Hepatitis E virus in Israel

Transcription

1 Hepatitis E virus in Israel Daniela Ram 1, Yossi Manor 1, Yael Gozlan 1, Rachel Shirazi 1, Eli Schwartz 2,3, Ziv Ben-Ari 3,4, Ella Mendelson 1,5, Pozzi Shaul 6, Orna Mor 1 1 Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Ramat-Gan; 2 Center for Geographic Medicine and Tropical Diseases, Sheba Medical Center, Tel Hashomer, Ramat- Gan; 3 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; 4 Liver Diseases Center, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan; 5 Public School of Health, Tel-Aviv University, Tel-Aviv; 6 Ministry of Agriculture, Veterinary Services, Beit Dagan Liver research meeting, Eilat 2016

2 Every year : Background estimated 20 million hepatitis E infections over 3 million symptomatic cases of hepatitis E hepatitis E-related deaths. Infections result in acute self-limiting and symptomatic presentation that varies in severity from subclinical to fulminant cases

3 The virus It is a member of the Hepeviridea family Has a linear, positive sense, non enveloped, single-stranded ~7.2-kb-long RNA containing three open reading frames (ORFs). ORF1 encodes non-structural proteins ORF2 encodes the capsid proteins ORF3 which overlaps ORF1, encodes a phosphoprotein.

4 Mammalian HEV genotypes HEV G1 and G2 infect humans developing countries epidemic outbreaks infect all ages, seasonal contaminated water HEV G3 and G4 infect humans & animals developed countries sporadic, autochthonous, chronic infections Mainly in >40 years old Asymptomatic cruise ship G3 outbreak -11 acute hepatitis ;22 asymptomatic infections (Said et al., EID 2009, 15, 1738) Pérez-Gracia et la., Infect Genet & Evol 22 (2014) 40 59

5 Percent Prevalence of antibodies to hepatitis E virus in Israel % 40% 35% 30% 25% 20% 15% 10% 5% 0% 40% 12% 0% 1% 1% 1% 3% Age groups Mor et al., EID, 21,4:692-4, 2015

6 Study conclusions Overall anti IgG HEV rates in Israel is 10.6%, HEV Seroprevalence is highly age dependent Between 1993 and 2013, 68 cases (~ 3/year) of acute HEV were diagnosed (from Lachish et al, JCV 2015, 73: 20-24) It is possible that HEV infections are silent, subclinical or un-noticed Mor et al., EID 21,4:692-4, 2015; Lachish et al. JCV 73:20-4, 2015

7 Enviormomental surveillance Environmental surveillance has become a very useful tool for population-based alert and monitoring of microbial and viral activities. In Israel, a national program for surveillance of the poliovirus in sewage has been ongoing since It led to the identification of wild poliovirus in 2013, which activated a major emergency response by the Public Health Services There is no environmental monitoring of HEV in Israel

8 France G1+G3 Clin+Sew Spain G1+G3 Clin+Sew Morocco G1; no info on sewage Tunisia G1+G3 Clin+Sew Italy G1+G3 Clin+Sew Greece G1 None in sew?? Egypt G1 None in sew

9 Methodology for urban sewage samples 500 ml sewage sample Concentrate (filter and centrifuge) to 15 ml Shafdan STF Extract NA from 1ml Real-Time PCR (Altona) HEV negative HEV positive RT-PCR ORF1 and sequence

