TA Review Flashcards
(223 cards)
1
Q
4 Basic Properties
A
-obligate parasite -composed of nucleic acids -small, pass through filters -cannot be directly observed
2
Q
Lytic vs. chronic vs. latent
A
Lytic –> Virus is replicating, with symptoms Chronic –> Virus is replicating, asymptomatic presentation Latent –> Virus is not replicating, asymptomatic
3
Q
General Stages of Replication Cycle
A
- Attachment and penetration 2. Uncoating 3. Fusion 4. Replication/translation/maturation 5. Assembly 6. Budding
4
Q
Ebola Replication Cycle
A
- Attachment 2. Macropinocytosis 3. Fusion at endosome 4. Negative strand with RNA virus transcription –> translation into viral proteins. 5. Negative strand RNA virus replication 6. Assembly of parts from 4 and 5 7. Budding
5
Q
RNA Virus classification card
A
6
Q
DNA Virus Classification Card
A
7
Q
What are DNA Viruses
A
HHAPPPP(y)
Hepadna (HBV), Herpes, Adeno, Pox, Parvo_, P_apilloma, _P_olyoma
8
Q
Characteristics of DNA Viruses
A
- Double-stranded (except parvo – it’s only “ part of” a virus)
- Replicate in nucleus (except pox – it’s weird)
- Are Icosahedral (except pox – it’s weird)
9
Q
Geography of Ebola
A
West Africa
10
Q
Transmisison of Ebola
A
Direct Contact: Blood, secretions, organs, & other body fluids –
Indirect Contact: Contaminated environment –
Airborne Transmission: During aerosol generating procedures –
Individuals are Infectious as long as Ebola virus present in blood, breast milk, and other secretions.
11
Q
Diagnosis of Ebola
A
Presenting Symptoms: ELISA; PCR; virus isolation –
Late in Disease or After Recovery: IgM and IgG antibodies
12
Q
Ebola incubation period
A
2-21 days
13
Q
Ebola presenting symptoms
A
- Acute Onset: Fever, Myalgia, Headache
- After 5 days: N&V, Abdominal pain, Diarrhea, Chest pain, Cough, Pharyngitis
- Other Symptoms: Photophobia, Lymphadenopathy, Conjunctivitis, Jaundice, Pancreatitis, CNS Symptoms (decreased mental status, delirium, coma)
14
Q
Ebola disease progression
A
Erythematous maculopapular rash: face, neck, trunk, arms with desquamation
- Bleeding Manifestations: petechiae, ecchymosis, & hemorrhage (less common).
- Fatal Progression: Shock, DIC, liver & renal failure. Death between 6-16 days.
- Protracted Convalescence: Arthralgia, orchitis, uveitis, transverse myelitis
15
Q
Tx Ebola
A
Current: Supportive
Investigational: Zmapp (3 monoclonal antibodies) after onset of treatment; Vaccines
16
Q
Pathogenesis of Ebola
A
Infects macrophages and dendritic cells –> Leads to supression of Type I IFN, and systemic dissemination –> Causes direct tissue injury in liver, spleen, and adrenals–> Host IR causes damage also via cytokines.
17
Q
Influenza Virus A/B/C family
A
Orthomyxoviridae
18
Q
Influenzae Morphology
A
Enveloped
Single Strand RNA virus
Negative sense
Segmented
Helical Capsid
19
Q
Influenzae pathogenesis/infectious properties
A
Hemaagglutin (HA) –> Binds Sialic Acid which leads to endocytosis into respiratory endothelium and agglutination of RBCs
Neuroaminidase (NA) –> Cleaves HA sialic acid bond and allows for spread of viral copies
M2 –> forms a proton channel, facilitates uncoating
20
Q
Standard clinical manifestation of influenzae
A
Primarily: “flu symptoms” including malaise and myalgia
21
Q
Clinical complications of Influenzae
A
pneumonia/secondary bacterial pneumonia
otitis media
Reye’ s syndrome (w/aspirin in peds) –> Rash, vomiting, liver damage due to swelling in liver and brain
Encephalitis
myositis/cardiac involvment
22
Q
Diagnosis of Influenzae
A
Often made on clinical grounds
Rapid antigen, culture, serotyping are available
GO back to lecture for this!! more info on slides.
23
Q
Influenzae Antigenic Shift
A
(major reassortment, Flu A only). Responsible for Pandemics, happen every 50 years
24
Q
Antigenic Drift Influenzae
A
(yearly changes/mutations). Three strains: A, B, and C. Responsible for yearly outbreaks
25
Treatment of Influenzae
NA Inhibitors (Tamiflu/Oseltamavir) and M2 Channel Blockers (Amantadine) Vaccines (live + inactivated)
26
Virus in family paramyxoviridaie
Parainfluenzae
RSV
hMPV
27
Adenovirus morphology
Nonenveloped
linear
dsDNA
Icosahedral capsid
28
Adenovirus infectious properties
HA (hemaglutinin) --\> binds sialic acid and mediates endocytosis
29
Transmission of Adenovirus
Fecal Oral
\*(TA Review is wrong when it says Fomites, Droplet, contact)
30
Epidemiology of adenovirus
Outbreaks in congregate settings, different serotypes target different tissues
31
Clinical presentation of adenovirus
• Pharyngitis, pneumonia, & other respiratory tract infections •
## Footnote
**Common Cold (#3 cause) •**
**Conjunctivitis (“pink eye”) •**
**Gastroenteritis (#2 viral cause of diarrhea), hemorrhagic cystitis (hematuria & dysuria)**
32
Adenovirus diagnosis
DFA (direct fluorescent antibodies); PCR; culture
Not routinely done --\> check on this in lecture
33
Tx and Prevention of adenovirus
Supportive. Live attenuated vaccine used in military (congregate setting)
Cidofovir used in immunocompromised hosts
34
Coronavirus morphology
Enveloped,
(+) ss RNA;
helical capsid (RNA genome + N protein)
35
Coronavirus infectious properties
E2 glycoproteins form “halo-like” projections surrounding the envelope (crown!)
