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Eight types of herpesviruses infect humans (see Table 1: Herpesviruses: Herpesviruses That Infect Humans ). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate or be shed. Herpesviruses do not survive long outside a host; thus transmission usually requires intimate contact, although varicella-zoster virus (VZV) may spread by aerosol. Because the virus remains latent, transmission sometimes occurs from asymptomatic infected people. Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma–associated herpesvirus (KSHV), are tightly linked with malignancy.
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Table 1
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Herpesviruses That Infect
Humans
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Common Name
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Other Name
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Typical Manifestations
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Herpes simplex virus type 1
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Human herpesvirus 1
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Gingivostomatitis; keratoconjunctivitis; cutaneous herpes; genital herpes; encephalitis; herpes labialis; esophagitis*; pneumonia*; hepatitis*†
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Herpes simplex virus type 2
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Human herpesvirus 2
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Genital herpes; cutaneous herpes; gingivostomatitis; neonatal herpes; aseptic meningitis; disseminated infection*; hepatitis*†
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Varicella-zoster virus
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Human herpesvirus 3
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Chickenpox; herpes zoster; disseminated herpes zoster*
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Epstein-Barr virus
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Human herpesvirus 4
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Infectious mononucleosis; hepatitis; encephalitis; nasopharyngeal carcinoma; lymphoproliferative syndromes*; oral hairy leukoplakia*
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Cytomegalovirus
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Human herpesvirus 5
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Infectious mononucleosis; hepatitis; congenital cytomegalic inclusion disease; hepatitis*; retinitis*; pneumonia*; colitis*
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Human herpesvirus 6
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Roseola infantum; otitis media with fever; encephalitis
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Human herpesvirus 7
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Roseola infantum
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Human herpesvirus 8
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Kaposi's sarcoma–associated herpesvirus
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Not a known cause of acute illness but has a causative role in Kaposi's sarcoma (see Cancers of the Skin: Kaposi's Sarcoma)* and AIDS-related non-Hodgkin lymphomas that grow primarily in the pleural, pericardial, or abdominal cavities as lymphomatous effusions
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*In immunocompromised hosts.
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†Uncommonly causes fulminant hepatitis in the absence of cutaneous lesions in immunocompetent hosts.
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Drug Treatment
Drugs that have activity against herpesviruses include acyclovir , cidofovir , famciclovir , fomivirsen , foscarnet , ganciclovir , idoxuridine, penciclovir , trifluridine , valacyclovir , valganciclovir , and vidarabine.
Acyclovir:
Acyclovir is a purine nucleoside analog with activity against herpesviruses (in order of potency): herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), VZV, and EBV. It has minimal activity against cytomegalovirus (CMV). It terminates viral DNA synthesis in a process that requires viral thymidine kinase; immunocompromised patients who require prolonged treatment may develop resistance via a mutation in viral thymidine kinase. Adverse effects are infrequent with oral administration but may include nausea, vomiting, diarrhea, headache, and rashes. IV acyclovir is indicated when a higher serum drug level is required, as in herpes encephalitis. Adverse effects include renal failure, phlebitis, rash, and neurotoxicity (lethargy, confusion, seizures, coma). Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported in immunocompromised patients receiving acyclovir .
Cidofovir:
Cidofovir is a nucleotide analog that has a long duration of action and in vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, human papillomavirus (HPV), and human polyomavirus. Topical cidofovir is used for mucocutaneous HSV unresponsive to oral or IV acyclovir .
Famciclovir:
Famciclovir is a prodrug of the active antiviral penciclovir and has an antiviral spectrum similar to acyclovir . It inhibits viral DNA polymerase in a thymidine kinase–dependent process. Famciclovir is as effective as acyclovir for genital herpes and herpes zoster and is more bioavailable. Strains resistant to acyclovir are also resistant to famciclovir . Adverse effects of famciclovir are similar to those of oral acyclovir .
