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Biomedical subjects

L R Stanberry

Publications and source records attributed to L R Stanberry.

At least 19 recordsLinked to original sources
PubMed2006

The psychosocial impact of serological diagnosis of asymptomatic herpes simplex virus type 2 infection.

OBJECTIVES: To evaluate the impact of a positive herpes simplex virus type 2 (HSV-2) serological test on psychosocial functioning among people with no known history of genital herpes. METHODS: Individuals (age 14-30 years) without a history of genital herpes were recruited from an urban university setting and sexually transmitted diseases (STD), primary care, and adolescent clinics. Participants completed a questionnaire addressing psychological functioning, psychosocial adjustment, and perceived quality of sex and were offered free HSV-2 antibody testing. 33 HSV-2 positive people and 60 HSV-2 negative people demographically matched from the same source of recruitment were re-evaluated at a 3 month follow up visit. HSV-2 positive participants also completed a genital herpes quality of life (GHQOL) measure. RESULTS: Of the 33 who were HSV-2 seropositive, four did not recall their diagnosis. In comparing those who were HSV-2 positive with those who were negative, repeated measures analysis of variance indicated there were no significant differences over time on any of the measures. None the less, many HSV-2 positive individuals indicated that the diagnosis had a notable impact on their quality of life. Also, among the HSV-2 positive people, lower GHQOL at the 3 month follow up was predicted by higher interpersonal sensitivity (r = -0.44, p<0.05), lower social support (r = 0.40, p<0.05), and quality of sex (r = 0.62, p<0.01) at baseline. CONCLUSIONS: A diagnosis of asymptomatic HSV-2 infection does not appear to cause significant lasting psychological difficulties. Those for whom the diagnosis had the greatest impact were interpersonally vulnerable before the diagnosis. These results suggest that assessment of interpersonal distress may be important to include as part of pretest and post-test counselling.

Adaptation, Psychological↗
PubMed2005

Gender-specific predictors of genital herpes vaccine acceptance in a college population.

Vaccines represent one promising method for reducing the sexually transmitted disease (STD) epidemic. This study evaluated whether influences on the decision to accept a genital herpes vaccine differed by gender. In all, 518 college students completed a questionnaire on sexual history, health beliefs, and acceptance of a potential genital herpes vaccine. Each predictor variable plus a gender interaction term were analysed in separate logistic regression models. Follow-up analyses were performed by gender for outcomes that displayed significant interactions. Results indicated that a prior history of an STD and increased perception of risk for acquiring genital herpes were significant predictors of vaccine acceptance for men, while younger age and concerns about vaccine safety were significant predictors for women. Endorsement of a vaccine strategy targeting sexually experienced people was an influential factor for both genders, but was a much stronger one for women. Results suggest that gender-specific strategies may be crucial to genital herpes vaccine acceptance.

Adolescent↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

Patient satisfaction with care for genital herpes: insights from a global survey.

OBJECTIVE: To describe patient experiences and views regarding genital herpes management. METHODS: Between February 2002 and January 2003, subjects with genital herpes were recruited via the International Herpes Alliance website and through banners on additional sites. Surveys were available in English, French, Spanish, Italian, and German and assessed views on access to care, diagnosis, related emotional experiences, educational resources, counselling, pharmacotherapy, and satisfaction with care. RESULTS: 2075 patient responses from 78 countries were analysed. 49% reported their diagnosis was by culture (or other direct detection) and 9% by antibody test, while 34% reported they had been diagnosed by examination alone. 65% used a prescription antiviral therapy, 18% a topical antiviral therapy, and 17% an alternative therapy. Of 901 subjects who reported on frequency of antiviral use, only 30% reported a frequency consistent with a suppressive regimen while 59% of respondents said they would be likely to take daily therapy if it reduced the frequency of outbreaks. Patient satisfaction with management of physical symptoms was independently associated with duration of initial visit >or=15 minutes (adjusted odds ratio (OR) = 4.52), receiving a prescription (adj OR = 2.34) and receipt of a brochure/fact sheet (adj OR = 2.14). Satisfaction with attention to emotional issues also correlated with the first two of these factors. CONCLUSIONS: Genital herpes management may be improved by including the use of confirmatory laboratory testing, employing a full range of antiviral therapy options, providing educational materials, and committing more time to counselling at the initial visit.

Adult↗
PubMed2003

Poly(sodium 4-styrene sulfonate): evaluation of a topical microbicide gel against herpes simplex virus type 2 and Chlamydia trachomatis infections in mice.

OBJECTIVE: To investigate the in vivo activity of poly(sodium 4-styrene sulfonate) (T-PSS) gel formulations as topical microbicides. METHODS: The ability of the gel formulations to reduce the incidence of infection when applied prior to pathogen challenge was examined in mouse models of vaginal herpes simplex type 2 (HSV-2) and Chlamydia trachomatis infection, and rectal HSV-2 infection. RESULTS: In the vaginal HSV-2 challenge studies, 10% T-PSS gel provided significant protection against infection, even when administered 60 min prior to virus challenge (P < 0.0001). Both 5% and 10% T-PSS gel formulations significantly reduced the incidence of upper genital tract C. trachomatis infection in animals treated up to 5 min before challenge (P < 0.001). However, no protection against C. trachomatis infection was seen in animals treated 30 min before challenge. In mice challenged rectally with HSV-2, both the 5% and 10% T-PSS gels significantly reduced infection at 20 s (P < 0.01 for both). However, only the 10% gel provided significant protection when administered 5 min before challenge (P < 0.01). CONCLUSIONS: T-PSS gel formulations have promising in vivo activity as topical microbicides.

