Herpesviral Diseases

Question 1

HSV-1 (α): Shedding

Answer 1

• In oral/genital secretions
• Shedding in both latent and active phases

Question 2

HSV-1 (α): lytic features

Answer 2

• Gingivostomatitis
• Genital herpes
• Herpetic keratitis
• Neonatal herpes
• Herpetic whitlow
• Encephalitis
• Dissemination
• Reactivation

Question 3

HSV-1 (α): latent feature

Answer 3

• Trigeminal ganglion

Question 4

HSV-1 (α): disease of immunocompromised

Answer 4

• Reactivation common
• Severe in people with defective T-cell immunity
• Prophylactic antivirals used during chemo, etc.
• Neonatal HSV (severe/fatal)
• Important role for antiviral therapy

Question 5

HSV-2 (α): shedding

Answer 5

• In genital/oral secretions
• Shedding in both latent and active phases

Question 6

HSV-2 (α): lytic feature

Answer 6

• Same as HSV-1:
  
  • Gingivostomatitis
  • Genital herpes
  • Herpetic keratitis
  • Neonatal herpes
  • Herpetic whitlow
  • Encephalitis
  • Dissemination
  • Reactivation

Question 7

HSV-2 (α): latent feature

Answer 7

• Sacral ganglion

Question 8

HSV-2 (α): disease of immunocompromised

Answer 8

• Reactivation common
• Severe in people with defective T-cell immunity
• Prophylactic antivirals used during chemo
• Neonatal HSV (severe/fatal)
• Important role for antiviral therapy

Question 9

VZV (α): shedding

Answer 9

• Varicella: shed before rash erupts via respiratory drops
• Zoster: by fomites

Question 10

VZV (α): lytic feature

Answer 10

• Varicella: chicken pox
  
  • Fever, malaise, headache, dew drop on rose petal rash
• Zoster: shingles
  
  • Prodrome, dermatomal vesicles, unilateral, post-herpetic neuralgia

Question 11

VZV (α): latent feature

Answer 11

• Any ganglion
• Usually dorsal root (spinal) ganglion

Question 12

VZV (α): diseases in immunocompromised

Answer 12

• Bacterial superinfection
• Severe infection in immunocompromised children and adults
• T-cell mediated immunity decrease provides opportunity for VZV to progress to shingles

Question 13

CMV (β): shedding

Answer 13

• Pharynx shedding
• Infection can occur at any age
  
  • In utero through placenta
  • Shedding during delivery or in neonatal period
  • From childhood playmates
  • From sexual partners
  • From blood products and transplanted tissue

Question 14

CMV (β): lytic feature

Answer 14

• Mono-like syndrome in adults
• Congenital disease has multi-system disease with:
  
  • Hepatitis
  • Thrombocytopenia
  • Small brain
  • Seizure
  • Chance of hearing loss

Question 15

CMV (β): latent feature

Answer 15

• Latency in myeloid precursors, endothelial cells, possibly others

Question 16

CMV (β): disease in immunocompromised

Answer 16

• T-cell mediated immunity decrease (with age) provides opportunity for CMV
• Disease in newborn:
  
  • Maternal Ab leads to asymptomatic infection
• Primary infection in mom during pregnancy –> severe disease (3-5% of the time)

Question 17

HHV 6 + 7 (β): shedding

Answer 17

• Saliva shedding
• Sometimes nearly constant

Question 18

HHV 6 + 7 (β): lytic feature

Answer 18

• Exanthema subitum
  
  • aka roseola infantum
• Presents as:
  
  • Lethargy, irritability, fever
  • Injection of pharynx, tonsils, tympanic membranes
• Possible diarrhea, vomiting, adenopathy
• Diffuse maculopapular rash as fever subsides
• Mononucleosis syndrome possible

Question 19

HHV 6 + 7 (β): latent feature

Answer 19

• Viruses infect tissues, probably epithelial cells, in back of throat
• Circulating B and T cells then become infected –> spread virus throughout rest of body to cause characteristic illness

Question 20

HHV 6 + 7 (β): disease in immunocompromised

Answer 20

• Defective T-cell mediated immunity: multiorgan disease
  
  • Pneumonia, colitis, hepatitis, bone marrow suppression, colitis, encephalitis
• Disease in infant
  
