Monitoraggio delle epatiti virali in Europa Pier Luigi Lopalco Università di Bari Roma, 17 Dicembre 2015
By courtesy of the Programme for HIV, STI and Viral Hepatitis B and C infections, ECDC Surveillance of hepatitis B and C in the EU/EEA
Surveillance of hepatitis B & C - Principles Surveillance programme coordinated by ECDC Data from 31 Member States are uploaded annually into the European Surveillance System (TESSy) Case-based and aggregate reporting possible Countries requested to follow the EU 2012 case definitions, including acute and newly diagnosed chronic infections Data collected on 33 variables Data validated by Member States
Surveillance of hepatitis B & C - Objectives Epidemiological objectives 1. To monitor the incidence and routes of transmission of newly diagnosed cases of hepatitis B and C in the general and vulnerable populations To monitor: Incidence Prevalence Route of transmission Genotype and sequence distribution 2. To monitor the prevalence of chronic hepatitis B and C virus infection to determine burden of infection (and estimate the proportion undiagnosed) in the general and vulnerable populations 3. To monitor the proportion of chronic hepatitis B and C cases that are engaged in care (continuum of care) 4. To monitor the proportion of newly diagnosed chronic hepatitis B and C presenting late 5. To determine genotype and sequence distributions of newly acquired hepatitis B and hepatitis C viruses to better follow transmission patterns, the Proportion emergence of resistance of and vaccine co infections escape mutants and potentially more virulent virus strains (priority on hepatitis C infections) Proportion of HCV re infections 6. To determine and describe the proportion of co infections (HIV/HBV/HCV/HDV) 7. To determine the proportion of HCV re infections (especially among key risk groups with high incidence e.g. PWIDs)
Surveillance of hepatitis B and C: data completeness in 2013 Age Gender StageHEP Imported Outcome Testing location Health care worker Transmission Country of nationality Country of birth Probable country of infection Hepatitis B Hepatitis C Sex worker Complications HIV status Genotype 0 20 40 60 80 100 Data completeness (%)
Hepatitis B data: reporting countries and case definitions 28 countries provided hepatitis B data in 2013 Six countries could only provide data on acute cases Case definitions varied: 18 countries used the EU 2012 case definition Six countries used the EU 2008/EU 2002 case definitions Four countries used national case definitions 24 countries were able to classify cases as acute or chronic according to the EU 2012 case definition
Rate of reported acute hepatitis B cases in 2013* *Data for UK exclude Scotland
Rate of reported chronic hepatitis B cases in 2013* *Data for UK excludes Scotland
Hepatitis B data: reported cases, rates and stage of infection In 2013, 19 101 cases* (4.4 cases per 100 000) Acute: 2 896 (15%) Chronic: 13 629 (71%) Unknown: 2 138 (11%) Variation in numbers and rates between countries Acute infections: from 0.1/100 000 in France and Portugal to 4.3/100 000 in Latvia Chronic infections: from 0.1/100 000 in Romania to 15.5 in Sweden *438 cases (2.3%) could not be classified by disease status due to incompatible format of the data provided
Rate of acute and chronic hepatitis B cases in EU/EEA countries, 2006-2013 Logarithmic scale 10,0 Rate per 100 000 1,0 Acute Chronic 0,1 2006 2007 2008 2009 2010 2011 2012 2013 Source: country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).
Hepatitis B by age and disease status: rate of reported cases per 100 000, 2013 30 25 35% Rate per 100 000 20 15 10 5 15% Acute Chronic M:F = 1.5:1 0 <5 5 14 15 19 20 24 25 34 35 44 45 54 55 64 65 Age group (years) Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).
Reported transmission category for acute and chronic hepatitis B cases, 2013 Heterosexual transmission Transmission category Nosocomial (includes hospital, nursing home, etc.) Injecting drug use Men who have sex with men (MSM) Non occupational injuries (needle stick, bites, tattoos, piercings) Other Sexual transmission (not specified) Household Blood and blood products Migration variables poorly reported but 50% of cases with complete information were classified as imported Acute Chronic Mother to child transmission Needle stick and other occupational exposure Haemodialysis Organ and tissues 0 10 20 30 40 50 Proportion of cases (%) Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).
