OVERVIEW of HBV:

INFECTIONSROUTE of TRANSMISSIONVACCINATION

byMERAL A ÇIBLAK

SELİM BADUR

İstanbul School of Medicine, İstanbul University,TR

1

TURKEY

POPULATION ~72 millionUrban Population 59,01 %Rural Population 40,99 %

Ages 0-14 29.7 %Ages 20-24 9.9 %Ages 25-45 29.3 %OVER 45 31.1%

2

TurkeyA Country of “Intermediate Endemicity”

for HBV Infections

3-8 % of population is (+) for HBsAg 1/3 of the population is (+) forAnti-HBs

Characteristics of HBV Infections inTurkey

HDV co/superinfectionPrecore MutantsGenotype D (>99 %)

3

Number of Hepatitis B Cases

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

1990 1992 1994 1996 1998 2000 2002 2004

Data from MoH, Turkey

4

AETIOLOGICAL CLASSIFICATION OF HOSPITALIZEDACUTE VIRAL HEPATITIS CASES IN TURKEY (ADULTS)

CITY STUDYGROUP

N HBV(%)

HAV(%)

HCVHCVHCV(%)(%)(%)

HEVHEVHEV(%)(%)(%)

ANKARA Kurt, 1995 1022 76.0 17.1 6.86.86.8 NANANA

BURSA Mıstık, 1998 135 55.2 42.3 2.22.22.2 NANANA

DİYARB. Geyik, 1998 148 61.1 22.9 2.02.02.0 14.814.814.8İSTANBUL Özgüneş, 1998 720 68 26 1.41.41.4 NANANA

İZMİR Okan, 2000 518 61.3 28.1 2.02.02.0 NANANATOTAL 4471 60.4 27.5 5.55.55.5 0.50.50.5

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AETIOLOGICAL CLASSIFICATION OF HOSPITALIZED ACUTEVIRAL HEPATITIS CASES IN TURKEY (CHILDREN )

CITY STUDYGROUP

N HBV(%)

HAV(%)

HCVHCVHCV(%)(%)(%)

ADANA Şahin, 1998 338 35.8 38.6 0.50.50.5

ANKARA Uysal, 1998 364 7.7 87.9 0.30.30.3

İSTANBUL Sıdal, 1990 160 24.0 66.0 10.010.010.0

TOTAL 912 22.4 63.1 2.12.12.1

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AETIOLOGICAL CLASSIFICATION OF CHRONIC HEPATITIS IN İSTANBUL (%)

YEAR HBV HCV HBVHBVHBV+++HDVHDVHDV

HBVHBVHBV+++HCVHCVHCV

OTOIOTOIOTOIMMM---

CRYPTOCRYPTOCRYPTO--- DRUG DRUG DRUG

1991-1994n=296

56 23 6.86.86.8 333 1.51.51.5 0.70.70.7 0.7 0.7 0.7

1994-1997n=527

46.5 35 4.54.54.5 333 1.51.51.5 0.20.20.2 0.20.20.2

1998-2001n=1104

56.9 38.1 2.92.92.9 0.70.70.7 1.91.91.9 000 000

Ökten A, 2005, İstanbul

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AETIOLOICAL CLASSIFICATION of CIRRHOSIS IN İSTANBUL (%)

YEAR HBV HCV HDVHDVHDV HBV+ HBV+ HBV+ HCVHCVHCV

ALCOALCOALCO CRYPCRYPCRYP MISCMISCMISC

1990-1993n=436

56.5 25.2 14.614.614.6 3.73.73.7 12.612.612.6 22.722.722.7 888

1994-1997n=393

42.6 34.5 15.715.715.7 1.21.21.2 10.910.910.9 16.816.816.8 12.812.812.8

1998-2001n=573

45.9 31.3 19.619.619.6 3.23.23.2 12.412.412.4 16.416.416.4 12.112.112.1

Ökten A, İstanbul, 2005

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COMPARISON of AETIOLOGICAL CLASSIFICATION OF HEPATOCELLULAR CARCINOMA

Low Risk Countries(America-Europe)

(%)

Turkey(%)

High Risk Countries

(Africa-Asia)(%)

HBV <15 56 60

HCV 60 21 <10

ALCOHOL <15 16 11-30

CRYP. - 13 -

Ökten A et al., İstanbul, 2005

7/34

8.8/44.4

8.9/41.2

4.5/17

6.7/27.5

6.9/50

4.6/21.3

4.9/34

7.9/28

3.7/21.6

4.4/16

3.5/19.8

Regional Differences in HBsAg/Anti-HBs Positivity (%)

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WHY REGIONAL DIFFERENCES?

