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S Spruance

Publications and source records attributed to S Spruance.

9 recordsLinked to original sources

Introduction: Is viral shedding a surrogate marker for transmission of genital herpes?

Genital herpes, caused by either herpes simplex virus type 1 or 2 (HSV-1 and HSV-2), is a significant public health problem worldwide. It increases the risk of infection with HIV, upregulates HIV after infection and can be associated with serious morbidity and mortality. It is now known that clinical and subclinical viral reactivation with resultant shedding from anogenital mucosa occurs frequently, resulting in transmission during sexual contact. Sexual transmission of HSV infection is common, even between monogamous individuals. Antiviral therapy reduces the frequency and degree of viral shedding and lowers the transmission rate in discordant monogamous couples, although transmission can still occur in people prescribed antiviral therapy. These encouraging data raise important questions for the management of genital HSV infection, particularly with regard to the prevention of transmission. Although the quantity of virus present is clearly important in transmission of some viruses, it is not clear whether this is the case for HSV transmission. Ideally, a surrogate marker needs to be able to identify individuals with detectable amounts of virus, and differentiate them from individuals with detectable amounts of virus that are transmissible. The aim of this supplement is to explore the issues surrounding the validation of surrogate markers of transmission of HSV, using examples from other human viral diseases, and to review the available evidence. In the future, exploration of these issues may shed light on management and prevention strategies. In particular, the results may clarify what evidence is required to warrant prescribing a drug for reducing HSV transmission, and for which patient populations this strategy is appropriate.

Biomarkers↗

Lessons from HIV and hepatitis viruses.

Surrogate markers are an important component in the process of investigating management and prevention strategies, and for increasing understanding of viral diseases. The importance of surrogate markers and applied statistical models is particularly true for HIV. For HIV infection, the development of such methods provides new approaches for evaluation of HIV therapies and vaccines, and for the study of HIV transmission and its pathogenesis. The complex natural history of hepatitis B infection demonstrates that viral load is not the only predictor of transmission of this virus; for hepatitis C infection, viral load per se is not a prognostic factor for disease progression, but cumulative viral load may affect the outcome, and therapy is aimed at eliminating active viral replication.

Biomarkers↗

HSV shedding.

Viral shedding of HSV occurs frequently in infected individuals. HSV is shed asymptomatically from multiple anatomical sites and shedding, like exposure, is a significant risk for transmission. However, the relationship between shedding frequency, viral titer and transmission is unknown. HSV-2 shedding is affected by the site and time since acquisition of infection. The advent of sensitive PCR techniques has shown that the magnitude and frequency of viral shedding is higher than shown previously with viral culture techniques. It has also clearly demonstrated that suppressive (daily) antiviral therapy reduces clinical and subclinical reactivation rates, and has been successfully used in the prevention of recurrent oral and genital HSV infections. A recent study has demonstrated that daily antiviral therapy with valaciclovir can significantly reduce transmission of HSV-2 between discordant heterosexual couples in monogamous relationships.

Acyclovir↗

HSV-2 transmission.

A number of important risk factors for the acquisition of HSV-2 have been established including female gender, black or Hispanic ethnic origin, HIV infection, age, and increased number of sexual partners. Transmission is influenced by a number of biological factors such as sexual behavior, use of condoms, duration of relationships, and knowledge of a partner's serologic status. Vertical transmission (transmission of HSV from mother to neonate) is potentially life-threatening; neonatal HSV infection is associated with significant morbidity and mortality. The valaciclovir transmission study provides evidence that an antiviral agent can interrupt the transmission of a viral sexually transmitted disease between serologically discordant sexual partners. This review explores the importance of the cofactors that affect transmission, and makes recommendations on considerations for the prophylactic use of antiviral agents for the prevention of transmission in other patient populations.

Acyclovir↗

Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts.

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.

Administration, Topical↗

Acyclovir in human breast milk.

Acyclovir concentration was measured by radioimmunoassay in the serum and milk of a lactating woman who was treated with oral acyclovir for herpes zoster. Daily serum and milk samples showing milk concentrations that averaged being 3.24-fold higher than serum levels suggest a low infant dose. The elimination phase demonstrated a half-life of 2.8 hours in milk.

Acyclovir↗

Vidarabine therapy for mucocutaneous herpes simplex virus infections in the immunocompromised host.

Eighty-five immunocompromised patients were entered into a randomized, controlled, crossover study of mucocutaneous herpes simplex virus (HSV) infections. Thirty-nine patients (group A) received vidarabine for seven days followed by placebo for an additional seven days. Forty-six patients (group B) received the reverse regimens. Therapy did not significantly accelerate healing for the total population as assessed by loss of virus from lesions, cessation of lesion formation, and time to crusting. Group A patients demonstrated accelerated loss of pain from lesions (P = 0.0099) and defervescence (P = 0.03). Patients in group A who had HSV type 1 (HSV-1) infections or who were over 40 years of age did clear virus from lesions more rapidly (P = 0.04 and P = 0.03, respectively). No toxicity or significant adverse effects could be attributed to vidarabine administration. Benefit from vidarabine therapy is limited to immunocompromised patients over 40 years of age with HSV-1 infections.

Adolescent↗

Recurrent herpes labialis in skiers. Clinical observations and effect of sunscreen.

Recurrent orofacial herpes infection may be triggered by high altitude skiing, presumably because of solar ultraviolet radiation exposure. Six (12%) of a group of 51 subjects with a history of skiing-triggered herpes observed during 1 week of high altitude skiing experienced reactivations of orofacial herpes a median of 3 1/2 days after exposure. Within this group, application of a sunscreen with a sun protection factor (SPF) of 15 failed to influence the reactivation rate as compared with a placebo. Reactivation of herpes triggered by skiing is common. As application of a sunscreen with an SPF of 15 did not appear to influence the reactivation rate, alternate approaches to the control of recurrent orofacial herpes are needed.

Adult↗