Viral Hepatitis
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- Pages: 40
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INTRODUCTION
Hepatitis – causes inflammation of LIVER Primarily attack HEPATOCYTES
Healthy Liver
Inflammation of the liver
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TYPES
Different types of Hepatitis virus Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis D Virus (HDV) Hepatitis E Virus (HEV) Hepatitis F Virus (HFV) Hepatitis GVirus (HGV)
Clinical features are similar but Hepatitis B & C are also responsible for Hepatocellular carcinoma INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS B VIRUS INTRODUCTION HBV
1960s – Blumberg & his collegues observed an antigen in haemophiliacs from Australian and named Australia antigen (Au)
1968 – this antigen associated with acute & chronic hepatitis
named as HBV INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
MORPHOLOGY
Family – Hepadnavirida Icosahedral, spherical, enveloped, complex 42nm double shelled particle
ANTIGENIC STRUCTURE
Envelope contains – HB surface antigen (HBsAg) Core contains HB core antigen (HBcAg) (antibodies produce against HBcAg during primary infection) HBe antigen – not a viral particle, translated from RNA (reliable marker for infectivity)
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Under Electron microscope HBsAg has three parts
Spherical – 22nm in diameter
Tubular or Filamentous – 22nm in diameter
Dane particle – double shelled 42nm in diameter resembles original HBV structure INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SOURCE Blood and blood
products All secretions (saliva, sweat, vaginal etc) All fluids (CSF, semen etc)
MODE OF TRANSMISSION Sexual
contact Vertical transmission Injecting drug users Nosocomial exposure Community used razor and tooth brushes INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SUSCEPTIBLE HOST
Health care personnel IV drug users Haemophiliacs Renal dialysis patients Infants born to infected mothers
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SECRETIONS
BLOOD
FLUIDS
HBV PATHOGENESIS LIVER
PRIMARY
CHRONIC
IMMUNE COMPLEX
TISSUE DAMAGE
SERUM SICKNESS
NECROTIC FOCI
POLYARTERITIS NODOSA
HEPATOMEGALY
RECOVERY CIRRHOSIS HEPATOCELLULAR CARCINOMA
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
MGN
HEPATOCELLULAR CARCINOMA
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CLINICAL FEATURES
Incubation period – 40 to 180 days Manifestation: Primary Hepatitis Chronic Hepatitis Combined Hepatitis Primary hepatitis: Signs & symptoms begin 60 to 110 days after exposure to HBV INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SIGNS –Fever, urticaria, arthralgia, arthritis, rashes.
SYMPTOMS – Fever, anorexia, malaise, vomitting, headache, intense itching.
Many patients are anicteric; some develop hepatomegaly Adults – recover in 4 to 7 weeks Children – recover about 2 weeks Death is rare Associated with HDV coinfection
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CHRONIC HEPATITIS
About 1 to 10 % of adults & 80 to 95 % of infants recover from primary hepatitis will become chronically infected - CPH or CAH Chronic persistent hepatitis (CPH) – patients develop no liver damage Chronic active hepatitis (CAH)– continuous regenerative type of liver damage leads to cirrhosis, hepatocellular carcinoma or both
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
COMBINED INFECTION
HBV associated with HDV infection Patient develop single episode of combined infection (HBV&HDV) HBV disease followed by HDV Co–infection or super infection is more severe & mortality rate is high (20 %)
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CARRIER STATE
Two types of carriers – simple & super carriers
Simple carriers – have surface antigens of HBV
Super carriers – have both surface and early antigen of HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
LAB DIAGNOSIS
By clinical data Liver function test Alanine amino transferase – gradual rise with longer duration indicates HBV infection Bilirubin & serum globulin increases; serum albumin decreases. SEROLOGY Surface antigen – ELISA, Latex agglutination test Antigens – immunoflourescent test
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SEROMARKERS Recent infection – HBsAg & IgM antibodies to HBcAg (3-5 wks before onset of symptoms) Chronic infection – anti HBcAg Past infection – IgG antibodies
MOLECULAR TECHNIQUES detection and quantitation of viral DNA by PCR
DEMONSTRATION OF HBV (not in routine diagnosis) Human & Simion cells are used Produce cytopathic effect INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TREATMENT Alpha interferon + Lamivudin
PREVENTION Prevented by administration of immune prophylaxis - VACCINATION Plasma derived vaccine / pooled hyper immune sera Prepared from donors with high titre of anti HBsAg
Recombinant DNA vaccine -Produced by cloning HBsAg in yeast cells ( Saccharomyces cerivasiae)
