Bloodborne Viral Infections Flashcards
Hepatitis B Virus: family, transmission, clinical course of infection, outcomes (2), factors increase risk of chronic HBV (4)
Hepadnaviridae (40-45 nm, dane particles)
Transmission:
- vertical – mother to infant, mainly perinatal
- horizontal – sexual, blood-borne (IVDA, sharps injury, tattoo, transfusion/ transplant rare now)
Clinical Course:
- incubation: 2-6 months
- asymptomatic: children, neonates, 30-50% adults
- Acute hepatitis: symptoms include fever, jaundice, malaise (symptomatic = more likely to recover)
- fulminant hepatitis <1%
Outcome:
- full recovery with clearance of virus – immune
- 5-10% chronic hepatitis –> asymptomatic carrier for 20-40 years == lead to chronic active hepatitis, cirrhosis and increase risk of HCC (200x)
Factors increasing risk of chronic Hep B:
- asymptomatic primary infection (usually children)
- immunocompromised
- male
- infant (young) - 90%!!
HBV Epidemiology: prevalence and related transmission routes, carrier rates in HK
Worldwide
- high and intermediate prevalence –> mainly vertical transmission
- low prevalence e.g. HK –> horizontal transmission or acquired overseas
Approx 100% vaccination rate in HK
- universal immunisation in 1988
- low HBV carrier rate in younger generation
- antenatal women, older patients and certain risk groups e.g. TB, HIV, IVDA still have high carrier rate
- 0.9% of HK blood donors
- Carriers in HK: overall 2%, IVDA 10%
350 million carriers worldwide, 1 million deaths/yr
HBV diagnosis: markers and their interpretation
HBsAg: marker of INFECTION, acute or chronic (if >6 months)
- infective and inactive carriers both +ve
Anti-HBs IgG: marker of recovery from previous infection or vaccination – IMMUNE
- protective Ab
Anti-HBc: marker for INFECTION
- IgM = ACUTE (occasionally present at low levels in carriers)
- IgG = CHRONIC/ RECOVERED – marker of NATURAL infection
- non-protective Ab
- only marker in “window period”
- IgG in both infective and inactive carriers
HBeAg/ HBV DNA: INFECTIVITY
- signify ongoing replication
- detectable shortly after HBsAg
- acute infection, infective carriers
Anti-HBe: low infectivity
- appears after HBeAg disappears
- inactive carriers
HBV prevention: vaccine, prophylaxis indications, efficacy
Vaccination
- recombinant vaccine based on HBsAg
- 3 doses (0-1-6 months)
- effective >97%, safe
- universal to all newborns since 1988
- post-vaccination check or booster not routinely needed (only for health care workers after sharps injury)
- possible to have non-responders (counsel on prevention and HBIG)
Hepatitis B immunoglobulin (HBIG)
- post-exposure prophylaxis
- immediate but short duration (1 month)
- newborns with HBsAg +ve mothers (+ vaccine)
- sharps injury in non-immune healthcare workers
HBV treatment
Slow disease progression, reduce liver damage and prevent cirrhosis and HCC but doesn’t eliminate infection
- Peg-interferon
- Nucleotide analogues (more common) - viral polymerase inhibitors
e. g. Entecavir, Tenofovir (lower resistance), lamivudine, adefovir, telbivudine - Tenofovir also used in pregnant lady (at 28-32 wks) with high viral load to decrease maternal foetal transmission
Hepatitis C Virus: transmission, acute infection, risk of chronic infection, prevalence, prevention
Transmission: same as HBV but less infectious (vertical - 3-5%, higher in HIV +ve, and horizontal)
Acute infection:
- incubation: 6-7 wks
- most are asymptomatic
- <1% fulminant hepatitis
*Chronic carriers: VERY COMMON - 80% infections progress to chronic carrier, cirrhosis and HCC
Low prevalence in most parts of the world (rarely >5%)
- 0.06% of HK blood donors
- Carriers in HK: overall 0.3%, **IVDA >50% in HK
- 150 million carriers, 0.35 million deaths/yr
Prevention: no vaccine or prophylaxis available, behaviour modification only e.g. blood product screening, safe sex, needle risks
HCV diagnosis
Serology
- IgG or total HCV Ab
- seroconversion 1 wk after ALT increase or 4-10 wks after exposure
- Limitations: false -ve/+ve – low prevalence so PPV is lower
Screening: EIA
Confirmatory assays: RIBA (recombinant immunoblot assay) - less commonly used now as need RNA detection to determine active infection
- non-protective Ab
Direct detection
- PLASMA: HCV RNA (detectable in 2-22 days; 70%) - shortens diagnostic window
- HCV core antigen in 95% of HCV RNA+ve
Combined test:
- both HCV IgG and core antigen detection
- higher sensitivity
HCV treatment: goal, choices of drugs and their benefits/disadvantages
