Download Epidemiology and Prevention of Viral Hepatitis A to E:

Epidemiology and Prevention
of Viral Hepatitis A to E:
An Overview
Hepatitis Branch
Centers for Disease Control and Prevention
Viral Hepatitis - Historical Perspective
“Infectious”
Viral hepatitis
“Serum”
A
E
Enterically
transmitted
C
Parenterally
transmitted
NANB
B D
F, G,
? other
Viral Hepatitis - Overview
Type of Hepatitis
A
Source of
virus
Route of
transmission
Chronic
infection
Prevention
B
C
D
E
feces
blood/
blood/
blood/
blood-derived blood-derived blood-derived
body fluids
body fluids
body fluids
feces
fecal-oral
percutaneous percutaneous percutaneous
permucosal
permucosal
permucosal
fecal-oral
no
yes
pre/postexposure
immunization
pre/postexposure
immunization
yes
yes
blood donor
pre/postscreening;
exposure
risk behavior immunization;
modification risk behavior
modification
no
ensure safe
drinking
water
Acute Viral Hepatitis by Type, United States, 1982-1993
34%
47%
16%
3%
Source: CDC Sentinel Counties Study on Viral Hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis
Non-ABC
Estimates of Acute and Chronic Disease
Burden for Viral Hepatitis, United States
Acute infections
(x 1000)/year*
Fulminant
deaths/year
Chronic
infections
Chronic liver disease
deaths/year
HAV
HBV
HCV
HDV
125-200
140-320
35-180
6-13
100
150
?
35
0
1-1.25
million
3.5
million
70,000
5,000
8-10,000
1,000
0
* Range based on estimated annual incidence, 1984-1994.
Hepatitis A Virus
Hepatitis A - Clinical Features
• Incubation period:
• Jaundice by
age group:
• Complications:
• Chronic sequelae:
Average 30 days
Range 15-50 days
<6 yrs,
<10%
6-14 yrs, 40%-50%
>14 yrs, 70%-80%
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
None
Age-specific Mortality Due to Hepatitis A
Age group
(years)
<5
5-14
15-29
30-49
>49
Total
Case-Fatality
(per 1000)
3.0
1.6
1.6
3.8
17.5
4.1
Source: Viral Hepatitis Surveillance Program, 1983-1989
Hepatitis A Virus Infection
Typical Serologic Course
Symptoms
Total anti-HAV
Titer
ALT
Fecal
HAV
0
1
IgM anti-HAV
2
3
4
5
6
Months after Exposure
12
24
Concentration of Hepatitis A Virus
in Various Body Fluids
Body Fluid
Feces
Serum
Saliva
Urine
100
102
104
106
Infectious Doses per ml
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
108
1010
Hepatitis A Virus Transmission
• Close personal contact
(e.g., household contact, sex contact, child
day care centers)
• Contaminated food, water
(e.g., infected food handlers, raw shellfish)
• Blood exposure (rare)
(e.g., injecting drug use, transfusion)
Sources of Hepatitis A Virus Infection by
Mutually Exclusive Groups, United States, 1983-93
Percentage of Cases
40
30
Personal contact
20
Day care center
10
Foreign travel
Drug use
Outbreak
0
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993
Year
Source: CDC, Viral Hepatitis Surveillance Program
Geographic Distribution of HAV Infection
Anti-HAV Prevalence
High
Intermediate
Low
Very Low
Hepatitis B Virus
Hepatitis B - Clinical Features
• Incubation period:
Average 60-90 days
Range 45-180 days
• Clinical illness (jaundice): <5 yrs, <10%
³5 yrs, 30%-50%
• Acute case-fatality rate:
• Chronic infection:
0.5%-1%
<5 yrs, 30%-90%
³5 yrs, 2%-10%
• Premature mortality from
chronic liver disease:
15%-25%
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titer
0
4
anti-HBs
IgM anti-HBc
HBsAg
8
12
16
20
24
28
32
36
Weeks after Exposure
52
100
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
0
4
8 12 16 20 24 28 32 36
Weeks after Exposure
52
Years
Rate (per 100,000)
Rate of Reported Hepatitis B by Age Group
25
United States, 1990
20
15
10
5
0
0-14
15-19
20-29
Age Group (Years)
Source: CDC Viral Hepatitis Surveillance Program
30-39
40+
Chronic Infection (%)
100
Outcome of Hepatitis B Virus Infection
by Age at Infection
100
80
80
60
60
Chronic Infection
40
40
20
20
Symptomatic Infection
0
Birth
1-6 months
7-12 months
Age at Infection
1-4 years
0
Older Children
and Adults
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