10 36 sampling sites 169 sewage samples

11 Region Participating sewage treatment facilities (STFs) or sewage lines and RT-PCR results on sewage samples Sewage treatment facilities (STFs)/lines Population Equivalents served by STFs/lines Number of municipalitie s served by STFs/ines Number HEV-positive samples/total collected Q1 Q2 Q3 Q4 (Jan- (Apr- (Jul- (Oct- Mar) Jun) Sep) Dec) Total # of HEVpositive samples Total # of samples (#PCR failures) South Beer Sheva 1, 702, /3 1/12 0/13 0/ (2) Ashdod, Kiryat Gat, Rahat, Arara, Shoket, Kseifa,Tel sheva Central Ayalon, Baka, 411, /4 0/2 0/4 0/ (2) Horashim, Tnuvot Jerusalem Sorek, Og, Kidron 820, /8 0/1 0/0 0/ (1) North east Manda, El Hamra, Zfat, Tel Adashim 204, /7 0/0 0/4 0/ (1) North west Eron 97, /0 0/1 0/1 0/1 0 3 Akko 120, /5 0/0 0/1 0/2 0 8 Haifa Metropolitan, Nesher, Kryaot, Tirat hacarmel 555, /7 4/7 1/1 2/ Shafdan, Line B, 1,800, /8 0/7 1/8 0/ (1) Line C Tel Aviv Metropolitan Palestine 8 facilities NA 2 NA 2 0/10 0/0 0/3 0/ (2) Total /52 5/30 2/35 2/ (9)

12 Clinical samples Between , 49 samples from patients presenting with non A - B -C acute hepatitis were analyzed Real-Time HEV PCR assay was employed (Altona) 3/49 were HEV positives Travelers returning from India

13 AY535004_Avian AJ272108_G4_Japan AB091394_G3_Japan AP003430_G3b_Japan AB291963_G3b_Japan 590 AB074920_G3a_Japan AB082549_Japan AB082555_G3_Japan AB089824_G3a_Japan AF060668_G3a_USA AF060669_G3_USA HQ709170_G3_USA AB248520_G3_Japan AB291958_G3e_Japan KU315223_SEW_8940_Israel KU315225_SEW_8610_Israel KU315224_SEW_9275_Israel KU315220_SEW_8723_Israel 423 KU315226_SEW_8925_Israel AF195065_Spain AB369687_G3f_Japan AB291961_G3f_Japan AF195064_Spain JN906975_G3f_France JN906974_G3f_France KC166970_G3_France KC16697_France EU495148_G3f_France 986 FJ956757_G3f_Germany JQ953666_G3f_France M74506_G2_Mexico KU315222_HEP_71_Israel KU315221_HEP_59_Israel KU315219_HEP_8_Israel 960 JF443723_G1_India 699 AF459438_G1_India M73218_G1_Burma L08816_G1_India M80581_G1_Pakistan KU315218_HEP_371_Israel AY230202_G1_Morocco AY204877_G1_Chad G1 G2 G4 G3

14 Summary 8.3% (14/169 samples) of sewage samples were HEV PCR positive Positivity located mainly in Haifa but also in Tel Aviv and Beer Sheva regions (all good sanitary conditions and middle- high socioeconomic population) All were HEV Genotype 3 6.1% (3/49) of patients with acute hepatitis were HEV positive All were HEV Genotype 1

15 HEV in pigs in Israel Estimated total # of pigs in farms* % positive for HEV RNA** % positive for HEV IgG *** Pigs North (20 farms, West Galilee) Pigs South (1 farm, Lahav) Sewage (North and South farms) 80,000-90,000 0% (30/30) 15,000-20,000 0% (30/30) 88% (14/16) 100% 16/16 North positive Not relevant South North positive negative Feces (North farms) 7% (2/28 samples) Not relevant Number of pigs to be tested was calculated based on estimated prevalence of 10%, 95% CI All pigs were 4-6 months old ** HEV real-time PCR, Altona *** HEV-IgG ELISA, Wantai

16 Conclusions The identification of HEV G3 in sewage in Israel The identification of HEV in pigs in Israel (must be G3) The absence of any G3 in patients The high prevalence of anti HEV antibodies mainly in adults Better surveillance, e.g. sewage? Increase awareness? extra-hepatic manifestations? Zoonotic HEV G3 transmission? may suggest : 1. silent circulation 2. lack of awareness HEV G3?