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Term 5: Infectious Disease > 6/23- Human Herpes Viruses II > Flashcards

6/23- Human Herpes Viruses II Flashcards

1
Q

What is the genetic material of herpes viruses?

A

ds-DNA

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2
Q

When are infectious rates of CMV highest?

A
  • Childhood and young adulthood
  • Seroprevalence varies among poulations
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3
Q

Modes of CMV transmission?

A
  • Congenital/perinatal
  • Direct contact (including sexual)
  • Parenteral
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4
Q

Which pts may experience reactivation disease?

A

Immunocompromised hosts

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5
Q

Pathogenesis of CMV Infections? Immune response?

A
  • Spread by direct contact with infectious materials (saliva, urine, blood, genital secretions), via placenta, and blood products
  • Viremia and viruria are common
  • Neutralizing Abs and T cell responses develop
  • CMI (T and NK cell) responses are particularly important for recovery
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6
Q

Disease syndromes caused by CMV?

A
  • Congenital infection
  • Mononucleosis-like illness
  • Severe visceral/disseminated disease in immunocompromised pts
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7
Q

When is congenital infection with CMV most severe?

A

When primary infection occurs during pregnancy

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8
Q

What are some symptoms of severe visceral/disseminated disease in immunocompromised hosts?

A
  • Pneumonia
  • Chorioretinitis
  • Hepatitis
  • Gastroenteritis
  • CNS disease
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9
Q

Question 1:

Which of the following agents is least likely to be associated with congenital infectious complications?

A. Rubella

B. Cytomegalovirus

C. Rotavirus

D. Toxoplasmosis

A

Question 1:

Which of the following agents is least likely to be associated with congenital infectious complications?

A. Rubella

B. Cytomegalovirus

C. Rotavirus

D. Toxoplasmosis

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10
Q

Symptoms of Congenital CMV infection?

A
  • Jaundice
  • Petechiae
  • Hepatosplenomegaly
  • IUGR
  • Preterm birth
  • MIcrocephaly
  • Hydranencephaly
  • Death
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11
Q

Clinical sequelae of Congenital CMV?

A
  • Sensorineural hearing loss
  • Low IQ
  • Chorioretinitis (choroid = middle or vascular coat of the eyeball)

Other

  • Microcephaly
  • Seizures
  • Paresis or paralysis
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12
Q

Symptoms of CMV Mononucleosis?

A
  • Fever (mean 19 days)- common
  • Pharyngitis (rare)
  • Lymphadenopathy (occasional)
  • Lymphocytosis (55-86%)
  • Mild hepatitis (high LFTs)- common
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13
Q

Etiologies causing mono-like illness?

A
  • EBV
  • CMV
  • HIV
  • Toxoplasma
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14
Q

CMV retinitis is associated with what? What is it/symptoms?

A

Associated with advanced immunosuppression (esp AIDS in pre-HAART era)

  • Affects neurosensory retina producing necrotizing retinitis
  • Often presents with bilateral disease (will go from one eye to the other)
  • If untreated, will progress to blindness
  • “pizza pie- cheese and ketchup”
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15
Q

What is this?

A

CMV pneumonia

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16
Q

What is this?

A

CMV colitis

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17
Q

How is CMV diagnosed?

A
  • Cytopathology (CMV “owl’s eyes” inclusions)
  • Antigen/nucleic acid detection
  • Culture of tissue, blood, urine, or secretions
  • Serologic methods (IgM, rising IgG)

For HIV/AIDS pt, need tissue or positive appearance in eye exam!

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18
Q

What is this?

A

“Owl’s eyes” inclusions of CMV (cytopathic effect)

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19
Q

What is this?

A

Cytopathic effect (CPE) of CMV:

  • Develops slowly
  • Note the linear pattern
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20
Q

Prevention and Control of CMV infections?