Geographic Distribution of Chronic HBV Infection
HBsAg Prevalence
³8% - High
2-7% - Intermediate
<2% - Low
Concentration of Hepatitis B Virus
in Various Body Fluids
High
Moderate
blood
serum
wound exudates
semen
vaginal fluid
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breastmilk
Hepatitis B Virus
Modes of Transmission
• Sexual
• Parenteral
• Perinatal
Elimination of Hepatitis B Virus Transmission
United States
Strategy
•
•
•
•
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk groups
Vaccination of adolescents
– all unvaccinated children at 11-12 years of age
– “high-risk” adolescents at all ages
• Vaccination of adults in high-risk groups
Hepatitis D (Delta) Virus
d antigen
HBsAg
RNA
Hepatitis D - Clinical Features
• Coinfection
–severe acute disease
–low risk of chronic infection
• Superinfection
–usually develop chronic HDV infection
–high risk of severe chronic liver disease
Hepatitis D Virus
Modes of Transmission
• Percutanous exposures
–injecting drug use
• Permucosal exposures
–sex contact
HBV - HDV Coinfection
Typical Serologic Course
Symptoms
ALT Elevated
Titer
anti-HBs
IgM anti-HDV
HDV RNA
HBsAg
Total anti-HDV
Time after Exposure
HBV - HDV Superinfection
Typical Serologic Course
Jaundice
Symptoms
Total anti-HDV
Titer
ALT
HDV RNA
HBsAg
IgM anti-HDV
Time after Exposure
Geographic Distribution of HDV Infection
Taiwan
Pacific Islands
HDV Prevalence
High
Intermediate
Low
Very Low
No Data
Hepatitis D - Prevention
• 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 C:
Leading-Edge Scientific
and Clinical Advances
Features of Hepatitis C Virus Infection
Incubation period
Acute illness (jaundice)
Case fatality rate
Chronic infection
Chronic hepatitis
Cirrhosis
Mortality from CLD
Average 6-7 weeks
Range 2-26 weeks
Mild (<20%)
Low
75%-85%
70% (most asx)
10%-20%
1%-5%
•
Chronic Hepatitis C
Factors Promoting Progression or
Severity
Increased alcohol intake
• Age > 40 years at time of infection
• HIV co-infection
• ?Other
– Male gender
– Other co-infections (e.g., HBV)
Serologic Pattern of Acute HCV Infection
with Recovery
anti-HCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
Time after Exposure
2
3
Years
4
Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
anti-HCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
Time after Exposure
2
3
Years
4
Decline in injection
drug users
Decline in
transfusion recipients
/
New Infections
,
Estimated Incidence of Acute HCV
Infection
United States, 1960-1999
Year
Source: Hepatology 2000;31:777-82; Hepatology 1997;26:62S-65S
Transmission of HCV
• Percutaneous
–
–
–
–
Injecting drug use
Clotting factors before viral inactivation
Transfusion, transplant from infected donor
Therapeutic (contaminated equipment, unsafe injection
practices)
– Occupational (needlestick)
• Permucosal
– Perinatal
– Sexual
Sources of Infection for
Persons with Hepatitis C
Injecting drug use 60%
Sexual 15%
Transfusion 10%
(before screening)
Other* 5%
Unknown 10%
*Nosocomial; Health-care work; Perinatal
Source: Centers for Disease Control and Prevention
Posttransfusion Hepatitis C
%
of Recipients Infected
All volunteer donors
HBsAg
Donor Screening for HIV Risk Factors
Anti-HIV
ALT/Anti-HBc
Anti-HCV
Improved
HCV Tests
Year
Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997
HCV Prevalence by Selected Groups
United States
Hemophilia
Injecting drug users
Hemodialysis
STD clients
Gen population adults
Surgeons, PSWs
Pregnant women
Military personnel
Average Percent Anti-HCV Positive
HCV Testing Routinely Recommended
Based on increased risk for infection
•
•
•
•
•
Ever injected illegal drugs
Received clotting factors made before 1987
Received blood/organs before July 1992
Ever on chronic hemodialysis
Evidence of liver disease
Based on need for exposure management
• Healthcare, emergency, public safety workers after
needle stick/mucosal exposures to HCV-positive blood
• Children born to HCV-positive women