Administered in three doses (0 month, 1 month after 1st dose and 6 months after 1ST dose) Children – (0.5 ml three doses) 0m, 1m, 6m Adult – (1 ml three doses) 0m,1m, 6m INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Who should be vaccinated? Post exposure prophylaxis (PEP) Haemodialysis patients Homosexually active men Drug user Infants born to infected mother Personal contact with HBV patients Other high risk population like health Care workers Now it is part of the regular immunization schedule for children INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
UNIVERSAL PRECAUTION HEALTH CARE WORKERS
Wear personal protective equipment (gloves, gowns etc) Hand hygiene Use disposable and sterile needles Do not recap the used needles Avoid mouth pipetting Always transport the specimen with BioHazard sign INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Other prevention methods: Pre-screening of blood, blood products and donors for organ or tissue transplant for HBV,HCV, HIV is mandatory
Change in life style - ie avoid exposure to HBV carriers or patients
Avoid sharing personal hygiene products
Use sterile and disposable needles
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS C VIRUS
Parenterally transmitted non A – non B Hepatitis (NANB) Small, enveloped,35 to 60 nm in size contains positive sense,single stranded RNA virus Related to human Flaviviruses Placed in the genus Hepatitis C Virus
TRANSMISSION Same as HBV Verticle & sexual transmission is less than HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INCUBATION PERIOD – 5 to 12 weeks Peak onset of disease 7 to 8 wks after infection CLINICAL MANIFESTATION 80 % are asymptomatic in acute phase Symptoms – Fatigue, loss of appetite, jaundice, abdominal pain, itching, hives, joint pain, nausea, vomitting Chronic infection cause above symptoms + weakness, severe fatigue Serious complication of HCV include Cirrhosis of liver & progressive liver damage Increased risk of liver cancer
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
DIAGNOSIS By clinical data
Liver function test ALT shows fluctuating rise
Serology Detection of anti HCV antibodies by ELISA & Recombinant Immuno Blot Assay (RIBA) Detection & quantitation of genetic material from the viruses by RT-PCR
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Hepatitis C Virus Infection Typical Serologic Course anti-HCV
Titer
Symptoms
ALT
Normal 0
1
2
3 4 Months Months
5
6
1
2 3 Years
Time after Exposure INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
4
TREATMENT Recombinant alpha interferon is the only therapeutic agent approved by US No vaccine is available PREVENTION Tranfusion of safe blood & blood products All HCV positive persons – infectious Do not allow HCV positive persons or carriers to donate blood or organs Other control measures are same as HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS A VIRUS INTRODUCTION
Also known as Infectious Hepatitis Family – Picornaviridae Genus – Enterovirus type 72
HAV
MORPHOLOGY
Icosahedral, spherical, naked virus of 27 nm in diameter. Virus contains ssRNA as genome.
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SOURCE Sewage
contaminated water, Contaminated food.
MODE OF TRANSMISSION *Feco-oral route. *Affect food handlers &
in area with poor sanitation.
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
PATHOGENESIS FOOD
WATER INGESTION INTESTINE BLOOD PARENCHYMAL
KUPFFER
LIVER REPLICATION BILE
STOOL
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CLINICAL MANIFESTATION
SUB CLINICAL – anicteric, undiagnosed.
CLINICAL – preicteric and icteric Incubation period – 2 to 6 weeks (mean – 28 days)
Preicteric : fever, chills, nausea, vomitting, abdominal discomfort.
Icteric : appearance of dark colour urine, clay coloured stool, jaundice of sclera & skin, hepatomegaly (right quadrant abdominal pain) INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
DIAGNOSIS
By clinical data Liver function test (Biochemical analysis) Alanine amino transferase – sharp rise with short duration Bilirubin increases upto 5 – 20 mg/dl Serum albumin increases& globulin decreases. Serology Antigen detection – Immunoflourescent test Antibody (IgM) detection – ELISA Presence IgG indicates past infection
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TREATMENT No specific drug is available
PREVENTION Personal hygeine Good sanitation
VACCINE Formalin inactivated cell culture derived vaccine Recommended for – children at 1 yr of age and high risk population
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS E VIRUS
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
STRUCTURE
Small round non enveloped virus Contains positive ssRNA genome Size 29nm Belongs to the family Calcivirus
SALIENT FEATURES Resembles HAV Adults are morre infected Occurs as outbrreaks No vaccine is available INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Mortality rate is high if women affected in third trimester stage of pregnancy SOURCE faecally contaminated water
MODE OF TRANMISSION Oro faecal route PATHOGENESIS Not clear
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
LAB DIAGNOSIS
Detection of IgM or IgG antibodies – ELISA HEV detectiion by PCR is under development.
