Herpes latency, meningitis, radiculomyelopathy and disseminated infection.

Abstract

Introduction Genital herpes simplex virus (HSV) infection affects a large proportion of the population. A recent seroepidemiologic survey of individuals in the United States of America found that 16.4% of the population were seropositive for herpes simplex virus (HSV) type 2 (HSV-2).1 Most HSV-2 transmission originates with an asymptomatic partner.2 Because the majority of affected individuals are asymptomatic and experience periodic virus reactivations, a large reservoir of infectious virus persists. A fundamental characteristic of all of the herpes viruses is their ability to achieve a state of latency from which they can reactivate. Viral reactivations become clinically evident in a-minority of patients. Severity of disease manifestations are dependent upon a variety of virus and host factors. The site of inoculation will usually determine initial disease location(s), if the disease is symptomatic at the time of its primary acquisition. Sites of recurrent disease, on the other hand, are determined by the routing of neural pathways emanating from the site(s) of neuronal latency. For example, HSV type 1 (HSV 1) or HSV-2 may be inoculated initially at any site with subsequent local recurrences also possible in or near that 'location. Because the majority of human host interactions involve either genital or facial skin or mucous membranes, the majority of HSV disease is manifest on the face and/or genital region. The vast majority of genital herpes is caused by reactivation from latency of HSV-2. Primary genital disease, however, while more commonly caused by,-transmission of-HSV-2, may oftenbe caused by HSV-1, transmission occurring via genital-genital or oral-genital routes, respectively. The converse is true for orallabial disease which is predominantly HSV-1 and results from face-to-face contact. Recurrent disease locations are determined by the nature of the individual's neural recurrence pathway, which, in turn, must also reflect the specific transmission event which identified the initial site of viral inoculation into the new host. Thus, disease manifestations may be highly variable. For example, oral-labial herpes in one person may be transmitted to any target in the new host which directly contacts the mouth. The most common site is the mouth or lips of the viral recipient. However, inoculation to the ophthalmic division of the trigeminal nerve may instead lead to ophthalmic HSV and recurrent keratitis or deeper stromal disease. Inoculation to the finger or hand may be a more likely endpoint for an intensivist or a dental 'hygienist delivering mouth care. Infection of the cribriform plate and the overlying olfactory bulb, may lead to a less common, potentially lethal form of localized HSV infection, herpes encephalitis. Encephalitis passed via this route in adults is caused by HSV-1. HSV-2 encephalitis generally occurs in neonates and results from intrapartum transmission, and less commonly occurs in immunocompromised adults with disseminated infection. Just as the nature of the disease caused by mucocutaneous HSV depends upon the site of infection, HSV may cause a variety of neurological syndromes, ranging from aseptic meningitis to radiculomyelopathy, all ofwhich are defined by the site(s) of involvement. This review will focus on these latter syndromes, specifically addressing what is known of their pathogenesis, manifestations and treatmnent.