Hepatitis C data: reporting countries and case definitions 26 countries provided hepatitis C data in 2013 Four countries could only provide data on acute cases Case definitions varied: 14 countries used the revised EU case definition Seven countries used the EU 2008 case definition Five countries used national case definitions 17 countries were able to classify cases as acute or chronic According to the EU 2012 case definition
Hepatitis C data: reported cases, rates and stage of infection In 2013, 31 513 hepatitis C cases* were notified representing a rate of 9.6 cases per 100 000: 569 (2%) Acute 4 776 (15%) Chronic 23 230 (74%) Unknown** Variation in overall numbers and rates between countries Acute infections: rates from <0.1/100 000 in Portugal and Greece to 2.6/100 000 in Latvia Chronic infections: rates from 0.1/100 000 in Romania to 60.1/100 000 in Latvia *2 938 cases (9%) could not be classified by disease status due to incompatible format of the data provided **As acute hepatitis C is difficult to diagnose clinically or serologically, most unknown cases are likely to be chronic infections.
Rate of all reported hepatitis C cases across EU/EEA countries, 2006-2013 12 10 8 Rate per 100 000 6 4 2 0 2006 2007 2008 2009 2010 2011 2012 2013 Source: country reports; Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom.
Rate of reported hepatitis C cases in 2013 (including acute, chronic and unknown stage)* *Countries included if their surveillance systems captured data on both acute and chronic cases..
Rate of reported hepatitis C cases per 100 000 by age and gender, 2013 (includes acute, chronic and unknown stage) 35 30 54% Rate per 100 000 25 20 15 10 9% Male Female M:F = 1.9:1 5 0 <5 5 14 15 19 20 24 25 34 35 44 45 54 55 64 65 Age group (years) Source: Country reports: Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom.
Reported transmission category for acute and chronic hepatitis C cases in 2013 Injecting drug use Transmission category Blood and blood products Sexual transmission (not specified) Heterosexual transmission Other Nosocomial (includes hospital, nursing home, etc.) Non occupational injuries (needle stick, bites, tattoos, piercings) Needle stick and other occupational exposure Mother to child transmission 9% of cases with complete information were classified as imported Acute Chronic Haemodialysis Household Men who have sex with men (MSM) Organ and tissues 0 20 40 60 80 100 Proportion of cases (%) Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom.
Summary of key findings High numbers of newly diagnosed hepatitis B and C cases notified across Europe Hepatitis C rate is more than twice the hepatitis B rate Chronic cases dominate across both diseases Marked variation between countries Hepatitis B: a decrease in acute cases a rise in newly reported chronic infections Hepatitis C: strong geographical trend affected by different testing practices across Europe Transmission routes for hepatitis B differ from hepatitis C, and for hepatitis B these routes vary by disease status Imported cases are significant, especially for hepatitis B
Key limitations of the data Different case definitions used by countries Some countries still only report acute hepatitis cases Difficulties with ascertaining stage of diseases according to case definition High proportion of cases coded as unknown particularly for Hepatitis C Some countries use their own criteria Data completeness low for certain variables: Genotype, complications, country of nationality, HCV status (for HBV cases), HBV status (for HCV cases), HIV status, sex worker, healthcare worker Under-reporting major issue reported by some countries Due to the largely asymptomatic nature of hepatitis infections, data are strongly related to local testing practices
Acknowledgements Thank you to the following groups and individuals: The European Hepatitis B and C Network and Coordination Committee. EU/EEA country hepatitis and surveillance contact points. Surveillance colleagues at ECDC: Catalin Albu, Julien Beauté, Denis Coulombier, Catia Cunha, Gaetan Guyodo, Frantiska Hruba, Valentina Lazdina, Klaus Weist, Phillip Zucs. Colleagues in the programme on HIV/AIDS, STI and Viral Hepatitis B and C: Andrew Amato-Gauci, Caroline Daamen, Gianfranco Spiteri.