36
Transmisison of coronavirus
Fomites, person:person
37
Clinical presentation/epidemiology/diagnosis of coronavirus
**Common Cold (#2 cause)** & other respiratory infections; --\>Diagnosis is clinical picture, seen all over the world
Gastroenteritis
* Severe Acute Respiratory Syndrome (SARS): fever, respiratory distress & pneumonia, diarrhea; 10% mortality. Diagnosis is done via PCR/EM/Antibody Assay, seen in Asia did spread from China to worldwide.
* Middle East Respiratory Syndrome (MERS): fever, respiratory distress & pneumonia, diarrhea. Diagnosis is done via PCR/EM/Antibody Assay. Seen in Saudi Arabia.
38
SARS/MERS
Both caused by coronavirus
* Severe Acute Respiratory Syndrome (SARS): fever, respiratory distress & pneumonia, diarrhea; 10% mortality. Diagnosis is done via PCR/EM/Antibody Assay, seen in Asia did spread from China to worldwide.
* Middle East Respiratory Syndrome (MERS): fever, respiratory distress & pneumonia, diarrhea. Diagnosis is done via PCR/EM/Antibody Assay. Seen in Saudi Arabia.
39
TX coronavirus
All treated with supportive care
40
Parainfluenzae Virus morphology
Enveloped,
ss (-) linear,
non-segmented RNA;
helical capsid
41
Respiratory Syncytial Virus (RSV) morphology
Paramyxoviridae:
Enveloped,
ss (-) linear,
non-segmented RNA;
helical capsid
42
Human Metapneumovirus (hMPV) morphology
Paramyxoviridae:
Enveloped,
ss (-) linear,
non-segmented RNA;
helical capsid
43
Parainfluenzae Infectious Properties
HN protein functions with combined HA and NA activity: mediates fusion and endocytosis (H) and cleaving for spread (N)
44
Parainfluenza Transmission
Respiratory droplets & Contact
45
Parainfluenzae clinical presentation/epidemiology
Croup (laryngotracheobronchitis – barking seal cough) --\> See the steeple sign on xray, the narrowing of the airway
seen in kids age 3-5, most people get it by age 5. Seen in Fall and Spring.
bronchiolitis Pneumonia in kids (URI + LRI);
Common cold in adults (URI only)
46
Diagnosis of Parainfluenzae
DFA and PCR and culture
47
Treatment of Parainfluenza
Supportive and corticosteroids to open up the airway
48
RSV infectious properties
G protein mediates attachment and release, instead of HA/NA in other parmyxoviruses (such as parainfluenze and hMPV)
49
Transmission of RSV
Fomites or direct contact with secretions
50
Clinical presentations of RSV
* Kids/Infants: Pneumonia & bronchiolitis
* Immunocompetent Adults: Common Cold
* Immunocompromised Adults: Pneumonia
51
Epidemiology of RSV
Most infected by 2 years of age. Reinfection throughout life is common.
* Risk Groups: Premature / Elderly, Congenital Heart Defects, Bronchopulmonary Dysplasia (BPD – formerly chronic lung disease of infancy)
* Outbreaks in winter & spring
52
Diagnosis of RSV
Rapid antigen test, DFA, PCR (not used clinically)
53
Treatment of RSV
* Supportive care.
* Prevention of severe RSV disease for high risk infants: palivizumab (vs F protein). High risk infants are pre-mes, congenital heart defect babies, infants with bronchopulmonary dysplasia
54
hMPV clinical presentation
Bronchiolitis Pneumonia in kids, elderly, and immunocompromised;
URI in healthy adults
55
Epidemiology/Transmission of hMPV
Outbreaks: Jan-April (winter).
Recurrent infections throughout life.
Highest risk: immunocompromised, preemies, transplant, cardiopulmonary disease.
Transmission by contact with contaminated secretions.
56
Clinical presentation of hMPV
Bronchiolitis Pneumonia in kids, elderly, and immunocompromised;
URI in healthy adults
57
Treatment of hMPV
Supportive
58
Diagnosis of hMPV
PCR/DFA, probably not used clinically at all
59
Measles is caused by
Rubeola, Morbillivirus
60
Measles/Rubeola morphology
single strand negative sense RNA genome
non segmented
helical capsid
enveloped
single serotype
61
Infectious properties of Measles
HA --\> sialic acid binding, endocytosis
M protein --\> assembly
62
Measles transmission
Aerosol, need ot keep under negative pressure isolation
63
Clinical Presentation of Measles
* Incubation: 10 days;
* Prodrome (pre-rash): 3 days of cough, coryza, conjunctivitis, photophobia **(CCCP)**;
* Disease: **Koplik’s spots** in mouth, **maculopapular rash** starts at head moves to feet.
