Herpes Simplex and Varicella-Zoster

Virus Infections

David Kramer, M.D.

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 HSV Infections

Asymptomatic, mucocutaneous, neonatal, CNS, latent

Type 1: gingivostomatitis, whitlow, keratoconjunctivitis, encephalitis, eczema

herpeticum
Type 2: genital HSV, meningitis

Classification: primary; non primary, first episode; recurrent, reinfection

Latency: sensory or autonomic neurons; LATS Reactivations: trauma, sunlight,
stress (despite antibodies)
Host: normal vs. immunocompromised

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 Neonatal HSV Infections

Congenital 5%; most HSV 2 (poorer prognosis)

Most mothers asymptomatic; antibodies may modify
Attack rate after primary maternal infection over 50% (> 10 times
than after recurrent infection)
Cesarean section controversial in women with recurrent HSV at delivery
Culture baby (eye, skin, throat) after 24 hours old
Categories, prognosis: skin/eye/mouth, CNS, disseminated
Symptoms: skin vesicles, fever, intractable seizures, pneumonia, DIC,
conjunctivitis, recurrent skin vesicles after therapy

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 HSV Encephalitis

Most common sporadic, focal encephalitis in US.

Estimate 1,000 cases yearly in U.S.
May be due to 1E or reactivation HSV infection; skin lesions a "red herring"
Symptoms: headache, fever, personality change, focal seizures
Differential diagnosis: TB meningitis, arbovirus, enterovirus,
Mycoplasma, mumps, tumor, toxoplasmosis, aneurysm

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 HSV Infections, Diagnosis

Isolate HSV, identify HSV antigen (immunofluorescence) in skin

CSF: abnormal; virus isolation + rare (except HSV 2 meningitis)
Antibody titers don't differentiate 1 vs. 2 (except g G)
Encephalitis: EEG, CT/MR, DNA/PCR, brain biopsy, antigen, antibody

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HSV Infections, Therapy: Acyclovir (ACV) PO or IV

Resistance: Especially with Repeated Treatment immunocompromised; TK

negative (less virulent) foscarnet
Indications: neonatal, encephalitis, primary/recurrent in immunosuppressed,
primary genital, eczema
Questionable efficacy: gingivostomatitis, recurrent infections
Keratitis: topical trifluorothymidine + ACV; ophthalmologist
Encephalitis: poor outcome if late, in coma, adult

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Morbidity, Mortality after Neonatal HSV 30 Mg/kg
IV

Morbidity Mortality
Untreated ACV Untreated ACV
stage of illness
Skin, eye, mouth 2% 2% 0 0
CNS over 80% 60% 40% 15%
Disseminated over 80% 40% 70% 60%

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 HSV, Consider Suppressive Therapy

Over 6 genital recurrences yearly

Recurrent skin lesions in first 6-12 months after neonatal
Immunocompromised patient at risk for disseminated, severe HSV

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 Natural History of Varicella-zoster Virus (VZV)

Primary infection: varicella

Secondary infection: zoster
Zoster due to reactivation of VZV: epidemiology, viral DNA & RNA in sensory
ganglia (several genes expressed) restriction enzyme studies after varicella and
zoster in same patient

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 Natural History of Varicella

Normal Host: Usually Mild Infection Immunocompromised Host: May Be Severe

or fatal (10% in pre-antiviral era)
Highly contagious (80-90% attack rate after household exposure)
Major nosocomial problem (95% of adults immune; 75% immune even with no
history)

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 Natural History of Zoster

Normal hosts: usually self-limited in the young

May be presentation of AIDS
Immunocompromised hosts: the more immunocompromised, the greater the
likelihood of zoster
Infectious to susceptibles as varicella (not as zoster)
Increased incidence over age 50 (decreased CMI), varicella in utero

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 Varicella

Mainly in children < 10 years old

Symptoms: vesicular rash, fever (2 viremias)
Complications: hepatitis, streptococcal/staphylococcal superinfection
(pneumonia, cellulitis, fasciitis, osteomyelitis) cerebellar ataxia,
encephalitis
Rare: myocarditis, AGN, Reye's syndrome
In immunocompromised: DIC, primary (viral) pneumonia, death
Congenital varicella syndrome (2%)
scarred rash, hypoplastic limb, eye, CNS damage, early zoster maternal
varicella 8th-28th week

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 Varicella, Epidemiology

Airborne spread
Incubation period 10-21 days (VZIG may prolong)
Contagious 2 days before-3 days after rash onset
Immunity: humoral and CMI develop after rash onset
4 million annual cases in US, 9,000 hospitalizations, 100 deaths
More severe in adults than children (low CMI)
Nosocomial exposures: expensive; nursery transmission rare

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 Varicella, Diagnosis

Differential: HSV, scabies, Stevens-Johnson, rickettsial pox,

Coxsackie A
Laboratory: (usually unnecessary)
Test skin lesions (not throat) for VZV
culture, PCR, immunofluorescence, in situ hybridization
Tzanck smear not specific
Antibody titers; IgM; heterologous crosses

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 Varicella, Passive Immunization

VZIG within 3-5 days of exposure to varicella or zoster

30-50 x more VZV antibody than IG
Criteria for VZIG: intimate exposure and high risk susceptible
(immunocompromised, steroids, HIV, malignancy, premature, newborn
of mother with varicella)
VZIG does not prevent nosocomial spread
VZIG not useful for therapy
If varicella develops after VZIG, usually not necessary for antivirals

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 Varicella, Antiviral Therapy

ACV interferes with viral DNA synthesis (chain terminator, inhibits polymerase)
Immunocompromised patients, primary pneumonia
Dose higher than that for HSV
Orally to children with chickenpox, shortens course by 1 day
poor GI absorption, within 24 hours, no effect on spread
Foscarnet if resistant
Valacyclovir, famciclovir: no data in children

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 Varicella Vaccine

"Live" attenuated
90% protection against disease
Prevents severe varicella in children, adults
Adolescents, adults require 2 doses, 4-8 weeks apart
Safe vaccine: adverse effects are fever (10%), mild rash (5%)
potential for spread to others (rare)
Long term concerns: zoster, waning immunity? (boosting)
In leukemics, less zoster if vaccinated
Contraindications: pregnancy, immunocompromised, allergy
Most American adults who think they are susceptible are immune
No problems if inadvertently immunized

References

Annunziato, P, Gershon, A. Herpes Simplex Virus Infections. Pediatrics in

Review 17: 415-423.

Arvin, A., Gershon, A. Live attenuated varicella vaccine. Annu. Rev. Microbiol.
1996; 59-100.

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