A
  • Careful handwashing & hygiene
  • Avoid contact with infected materials
  • Use blood or tissues from seronegative donors for seronegative infants or transplant recipients
  • CMV Ig, or antiviral therapy or prophylaxis (acyclovir, ganciclovir, valganciclovir, foscarnet) should be considered for high risk populations

- Cellular immunotherapy appears promising in transplant patients

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21
Q

Question 2:

Cytomegalovirus has been associated with all but which one of the following syndromes?

A. Congenital infection

B. Mononucleosis-like illness in adults

C. Pneumonia in immunocompromised hosts

D. Symptomatic reactivation disease in immunocompetent adults

A

Question 2:

Cytomegalovirus has been associated with all but which one of the following syndromes?

A. Congenital infection

B. Mononucleosis-like illness in adults

C. Pneumonia in immunocompromised hosts

D. Symptomatic reactivation disease in immunocompetent adults

Immunocompetent hosts can be CMV + but have no symptoms (typically)

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22
Q

How many people are seropositive for EBV?

A

90-95% of adults

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23
Q

T/F: Most childhood infections of EBV are asymptomatic

A

True

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24
Q

What is the major mode of transmission of EBV?

A

Direct contact with secretions

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25
Q

EBV is associated with which human malignancies?

A
  • African Burkitt’s lymphoma
  • Nasopharyngeal carcinoma
  • Some B cell lymphomas
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26
Q

Pathogenesis of EBV Infections?

A
  • Acute infection proceeds to persistent and latent infection
  • Main control of virus is CTLs and NK cells in immunocompetent individuals
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27
Q

Disease syndromes caused by EBV?

A
  • Infectious mononucleosis (initially described with EBV, although other viruses may produces similar symptoms): pharyngitis, lymphadenopathy, atypical lymphocytes on blood smears
  • Oral hairy leukoplakia in HIV-infected persons
  • Fatal infection in pts with X-linked lymphoproliferative syndrome
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28
Q

T/F; With EBV, reactivation disease may occur in recognized normal hosts?

A

False

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29
Q

Clinical manifestations of EBV mononucleosis?

A
  • Fever (76%)
  • Pharyngitis (84%)
  • Lymphadenopathy (94%)
  • Splenomegaly (52%)**
  • Lymphocytosis (70%)
  • Elevated LFTs (hepatitis) (50-100%)
  • Hepatomegaly

**Avoid exercise/strenuous activity to prevent splenic rupture!

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30
Q

What is the DDx for pharyngitis?

A
  • HSV
  • Adenovirus
  • Mycoplasma
  • Bacteria….
31
Q

What is this?

A

Development of a rash is particularly common among pts with EBV who are treated with ampicillin

32
Q

Complications of EBV infections?

A

Hematalogic:

  • Hemolytic anemia
  • Neutropenia
  • Thrombocytopenia

Respiratory:

  • Airway obstruction
  • Pneumonia
  • Otitis media

Neurologic:

  • Encephalitis
  • Meningitis
  • Myelitis
  • Optic neuritis
  • CN palsies
  • Seizures
  • Guillain-Barre syndrome
  • Reye syndromes

Cardiac:

  • Myocarditis
  • Pericarditis
  • MI

GI:

  • Hepatitis
  • Pancreatitis
  • Splenic rupture

Renal:

  • Nephritis
  • Nephrosis
33
Q

What is this?

A

Oral hairy leukoplakia seen with EBV

  • grey patch on side of tongue
34
Q

What is this?

A

“Starry night” histology seen with Burkitt’s lymphoma (can be caused by EBV)

35
Q

What is this?

A

Sign of Burkitt’s lymphoma (can be caused by EBV)

36
Q

What is this? Also seen when?

A

Atypical lymphocytes seen in EBV mononucleosis

- CTLs- the prmary mediators of recovery and control

Also seen in : CMV, Toxoplasmosis, Hepatitis, Rubella, Roseola, Mumps, Drug reactions

37
Q

Diagnosis of EBV?

A

Heterophile Abs

38
Q

What antibodies are looked at in serodiagnosis of EBV? When is each seen?