Fomivirsen:
Fomivirsen is a phosphorothioate oligonucleotide. Oligonucleotides bind to viral RNA, blocking its expression (antisense mechanism). Fomivirsen has potent activity against CMV; it inhibits CMV protein synthesis. It is given by intravitreal injection for patients with HIV infection and CMV retinitis that is resistant to other therapies. Adverse effects include increased intraocular pressure and corticosteroid-responsive uveitis.
Foscarnet:
Foscarnet is an organic analog of inorganic pyrophosphate. It selectively inhibits virus-specific DNA polymerase and reverse transcriptase. Its mechanism does not involve viral thymidine kinase; it is active against EBV, KSHV, human herpesvirus 6, acyclovir -resistant (and acyclovir -susceptible) HSV and VZV, and ganciclovir -resistant (and ganciclovir -susceptible) CMV. Foscarnet 's efficacy is similar to that of ganciclovir for treating and delaying progression of CMV retinitis, and it has some anti-HIV activity.
Ganciclovir and valganciclovir:
Ganciclovir is a nucleoside analog of 2′-deoxyguanosine that differs only slightly from acyclovir chemically. It has in vitro activity against all herpesviruses, including CMV, but HSV strains resistant to acyclovir are cross-resistant to ganciclovir . Ganciclovir is primarily used in patients with both HIV and CMV retinitis. It inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerase in a viral thymidine kinase–dependent process. Its primary adverse effect is bone marrow suppression, particularly neutropenia. Severe neutropenia (< 500 neutrophils/μL) requires bone marrow stimulation with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor or drug discontinuation. Less common adverse effects include rash, fever, azotemia, liver function abnormalities, nausea, and vomiting. Oral ganciclovir is only 6 to 9% bioavailable. The formulation, which requires 12 capsules/day for a standard dose (1 g tid), limits its usefulness. A more bioavailable formulation is valganciclovir , which is taken as two 450-mg tablets once/day or bid.
Idoxuridine:
Idoxuridine (IDU) irreversibly replaces thymidine in newly synthesized DNA, rendering DNA essentially nonfunctional in viral as well as host cells. Because of its high systemic toxicity, IDU has been limited to topical therapy of herpes simplex keratoconjunctivitis. IDU may cause irritation, pain, photophobia, pruritus, and inflammation or edema of the eyelids; allergic reactions occur rarely.
Penciclovir:
Penciclovir is a phosphorylated guanosine analog that competitively inhibits viral DNA polymerase. Penciclovir cream is used for recurrent herpes labialis in adults.
Trifluridine:
Trifluridine (trifluorothymidine), a thymidine analog, impairs DNA synthesis and is effective in treating primary keratoconjunctivitis and recurrent keratitis or ulceration caused by HSV-1 and HSV-2. Trifluridine is as effective as vidarabine and may be effective in patients who have not responded to IDU or vidarabine. The marrow-suppressive effect of trifluridine precludes systemic use. Adverse effects include ocular stinging, palpebral edema, and, less frequently, punctate keratitis and allergic reactions.
Valacyclovir:
Valacyclovir is converted to acyclovir by 1st-pass metabolism, which makes it 3 to 5 times more bioavailable than acyclovir . Its antiviral spectrum and adverse effects are similar to acyclovir . Because patients with advanced HIV and transplant recipients who have received high-dose valacyclovir have had TTP/HUS, it should be used with caution in these patients.
Vidarabine:
Vidarabine (adenine arabinoside, ara-A) impairs viral DNA synthesis and is effective against HSV infections. Vidarabine appears less susceptible to the development of drug resistance than IDU, and IDU-resistant infections often respond to vidarabine. Ophthalmic preparations of vidarabine are effective for acute keratoconjunctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2. Possible adverse effects include superficial punctate keratitis with tearing, irritation, pain, and photophobia.
Last full review/revision November 2005
Content last modified November 2005
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