Professional Documents
Culture Documents
- The 2 closely related herpes simplex viruses (HSVs), HSV type 1 (HSV-1) and HSV type 2 (HSV-2), cause a variety of illnesses
depending on
o the anatomic site where the infection is initiated,
o the immune state of the host, and
o whether the symptoms reflect primary or recurrent infection.
- Infections tend to be mild and self-limiting, except in the immunocompromised patient and newborn infant, where the infection
may be severe and life threatening.
- Primary infection occurs in individuals who have not been infected previously with either HSV-1 or HSV-2.
- Nonprimary 1st infection occurs in individuals previously infected with 1 type of HSV (HSV-1) who have become infected for the 1st
time with the other HSV type (HSV-2).
o nonprimary 1st infections tend to be less severe than true primary infections.
- During primary and nonprimary initial infections HSV establishes latent infection in regional sensory ganglion neurons. Virus is
maintained in this latent state for the life of the host but periodically can reactivate and cause recurrent infection.
o Less severe
Etiology
- HSVs contain a double-stranded DNA genome of approximately 152 kb that encodes at least 84 proteins.
- The DNA is contained within an icosadeltahedral capsid, which is surrounded by an outer envelope that is composed of a lipid bilayer
containing at least 12 viral glycoproteins.
o These glycoproteins are the major targets for humoral immunity
o other nonstructural proteins are important targets for cellular immunity.
Epidemiology
- HSV infections are ubiquitous and there are no seasonal variations in risk for infection.
- The only natural host is humans.
- Mode of transmission is direct contact between mucocutaneous surfaces.
- All infected individuals harbor latent infection with recurrent infections, which may be symptomatic or go unrecognized, and are
periodically contagious
- HSV seroprevalence rates are highest in developing countries and among lower socioeconomic groups.
- Incident HSV-1 infections are more common during childhood and adolescence but are also found throughout later life.
- Neonatal herpes is an uncommon but potentially fatal infection of the fetus or more likely the newborn.
- The risk for transmission is greatest during a primary or nonprimary 1st infection (30–50%) and much lower when the exposure is
during a recurrent infection (<2%).
- Infants born to mothers dually infected with HIV and HSV-2 are also at increased risk for acquiring HIV compared with infants born
to HIV-positive mothers who are not HSV-2 infected.
Perinatal Infection
- HSV infection may be acquired in utero, during the birth process, or during the neonatal period.
- Intrauterine and postpartum infections are well described but occur infrequently.
- Postpartum transmission may be from the mother or another adult with a nongenital (typically HSV-1) infection such as herpes
labialis.
- Most cases of neonatal herpes result from maternal infection and transmission, usually during passage through a contaminated
infected birth canal of a mother with asymptomatic genital herpes.
Diagnosis
- Isolation of virus or detection of viral antigen or more often viral DNA by polymerase chain reaction (PCR).
- Histologic findings or imaging studies may support the diagnosis but should not substitute for virus-specific tests.
- HSV immunoglobulin M (IgM) tests are notoriously unreliable.
- Virus culture -- gold standard for diagnosing HSV infections.
o The highest yield comes from rupturing a suspected herpetic vesicle and vigorously rubbing the base of the lesion to
collect fluid and cells.
- Evaluation of the neonate with suspected HSV infection should include cultures of suspicious lesions as well as eye and mouth
swabs, and PCR of cerebrospinal fluid.
Laboratory Findings
- Mucocutaneous infections
o moderate polymorphonuclear leukocytosis.
- HSV meningoencephalitis
o increase in lymphocytes and protein,
o the glucose may be normal or reduced,
o and red blood cells may be present.
o The electroencephalogram and MRI of the brain may show temporal lobe abnormalities in HSV encephalitis beyond the
neonatal period.
o Encephalitis in the neonatal period tends to be more global, that is, not limited to the temporal lobe.
- Disseminated infection may cause elevated liver enzymes, thrombocytopenia, and abnormal coagulation.
Treatment
- Acyclovir
o Has the poorest bioavailability and hence requires more frequent dosing.
o Only acyclovir has an intravenous formulation.
- Valacyclovir
o a prodrug of acyclovir. Has very good oral bioavailability and are dosed once or twice daily.
- Famciclovir
o a prodrug of penciclovir. Has very good oral bioavailability and are dosed once or twice daily.
All infants with proven or suspected neonatal HSV infection should be begun promptly on high-dose intravenous acyclovir (60 mg/kg/day
divided every 8 hr IV). Treatment may be discontinued in those infants shown by laboratory testing to not be infected. Infants with HSV disease
limited to skin, eyes, and mouth should be treated for 14 days, while those with disseminated or central nervous system disease should receive
21 days of therapy. Patients receiving high-dose therapy should be monitored for neutropenia.
Drug Index