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Herpesviruses

The herpesvirus group of the family Herpesviridae comprises large, enveloped, double-stranded DNA viruses found in both animals and humans. They are ubiquitous and produce infections ranging from painful skin ulcers to chickenpox to encephalitis. The major members of the group to infect humans are the two herpes simplex viruses (HSV-1 and -2), cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), herpesvirus 6, and the recently discovered human herpesvirus types 7 and 8. Occasionally, the simian herpesvirus, herpes B virus, has caused human disease.

Herpesviruses

All herpesviruses are morphologically similar with an overall diameter of 180-200 nm. The nucleic acid core is ~ 30-45 nm in diameter, surrounded by an icosahedral capsid. The capsid is covered by a tegument and a lipoprotein envelope derived from the nuclear membrane of the infected host cell. The envelope contains at least nine glycoproteins that protrude beyond it as spikelike structures, while the tegument is a protein-filled area between the capsid and the envelope. Despite the morphologic similarity between these agents, substantial differences in the molecular composition of their genomes are reflected in their structural glycoproteins and polypeptides. Antigenic analysis is an important means for differentiation among herpesviruses despite some cross-reactions (eg, between HSV and VZV).

Susceptible tissue cultures vary significantly for the individual agents. HSV has the widest range; it replicates in numerous animal and human host cells. VZV is best grown in cells of human origin, although some laboratory-adapted strains can grow in primate cell lines. Human CMV replicates well only in human diploid fibroblast cell lines. EBV does not replicate in most commonly used cell culture systems but can be grown in continuous human or primate lymphoblastoid cell cultures. Human herpesvirus type 6 grows in lymphocyte cell cultures.

Herpesviruses

Characteristically, all of these agents produce an initial infection followed by a period of latent infection in which the genome of the virus is present in the cell, but infectious virus is not recovered. Reactivation of virus may then result in the first episode of clinically apparent disease or as recurrent disease. Complex host-virus interactions determine the expression of disease. With all of these agents, immunocompromised patients, especially those with altered cellular immunity, have more frequent and severe episodes, including clinically severe disease from reactivation of virus.

Herpes Simplex Virus

Varicella-Zoster Virus

Cytomegalovirus

Epstein-Barr Virus

Human Herpesvirus Type 6

OTHER HERPESVIRUSES

HERPESVIRUS TYPE 7

Isolation of human herpesvirus type 7 (HHV-7) was first reported in 1990. The virus was isolated from activated CD4+ T lymphocytes of a healthy individual. HHV-7 is distinct from all other known human herpesviruses but is most closely related to HHV-6. Seroepidemiologic studies indicate that this virus usually does not infect children until after infancy, and ~ 50% of infants are antibody positive by 2-4 years of age. As with HHV-6 this virus is frequently isolated from saliva, and close personal contact is the probable means of transmission. Also like HHV-6 this virus appears to be a cause of exanthem subitum. The diagnosis of acute infection can be made by the demonstration of seroconversion. No treatment has been identified.

HUMAN HERPESVIRUS TYPE 8 (Kaposi's sarcoma-associated herpes virus [KSHV])

KSHV was discovered in 1994 by identification of unique viral DNA sequences in an AIDS patient's Kaposi's sarcoma (KS) tissue. The method used was representational difference analysis. Specific HHV-8 DNA sequences are found in the great majority of KS tissues in the United States, including those from non-AIDS cases, and occasionally in other specimens including lymphomas. Recently the virus was isolated in culture and, when characterized, seemed most closely related to EBV. Serologic and virologic data suggest that this virus is at least a cofactor in the pathogenesis of KS.

BOX  1. Herpes Simplex Infection

Children

Adults

More Common

  • Mucocutaneous lesions, oral or genital

Less Common

  • HSV stomatitis
  • HSV encephalitis
  • HSV disseminated
  • HSV meningitis, encephalitis

BOX 2. Treatment of Herpes Simplex Infection

Children

Adults

First Choice

  • Acyclovir
  • Acyclovir

Second Choice

  • Valacyclovir
  • Famciclovir

BOX 3. Control of Herpes Simplex Infection

Prophylactic Measures

  • Avoidance of contact with HSV positive lesions, secretions
  • Daily acyclovir (OR valaciclovir, famiciclovir) suppresses recurrences of HSV infections
  • Vaccine ineffective for treatment; under study for prophylaxis

BOX 4. Syndromes Caused by Varicella Infection

Children

Adults

More Common

  • Varicella
  • Zoster (shingles)

Less Common

  • Zoster (shingles)
  • VZ encephalitis
  • Varicella
  • VZ encephalitis

BOX 33-5. Treatment of Varicella Infection

Children

Adults

First Choice

  • Acyclovir for children > 12 years who have varicella but no definite consensus
  • Varicella: acyclovir, 800 mg 5 times/day
  • Zoster: acyclovir, 800 mg 5 times/day; famciclovir, 500 mg/8 h; or valacyclovir, 1.0 g 3 times/day

Pediatric Considerations

  • An antiviral agent is not recommended for children <12 years

BOX 6. Control of Varicella Infection

Prophylactic Measures

An attenuated VZV vaccine is now recommended for healthy children >1 year of age

VZ-specific immune globulin can diminish illness if given within 72 h of exposure. This is reserved for immunocompromised susceptible patients or other special circumstances

Isolation Precautions

If at all possible, patients with varicella or disseminated zoster should not be admitted to hospital; if unavoidable, these patients should be in strict isolation.

BOX 7. Cytomegalovirus Disease Syndromes

Children

Adults

More Common

Perinatal infection, "Daycare" infection

Less Common

Congenital infection

CMV retinitis (AIDS)

  • pneumonia (transplant recipients)
  • CMV enteritis, neurologic disease (all immunocompromised patients)
  • CMV mononucleosis

BOX 8. Treament of Cytomegalovirus Disease

Children

Adults

First Choice

Ganciclovir

Ganciclovir, 5 mg/kg/d IV or valgauciclovir 900-1800 mg orally

Second Choice

  • Foscarnet, 90-120 mg/kg/d IV
  • Cidofovir, 5 mg/kg/q 2 weeks IV

Pediatric Considerations

No experience with treatments other than ganciclovir

BOX 9. Control of Cytomegalovirus Disease

Prophylactic Measures

  • Avoid organ transplantation or blood donation from CMV seropositive to CMV seronegative
  • Preemptive ganciclovir diminishes CMV disease in seropositive AIDS patients. Prophylactic ganciclovir or valacyclovir diminshes CMV disease in seropositive or mismatched transplant recipients. Preemptive ganciclovir disminshes CMV disease in seropositive or mismatched transplant recipients.
  • Vaccine trials are in progress

BOX 10. Epstein-Barr Virus Infection

Children

Adults

More Common

Infectious mononucleosis

Less Common

EBV lymphoproliferaliferative disease

EBV lymphoproliferative disease

BOX 11. Treatment of Epstein-Barr Virus Infection

First Choice

None

Second Choice

Corticosteroids if severe toxicity or airway obstruction

Acyclovir and/or decrease immunosuppression for post transplant lymphoproliferative disease

BOX 12. Exanthem Subitum Syndromes

More Common

Exanthem subitum

Less Common

Meningitis, encephalitis fever in transplant recipients

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