Block 11 - L10-L11 Flashcards
1
Q
Compare Hepatitis A and E (Structure, transmission, onset, incubation period, severity, mortality, chronicity/carrier state, disease associations, lab diagnosis).
A
A: picornavirus; capsid, RNA
E: calcivirus-like capsid, RNA
Transmission: fecal-oral
Onset: abrupt
Incubation period: 15-50 days
Severity: mild (E severe in pregnant women)
Mortality: A <0.5%, E 1-2% (normal), 20% (pregnant)
Chronicity/carrier state: no
Disease associations: none
Laboratory diagnosis - A: symptoms + anti-HAV IgM
2
Q
Compare Hepatitis B, C, and D (Structure, transmission, onset, incubation period, severity, mortality, chronicity/carrier state, disease associations, lab diagnosis).
A
B: hepadnavirus; envelope, DNA
C: flavivirus; envelope, RNA
D: viroid-like; envelope, circular RNA
Transmission: parenteral, sexual
Chronicity/carrier state: yes
Disease associations: primary HCC, cirrhosis, + fulminant hepatitis (D only)
Lab diagnosis:
B - symptoms + serum levels of HBsAg, HBcAg, and anti-HBc IgM
C - symptoms + anti-HCV ELISA
D - anti-HDV ELISA
3
Q
Describe the structure of HBV.
A
Partially double-stranded DNA virus in a capsid that is made up of self-assembling surface antigens
4
Q
How does HBV replicate?
A
Virus enters the cytoplasm and completes the double-stranded DNA genome. This enters the nucleus and is transcribed. mRNA moves back to the cytoplasm, is translated, then reverse transcribed
5
Q
How is HBV transmitted?
A
Blood products, mother to child
6
Q
What are the outcomes of acute HBV infection?
A
- Resolution (90%)
- Infection continues for 6+ months (9%)
- Fulminant hepatitis (1%)
7
Q
What are the outcomes if acute hepatitis B infection persists?
A
- Resolution (50%)
- Asymptomatic carrier state
- Chronic persistent hepatitis
- Chronic active hepatitis
8
Q
What are the outcomes of chronic persistent hepatitis due to HBV infection?
A
Extrahepatic disease (polyarteritis nodosum and glomerulonephritis)
9
Q
What are the outcomes of chronic active hepatitis due to HBV infection?
A
Cirrhosis
Hepatic cell carcinoma
Extrahepatic disease (polyarteritis nodosum and glomerulonephritis)
10
Q
What are the stages of HBV infection?
A
- Incubation period
- Pre-icteric
- Icteric
- Convalescent period
11
Q
What are the symptoms of acute HBV?
A
Fever, rash, arthritis Jaundice Dark urine Malaise Anorexia Nausea RUQ pain Itching (10%)
12
Q
Discuss the Ag and Ab seen in acute self-limiting HBV infection.
A
- Incubation (4-12 weeks) - nothing
- Acute viremia (4-12 weeks) - Increase and decrease of HBsAg and HBeAg + increase in anti-HBc
- Convalescence (2-16 weeks) - anti-HBc, anti-HBe, anti-HBs
- Healthy (years) - anti-HBc remains elevated, anti-HBe and anti-HBs slowly decline
13
Q
Discuss the Ag and Ab seen in chronic active HBV infection.
A
- Incubation (4-12 weeks) - nothing
- Acute viremia (6 months) - increase in HBsAg and HBeAg + anti-HBc
- Chronic viremia (years) - #2 levels maintained
14
Q
What is the window period of HBV infection?
A
The period of time when HBsAg is negative and anti-HBs has yet to appear
15
Q
Interpret the serologic assay for HBV:
HBsAg: negative HBeAg: negative anti-HBc: negative anti-HBe: negative anti-HBs: negative
A
No evidence of present or past HBV infection
16
Q
Interpret the serologic assay for HBV:
HBsAg: positive HBeAg: negative anti-HBc: negative anti-HBe: negative anti-HBs: negative
A
Incubation period of HBV
17
Q
Interpret the serologic assay for HBV:
HBsAg: positive HBeAg: positive anti-HBc: positive anti-HBe: negative anti-HBs: negative
A
Early in acute infection with HBV or chronic HBV infection with high infectivity
18
Q
Interpret the serologic assay for HBV:
HBsAg: positive HBeAg: negative anti-HBc: positive anti-HBe: positive anti-HBs: negative
A
Later in acute infection, or chronic HBV infection with lower infectivity
19
Q
Interpret the serologic assay for HBV:
HBsAg: negative HBeAg: negative anti-HBc: positive anti-HBe: positive/negative anti-HBs: negative
A
Window period late in acute HBV infection
20
Q
Interpret the serologic assay for HBV:
HBsAg: negative HBeAg: negative anti-HBc: positive anti-HBe: positive anti-HBs: positive
A
Convalescent from HBV
21
Q
Interpret the serologic assay for HBV:
HBsAg: negative HBeAg: negative anti-HBc: positive anti-HBe: negative anti-HBs: positive
A
Later in convalescence (anti-HBe has waned)
22
Q
Interpret the serologic assay for HBV:
HBsAg: negative HBeAg: negative anti-HBc: negative anti-HBe: negative anti-HBs: positive
A
Response to HBV vaccine or recent administration of hyperimmune anti-HB’s immunoglobulin
23
Q
How is HBV infection treated?
