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Epidemiology of hepatitis
Presenter : Dr.L.Karthiyayini
Moderator: Dr. AbhishekV Raut
Framework
 Introduction
 Hepatitis A,E,B,C,D&G
Magnitude
Natural history of the disease
Epidemiological determinants
Mode of transmission
Clinical feature
Sero epidemiology
Prevention & control
 Hepatitis & HIV
 Global policy report on hepatitis-status of India
 WHO position of hepatitis vaccine
Introduction
 VIRAL HEPATITIS IS A MAJOR PUBLIC HEALTH PROBLEM
 Hepatitis A & E - 0.5-4 % mortality
 World wide 500 million people have chronic HBV & HCV
infection
 In India, 45 million people with HBV 500,000 to
1,000,000 people die every year of HBV-related chronic
Hepatitis, cirrhosis or liver cancer
 Out of nearly 22.6 million children born in India every
year, over 9 million will acquire the infection in their
lifetime.
 Hepatitis is the inflammation of liver by any cause
 Viral hepatitis is mainly caused by
 Hepatitis A & E virus - Faeco-oral route
- Acute & self limiting
 Hepatitis B,C & D virus- Parenteral route
-Acute & chronic
 Other viruses- cytomegalovirus, rubella virus, epstein
barr virus, yellow fever virus ,herpes zoster virus,etc.
 Other hepatitis Alcoholic hepatitis (50% of CLD)(mortality : M11/100000 & F-6/10000)
 Auto immune hepatitis,
 toxic & drug induced hepatitis,
Natural history of acute hepatits
HEPATITIS A
Source:CDC
MAGNITUDE
 GLOBAL:
 Prevalence of anti-HAV antibodies in general
population -15%-100%
Worldwide 1.5 million clinical cases yearly
Outbreaks
 INDIA:
 seroprevalence of anti-HAV:
54.5%- high socio-economic status
85% in low socio-economic status
EPIDEMIOLOGICAL DETERMINANTS
 AGENT:
 Picarnovirus family
 4 human genotypes
 1 serophytype
 HOST:
Low endemic area
 Adolescents & adults(homosexual, IV drug users)
 Travellers
Intermediate endemic area
 Late childhood(faeco oral route)
 Early adult hood
High endemic area
 Early childhood
 ENVIRONMENTAL FACTORS:
Water borne & food borne epidemics
Sanitation & overcrowding
 MODE OF TRANSMISSION:
Faeco-oral route
Parentral route – stage of viremia
Sexual transmission- homosexual due to ano-oral contact
 Secondary attack rate among household contacts is 30%
 INCUBATION PERIOD
 28 days
CLINICAL FEATURES
Symptoms & signs
Fever
Anorexia
Malaise
Nausea
Abdominal discomfort
Dark urine
Jaundice
Complications:
Relapsing hepatitis
Cholestatic hepatitis
Fulminant hepatitis(0.1%)
SERO EPIDEMIOLOGY
 IgM- Detectable from 5 days prior to onset of symptoms
& declines to undetectable levels within 6 months.
 IgG-Detect previous infection, persists life long
 Elevated levels of serum bilirubin
 Elevated hepatic enzymes(AST,ALT)
HAV INFECTION-TYPICAL SEROLOGICAL COURSE
Source:Yim, H. J., et al., (2006). Hepatology.
PREVENTION & CONTROL
 Control of reservoir:
 Complete bed rest
 Disinfection of faeces & fomites
 0.5% sodium hypochlorite
 Control of transmission:
 promoting personnel & community hygiene
 Purification of community water supplies
 Proper sanitation & waste disposal
 During epidemics, boiling of water is preferred
Active immunization
 Inactivated vaccines & live attenuated vaccines
 Parenterally (IM), 2 dose,6-18 months apart.
 Combined vaccine(inactivated hepatitis A & recombinant
hepatitis B) -0,1,6 mths.
Passive immunization
HAV IG –Pre & Post exposure prophylaxis
-single I.M dose,0.02 ml/kg within 2
weeks
HEPATITIS E
MAGNITUDE
 GLOBAL
 SEAR
 INDIA
 MAHARASHTRA
Source:CDC
MAGNITUDE
 GLOBAL:
 Overall attack rates during hepatitis E outbreaks - 1% to 15%.
