VIRAL HEPATITIS
Kolářová M., Spring 2018
1970
1960A“Infectious”
“Serum”
Viral
hepatitis
Enterically
transmitted
Parenterally
transmitted
other
E
“NANB”
B D;1977
C
VIRAL HEPATITIS
HISTORICAL PERSPECTIVE
VIRAL HEPATITIS A
• HEPATITIS A (Hepatitis A virus)
Clinical Criteria
Any person with a discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, intermittent
nausea and vomiting)
AND
At least one of the following three:
• — Fever
• — Jaundice
• — Elevated serum aminotransferase levels
Laboratory Criteria
• At least one of the following three:
• — Detection of hepatitis A virus nucleic acid in serum or stool
• — Hepatitis A virus specific antibody response
• — Detection of hepatitis A virus antigen in stool
Epidemiological Criteria
• At least one of the following four:
• — Human to human transmission
• — Exposure to a common source
• — Exposure to contaminated food/drinking water
• — Environmental exposure
• HEPATITIS A (Hepatitis A virus)
• Case Classification
• A. Possible case NA (not applicable)
• B. Probable case
• Any person meeting the clinical criteria and with an epidemiological link
• C. Confirmed case
• Any person meeting the clinical and the laboratory criteria
HEPATITIS A VIRUS
HEPATITIS A VIRUS
• RNA Picornavirus
 Single serotype worldwide
 Acute disease and asymptomatic infection
• No chronic infection
 Protective antibodies develop in response to
infection - confers lifelong immunity
HEPATITIS A - CLINICAL FEATURES
•Jaundice by <6 yrs <10%
age group: 6-14 yrs 40%-50%
>14 yrs 70%-80%
•Rare complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
•Incubation period: Average 30 days
Range 15-50 days
•Chronic sequelae: None
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Week
Response
Clinical illness
ALT
IgM IgG
HAV in stool
Infection
Viremia
EVENTS IN HEPATITIS A VIRUS INFECTION
CONCENTRATION OF HEPATITIS A VIRUS
IN VARIOUS BODY FLUIDS
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
Feces
Serum
Saliva
Urine
100 102 104 106 108 1010
BodyFluids
Infectious Doses per mL
GEOGRAPHIC DISTRIBUTION OF
HEPATITIS A VIRUS INFECTION
2014 = 1 395 cases ( 0,4/100 000 population)
2015 = 2 800 cases (0,4/100 000 population
VHA – TESSY (The European Surveillance System)
 Close personal contact
(e.g., household contact, sex contact, child daycare
centers)
• Contaminated food, water
(e.g., infected food handlers)
• Blood exposure (rare)
(e.g., injection drug use, rarely by transfusion)
HEPATITIS A VIRUS TRANSMISSION
Unknown
46%
Contact of day-
care
child/employee
6%
Other Contact
8%
Child/employee in
day-care 2%
Food- or
waterborne
outbreak 4%
Injection drug use
6%
Sexual or
Household
Contact 14%
Men who have
sex with men
10%
International
travel 5%
RISK FACTORS ASSOCIATED WITH
REPORTED HEPATITIS A,
1990-2000, UNITED STATES
Source: NNDSS/VHSP
PREVENTING HEPATITIS A
• Hygiene (e.g., hand washing)
• Sanitation (e.g., clean water sources)
• Hepatitis A vaccine (pre-exposure)
• Immune globulin (pre- and post-exposure)
PREPARATION OF INACTIVATED
HEPATITIS A VACCINES
• Cell culture adapted virus grown in human
fibroblasts
• Purified product inactivated with formalin
• Adsorbed to aluminum hydroxide adjuvant
• Highly immunogenic
• 97%-100% of children, adolescents, and adults have
protective levels of antibody within 1 month of
receiving first dose; essentially 100% have protective
levels after second dose
• Highly efficacious
• In published studies, 94%-100% of children protected
against clinical hepatitis A after equivalent of one
dose
HEPATITIS A VACCINES
DURATION OF PROTECTION AFTER
HEPATITIS A VACCINATION
• Persistence of antibody
• At least 5-8 years among adults and children
• Efficacy
– No cases in vaccinated children at 5-6 years of follow-up
• Mathematical models of antibody decline suggest
protective antibody levels persist for at least 20 years
• Other mechanisms, such as cellular memory, may
contribute
VIRAL HEPATITIS B
The hepatitis B virus is a DNA virus belonging to the
Hepadnaviridae family of viruses.
