7. Blood Borne Viruses Flashcards
Hepatitis viruses - basic definition
—> inflammation of the liver
Acute hep
• Acute = less than 6 months
Chronic hep
• Chronic = longer than 6 months
Strains of hep - basics
- 5 main strains of the hepatitis virus referred to as A,B,C,D and E.
- While each virus can cause similar symptoms, they are transmitted differently and can affect the liver in different ways.
- Hepatitis A and E cause short term infections – fecal oral route .
- Type B and C can lead to chronic disease and together are the most common cause of liver cirrhosis worldwide. - chronic liver disease
Importance of hepatitis viruses
- Disease burden and economic burden due to chronic hepatitis related liver cirrhosis, liver cancer, liver transplant and mortality from the disease.
- Hepatitis B is preventable due to vaccine. Universal vaccination introduced to UK infant schedule 2017.
- Hepatitis C is treatable with direct acting antiviral drugs. NICE licensed.
HAV structure
•HAV is a non enveloped RNA virus in the picornavirus
HBV - structure
•HBV is an enveloped partially double stranded DNA virus in the hepadnavirus family
HCV - structure
•HCV is an enveloped single strand RNA virus in the flavivirus family.
HDV - structure
•HDV is a defective virus can’t infect a hepatocyte unless already infected with HBV
HEV - structure
•HEV is a non enveloped RNA virus in the Hepeviridae family
Non enveloped RNA hep viruses
HAV and HEV – non enveloped RNA
Enveloped virus
Hep b- enveloped double strand DNA
Hep C_ - enveloped single strand RNA
Defective virus
Hep D- only infect those with hep B
HEP A - details
—> RNA virus Picornaviridae
- Oral-Faecal Route – contaminated food or water
- Incubation 2-6 weeks
- Vaccine available
- Self limiting, complications rare
- HAV IgM in an active infection
- HAV IgG recovery/vaccination - can develop over time in the virus
HEP E - details
—> RNA virus Hepeviridae
- Oral-Faecal Route
- Incubation 40 days
- Dangerous in pregnant women
- Self limiting- off licence medications Ribavarin
- HEV IgM in active infection
- HEV IgG recovery produced later
HEP B - details
—-> blood borne virus – spread by blood, semen or bodily fluids
- Sexual contact
- IVDU - IV drug users
- Blood Products
- Needlestick injuries
- Incubation : 6/52-6/12
- Chronicity. = younger you are the worse repsonse you have to hep B
- Vaccine available but no cure – babies screened asap vertical transmission
Hep B - vertical transmission
Vertical Transmission (75% globally) = passage from mother to child (just after childbirth normally, perinatal) • Without treatment and precautions for hep B postiitve women there is 40% chance to pass to newborn but the newborn won't show symptoms – only release later down the line, when shown in chronic liver disease • All preg women are screened for hep B
HEP C - details
•IVDU (90%) iv drug users •Sexual contact <1% •Infants born to HCV +ve (vertical transmission) •Blood products prior to 1991 – as before then blood products weren't screened •Needlestick injuries sharing needles •Incubation: 2/52-6/12 •Chronicity 80% •No vaccine but may be cured
Screened for as it can be symptom free
Pathophysiology of hepatitis
- Acute infection after inoculation/ingestion
- Virus enters hepatocytes (liver cells) which are the main site of replication
- This triggers a cellular immune response by the host’s defence mechanisms and release of cytotoxic cytokines and natural killer cells
- Attack the infected hepatocytes leading to destruction of the hepatocytes and release of liver enzymes
- Oedema and necrosis
- Cholestasis- altered blood flow through the liver
Long term effects of hepatitis
- Fibrosis- scarring
- Cirrhosis- severe scarring
- Carcinoma
Symptoms
- Malaise
- Lethargy
- Fever
- Nausea
- Anorexia
- Abdo pain
- Jaundice- yellow discoluration of skin and/or sclera
- Pruritis - itching of skin
- Dark urine, pale stools
No symptoms = acute hep can be asymptomatic or vague or mild, general or non-specific
Signs of hepatitis
Fever
•Jaundice
•Hepatomegaly,- enlargement of liver - tender
Signs of chronic liver disease
- Later signs of liver cirrhosis- palmar erythema (red palms and finger tips), spider naevi (spidery veins under skin), gynaecomastia,(breast tissue developemnt in men)
- abdominal distension, (swelling of abdomen), caput medusae, (portal vein hypertension) encephalopathy.(confusion)
Investigations for acute hep
Blood tests
•Liver function tests;
•Immunology - screening for all hep A, B, C and E
•Imaging- not usually required for diagnosis
•USS, CT scan, liver biopsy
•Liver function tests;
» Liver transaminases : (marker of HC damage when liver is destroy) ALT & AST
» Alkaline Phosphatase : (located on the outer layer of cell membrane/indicator of BT cell damage/cholestasis)
» Albumin ( protein synthesised in the liver) - decrease in chronic phase
» Coagulation tests (clotting factor are synthesised in the liver) INR PT – INR and prothrombin time
Hep B serology
.