Poor socio-economic status

Traditional life-styles

Infrastructure

Lack of access to “sufficient” health services

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Age Dis tribution of HBV Infections ,Turkey

0

10

20

30

40

50

60

Age groups

Hbs Ag 1.4 1.7 4.3 9.9 10.6 8.6 7.1 8.1 2.8 6.5 10.3 0 2.1

anti-HBs 6.9 3.4 19 25.3 14 21.8 34.7 35.5 31.3 21.7 48.7 37.5 29.2

0--5 6--10 11--15 16--20 21--25 26--30 31--35 36--40 41--45 46--50 51--55 55--60 60 +

Tansuğ, 1999, İzmirEmiroğlu, 2000, Şırnak

Şahin, 1998, AdanaYousefi, 1999, AnkaraPahsa, 1999, İstanbul

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Anti-HBc Positivity in Various Age Groups

Age Group Number Anti-HBc Positivity (%)

0-1 57 1.8

2-5 132 0.8

6-10 178 1.7

11-14 147 6.8

15-19 203 11.8

Total Number 717 5.4

Oktun M et al., 2001, Edirne

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HBV Seropositivity in Children at a Children’sShelter

Age Group Number HBV Seropositivity (%)

0-6 32 25

7-12 45 63

13-22 40 60

Mıkla Ş et al., 1995, İstanbul

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Age Distribution of HBV Cases,Turkey

(1997-2005)

0

1000

2000

3000

4000

5000

6000

7000

8000

0 1-4 5-9 10-14 15-44 45-64 65+ Total

1997 1998 1999 2000 2001 2002 2003 2004 2005

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Routes of Transmission for Acute HBV Cases

Probable Route USA(%)

FR(%)

TR1

(%)

TR2

(%)

Unknown 26 31.5 44.4 38.1

Sexual 55 34 9.2 1.03

IVDU 12 25 0.2 -

Close Contact 4 4 7.5 8.2

Surgical Intervention 2 2 22.1 38.1

Others 1 2.5 15.2 14.41 Mıstık, 19972 Birengel, 2003

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HBsAg Positivity in Pregnant Woman in VariousRegions, Turkey, 1990s

City Study Group N HBsAg (+)%

Kayseri Abacı IM et al.,1995 400 3.8

İstanbul Çepni İ et al.,1996 4078 4.4

İzmir Erensoy S et.al, 1996 760 4.2 (HBeAg %15)

Denizli Kaleli İ et al.,1997 312 7.7 (HBeAg % 8.3)

Sivas Poyraz Ö et al., 1999 95 6.3 ( HBeAg % 1.1)

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HBsAg Positivity in Pregnant Woman in VariousRegions, Turkey, 2000s

City Study Group N HBsAg (+)%

Ankara Biri et al., 2001 451 7

Diyarbakır Turhanoğlu M et al., 2001 260 12.3(HBeAg % 4.6)

İstanbul Karaca Ç et al., 2003 460 4.7

Şanlıurfa Harma M et al., 2003 136 7.3

Afyon Yılmazer M et al.,2004 244 2.9

Mersin Börekçi G et al., 2004 114 3.5

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VACCINATION

EPI, 1991WORLD HEALTH ASSEMBLY, 1992WHO, 1994

THE GOAL?

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Still a lot of high endemicregions to cover

168 countries in theworld have a universalhepatitis B programme

by the end of 2005

Fig 1. Global status of countries using HepB vaccine in theirnational immunization system, May 2002

Yes No

June 2002

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which theremay not yet be full agreement.

Routine HepB implementation status

MoH Recommendations for HBV Immunization (1998)

1. DOSE At birth

2. DOSE 3th month

1. DOSE 3rd month

1. DOSE Anytime

2. DOSE 1 mo.after the 1st 3. DOSE 5 mo. after the 2nd

3. Alternative( For infants >3 month)

2. DOSE 4th month2. Alternative(Infants born outsideHealth facilities)

3. DOSE 9th month

3. DOSE 9th month

1. Alternative( routine

immunisation)

MoH Recommendations for HBV Immunization (2003)

1. DOSE At birth

2. DOSE 3th month

1. DOSE 3rd month

1. DOSE Anytime

2. DOSE 1 mo.after the 1st 3. DOSE 5 mo. after the 2nd

3. Alternative( For infants >3 month)

2. DOSE 4th month2. Alternative(Infants born outsideHealth facilities)

3. DOSE 9th month

3. DOSE 9th month

1. Alternative( routine

immunisation)

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Hep B Immunization PolicyWHO European Region, 2004

Universal infant

Universal newborn

Universal adolescentNo universal HepBimmunization

23

MoH Recommendations for HBVImmunization (2006)

1st Dose At birth2nd Dose At the end of 2nd month3rd Dose At the end of 9th month

andAll Three Doses For 8th Graders (15 years of age)

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7267

64

7773

66

8380

72

7876

72

7874

68

88 87

77

0

10

20

30

40

50

60

70

80

90

100

Cov

erag

e ra

te (%

)

1999 2000 2001 2002 2003 2004Ye ar

Hepatitis B Vaccination Coverage, 0 Age Group,

Turkey, 1999-2004

HBV-1HBV-2HBV-3

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0 Age Group Vaccination Rates 2001-2005, Turkey

( MoH Vaccination)

82 83

72

84

38

77 7872

82

37

76

68 68

75

37

7985

7781

41

8884

8084

47

%30

%40

%50

%60

%70

%80

%90

%100

BCG DPT-3 HBV-3 Measels TT-2+2001 2002 2003 2004 2005

26

Regional Rates for 3-dose-HBV Vaccination

% Coverage<50%50-79%80-89%

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FUTURE DIRECTION