64
Complications of Measles
* Bacterial Superinfection, Pneumonia, Encephalitis (1 in a thousand)
* Subacute Sclerosing Panencephalitis (1 in a million; occurs years later)
* Transient Immunosuppression: TB susceptibility in endemic regions
65
Measles diagnosis
clinical findings, direct fluorescent antibody (urine)
66
measles tx and prevention
MMR vaccine; pooled immunoglobulins (prophylaxis in unvaccinated)
Treatment: Supportive care. Vitamin A supplementation
67
mumps morphology
negative sense single strand RNA, non-segmented, helical capsid, enveloped
68
infectious properties/transmisison of mumps
HN does both entry and exit, like parainfluenzae
Respiratory transmission
69
Clinical manifestation of mumps
Incubation - 7-10 days;
Viremia - 15 days
Disease manifestations – 18+ days: Parotitis (swollen parotid gland), orchitis (testis pain), mastitis, aseptic meningitis, encephalitis (Mumps gives you bumps!)
70
mumps diagnosis
clinical findings, serology
71
tx/prevention of mumps
No tx, vaccine coverage not quite as good as it was with measles. See some outbreaks amongst the vaccinated
72
Rubella/German Measles morphology
Togaviridae- Rubivirus,
enveloped,
(+)ssRNA,
non-segmented,
Icosahedral,
single serotype.
73
Infectious properties of Rubella
Only Togavirus not transmitted by Arthropod
74
Clinical presentation of Rubella
Fever followed by descending rash (mild disease);
Congenital rubella (toRches)- if mother infected in 1st trimester:
fetal deafness,
cataracts,
heart defects (PDA),
mental retardation,
blueberry muffin rash.
75
Rubella Diagnosis
Detection of IgM Rubella antibodies
76
Rubella transmission
respiratory droplets
77
Treatment/prevention of German measles
No Tx, MMR vaccine
78
Enteroviruses
“PERCH”
Poliovirus
Echovirus
Rhinovirus
Coxsackievirus A & B
Hepatitis A
79
Polio morphology
Enterovirus, Picornaviridae
non-enveloped, (+)ssRNA, nonsegmented, icosahedral
80
Infectious Properties of Polio
Stable at low gastric pH,
hidden binding sites,
inhibits host ribosomes
81
Clinical Presentation of Polio
Replicates in lymph of GI --\> viremia --\> anterior horn of spinal cord
Can cause meningitis and paralysis
82
Diagnosis of Polio
Done on Serology
83
Epidemiology of Polio
Fecal Oral in developing countries
84
Treatment/Prevention of Polio
IPV – Salk vaccine (killed)
OPV – Sabin (live attenuated)
85
Echo and Coxsackie morphology
Enteroviruses, picorniveridae
very small, non enveloped
Positive sense single strand RNA
nonsegmented
icosahedral
86
Infectious properties of echo and coxsackie
Stable at low gastric pH, hidden binding sites
87
Clinical Presentation Coxsackie A
herpangina, vesicular lesions, **hand-foot-and-mouth diseases**, throat pain, anorexia
common cold, fever, rash, meningitis in summer
88
Clinical Presentation of Coxsackie B
myocarditis, pleurodynia (painful pleuritic chest pain), fever,
common cold, fever, rash, meningitis in summer
89
Clinical Presentation Echovirus
Neonatal Disease
common cold, fever, rash, meningitis in summer
90
Epidemiology of Echo/Coxsackie
Fecal oral transmission, kids = hand/foot/mouth
91
Treatment of Echo Coxsackie
Symptomatic
92
Different types of Meningitis, CSF analysis
93
Rhinovirus morphology
Enterovirus, picorniviridae,
very small, non enveloped
ssRNA positive sense
non segmented
icosahedral
94
Infectious Properties of Rhinovirus
Over 100 serotypes, so reinfection of same host
95
Clinical presentation of rhinovirus
Also - pharyngitis, otitis media.
Less common - bronchiolitis and pneumonia.
NUmber one cause of the common cold
96
Diagnosis Rhinovirus
Treatment Rhinovirus
Diagnosis clinical
Tx supportive
97
Rhinovirus epidemiology
Everywhere and everyone;
Transmitted by aerosols and fomites.
Hands thought to be major vector.
Early autumn and late spring.
98
Rotavirus morphology
non-enveloped;
inner and outer capsids
Segmented dsRNA genome
dsRNA --\> unique to reovirus aka this family
99
Rotavirus infectious properties
Enterotoxin (“NSP4”) --\> causes dirrhea
replication in host cytoplasm
Highly resistant to desiccation -- can survive in feces for months!
100
Rotavirus Clinical presentation
Diarrhea (watery), fever, vomiting, dehydration;
worse in immunodeficient 48 hr incubation;
subsequent reinfections are milder thanks to imperfect antibodies.
