Hepatitis B virus:

1
Hepatitis B virus Burden of disease in South
Africa Vaccine strategies
2
Sub-saharan Africa
High endemnicity
gt75 adults have evidence of exposure 10
carriage
Mode of transmission
High Close personal contact All Childhood
Low parenteral high risk groups adulthood
Adult levels of exposure by 5 years
High HBsAg carriage rate
3
South Africa
Indiginous people carriage as for the rest of
SSA
Prevalence studies
Adult black men Mine worker study
4
Children
Age of acquisition
Vertical transmission is uncommon
Acquisition occurs mainly between 1-5
years Siblings, houshold contacts
5
Preimmunisation epidemiology of hepatitis B
infection in South African children. Vadas et
al. J Med Virol (1999) 58 p111-115 Eastern
Cape 2 299 children 0-6 years
6
(No Transcript)
7
Carriage rates in females is lower Mean ratio in
various studies 2,61
Other races
White 0.23 0.18 Coloured 1.78 0.88 Asian 0.
3 0.23
Overall burden of HBV infection
Estimation of the total size of the HIV and
hepatitis B epidemics in South Africa B.D.
Schoub SAMJ (1992) 81 p 63-66
Total number of carriers 1,4 million 88 rural
black population
8
HBV associated disease
10th leading cause of death world wide
Acute hepatitis
Chronic hepatitis
20-25 carriers disease hepatocellular
carcinoma chronic active hepatitis and
cirrhosis glomerular nephritis
E antigen positivity
9
Hepatocellular carcinoma
Carriers 100 fold
(HBV not the only cause)
94.2 HBV infection 56.5 HBsAg positive
MF 4-51
20 of tumours in black men
(65 in Mozambique)
Commonest in rural black men who live their
entire lives in a rural environment
Caucasian men uncommon
10
Chronic Active hepatitis and cirrhosis
Little published information on this in SA
SAMJ 1981, Asvat and Hodkinson HBV accounts for
10 CAH in black patients inJohannesburg Ann
Trop Paed 1984, Mackenjee and Coovadia HBV
infection commonest cause of CLD in
children 60 cirrhosis 85 CAH
Co-infection with HIV known to increase the
severity of chronic HBV
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HBV vaccines
Surface antigen protein
226 amino-acid small S antigen
2 vaccines available since early 1980s Serum
derived Recombinant protein
3 doses seroconversion in 95 adult vaccine
recipients
Antibody levels wane, but boosters are not
necessary
Individuals at risk of HBV infection
12
Childhood immunisation
X
HBV reservoir
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HBsAg carriage lt15 years 9,8 1984 0.7 1999
Incidence of HCC in children 6-14
years 1981-1986 0.7 per 100 000 1990-1994 0.36
per 100 000
Fulminant hepatitis in neonates
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In 1992, the World Health Assembly recommended
that HB vaccination should be integrated into
national immunisation programs in all countries
with a hepatitis B carrier prevalence (HBsAg) of
8 or greater by 1995 and in all countries by
1997.
By 2001 130 of 216 countires had introduced it
expense
South Africa vaccination of all infants
introduced in 1995
6, 10 and 14 weeks at the same time as DPT, Hib
and polio
Vertical transmission uncommon Peak acquisition
1-5 years
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1. HBV vaccine coverage of infants
South Africa Demographic and Health survey
Preliminary report (2001)
85,4 1st dose 78.2 2nd dose 62.0 3rd dose
2. Vaccine efficacy
The first 5 years of universal HBV vaccination in
South Africa Khomotso et al. Vaccine (2001) 19
p3919-3926
Northern Province
Cross sectional analysis, monitored 598 vaccine
recipients
HBsAb immunity (gt10 mIU) HBsAg HBV
viraemia HBcAb exposure to HBV
16
Seroprotection in vaccine recipients 86.8 (gt
10 mIU)
Antibody levels waned with time
Age (months) year of immunisation gt10
mIU 8-12 1998-1999 95.6 13-24 1997-1998 87.1
25-36 1996-1997 88.8 37-48 1995-1996 69.6
None (0/598) HBsAg positive
(Historical carriage 7-10 )
3. Reduction in HBV associated disease in South
Africa..
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Impact of HBV vaccination on the incidence of
HBV-associated Membranous Nephropathy Bhimma et
al. Arch Paed Adolesc Med 2003 157 1025-1030
Incidence of HBV-associated MN in children 0-14
years in KZN
age group Year 0-4 5-9 1984-1985 2
7 1986-1987 2 6 1988-1989 3 7
1990-1991 3 9 1992-1993 4 7
1994-1995 1 10 1996-1997 8 16
1998-1999 0 7 2000-2001 0 2
Total 23 71
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Are current vaccines good enough?
No perfect vaccine Non responders 95 adult
vaccinees develop detectable levels of
antibodies Lower in children (86.8)
Lack HLA combination capable of presenting
peptides derived from the vaccine
Newer vaccines pre S2 and pre S1 regions
included Adjiuvants DNA vaccines
Expensive Does not substantially improve response
19
Waning response
Levels of antibody decline over years
Duration of protection is unknown
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Escape mutants
Neutralising antibodies bind
Mutations in this region may alter antigenicity
Most famous mutation Gly arg at amino acid
145
Isolated from an infant of HBV positive mother
who became infected despite the receipt of HBV
vaccine
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Conclusion
universal infant immunisation has been highly
effective at reducing infection in hyper endemic
areas
sAg carriage in children
Samoa 7.5 0 Gambia 10.3 0.6 Italy 3.4 0.9 Sa
udi Arabia 6.7 0.3
Reduction in HBV diseases acute fulminant
hepatitis childhood HCC membranous nephropathy
Major challenge is to expand the program to the
poorest countries