Hepatitis of microbial origin Flashcards
Hepatitis caused by what organisms besides virus?(2)
Bacterial
Fungal
Hepatitis caused in what bacterial disease?(2)
Any systemic bacterial infection:
- Leptospirosis
- Q fever (Coxiella burnetii)
hepatitis caused by what fungal disease?(3)
Histoplasmosis
Disseminated candidiasis
Invasive aspergillosis
LEPTOSPIROSIS
Causal agent
Transmission
Route
excreted
High risk group
Leptospira interrogans
Zoonosis of rodents, cattle, pets
fecal-oral route
Leptospirae excreted in urine
Veterinarians, pet shop owners Sewage workers Farmers
- Pathogenesis of LEPTOSPIROSIS
2. Outcome /Clinical Presentation
1.Entry through mucous membranes or skin–>bacteraemia to
liver, kidneys, CNS, lungs
- Outcome /Clinical Presentation
a) PHASE 1 type 1 Anicteric leptospirosis –fever, chills, headache, myalgias- “Influenza-like illness”
b)PHASE 2: type 2Weil’s sydrome
1.aseptic meningitis
2.hepatitis
3.uraemia
4.haemorrhages
Mortality : 5%-40%
Diagnosis-investigation for LEPTO
Microbiological
- Isolation of leptospirae
- blood : first 1 - 2 weeks of illness
- urine : several weeks to months
- Culture & identification
- Microscopy
- Detection of antibodies-ELISA
- LEPTO dipstick assay
Liver Function tests
- Serum bilirubin : marked increase
- Alkaline phosphatase : marked increase
- Aminotransferases : moderate increase
Urine examination
- Microscopic changes
- Proteinuria
Blood tests * Leucocytosis : marked * Thrombocytopaenia \: mild * ESR : elevated
LEPTO Prevention
Avoid contact : Skin / Mucous membrane * Occupational hazard * Pre or Post exposure prophylaxis \: Doxycycline 200 mg per week \: Period of potential exposure * Vaccination: Human - Killed whole cell leptospiral vaccine
1.Viral Hepatitis
A,B,C,D,E,F,G?
2.What are hepatitis other than A & B called?
1. Infectious-A Serum-B, D Parentally-C Enterically-E Others- F,G
- non-A non-B (NANB
State for HEP A B C D E F G:
virus name
virus family
dna/rna
envelope
HAV : Hepatovirus : Picornaviridae : RNA : Env (-)
HBV : Orthohepadnavirus : Hepadnaviridae : DNA: Env (+)
HCV : Hepacivirus : Flaviviridae : RNA: Env (+)
HDV : Deltavirus : Deltaviridae : RNA: Env (+)
HEV : Hepevirus : Hepeviridae : RNA: Env (-)
HFV : Uncertain : :DNA:
HGV : Flaviviridae : RNA: Env (+)
A
1.Source of
virus
2.Route of
transmission
3.Chronic
infection
4.Prevention
- feces
- fecal- oral
- not chronic
- pre/post exposure/ immunization
B
1.Source of
virus
2.Route of
transmission
3.Chronic
infection
4.Prevention
- blood/ Blood derived body fluids
- Body contact
- yes
- pre/post exposure/ immunization
C
1.Source of
virus
2.Route of
transmission
3.Chronic
infection?
4.Prevention
- blood/ Blood derived body fluids
- Body contact
- yes
- blood donor Screening, risk behavior modification
D
1.Source of
virus
2.Route of
transmission
3.Chronic
infection?
4.Prevention
- blood/ Blood derived body fluids
- Body contact
- yes
4.pre/post exposure
/ immunization, risk behavior modification
E
1.Source of
virus
2.Route of
transmission
3.Chronic
infection?
4.Prevention
- feces
- fecal- oral
- no
- Drink safe water
F
1.Source of
virus
2.Route of
transmission
3.Chronic
infection?
4.Prevention
- feces
- fecal- oral
- UNKNOWN
- Drink safe water
G
1.Source of
virus
2.Route of
transmission
3.Chronic
infection?
4.Prevention
- blood/ Blood derived body fluids
- Body contact
- UNKNOWN
- risk behavior modification
Hepatitis A Virus
- Virus family
- virus shape
- presence of envelope
- DNA/RNA (SS OR DS?)
- Incubation period
6.Jaundice by
age group
- Complications
Picornaviridae
Icosahedral symmetry
Envelope (-)
ssRNA
Average 30 days
Range 15-50 days
> 14 yrs
Fulminant hepatitis (acute liver failure) Cholestatic hepatitis Relapsing hepatitis
PATHOGENESIS OF HEPATITIS A
Virus replicates in GI tract —>blood stream—>liver
Infected hepatocytes damaged by cytotoxic T cells
Infection cleared, no chronic infection, no carrier
Clinical Course of hepatitis A
symptoms of most infections
incubation period length
presence of chronic hepatitis
liver cancer presence
Most infections are asymptomatic
Fever, anorexia, nausea, vomiting and jaundice
Incubation Period : short (2 - 5 week)
No chronic hepatitis
No predisposition to liver cancer
Typical Serological Course of Hep A
SLIDE
Laboratory Diagnosis
HEP A
Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.