A
- Lamivudine
2. Hepsera (adefovir)
24
Q
What are the MOAs of lamivudine and hepsera (adefovir)?
A
Nucleoside analogues that inhibit reverse transcription and reduce HBV DNA
25
What is a unique indication of adefovir?
Works against laminvudine resistant HBV
26
How does the HBV vaccine work?
Sub-unit vaccine using HBsAg
27
What is unique about HDV?
Must co-infect with HBV, as it is a circular single-stranded RNA virus that encodes one protein (delta Ag) - surrounds itself with HBsAg to make the virus particle
28
What is a ribozyme?
Enzyme that cleaves and ligates RNA; found in the hepatitis D virus
29
True or false - vaccination with HBV protects from HDV.
True
30
Describe the structure of HCV.
Positive strand RNA virus of the flavivirus family
31
How is HCV treated?
Direct acting anti-virals (DAAs) -
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Protease inhibitors (NS3)
Phsophoprotein inhibitors (NS5A)
Polymerase inhibitors (NS5B)
```
Multiple drug regimen most effective
32
What are the outcomes of acute HCV infection?
1. Recovery and clearance (15%)
2. Cirrhosis - rapid onset (15%)
3. Persistent infection (70%)
33
What are the outcomes of persistent infection with HCV?
Chronic hepatitis
| 40% are asymptomatic
34
What are the outcomes of chronic hepatitis due to HCV?
1. Liver failure (6%)
2. Cirrhosis (20%)
3. HCC (4%)
35
What factors influence HCV disease progression?
1. Females who are young at infection - slower progression
| 2. Alcohol use, coinfection - faster progression
36
How is HCV diagnosed?
Serologic assays (screen for anti-HCV, supplemental Ab test)
Molecular assays (qualitative test for HVC RNA, quantitative tests for viral RNA, HCV genotype tests)
37
What was the original treatment for HCV, and what was the typical outcome?
Interferon - worked for a few weeks, then relapsed
38
Where is HEV primarily seen?
SE Asia (India, Nepal)
39
What is the family and genome of Hepatitis A virus?
Single stranded positive RNA Enterovirus
40
How is HAV most commonly transmitted?
Fecal-oral
41
What is the recommended current method of detection for Hepatitis A infection?
Serology by antibody capture for HAV specific IgM
42
What is the mechanism of pathogenesis for HAV?
Viremia resulting in targeting of the liver
43
Are there anti-viral therapies available against HAV?
Vaccine can be administered during the prodrome period of infection
44
Is there a vaccine available for protection against HAV?
Killed-virus injected vaccine
45
Are there long term consequences of a HAV infection?
Long-lived protective immunity
46
What is the family and genome of Hepatitis B virus?
Partly Single stranded DNA Hepadnavirus
47
How can HBV be transmitted?
1. Sexual
2. Transfusion/sharing needles
3. Mother to newborn
48
What is the recommended current method of detection for Hepatitis B virus infection?
Serology by antibody capture for HBV specific antibodies
49
What is the mechanism of pathogenesis for HBV?
Viremia resulting in targeting of the liver
50
Are there anti-viral therapies available against HBV?
Nucleoside reverse transcriptase inhibitors (NRTIs) such as Lamivudine or Adefovir Dipivoxil
51
Is there a vaccine available for protection against HBV?
Subunit vaccine
52
What is the most clinically significant long term consequence of HBV infection?
Hepatocellular carcinoma
53
What is the family and genome of Hepatitis C virus?
Single stranded positive RNA Enveloped Flavivirus
54
How is HCV most commonly transmitted?
Transfusion, needle sharing, contact with blood
55
What is the recommended current method of detection for Hepatitis C infection?
RT-PCR and sequencing for genotype
56
What is the mechanism of pathogenesis for HCV?
