M24: Disease Transmission VI: Blood and Transplant-Associated Infections Flashcards
Bloodborne Infections:
Mechanisms of transmission:
Agents
vertical
horizontal
sexual
percutaneous
iatrogenic
- transfusion
- _ or _
transmissible if circulating in blood
mother to infant, e.g. HIV
incidental contact, splash to mucosa
micro abrasions
sharing needles, razors
medical procedure related e.g. HBV
- RBC, platelets, plasma, clotting factors
- contaminated multi-use vials or re-using non-sterile needles
Bloodborne Infections:
Mechanisms of transmission:
Agents
vertical
horizontal
sexual
percutaneous
iatrogenic
- transfusion
- _ or _
transmissible if circulating in blood
mother to infant, e.g. HIV
incidental contact, splash to mucosa
micro abrasions
sharing needles, razors
medical procedure related e.g. HBV
- RBC, platelets, plasma, clotting factors
- contaminated multi-use vials or re-using non-sterile needles
Bloodborne Infections:
Risks:
(8)
The risk of _ due to transfusion has decreased from ~1 in 1000 units in the late 60s to less than 1 in 100,000 units today (less than 1 in a million for HIV) due to improved screening procedures.
Risk of infection from a _ injury from a patient known to be infected (Massachusetts Sharps Injury Surveillance System, 2002): HBV ~30% HCV~ 3% HIV~ 0.3%
Increased risk: higher _ (inoculum), visible _, hollow _, _ of puncture
Reduced risk: use of _, safety-engineered _, proper use of _
Intravenous drug use, blood transfusion, hemodialysis, health care worker with exposure to human blood products, tattooing, piercing, sexual exposure, birth to infected mothers.
viral hepatitis
needle stick
viral load
blood
bore
depth
gloves
sharps
sharps containers
Bloodborne Infections:
Prevention:
_ of blood products.
- All blood in the U.S. is screened for antibodies to the following infectious agents: (7)
- Screening by _ (NAT) for HCV, HIV, and West Nile virus.
Testing of blood products for surrogate markers of hepatitis B/C infection: _ enzymes (_).
Pre-screening interviews of _ to identify high risk individuals:
- _ use (HIV, HCV, HBV)
- Recent _ (malaria-endemic area)
- Stay in _ (variant Creutzfeldt-Jakob disease (vCJD)
Use of alternative products, e.g. recombinant factors _ and _, erythropoietin, etc.
Universal _ and _ precautions
_ vaccination. All health care workers and at-risk individuals should be vaccinated while universal hepatitis Bvaccinations for newborns has been implemented world-wide.
Screening
- HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), HTLV I/II, Chagas disease (T.cruzi) and syphilis (T. pallidum).
- nucleic acid testing
serum liver (ALT)
blood donors
- IV drug
- travel
- UK
VIII and IX
blood and body fluid
Hepatitis B
Viral Hepatitis:
There are 5 major hepatitis viruses _
Different families of viruses that share _.
Hepatitis can also be caused by other agents as part of a more systemic infection, such as (4).
(A, B, C, D, E)
hepatotropism
cytomegalovirus (CMV), Epstein-Barr virus (EBV), yellow fever virus, dengue virus
HAV:
1) Virus family
2) Genome
3) Transmission
4) Severity of hepatitis
5) Chronic infection (yes, _ / no)
6) Liver cancer (HCC) (yes / yes, anytime / yes, after cirrhosis / no)
7) Prophylaxis
8) Therapy
1) Picornavirus
2) (+) RNA
3) Fecal-oral
4) Mild, self-resolving
5) no
6) no
7) HAIG, vaccine
8) none
HBV:
1) Virus family
2) Genome
3) Transmission
4) Severity of hepatitis
5) Chronic infection (yes, _ / no)
6) Liver cancer (HCC) (yes / yes, anytime / yes, after cirrhosis / no)
7) Prophylaxis
8) Therapy
1) Hepadnavirus
2) Incomplete dsDNA
3) Parenteral, Sexual, Perinatal
4) Sometimes severe
5) Yes, in adults 3-10%, in neonatal infections 90-95%
6) Yes, anytime
7) HBIG, vaccine
8) Interferon, Lamivudine, Emtricitabine, Tenofovir, Telbivudine, Entecavir, Adefovir
HCV:
1) Virus family
2) Genome
3) Transmission
4) Severity of hepatitis
5) Chronic infection (yes, _ / no)