101
Diagnosis of rotavirus
ELISA, latex agglutination in stool, PCR, EM
102
Epidemiology of Rotavirus
**#1 cause of Diarrhea in kids in the US and worldwide;**
almost everyone’s had it by age 4
Spread via Fecal-oral route;
patients shed virus both pre- and post-infection.
More common in winter months
103
Rotavirus treatment and prevention
Prevent with \*Live\* Vaccine;
Oral Rehydration therapy in active infection
104
Norovirus morphology
Calicivirus family.
Non-enveloped,
(+) ssRNA,
non-segmented genome
105
Infectious Properties of norovirus
Infects the upper GI tract, replicates there
Host creates antibodies against norovirus, but they have a short effective half life
106
Clinical presentation of norovirus
Watery diarrhea +/- fever, headache, and constitutional symptoms
More diarrhea in adults, more vomiting in kids
1-2 day incubation --\> 1-2 day illness --\> 2 weeks shedding
107
Diagnosis of norovirus
Usually from clinical picture
108
Epidemiology of Norovirus
#1 cause of Adult watery diarrhea, often with large outbreaks (think cruise ships)
Fecal-oral spread; affects older children and adults
Some are asymptomatic carriers, some are totally immune (“secretor negative”)
109
Treatment of norovirus
Supportive
110
What does hepatitis look like clinically
upper right quadrant pain
nausea/vomiting
jaundice
itching
fatigue
111
Hepatitis Morphologies
Hep A - Picorniviridae, non-enveloped, **(+)ssRNA**, nonsegmented, icosahedral
Hep B - Hepadnavirus, **circular dsDNA** Enveloped, icosahedral **(carries own reverse txase)**
Hep C - Flaviviridae, Enveloped, **+ssRNA**, linear, icosahedral
Hep D - Circular genome, **ss-RNA**
Hep E - Hepevirus (calcivirus) non-enveloped, **+ssRNA**, icosahedral
112
Hepatitis Transmissions
Hep A - Fecal Oral
Hep B - Parenteral, Vertical, sexual (?)
Hep C - Parenteral (mostly)
Hep D - Parenteral, Vertical, Sexual
Hep E - Fecal Oral (waterborne)
113
Incubation/clinical presentation of Hepatitis
Hep A - Short --\> Abrupt presentation.
Hep B - Long (months).
Hep C - Long
Hep D - Depends
Hep E - Short
114
Hepatitis Clinical Presentations
**Hep A --\>** Mild/self limited disease. Rarely see hepatic failure secondary to host IR.
**Hep B --\>** Acute (after the long incubation) OR
Chronic (latent carrier state possible) hepatitis: ALT \> AST
Cirrhosis
HCC (hepatocellularcarcinoma) (DNA oncogene; don’t need cirrhosis)
**Hep C--\>** 20% self limited 80% progress to asymptomatic carrier or chronic active Hep C (at risk for HCC or cirrhosis)
Hep D --\> Co-infection with Hep B, causes Superinfection (worse outcomes)
Hep E --\> Acute (short incubation), self-limited, NOT chronic
High mortality pregnant women in 3rd trimester
115
Hepatitis Infectious Properties
Hep A - Stable in the soil and water
Hep B - Targets hepatocytes, but it's mostly the immune response that causes damage
Hep C - E2 mediated cell attachment, RNA polymerase= high mutation rate, NS3/4A protease prevents IFN-b induction
Hep D - Needs Hep B for envelope proteins or else no infectious
116
Hepatitis Diagnoses
Done with serology mostly
Hep A - anti HAV IgM (acute) anti HAV IgG (prior or vaccination)
Hep B - HBsAg – surface antigen, indicates current infection Anti-HBs – Immunity (either exposure or immunization) Anti-HBc – Indicates exposure (IgM: acute, IgG: resolved) HBeAg– Contagious
Hep C - anti-HCV Ab, PCR (HCV RNA), biopsy
Hep D - HBV and HDAg S and L
Hep E - Clinical
117
Epidemiology of Hepatitis
Hepatitis A - Fecal oral transmission - Shellfish outbreaks Endemic areas, crowding, military, children
Hep B - Endemic S. Europe, Africa, Asia
Hep C - HIV coinfection, IV drug use
Hep D - Pts with HBV
Hep E - Developing countries
118
Hepatitis treatments
Hep A --\> Supportive/vaccine
Hep B --\> Vaccine, IFNa, HBV LATTE (RT-I) which doesn't really work that well
Hep C --\> OLD: Pegylated IFN-a + Ribavirin (duration based on genotype)
Hep C --\> OLD: PegIFN + Ribavirin NEW: PegIFN + Ribavirin + Protease Inhibitor (Telaprevir or Boceprivir). No Vaccine.
Hep D --\> Treat Hep B
Hep E --\> Supportive
119
All the herpes viruses
Herpes Simplex Virus --\> HSV-1;
HSV-2;
Varicella Zoster Virus --\> VZV;
Epstein Barr Virus --\> EBV;
Cytomegalovirus --\> CMV;
Human Herpes Virus --\> HHV-6 & HHV-7;
HHV-8
120
HSV1 and HSV 2 morphology
dsdna, enveloped icosahedral
121
HSV 1 and 2 pathogenesis
Surface glycoproteins: attachment and fusion, bind complement, bind Fc of IgG.
