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Hepatitis E virus sero-prevalence: Does locally acquired infection occur more frequently than we think? Helen Faddy, Ashish Shrestha, Robert Flower 31st Annual NRL workshop on infectious diseases 31st July 2014 Hepatitis E Virus (HEV) Morphology: Icosahedral, 27-34 nm, non-enveloped virus1 Genome: ssRNA, three ORFs Genotypes: 1-4 (24 subgenotypes) Case fatality rate: 0.2-4% (epidemics)1 Clinical features: Epigastric pain, diarrhoea, jaundice, hepatomegaly 1. Kamar N., et al., Lancet 379, 2477-2488 (2012). Modes of transmission Drinking contaminated water Transfusion-transmission Congenital Consumption of uncooked infected meat Contact with infected animals Organ transplantation Immune Response Virus (RNA) in blood Virus in Stool Jaundice Titre Serum Transaminase HEV IgG (persists: 2-12+ years) HEV IgM (persists: 6 months) 0 1 2 3 4 5 6 7 8 9 Number of weeks post-infection 1. Kamar N., et al., Lancet 379, 2477-2488 (2012). 10 11 12 13 14 Source: Kamar et al., 2012 Confidential Global HEV IgG seroprevalence 4.7% (Scotland)2 15.8% (UK)3 32.6%6 (China) 18.8%(USA)4 52.5% (France)5 15.2%8 (PNG) 4.2%7 (New Zealand) Source: Kamar et al., 2012 1. Kamar N., et al., Lancet 379, 2477-2488 (2012); 2. Cleland A., et al., Vox Sang 105(4),283-289 (2013); 3. Dalton HR., et al., Clin Microbiol Infect Dis 27(7), 579-585 (2008); 4. Xu C., et al., Transfusion 53(10Pt2),2505-2511 (2013); 5. Mansuy JM., et al., Emerg Infect Dis 17(12), 2309-2312 (2011); 6. Guo QS., et al., J Clin Microbiol 48(1), 317-318 (2010); 7. Dalton HR., et al., J Gastroenterol Hepatol 22(8),1236-1240 (2007); 8. Halliday JS., et la., Emerg Infect Dis 6(20), (2004) HEV in Australia National yearly notifications1 50 Number of notified cases 45 Nationally notifiable disease1 • 40 • 35 30 25 • 20 15 Average of 25 cases nationally/year Majority in NSW (41%) and VIC (31%) Majority in adults >20 years 10 5 WA 8% 2013 2012 Majority in who reported recent travel to areas where the disease was endemic2 • NSW 42% QLD 13% 2011 2010 ACT 4% VIC 31% TAS SA 1% 0% 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 0 NT 1% Locally acquired infection described in NT3 Asymptomatic infection is possible thus incidence of the disease is unknown Cases notified by state/territory 1. Australia’s Notifiable Diseases Status: Annual report of the National Notifiable Diseases Surveillance system (2014); 2. Cowie, B. et al., Emerging Infectious Diseases 11, 482-484 (2005); 3. Heath, T., et al., Medical Journal of Australia 162 318-319 (1995) Prevalence in Australia – little is known Humans1: • Pigs2: • Sero-prevalence ranges from 0.4% blood donors (n=279) to 7.7% refugees (n=182) and patients (non-A, non-B hepatitis; n=13) Sero-prevalence ranges from 30-95% in piggeries to 17% in wild pigs Birds3: • HEV strains detected in Australian chickens 1. Moaven, L., et al., Journal of Medical Virology 45, 326-330 (1995); 2. Chandler, J. D., et al., Veterinary Microbiology 68, 95-105 (1999); 3. Bilic, I., et al., Journal of General Virology 90, 863-873 (2009) HEV & blood safety HEV RNA detected in blood donors from China, UK, Germany, Japan, the Netherlands, Scotland1 Documented TT-HEV in UK, France, Japan, Saudi Arabia, and Germany1-6 • Including in Intercept PRT treated plasma7 Chronic HEV