Goal is to eradicate HCV RNA i.e. absence of detectable HCV RNA in blood 6 months after stopping treatment
- Peg-interferon (injection) and Ribavirin (anaemia side effect)
- -> sustained virological response in 60-80% depending on genotypes e.g. Genotype 1 in HK not very effective (<50%)
- -> range from 24-48 wks Tx
- Direct acting antiviral agents (DAA)
- -> protease inhibitors, NS5A and NS5B inhibitors
- -> combination of oral therapy with less adverse effects
- -> better compliance
- -> 12-16 wks duration, SVR >90%
- -> very expensive
Hepatitis D Virus: features of infection, serology
HDV only occurs as co-infection or superimposed infection with HBV
Co-infection: HBV established first to provide HBsAg necessary for production of complete HCV virions
- 4% fulminant hepatitis and 5% chronic infection
Superinfection in chronic HBV: chronic HDV in 80-90%, 10% fulminant
Serology: Anti-HDV IgM
Human Immunodeficiency Virus: basic infective mechanism, route of transmission
Retrovirus
- ssRNA –> dsDNA by reverse transcriptase (target of antiviral)
- viral dsDNA integrates into host genome (difficult to clear once infected)
- polyproteins cleaved by viral protease into component proteins & assemble to mature virion (target of antiviral)
Route of transmission:
- sexual (higher risk in genital ulcers e.g. syphillis, HSV)
- vertical – 15-40% risk during delivery and breast feeding; decrease risk by antiviral treatment in pregnancy
- blood and body fluid rare
HIV clinical course: 3 phases
Acute phase: 2-4 wks
- 30% develop “acute disease syndrome” or “sero-conversion illness” with fever, enlarged LN, non-specific flu-like, rash, neutropenia (IM-like)
- high viral load (risk of transmission)
Latent phase: 6-10 yrs
- asymptomatic
- lower viral load but still highly infectious
- CD4 T cells continuously destroyed by virus and levels decrease gradually
AIDS:
- CD4 T cells very low <200/microL or <14%
- immune function impaired
- AIDS defining illnesses
- –> opportunistic infections: zoster, TB, cryptococcus, PCP, toxoplasma
- –> malignancy: Kaposi’s sarcoma (HHV-8), Non-hodgkin lymphoma (EBV), cervical or anal cancer (HPV)
HIV diagnosis
Window period 2-8 wks
- infectious but Ab not developed yet
HIV Ab
- 97% develop within 3 months
- screening ELISA, confirmation western blot
- but 3 months too long as there is risk of transmission
HIV RNA PCR if highly suspicious - 2 wks detection
Ag-Ab combo assay (4th gen ELISA) - 3-4 wks detection
(new algorithm: 4th gen ELISA –> if +ve, HIV-1/2 antibody differentiation assay –> if -ve or indeterminate then HIV RNA)
HIV burden of disease and epidemiology
High burden of disease
- 34 million infected, 3.4 million children <5 yrs
- 2.2 million die/yr
HK
- 600 HIV cases
- 80 reported each year
- 75% male, 70% Chinese
- mostly from sexual contact, perinatal infections rare, IVDA carriers uncommon (3.9%)
HIV prevention and treatment regime/ aim, drugs involved and mechanism (3 categories)
No vaccine
- safe sex, blood/organ screening
Highly Active Antiretroviral Therapy (HAART)
- start treatment regardless of CD4 count
- lower viral load to undetectable levels
- requires good compliance – re-emerge if stop or poor compliance i.e. INCURABLE
- always check genotype resistance first
- combination of at least 3 drugs (2 NRTI +1 NNRTI/PI/INSTI)
Reverse Transcriptase inhibitors
- prevent copying of HIV RNA into proviral genome
- nucleotide analogue (NRTI): zidovudINE, lamivudINE
- non-nucleoside RT inhibitors (NNRTI): nevirapINE
Protease inhibitors
- inhibit cleavage of viral polyproteins into mature proteins
- RitoNAVIR
Integrase inhibitors
- inhibit integration of proviral DNA into cellular DNA
- RalTEGRAVIR
Other drugs:
- fusion inhibitors: enfuvirtide
- CCR5 co-receptor antagonist: maraviroc
Sharps injury management: primary prevention, minimise accident, management of accident, wound care
Primary prevention:
- HBV vaccination
- post-vaccination check
- no vaccine for HIV or HCV
Minimise accident:
- standard precautions (gloves, PPE etc)
- engineering controls e.g. sharps disposal
- work place controls
Management of accident:
- immediate wound care
- reporting
- risk assessment (infection status of source; usually HBV/HIV) –> any need for post-exposure prophylaxis
- advice and medical FU
Wound care -
- intact skin – wash off blood under running water with skin antisepsis; avoid brushes
- percutaneous – wash with soap and water, no scrubbing; encourage bleeding for minor injuries; disinfect and dress
- mucosal/eye – flush with water/saline