 The rates are highest among young adults (3%-30%
 Case-fatality rates - 0.5% to 4%
 During outbreaks mortality rates - 0.07–0.6%
 INDIA:
 Proportion- 10%
 Seroprevalence of anti-HEV antibodies-upto 50%
EPIDEMIOLOGICAL DETERMINANTS
 AGENT
 Hepatitis E like virus
 HOST
 15-40yrs
 Pregnant mothers-20% fulminant(0.5% mortality)
 MODE OF TRANSMISSION:
 Faeco oral route
 Water borne disease
 Ingestion of raw or uncooked shell fish- sporodic cases
 Vertical transmission
 Secondary attack rates 0.7-2.2%
 INCUBATION PERIOD: 2-9 weeks
CLINICAL FEATURES
Symptoms
 Abdominal pain
 Nausea
 Vomiting
 Anorexia
Signs
 Jaundice
 Hepatomegaly
SERO EPIDEMIOLOGY
 Elevated antibody levels-RT-PCR
Hepatitis E Virus Typical
Serologic
Infection
Course
Symptoms
IgG anti-HEV
ALT
Titer
IgM anti-HEV
Virus in stool
0
1
2
Source: Yim, H. J., et al.,
(2006). Hepatology.
3
4
5
6
7
8
9
Weeks after Exposure
1
0
1
1
1
2
1
3
PREVENTION & CONTROL
 Good personnel hygiene
 High quality standards of public water supply
 Proper disposal of sanitary waste
 Vaccines – undergoing clinical trails
HEPATITIS B
Source:CDC
MAGNITUDE
 GLOBAL:
 2million
 240 billion carriers
 60-80% of all primary liver cancer
 High endemicity, intermediate endemicity & low endemicity
 INDIA:
 Point prevalence of hepatitis B is 2.1%
 chronic carrier rate 1.7%
 HCC 1.6% of all cancers
 High carrier state among health workers 11% & in general population
5%
Global Patterns of Chronic HBV
Infection
High (>8%): 45% of global population
 lifetime risk of infection >60%
 early childhood infections common
Intermediate (2%-7%): 43% of global population
 lifetime risk of infection 20%-60%
 infections occur in all age groups
Low (<2%): 12% of global population
 lifetime risk of infection <20%
 most infections occur in adult risk groups
NATURAL HISTORY OF DISEASE
NATURAL HISTORY OF CHRONIC HBV INFECTION - seroepidemiology
Source:Yim, H. J., et al., (2006). Hepatology.
EPIDEMIOLOGICAL DETERMINANTS
 AGENT:
 DNA virus- hepadnaviridae family
3 morphological forms-small spherical particles, tubules &
Dane particle(infectious)
HBsAg, HBcAg, HBeAg(Viral replication)
Only reservoir - Man
Infective material-contaminated blood, saliva, vaginal
secretions, semen
Resistance – stable for 7 days in environmental surface,
destroyed by sodium hypochlorite & by heat sterilization
30-60 mins
 HOST:
Age:
 Acute hepatitis - 1% of perinatal cases,10% of early
chidhood, 30% of late childhood
Chronic hepatitis – 80-90% -perinatally, 30% in early
chilhood, 5% infected after 6 yrs
High risk groups:
 Surgeons have 50% more chance
Others- recipients of blood transfusion, health care &
laboratory care personnels,percutaneous IV drug
abusers, homosexuals, infants of HBV carrier
mothers,immunocompromised patients.
 MODE OF TRANSMISSION
Parenteral route -Blood borne disease
Perinatal route
Sexual transmission
Horizontal transmission
 INCUBATION PERIOD
30-180 days(75 days)
COURSE OF SYMPTOMS IN ACUTE HEPATITIS
SERO EPIDEMIOLOGY
 HBsAg:
Appears first & persists throughout the illness
Indicates infectivity
 Anti-HBs:
Signal recovery, non-infectivity & immunity
 Anti-HBc:
Appears shortly after HBsAg is detected
Indicates a diagnosis of acute hepatitis
IgM anti-HBc persists for 3-6 mths.
Reappears during the flares of previously inactive chronic
hepatitis B
IgG anti-HBc also appears
Persists indefinitely
SERO EPIDEMIOLOGY
 HBeAg:
Appears in the incubation period shortly after HBsAg
Indicates viral replication & infectivity
Persistence beyoun 3 mths – chronic hepatitis B
 HBV DNA:
Parellels the presence of HBeAg
Senisitve & precise marker
PCR
Acute Hepatitis B Virus Infection with Recovery
Source:Yim, H. J., et al., (2006). Hepatology.