Past Infection i.e. immunity is determined by the detection of
HAV-IgG by EIA.
- Hepatitis A Virus Transmission
- Who are reservoirs?
- Who are commonly infected?
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)
Humans are the only reservoirs
Children are more commonly infected
Specific Measures HEP A
Inactivated HAV vaccine (ACTIVE IMMUNITY)
Immune serum globulin (PASSIVE IMMUNITY)
Combined active & passive immunity
Hep B morphology
- what particles present?
- describe these particle:
- shape
infectious?
- non infectious spherical particle HBsAg
- non infectious tubular filaments of various lengths
- infectious dane particle with outer envelope and
nucleocapsid containing protein, DNA genome and DNA polymerase
Structural components of HBV
Hepatitis B Surface
Antigen
Hepatitis B Core Antigen
Hepatitis B “e “ Antigen
Viral DNA
Clinical Course HEP B
- incubation period
- symptoms of infection
- what levels are elevated/ decreased?
- spectrum of disease
1.Incubation Period : long (6 - 24 weeks)
- Many infections are asymptomatic
Fever, anorexia, nausea, vomiting, jaundice - Elevated transaminase levels
- Wide range of disease spectrum
Incubation period of hep B
60-90 days
Flow of Acute HBV infection
slide
Spectrum of Chronic Hepatitis B Diseases
1Chronic Persistent Hepatitis - asymptomatic
Chronic Active Hepatitis - symptomatic exacerbations of hepatitis
Cirrhosis of Liver
Hepatocellular Carcinoma
PATHOGENESIS of HEP B
- how it enters body and what happens in body
- can predispose to?
1.Virus enters via skin/mucosa blood stream liver
Infected hepatocytes damaged by cytotoxic T cells
Chronic infection/ carrier state in 5 – 10 % of patients
- Chronicity predisposes to hepatocellular carcinoma
Typical Serologic Course of Acute Hepatitis B Virus Infection with Recovery
Three antigen-antibody
system
1) HBsAg– anti-HBs system:
HBsAg appears 1-2 weeks (late to 11-12 weeks)
after exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B.
In chronic patients or carrier, HBsAg persist many years
HBsAg antigencity but no infectivity
HBsAg is the marker of infectivity
HBsAg can be found in humors and secretions:
salive, urine, semina, tears, sweat and breast milk
Anti-HBs appear after HBsAg disappear several
weeks (or months) anti-HBs is protective antibody, can persist for many years
2 . HBcAg—anti-HBc system
HBcAg can be found in the nuclei of liver cells, no free HBcAg in serum
HBcAg is the marker of replication of HBV
The stage called window phase
Anti-HBc IgM is a marker of acute infection and acute attack of chronic infection of HBV. Anti-HBc IgG is the marker of past infection, high titer means low level replication of HBV
- HBeAg—anti-HBe system
HBeAg is a soliable antigen
HBeAg is a reliable indicator of active replication
of HBV
Anti-HBe is a marker of reduced infectivity. If exist long may be a marker of integration of HBV into liver cell
Progression to Chronic Hepatitis B Virus Infection
slide
Concentration of Hepatitis B
Virus in Various Body Fluids
- high in ?
- moderate in ?
- Low/ not detectable in?
- blood, serum, wound exudate
- semen, vaginal fluid, saliva
- urine, feces, sweat, tears breastmilk
Hepatitis B Virus
Modes of Transmission
Sexual - sex workers and homosexuals are particular at risk.
Parenteral - IVDA, Health Workers are at
increased risk.
Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.
Treatment of hep b
Chronic HB treatment goals-Suppression of virus, Prevention of drug-resistant strains and Remission of liver disease
Interferon - for HBeAg +ve carriers with chronic active
hepatitis. Response rate is 30 to 40%.
Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.
Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.
3 Prevention hep b
1.Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.
- Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B
i. e. whose mothers are HBsAg and HBeAg positive. - Other measures - screening of blood donors, blood and body fluid precautions.
HCV Family Genus Morphology RNA STRAND , ENVELOPE Genotypes
Family :Flaviviridae
Genus : Hepacivirus
Morphology:
55-65 nm \: Icosahedral symmetry \: Enveloped \: Single-strand RNA
Six
: Determine potential response to therapy
Hepatitis C - Clinical
Features
- Incubation period
- Clinical illness (jaundice):
- Chronic hepatitis:
- Persistent infection:
- Immunity:
1.Average 6-7 wks
Range 2-26 wks
- 30-40% (20-30%)
- 70%
- 85-100%
5.No protective antibody response
identified
Clinical Manifestations HEP C
Fever, anorexia, nausea, vomiting
Jaundice
* Milder than hepatitis B
NATURAL HISTORY OF HEP C INFECTION
SLIDE
DESCRIBE Chronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.
All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.