6) Liver cancer (HCC) (yes / yes, anytime / yes, after cirrhosis / no)
7) Prophylaxis
8) Therapy
1) Flavivirus
2) (+) RNA
3) Parenteral
4) Moderate
5) Yes, 70-90%
6) Yes, after cirrhosis
7) None
8) Interferon, Ribavirin, Boceprevir, Teleprevir, Sofosbuvir
HDV:
1) Virus family
2) Genome
3) Transmission
4) Severity of hepatitis
5) Chronic infection (yes, _ / no)
6) Liver cancer (HCC) (yes / yes, anytime / yes, after cirrhosis / no)
7) Prophylaxis
8) Therapy
9) Only seen as a _ or _ of _
1) Defective, unclassified
2) (-) RNA
3) Parenteral
4) Severe
5) Yes (most)
6) Yes
7) HBV vaccine
8) None
9) co-infection or super-infection of HBV
HEV:
1) Virus family
2) Genome
3) Transmission
4) Severity of hepatitis
5) Chronic infection (yes, _ / no)
6) Liver cancer (HCC) (yes / yes, anytime / yes, after cirrhosis / no)
7) Prophylaxis
8) Therapy
1) Calcivirus
2) (+) RNA
3) Fecal-oral
4) Mild, self-resolving
5) No
6) No
7) None
8) None
Hepatitis B Virus (HBV):
Characteristics:
_ family (Hepatitis DNA virus).
(Circular / Linear) incompletely (single / double) stranded (DNA / RNA) genome.
Viral Replication. HBV has a unique strategy of replication using a viral _.
3 kb genome with 4 genes: (4)
Hepatitis B particles
Hepadnavirus
Circular
double
DNA
reverse transcriptase
Surface (S), core (C), pol (P), and X
Hepatitis B Virus (HBV):
Pathogenesis:
1) Entry via (3), etc.
(Bloodstream)
2) Extensive virus replication in _, Viral receptor is unknown
- ~80% subclinical (inapparent) infection
- ~20% acute hepatitis with jaundice
- rare fulminant hepatitis (severe, life-threatening)
3) _ damage is thought to result from cellular immune responses to infected cells. (IMMUNOPATHOGENESIS)
- ~90-97% clear infection (become HBsAg (positive / negative))
- chronic persistent infection (3-10% of adults, >90% of neonates, HBsAg (positive / negative))
- -> hepatocellular carcinoma (HCC)
blood, intimate contact, birth to infected mothers
liver (Kupffer cells, hepatocytes)
Hepatocyte
- negative
- positive
Hepatitis B Virus (HBV):
Diagnosis:
Detection of circulating HBV _ in blood by PCR = marker of _.
HBV Serology:
- Antigens (Ag): (3)
- Antibodies: (3)
Virulence factors
- Ability to establish _ infection.
- _ may act as an immune decoy.
DNA
ongoing viral replication
- surface (S), core (C), e antigen
- anti-HBs (=HBsAb), anti-HBc (=HBcAb), anti-HBe (=HBeAb)
- chronic
- HBsAg
Hepatitis B Virus (HBV):
Prevention: Hepatitis B Vaccine.
Recombinant vaccine made up of _.
Requires initial injection + 2 booster shots (0,1,6 months)
_ in >97% of recipients
Recommended for (5)
Currently recommended as routine vaccination for all infants and adolescents worldwide.
HBsAg
Immunity
health care workers, contacts of HBV infected individuals, newborns of infected mothers, hemodialysis patients, and IV drug users.
Hepatitis B Virus (HBV):
Treatment:
Acute infection
- _ - recommended along with vaccine for newborns of infected mothers and exposed, unvaccinated individuals.
Chronic infection
- _, pegylated (immune modulator)
- _ (a nucleoside analogue) – Resistance is a problem due to mutations in viral polymerase (reverse transcriptase).
- (5) (nucleos/tide analogues)
Cirrhosis/ end-stage liver disease
- _ – aggressive treatment with _ and _ to prevent re-infection of liver
Prevention of reactivation
- In patients with past HBV infection, the infection can flare up when _ immunity is compromised (Bone Marrow transplantation, monoclonal Ab’s against B-cells) and _ is used as prophylactic agent.
- HBIG (Hepatitis B Immune Globulin)
- Alpha-interferon
- Lamivudine
- Tenofovir, Adefovir, Entecavir, Emtricitabine, Telbivudine
- Liver Transplantation, HBIG and Lamivudine
- B-cell, lamivudine
Hepatitis Delta Virus:
Characteristics:
Defective (DNA / RNA) virus that requires _ for infection
virus-like particle – containing _ and _ Ag – both enveloped with _ envelope (_)
RNA has self-_ and self-_ capabilities - Similarity to plant virus satellites, viroids.