Progression to Chronic Hepatitis B Virus Infection
Source:Yim, H. J., et al., (2006). Hepatology.
PREVENTION & CONTROL
 Hepatitis B vaccine
 Hepatitis B immunoglobulin
 Passive active immunization
 Other measures





HEPATITIS B VACCINE
Recombinant hepatitis B vaccine-1986
Monovalent & Fixed combination(DPT, Hib, hepatitisA,
inactivated polio)
Storage : 2-8˙C (avoid freezing)
Dose:
Adults:
• 10-20 micrograms
• Deltoid
Children :
• Half the dose
• Antero lateral aspect of thigh
Schedule: 0,1,6 mths
 National immunization schedule:
3 dose schedule :At birth, along with 1st & 3rd dose of DPT
4 dose schedule: At birth, 6,10,& 14 weeks
Monovalent or combined
Minimum interval between the doses are 4 weeks
If prevalence is > 8%- within 24 hrs of birth
 Duration of protection: 15 yrs
 Protective antibody levels-> 95% (infants, children & young
adults)
 More than 40yrs – protection <90%
 More than 60yrs- protection 65-75%
 Low birth weight babies
 Reduced immunogenicity:
Diabetes
Chronic renal failure
Chronic liver disease
HIV infection
 If interrupted ?
as soon as possible
 restarting not required
 Recommnended for:
< 18 yrs of age
High risk group
International travellers
 Contraindicated:
H/O allergy to vaccine components
Hepatitis B immunoglobulin
 Immediate protection
 Used for acutely exposed: surgeons, lab workers, nurses,




newborns of carrier mothers, sexual contacts of hepatitis B
patients, liver transplanted patients
Within 6 hrs-48 hrs
Recommended dose: 0.05-0.07 ml/kg (2 doses,30 days apart)
Short term passive protection – 3 mths
No long term prophylaxis
 limited availability
 High cost
 Risk complications
Passive-active immunization
 Combined HBIG & hepatitis B vaccine more efficacious
 Recommended:
newborn babies of carrier mothers
Accidental exposure
 Dose: 0.05-0.07 ml/kg within24 hrs
 Hepatitis B vaccine 1.0ml, IM within 7 days of exposure,
2nd & 3rd dose at 1 & 6 months after 1st dose
Other measures
 Screening of blood donors
 Adequate sterilization
 Practice simple hygiene measures
 Carriers- no sharing, barrier contraception, no blood
donation
HEPATITIS C
MAGNITUDE
 GLOBAL:
 worldwide 3% infected
 3-4 million persons newly infected every year
 70% among newly infected- chronic hepatitis
 INDIA:
 1/4th of all chronic liver cases
 12.5 million carriers
 Seroprevalence among donors- 0.48%(Vellore) – 1.85%(Delhi)
NATURAL HISTORY OF DISEASE
EPIDEMIOLOGICAL DETERMINANTS
 AGENT:
 Flaviviridae family
6 genotypes & 100 sub types
 HOST:
High risk group - recipients of blood transfusion, health care
personnel, homosexuals, drug abusers & infants of carriers
 MODE OF TRANSMISSION:
Parenteral route
Perinatal route
Sexual transmission
 INCUBATION PERIOD:
 15-150 days
CLINICAL FEATURES
 80% -asymptomatic
 15-30% - develop jaundice
 80% of newly infected develop chronic hepatitis
 Cirrhosis-10-20%
 Liver cancer-5-10% (in 20-30 yrs)
SERO EPIDEMIOLOGY
 Enzyme immunosorbant assay(EIA):
Detection of HCV specific antibodies
Detects 95% of chronic cases & 50-70% of acute cases
 Recombinant immunoblot assay (RIBA):
Identifies antibodies that react with individual HCV
antigens
Supplement test for confirmation of positive EIA
 PCR:
Confirmation of serological results
Assessing effectiveness of antiviral therapy
Hepatitis C Virus Infection
Typical Serologic Course
antiHCV
Symptoms
Titre
ALT
Normal
0
1
2
3
4 5 6
Month
s Time after
Exposure
1
2
3
Years
4
TREATMENT :
 Interferon alone effective in 10-20%
 Interferon with Ribavirin effective in 30-50%
 New therapeutic agents :
 Telaprevir
boceprevir
PREVENTION & CONTROL
Screening blood donors
Virus inactivation in plasma derived products
Promotion of behaviour change
HEPATITIS D
Source:CDC
MAGNITUDE
 GLOBAL:
 Global pattern corresponds to prevalence of HBV
 Highest prevalence in Amazon basin & Romania(20% of chronic
HBV & 90% of HBV-chronic liver disease)
 Moderate prevalence-Spain, northern Italy, Turkey &
Egypt(asymptomatic HBVcarriers10-20% & 30-50% of HBVchronic liver disease)