Viremia resulting in targeting of the liver and persistent infection in the majority of patients
57
Are there anti-viral therapies available against HCV?
Direct acting anti-virals (DAAs) including protease inhibitors and polymerase inhibitors
58
Is there a vaccine available for protection against HCV?
No
59
What is the most clinically significant long term consequence of HCV infection?
Hepatocellular carcinoma
60
What is the genome of Hepatitis D virus?
Single-stranded RNA viroid
61
How is HDV most commonly transmitted?
Sexual, transfusion/sharing needles, mother to newborn
62
What is the recommended current method of detection for Hepatitis D infection?
Serology by antibody capture for HDV specific IgM
63
What is the mechanism of pathogenesis for HDV?
Co-infection with HBV, viremia resulting in targeting of the liver and fulminant disease
64
Are there anti-viral therapies available against HDV?
Nucleoside reverse transcriptase inhibitors (NRTIs) such as Lamivudine or Adefovir Dipivoxil
65
Is there a vaccine available for protection against HDV?
Subunit vaccine to HBV
66
Are there long term consequences of a HDV infection?
Reinfection is common with lesser severity
67
What is the family and genome of Hepatitis E virus?
Single stranded positive RNA Calicivirus
68
How is HEV most commonly transmitted?
Fecal-oral
69
What is the recommended current method of detection for Hepatitis E infection?
Serology or RT-PCR by the public health department
70
What is the mechanism of pathogenesis for HEV?
Viremia resulting in targeting of the liver
71
Are there anti-viral therapies available against HEV?
No
72
Is there a vaccine available for protection against HEV?
No
73
Are there long term consequences of a HEV infection?
Long-lived protective immunity in healthy individuals; higher chance of mortality in pregnant women
74
Discuss the global localization of HIV infections.
Africa - 70%
Asia - 14%
US - 3%
75
What percent of people with HIV infections are getting antiretroviral treatment?
57%
76
Which groups have experienced increased rates of new HIV infections in the US since 2011?
Black and Latino MSM
| MSM category comprises the majority of infections in the US - 67%
77
What is the average life span of a 20 y/o diagonosed with HIV today and treated with ART?
53-56 years (normal would be 66 years)
78
Why is the prevalence of HIV infection increasing in the US?
People are living longer
79
How does acute/primary HIV infection present?
```
Fever, fatigue (90%)
Pharyngitis, weight loss (75%)
Myalgias (60%)
Lymphadenopathy (50%)
Thrombocytopenia, leukopenia (40-45%)
Maculopapular rash (35%)
Oral ulcers, headache , diarrhea, nausea, aseptic meningitis
```
50-90% have a least some symptoms
Onset: 1-4 weeks after exposure
Non-specific symptoms with many mimics
80
What are the characteristics of acute/primary HIV infection (labs)?
High viral load and below normal CD4 count (normal = 500-1200 cells/mm3)
81
When is risk of transmission of HIV highest?
Acute/primary HIV infection
82
What are the CDC recommendations regarding HIV testing?
1. All people 13-64 (opt-out rather than opt-in)
2. People at high risk annually (IVDU, HIV-infected partner, multiple partners, exchanging sex for drugs)
3. People with STI, TB, illnesses compatible with HIV
4. All pregnant women
83
Which age group in the US are most likely to be unaware of their HIV infection?
Young people ages 13-24, especially high school students
84
Until recently, HIV diagnosis was made using what tests?
HIV ELISA and a confirmatory Western blot (antibody testing)
85
What is the current recommendation to test for HIV?
Combined antibody/antigen assay
86
What is involved in a 4th generation HIV test?
Detects HIV Ab as well as circulating virus (p24 Ag)
87
Why is Western blot testing no longer recommended for detecting HIV infection?
False negatives or indeterminate results
88
What should be done if a test is p24 Ag positive but HIV Ab negative?
HIV nucleic acid testing (NAT)
89
What else is HIV RNA PCR used for?
Follow response to ART
90
What are important components of the history and physical when evaluating a new case of HIV?
Complete history, including other STIs, immunization status, travel history, sexual history, substance use, depression, ROS directed at possible opportunistic complications
Look for evidence of more advanced HIV/opportunistic complications and STIs on exam
91
What labs should be done as part of a baseline evaluation of HIV?
1. HIV RNA PCR (viral load) and CD4 count
2. HIV resistance testing (mutations to HIV meds)
3. Chemistries, CBC, lipids, UA
4. STI screening (gonorrhea/chlamydia screening, RPR)
5. TB screening
6. Hepatitis screening
7. Cervical pap smear
8. Toxoplasma IgG
9. Labs for medication side effects (e.g., HLA B5701)
92
When should ART be started?