RNA
HBV
RNA
delta
HBV
HBsAg
cleaving
ligating
Hepatitis Delta Virus:
Epidemiology/ Clinical disease:
Simultaneous infection with _ or superinfection of persistent _-infected patients
High prevalence among _
Distribution varies worldwide: ~ 6%-20% of HBV+ in U.S.; >60% of HBV+ in Middle East, Central Asia, Amazon basin, West Africa
Clinical syndrome of HDV infection (more / less) severe than HBV infection alone:
i. Acute hepatitis (more / less) severe than hepatitis B alone
ii. Chronic hepatitis - (more / less) prevalent and severe than hep B alone.
iii. Likely direct _ effect
HBV
HBV
injection drug users
more
i. more
ii. more
iii. viral cytopathic
Hepatitis Delta Virus:
Diagnosis
- Serology for antibody to _.
Treatment and Prevention
- _ vaccine is preventative for HDV.
- _
- _ transplantation.
- delta Ag
- Hepatitis B
- Interferon-α
- Liver
Hepatitis C Virus (HCV):
Characteristics:
(Positive / Negative) sense (DNA / RNA), (enveloped / non-enveloped) virus – member of the _ family.
(High / Low) mutation rate
• Due to lack of _ capability and high error rate of viral _.
Present in the blood as a population of heterogeneous _.
• Multiple sequence isolates present at any one time.
• Due to sequence diversity in the hypervariable region of the envelope gene.
• May be a mechanism of immune escape.
Six different genotypes
• Genotype _ most prevalent in US, worst response to traditional _ / _ therapy.
Positive
RNA
enveloped
flavivirus
High
- proofreading
- RNA polymerase
quasispecies
- 1
- IFN / ribavirin
Hepatitis C Virus (HCV):
Clinical Disease:
Transmission risks: (4)
Outcomes of infection.
• 80%-90% have persistent chronic _
• 10-20% develop chronic _
• Associated with immune mediated disease – _
• Risk of _ and then _ (when chronic hepatitis)
~1.5% of the U.S. population is chronically infected – many are asymptomatic.
Chronic Hepatitis C is the leading indication for _ transplantation in U.S.
injection drug use, blood exposure, transfusion, sexual (predominantly male sex to male)
- viral infection
- hepatitis
- cryoglobulinemia
- cirrhosis, hepatocellular carcinoma
liver
Hepatitis C Virus (HCV):
Virulence Factors:
- High mutation rate/ variability of the viral genome prevents an effective antibody response due to _
- _ blocks immune activation of infected cell.
Diagnosis:
- Serology for _ antibodies
- _ for presence of circulating virus
i. Used to confirm positive serology
ii. Used to specify _ (1-6)
iii. Positive during _ infection
iv. Used for diagnosis after _ – i.e. window period for serologic markers
antigenic variation
- Protease
- anti-HCV
- RT- PCR (reverse transcriptase-PCR)
ii. genotype
iii. chronic
iv. needle sticks
Hepatitis C Virus (HCV):
Treatment:
- No prophylaxis with _.
- Standard therapy:
i. _ (pegylated)
ii. _ is nucleoside analog with activity against RNA viruses
iii. Predictors of response to therapy: _ genotype; also gender, age, race, viral load, viral genotype - New protease inhibitors (2014)
i. (4)
ii. Added to standard therapy for now, but some may be effective even without IFN
iii. Increases virologic response, even with “bad” IL28 genotype or genotype 1 virus.
Vaccine: _
_ transplantation: #1 indication in U.S.
immunoglobulin
i. Alpha-interferon
ii. Ribavirin
iii. IL28B
il Boceprevir, Teleprevir, Sofosbuvir, Simeprivir
No vaccine available
Liver
Transplantation-associated Infections:
Risks. The major risk of infections in transplant patients is due to the use of _ agents that suppress the cellular immune response. (_ = caused by physicians)
- Different types of immunosuppressive medications, differ in risk of infection (3) > (2)
- Risk of acquiring new infections (_ = hospital acquired): bacterial, viral, fungal and parasitic infections.
