HEPATITIS.pptx microbiology ppt highly recommend

Microbiology

1. HEPATITIS VIRUSES Hepatitis is an inflammation of the liver usually caused by viruses. Viral hepatitis is a systemic disease. Viral hepatitis is caused by Hepatitis A , B , C , D , E and G

2. HEPATITIS B VIRUS Most widespread and important type of viral hepatitis is Hepatitis B, caused by Hepatitis B virus. They belong to family Hepadnaviridae and Genera Orthohepadnavirus HBV is DS DNA virus of 42 nm in size with an outer envelop and inner icosahedral core that encloses DS DNA and a DNA polymerase. HBV genome consists of 2 linear strands of DNA held in a circular configuration. One of the strand is incomplete so the DNA appears partially double stranded and partially single stranded. HBV is the unique DNA virus, instead of replicating its DNA directly, it passes through an intermediate RNA stage where DNA is synthesized from an RNA template by “reverse transcription” resembling Retrovirus (HIV)

3. Electron microscopy of Hepatitis B patient’s blood reveals 3 types of Hepatitis ‘B’ particles. Tubular / Filamentous particle –(Unassembled component) These particles measure 22 nm dia of varying length. Spherical particle (Unassembled component) These are most abundant particles which measure 22 nm dia. 3. Dane particles ( very few in number) These particles are double walled spherical structure measuring 42 dia . These particles are complete HBV.

4. ANTIGENIC PROERTIES - HBs Ag (Formerly Australia Ag ) - It is an envelop glycoprotein found on the surface of Dane particles, spherical and filamentous particle. HBc Ag - It is an Antigen expressed on the nucleocapsid core 3. HBe Ag - It is soluble nonparticulate nucleocapsid protein. All these 3 antigens induce specific antibodies. Hepatitis B virus Mutants – Mutation in genes of HBV leads to emergence of mutants Precore mutants - Severe Chronic Hepatitis identified in Mediterranean countries and Europe. Escape mutants – Observed in infants born to HBe Ag + ve mothers or in liver transplant recipients or in recipients of active and passive immunization. YMDD mutants – Hep B patients treated with lamivudine therapy may develop drug resistant mutant.

5. MODE OF TRANSMISSION - HBV is highly infectious than HIV. Parenteral route – It is the most efficient mode of transmission. Transfusion of blood / sera of patients and carriers is most important source of transmission. Super carriers (More HBe Ag with a high titre of HBs Ag, DNA polymerase an HBV in blood). Simple carriers ( No HBe Ag and low level of HBs Ag in blood with no HBV and DNA polymerase) Number of Therapeutic , Prophylactic and Diagnostic procedures can convey the infection. Very minute amount of sera (0.00001 ml) can transmit the disease which include sharing of personal articles such as razors , nail clips , ear/nose ornaments and even comb can transmit the disease. The practices such as Tattoing , acupuncture , ear/nose piercing and field camps of surgery or blood tests for diagnosis, where sterile equipment's are not used are important source of infection. Professionals using sharp articles like Dentists , doctors and barbers may unwittingly infect clients. Infection by direct contact with open skin lesions such as pyoderma , eczema , cuts and scratches is common in young children.

6. 2. Sexual contact – The virus may also be present in the body fluids and excretions, such as saliva , semen , vaginal secretions , milk , urine and bile . Of these, semen and saliva are known to transmit the disease efficiently. The risk of transmission increases with the number of exposures. 3 . Perinatal and postnatal True congenital infection is rare ( Tansplacentally ) HBV is transmitted from infected mother to infants during birth by contact of maternal blood with the skin and mucosa of the foetus or postnatally from infected mother’s milk. HBV infected neonates generally do not suffer from any clinical illness, but remain carriers for life and some of them may develop Hepatocellular Carcinoma after many decades. 4. Occupational risk Medical , Dental and Paramedical staff , staff of Blood bank , dialysis unit , medical lab, are at high risk of infection. Dentist and surgeons have been responsible for small outbreaks.

7. PATHOGENICITY - The incubation period is long 2-6 months. After entry into the host, virus replicates in hepatocytes after which the infection proceeds for a long time without symptoms. (During this period, copies of HBV DNA integrate into hepatocyte genome and remain latent) The course of clinical illness is grouped into Acute infection Chronic infection Acute infection Pre-icteric phase – Onset is insidious, symptoms include malaise, anorexia, nausea, vomiting, abdominal discomfort but not fever. Icteric phase – Characterised by yellowing of skin and eyes due to impaired liver function. The damaged liver excretes bilirubin pigment slowly (yellow in colour), that accumulate in the body tissue and in urine. This symptom is commonly known as jaundice.