When HIV is diagnosed, regardless of CD4 and VL
93
What is the rate of HIV transmission from an HIV-infected person on ART to his/her partner if the viral load in the person with HIV is < 200 copies/ml?
0% - when ART results in viral suppression (<200 copies/mL = undetectable), it prevents sexual transmission
94
How is HIV monitored?
1. CD4 and VL - baseline, check every 3-6 months
2. Check VL 2-8 weeks after starting/changing ART
3. Regular chemistries and CBC to monitor side effects
4. Yearly screenings for TB/STIs
95
What are the complications of HIV seen at >500 CD4 count?
Neuropathy
Bell's palsy
Low platelets
96
What are the complications of HIV seen at 200-500CD4 count?
Herpes zoster
TB
Pneumonia (bacterial)
Non-CNS lymphoma
97
What are the complications of HIV seen at <200 CD4 count?
```
Thrush
PJP
KS
Cryptococcus
MAC
CMV
PML
CNS lymphoma
Toxoplasma
```
98
What is the indication for prophylactic treatment of pneumocystis carinii in HIV?
CD4 <200 OR
Oral candida OR
Cd4% <14% OR
AIDS-defining illness
99
What is the prophylactic treatment of pneumocystis carinii in HIV?
TMP-SMX
100
What is the indication for prophylactic treatment of toxoplasma in HIV?
CD4 <100 AND positive Toxo IgG
101
What is the prophylactic treatment of toxoplasma in HIV?
TMP-SMX
102
What is the indication for prophylactic treatment of mycobacterium TB in HIV?
Positive screening test for LTBI
103
What is the prophylactic treatment of mycobacterium TB in HIV?
INH 300 mg daily x 9 months + pyridoxine
104
What is the indication for prophylactic treatment of Mycobacterium avium complex (MAC) in HIV?
CD4 <50
105
What is the prophylactic treatment of MAC in HIV?
Azithromycin 1200 mg weekly OR
600 mg 2x weekly OR
Clarithromycin
106
What are some early physical HIV manifestations?
Seborrheic dermatitis
Oral hairy leukoplakia
Herpes zoster (dewdrops on a rose petal)
107
What are common lung diseases in HIV?
```
PJP
Bacterial pneumonia (S. pneumo)
TB
Histoplasmosis
Blastomycosis
Coccidioidomycosis (in SW US)
Cryptococcus
Respiratory viruses (influenza)
Tumors - lymphoma, Kaposi's sarcoma
```
108
How does pneumocystis pneumonia present?
Insidious symptoms present for weeks; exam is often normal, may desaturate on walking
Elevated LDH
CXR - bilateral reticulonodular interstitial infiltrates, perihilar (may be normal)
CT
109
What are 3 common ring-enhancing brain lesions in HIV?
1. CNS lymphoma
2. Bacterial abscess (IVDU)
3. Chagoma
110
What are less common ring-enhancing brain lesions in HIV?
Tuberculoma
Cryptococcoma
Histoplasoma
Metastatic cancer
111
How does one get toxoplasmosis?
Eating undercooked meat with tissue cysts or ingesting cysts that have been shed in cat feces
112
How does toxoplasmosis manifest?
Encephalitis with multiple brain lesions (often ring-enhancing)
113
How is toxoplasmosis treated?
Sulfadiazine + pyrimethamine
Clindamycin + pyrimethamine
TMP-SMX
114
What is the usual cause of CNS lymphoma in HIV?
EBV reactivation
115
How does CNS lymphoma appear on MRI?
Single lesion with contrast enhancement and edema/mass effect
116
How is CNS lymphoma treated in HIV?
Chemo, radiation, ART
117
How does cryptococcus present?
Fever, HA, altered mentation, pneumonia, skin lesions
118
How is cryptococcus treated?
Amphotericin B + 5-flucytosine then fluconazole
119
What retinal disease is common in HIV?
CMV retinitis
120
How does CMV retinitis appear on PE and what is an initial symptom?
Scrambled eggs and ketchup; floaters
121
How is CMV retinitis treated?
Ganciclovir
122
What is immune reconstitution inflammatory syndrome (IRIS)?
Systemic infalmmatory syndrome with signs and symptoms identical to the infection; occurs after ART initiation/increase in CD4
Not related to uncontrolled infection, but to the improved immune response from ART - leads to a paradoxical worsening of infection
123
What is PrEP?
Tenofovir-emitricitabine, approved for use in high-risk HIV-negative persons to prevent transmission