Latent in CNV ganglion (HSV-1) or sacral ganglion (HSV-2)
122
Transmission HSV 1 and 2
HSV 1: Respiratory secretions, saliva, HSV 2: Sexual, perinatal
123
Clinical Presentation of HSV 1 and 2
Many asxatic. Oral/genital lesions- crops of small, painful blisters that ulcerate. Encephalitis.
In neonates: diarrhea, recurrent infections. (ToRCHES).
124
Diagnosis of HSV 1 and 2
Culture, DFA, PCR, Tzanck smear (scraping of ulcer for cells)
125
Epidemiology of HSV 1 and 2
HSV1 = most people have it,
HSV2: usually sexually transmitted
126
Treatment of HSV 1 and 2
Acyclovir, Valacyclovir
127
Varcicella Zoster Virus (“VZV,” or Human Herpes Virus-3) morphology
dsDNA, enveloped, icosahedral
128
Pathogenesis of VZV/Zoster
Similar to HSV 1/2
Surface glycoproteins: bind complement, bind Fc of IgG and enter cells. Latent in DRG
129
Clinical presentation/transmission of VZV/Zoster
Transmission: respiratory droplets
Primary (varicella): Chickenpox (“dew drop on rose petal” vesicles of different ages)
Reactivation (zoster): Shingles (vesicles & pain in dermatomal distribution from DRG) seen in Immunopromised /pregnant also with pneumonia or encephalitis
130
Diagnosis of VZV/Zoster
Made on history of chicken pox, clinical.
131
Epidemiology of Zoster/VZV
Primary disease worse in adults, reactivation in immunocompromised
132
Treatment of VZV and Zoster
VZV vaccines, (Val)Acyclovir, Human Pooled IgG
133
Epstein-Barr Virus (“EBV” or Human Herpes Virus-4) morphology
dsDNA, enveloped, icosahedral
134
EBV transmssion/pathogenesis
TM by saliva, requires close contact.
Infects B cells via CD21, causes B cell transformation
(immortalization), remains latent in B cells for life. Can cause via this immortilazation atypical lymphocytosis (T cells).
135
EBV clinical presentation
Mononucleosis: fatigue, fever, lymphadenopathy, pharyngitis, hepatosplenomegaly, rash (worse with amoxicillin). Resolves in 2-3 weeks. --\> mono sucks, you feel really tired
Complications in immunosuppressed: lose control of transformed B cells, complications range from minor to malignancy
136
Diagnosis of EBV
MONOspot test- IgM heterophile (nonspecific) antibody
\*Not sensitive for children under 5 yrs old
137
Epidemiology of EBV
50% of children infected, 70% of US by age 30
African endemic Burkitt’s, HIV-associated lymphomas, Hodgkin’s
138
Treatment EBV/mono
Rest, reduce immunosupression
139
CMV human herpes virus 5 morphology
dsdna
icosahedral
enveloped
140
Pathogenesis of CMV
Infects lymphocytes,
Downregulates MHC I, Contains UL97 and UL 54.
141
Clinical presentation of CMV
EBV negative Mono
Congenital infection --\> (hearing loss) TOR**C**HES CMV is the most common congenital infection
Severe disease in immunocompromised (pneumonia, retinitis, etc)
Other: Guillain-Barre syndrome
Shed in secretions, blood transmission
142
TORCHES congenital infections
T – Toxoplasmosis / Toxoplasma gondii
O – Other infections (see below)
R – Rubella
C – Cytomegalovirus
H – Herpes simplex virus-2 or neonatal herpes simplex
The "other agents" under O include:
Coxsackievirus
Chickenpox (caused by varicella zoster virus)
Chlamydia
HIV
Human T-lymphotropic virus
Syphilis
143
Diagnosis of CMV and
**Owl’s eye inclusions,** biopsy and culture, PCR, urine cultures
144
Epidemiology of CMV
Most people are CMV positive, but disease is bad in immunocompromised.
145
Treatment of CMV
Treatment is reserved for immunocompromised. Can treat prophylactically
## Footnote
1st Line: (Val)Gancyclovir.
2nd Line: Foscarnet or Cidofovir if viral TK (UL97) resistance. 2nd line drugs are very toxic, esp. Cidofovir (nephrotoxic)
146
HHV-6 (and HHV-7) morphology
dsDNA, enveloped, icosahedral
147
HHV-6 (and HHV-7) pathogenesis
Infects lymphocytes; Persists in Macrophage
148
HHV-6 (and HHV-7) clinical presentation
Sixth Disease or Roseola
```
Roseola (Exanthema subitum): Child with 2 days of fever, then fever disappears and total body rash suddenly appears.
Febrile seizures (benign condition)
```
149
Diagnosis of HHV-6 (and HHV-7)
Made on clinical presentation:
## Footnote
```
Roseola (Exanthema subitum): Child with 2 days of fever, then fever disappears and total body rash suddenly appears.