EU Definition VHB
• HEPATITIS B (Hepatitis B virus)
• Clinical Criteria
• Not relevant for surveillance purposes
• Laboratory Criteria
• Positive results of at least one or more of the following tests or combination of tests:
• — IgM hepatitis B core antibody (anti-HBc IgM)
• — Hepatitis B surface antigen (HBsAg)
• — Hepatitis B e antigen (HBeAg)
• — Hepatitis B nucleic acid (HBV-DNA)
• Epidemiological Criteria
• Not relevant for surveillance purposes
• Case Classification
• A. Possible case NA
• B. Probable case NA
• C. Confirmed case
• Any person meeting the laboratory criteria
VIRAL HEPATITIS TYPE B
Hepatitis B virus, HBV, Hepadnavirus, the so-called Dane particle with a core
(formed by DNA, DNA polymerase, and a nucleocapsid protein with the
hepatitis B core antigen (HBcAg) and a coat of hepatitis B surface antigen
(HBsAg) ). The whole virus is infectious with a diameter of 42 nm.
Two months in the ende of incubation period, the sick or carriers.
Parenteral transmission - blood, blood products and inoculation of the infectious material
are of principal significance in the transmission.
Professional risk to medical personnel (injury by needle - transmission in 7 - 30 %,
contaminated instruments, blood transfusions - transmission in 90 %).
i.v. drug addicts - injury during tattooing, possibly other minute injuries of the skin and
mucosa.
By sexual intercourse in homosexuals, bisexuals, and prostitutes.
Vertical - perinatal transmission from mother to child when the mother is the virus carrier
or the sick person. About 95 % of newborns infect intranatally and 5 % intrauterinely.
General
General
The source of
infection
Route of
transmission
Susceptibility
Etiology:
Preventive measures:
VIRAL HEPATITIS TYPE B
Preventive measures:
Health education - to emphasize the extent of risk
Observance of epidemic measures in medical establishments.
Handling biological material and contaminated instruments,
consistent disinfection and sterilization,
application of single-use needles and syringes,
use of closed hemodialysis systems,
smoking and drinking in workplaces with biological material is forbidden.
Postexposure prophylaxis - passive and active immunization (newborns).
Examination of blood-donors - exclusion of HBsAg carriers from blood donation
Designation and inspection of sanitary-epidemic
measures in non-medical establishments (hair-dressing salons, barber shops, etc.)
Active immunization in persons with a high risk of infection (stated by public notice)
.
.
Estimate: more than 10 million Europeans suffer from chronic viral hepatitis.
The prevalence of HBV is estimated to be around 0.9% and of HCV about 1.1% in the
EU/EEA, with an estimated total of 4.7 million chronic HBV cases and 5.6 million HCV cases.
Overall, countries in the eastern and southern part of the EU/EEA were found to have a
higher HBV and HCV prevalence than countries in the northern and western parts.
The HBV prevalence ranged from 0.1% in Ireland to 4.4% in Romania, while the report found
that the prevalence of anti-HCV ranges from 0.1% in Belgium, Ireland and the Netherlands, to
5.9% in Italy. As expected, groups at higher risk of hepatitis infection, such as people who
inject drugs, prisoners and certain migrant groups were found to have higher prevalence,
compared to the general population.
The symptoms can vary greatly and many of those
infected with HBV never develop any symptoms at
all.
Those who do get symptoms (30-50% of cases)
usually suffer from tiredness, loss of appetite,
abdominal discomfort, nausea, vomiting and fever.
The vast majority of healthy adults who get acute
hepatitis B will recover with no liver damage in 4–12
weeks but the death rate can reach 2% in the
elderly.
Chronic infection is most likely to develop in young
babies.
