Exam #6: Viral STIs II Flashcards
What is the difference between initial genital infection & primary infection?
Primary= first time that the person has EVER had HSV infection, regardless of the location of infection
Initial Genital Infection= when primary infection is of the genitals (vs. mouth)
What are the symptoms of HSV genital infection?
Genital lesion
Fever
Inguinal adenopathy
Malaise
Symptoms more severe in women
Describe the lesion seen in HSV.
Progression from macules, papules, vesicles, pustules, to ulcers
Last 3 weeks
What is a recurrent lesion?
Lesion that re-appears after first infection
- 3-5 lesions on the shaft of the penis in males
- Vulvar irritation or lesions in females
- Prodrome of tingling & pain where the lesions will form
List the characteristics of HSV.
Herpesvirus family
Enveloped
dsDNA genome
HSV-2 is most common (HSV-1 causes outbreaks but no recurrence)
Encodes own enzymes for genome replication that is the target of antivirals
What else can HSV cause?
- Herpetic Whitlow
- Herpes labialis (cold sore)
- Herpes simplex keratits
- Herpes simplex encephalitis
What is Neonatal Herpes Infection? What is it important to remember regarding Neonatal Herpes Infection?
- Baby comes into contact with Herpes Simplex Virus during birthing process & develops Herpes
- Process is almost always symptomatic, & can be fatal
What are the three presentations of Neonatal Herpes Infection?
1) Disease localized to skin, eyes & mouth
~30% –if untreated–will develop blindness, microcephaly, & spastic quadriplegia
2) Encephalitis
~ 1/3 infants with Herpes infection will develop encephalitis; of these, 1/2 will die
3) Disseminated Infection that involves the skin & visceral organs; 8/10 will die
What are the symptoms of encephalitis?
Seizures Lethargy Irritability Tremors Poor feeding Temp instability Bulging fontanel
What are the characteristics of Neonatal Disseminated HSV?
Lesions in visceral organs & skin
How is Neonatal HSV infection prevented?
1) Examine mother with known HSV history for lesions & perform & c-section if suspicious
2) Remove healthcare workers with Herpetic Whitlow from NICU & mask those with orolabial lesions
How is Neonatal HSV infection treated?
IV administration of antivirals (for all three presentations)
Describe the mechanism of HSV infection.
1) HSV attack
2) Virus replication in peripheral epithelial tissues
3) Retrograde transmission via sensory neurons
4) Latency in cell body
Describe the mechanism of HSV infection that occurs with spontaneous reactivation.
1) Reactivation
2) Anterograde transmission via neuron
3) Replication in peripheral tissue
4) HSV shedding with new lesions
What is the difference between HSV-1 & HSV-2?
HSV-1= oral
- Peak primary infection is before age 4
HSV-2= genital
- associated with sexual activity
How is HSV transmitted?
- Direct contact with lesion
- Saliva
- Sexual
How is HSV diagnosed?
Clinically by the appearance of lesions
- Tzanck smear
- PCR
- Immunohistochemistry to detect antigens
How is HSV treated?
Oral lesion= NOT treated
Genital=
- Primary= oral antiviral
- Recurrent= long-term
oral antiviral
Neonatal=
- IV antiviral
Ocular=
- topical antiviral
*Note that these drugs do NOT act on the latent stage; goal is to shorten time to lesion healing & increase time between outbreaks
What are the two classes of HSV antivirals?
Nucleoside analog
Nonnucleoside inhibitor
Describe the mechanism of action of the nucleoside analogs.
E.g. acyclovir, valacyclovir, & pencyclovir
- Administered drug is a “prodrug”
- Viral enzyme “Thymidine kinase” cleaves into active drug
- Active form inhibits viral DNA polymerase & can incorporate into DNA chains & terminate them
*Low cytotoxicity because of dependence on thymidine kinase
Describe the mechanism of action of Non-nucleoside inhibitors.
E.g. Foscarnet
- Administered IV
- Binds pyrophosphate binding site of viral DNA polymerase, preventing DNA replication
- DOES NOT rely on viral thymidine kinase & is associated with higher levels of toxicity
*Used in HSV infections that are resistant to the nucleoside analogs
List the characteristics of HPV.
Popovaviridae family
Nonenveloped
dsDNA
Replication tied to the differentiation status of the tissue it infects
What does HPV cause?
- Genital warts
Condyloma acuminatum - Respiratory Papillomatosis
List the characteristics of genital warts.
Hyperkerototic
Firm
Exophilic papules
How can you tell the difference between wart & normal tissue?
3-5% acetic acid solution will turn warts white
What is Respiratory Papillomatosis?
- Nodules on ciliated & squamous epithelial junction of larynx
- Caused by HPV-6 & HPV-11 passed from mother to child
*Note that c-section has NOT been proven to reduce risk
What are the symptoms of Respiratory Papillomatosis ?
Altered cry
Hoarseness
Stridor
Respiratory distress
How is Respiratory Papillomatosis treated?
Surgical removal
What serotypes of HPV effect cause Laryngeal Papillomas?
6
11
What serotypes of HPV effect cause Anogenital Warts?
Noncancerous:
- 6
- 11
Cancerous
- 16
- 18
- 31
- 33
What serotypes of HPV effect cause Common Warts?
2
3
10
What serotypes of HPV effect cause Plantar Warts?
1
4
What is the connection between HPV and cervical cancer?
Certain types of HPV infection are associated with increased risk for developing cervical cancer
- Specifically, HPV-16 & 18
How does HPV cause cancer?
- E6 & E7 are two early genes expressed by HPV
- These proteins are normally blocked by the transcriptional repressor, E2
- In cancer causing strains, HPV DNA is linearized & integrated into host DNA without functional E2
- E6 inhibits p53 & E7 inhibits normal Rb function
- These proteins that normally prevent transcription and progression through G1-S phase of the cell cycle are inhibited
- Thus, these two gene products promote aberrant growth of infected cells
When is peak HPV infection?
15-25
When are most precancerous lesions seen?
28-30 years
When is HPV cancer most prevalent?
40
How is HPV transmitted?
Sexual transmission
How is HPV diagnosed?
Clinically–hyperkeratosis & koilocytes (Pap Smear)
PCR , 12, 16, & 18 (high risk)
What is a Koilocyte?
- Enlarged keratinocyte
- Irregular hyperchromatic nuclei
- Halo
How is HPV treated?
Genital warts
- Cryotherapy
- CO2 laser
Pre-malignant & malignant
How is HPV prevented?
Pap smears
Reduce risk behavior
HPV vaccine
What is the HPV vaccine
Capsid proteins L1 that form the natural shape of the HPV capsid
What are the vaccination recommendations for males & females.
It is recommended that BOTH sexes be vaccinated between 11 & 12 years.
- Females= bivalent or quadrivalent vaccine
- Males= quadrivalent
Bivalent= HPV-16 & 18 ONLY (most common cancer) Quadrivalent= same as bivalent + 6 & 11, causes of genital warts
