WK 11- Blood Borne Viruses Flashcards
What are the 3 enzymes that HIV contains
reverse transcriptase, integrase and protease
What is the viral structure of HIV
2 x ssRNA and 3 enzymes
What is the most common type of HIV
HIV-1
What are the 4 major groups of HIV-1
M (major) group, O (outlier) group & 2 new groups (N & P)
Where are rates of HIV highest
- present in all countries of the world but rates are highest in Sub-Saharan Africa and South Africa
- Infections in women are increasing
How is HIV transmitted
-sexual (MSM), blood or blood products (transfusions, IVDU), vertical (mother to baby- if you treat the mother with antivirals during pregnancy you can reduce viraemia and prevent transmission to baby), oral transmission
What are the 3 clinical stages of HIV
- Acute infection
- Clinical latency
- AIDS
What symptoms are associated with acute infection
flu-like symptoms that are non-specific- 2-4 wks post exposure
→ fever, lymphadenopathy, headache, rash
What symptoms are associated with clinical latency
flu-like symptoms disappear and person may not have symptoms, but as T cells decline they may get lymphadenopathy and chronic diarrhoea – but mainly asymptomatic and last 3-20 years
→ fever, weight loss, GIT disturbances, muscle pains
What symptoms are found in AIDS
T cells are completely depleted and there will be systemic symptoms and viral induced cancers (Kaposi’s sarcoma)
→ prolonged fevers, night sweats, unexplained weight loss
How is HIV diagnosed in the lab
- Screening with HIV Ag/Ab combination test (Automated EIA)
- Positive screening are referred for confirmation testing by looking for p24 Ag and then performing western blot
How can a western blot detect HIV
- Have filter paper with viral proteins attached (gp120, reverse transcriptase, gp41, p24→ depending on what stage of illness the pt is at determines the antigens that will be detected)–> add pt serum, if there is Ab in the patient serum the Ab will bind and cause a colour change
- the more colour changes (lines)-> the more progressed the infection
What is HIV-genotyping
once HIV genome is integrated into human genome it produces pro-viral DNA→ pro-viral DNA is able to be detected in the patients lymphocytes→ allows you to test babies and determine vertical transmission
What is the tx for HIV
-HAART = Highly Active Anti-Retroviral Therapy
-Combination of at least 3 drugs that suppress HIV
replication & decreased risk of developing resistance
What drugs are used for HIV tx
- NRTI (nucleoside reverse transciptase inhibitor)
- integrase inhibitor
- protease inhibitor
- NNRTI (non-nucleoside reverse transcriptase inhibitor)
- fusion inibitors
How can HIV be prevented and controlled
-Education
-Safe sex, needle exchange
-Antiviral treatment of pregnant HIV +ve
women
-PREP→ pre-exposure prophylaxis
-No vaccine yet→ due to rapid mutation
What is the viral structure of HTLV
- RNA retrovirus
- Genome: 2 copies linear +ve sense ssRNA
What is the difference between HIV and HTLV
HIV-1 was originally known as HTLV-3 but now HTLV3 causes lymphocytosis, and HIV causes lymphopaenia
What cell does HTLV1 infect and what is the result
predominantly infects
CD4+ve T-lymphocytes-> causes lymphocytosis
How is HTLV-1 transmitted
-HTLV enters body inside infected CD4+ve T lymphocytes in blood or semen, as well as
vertically via breast milk and possibly transplacentally
-Intrauterine & peripartum transmission
What are the 3 categories of symptoms of HTLV1
Malignant, Inflammatory, Infective
What are the malignant symptoms of HTLV1
-Acute T-cell leukaemia/lymphoma (rapidly fatal), Chronic T-cell leukaemia/lymphoma, Cutaneous T-cell lymphoma
What are the inflammatory symptoms of HTLV1
-HTLV-Associated Myelopathy (“HAM” or “Tropical Spastic Paralysis”) -Uveitis -Arthropathy -Sjogren’s syndrome -Polymyositis -Thyroiditis
What are the infective symptom of HTLV1
- Strongyloidiasis
- Crusted scabies
- Bronchiectasis
- Infective dermatitis
- TB, leprosy
How is HTLV1 diagnosed
- PCR is used to determine whether the Ag are mothers or babies→ used in vertical transmission as not always sure whether the Ag is due to infected mother or foetus
- Detection of HTLV-specific Ab by serology
How is HTLV-1 prevented
- No specific treatment
- Breastfeeding considerations
- Screening of donated blood products
- Barrier protection to prevent sexual spread
- IVDU avoid needle sharing
What family does HBV belong to
Hepadnaviridae
-partially ds circular DNA
What are the 3 important viral antigens
HB surface Ag (HBsAg, viral envelope protein)
- HB core Ag (HBcAg)
- HBeAg
What is the epidemiology of HBV
endemic in the asia-pacific area→ risk groups include indigenous Australians, IVDU, high risk sexual activity, those born overseas in endemic areas
How is HBV transmitted
Transmission:
-Parenteral & mucosal (esp. sexual) exposure
to infected blood or body fluids (saliva, semen,
vaginal secretions, breast milk)
-Transmission to foetus during pregnancy & at
delivery→ every pregnant woman is screened for HBV so normally under control before birth
-IVDU
-Needle-stick injuries
-Reuse of needles
-Child to child transmission (biting, etc)
-Sharing of personal items (razors, toothbrushes,
nail clippers, etc)
Where does HBV replicate
replicates in hepatocytes in the liver
What is the pathogenesis of HBV
HBV travels to liver via bloodstream →Mechanisms by which HBV infects
hepatocytes not yet well understood
-Virus infects healthy liver cells & triggers immune