Routine HCV Testing Not Recommended
(Unless Risk Factor Identified)
• Health-care, emergency medical, and
public safety workers
• Pregnant women
• Household (non-sexual) contacts of
HCV-positive persons
• General population
HCV Infection Testing Algorithm
for Diagnosis of Asymptomatic Persons
Negative
(non-reactive)
STOP
EIA for Anti-HCV
Positive (repeat reactive)
OR
RIBA for Anti-HCV
Negative
STOP
Negative
Indeterminate
Additional Laboratory
Evaluation (e.g. PCR, ALT)
Negative PCR,
Normal ALT
Positive PCR,
Abnormal ALT
Source: MMWR 1998;47 (No. RR 19)
RT-PCR for HCV RNA
Positive
Medical
Evaluation
Positive
HCV Counseling
• Prevent transmission to others
– Direct exposure to blood
– Perinatal exposure
– Sexual exposure
• Refer to support group
HCV Counseling
Preventing HCV Transmission to Others
Avoid Direct Exposure to Blood
• Do not donate blood, body organs, other
tissue or semen
• Do not share items that might have blood on
them
– personal care (e.g., razor, toothbrush)
– home therapy (e.g., needles)
• Cover cuts and sores on the skin
HCV Counseling
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
– Consider testing any children born since woman became
infected
– Evaluate infected children for CLD
HCV Counseling
Sexual Transmission of HCV
Persons with One Long-Term Steady Sex Partner
• Do not need to change their sexual practices
• Should discuss with their partner
– Risk (low but not absent) of sexual transmission
– Routine testing not recommended but 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
HCV Counseling
Sexual Transmission of HCV
Persons with High-Risk Sexual Behaviors
• 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
HCV Counseling
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
HCV Has Broad Global Prevalence
<1 %
1–2.4 %
2.5–4.9 %
5–10 %
> 10 %
No data available
Hepatitis E Virus
Hepatitis E - Clinical Features
• Incubation period:
• Case-fatality rate:
Average 40 days
Range 15-60 days
Overall, 1%-3%
Pregnant women, 15%-25%
• Illness severity:
Increased with age
• Chronic sequelae:
None identified
Hepatitis E Virus Infection
Typical Serologic Course
Symptoms
ALT
IgG anti-HEV
Titer
IgM anti-HEV
Virus in stool
0
1
2
3
4
5
6
7
8
Weeks after Exposure
9
10
11
12
13
Hepatitis E Epidemiologic Features
• 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
Geographic Distribution of Hepatitis E
Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis
Prevention and Control Measures for
Travelers to HEV-Endemic Regions
• 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?
‫نحوه برخورد با بيماران هپاتيتي‬
‫شك به هپاتيت‬
‫‪ .1‬فاز مقدماتي زودرس )‪:(Prodromal‬‬
‫تب‪ ،‬آرترالژي‪ ،‬آرتريت‪ ،‬راش‬
‫‪ .2‬فاز قبل از ايكتر‪:‬‬
‫بيحالي‪ ،‬خستگي‪ ،‬بياشتهايي‪ ،‬درد عضالني‪ ،‬تهوع‪ ،‬استفراغ‪ ،‬تغييرات بويايي و چشايي‪،‬‬
‫عاليم شبيه سرماخوردگي‬
‫در معاينه فيزيكي‪ :‬هپاتومگالي‪ ،‬لنفادنوپاتي زنجيره خلفي گردن ‪10‬ـ‪%5‬‬
‫‪ .3‬فاز ايكتريك‪:‬‬
‫اسكلرا و پوست زرد‪ ،‬مدفوع كم رنگ‪ ،‬ادرار تيره رنگ‪ ،‬كاهش درجه حرارت بعد از شروع‬
‫زردي‬
‫‪ .4‬فاز نقاهت‪:‬‬
‫كاهش زردي بعد از چند هفته و بهبود عاليم عمومي‬
‫آزمايشات درخواستي اوليه‬
‫)‪ALT – AST – LDH – ALP – Bil (D-T‬‬
‫‪PT‬‬
‫مورفولوژي خون محيطي‬
‫‪U/A‬‬
‫اثبات هپاتيت‬
‫با بررسي آنزيمهاي كبدي‬
‫‪ALT‬‬
‫‪10‬ـ‪ 8‬برابر‬
‫‪AST‬‬
‫انديكاسيونهاي بستري‬
‫‪ PT .1‬طوالني‪ :‬بيشتر از ‪ 3‬ثانيه‬
‫‪ Bil .2‬افزايش يابنده بيشتر از ‪20 mg‬‬
‫‪ .3‬شواهد نارسايي كبد‬
‫‪ .4‬بي اشتهايي ‪ ,‬استفراغ هاي مكرر‬
‫‪ .5‬خانم حامله با سوءتغذيه شديد‬
‫اثبات اتيولوژي‬
‫عفوني‬
‫دارويي توكسيك‬
‫آنوكسي حاد كبد‬
‫عوامل كمك كننده به تشخيص‬
‫شرح حال‬
‫اپيدميولوژي‬
‫تست هاي آزمايشگاهي‬
‫ماركرهاي سرولوژيك‬
‫اثبات اتيولوژي‬
‫عفوني‬
‫دارويي توكسيك‬
‫آنوكسي حاد كبد‬
‫عوامل كمك كننده به تشخيص‬
‫شرح حال‬
‫اپيدميولوژي‬
‫تست هاي آزمايشگاهي‬
‫ماركرهاي سرولوژيك‬
Suspicion of acute viral hepatitis based upon:
• History, physical exam, epidemiologic situation
•Elevated serum aminotransferase activity (ALT/AST)
Diagnosis:
Acute hepatitis A infection
Anti-HBc IgM positive
With or without HBsAg
Diagnosis:
Acute hepatitis B infection
Anti-HCV positive
Diagnosis: Acute HCV
infection or exacebation of
chronic HCV infection
‫براي تشخيص يا اثبات‬
‫اتيولوژي هپاتيت‬
Obtain viral serologies:
• Anti-HAV IgM
•HBsAg and Anti-HBc IgM
•Anti-HCV (EIA or RIBA)
Anti-HAV IgM positive
‫آزمايشات تكميلي‬
Negative serologies
Consider non-viral etiologies (e.g.,
Ischemia, toxins) or other infectious
Etiologies (e.g., CMV, EBV)
Check HBsAg and ALT/
AST in 6-9 months
Consider possibility of HEV
Infection if recent foreign
travel
Anti-HDV positive
HBsAg positive with or without
Abnormal aminotransferase
Re-check anti-HCV
In 3-6 months
Diagnosis: HBV/HDV
Co-infection
Diagnosis: Chronic
HBV infection
Suspicion of HDV co-infection based on:
• Risk factors (e.g., IVDA)
• Clinical signs of severe hepatities
Check anti-HDV
‫درمان غيراختصاصي و پيگيري بيمار‬
‫‪ .1‬رژيم غذايي‬
‫‪ .2‬سرم قندي‬
‫‪ .3‬استراحت نسبي در بستر‬
‫‪ .4‬تست هاي آزمايشگاهي‪:‬‬
‫‪T.A‬‬
‫‪ 2 .1‬هفته اول هفته اي ‪ 2‬بار‬
‫‪ 2 .2‬هفته دوم هفته اي ‪ 1‬بار‬
‫بررسي ‪ HBS Ag‬هر دوماه تا منفي شدن ‪HBS Ag‬‬
Needle Stick
HBV
30%
HCV
3%
HIV
0.3%
‫واكسيناسيون‬
Can my baby die from hepatitis B?
• Most babies do not die from hepatitis B.
• Up to 9 out of 10 babies born to infected mothers will
end up being hepatitis B carriers for the rest of their
lives, if they do not get the shots.
carriers
• If you make sure your babies get all 3 shots, plus a
shot called H-BIG, they have a 95% chance of being
safe from hepatitis B for life.
Baby Shots
for Hepatitis B
if the mother has Hepatitis B
1 - 2 months old
Birth
Hepatitis B
Vaccine
+
Hepatitis B
Vaccine
H-BIG
6 months old
Hepatitis B
Vaccine
Hepatitis B can be prevented!
If you have never had hepatitis B,
you can get 3 shots . . .
1
2
3
. . . and get long lasting protection.
What if my baby does not
get these shots?
Up to 9 out of 10 babies born to infected
mothers will end up being carriers for the
rest of their lives, if they do not get the
shots.
Babies who end up as carriers have a 1 out
of 4 chance of dying from liver problems.
19 out of 20 babies who get the shots
will be protected for life!
Hepatitis D - Prevention
• 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 A Prevention - Immune Globulin
• Preexposure
– travelers to intermediate and high
HAV-endemic regions
• Postexposure (within 14 days)
Routine
– household and other intimate contacts
Selected situations
– institutions (e.g., day care centers)
– common source exposure (e.g., food prepared by
infected food handler)
Hepatitis A Vaccination Strategies
Epidemiologic Considerations
• Many cases occur in community-wide outbreaks
– no risk factor identified for most cases
– highest attack rates in 5-14 year olds
– children serve as reservoir of infection
• Persons at increased risk of infection
– travelers
– homosexual men
– injecting drug users
ACIP Recommendations - Hepatitis A Vaccine
Preexposure Vaccination
• Persons at increased risk for infection
– travelers to intermediate and high
HAV-endemic countries
– homosexual and bisexual men
– drug users
– persons with chronic liver disease
• Communities with high rates of hepatitis A
(e.g., Alaska Natives, American Indians)
Estimated Incidence of Acute Hepatitis B
United States, 1978-1995
Cases per 100,000 Population
80
Vaccine
licensed
70
HBsAg screening
Infant
of pregnant
immunization
women
recommended recommended
60
OSHA Rule
enacted
50
Adolescent
immunization
recommended
40
30
20
Decline
among
homosexual
men & HCWs
10
0
Decline among
injecting
drug users
*
78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
* Provisional date
Year
•
Postexposure Management for
HCV for prophylaxis
IG, antivirals not recommended
• 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 by PCR at 4-6 weeks
– Confirm all anti-HCV results with RIBA
• Refer infected worker to specialist for medical
evaluation and management