TREATMENT & CONTROL No specific treatment Prevented by safe drinking of water No vaccine available
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INTRODUCTION
Hepatitis – causes inflammation of LIVER Primarily attack HEPATOCYTES
Healthy Liver
Inflammation of the liver
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TYPES
Different types of Hepatitis virus Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis D Virus (HDV) Hepatitis E Virus (HEV) Hepatitis F Virus (HFV) Hepatitis GVirus (HGV)
Clinical features are similar but Hepatitis B & C are also responsible for Hepatocellular carcinoma INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS B VIRUS INTRODUCTION HBV
1960s – Blumberg & his collegues observed an antigen in haemophiliacs from Australian and named Australia antigen (Au)
1968 – this antigen associated with acute & chronic hepatitis
named as HBV INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
MORPHOLOGY
Family – Hepadnavirida Icosahedral, spherical, enveloped, complex 42nm double shelled particle
ANTIGENIC STRUCTURE
Envelope contains – HB surface antigen (HBsAg) Core contains HB core antigen (HBcAg) (antibodies produce against HBcAg during primary infection) HBe antigen – not a viral particle, translated from RNA (reliable marker for infectivity)
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Under Electron microscope HBsAg has three parts
Spherical – 22nm in diameter
Tubular or Filamentous – 22nm in diameter
Dane particle – double shelled 42nm in diameter resembles original HBV structure INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SOURCE Blood and blood
products All secretions (saliva, sweat, vaginal etc) All fluids (CSF, semen etc)
MODE OF TRANSMISSION Sexual
contact Vertical transmission Injecting drug users Nosocomial exposure Community used razor and tooth brushes INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SUSCEPTIBLE HOST
Health care personnel IV drug users Haemophiliacs Renal dialysis patients Infants born to infected mothers
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SECRETIONS
BLOOD
FLUIDS
HBV PATHOGENESIS LIVER
PRIMARY
CHRONIC
IMMUNE COMPLEX
TISSUE DAMAGE
SERUM SICKNESS
NECROTIC FOCI
POLYARTERITIS NODOSA
HEPATOMEGALY
RECOVERY CIRRHOSIS HEPATOCELLULAR CARCINOMA
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
MGN
HEPATOCELLULAR CARCINOMA
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CLINICAL FEATURES
Incubation period – 40 to 180 days Manifestation: Primary Hepatitis Chronic Hepatitis Combined Hepatitis Primary hepatitis: Signs & symptoms begin 60 to 110 days after exposure to HBV INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SIGNS –Fever, urticaria, arthralgia, arthritis, rashes.
SYMPTOMS – Fever, anorexia, malaise, vomitting, headache, intense itching.
Many patients are anicteric; some develop hepatomegaly Adults – recover in 4 to 7 weeks Children – recover about 2 weeks Death is rare Associated with HDV coinfection
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CHRONIC HEPATITIS
About 1 to 10 % of adults & 80 to 95 % of infants recover from primary hepatitis will become chronically infected - CPH or CAH Chronic persistent hepatitis (CPH) – patients develop no liver damage Chronic active hepatitis (CAH)– continuous regenerative type of liver damage leads to cirrhosis, hepatocellular carcinoma or both
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
COMBINED INFECTION
HBV associated with HDV infection Patient develop single episode of combined infection (HBV&HDV) HBV disease followed by HDV Co–infection or super infection is more severe & mortality rate is high (20 %)
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CARRIER STATE
Two types of carriers – simple & super carriers
Simple carriers – have surface antigens of HBV
Super carriers – have both surface and early antigen of HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
LAB DIAGNOSIS
By clinical data Liver function test Alanine amino transferase – gradual rise with longer duration indicates HBV infection Bilirubin & serum globulin increases; serum albumin decreases. SEROLOGY Surface antigen – ELISA, Latex agglutination test Antigens – immunoflourescent test
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SEROMARKERS Recent infection – HBsAg & IgM antibodies to HBcAg (3-5 wks before onset of symptoms) Chronic infection – anti HBcAg Past infection – IgG antibodies
MOLECULAR TECHNIQUES detection and quantitation of viral DNA by PCR
DEMONSTRATION OF HBV (not in routine diagnosis) Human & Simion cells are used Produce cytopathic effect INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TREATMENT Alpha interferon + Lamivudin
PREVENTION Prevented by administration of immune prophylaxis - VACCINATION Plasma derived vaccine / pooled hyper immune sera Prepared from donors with high titre of anti HBsAg
Recombinant DNA vaccine -Produced by cloning HBsAg in yeast cells ( Saccharomyces cerivasiae)
Administered in three doses (0 month, 1 month after 1st dose and 6 months after 1ST dose) Children – (0.5 ml three doses) 0m, 1m, 6m Adult – (1 ml three doses) 0m,1m, 6m INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Who should be vaccinated? Post exposure prophylaxis (PEP) Haemodialysis patients Homosexually active men Drug user Infants born to infected mother Personal contact with HBV patients Other high risk population like health Care workers Now it is part of the regular immunization schedule for children INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