DESCRIBE SEROLOGICAL OF HCV ACUTE INFECTION
TITRE:
SYMPTOMS
HCV RNA
ANTI HCV
ALT
SLIDE
7 Risk Factors Associated
with Transmission of HCV
- Transfusion or transplant from infected donor
- Injecting drug use
- Hemodialysis (yrs on treatment)
- Accidental injuries with needles/sharps
5.Sexual/household exposure to anti-HCV-positive
contact
- Multiple sex partners
- Birth to HCV-infected mother
- Laboratory Diagnosis HCV
HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.
2 Treatment OF HCV
Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment.
Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.
3 Prevention of Hepatitis C
- Screening of blood, organ, tissue donors
- High-risk behavior modification
- Blood and body fluid precautions
Hepatitis D (Delta) Virus
- DESCRIBE STRUCTURE
- Genus :
- REPLICATION
- CO-INFECTION
SLIDE
- -Spherical virion
- Envelope (HBsAg) - DELTA VIRUS
- In vivo replication
- coinfection with HBV
- PATHOGENESIS OF HEP D
- CLINICAL COURSE SEVERITY
- MORTALITY
- Virus enters via skin/mucosa blood stream
liver - Defective virus : Replicates only in presence of HBV
- Infected hepatocytes damaged by
cytotoxic T cells - Coinfection with HBV & HDV
- Clinical course : more severe
- Mortality : higher
Hepatitis D - Clinical Features
2 TYPES PF CLINICAL FEATURES
- Coinfection
severe acute disease.
low risk of chronic infection. - Superinfection
usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis
- Hepatitis D Virus Modes
of Transmission
Percutanous exposures
injecting drug use
Permucosal exposures
sex contact
HBV-HDV Typical COINFECTION Serologic Course
TITRE
:
Symptoms
ALT
SLIDE
ALT ELEVATED
HBV - HDV SUPERINFECTION Typical Serologic Course
SLIDE
LABORATORY DIAGNOSIS
- FOR HDV
- HBV
- HDV
2.Total anti-HDV / IGM
antibodies
3.Detection of delta
antigen in serum
- HBV
* Serologial markers for HBV infection
Monitor ongoing HDV infection
: HDV-RNA: Reverse transcriptase-PCR (RT-PCR)
Hepatitis D - Prevention
1.HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent HBV infection.
2.HBV-HDV Superinfection
Education to reduce risk behaviors among persons with chronic HBV infection
Hepatitis E Virus
GENUS:
SHAPE
ENVELOPE
RNA SS OF DS
Hepevirus
Icosahedral
: Non-enveloped
: Diameter 34 nm
: Single strand of RNA
- Pathogenesis OF HEP E
- Clinical course
- Most infections are
- CLEARANCE OF INFECTION
- chronic infection, carrier
- Virus replicates in GI tract –>blood stream–> liver
- 2-4 weeks
- asymptomatic/mild
- Infection cleared completely
No chronic infection, no carrier
CLINICAL FEATURES HEP E:
Incubation period:
Case-fatality rate:
Illness severity:
Chronic sequelae
- Average 40 days
Range 15-60 days
2 .Overall, 1%-3%
- Pregnant women,
15%-25% - Increased with age
- None identified
TYPICAL SEROLOGICAL COURSE OF HEP E
SLIDE
LABORATORY DIAGNOSIS HEP E
Serum : anti-HEV IgM
anti-HEV IgG
HEV RNA
Stool : HEV-RNA
TRANSMISSION OF HEP E
Ingestion : Faecal -
oral route
Associated with large water – borne outbreaks
2 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.
Recombinant hep. E vaccine-HEV 239
VIRAL HEPATITIS F
AKA?
TRANSMISSION
IDENTIFIED IN? USING?
Non A – E hepatitis
Transmitted through fecal - oral route
Can be identified in stool samples-
Electron microscopy
- HEP G AKA?
- ASSOC WITH
- FAMILY OF VIRUS
- TRANSMISSION
- MOST INFECTIONS ARE ? (SYMPTOMS)
Hepatitis G Virus HGV, now known as GBV-C
Associated with post-transfusion
hepatitis
Member of Flaviviridae
Parenteral, sexual, vertical transmission
Most infections are asymptomatic / mild
PATHOGENESIS OF HEP G
- REPLICATION PRIMARILY IN ? POORLY IN?
- SURVIVAL… WHY?
Replicates primarily
in lymphocytes
Replicates poorly in
hepatocytes
HIV patients with GBV-C : survive longer- Slows progression of HIV infection
DIAGNOSIS HEP G
Anti-HGV antibody
HGV RNA- RT-PCR
1.WHICH VIRUS REPLICATE IN LIVER?
- Which viruses cause elevated liver
Enzyme level? - Viral haemorrhagic fever By what viruses ?
- Hepatitis is major feature of ?
- Herpesviruses- HSV, CMV, EBV-
- AdV, coxsackieviruses, measles-
- YFV, Marburg, Ebola virus, Lassa virus, Crimean- Congo hemorrhagic fever
- Hepatitis is major feature of most disseminated viral infection in neonates and immunocompromised patient
