HEV-3ra C2 C1 Piscihepevirus HEV-7 Cutthroat Trout IAFP Europe April 24-26 2019 Doceul et al 2016
Animal reservoirs of HEV Anti-HEV antibodies Anti-HEV antibodies and HEV RNA HEV RNA IAFP Europe April 24-26 2019
Sources/vehicules of HEV3 and HEV4 Swine Slurry Slaughterhouse Personnel (hands) Surfaces, ustensiles (knife, hook) Di Bartolo et al, 2012 Effluents Nantel-Fortier et al, 2016 Transportation vehicules Waste Water Treatment Plant Spain and France (Clemente-Casares et al, EID 2003) Switzerland (Masclaux et al 2013) Italy (Iaconelli et al 2015) Surface water in non endemic region (The Netherlands) (Rutjes SA, EID 2009) Strawberries (Fields) (Brassard J, et al, 2012) Berry fruit (Maunula et al, 2013) Shell fish Corbicula Japonica, Japan (Li et al Am J Trop Med Hyg. 2007) Food Outbreak on Cruise Ship (Oyster HEV-3) (Said et al 2009) UK Mussels up to 92% HEV RNA (Crossan et al EID 2012) Animal Bioaccumulation in Oyster (Grodski et al 2014) reservoirs Green leafy salads (Kokkinos et al 2012) Herb and Spices (Loisy-Hamon 2015) IAFP Europe April 24-26 2019
Sources/vehicules of HEV3 and HEV4 Pork Liver contaminated with HEV : grocery stores, slaughterhouse USA (Feagins et al., 2007) 11% RNA+; 2/3 infectious The Netherlands (Bouwknegt et al., 2007) 6.5% (Boxman, et al 2019) 12,7% Japan (Yazaki et al., 2003) 1.9% Korea (Jung et al., 2007) 10.8% India (Kulkarni et al., 2008) 0.83% France (Rose et al 2011) 4% Germany (Wenzel JJ, 2011) 4% Italy (Di Bartolo et al 2012) 6% Canada (Wilhelm et al 2014) 3,5% Pork Liver sausages contaminated with HEV France (Pavio et al 2014) 30% Germany (Szabo et al et al 2015) 22% Italy (Di Bartolo et al 2014) 24 % Switzerland (Moor et al 2018) 19% The Netherland (Boxman, et al 2019) 70% Pork sausages UK (Berto et al 2012) 10% Germany (Szabo et al 2015) 20% Switzerland (Moor et al 2018) 6% IAFP Europe April 24-26 2019
HEV experimental infection in pigs Hepatitis E Virus dynamic in pigs Theoretical HEV infection in natural setting HEV fecal excretion anti-HEV IgG Maternal Anti-HEV antibodies AST ALT anti-HEV IgM HEV Infection Cholesterol Triglycerides 16 0 2 10 12 14 18 24 4 6 8 20 22 Age in weeks IAFP Europe April 24-26 2019 Rogée et al 2015
Hepatitis E Virus dynamic in pig herds Salines in revision IAFP Europe April 24-26 2019
Co-infection with Hepatitis E and Porcin Reproductive and Respiratory Syndrom viruses Inoculated pigs Contact pigs Log(ge HEV) / g feces Log(ge HEV) / g feces Days post-infection Days post-infection HEV + PRRSV : HEV chronic infection Increased risk of HEV in other organs (muscles) Salines et al 2015 IAFP Europe April 24-26 2019
Co-infection with Hepatitis E and Porcin Reproductive and Respiratory Syndrom viruses HEV RNA in muscle at 49 dpi (RNA HEV RNA in HEV RNA in Viremia kinetic (RNA copies/mL serum) copies/g) feces at 49 dpi liver at 49 dpi (RNA copies/g) (RNA copies/g) dpi 7 14 21 28 35 42 49 FB PM DP Control nd nd nd nd nd nd nd nd nd nd nd nd Control nd nd nd nd nd nd nd nd nd nd nd nd 3.56.10 3 1.43.10 4 1.91.10 4 1.70.10 3 1.49.10 7 1.46.10 6 Inoculated nd nd nd nd nd nd 4.22.10 4 3.85.10 4 7.70.10 4 2.14.10 4 4.02.10 3 5.85.10 7 1.87.10 6 Inoculated nd nd nd nd nd 1.33.10 4 2.92.10 4 7.49.10 4 5.21.10 4 2.15.10 4 1.43.10 4 6.40.10 7 1.02.10 6 Inoculated nd nd nd nd Group 1 2.12.10 4 2.80.10 4 9.44.10 3 4.87.10 7 8.72.10 5 Contact nd nd nd nd nd nd nd 3.49.10 5 Contact nd nd nd nd nd nd nd nd nd nd nd 1.20.10 6 Contact nd nd nd nd nd nd nd nd nd nd nd 4.51.10 3 2.07.10 4 2.24.10 4 4.33.10 3 6.23.10 3 1.45.10 5 1.56.10 3 Inoculated nd nd nd nd nd 2.16.10 4 2.43.10 4 2.05.10 4 1.24.10 4 2.18.10 4 2.70.10 3 6.80.10 6 2.42.10 6 Inoculated nd nd nd nd 6.31.10 4 1.69.10 4 5.55.10 4 2.80.10 4 8.14.10 3 3.55.10 3 5.40.10 3 4.86.10 6 3.59.10 5 Inoculated nd nd nd Group 2 2.64.10 4 7.33.10 3 5.91.10 4 6.75.10 5 6.42.10 3 5.55.10 7 1.12.10 6 Contact nd nd nd nd nd 2.65.10 4 6.82.10 3 2.12.10 4 2.28.10 