 Low prevalence-southeast Asia & china
 INDIA:
 Acute hepatitis-10.7- > 30%
 Chronic hepatitis-8-21%
 Cirrhosis-15-19%:
EPIDEMIOLOGICAL DETERMINANTS
 AGENT:
 RNA virus
 Satellite virus or sub viral agent
 HOST:
 high risk group
 MODE OF TRANSMISSION:
 Parenteral route
 Perinatal route
 Sexual transmission
 INCUBATION PERIOD:
 30-180 days
CLINICAL FEATURES
Co-infection:
Simultaneous infcetion
Acute form of HBV & HDV
Self limiting
Chronic form -< 5%
Super infection:
HDV infection of chronically infected HBV
Severe acute hepatitis – chronic hepatitis (80%)
Associated – fulminant acute hepatitis, severe chronic
active hepatitis-cirrhosis
HBV - HDV
Coinfection Typical
Symptoms
Serologic
Course
ALT Elevated
Titre
anti-HBs
IgM anti-HDV
HDV RNA
HBsAg
Total anti-HDV
Time after Exposure
HBV - HDV Superinfection
Typical Serologic Course
Jaundice
Symptoms
Titre
Total anti-HDV
ALT
HDV RNA
HBsAg
IgM anti-HDV
Time after
Diagnosis:
 RT-PCR
 EIA
Treatment:
 A-interferon (9million units, TDS weekly for 12 months or
5 million units daily for 12 months)
Prevention & control:
 Pre & post exposure prophylaxis of HBV
 Health education to reduce risk behaviour
HEPATITIS G
 1995-Flavivirus family
 GBV-A,GBV-B,GBV-C
 GBV-C affects man.
 Transmission :
 blood transfusion
Sexual contact
Vertical transmission
Intravenous drug users
 Globally 1-3% in volunteer blood donors
 Incubation period-30-120 days
 HGV co-infection is observed in 6% of chronic HBV infections
& in 10% of chronic HCV infections.
HEPATITIS & HIV
 About one-third of HIV-infected persons are coinfected
with hepatitis B or hepatitis C, which can cause long-term
(chronic) illness and death.
 10% of 40 million people of HIV are co-infected with
HBV
 Viral hepatitis progresses faster among persons with HIV
infected persons
 HIV/HBV & HIV/HCV coinfection -leading cause of
non-AIDS-related deaths
HEPATITIS & HIV
 Coinfection with hepatitis -complicate the management of
HIV infection.
 To prevent coinfection with hepatitis B, universal hepatitis
B vaccination of susceptible patients with HIV infection or
AIDS & high risk groups is recommended
 All persons living with HIV should be tested for hepatitis B
and hepatitis C
 Coinfected persons should be counseled about drug
interacions and side efects of hepatitis and HIV treatments.
Global policy
2010 World Health Assembly – to generate reliable
information as a foundation for building prevention and
control measures that match the local epidemiological profile
and health system capacities.
 Survey conducted in mid-2012 by the World Health
Organization and the World Hepatitis Alliance.
 Aim :
 To gather country-specific baseline data on hepatitis policies
in WHO Member States in all six regions.
 offers insight into conditions in specific countries
 Gaps that need to be filled are identified

Issues addressed
 National coordination
 Awareness raising & partnerships
 Evidence based policy & data for action
 Prevention of transmission
 Screening care & treatment
National coordination
 Written national strategy plan-raising awareness, surveillance,
vaccination, prevention of transmission via injecting drug use,
in health-care settings, in general, and treatment and care.
 There is a designated governmental department :
For coordinating and/or carrying out viral hepatitis related
activities
Four staff members
Not known how many people work full-time in all
government agencies/bodies.
 The government has a viral hepatitis prevention and control
programme:
 activities targeting health-care workers, including health-care
waste handlers
Awareness raising & partnerships
Not known
 whether the government held events for World Hepatitis
Day 2012
 Funding-other viral hepatitis public awareness campaigns
since January 2011.
 The government does not collaborate with in-country
civil society groups to develop and implement its viral
hepatitis prevention and control programme
Evidence based policy & data for action
 There is no routine surveillance for viral hepatitis.