- Risk of reactivation of _ infections or recurrence of chronic infections
i. Reactivation of latent _ infections.
ii. Most transplants for HBV and HCV-associated cirrhosis are associated with re-infection of the new transplanted liver due to chronic _ and _.
iii. (7) - Donor-organ associated transmission. (4)
Prevention
- Screening of _ for infectious agents that can be persistent.
- _ antiviral and antibiotic therapy, hyperimmune globulin.
- _ of transplant recipients.
immunosuppressive
iatrogenic
- Corticosteroids, azathioprine, alemtuzumab > cyclosporine, rapamycin
- nosocomial
- latent
i. herpesvirus
ii. HBV and HCV
iii. Trypanosoma cruzi (Chagas disease), Toxoplasma gondii, Strongyloides stercoralis, Tuberculosis, Histoplasma capsulatum, Cryptococcus, Coccidiomycosis - Prion disease (Creutzfeldt-Jakob disease), CMV, EBV, T. cruzi
- donor organs
- Prophylactic
- Vaccination
Transplant-associated Herpesvirus Infections:
- All herpesviruses establish (short-lived / life-long) latency in their host and can _ in immunosuppressed patients.
- Risk of transmission by donor organ transplantation to _ recipients.
- More severe disease associated with _ infection (_ infection) compared with _ (_ infection).
- life-long, reactivate
- non-immune
- first-time (primary)
reactivation (secondary)
Epstein-Barr Virus (EBV):
Characteristics:
(DNA / RNA) virus; member of the _ family
Infects _ cells – via specific receptor (_ = complement receptor CR2), or _ cells by CD-21-like receptor.
Can establish _ and _ human B cells.
High seroprevalence and intermittently shed.
DNA
herpesvirus
B
CD21
nasopharyngeal
latency
immortalize
Epstein-Barr Virus (EBV):
Clinical disease:
Acute infection can be asymptomatic or associated with _.
• Features: (4)
• Acute infection in immunosuppressed patients can be associated with severe IM.
Chronic infection
• EBV is associated with several human cancers: (4).
• Risk of _ in immunosuppressed patients
- Lymphoproliferation of immortalized B cells – can progress to lymphoma
infectious mononucleosis (IM) - Fever, pharyngitis, lymphadenopathy, atypical lymphocytosis
- Burkitt’s lymphoma, nasopharyngeal carcinoma, most non-Hodgkin’s and some Hodgkin’s lymphomas
- post-transplant lymphoproliferative disease (PTLD)
Epstein-Barr Virus (EBV):
Pathogenesis:
Transmission is primarily by _
Primary replication in the _ epithelium or _ B cells.
Spread via the _
Infects _ lymphocytes and sets up a _ infection in these cells for the lifetime of the infected individual.
• Latent infection is (symptomatic / asymptomatic), unless the patient becomes immunosuppressed.
_ recognize latent EBV antigens and eliminate most latently infected B cells.
• _ (atypical lymphocytosis) is due to this response to infected B cells.
During long-term latency only one latent antigen (_) is produced which cannot be processed and presented by MHC I, thus _ immune recognition.
PTLD: Lack of _ recognition of EBV latent antigens in immunosuppressed hosts probably allows _ of latently infected B cells.
saliva
pharyngeal
tonsillar
bloodstream
B
latent
- asymptomatic
CTL
- Mononucleosis
EBNA-1
evading
CTL
outgrowth
Epstein-Barr Virus (EBV):
Diagnosis:
Acute infection ()
• _ – test for antibodies that are present during acute EBV infection ( antibodies)
• Microscopic examination of _ for atypical lymphocytosis (not specific)
Recent or Past infection
• Detection of specific _ antibodies: (3)
PTLD
• Quantitative _ to determine EBV viral load may identify patients at risk
• Biopsy for detection of _ disease.
Infectious mononucleosis
- Monospot test, Heterophile
- blood
- anti-EBV
- anti-EA (early antigen), anti-VCA (viral capsid antigen, IgM), anti-EBNA (Epstein-Barr nuclear antigen)
- PCR
- lymphoproliferative
Epstein-Barr Virus (EBV):
Prevention and Treatment
Vaccine?
No treatment indicated for _
PTLD
- Decrease in _ most important to allow EBV-specific CTL response to recover
- _ and _ have minimal efficacy against EBV during the replicative cycle, but are NOT effective during latency.
- Immune therapy
• _ therapy in bone marrow transplant patients
• _ therapy (B-lymphocyte surface antigen)
No vaccine
acute infectious mononucleosis
- immunosuppressive therapy
- Acyclovir and Ganciclovir
- CTL
- Anti-CD20