3 3.72.10 3 5.24.10 6 1.69.10 6 Contact nd nd nd nd nd 1.76.10 4 6.64.10 4 2.94.10 3 6.92.10 3 3.07.10 8 3.44.10 6 Contact nd nd nd nd nd nd 4.40.10 3 2.08.10 4 2.11.10 4 1.22.10 4 2.08.10 8 3.24.10 6 Inoculated nd nd nd nd nd nd 8.68.10 3 1.72.10 4 1.92.10 4 1.59.10 4 6.17.10 3 5.75.10 7 2.04.10 4 Inoculated nd nd nd nd nd 4.10.10 4 1.95.10 4 1.46.10 4 1.00.10 4 1.15.10 3 1.09.10 6 1.62.10 4 5.61.10 7 9.63.10 5 Inoculated nd nd nd Group 3 7.39.10 5 Contact nd nd nd nd nd nd nd nd nd nd nd 5.32.10 3 1.03.10 8 5.87.10 5 Contact nd nd nd nd nd nd nd nd nd 8.29.10 5 Contact nd nd nd nd nd nd nd nd nd nd nd Salines et al 2018
HEV-PRRSV During intercurrent infection (PRRSV): HEV is detected in pork meat muscles Psoas Major (Filet Mignon) • Up to 10 6 /g = possible transmission Food consumption Biceps femoris (Ham) • Risk assessement in Public Health: Inactivation procedure: heating time/temperature Drying, curing • Recommendation: deep cooking of pork meat Barnaud et al 2012 71°C during 20 min • Survey at slaughterhouse: test faecal samples to detect pig at risk of HEV positive meat IAFP Europe April 24-26 2019
Hepatitis E Virus in Muscle at Slaughterhouse positive Prevalence 95% Confidence Sample size samples estimate (%) interval HEV serology 1034 629 60 57.8-63.7 HEV RNA (muscles) 1034 0 0 0-0.003 HEV RNA (liver) 1034 29 2.8 1.9-3.9 14 Different muscle: gluteus medius or semi-membranosus 12 No indication PRRSV status Number of livers 10 8 Perspectives: 6 • Larger sampling 4 • HEV, PCV2 and PRRSV status 2 • Biceps or Psoas 0 [10^3 - 10^4] [10^4 - 10^5] [10^5 - 10^6] [10^7 - 10^8] [10^8 - 10^9] copies of HEV RNA per gram IAFP Europe April 24-26 2019 Feurer et al 2017
HEV RNA +: 33/36 batches of (non- heated) liquid products 7/24 spray dried powder products IAFP Europe April 24-26 2019
Frequent Hepatitis E Virus Contamination in Food Containing Raw Pork Liver, France Food category number of samples RNA Quantification (Min-Max Prevalence and analyzed (394 total) in copies of HEV RNA/g)* [ 95% CI] Figatelli and fitone 140 1.7 10 2 -6.9 10 5 30 [23, 38] Dried salted liver 30 6.9 10 5 3 [0, 1] 2.6 10 2 -2.83 10 5 Quenelle and quenelle paste 55 25 [15, 37] 1 10 2 -2.3 10 6 Dried or fresh liver sausages 169 29 [22, 36] Pavio et al 2014 EID Berto et al.2013 EID
Phylogeny of HEV sequences present in raw pork liver foods. Food/ human SPAIN Food/ human FRANCE All HEV genotype 3 Food/pig High sequence identity : 99% (n=16) Food/ human sequences (France, UK, Spain) Food/pig sequences (France) Food/pig Swine Human (France) Human (other) Food Food/ human UK Pavio et al EID 2014 IAFP Europe April 24-26 2019
Direct foodborne transmission of HEV IAFP Europe April 24-26 2019 Guillois et al CID 2015
Foodborne transmission of HEV IAFP Europe April 24-26 2019 Yapa et al 2016
Foodborne transmission of HEV Case-control study among hepatitis E cases (n=270) aged 18 years or older notified between January 2012 and January 2014 and matching controls (n=1,159). => Consumption of undercooked pork liver, pork, wild boar meat, frankfurters, liver sausage and raw vegetables; contact with waste water (occupational). Pork liver>Wild boar>Pork>Liver sausage or liver pâté>Boiled sausage>Raw vegetables IAFP Europe April 24-26 2019 Faber et al 2018
Foodborne transmission of HEV 75 % foodborne origin of HEV Van Cauteren et al, 2018 A nationwide case-control study June 2015 and October 2017 (n=597). Traditional Dutch dry raw sausages of pork muscle meat, called , “ cervelaat ”, “ snijworst ”, and “boerenmetworst”were reported by 72% of the patients, and 46% of controls (OR 3.0; 95% CI 2.2 – 4.1) Direct contact with pigs and working with a septic tank were strong risk factors (aOR 3.1; 95%CI 1.3 – 7.3 and aOR 6.9; 95%CI 1.2 – 40.8, respectively), Kamar et al 2012 IAFP Europe April 24-26 2019 Tulen et al 2019
IAFP Europe April 24-26 2019
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