3. HISTORY
outbreak of jaundice 2-8
mths after smallpox
vaccine
1885
larger outbreak of jaundice
after yellow fever vaccine
1937
surface protein of HBV
discovered by BLUMBERG
was called Australian Ag
1965
Dane Cameron and Briggs
visualized the HBV virion-
Dane particle
1970
HBsAg testing of donated
blood begins
1971
HBsAg testing begins in
India
1975
Indirect Tests for HBV
anti- HBc and ALT
implemented
1987
7. STRUCTURE
• Partially double stranded DNAvirus.
• Composed of a 27nm nucleocapsid core (HBcAg)
• Surrounded by an outer lipoprotein coat also called envelope, containing the
surface antigen (HBsAg)
• Contain DNA dependent polymerase which repair the gap in DNA template and
have reverse transcriptaseactivity.
8.
9. MORPHOLOGY OF VIRUS
• Ultra structure shows three distinct morphology :
• Small, spherical, noninfectious particles, 17 to 25 nm in diameter.
• Tubular, filamentous form of various length.
• Complex, spherical, double shelled particle of 42 nm which is the Hepatitis B virion.
10.
11. GENOME
• CircularDNA :
Partially double stranded
Long strand: 3020–3320nucleotides
Short strand: 1700–2800nucleotides
• Oneendof the long strand islinked to the viral DNA polymerase
• 4ORFs
• 7Proteins
12.
13.
14.
15. EPIDEMIOLOGY
Ubiquitous virus with global distribution.
More than one third of the world’s population has been infected.
About 5% of the world population are chronic carrier
In endemic area of Africa and Asia infant and children are more affected
than adult
while in low endemic area it’s reverse
16.
17. Prevalence of chronic HBV infection
Early in life Adolescent /young
adult
Adults, welldefined
risk groups
Asia, Middle East,
Pacific islands,
Africa 6/29/2014
India, Japan
Sunil Pandey- Medical Microbiology
US, Canada
29. LABORATORY DIAGNOSIS
1. SEROLOGICAL METHODS
• ELISA
• Rapid test
2. MOLECULAR METHODS (NAT/PCR)
• Detection in window period
• Fulminant hepatitis
• HBsAg –ve
• Response
30. SEROLOGICAL METHODS
Three clinically useful antigen-antibody systems :
• Hepatitis surface antigen(HBsAg) and antibody to it (anti-HBsAg)
• Antibody (anti-HBc IgM and anti-HBc IgG) to core antigen (HBcAg)
• Hepatitis e antigen (HBeAg) and antibody to it (anti-HBeAg)
31. 31
HBsAg- anti-HBs system:
HBsAg appears 1-2 weeks (late up to 11-12 weeks) after exposure,
persists for 1-6 weeks( even 5 months) in acute hepatitis B.
In chronic patients or carrier, HBsAg persist many years
HBsAg is the marker of infectivity
Found in blood and secretions: saliva, urine, semen, tears, sweat and breast milk
Anti-HBs Ab appear after HBsAg disappear
Anti-HBs is protective antibody, can persist for many years
32. HBcAg—anti-HBc system
HBcAg can be found in the nuclei of liver cells, no free HBcAg in serum
HBcAg is the marker of replication of HBV
Anti-HBc IgM is a marker of acute infection and acute attack of chronic infection .
Anti-HBc IgG is the marker of past infection, high titer means low level replication .
32
33. HBeAg—anti-HBe system
33
HBeAg is a soluble antigen
HBeAg is a reliable indicator of active replication of HBV
Anti-HBe is a marker of reduced infectivity.
38. Reduction in window period
SEROLOGICAL METHODS :
3RD GEN ELISA : 50 Days
4TH GEN ELISA: 30 Days
MOLECULAR METHODS :
NAT MP: 30 Days
NAT ID : 25 Days
40. HEPATITIS B VACCINE
• Hepatitis B vaccines available since early 1980’s.