A

IgM-VCA (primary infection)

IgG- VCA (marker of infxn at some time)

IgG-EBNA (appears late; absence or seroconversion indicates primary infection)

39
Q

Serologic

Profile of EBV infections for:

  • Never exposed
  • Acute infection
  • Recent infection
  • Past infection
A
40
Q

Management of EBV mononucleosis?

A
  • Antivirals do not have clinical benefit (ACV has antiviral effect)
  • Steroids indicated for severe complications
  • Should avoid contact sports and heavy lifting during acute illness
41
Q

Question 3:

An 18 year old college freshman presents with a several week history of illness characterized by sore throat, fatigue, fever and swollen lymph nodes in the neck, axillae and inguinal region. On exam, she is noted to have fever to 102’F, exudative pharyngitis, lymphadenopathy, and hepato-splenomegaly. CBC shows lymphocytosis with atypical lymphocytes. Which of the following is MOST likely to yield the specific diagnosis?

A. Routine throat culture for virus

B. IgM against EBV VCA

C. IgG titer vs. EBNA

D. Positive rapid strep test

A

Question 3:

An 18 year old college freshman presents with a several week history of illness characterized by sore throat, fatigue, fever and swollen lymph nodes in the neck, axillae and inguinal region. On exam, she is noted to have fever to 102’F, exudative pharyngitis, lymphadenopathy, and hepato-splenomegaly. CBC shows lymphocytosis with atypical lymphocytes. Which of the following is MOST likely to yield the specific diagnosis?

A. Routine throat culture for virus

B. IgM against EBV VCA

C. IgG titer vs. EBNA

D. Positive rapid strep test

  • Doesn’t have strep b/c this has been several weeks; subacute
42
Q

Question 4:

Serum antibody responses against EBV VCA are the most important mediators of recovery from and control of EBV infections.

A. True

B. False

A

False

  • It’s the lymphocytes (cell-mediated immuno-response)
43
Q

When is HHV 6 mostly acquired?

A
  • Early in childhood (6 mo-2 yrs)
44
Q

Transmission of HHV 6?

A
  • Direct contact
  • Respiratory route
45
Q

Two variants of HHV 6?

A

6A and 6B

46
Q

Disease manifestations of HHV6 (overall)?

A
  • Roseola (6B) aka “Sixth disease”
  • Other febrile illness in infancy
  • Mono-like illness in adults
  • Visceral disease in immunocompromised
  • Gliomas?
47
Q

Clinical manifestations of primary HHV 6 infections?

A
  • High fever (>39’C)
  • Irritability, malaise
  • Inflamed tympanic membrane
  • Nasal congestion
  • Other: diarrhea, cough, abnormal breath sounds, vomiting, rash, seizures (a viral illness in a kid that lasts a little too long)

In Roseola, the rash isn’t actually all that common (10-20%ish)

48
Q

Timeline of Roseola (HHV 6)?

A
  • Febrile illness for 3-5 days
  • Followed by development of a diffuse rash as the fever abates
49
Q

How can HHV 6 present in immunocomproimsed pts?

A
  • Asymptomatic reactivations
  • Primary infection with fever and rash
  • Graft dysfunction/rejection, pneumonitis, encephalitis
50
Q

Diagnosis of HHV6?

A
  • Clinical manifestations of typical illness
  • Significant increase in Ab titers
  • Nucleic acid and antigen detection
  • Culture of HHV 6 from peripheral blood
51
Q

Treatment of HHV 6?

A

Anecdotes support effectiveness of ganciclovir and foscarnet for treatment of severe disease

52
Q

What are some characteristics of HHV 7?

A
  • Most closely related to HHV6
  • Common childhood infection
53
Q

How do the time and rate of infection vary between HHV6 and 7?

A

Infections of HHV7 are later and at a slower rate than HHV6

54
Q

When does viremia occur with HHV7?

A
  • Primary infection
  • Reactivated infection
55
Q

What are some clinical manifestations of HHV7?