* Incubation period: Average 60-90 days
Range 45-180 days
* Clinical illness <5 yrs, <10%
(jaundice): >5 yrs, 30%-50%
* Acute case-fatality rate: 0.5%-1%
* Chronic infection: <5 yrs, 30%-90%
>5 yrs, 2%-10%
* Premature mortality from chronic liver disease:
15%-25%
Hepatitis B – Clinical Features
Outcome of HBV Infection
Infection
Asymptomatic
Symptomatic
acute hepatitis B
Resolved
Immune
Chronic infection
Asymptomatic
Cirrhosis
Liver cancer
Resolved
Immune
Chronic
infection
Asymptomatic
Cirrhosis
Liver cancer
Weeks after Exposure
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc
anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Titer
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52
Weeks after Exposure
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
• Sexual
• Parenteral
• Perinatal
HBV Modes of Transmission
Low/Not
High Moderate Detectable
semen
serum vaginal fluid
blood
wound exudates
urine
feces
sweat
tears
breast milk
Concentration of HBV in Various Body Fluids
 Prevent perinatal HBV transmission
 Routine vaccination of all infants
 Vaccination of children in high-risk
groups
 Vaccination of adolescents
— all children up through age 18
 Vaccination of adults in high-risk
groups
Strategy
Elimination of HBV Transmission,
• Licensed in 1982; currently recombinant (in US)
• 3 dose series, typical schedule 0, 1-2, 4-6 months - no
maximum time between doses (no need to repeat missed
doses or restart)
• Protection ~30-50% dose 1; 75% - 2; 96% - 3;
• lower in older, immunosuppressive illnesses (e.g., HIV,
chronic liver diseases, diabetes), obese, smokers
Hepatitis B Vaccine
• Routine infant
• Ages 11-15 “catch up”, and through age 18(VFC eligible)
• Over 18 – high risk
– Occupational risk (HCWs)
– Hemodyalisis patients
– All STD clinic clients
– Multiple sex partners or prior STD
– Inmates in Correctional settings
– MSM
– IDU
– Institution for developmental disability
• Pre-vaccination testing – if cost effective
• Post-vaccination testing – 1-2 months after last
shot, if establishing response critical (HCW)
Hepatitis B Vaccination ACIP Recommendations
VIRAL HEPATITIS C
EU Definition VHC
• HEPATITIS C (Hepatitis C virus)
• Clinical Criteria
• Not relevant for surveillance purposes
• Laboratory Criteria
• At least one of the following three:
• — Detection of hepatitis C virus nucleic acid (HCV RNA)
• — Detection of hepatitis C virus core antigen (HCV-core)
• — Hepatitis C virus specific antibody (anti-HCV) response confirmed by a confirmatory (e.g. immunoblot) antibody
test in persons older than 18 months without evidence of resolved infection)
• Epidemiological Criteria NA
• Case Classification
• A. Possible case NA
• B. Probable case NA
• C. Confirmed case
• Any person meeting the laboratory criteria
VIRAL HEPATITIS TYPE CHepatitis C virus is a RNA-virus measuring 50 nm. It is classed into a separate genus,
Hepacavirus of the Flaviviridae family.
Long-term in viremia (in the ende IP), chronic infections.
Parenteral transmission. Sporadically, vertical and sexual
transmissions were reported carrier or the sick person.
Susceptibility is general.
The source of
infection
Route of
transmission
Susceptibility
Etiology:
Preventive measures:
The same as for HBV, exclusive immunization.