8. The pathogenesis of hepatitis is due to damage caused by CMI and inflammatory reactions . Since liver cells carry viral Ags , they are subject to Ab-dependent NK cell and cytotoxic T cell attack. HBV infection also promotes hypersensitivity reaction due to immune complexes of Ag-Ab reaction , that leads to extrahepatic complications such as Arthralgia (joint pain) Urticaria (skin rashes) Polyarthritis ( rheumatic disease of joints) Vasculitis (inflammation of blood vessels wall) Glomerulonephritis About 90-95% of the adults with acute hepatitis B infection recover within 1-2 months of onset and they eliminate the virus from the body within 6 months.

9. II. Chronic infection - About 5-10% of the patients become chronically infected. Some of them become asymptomatic carriers while in other it progress to fatal cirrhosis and liver failure A few of them develop Primary Hepatocellular Carcinoma (PHC) . The latency period b/w HBV infection and PHC may be as short as 9 yrs or as long as 35 yrs. LAB DIAGNOSIS – I- Detection of viral markers – Lab diagnosis of HBV infection is carried out by detection of various types of HBV Ags and their HBV Abs (referred as viral markers ) in the patient serum by ELISA The sequence of appearance of these viral markers in the blood is important in describing the course and nature of disease /stage of the disease and it also gives a good idea of degree of infectivity to others. II – Detection of DNA polymerase – appears in the serum during pre-icteric phase III – Polymerase Chain Reaction (PCR)- HBV DNA level can be detected by PCR

10. HBs Antigen and its antibody (anti-HBs) – It is the first Ag marker to appear in the blood after infection, being detectable even before onset of clinical illness. It remains in the blood through out Icteric course and persists for 6 mnths . HBs disappears with recovery from clinical disease and when it is no longer detectable its Ab Anti-HBs appears with in a week and remain for several yrs. 2. HBc Antigen and its antibody (anti- HBc ) – HBc Ag is not detectable in the sera of patients but can be detected in the liver cells by immunofluorescence technique. Its antibody anti- HBc appears early within few wks or after appearance of HBs Ag. Thus it is the earliest antibody marker to be seen in the blood (before anti- HBe or anti-HBs) and it remains for a longer period of time, may be for a life time. 3. Hbe Ag and its antibody (anti- HBe ) It appears in the blood at the same time as HBs Ag. Sera containing HBe Ag are believed to be highly infectious( Super Carriers ) and continued finding of HBe Ag in the blood indicate adverse prognostic sign. HBe disappears within a few wks , followed by the appearance of its antibody anti- HBe , signalling the start of resolution. This Ab persists for several months.

11. Anti- HBc persists life long Anti-HBs persists for several yrs. Anti- HBe persists for few mnths . Earliest Ag marker HBs Ag Earliest Ab marker Pre-icteric phase Icteric phase

12. PROPHYLAXIS I – General preventive measures Avoiding direct/ Indirect contact with blood, sera or other body fluids of patients and carriers. Screening of HBs Ag and HBe Ag of blood/sera of donors. Health education, Strict attention to sterility. II - Immunisation – Both active and passive methods Active immunisation - More effective a) Recombinant vaccine - Produced by genetically engineered, recombinant DNA in yeast. Gene responsible for production of HBs Ag is incorporated into yeast DNA. HBs Ag produced by them are extracted , purified and used as vaccine. More immunogenic if conjugated with alum adjuvant . 3 doses of IM injection given at--- 1 st _ 0 month 2 nd _ 1st month constitute full course ----- Protection is longer 3 rd - 6th month

13. 2. Passive immunisation Used in accidental exposure to hepatitis B infection. Hyperimmune hepatitis B immunoglobulin (HBIG) of 300-500 IU dose given as IM injection and is given immediately after exposure. It may not prevent infection, but gives protection against illness and development of carrier state. 3. Combined immunisation Combined is recommended for non-immune persons exposed to HBV. For babies born to carrier mothers, a single injection of 0.5 ml of HBIG given IM immediately after birth, which is followed by full course of vaccine at different site. The first dose being given within 12 hrs of birth.

14. TREATMENT No specific treatment is available for acute HBV infection. Interferon alpha , alone or in combination with other antiviral drug such as lamivudine, telbivudine and famcyclovir , has been beneficial in some cases of chronic hepatitis. *******************************