Epidemiology of Hepatitis A and E Epidemiology of Hepatitis A and E R. C. Coppola 21th VHPB meeting Prevention of viral hepatitis in Italy: Prevention.

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Epidemiology of Hepatitis A and E Epidemiology of Hepatitis A and E R. C. Coppola 21th VHPB meeting Prevention of viral hepatitis in Italy: Prevention of viral hepatitis in Italy: lessons learnt and the way forward 21th VHPB meeting Prevention of viral hepatitis in Italy: Prevention of viral hepatitis in Italy: lessons learnt and the way forward Catania, 7-8 November 2002

CDC, 1999

Epidemiology of HAV infection Reported cases of HAV underestimate the true incidence of the infection because of: subclinical infections, very common subclinical infections, very common in young people in young people underreporting underreporting

YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 YearYear Reported Acute Cases Reported Acute Cases Estimated Acute Cases Estimated Acute Cases Estimated TotalNew InfectionsEstimated TotalNew Infections ,08729, ,000124, ,000234, ,80225, ,000110, ,000223, ,40423, ,000100, ,000228, ,53421,534 92,00092, ,000221, ,03822,038 94,00094, ,000232, ,21123,211 99,00099, ,000228, ,42923, ,000100, ,000239, ,28025, ,000108, ,000255, ,50628, ,000122, ,000305, ,82235, ,000153, ,000380, ,52231, ,000135, ,000373, ,21924, ,000104, ,000288, ,11223,112 99,00099, ,000274, ,23824, ,000104, ,000284, ,79626, ,000115, ,000333, ,58231, ,000135, ,000356, ,03231, ,000133, ,000335, ,02130, ,000128, ,000341, ,29923,299 99,00099, ,000243, ,04717,047 73,00073, ,000181, ,39713,397 57,00057, ,000143, ,61610,616 45,00045,000 93,00093,000 CDC,Viral Hepatitis Surveillance

Incubation period:Average 30 days Range days Jaundice by 14 yrs, 70%-80% Complications:Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae:None Hepatitis A: Clinical Features

Distribution of acute hepatitis in 1998 ISS, SEIEVA 2000

Non-ABCDE Source: CDC Sentinel Counties Study 55% 32% 12% 1% Hepatitis A Hepatitis B Hepatitis C Acute Viral Hepatitis by type United States,

Distribution of notified cases of viral hepatitis ISS, SEIEVA 2002

ISS, SEIEVA 2001 Incidence of hepatitis A in Italy Rates x

Hepatitis A :incidence rates n° cases/ ITALY 3/ ISS, SEIEVA 2001

Area and sex specific incidence of hepatitis A (2001) ISS, SEIEVA 2001 Rates x

Endemicity Disease Rate Peak Age of Infection Transmission Patterns HighLow to High Early childhood Person to person; outbreaks uncommon Moderate High Late childhood/ young adults Person to person; food and waterborne outbreaks Low Young adults Person to person; food and waterborne outbreaks Very low AdultsTravelers; outbreaks uncommon

Epidemiology of Hepatitis A from high to intermediate endemicity As a consequence of better sanitation and hygienic conditions decline of HAV infection in children of Western countries increasing proportion of adults is becoming susceptible to the virus

Hepatitis A Shifting epidemiological pattern HIGHHIGH INTERMEDIATELOWINTERMEDIATELOW

Age specific incidence of hepatitis A in Italy Rates x ISS, SEIEVA 2002

Age-specific incidence of hepatitis A in South and islands Rates x ISS SEIEVA, 2002

Age-specific incidence of hepatitis A in North Center Italy Rates x ISS SEIEVA, 2002

Age and sex specific incidence 0-14 years ISS, SEIEVA 2001 Rates x

>25 years (2001) years (2001) Age and sex specific incidence of Hepatitis A ISS, SEIEVA 2001

Epidemiology of Hepatitis A in Italy Shifting epidemiological pattern: high intermediate-low

Prevalence of anti-HAV in the general population of Cagliari (Sardinia) in 1988 (no.299) and in 1995 (no. 714) Coppola,1998 =p<0.01 % 96

Anti-HAV prevalence in general population in 1988 and 1995 (Cagliari) Coppola,1998 Classi di età =p<0.01 %

Prevalence of anti-HAV among Italian recruits (range years) Prevalence of anti-HAV among Italian recruits (range years)

Anti-HAV prevalence in recruits in Cagliari (2000) No. 218No.279 No.22 (Coppola,submitted)

Anti-HAV prevalence in Health Care Workers (1998) and general population (1995) in Cagliari

Anti-HAV prevalence in students of Cagliari Masia.1996 Age (years) =p<0.01

Risk factors for hepatitis A SEIEVA 2001

Geographic Distribution of Hepatitis E Outbreaks or Confirmed Infection in >25% of Sporadic Non- ABC Hepatitis CDC

Distribution of notified cases of viral hepatitis ISS, SEIEVA 2002

Prevalence of antibody to hepatitis E virus among normal human populations Prevalence of antibody to hepatitis E virus among normal human populations Country% Anti-HEV positivesreference Endemic country India4 Khuroo MS, 1994 Bangladesh7,3 Sheikh A, 2002 Brasile2,4 Santos DC, 2002 Non-endemic country Italy 0,6 Coppola R.C., ,7-0,8 Pavia M, ,6 Stroffolini T, ,6 Gessoni G, ,74-1,94 Zanetti A, 1994 Germany2,1 Ritter A,1994 France0,9 Ritter A,1994 Spain2,8 Mateos M.L Grecia2,2 Psichogiou M.,1996

Anti-HEV in the general population of Cagliari in 1988 (691 subjects) and 1995 (751 subjects) Syn=Synthetic antigens (ORF 2,3) (Immunodiagnostics, Ca,USA) (Coppola,1997) % Age classes (years)

Anti-HEV in the general population of Cagliari in 1988 (691) and 1995 (751) Synthetic and recombinants Antigens from ORF 1 (Alfa Scientific, San Diego, Ca) Age classes (years) (Coppola, personal data) %

Anti-HEV in the general population of Cagliari (2 different assays) Syn+Rec= Synthetic and recombinants Antigens from ORF 1 (Alfa Scientific, San Diego, Ca) Syn= Synthetic antigens (ORF 2,3) (Immunodiagnostics, Ca,USA) Age classes (years)

Anti-HEV in the general population of Cagliari Synthetic antigens from ORF2 and ORF3 (BioChem, ImmunoSystem; Bologna, Italy) 1988 (no. Subjects) (214) (229)(237) 1995 (230) (200)(321) 2000 (193) (148)(120) Age classes (years) (Coppola, personal data) %

HEV epidemiology in non endemic areas  The diagnostic tool is crucial for the real interpretation of HEV epidemiology in non- endemic areas