3 Hepatitis B Markers
– HB Surface Antigen = surface protein in both chronic and acute hep, used to generate vaccine
– HB Surface Antibody = indicates recovery and immunity
– HB Core Antibody = show previous or ongoing infection
• IgG in chronic, IgM in acute
– HB Surface Antigen
– HB Surface Antigen = surface protein in both chronic and acute hep, used to generate vaccine
– HB Surface Antibody
– HB Surface Antibody = indicates recovery and immunity
– HB Core Antibody
– HB Core Antibody = show previous or ongoing infection
Hep B management
- Refer anyone who is HBsAg positive to a gastroenterologist or infectious disease specialist. - determine treatment
- Notifiable to PHE
- No cure-integrates into host genome
- Life long anti-virals suppress viral replication e.g. entecavir, tenofovir, lamivudine.
3 Life long anti-virals suppress viral replication
entecavir, tenofovir, lamivudine.
Hep B vaccination - what is it
- Genetically engineered surface Ag
- 3 doses + boosters if required
- Produces surface antibody response
- Universal UK infant schedule in 2017;
- 6 in 1 vaccine
- Given at 2,3,4 months
Hep B vaccination - who receives it
• At risk population including babies born to infected mothers, close family or sexual partner, receive regular blood transfusions or products, people whose work puts them at risk, prisoners, IVDU iv drug users, MSM – male sex with male .
Hep C serology
- Serology anti Hepatitis C antibody only
- Remains positive even after cure
- Not protective can get re-infected
- Viral PCR- if positive confirm chronicity
Hep C management
- Refer to specialist gastroenterologist or specialist hepatologist
- Directly acting antiviral drug combo 8-12 weeks
- > 90% chance of cure
- Can get re-infected – identify and avoid risks
Importance of HIV
- Important clinical condition
- Preventable & treatable
- Also a chronic infection – you are never really cured as you will always be a chronic carrier of HIV
- High rates of late diagnosis – partially due to stigma
What is HIV
• Human Immunodeficiency Virus (HIV-1 and HIV-2)
• Retrovirus (“backwards”)
– ssRNA DNA ssRNA
How does HIV impact cells
• Infects cells with CD4 molecules – T helper cells and macrophages • surface receptor – T-helper lymphocytes – (Monocytes / macrophages) • Glycoproteins gp41 and pg120 • Reverse transcriptase • Protease • Integrase – integrates viral DNA into cell DNA
• HIV replicates inside cells ➔ Spreads to / infects more cells
Replication of HIV
- Fusion of HIV to the host cell surface
- HIV has RNA, reverse transcriptase, gp41. Gp120
- Gp120 attaches to CD4 on surface of the cell – a co factor CCR5 CXR4 are there to ensure attachment
- Gp120 pulls HIV in and fuses with the cell membrane – RNA and enzymes released into cell
- Reverse transcriptase converts RNA-DNA
- Integrase acts in cell nucleus to integrates viral DNA into cells double stranded DNA = proviral DNA
- New proviral DNA is transcribed to RNA
○ Some used as mRNA
○ Some used to make proteins - New virus forms, bud off from the cell and is released
Progression of CD4+ T lymphocyte count in HIV infection
- As virus is multiplying there is a decrease in CD4 T cells as they are being infected
- But immune system gears up and eventually it starts to try and destroy the virus so T cells can recuperate – this balance level maintains for years
- But when triggered there can be a continuous decrease in CD4 t helper cells until it leads to aids
Relationship in number of virus cells and body cels
As virus particles go up, number of cells goes down and vice versa
When body can’t control virus particles body cell number completely go down
3 Conditions associated with AIDS
- Varicella zoster virus – chicken pox
- Shingles
- Herpes simplex
3 types of HIV transmission
Contact of infected bodily fluids with mucosal tissue/blood:
Medical procedures:
Vertical transmission:
Transmission
Contact of infected bodily fluids with mucosal tissue/blood:
- Unprotected sexual intercourse (anal/vaginal)
* IV drug users (sharing needles)
Transmission
Medical procedures:
- Blood/blood-products transfusion
- Surgery
- Needlestick injury
- skin grafts, organ transplant
Transmission
Vertical transmission:
• Mother to baby (during pregnancy, at the time of birth, breast milk)
Factors affecting HIV transmission
- Type of exposure
* Viral level (viral load) in blood
• Type of exposure to HIV
– type of sexual act (use of condoms)