0 2000 4000 6000 8000 10000 12000 14000 16000
Austria
Bulgaria
Croatia
Cyprus
Czech Republic
Denmark
Estonia
Finland
Germany
Greece
Iceland
Ireland
Italy
Latvia
Luxembourg
Malta
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Sweden
United Kingdom
VHC
Features of Hepatitis C Virus Infection
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (<20%)
Case fatality rate Low
Chronic infection 60%-85%
Chronic hepatitis 10%-70% (most asx)
Cirrhosis <5%-20%
Age-
related
Chronic Hepatitis C
Factors Promoting Progression or Severity
• Increased alcohol intake
• Age > 40 years at time of infection
• HIV co-infection
• Other
– Male gender
– Chronic HBV co-infection
Serologic Pattern of Acute HCV Infection
with Recovery
Symptoms +/Time
after Exposure
Titer
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV RNA
Serologic Pattern of Acute HCV Infection with Progression to
Chronic Infection
Symptoms +/Time
after Exposure
Titer
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV RNA
Exposures Known to Be Associated With HCV Infection
• Injecting drug use
• Transfusion, transplant from infected donor
• Occupational exposure to blood
– Mostly needle sticks
• Iatrogenic (unsafe injections)
• Birth to HCV-infected mother
• Sex with infected partner
– Multiple sex partners
Injecting Drug Use and HCV Transmission
• Highly efficient
– Contamination of drug paraphernalia, not just needles
and syringes
• Rapidly acquired after initiation
– 30% prevalence after 3 years
– >50% after 5 years
• Four times more common than HIV
Posttransfusion Hepatitis C
0
5
10
15
20
25
30
1965 1970 1975 1980 1985 1990 1995 2000
Year
%ofRecipientsInfected
All volunteer donors
HBsAg
Donor Screening for HIV Risk Factors
Anti-HIV
ALT/Anti-HBc
Anti-HCV
Improved
HCV Tests
Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997
Occupational Transmission of HCV
• Inefficient by occupational exposures
• Average incidence 1.8% following needle stick from
HCV-positive source
– Associated with hollow-bore needles
• Case reports of transmission from blood splash to
eye; one from exposure to non-intact skin
• Prevalence 1-2% among health care workers
– Lower than adults in the general population
– 10 times lower than for HBV infection
HCV Related to Health Care Procedures
• Recognized primarily in context of outbreaks
– Chronic hemodialysis
– Hospital inpatient setting
– Private practice setting
– Home therapy
• Unsafe injection practices
– Reuse of syringes and needles
– Contaminated multiple dose medication vials
Perinatal Transmission of HCV
• Transmission only from women HCV-RNA
positive at delivery
– Average rate of infection 6%
– Higher (17%) if woman co-infected with HIV
– Role of viral titer unclear
• No association with
– Delivery method
– Breastfeeding
• Infected infants do well
– Severe hepatitis is rare
Sexual Transmission of HCV
• Case-control, cross sectional studies
– Infected partner, multiple partners, early sex, non-use
of condoms, other STDs, sex with trauma, BUT
– MSM no higher risk than heterosexuals
• Partner studies
– Low prevalence (1.5%) among long-term partners
• infections might be due to common percutaneous exposures
(e.g., drug use), BUT
– Male to female transmission more efficient
• more indicative of sexual transmission
Sexual Transmission of HCV
• Occurs, but efficiency is low
– Rare between long-term steady partners
– Factors that facilitate transmission between partners
unknown (e.g., viral titer)
• Accounts for 15-20% of acute and chronic
infections
• Sex is a common behavior
– Large chronic reservoir provides multiple opportunities
for exposure to potentially infectious partners
Household Transmission of HCV
• Rare but not absent
• Could occur through percutaneous/mucosal
exposures to blood
– Contaminated equipment used for home therapies
• IV therapy, injections
– Theoretically through sharing of contaminated personal
articles (razors, toothbrushes)
Other Potential Exposures to Blood
• No or insufficient data showing increased risk
– intranasal cocaine use, tattooing, body piercing, acupuncture, military
service
• No associations in acute case-control or population-based studies
• Cross-sectional studies in highly selected groups with inconsistent
results
– Temporal relationship between exposure and infection usually unknown
– Biologically plausible, but association or causal relationship not established
Sources of Infection for Persons With Hepatitis C
Sexual 15%
Other 1%*
Unknown 10%
Injecting drug use 60%
Transfusion 10%
(before screening)
* Nosocomial; iatrogenic; perinatal
Source: Centers for Disease Control and Prevention