  • 20% of all fever in this age
  • Including febrile seizure

Question 21

HHV 4 (ɣ) aka EBV: shedding

Answer 21

• Salivary shedding
  
  • > 95% of adults have antibody
• Shedding is common and often

Question 22

HHV 4 (ɣ) aka EBV: lytic feature

Answer 22

• Mononucleosis:
  
  • Fever, chills, sweats, headache, pharyngitis with exudates, lymphadenopathy, splenomegaly, hepatitis, eyelid edema

Question 23

HHV 4 (ɣ) aka EBV: latent feature

Answer 23

• Becomes latent in memory B-cells (1/105 to 1/106)
  
  • Source of salivary infection (and shedding) and cause of some complications

Question 24

HHV 8 (ɣ) aka KSHV: shedding

Answer 24

• Periodically shed asymptomatically in saliva - explains ease of spread within families

Question 25

HHV 8 (ɣ) aka KSHV: lytic feature

Answer 25

• Kaposi Sarcoma
  
  • Angioproliferative inflammatory lesion
  • Facilitated by suppressed immune function, also probably by HIV proteins, cytokines, growth factors coded for or induced by HHV-8

Question 26

HHV 8 (ɣ) aka KSHV: latent features

Answer 26

• Latency in B cells

Question 27

HHV 8 (ɣ) aka KSHV: disease in immunocompromised patients

Answer 27

• Kaposi’s sarcoma
• Primary effusion lymphoma (PEL)
  
  • B-cell malignancy of serosal surfaces (HIV+)
• Multicentric Castlemen’s Disease (MCD)
  
  • Lymphoid tumor (both HIV+ and HIV- people)

Question 28

Mononucleosis: incubation period, virus infection

Answer 28

• 2-4 week incubation period
• Followed by fever, malaise, adenopathy
• Mild hepatitis occurs, as well as sore throat
• Most tissue damage due to cell-mediated response, not the virus

Question 29

EBV vs. CMV mononucleosis

Answer 29

• CMV mononucleosis does not have heterophile antibodies
  
  • Common diagnostic test for EBV mononucleosis
• Have similar symptoms

Question 30

Infectious mononucleosis (IM)

Answer 30

• Most often caused by EBV
• The older a patient is when first infected with EBV, the more likely (>25%) they are to have classic IM syndrome
  
  • But young children can also develop IM
• EBV infected B cells in tissues –> you can predict IM signs and symptoms
• After 4-6 week incubation period during which specific T-cell mediated immunity develops, EBV infected B cells destroyed by cytotoxic T cells

Question 31

Infectious mononucleosis s/s

Answer 31

• Prolonged fever and profound malaise
  
  • from release of numerous cytokines
• Exudative pharyngitis
  
  • EBV is 1 of 4 causes of severe exudative pharyngitis (streptococcus, adenovirus, HSV in adolescents)
• Lymphadenopathy
• Splenomegaly
• Hepatomegaly and/or hepatitis
• Rash common in patients treated with abx
  
  • Atypical reaction to drugs, does not imply true allergic reaction
• Soft palate petechiae, eyelid edema - occasional findings

Question 32

IM without positive Monospot test

Answer 32

• “Monospot-negative” IM
• May have several causes:
  
  • Most likely - false-negative test demonstrated by specific serology
  • CMV
  • Other viral infections - rubella, Hepatitis A, HHV 6/7, toxoplasmosis

Question 33

Replicative and latent infection of ɣ-herpesviruses

Answer 33

• EBV from secretions from shedder infects epithelial cells in pharynx of contact
• Cells are unique in close association with lymphoid tissue (peritonsillar and other tissues in pharynx)
• At this location, B cells infected –> resulting viremia seeds multiple tissues, especially lymphoid and reticuloendothelial strutures
• During incubation period EBV-specific T-cell mediated immunity develops
• Eventually detects and destroys EBV-infected cells, but in doing so causes inflammation and tissue damage (signs and symptoms of EBV infection)
• Also becomes latent in memory B-cells - sources of salivary infection and shedding, cause of some complications