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Hepatitis A-E

Hepatitis A-E

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MicrobiologyHepatitis A-E Viruses (An Overview)13 December 2007
 
HEPATITIS A – E VIRUSES: An OverviewViral Hepatitis – Historical Perspectives
AA
InfectiousInfectiousSerumSerumViralViralhepatitishepatitis
EntericallyEnterically
transmittedtransmittedParenterallyParenterallytransmittedtransmittedF, G, TTVF, G, TTV? other? other
EE
NANBNANB
BBDDCC
 Type of Hepatitis
ABCDESource of virusFecesBlood/blood-derivedbody fluidsBlood/blood-derivedbody fluidsBlood/blood-derivedbody fluidsFecesRoute of transmissionFecal-oralPercutaneouspermucosalPercutaneouspermucosalPercutaneouspermucosalFecal-oralChronicInfectionNoYesYesYesNoPreventionPre/post-exposureimmunizationPre/post-exposureimmunizationBlooddonorscreening;RiskbehaviormodificationPre/post-exposureimmunization: RiskbehaviormodificationEnsuresafedrinkingwater
Hepatitis A VirusA.Clinical Features
o
Incubation period:Average:30 daysRange: 15-50 days
o
 Jaundice by age group:<6 yrs: <10 %6-14 yrs: 40 - 50%>14 yrs: 70 - 80 %
o
Complications:Fulminant hepatitisCholestatic hepatitisRelapsing hepatitis
o
Chronic sequelae:NoneB.Serological course
C.
Mode of Transmission
o
Close personal contact
e.g. household contact, sex contact, child daycare centers
o
Contaminated food, water
e.g. infected food handlers, raw shellfish
o
Blood exposure
Rare
e.g. injecting drug use, transfusion
Global Patterns of Hepatitis A Virus Transmission
Endemicity
DiseaseRatePeak Ageof Infection TransmissionPatterns
High
Low to high EarlychildhoodPerson toperson;outbreaksuncommon
Moderate
HighLatechildhood/young adultsPerson toperson; foodandwaterborneoutbreaks
Low
LowYoung adultsPerson toperson; foodandwaterborneoutbreaks
Very low
Very lowAdultsTravelers;outbreaksuncommon
D.Geographic DistributionE.Laboratory Diagnosis
o
Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA
o
Past infection i.e. immunity is determined by thedetection of HAV-IgG by EIA
F.
Vaccination Strategies: Epidemiologic Considerations
o
Many cases occur in community-wide outbreaks
no risk factor identified for 40-50% of cases
highest attack rates in 5-14 year olds
children serve as reservoir of infection
o
Persons at increased risk of infection
travelers to developing countries
homosexual men
injecting drug users
G.
Prevention: Immune Globulin
o
Pre-exposure
travelers to intermediate and highHAV-endemic regions
o
Post-exposure (within 14 days)
Routine
household and other intimatecontacts
Selected situations
institutions (e.g., day care centers)
common source exposure (e.g., foodprepared by infected food handler)
Hepatitis B Virus
 
virns1 of 5
 
Microbiology –
Hepatitis A-E Viruses: An Overview 
by 
 Dra de Castro
Page
2
of 5
A.Clinical Features
o
Incubation period:Average 60-90daysRange 45-180 days
o
Clinical illness (jaundice):<5 yrs, <10%>5 yrs, 30%-50%
o
Acute case-fatality rate:0.5%-1%
o
Chronic infection:<5 yrs, 30%-90%>5 yrs, 2%-10%
o
Premature mortality fromchronic liver disease:15%-25%B.Spectrum of Chronic Hepatitis B Diseases
o
Chronic Persistent Hepatitis
Asymptomatic
o
Chronic Active Hepatitis
Symptomatic exacerbations of hepatitis
o
Cirrhosis of liver
o
Hepatocellular carcinomaC.Serological courseAcute Hepatitis B Virus Infection with Recovery Typical Serologic Course
 