A

(In viremic pts):

  • Fever
  • Seizures
  • URI
  • Gastroenteritis
56
Q

Question 5:

A 9-month old infant is brought to you by her father, who complains that she has had high fever and irritability for the past several days. This morning he noted that her fever was gone, but he is worried that she now has a skin rash. Her exam is normal except for a generalized maculopapular rash. What is the most likely etiology of this illness?

A. Herpes simplex type 1

B. Varicella-zoster virus

C. Cytomegalovirus

D. Human herpes type 6

A

Question 5:

A 9-month old infant is brought to you by her father, who complains that she has had high fever and irritability for the past several days. This morning he noted that her fever was gone, but he is worried that she now has a skin rash. Her exam is normal except for a generalized maculopapular rash. What is the most likely etiology of this illness?

A. Herpes simplex type 1

B. Varicella-zoster virus

C. Cytomegalovirus

D. Human herpes type 6

57
Q

What is the agent of HHV8? Similarity to what other virus?

A

Gamma-herpes virus

  • Genetic organization similar to EBV
58
Q

Mechanism of HHV 8 infection?

A
  • Encodes antigens expressed in lytic infection and during latency (used for serosurveys of infection)
  • Not readily isolated in culture
  • Common variants in host human genes may influence control of HHV8 infections
59
Q

Epidemiology of HHV8?

A

Seroprevalence rates vary:

  • Low among healthy heterosexuals in US
  • Somewhat higher in Mediterranean and East Africa
  • Highest rates among HIV-infected patients (especially those with KS), and among persons in some parts of Africa and South America
60
Q

Transmission of HHV8?

A
  • Patterns of infection suggest sexual transmission in some populations
  • Oral or other transmission possible in populations where disease is endemic
61
Q

Pathogenesis of HHV8?

A
  • Infects endothelial and spindle cells in vascular tumor tissue of Kaposi’s sarcoma
  • Genome encodes proteins associated with proliferation, mitogenic activity, and anti-apoptotic activity
62
Q

What are some clinical manifestations of HHV8?

A

Mononucleosis-like illness in HIV-infected pt Human tumors:

  • Kaposi’s sarcoma (almost always, these tumors are associated with HHV8)
  • Primary effusion and body cavitary lymphomas Multicentric Castleman’s disease (angiofollicular lymph node hyperplasia)
63
Q

What are some variant of Kaposi’s sarcoma?

Risk group?

Survival?

A
64
Q

What are the risk group and survival time of people with Kaposi’s sarcoma: classic variant?

A
  • Elderly men
  • E Europe and Mediterranean
  • Years to decades
65
Q

What are the risk group and survival time of people with Kaposi’s sarcoma: Endemic variant?

A
  • African children and adults
  • Months to years
66
Q

What are the risk group and survival time of people with Kaposi’s sarcoma: immunosuppression variant?

A
  • Organ transplant recipients
  • Months to years
67
Q

What are the risk group and survival time of people with Kaposi’s sarcoma: Epidemic or AIDS-associated variant?

A
  • Especially homo or bi-sexual men
  • Weeks to months (worst outcome)
68
Q

What is this?

A

Purplish lesion seen in Kaposi’s sarcoma (HHV8)

  • Seen commonly on extremities, but can be elsewhere
  • Often on skin/mucosa
69
Q

Treatment of HHV8?

A
  • Chemotherapy
  • Radiation
  • Antiviral therapy
  • Other
70
Q

What is herpes simiae? Infects who?

A

Herpes B

  • Common pathogen of old world monkeys
  • Highly pathogenic fo rhumans
71
Q

How is herpes simiae (herpes B) acquired?

A
  • Animal bites
  • Intimate contact with lesions
72
Q

Symptoms of herpes simiae (herpes B)?

A

CNS involvement is a common lethal complication

73
Q

Treatment for Herpes simiae (herpes B)?

A

Effective antiviral therapy

  • Must be instituted early in course of disease

Term 5: Infectious Disease (18 decks)

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