Animals↗
PubMed2003

Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.

Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

Animals↗
PubMed2001

Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo.

There remains a lack of agreement on the effect of antiviral therapy on herpes simplex virus (HSV) latency and subsequent reactivation. To gain insight into this important issue, a single-cell polymerase chain reaction assay was used to quantify the effects of high-dose acyclovir on latent infection in a mouse model. Treatment with 50 mg/kg of acyclovir every 8 h reduced the number of latently infected neurons by >90% when treatment was begun before 24 h after infection and by 80% and 70% when begun at 48 or 72 h after infection, respectively. The biologic significance of these reductions was evaluated by using a well-established in vivo reactivation model. The number of animals in which virus reactivated was reduced significantly, even when acyclovir therapy was delayed until 72 h after infection, a time when animals had developed lesions. These findings indicate that potent antiviral therapy during early primary HSV infection can reduce the magnitude of the latent infection, such that a significant decrease in reactivation is observed.

Acute Disease↗
PubMed2001

Adolescent girl's coping with an STD. Not enough problem solving and too much self-blame.

STUDY OBJECTIVE: Approximately three million teenagers are infected with an STD each year. The ways in which an adolescent girl copes with an STD may have implications for future risk and for psychological adjustment. The purpose of the current study was to compare whether coping with an STD was similar to coping with other stressors. SETTING: Urban, hospital-based adolescent medicine clinic. DESIGN AND PARTICIPANTS: Sixty-seven girls with a mean age of 15.9 (sexual debut was 13.8) yr completed the KIDCOPE in response to both an STD acquisition and an interpersonal stressor within the previous 6 months. RESULTS: Problem solving was used less often, and self-blame was used more often, in response to an STD acquisition. Frequency of use of self-blame was not correlated with perceived helpfulness. CONCLUSIONS: These findings suggest that clinicians need to help adolescent girls manage STD acquisition from the perspective of problem solving rather than self-blame.

Adaptation, Psychological↗
PubMed2000

Prospects for control of herpes simplex virus disease through immunization.

Herpes simplex viruses (HSVs) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy, HSV infections remain a significant worldwide public health problem. Vaccines offer the best hope for controlling spread and limiting HSV disease. This article discusses the pathogenesis and immunobiology of mucocutaneous HSV infections, summarizes the spectrum of diseases caused by HSV, and provides a review of the field of HSV vaccine research. This article also discusses what might be realistically expected of a vaccine intended for control of genital herpes and explores the question of whether a vaccine that is effective in controlling genital HSV disease might also be effective in controlling nongenital HSV disease. The efficacy of such vaccines for the full spectrum of HSV disease will eventually determine the timing and targeting of immunization, ranging from selective immunization in preadolescence to universal childhood immunization as part of the routine childhood regimen.

Female↗
PubMed2000

Poly(sodium 4-styrene sulfonate): an effective candidate topical antimicrobial for the prevention of sexually transmitted diseases.

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.

Animals↗
PubMed2000

Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection.

Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 microl of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.

Administration, Topical↗
PubMed2000

Attitudes regarding vaccinations of STDs and other diseases.

The purpose of this study was to examine, among 2 groups of individuals with different risk profiles, the similarity of their attitudes towards vaccines for sexually transmitted diseases (STDs) and non-STDs. Subjects were recruited from an undergraduate psychology class at an urban university (n=518) or were participants in genital herpes vaccine trials (n=87). The participants were asked to complete a questionnaire regarding their attitudes about vaccines for selected diseases. The results of this study revealed that, in general, both groups supported vaccination for most diseases. There were differences, however, between groups regarding 3 diseases: measles, genital warts, and chlamydia. The vaccine trial participants were more likely to accept vaccines for measles and the college students were more likely to accept vaccines for chlamydia and genital warts. The results of this study suggest that negative attitudes regarding vaccination to control STDs may not be a significant barrier to use.

Adolescent↗
PubMed1999

Effects of DNA immunization formulated with bupivacaine in murine and guinea pig models of genital herpes simplex virus infection.

The immunogenicity and efficacy of a herpes simplex virus type 2 glycoprotein D (gD2) DNA vaccine formulated with bupivacaine was evaluated using murine and guinea pig models of genital herpes. Animals received three doses of 100 microg of gD2 plasmid or control plasmid intramuscularly prior to intravaginal challenge with HSV-2. Immunization induced HSV ELISA and neutralizing antibody in serum and ELISA antibody in the vaginal secretions of all animals evaluated. Following intravaginal HSV-2 challenge, vaginal viral replication was reduced in both models with peak reductions of greater than 99%. Immunization also decreased the number of animals developing any clinical disease (p < 0.001) and the severity of the acute disease (total lesion score 6.4 versus 0.6 in guinea pigs, p < 0.001). Further recurrent lesion days were reduced from 14.5 to 4.9 days in immunized guinea pigs (p < 0.001). DNA immunization with gD2 + bupivacaine was effective in reducing clinical disease and viral replication in both guinea pigs and mice.

Animals↗