Febrile seizures (benign condition)
```
150
Epidemiology of HHV-6 (and HHV-7)
Most children have it by age 3 (95%)
151
Treatment of HHV-6 (and HHV-7)
Treating Sixth Disease or Roseola
Gets better on its own, supportive
152
HHV-8 is also called
(Kaposi Sarcoma Associated Herpesvirus)
153
Morphology of HHV-8
## Footnote
(Kaposi Sarcoma Associated Herpesvirus)
dsDNA, enveloped, icosahedral
154
Pathogenesis of HHV-8
Infects B cells primarily, encodes growth and anti-apoptotic factors
155
Clinical presentation of HHV-8
Kaposi Sarcoma: Vascular lesions w/bleeding and hemosiderin deposition
Primary effusion lymphoma --\> lymphoma in body cavities
Castleman’s disease --\> proliferation of lymph nodes
156
Diagnosis of HHV 8
History of Aids, Clinical presentation:
## Footnote
Kaposi Sarcoma: Vascular lesions w/bleeding and hemosiderin deposition
Primary effusion lymphoma
Castleman’s disease
157
Epidemiology of HHV-8
In the US: associated with HIV/AIDS, MSM, and drug users
Endemic in Africa, Mediterranean
158
Treatment of HHV-8
Antiretrovirals for HIV (or chemo if invasive)
159
Human Papilloma Virus (HPV) morphology
Unenveloped, circular dsDNA
160
HPV virulence factors
– Does not infect APCs--\>limited immune detection
– Viral proteins E6 and E7 inhibit tumor suppressor genes --\> oncogenicity
161
Clinical presentation of HPV
– Most asymptomatic
– Strains 6, 11 --\> Genital warts (condyloma accuminatum)
– Strains 16, 18 --\> Cervical cancer
162
Diagnosis of HPV
– Cytology (“Pap smear”): look for characteristic changes (koilocytes)
– Biopsy (if abnormal cells seen on pap): look for degree of cervical endothelial dysplasia
163
Epidemiology of HPV
– Exposure is EXTREMELY common; sexually active are at risk for high risk strain
infection.
– 99% of all cervical cancers assoc with HPV infection (also anal cancers
164
Treatment/Prevention of HPV
Bivalent (16, 18) and tetravalent (6, 11, 16, 18) vaccines available for women and men ages
Treat malignancy with chemoradiation
165
HIV morphology
- Enveloped, with 2 copies of + sense ssRNA
- Carries its own reverse transcriptase, a protease, and “integrase --\> targets for drugs
166
Infectious properties/pathogenesis of HIV
- A retrovirus: Inserts its genetic material into the host’s genome
- Selects for immune cells: CD4+ Helper T-Cells & Macrophages
- Evades effective immune response due to hyper-variability of envelope proteins & downregulation of MHC
167
Clinical course of HIV without HAART (aka AIDS)
- Acute Infection (~2-4 weeks) --\> Asymptomatic Period (avg ~8 yrs) --\> AIDS (~13 yrs)
- Opportunistic infections, increased risks of cancer, dementia, kidney disease, more.
168
Diagnosis of HIV
- ELISA for anti-HIV antibodies,
confirm with Western blot;
PCR for plasma viral RNA
169
Epidemiology of HIV
In US, highest risk is in MSM, IV drug users, and Immigrants from endemic areas
- Most new infections are in Blacks & Latinos; increasing % through heterosexual contact
170
Treatment of HIV
- Highly Active Anti-Retroviral Therapy (“HAART”)
will go into specifics on other cards
171
Specific important proteins/genes of HIV virus
**p24** --\> capsid protein encoded for by gene *gag*
**gp41 -**-\> fusion and entry
**gp120** --\> attachment to host T cell
**gp41** and **gp120** are both envelope proteins (outermost layer, surrounding capsid) encoded for by gene *env*
**Reverse transcriptase** --\> encodes dsDNA from (+) ssRNA encoded for by gene *pol*
**Integrase** --\> inserts dsDNA into host genome
172
Time course of HIV infection
Primary Infection --\> Low viral load, High T cell count
Acute HIV syndrome (wide dissemination of virus and seeding of lymphoid tissue) --\> High viral load and mid-low T cell count. Three weeks after primary infection.
Clinical Latency --\> Can last months to years. Viral load drops after acute HIV syndrome and then starts rising slowly. T cell count starts dropping slowly.
Constitutional symptoms --\> Happens when T cell count gets low enough/viral load gets high enough
Opportunistic Infections --\> When T cell count gets really low. Viral load very high.
Death --\> Usually due to an opportunistic infection/other sequealae.
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Common opportunistic infections
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Principles of HAART
- Strongly recommended for all pts at time of dx
- Required for pts CD4 count \<500 cells/mm3, or AIDS-defining illness
Use exactly 3 drugs:
- Use at least two different classes of drugs
- Usually: 2 NRTI + 1 integrase inhibitor
Lack of maintenance --\> breeding resistance to drugs.
