Herpes simplex: evolving concepts

A large body of molecular biologic research has begun to clarify some basic aspects of viral latency and reactivation. The clinical definition of herpes simplex virus infection is expanding, with the recognition that the disease is largely asymptomatic and that most transmission occurs during periods of asymptomatic viral shedding. With this awareness, serologic diagnosis has become increasingly important. New treatment modalities are now available, and other promising treatments are in development.A large body of molecular biologic research has begun to clarify some basic aspects of viral latency and reactivation. The clinical definition of herpes simplex virus infection is expanding, with the recognition that the disease is largely asymptomatic and that most transmission occurs during periods of asymptomatic viral shedding. With this awareness, serologic diagnosis has become increasingly important. New treatment modalities are now available, and other promising treatments are in development.

Nosocomial herpes simplex virus infection associated with oral endotracheal intubation.

BACKGROUND: To determine by culture the frequency of herpes simplex virus reactivation complicating oral endotracheal intubation. Additionally, clinical appearance and recognition of patient infection by attendant health care workers were studied. Last, evidence of any occupational acquisition of herpes simplex virus infection was sought. METHODS: In a prospective, non-randomized study, three serial viral cultures were taken of oro-facial or mucosal sites on the day of oral endotracheal intubation and in the subsequent 3rd and 5th or 7th days from 51 consecutive adults undergoing oral endotracheal intubation in a suburban community hospital. Clinical variables including appearances of lesions and therapeutic interventions were noted during serial assessments by study authors. Employee health records were reviewed for evidence of health care worker occupational herpes simplex virus infection associated with these cases. RESULTS: Of 51 patients, 4 were culture positive on the day of oral endotracheal intubation. Of the remaining 47 patients, serial cultures during the first week post intubation revealed herpes simplex virus in 25 (53.2%) patients. Of cohort variables studied, a history of prior oral herpes simplex virus was significantly associated with a subsequent positive viral culture for herpes simplex virus (relative risk, 2.29; 95% confidence interval, 1.48 to 3.56). Typical or atypical lesions were visible in only 52% of the herpes simplex virus culture-positive cases. No occupational transmission of herpes simplex virus was detected. Tape-securing practices appeared to contribute to the morbidity of herpes simplex virus eruptions. CONCLUSIONS: Nosocomial reactivation of herpes simplex virus infection complicated oral endotracheal intubation in our patient population in approximately one half of the patients who were intubated for more than 48 hours during the first week after the procedure. Clinically, the infection was recognizable in only one half of the virus culture-positive cases. Increased awareness of this infection is needed by health care workers, patients, and families. More information is needed on optimal therapy and prevention.

[Molecular biology of pathogenesis by herpesvirus]. / Biología molecular de la patogénesis por herpesvirus.

A distinguishing feature of Herpes simplex virus (HSV) infections is the ability of these viruses to persist for long periods in their host in nonreplicative or latent state. The study of pathogenesis of herpesvirus infections can be divided in: acute viral replication, establishment of latency, maintenance of latency and reactivation. In this paper we analyzed the viral genetic information which was identified as essential or very important for such events.

The effect of alpha blockade on iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Previous studies demonstrated that non-specific beta blockade promoted ocular shedding of latent HSV-1 in the mouse and rabbit iontophoresis models. The present study examined the effect of topical alpha blockers, thymoxamine and corynanthine, on reactivation and induced ocular shedding of latent HSV-1 W in different host animals. Latent trigeminal ganglionic infection was established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 W strain, and later confirmed by co-cultivation. Treatment with coded eye drops (thymoxamine, corynanthine or BSS was begun one day prior to iontophoresis induction and continued BID OU for 5 days. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. In Balb/c mice, topical administration of thymoxamine 0.5% or corynanthine 5% significantly reduced the number of virus-positive eyes, virus-positive mice, and total virus-positive swabs per experiment, whereas the inhibitory effect was minimal in NZ rabbits. We conclude that alpha blockade may alter the reactivation signal that is mediated via the adrenergic system, and that different host factors (as expressed in different species) may play an important role in this process.

Vanadate promotes reactivation and iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Vanadate is a potent inhibitor of calcium stimulated ATPase, Na, K-ATPase, and may have adrenergic activity. Using the iontophoresis method, we compared vanadate to a BSS control and the standard iontophoresis model (6-hydroxydopamine/epinephrine) by measuring induced ocular shedding of latent HSV-1 in different host animals. Latent trigeminal ganglionic infections were established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 [W] strain, and later confirmed by cocultivation. Latently-infected animals (greater than 1 month post-infection) were divided into three treatment groups. Each group was iontophoresed with BSS, vanadate 1% or 6-HD 1%, and then treated topically for 10 days with BSS, vanadate or epinephrine respectively. Reactivation and recovery of latent HSV-1 was detected by daily ocular swabbing, plating, and observing progressive viral growth in Vero cells. The vanadate group had more virus-positive eyes than the BSS control group in mice, (8/32 vs. 1/32 P less than .01), and also in rabbits (14/20 vs 6/22 P less than .01). Virus-positive animals and total positive swabs were also higher for vanadate than BSS in both mice and rabbits. Furthermore, while vanadate was associated with fewer virus-positive eyes than 6-HD & EPI (8/32 vs. 17/32 P less than .02) in mice, there were no significant differences in rabbits. We conclude that vanadate promotes ocular shedding of latent HSV-1, and may act through an adrenergic mechanism.