cases reported in immunocompromised patients1 Screening blood donors for HEV RNA has been proposed in Germany, Sweden, and France8 Screening of donations in the Hokkaido region of Japan9 1. Kamar N., et al., Lancet 379, 2477-2488 (2012); 2. Colson P., et al., Emerging Infectious Diseases 13, 648-649 (2007); 3. Boxall E., et al., Transfusion Medicine 16, 79-83 (2006); 4. Matsubayashi K., et al., Transfusion 44, 934-940 (2004); 5. Khuroo MS., et al., J Gastroenterol Hepatol 19(7), 778-84 (2004); 6. Huzly et al., Transfusion-transmitted hepatitis E in Germany, 2013. Eurosurveillance 19(21) (2014); 7. Hauser, et al., Blood 128, 796 (2014); 8. Féray, C., et al., The Lancet. 383(9913), 218 (2014); 9. IBPN 31(9) 130-131 (2014) RESEARCH AIM: Determine the current sero-prevalence of antibodies to HEV in Australian blood donors HEV IgG seroprevalence 194/3,237 (5.99%; 95% CI 5.18-6.18) donors HEV IgG positive Donors tested HEV IgG positive n % (95% CI) Odds ratio* p-value* Gender Female 1,453 78 5.37 (4.21-6.53) † - Male 1,784 116 6.50 (5.36-7.65) 1.23 (0.91-1.65) 0.177 ACT 406 25 6.16 (3.82-8.50) † - NSW 405 23 5.68 (3.42-7.93) 0.92 (0.51-1.64) 0.773 NT 407 26 6.39 (4.01-8.76) 1.04 (0.59-1.83) 0.892 QLD 402 18 4.48 (2.46-6.50) 0.71 (0.38-1.33) 0.289 SA 404 32 7.92 (5.29-10.55) 1.31 (0.76-2.25) 0.328 TAS 401 20 4.99 (2.86-7.12) 0.80 (0.43-1.46) 0.800 VIC 411 23 5.60 (3.37-7.82) 0.90 (0.50-1.62) 0.733 WA 401 27 6.73 (4.28-9.19) 1.10 (0.63-1.93) 0.739 State/Territory * Calculated using univariate analysis, † reference group Confidential HEV IgG seroprevalence: age * indicates (p< 0.05); multivariate analysis HEV IgG seroprevalence: overseas travel Donors tested HEV IgG positive Univariate analysis n % (95% CI) Odds ratio p-value 14 3.37 † - 6.38 1.96 0.017 (5.48-7.28) (1.12-3.40) Overseas travel No 416 (1.63-5.10) Yes 2,821 180 † reference group HEV IgG seroprevalence: no travel Donors tested HEV IgG positive n % (95% CI) Gender Female 180 6 3.33 (0.71-5.96) Male 236 8 3.39 (1.08-5.70) <45 254 5 1.97 (0.26-3.68) ≥45 162 9 5.56 (2.03-9.08) † reference group NSW 61 5 - NT 30 2 - QLD 75 1 - SA 66 4 - TAS 104 2 - VIC/WA/ACT 80 - - Age (years) State/Territory HEV IgM and RNA HEV IgM in IgG seropositive donors: 4/194 (2.06%; 95% CI 0.06-4.06) Sample Travel outside State Age Sex N62 NSW 60 M Y Malaria-related A177 NSW 72 M Y - W137 WA 45 F Y Malaria-related S122 SA 63 M Y Malaria related, food poisoning number Australia Prior deferrals Confidential Summary • ~6% of Australian donors had prior HEV infection • • Greatest in: - older donors - donors who traveled outside Australia HEV IgG in donors who did not report overseas travel A larger study (n=14,000 donations) based on detection of HEV RNA is planned to allow us to predict the risk of transfusion-transmitted HEV in Australia Acknowledgements Australian Red Cross Blood Service • R&D: Prof. Robert Flower, A/Prof. Catherine Hyland, Ashish Shrestha, Jesse Fryk, Kelly Rooks • MT&QS: Dr Clive Seed, Dr Anthony Keller, Dr Robert Harley, Dr Mark Chan, Dr Hung-Sing Yang, Philip Kiely • Manufacturing: Sue Ismay, Albert Fadel, Leo Lycett, Brian Fisher, Rebecca Rodda • Donor services staff Australian governments fully fund the Australian Red Cross Blood Service for the provision of blood products and services to the Australian community