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Life Cycle and linked Drugs
1. Attachment (Maravoric)
2. Fusion/Uncoating (Enfurvitide)
3. Reverse Transcription (NRTIs Exs: Abacavir, Tenofovir), NNRTIs Exs: NeVIRapine, EfaVIRenz, and EtraVIRine )
4. Integration (Integrase Inhibitor, Ex: Raltegravir)
5. Assembly
6. Maturation (Protease Inhibitors ex: idinavir all \_\_\_-navir)
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NRTIS mechanism of action and names and toxicities
Molecules that look like a normal nucleosides and competitively inhibit reverse transcriptase.
Examples: Zidovudine, Lamivudine, Emtricitabine, Abacavir,and Tenofovir
Toxicity for Entire Class: mitochondrial toxicity, peripheral neuropathy, hepatitis, lactic acidosis, dislipidemia, insulin resistance
Abacavir: Hypersensitivity reactions in pts with HLA-B5701 (we can test for this). We can test for this and prevent a possible fatal reaction.
Tenofovir: Renal toxicity, esp. if underlying renal disease; osteomalacia
Zidovudine: anemia
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NNRTIs mechanism of action, names, toxicities
Allosterically inhibit RT
## Footnote
NeVIRapine, EfaVIRenz, and EtraVIRine
Toxicities for entire class: Cytochrome p450 interactions, early resistance, rash
Nevirapine: Can cause severe **hypersensitivity** reaction with liver toxicity and rash, particularly in women with high CD4 counts.
Efavirenz: **Teratogen**, so avoid in pregnancy. Also causes neuropsychiatric symptoms like vivid dreams and/or depression; lipid elevation.
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Protease Inhibitors mechanism of action, names, toxicities
- Messes up the maturation of the drugs because the proteins need to be cleaved in order to be assembled.
- Lopinavir, Atazanavir, Darunavir, Fosamprenavir, Tipranavir
- Can also act as a pharmokinetic booster --\> Ritonavir +Cobicistat (cytochrome p450 inhibitors)
Toxicities entire class: Cause GI disturbances and metabolic syndrome (high cholesterol, diabetes, etc), lipodystrophy, CYP450 interactions.
Atazanavir: Can cause jaundice (without actually causing liver injury), kidney stones.
-
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Prophylaxis for Pneumocystic jiroveci
– CD4 count \<200
– TMP-SMZ
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• Prophylaxis for Mycobacterium avium- complex
– CD4 count \<50
– Azithromycin
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Immunology: Extracellular Bacteria
Innate Response:
– Phagocytosis
– Complement activation
Adaptive Response:
– Ab neutralization of pathogen
– Ab potentiation of innate response
* Opsonization
* ADCC (antibody dependent cell-mediated cytotoxicity)
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Immune evasion extracellular bacteria mechanisms
* Inhibition of complement (all)
* Resistance to phagocytosis (Strep. pyogenes)
* Biofilm (Staph. epidermis)
* Clot formation (Staph. aureus)
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Immunology intracellular bacteria adaptive and immune response
• Innate response: Transient control for a short period of time
– NK cells
– Phagocytes
• Adaptive response: Infection eradication
– Th1 cells --\> IFN gamma
– IFN gamma--\> phagocytes to destroy endocytosed bacteria
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Immune evasion intracellular bacteria
* Intracellularity!
* Inhibition of phagolysosome fusion (TB, Legionella)
• Destruction of phagosome membrane (Listeria)
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Immunology viruses
* Innate response: Link to adaptive\*
* Adaptive response: Potential eradication\*\*
– Th1 cells --\> IFN gamma
– IFNs --\> “antiviral” state
• Alpha/Beta: Recruit uninfected cells to put their defenses up, activate NKCs to kill viral infected cells.
• Gamma: Increases MHC I, II expression in all cells
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Immune evasion: Viruses
* Intracellularity!
* Inhibition of antigen presentation
• Manipulation of cytokine environment
– IL-1 blockade (all)
– Cytokine receptor decoys (poxvirus)
– Secretion immunosuppressive cytokines (EBV)
• Lysing of immune cells (HIV)
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Common immune evasion strategies
* Neutralization ROS (many bacteria)
* Multiple serotypes (bacteria & viruses)
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Viral vaccines: killed
Hepatitis A: Killed whole virus
Hepatitis B: Recombinant protein subunit (HBs)
HPV: Recombinant protein subunits
Rabies: Killed whole virus, Given as part of PEP
Influenza: Killed whole, Injected form only
Polio (Salk): Killed whole, Injected; 4 doses before school entrance. No mucosal immunity.
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Viral vaccines live
Measles/Mumps/Rubella: Live attenuated; Contraindicated in pregnant women, HIV pts with signs of immunodeficiency.
Yellow fever: Live attenuated; Given to those traveling to endemic areas
VZV: Chickenpox: Live attenuated
VZV: Shingles: Live attenuated; Given to pts \>60 y/o, 10x dose of chickenpox
Polio (Sabin): Live attenuated, 3 doses provide optimal immunity; 1 provides 50%
Rotavirus: Live human-bovine reassortant (Rotateq) OR Live human attenuated (Rotarix), Rotateq is pentavalent; Rotarix is monovalent but provides cross-protection. Both multi-dose.
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Viruses we provide passive immunity for
* Hepatitis A (IVIg)
* Hepatitis B (Hepatitis B Ig)
* Rabies (Rabies Ig)
* Varicella (Varicella Ig)
* RSV (palivizumab)
...and breast feeding!