Occupational 4%
Reduce or Eliminate Risks for Acquiring HCV Infection
• Screen and test donors
• Virus inactivation of plasma-derived products
• Risk-reduction counseling and services
– Obtain history of high-risk drug and sex behaviors
– Provide information on minimizing risky behavior,
including referral to other services
– Vaccinate against hepatitis A and/or hepatitis B
• Safe injection and infection control practices
MMWR 1998;47 (No. RR-19)
Reduce Risks for Disease Progression and Further Transmission
• Identify persons at risk for HCV and test to
determine infection status
– Routinely identify at risk persons through history,
record review
• Provide HCV-positive persons
– Medical evaluation and management
– Counseling
• Prevent further liver damage
• Prevent transmission to others
HCV Testing Routinely Recommended
• Ever injected illegal drugs
• Received clotting factors made before 1987
• Received blood/organs before July 1992
• Ever on chronic hemodialysis
• Evidence of liver disease
• Healthcare, emergency, public safety workers after needle
stick/mucosal exposures to HCV-positive blood
• Children born to HCV-positive women
Based on increased risk for infection
Based on need for exposure management
Postexposure Management for HCV
• IG, antivirals not recommended for prophylaxis
• Follow-up after needlesticks, sharps, or mucosal
exposures to HCV-positive blood
– Test source for anti-HCV
– Test worker if source anti-HCV positive
• Anti-HCV and ALT at baseline and 4-6 months later
• For earlier diagnosis, HCV RNA at 4-6 weeks
– Confirm all anti-HCV results with RIBA
• Refer infected worker to specialist for medical
evaluation and management
Routine HCV Testing of Uncertain Need
• Recipients of transplanted tissue
• Intranasal cocaine or other non-injecting illegal drug users
• History of tattooing, body piercing
• History of STDs or multiple sex partners
• Long-term steady sex partners of HCV-positive persons
Not confirmed as risk factor/prevalence low or unknown
Confirmed risk factor but prevalence of infection low
Mother-to-Infant Transmission of HCV
• Postexposure prophylaxis not available
• No need to avoid pregnancy or breastfeeding
– Consider bottle feeding if nipples cracked/bleeding
• No need to determine mode of delivery based
on HCV infection status
• Test infants born to HCV-positive women
– >15-18 months old
– Consider testing any children born since woman
became infected
– Evaluate infected children for CLD
Persons with One Long-Term Steady Sex Partner
Sexual Transmission of HCV
• Do not need to change their sexual practices
• Should discuss with their partner
– Risk (low but not absent) of sexual transmission
– Counseling and testing of partner should be
individualized
• May provide couple with reassurance
• Some couples might decide to use barrier precautions to
lower limited risk further
Persons with High-Risk Sexual Behaviors
Sexual Transmission of HCV
• At risk for sexually transmitted diseases, e.g.,
HIV, HBV, gonorrhea, chlamydia, etc.
• Reduce risk
– Limit number of partners
– Use latex condoms
– Get vaccinated against hepatitis B
– MSMs also get vaccinated against hepatitis A
Other Transmission Issues
• HCV not spread by kissing, hugging, sneezing,
coughing, food or water, sharing eating utensils
or drinking glasses, or casual contact
• Do not exclude from work, school, play, childcare
or other settings based on HCV infection
status
VIRAL HEPATITIS D
Hepatitis D (Delta) Virus
HBsAg
RNA
d antigen
• Coinfection
–severe acute disease
–low risk of chronic infection
• Superinfection
–usually develop chronic HDV infection
–high risk of severe chronic liver disease
Hepatitis D - Clinical Features
• Percutanous exposures
–injecting drug use
• Permucosal exposures
–sex contact
Hepatitis D Virus
Modes of Transmission
HBV - HDV Coinfection
Typical Serologic Course
Time after Exposure
Titer
anti-HBs
Symptoms
ALT Elevated
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Superinfection
Typical Serologic Course
Time after Exposure
Titer
Jaundice
Symptoms
ALT
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
Geographic Distribution of HDV Infection
HDV Prevalence
High
Intermediate
Low
Very Low
No Data
Taiwan
Pacific Islands
• HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection
• HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection
Hepatitis D - Prevention
VIRAL HEPATITIS E
Hepatitis E is caused by the Hepatitis E virus (HEV), a
positive-stranded RNA virus of the Hepeviridae family
genus Orthohepevirus, comprises 4 species,
Orthohepevirus A–D. Orthohepevirus A contains 7
genotypes (HEV-1–7).