• 1982 (plasma), 1986 (recombinant)
• Third generation vaccines( mammalian cell recombinant vaccines)
• First recommended for high risk groups only
• In 1991, the Global Advisory Group of EPI (Expanded Program on Immunization)
integrating the hepatitis B vaccination into national immunization programs
• Monovalent or in combination with other vaccines
• High immunogenicity (three dose, 95-99%) , Long-term protection
41. PRE EXPOSURE IMMUNIZATION
1. Infants (Universal immunization)
2. Infants and adolescents not vaccinated previously (catch-up vaccination)
3. Person with occupational risk
4. Haemodialysis patients
5. Recipients of blood and blood products
6. Susceptible drug abusers.
7. Sexually active men or women
8. Jail inmates
9. Household contacts and partners of HBV carriers
10. Population with a high incidence of disease
11. Travellers to area of high HBV endemicity
12. Transplant candidates.
42. PREVENTION & IMMUNOPROPHYLAXIS
Hepatitis B immunoglobulin (HBIG) :
• Effective for passive immunization if given prophylactically within hours
of infection.
• Hepatitis vaccine should always be given with HBIG.
• Indicated for sexual contacts , babies born to HBsAg+ mothers and parenteral
exposure (needle stick).
• 0.06ml/Kg HBIG plus first dose of Hepatitis B Vaccine and continue vaccine course.
44. MANAGEMENT–ACUTEHEPATITISB
• In healthy adults who present with clinically apparent acute hepatitis,
recovery occurs in ~ 99%
• Antiviral therapy is not required.
• In rare instances of severe acute hepatitis B, institution of antiviral therapy
with a nucleoside analogue (entecavir or tenofovir)
45. MANAGEMENT OF CHB
The currently approved treatment options include :
• Immunomodulatory Therapies : Conventional interferon alpha( IFNα), Pegylated
Interferon α
• Nucleoside Analogs (NA’s): Lamivudine, Entecavir, Telbivudine and Emtricitabine
• Nucleotide Analogs : Adefovir and Tenofovir
CONTINUING THE SERIES OF LECTURES ON TRANSFUSION TRANSMITTED INFECTIONS . TODAY I WILL BE COVERING HEPATITIS B VIRUS
I WILL BE COVERING THE TOPIC UNDER THE FOLLOWING HEADINGS
Vaccines were then prepared from human lymph SO IT WAS POSTULATED THAT THE LYMPH CARRIED HEPATITIS CAUSING PATHOGENS
1.DR BARUCH BLUMBERG DISCOVERED ACCIDENTLY THE HBSAG while searching for a polymorphic serum protein in Australian Aborigine
2.Initially called the “red antigen,” it was subsequently termed the Australia antigen (Au) and, later, the hepatitis B surface antigen (HBsAg).
3. the RED precipitin line formed between the aboriginal serum and that of a multiple transfused patient with hemophilia .
As we already know that all the other hepatitis causing viruses are RNA viruses excpt Hep B
Electron microscopic picture showing the 3 morphological forms of the virus
Small, spherical, noninfectious particles, 17 to 25nm in diameter.
Tubular, filamentous form Of various length.
Complex, spherical, double shelled particle of 42nm
eight major genotypes (A–H) four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes
Genotype c carries more risk of HCC.
Globally, chronic Hepatitis B affects approximately 257 million people and contributes to an estimated 700,000 deaths worldwide every year.
The risk of hep b transmission has always been the high all through BECAUSE OF ITS ABILITY TO SURVIVE OUTSIDE THE BODY AND ALSO BECAUSE OF THE PRLONG WINDOW PERIOD. Before the screening tests for hep c virus was discovered the transmission of hep c was more
But after the screening tests were discovered there has been a steady decline in the rates.
HBV MOST COMMON TTI
As per a study published in the Indian journal of community medicine .the transmission of hep b was found to be the highest .
The hepatitis B virus is 100 times more infectious than the AIDS virus.
THERE ARE 5 PHASES OF HEP B ONCE IT HAS INFECTED A PERSON
IGM ANTIBODY PRESENT IN WINDOW PHASE
HBS AG TITRE RAPIDLY STARTS RISING AFTER THE SECOND WEEK OF INFECTION AND THEN RAPIDLY FALLS AFTER WHICH THERE IS AB APPEARS AND PERSISTS
SIMILARLY THE IGM AB OF THE CORE ANTIGEN APPEARS FIRST AND THEN THE IGG AB APPEARS AND PERSISTS
In patients with chronic HBV infection, both HBsAg and IgG anti-HBc remain persistently detectable, for life.
HBeAg is variably present in these patients.
The presence of HBsAg for 6 months or more is indicative of chronic infection.
*In addition, a negative test for IgM anti-HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV
infection
Immunological memory for HBsAg can outlast the antibody detection providing long term protection SO BOOSTER DOSE MAY NOT BE REQUIRED IN ALL INDIVIDUALS