UNIVERSAL PRECAUTION HEALTH CARE WORKERS
Wear personal protective equipment (gloves, gowns etc) Hand hygiene Use disposable and sterile needles Do not recap the used needles Avoid mouth pipetting Always transport the specimen with BioHazard sign INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Other prevention methods: Pre-screening of blood, blood products and donors for organ or tissue transplant for HBV,HCV, HIV is mandatory
Change in life style - ie avoid exposure to HBV carriers or patients
Avoid sharing personal hygiene products
Use sterile and disposable needles
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS C VIRUS
Parenterally transmitted non A – non B Hepatitis (NANB) Small, enveloped,35 to 60 nm in size contains positive sense,single stranded RNA virus Related to human Flaviviruses Placed in the genus Hepatitis C Virus
TRANSMISSION Same as HBV Verticle & sexual transmission is less than HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INCUBATION PERIOD – 5 to 12 weeks Peak onset of disease 7 to 8 wks after infection CLINICAL MANIFESTATION 80 % are asymptomatic in acute phase Symptoms – Fatigue, loss of appetite, jaundice, abdominal pain, itching, hives, joint pain, nausea, vomitting Chronic infection cause above symptoms + weakness, severe fatigue Serious complication of HCV include Cirrhosis of liver & progressive liver damage Increased risk of liver cancer
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
DIAGNOSIS By clinical data
Liver function test ALT shows fluctuating rise
Serology Detection of anti HCV antibodies by ELISA & Recombinant Immuno Blot Assay (RIBA) Detection & quantitation of genetic material from the viruses by RT-PCR
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Hepatitis C Virus Infection Typical Serologic Course anti-HCV
Titer
Symptoms
ALT
Normal 0
1
2
3 4 Months Months
5
6
1
2 3 Years
Time after Exposure INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
4
TREATMENT Recombinant alpha interferon is the only therapeutic agent approved by US No vaccine is available PREVENTION Tranfusion of safe blood & blood products All HCV positive persons – infectious Do not allow HCV positive persons or carriers to donate blood or organs Other control measures are same as HBV
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS A VIRUS INTRODUCTION
Also known as Infectious Hepatitis Family – Picornaviridae Genus – Enterovirus type 72
HAV
MORPHOLOGY
Icosahedral, spherical, naked virus of 27 nm in diameter. Virus contains ssRNA as genome.
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
SOURCE Sewage
contaminated water, Contaminated food.
MODE OF TRANSMISSION *Feco-oral route. *Affect food handlers &
in area with poor sanitation.
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
PATHOGENESIS FOOD
WATER INGESTION INTESTINE BLOOD PARENCHYMAL
KUPFFER
LIVER REPLICATION BILE
STOOL
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
CLINICAL MANIFESTATION
SUB CLINICAL – anicteric, undiagnosed.
CLINICAL – preicteric and icteric Incubation period – 2 to 6 weeks (mean – 28 days)
Preicteric : fever, chills, nausea, vomitting, abdominal discomfort.
Icteric : appearance of dark colour urine, clay coloured stool, jaundice of sclera & skin, hepatomegaly (right quadrant abdominal pain) INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
DIAGNOSIS
By clinical data Liver function test (Biochemical analysis) Alanine amino transferase – sharp rise with short duration Bilirubin increases upto 5 – 20 mg/dl Serum albumin increases& globulin decreases. Serology Antigen detection – Immunoflourescent test Antibody (IgM) detection – ELISA Presence IgG indicates past infection
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
TREATMENT No specific drug is available
PREVENTION Personal hygeine Good sanitation
VACCINE Formalin inactivated cell culture derived vaccine Recommended for – children at 1 yr of age and high risk population
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
HEPATITIS E VIRUS
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
STRUCTURE
Small round non enveloped virus Contains positive ssRNA genome Size 29nm Belongs to the family Calcivirus
SALIENT FEATURES Resembles HAV Adults are morre infected Occurs as outbrreaks No vaccine is available INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
Mortality rate is high if women affected in third trimester stage of pregnancy SOURCE faecally contaminated water
MODE OF TRANMISSION Oro faecal route PATHOGENESIS Not clear
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
LAB DIAGNOSIS
Detection of IgM or IgG antibodies – ELISA HEV detectiion by PCR is under development.
TREATMENT & CONTROL No specific treatment Prevented by safe drinking of water No vaccine available
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
http://medicalmicro.blogspot.com
INVISIBLE YET INVINCIBLE © http://medicalmicro.blogspot.com
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