 There are standard case definitions for hepatitis.
 Hepatitis deaths are not reported to a central registry.
 No classification:“undifferentiated” or “unclassified” hepatitis
 HCC & HIV/hepatitis coinfection cases are registered
 The government does not publish hepatitis disease reports.
 Hepatitis outbreaks are reported & investigated
 There is inadequate laboratory capacity nationally to support
investigation of viral hepatitis outbreaks
 There is no national public health research agenda
 Viral hepatitis serosurveys are not conducted regularly
Prevention of transmission
 There is a national policy that specifically targets mother-to




child transmission of hepatitis B
There is no national policy on hepatitis A vaccination.
The government has not established the goal of eliminating
hepatitis B.
It is not known what percentage of newborn infants nationally
received the 1st dose of hepatitis B vaccine within 24 hours of
birth or what percentage of 1yr received 3 doses of hepatitis B
vaccine.
It is not known whether there is a specific national strategy for
preventing hepatitis in health-care settings.
Health-care workers are vaccinated against hepatitis B prior to
starting work
Contd..
 There is a national policy on injection safety in health-care






settings-auto-disable syringes
Single-use or auto-disable syringes, needles and cannulas are
always available in all health-care facilities.
Official government estimates of the number and percentage of
unnecessary injections administered annually in health-care
settings are not known.
There is a national infection control policy for blood banks.
All donated blood products nationwide are screened
It is not known whether there is a national policy relating to the
prevention of viral hepatitis among people who inject drugs.
The government has guidelines that address how hepatitis A and
hepatitis E can be prevented through food and water safety.
Screening care & treatment
 Health professionals obtain the skills and competencies through on







the job training.
Not known -national clinical guidelines for the management
The government does not have national policies relating to
screening and referral to care for hepatitis B or hepatitis C.
People testing are register by name & are kept confidential
Hepatitis testing are free of charge for all individuals and are
compulsory for blood donors.
Publicly funded treatment is not available for hepatitis
The following drug for treating hepatitis B & C is on the national
essential medicines list: lamivudine & ribavirin respectively
The GOI welcomes assistance from WHO in one or more areas of
viral hepatitis prevention and control
Who position of hepatitis vaccine
 All infants should receive their first dose preferably within 24 hrs
 Delivery of hepatitis B vaccine within 24 hours of birth should





be a performance measure for all immunization programmes.
To complete the primary series the birth dose should be
followed by 2 doses or, if convenient, by 3 doses
Minimum interval between doses is 4 weeks.
There is no evidence to support the need for a booster dose
Catch-up vaccination of children should be considered for
cohorts with low coverage.
The need for catch-up vaccination in older age groups,
including adolescents and adults, is determined by the baseline
epidemiology of HBV infection in the country.
Contd…
 The importance of vaccinating people with particular risk




factors for acquiring HBV infection is emphasized.
Eliminating HBV transmission must address- infections
acquired perinatally and during early childhood, by teenagers
and adults.
WHO strongly recommends that all countries develop goals
for hepatitis B control
Process indicators and the use of outcome measures are
critical to verifying achievement goals.
Primary tool to measure the impact of immunizationSerological surveys of HBsAg prevalence supplemented by
surveillance for acute disease
 Collection of mortality data
REFERENCE
1. Park k., text book of preventive and social medicine, 20th edition; p186 -189
2. Manson’s text book tropical disease;697-713
3. Harrison’s principles of internal medicine.17(2);p1945-1960
4. Berger SA. Infectious Diseases of India, 2012. 503 pages, 67 graphs, 4248
references. Gideon e-books,
http://www.gideononline.com/ebooks/country/infectious-diseases-of-india
5. Berger SA. Hepatitis D, E and G: Global Status, 2012. 99 pages, 36 graphs,
1116 references. Gideon e-books,
http://www.gideononline.com/ebooks/disease/hepatitis-d-e-and-g-globalstatus/
6.heahttp://www.who.int/immunization/topics/hepatitis_b/en/index.htmllth
7. Global policy report on the prevention and control of viral hepatitis in WHO Member
States.
8. http://www.who.int/immunization/documents/positionpapers/en/index.html
9.The Global Prevalence of Hepatitis A Virus Infection and Susceptibility:A Systematic
Review
10. The Global Prevalence of Hepatitis EVirus Infection and Susceptibility:A Systematic
Review
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