response that destroys the damage and destruction of the hepatocytes
→Hepatitis B is an immune mediated disease, as
opposed to HIV which destroys immune cells
What is acute infection of HBV
HBV infection considered acute during 1st 6
months following infection
What is a chronic infection of HBV
If HBsAg persists >6months the infection is considered
chronic (patient has been unable to clear the virus after 6 months→ failed to mount an immune response)
-Chronic infection can be life-long
What are the symptoms of acute HBV
- many cases are asymptomatic and can transmit unknowingly – common in children
- Symptoms common in adult infection:
- Loss of appetite
- Nausea & vomiting
- Tiredness
- Abdominal pain
- Muscle & joint pain
- Jaundice (usually occurs ~12wks post infection)
- Small % cases develop fulminant hepatitis
What are the symptoms of a chronic HBV infection
- again most cases are unaware and can be asymptomatic but can present with:
- Tiredness, depression, irritability
- RUQ pain
- Nausea & vomiting
- Loss of appetite
- Joint aches & pains
What is the course of a disease if an infant is infected with HBV
-Infants rarely experience symptoms of acute
infection, h/w 90% will develop chronic HepB (happens in endemic regions)
What is the course of a disease if a child is infected with HBV
Rarely experience symptoms of acute
infection, h/w 30% will develop chronic HepB
What is the course of a disease if an adult is infected with HBV
-Adults and adolescents commonly experience
symptoms of acute infection, h/w <5% will develop chronic HepB
Why do adults get symptoms of HBV but do not get chronic infection
Thought to be a result of a matured immune system-> this is why babies get chronic infection (unable to clear the infection) but do not get any symptoms (as HBV is immune mediated)
What is HBsAg
- Indicator of current infection
- Can be detected in acute & chronic HBV
What is HBsAb
-Indicator of immunity (prior infection or
vaccination)
What is HBeAg
- Indicator of virus replication & infectivity
- Presence indicates individual is highly infectious
What is HBeAb
-Indicator of recovery from infection
What is HBcIgM
-Indicator of recent infection
What is HBcTotal Ab
-Indicator of past infection
-Test may be performed if patient does not
seroconvert after vaccination
What is HBV DNA
May be used to clarify the stage of infection,
especially if LFTs are abnormal and if the HBsAg
and/or the HBeAg are detected
-Can be used for monitoring response to treatment
What other tests can be done to diagnose HBV
-LFTs: ALT (alanine aminotransferase) – released into blood when liver cells injured
-Liver biopsy: Not often used now
-AFP (alpha- foetoprotein): blood test to detect liver cancer, AFP is a tumour marker (i.e. An embryonic protein produced by
cancer cells)
-Coagulation profile: Will be deranged in hepatitis (no clotting factors will be produced)
What is the tx of HBV
-Number of antiviral agents available
→ no ‘cure’= aim is to reduce replication and transmission to other contacts and pt deterioration
-Australia use Tenofovir, IFN
-mainly only consider tx if liver damage has occurred
How is HBV prevented
- Vaccination→ Safe & effective, part of routine childhood vaccination schedule-> given at birth
- Plus recommended for other at-risk groups
- Avoid transmission risk
- HBIG (immunogloblulin) within 72hrs post exposure→ prevent acquiring HBV from needlestick
What family does Hep C belong to
- flavivirus (most are mosquito borne)
- Ss +ve sense RNA genome
What are the main strains of hep C in aus
3a, 1a, 1b
How is HCV transmitted
majority are due to IVDU
- other means= Non sterile tattooing/body piercing
- Non sterile medical procedures/vaccinations
- Needle stick injuries
- Household exposure
- Other blood to blood contact→ source of HCV infection unknown in some cases
What is the pathogenesis of HCV
-Direct invasion of hepatocytes
-Molecular mechanisms not fully understood
-HCV induces a strong early innate response but
seems to be resistant to the antiviral effects of this response, resulting in chronic infection in up to 80% cases
What complications can arise from HCV
Over the course of 10-20yrs of chronic
infection extensive scarring of the liver occurs
(fibrosis & cirrhosis) & in some cases hepatocellular cancer develops→ most people develop chronic infection
What are the factors that suggest someone will develop cirrhosis/liver cancer from HCV
male, alcohol intake, HBV/HIV co infection, obesity, age at time of infection (fastr disease if infected over 40)→ all increase the risk of developing cirrhosis or liver cancer
What tests are done to screen for HCV
Screening test: EIA for HCV Ab
- 2nd EIA for confirmation
- HCV Ag test if required
What lab diagnostic tests are available for HCV
HCV PCR
- Qualitative or quantitative (“viral load”)
- Useful for monitoring of treatment
- HCV genotyping: can be useful guide for duration of therapy
What family does HDV belong to
Deltavirus→ ssRNA
Why is HDV a ‘defunct’ virus
Lacks polymerase→ needs concurrent HBV infection
What diseases does hep D cause
- acute and chronic hepatitis
- Co-infections (if concurrent HBV infection) or super infections (someone who is a carrier of HBV)
What is the pathogenesis HDV
Dissemination via blood to liver – replicates in
hepatocytes→Hepatocytes are the only susceptible cells
-Highly pathogenic virus
What lab Dx are available for HDV
Lab diagnosis:
- look for HBV first→ if they don’t have HBV they will not have HDV
- Serology for Ab and HDAg
- PCR for HDV RNA