A time machine to prevent HAV outbreaks in the EU
Hepatitis A global endemicity levels and implication for vaccination strategy WHO estimates the level of endemicity based on the anti-hav seroprevalence. WHO recommends no vaccination in high endemicity areas, universal vaccination in intermediate endemicity areas and at-risk group vaccination in low and very low endemicity areas Source: KH Jacobsen et al. Vaccine 2010 WHO position paper on hepatitis A vaccines June 2012
Hepatitis A global endemicity levels and implication for vaccination strategy Source: KH Jacobsen et al. Vaccine 2010 WHO position paper on hepatitis A vaccines June 2012
Novel risk factors for HAV infection - 2 nd generation migrants visiting country of origin - New parents of adoptees from endemic countries - Foodborne transmission
2013/2014 HAV infection outbreaks HAV outbreak Declared Genotype Associated cases Vehicle of infection Nordic Countries March 2013 IB 77 confirmed 40 probable Frozen strawberries EU Ex Egypt April 2013 IB 21 confirmed 86 probable Fresh strawberries U.S.A May 2013 IB 167 confirmed Pomegranates Multinational EU May 2013 IA 270 confirmed 1200 probable Frozen berries
Systematic review: PRISMA flowchart Included Eligibility Screening Identification Records identified through Additional records identified database searching through other sources n =4465 n =81 Records after duplicates removed n =4276 Records screened Records excluded n =432 n =3844 Full text articles excluded n = 110 Full text articles assessed Non HAV: 3 for eligibility Non prevalence: 68 n =432 Non general population: 19 Not found/other: 20 Eligible studies for data extraction Not abstractable data n =322 n =94 Included studies n = 228
Definitions Seroprevalence levels * Risk of infection among adults >30 years * World Health Organization. WHO position paper on hepatitis A vaccine June 2012. WER 2012; 28 29: 261 276. Available at: http://www.who.int/wer/2012/wer8728_29.pdf?ua=1
Temporal evolution of anti-hav seroprevalence by country, 1975-2013 Case-study Portugal Summary of anti-hav seroprevalence in Portugal, by age group, 1983-2012 Quality score: 0 (non randomized sample and n<500); 1 (randomized sample or n 500); 2 (randomized sample and n 500)
Temporal evolution of hepatitis A seroprevalence by country Case-study Germany Summary of seroprevalence in Germany, by age and time period Quality score: 0 (non randomized sample and n<500); 1 (randomized sample or n 500); 2 (randomized sample and n 500)
Hepatitis A seroprevalence profile in the EU/EEA, 2000-2013 HAV seroprevalence profiles No data Very low Low Intermediate Seroprevalence classification Assessment criteria: HAV seroprevalence Very low <50% by age 30 years Low 50% by age 30 years, with <50% by age 15 Seroprevalence classification Intermediate High Assessment criteria: HAV seroprevalence 50% by age 15 years, with <90% by age 10 years 90% by age 15 years
Hepatitis A susceptibility in adults in the EU/EEA, 2000-2013 HAV susceptibility profiles No data Low Moderate High Very high Susceptibility classification Very high High Assessment criteria: HAV susceptibility >70% at 30 years; and >50% at 50 years 50 70% at 30 years; and 30 50% at 50 years Susceptibility classification Moderate Low Assessment criteria: 30 50% at 30 years; and <30% at 50 years <30% at 30 and 50 years
Human Development Index 2013
Temporal evolution of susceptibility to hepatitis A in the EU/EEA, 1975-2013
Acknowledgement ECDC Sandro Bonfigli Paloma Carrillo Pierluigi Lopalco Ettore Severi Johanna Takkinen Emma Bystrom ECDC Library Ana-Belen Escriva Irene Munoz Guajardo EPIET fellow Michael Edelstein All ECDC colleagues that helped with translation of articles Member States focal points for food- and water-borne and for vaccine preventable diseases Expert panel members Roman Chilbek, Czech Republic Angela Dominguez, Spain Caterina Rizzo, Italy Manolis Galanakis, Greece Denisa Janta, Romania Mira Kojouharova, Bulgaria Jördis Ott, Germany Noel Nelson, United States Daniel Shouval, Israel Ingrid Uhnoo, Sweden Vytauthas Usonis, Lithuania
Grazie per l attenzione