Herpes Simplex Virus

Herpes simplex virus (HSV-1 and HSV-2) infections are found worldwide, even in remote populations. Nearly all adults have antibodies to HSV-1 by the fifth decade of life, and the seroprevalence of HSV-2 has increased at an alarming rate over the last decade.

Herpes simplex virus (HSV) infections occur throughout the year. The incubation period ranges from 1 to 26 days (median 6-8 days). Contact with active ulcerated lesions or asymptomatically excreting persons can result in transmission. The efficiency of transmission is greater during symptomatic periods of viral excretion. HSV has been isolated from nearly all visceral and mucocutaneous sites and is associated with a variety of clinical syndromes including mucocutaneous infections, central nervous system and visceral infections. HSV infections vary widely in severity, from common cold sores to life-threatening infections in infants and immunocompromised hosts. Both viral subtypes, HSV 1 & 2, can cause genital and oral-facial infections.

HSV lesions persist 15 to 20 days in primary infections and about 10 days in recurrent infections. HSV lesions progress through several stages from maculopapules, vesicles, pustules, ulcers, and crusted surfaces. The amount of virus present in lesions is a function of the duration of the infection. The earliest lesions, maculopapules through pustules, contain the highest viral loads. The amount of recoverable virus declines precipitously once the epithelial surface ulcerates.

Genital herpes simplex virus (HSV) infection is among the most common sexually transmitted diseases and is frequently under-recognized due to subclinical infections. The seroprevalence of HSV-2 has increased steadily over the last decade, and genital infections due to HSV-1 are becoming more frequent. Differentiation of HSV-1 from HSV-2 is important prognostically, since genital HSV-2 infection is twice as likely to reactivate and recurs 8-10 times more frequently than genital HSV-1 infection. Recurrence of genital HSV-1 is less common after the first year of infection. Acquisition of new HSV-1 infection in an individual with HSV-2 antibodies is unusual, however women with genital HSV-1 infection are still at risk for HSV-2 acquisition. Extragenital complications of primary HSV infection include meningitis, urinary retention syndromes, and proctitis. The Centers for Disease Control (CDC) recently updated Sexually Transmitted Disease Guidelines (MMWR 2010;59, RR#12), including recommendations for herpes infection diagnostic testing.

In patients with new or recurrent genital ulcers, PCR testing is 1.5 to 4 times more sensitive than viral culture for diagnosis. HSV PCR differentiates between types 1 and 2, and is useful for lesions at any stage of healing. In the absence of lesions, or when PCR is negative despite high clinical suspicion, HSV IgG type-specific antibody testing is recommended. IgG antibody to HSV is detectable 2-12 weeks after infection and persists indefinitely. Importantly, seroconversion can take longer than 12 weeks in patients who are treated with anti-viral chemotherapy. False negative serologic results are most common in early stages of infection. Only tests based on detection of antibody to HSV glycoprotein G-2 are type-specific, due to cross-reactivity between viruses. Compared to Western blot, the sensitivity of type-specific HSV antibodies is 96-100%, with a specificity of 97-98%. Type-specific antibody testing of asymptomatic partners of persons with genital herpes is recommended to determine risk for acquiring new HSV infection. HSV IgM testing is not particularly useful in suspected primary genital infection due to low sensitivity (50%), ambiguity for primary vs. recurrent infection, and lack of type specificity.

The earliest lesions need to be sampled to decrease the incidence of false negatives. Fluid should be aspirated from vesicles with a tuberculin syringe and transferred to viral transport media.If lesions are crusted, remove the crust with a scalpel blade and swab the basal membrane to obtain infected epithelial cells. Specimens for PCR testing should be submitted on a swab in M4-RT viral transport media. Dacron, rayon, or cotton swabs should be used and not calcium alginate swabs. All specimens should be refrigerated after collection.

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