Weeks after Exposure
Symptoms
HBeAganti-HBe
Total anti-HBcIgM anti-HBcanti-HBsHBsAg
0 4 8 12 162024 28 323652 100
       T       i       t     e     r
Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course
IgM anti-HBcTotal anti-HBcHBsAgAcute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 81216 20 24 283236
52
Weeks after Exposure
       T       i       t      e      r
Outcome of Hepatitis B Virus Infectionby Age at Infection
   C   h  r  o  n   i  c   I  n   f  e  c   t   i  o  n   (   %   )
               S                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     y                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       m                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    p                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  t                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    o                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    m                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 t                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       i                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    c                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       n                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    e                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 c                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 t                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       i                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    o                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    n                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    (                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       %                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      )                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
100100
Symptomatic InfectionChronic Infection
                                                                                                                                                                                             B                                                                                                                                                                                             i                                                                                                                                           r                                                                                                                                                                                        t                                                                                                                                                                                               h                                                                                                                                                                                            1                                                                                -                                                                                                                                                                                            6                                                                                                                                              m                                                                                                                                           o                                                                                                                                              s                                                                                                                                                                                             7                                                                                -                                                                                                                                                                                            1                                                                                                                                                                                            2                                                                                                                                           m                                                                                                                                           o                                                                                                                                              s                                                                                                                                                                                               1                                                                                -                                                                                                                                                                                           4                                                                                                                                         y                                                                                                                                                                                                  r                                                                                                                                           s   
                                                                                                                                                                                               O                                                                                                                                                                                               l                                                                                                                                                                                           d                                                                                                                                              e                                                                                                                                              r                                                                                                                                                                                               C                                                                                                                                                                                                h                                                                                                                                                                                             i                                                                                                                                                                                             l                                                                                                                                                                                           d                                                                                                                                              r                                                                                                                                           e                                                                                                                                              n                                                                                                                                           a                                                                                                                                             n                                                                                                                                                                                           d                                                                                                                                                                                               A                                                                                                                                                                                           d                                                                                                                                            u                                                                                                                                                                                                l                                                                                                                                                                                        t                                                                                                                                             s   
020406080806040200
D.Global Patterns of Chronic HBV Infection
o
High (>8%): 45% of global population
lifetime risk of infection >60%
early childhood infections common
o
Intermediate (2%-7%): 43% of global population
lifetime risk of infection 20%-60%
infections occur in all age groups
o
Low (<2%): 12% of global population
lifetime risk of infection <20%
most infections occur in adult risk groupsE.Geographic DistributionF.Concentration of HBV in Various Body FluidsHighModerateLow/NotDetectablebloodserumwound exudatessemenvaginal fluidsalivaurinefecessweattearsbreast milk
G.
Mode of Transmission
o
Sexual
Sex workers and homosexuals are particularat risk
o
Parenteral
IVDA, health workers are at increased risk
o
Perinatal
Mothers who are HBeAg positive are muchmore likely to transmit to their offspring thanthose who are not
Perinatal transmission is the main means of transmission in high prevalence populationH.Laboratory Diagnosis
o
A battery of serological tests are used for thediagnosis of acute and chronic hepatitis Binfection
o
HBsAg
Used as a general marker of infection
o
HBsAb
Used to document recovery and/or immunitytoHBV infection
o
Anti-HBc IgM
Marker of acute infection
o
Anti-HBc IgG
Past or chronic infection
o
HBeAg
Indicates active replication of virus andtherefore infectiveness
o
Anti-HBe
Virus no longer replicating
However, the patient can still be positive forHBsAg which is made by integrated HBV
o
HBV-DNA
Indicates active replication of virus
More accurate than HBeAg especially in casesof escape mutants
Used mainly for monitoring response totherapyI.Treatment
o
Interferon
For HBeAg positive carriers with chronicactive hepatitis
Response rate is 30 to 40%
o
Lamivudine
A nucleoside analogue reverse transcriptaseinhibitor
Well, tolerated, most patients will respondfavorably
 
Microbiology –
Hepatitis A-E Viruses: An Overview 
by 
 Dra de Castro
Page
3
of 5
However, tendency to relapse on cessation of treatment
Another problem is the rapid emergence of drug resistance
o
Successful response to treatment will result in thedisappearance of HBsAg, HBV-DNA, andseroconversion to HBeAg J.Prevention
o
Vaccination
Highly effective recombinant vaccines arenow available
Vaccine can be given to those who are atincreased risk of HBV infection such as healthcare workers
It is also given routinely to neonates asuniversal vaccination in many countries
o
Hepatitis B Immunoglobulin
HBIG may be used to protect persons who areexposed to hepatitis B
It is particular efficacious within 48 hours of the incident
It may also be given to neonates who are atincreased risk of contracting hepatitis B i.e.whose mothers are HBsAg and HBeAgpositive
o
Other measures
Screening of blood donors, blood and bodyfluid precautionsHepatitis C VirusHCV genomeA.Clinical Features
o
Incubation period:Average 6-7weeksRange 2-26 weeks
o
Clinical illness (jaundice):30 40% (20 30%)
o
Chronic Hepatitis:70%
o
Persistent Infection:85 – 100%
o
Immunity:No protective antibodyresponse identifiedB.Chronic Hepatitis C Infection
o
 The spectrum of chronic hepatitis C infection isessentially the same as chronic hepatitis Binfection
o
All the manifestations of chronic hepatitis Binfection may be seen, albeit with a lowerfrequency i.e. chronic persistent hepatitis, chronicactive hepatitis, cirrhosis, and hepatocellularcarcinomaC.Serological course Typical Serologic Course of HCV Infection
 
Symptoms +/-
Time after Exposure
       T       i       t     e     r
Anti-HCVALTNormal01234561234
 YearsMonths
HCV RNA
D.Mode of Transmission
o
Risk Factors Associated with Transmission
 Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive contact
Multiple sex partners
Birth to HCV-infected motherE.Geographic DistributionF.Laboratory Diagnosis
o
HCV antibody
Generally used to diagnose hepatitis Cinfection
Not useful in acute phase as it takes at least4 weeks after infection before antibodyappears
o
HCV-RNA
Various techniques are available e.g. PCR andbranched DNA
May be diagnose HCV infection in the acutephase
However, its main use is in monitoring theresponse to antiviral therapy
o
HCV-antigen
An EIA for HCV antigen is available
It is used in the same capacity as HCV-RNAtests but is much easier to carry outG.Treatment
o
Interferon
May be considered for patients with chronicactive hepatitis
 The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment
o
Ribavirin
 There is less experience with ribavirin thaninterferon
However, recent studies suggest that acombination of interferon and ribavirin ismore effective than interferone aloneH.Prevention
o
Screening of blood, organ, tissue donors
o
High-risk behavior modification
o
Blood and body fluid precautionsHepatitis D Virus

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