– transfusion, needlestick, mucous membrane
– other STI (Inflammation of genital tract)
– sexual assault
• Viral level (viral load) in blood
– U=U - sustained undetectable viral load (VL) for 6/12 months in a row this means that HIV is untransmittable – so those people cannot transmit the virus from themselves to someone else
Detection of HIV
– Early detection Treatment
– Adherence to treatment = treatment helps to suppress virus
– Healthy living
• less or no Smoking, alcohol, metabolic problems
• Late detection = worse prognosis (x10 risk death in 1st year)
Oral candidiasis
• Decrease immune system
= suppress normal flora in mouth so candida gloer instead
Blood test – Serology
––> use this to pick up = HIV antigen (Ag) – viral capsid protein p24
– can also pick out HIV antibody (Ab) – early antibodies to p24 and gp41 (transmembrane protein). Appear at 3-12 weeks and persist for life
– Current test: detects both Ag and Ab
– Result on same day = rapid tests
– May get false negative result
PCR - what is it
– Detects HIV nucleic acid
– Highly sensitive
– Detects very early infection (few days)
– Expensive; results slow (few days)
– Used for follow-up / treatment response
Rapid tests
– low cost, <1hr – Usually detect HIV antibody – Blood test (finger-prick) – Oral (saliva) – In-Home tests – Postal testing
- If negative – accurate
- May get false positive result – Need to confirm with serology
Who should be tested for HIV
Patients presenting with the following:
• Respiratory: bacterial pneumonia / TB
• Neurology: meningitis/dementia
• Dermatology: Severe psoriasis Recurrent/multi-dermal shingles
• Gastroenterology: Chronic diarrhoea/weight loss ?cause
• Haematology: any unexplained blood abnormality
• Oncology: lymphoma, anal cancer
• Gynaecology: Cervical intrapithelial neoplasia (CIN)
• Sexually transmitted diseases: Hep B/ HepC
Test is offered to all pregnant women to prevent offspring getting HIV
Aims of HIV therapy
- Undetectable HIV viral load – aim to get rid of all the virus
- Reconstitute CD4 count /immune system – make a good CD4 cell count
- Reduce risk of transmission
- Good quality of life (low side effects, compliance)
- Normalise lifespan
5 Targets for HIV therapy
- Post attachment inhibitors
- Fusion inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
- Protease inhibitors
• Post attachment inhibitors
○ Drug inhibits HIV attachment to cell
• Fusion inhibitors
○ Drugs inhibit HIV fusion with cell membrane
• Reverse transcriptase inhibitors
○ Drug targets and inactivates reverse transcriptase in HIV
• Integrase inhibitors
○ Drug prevents integrase enzyme integrating DNA
• Protease inhibitors
○ Inhibit protease
ART – antiretrovirals actions
- Nucleoside reverse transcriptase inhibitor (NRTI)
- Non-nucleoside reverse transcriptase inhibitor (NNRTI)
- Protease inhibitor
- Integrase inhibitor
- CCR5 inhibitor
Why give 3 or more ART to HIV positive patients
- Virus mutates (changes/adapts) every 2-3 rounds
- Resistance to drugs can develop in days
- 1 drug – resistance develops quickly
- 3 drugs – harder to develop resistance - target different activites of the HIV
•Emergency anti-HIV medicine called post-exposure prophylaxis (PEP)
may stop individuals becoming infected if started within 72 hours of possible exposure to the virus – it’s recommended that they start it as soon as possible, ideally within 24 hours
Strategies for HIV prevention
- Education (understanding of spread/control, reduce stigma)
- Increase condom usage
- Prevention of mother-to-child transmission (testing)
- Increase testing
- Needle and syringe programmes (IV drug users)
- Male circumcision
- Post-exposure prophylaxis (PEP)
- Pre-exposure prophylaxis (PrEP) - for people who are at high risk of HIV infection, for example, those whose partner is HIV positive
- Development of vaccine(s)
Ethical dilemmas in HIV
- Psychological impact of diagnosis
- Dealing with stigma
• Patient confidentiality vs: – Health of mother – Health of unborn child – Health of sexual contact (husband) – Health of older child – Risk to patients / staff at workplace
• GMC guidance
Tuberculosis
Bacteria - mycobacterium Tb
Toxoplasmosis
Protozoa - toxoplasma Gondii
in inhaling infected food/dust
PCP pneumocystis pneumonia ‘
Fungus. -pneumocystsis jiirovecii
Lung infection
Cryptococcal disease
Fungus - cryptococcus neoformans
Lungs
CMV
Virus - human herpes virus, cytomegalovirus
