HERPES SIMPLEX-1 VIRUS

Structure 	Transmission	Pathogenesis	Clinical findings	Laboratory diagnosis	Treatment	
Family: herpevirus

Genome: linear double-strand DNA.

Size: 100m

Icosahedral nucleoapsid

Lipoprotein envelope

Single serotype

HSV-1 and HSV-2 are structurally and morphologically indistinguishable.	Transmitted primarily in saliva via close personal contact, e.g. kissing.

20% due to sexual contact. 

Infections occur mainly on face.

Humans are natural hosts.	Replicates in the skin or mucous membrane at initial site of infection.

Migrates up neuron and becomes latent in trigeminal ganglia.

Reactivated by sunlight, hormonal changes, trauma, stress & fever.

Reactivation does not stimulate a rise in titre of herpes antibody.

Skin lesion is a vesicle containing serous fluid filled with virus particles.

Multinucleated giant cells found at base of lesions.

Immunity is type-specific but some cross-protection exists.

Immunity is incomplete and both reinfection and reactivation occur in presence of IgG.

Cell-mediate immunity is important –its suppression results in reactivation, spread and severe disease.	Diseases fall into 2 categories:
Primary: when the virus is first encountered.
Reactivation: recurrent infections, due to reactivation of latent virus.

Primary infections are usually symptomless.

Symptoms of primary infection:
Gingivostomatitis:
- occurs primarily in children.
- fever, irritability, and vesicular lesions in mouth.
- vesicles ulcerate and become coated with greyish slough.
- lesions heal in 2-3 weeks.

Herpetic whitlow:
- due to implantation of virus into fingers.
- pustular lesion of the skin of finger or hand.
- can occur in medical personnel as a result of contact with patient’s lesions.

Keratoconjunctivitis:
- eyelids are swollen with vesicles and ulcers on them.
- corneal ulcers and lesions of the conjunctival epithelium.

Kaposi’s varicelliform eruption:
- superinfection of eczematous skin with extensive vesiculation, fever.
- seen mainly in young children
- serious disease with significant fatality rate.

Acute necrotizing encephalitis:
- sudden onset of fever, mental confusion and headache.
- site of infection is temporal lobe.
- high morbidity with neurological deficits.

Genital herpes: vesicular eruption of genital areas.

Generalized infection in adults:
- disseminated vesicular skin lesions.
- herpes hepatitis, esophagitis and pneumonia.
- common in immunocompromised.

Symptoms of reactivation:
Cold sores (herpes liabialis):
- vesicles at mucocutaneous junctions of nose and mouth, later with painful ulcers.
- these progress to pustules with crust formation.
- herpetic vesicles can occur rarely at other sites on skin.

Dendritic ulcer of cornea:
- lesions take form of a branching or dendritic ulcer.
- frequent recurrence leads to scarring, disease may progress to severe, destructive uveitis.	Type 1 and 2 share group-specific antigens, but can be differentiated by type-specific antigens and by DNA restriction enzyme analysis.

Isolation:
- swab or fluid from vesicles, skin, saliva, conjunctiva.
- corneal scrapings.
- brain biospy.

Diagnosis:
- isolate virus, grow in cell culture.
- produce CPE with ballooning and rounding of cells. 
- identified by fluorescence-antibody staining of infected cells.
- detect virus-specific glycoproteins by ELISAs.

Tzanck smear:
- rapid diagnosis from skin lesions.
- cells from base of vesicles stained with Giemsa’s stain.
- presence of multinucleated giant cells suggest infection.
Serology:
- complement fixation test useful for diagnosing primary infections.
- of little use in recurrent infections as many adults already have antibodies.

Direct demonstration of virus or viral antigen in vesicles by EM or immunofluorescence.

PCR is now used to detect herpes-specific DNA in CSF in cases of suspected encephalitis.	Acyclovir:
- treatment for encephalitis, systemic disease, primary and recurrent genital herpes.
- shortens duration of lesions.
- reduces extent of viral shedding.
- no effect on latent state, but long-term use can suppress clinical occurrences.
- administered intravenously, orally or topically.

Also used:
- valaciclovir
- famciclovir

Prevention:
- avoid contact with vesicular lesion or ulcers.
- cesarean section is recommended for women who are at term with genital lesions.