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Diseases caused by prions
Humans: Creutzfeldt-Jakob Disease (CJD), Kuru.
Other animals: Scrapie, Bovine spongiform encephalopathy, chronic wasting disease
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Infectious Properties seen in Prions
Infectious form of normal brain protein (PrP).
Domino effect: one misfolded molecule acts as template for other molecules to misfold.
Misfolded proteins are resistant to proteases. Accumulation leads to tissue damage and cell death.
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Clinical presentation of prion diseases
Long incubation period, slow but progressive neurologic deterioration (dementia, myoclonus, etc.). Uniformly fatal; most patients die within 6 months of symptom onset.
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Diagnosis of Prion diseases
Clinical; can perform EEG, MRI, CSF analysis.
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Epidemiology of prion diseases
Most cases are sporadic. Brain eaters, exposure to animal form, rarely familial.
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Treatment for prion diseases
none
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Arboviruses (arthropod borne viruses) types and names
Need to Know bolded ones
Family: Togaviridae (ss +RNA) Genus: Alphavirus
Viruses: **EEE\*, WEE\***, VEE
Family: Flaviviridae (ss +RNA) Genus: Flavivirus:
Viruses: **Dengue virus**, **West Nile Virus,** **Yellow fever**, **SLE\***
Family: Bunyaviridae (ss -RNA) Genus: Bunyavirus:
Viruses: **La Crosse\***, Hantaviruses (rodents)
\* are causes of mosquito borne encephalitis. EEE has very high mortality.
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Dengue Fever morphology/serotypes
Flavivirus, enveloped, (+)ss RNA, linear.
4 serotypes.
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Dengue Fever Clinical Presentation
```
Less severe (Dengue Fever): aka “Break-bone fever” due to muscle & joint pain. Also: fever, rash, bone marrow suppression.
More severe (Dengue Hemorrhagic Fever and Dengue Shock Syndrome): Severe hemorrhagic disease, leaky capillaries and multiorgan involvement.
```
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What causes more severe presentation of Dengue Fever
(Severe disease usually occurs with second infection with a different serotype (four serotypes), due to antibody-mediated immune enhancement = exacerbated cytokine release.)
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Diagnosis of Dengue Fever
Detection of anti-DenV IgM in serum, PCR
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Epidemiology of Dengue Fever
Tropical Areas where there are mosquitos. S. America, parts of Africa, South Asia/ South East Asia
203
Vector of Dengue Fever
Aedes aegypti mosquitos. Human and Monkey host.
204
Treatment of Dengue Fever
Supportive care, vaccine trials ongoing
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Yellow Fever Morphology
Flavivirus, enveloped, (+)ss RNA, linear
206
Yellow Fever Clinical Presentation
Majority: mild illness with fever, H/A, N/V, chills, back pain
Minority: enter a toxic phase with fever, jaundice (liver damage), GI hemorrhage
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Epidemiology of Yellow Fever
Africa, S. America, Central America
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Vector of Yellow Fever
Aedes aegypti mosquitos (same as Dengue)
Monkeys and Human reservoirs
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Treatment of Yellow Fever
Live attenuated vaccine available.
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West Nile Virus morphology
Flavivirus, enveloped, (+)ss RNA, linear
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Clinical presentation of West Nile Virus
Most cases are asymptomatic (80%)
Rarely can progress to neuroinvasive disease: flaccid paralysis, aseptic meningitis or severe encephalitis (\<1%)
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Epidemiology of West Nile Virus
Has become more wide-spread over the years within the United States, from 2000 to now. Now see cases in every state. In 2000 saw just in the north east.
More severe infection with age and immunosupression.
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Vector for West Nile Virus
Mosquito- Culex sp.
Human and Bird Host
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Treatment of west nile virus
Supportive care. No vaccine available.
Prevention with good mosquito control.
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Mosquito Borne encephalitis (other then west nile)
EEE (highest mortality) seen in Eastern NA, SA
WEE seen in Central and Western US, SA
SLE Americas. Seen in Urban epidemics.
La Crosse
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Rabies morphology
Rhabdovirus, (-)ssRNA, linear, enveloped,
Helical capsid with “Bullet shaped” appearance
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Rabies clinical presentation
Prolonged incubation in muscle (months to years).
Then, virus travels proximally to CNS via axons, causing acute encephalitis: mental status changes, delirium, paresthesias, pain, and death.
Onset of symptoms to death ~18days!
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Diagnosis of Rabies
DFA (direct fluorescent antibody test) on nape of neck biopsy, PCR, Negri bodies in brain (viral sharply lined eosinophilic nucleocapsid inclusions in cytoplasm of some infected cells)
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Epidemiology of Rabies
Rare in US, related to exposure to bats, raccoons, skunks, wild dogs
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Transmission of Rabies
Exposure of non-intact skin to saliva of infected animal ~2 cases/ year in USA
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Treatment of Rabies
Vaccine (prevention and as part of PEP)
IgG Post-exposure prophylaxis (administer w/in 72 hours)
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Viruses with helical capsid
-Myxo’s (para,ortho)
- Corona
- Rabies
Mumps
Measles/Rubeola
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