Genotypes 1 and 2 infect humans only, while
genotypes 3, and 4 are zoonotic and can infect
humans and other mammals; genotypes 5 and 6 infect
animals only. HEV-7 has been recently detected in a
dromedary camels and transmitted to an
immunosuppressed patient in the Middle East.
In Europe, autochthonous infections are mostly related
to HEV-3; however, sporadically also infections with
other genotypes can be detected that are either locally
acquired (HEV-4) or travel-associated.
HEV infection in humans is mostly an asymptomatic
infection. The majority of cases do not develop any
symptoms but seroconvert.
In acute cases the infection causes a self-limiting
hepatitis initially with fatigue, asthenia, nausea, fever
and jaundice. Other signs can be elevated liver
enzyme levels and abnormal liver function tests,
abdominal pain and hepatosplenomegaly.
HEV-1 and -2, endemic in African and Asian
countries, can cause severe disease and
fulminant hepatitis particularly in pregnant women,
with up to 21% mortality.
In Europe, where HEV-3 is endemic, the infection
is not associated with severe disease in pregnant
women and thus they are not considered as risk
group.
Hepatitis E Virus
Hepatitis E - Clinical Features
• Incubation period: Average 40 days
Range 15-60 days
• Case-fatality rate: Overall, 1%-3%
Pregnant women, 15%-25%
• Illness severity: Increased with age
• Chronic sequelae: None identified
Hepatitis E Virus Infection
Typical Serologic Course
Weeks after Exposure
Titer
Symptoms
ALT
IgG anti-HEV
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 10 11 12 13
• Most outbreaks associated with
fecally contaminated drinking water
• Minimal person-to-person transmission
• U.S. cases usually have history of travel
to HEV-endemic areas
Hepatitis E Epidemiologic
Features
Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis
• Avoid drinking water (and beverages with ice) of
unknown purity, uncooked shellfish, and uncooked
fruit/vegetables not peeled or prepared by traveler
• IG prepared from donors in Western countries does
not prevent infection
• Unknown efficacy of IG prepared from donors in
endemic areas
• Vaccine?
Prevention and Control Measures for
Travelers to HEV-Endemic Regions
Key characteristics of HAV, HBV, HCV, HDV, HEV
A B C D E
Causative agent
Picornaviridae Hepadnaviridae Raviviridae Deltaviridae Hepeviridae
RNA DNA RNA RNA RNA
Incubation period 2 – 6 weeks 2 - 6 months 2 - 6 months 3-7 weeks 2 - 10 weks
Characteristic of
acute hepatitis
Case fatality increases with age
Acute hepatitis more
common in adults
Acute hepatitis uncommon,
almost never fulminant
Superinfection with
HDV in chronic heptitis
B may lead to fulminnat
disease
High case fatality in
pregnant women -10-20 %;
other 1 -2 %
Biomarker of recent
infection
IgM anti-HAV IgM anti-HBc None IgM anti-HDV IgM anti-HEV
Chronic infection none
Chronic infection leading to
sequelae
Chronic infection leading to
sequelae
Chronic hepatitis that
copmlicated chronic
hepatitis B
Very rare
Cirrhosis and
hepatocelular Ca
No
Yes; 0,1 -1,0 % are
fulminant
Yes; 50 % can be fulminant
Yes; 5 - 20 % can be
fulminant
NO
The period of
infectivity
last 2 weeks of incubation period
last 2 months of incubation
period
last 2 months of incubation
period
?? ??first day of acute stage
entire period of acute stageentire period of acute stage
chronic disease, carriers chronic disease, carriers
Infectious biological
material
faeces blood blood blood faeces
viremia - 1. day of illnes genital secretions genital secretions meat of animals
Mode of
transmission
Person-to person Perinatal Blodborne Blodborne Waterborne
Foodborne Bloodborne Perinatal Foodborne
Waterborne Sexual Sexual Person-to person
Inactivated hepatitis A vaccines are Active (recombinant