Peter A. Leone

Efficacy Results of a Trial of a Herpes Simplex Vaccine

BACKGROUND Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women. METHODS We conducted a randomized, double-blind efficacy field trial involving 8323 women 18 to 30 years of age who were negative for antibodies to HSV-1 and HSV-2. At months 0, 1, and 6, some subjects received the investigational vaccine, consisting of 20 μg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant; control subjects received the hepatitis A vaccine, at a dose of 720 enzyme-linked immunosorbent assay (ELISA) units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20. RESULTS The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralizing antibodies to HSV-2. Overall, the vaccine was not efficacious; vaccine efficacy was 20% (95% confidence interval [CI], -29 to 50) against genital herpes disease. However, efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine efficacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (-8%; 95% CI, -59 to 26). CONCLUSIONS In a study population that was representative of the general population of HSV-1- and HSV-2-seronegative women, the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; ClinicalTrials.gov number, NCT00057330.).

The unexpected movement of the HIV epidemic in the Southeastern United States: transmission among college students.

Background:Approximately 16 million people are enrolled in institutions of higher learning in the United States. However, college students have not been perceived as at high risk for HIV infection. In early 2003, acute HIV infection was diagnosed in 2 men attending college in North Carolina. We describe an epidemiologic investigation of newly diagnosed HIV infection in men attending college in North Carolina. Methods:We reviewed state surveillance records examining new HIV diagnoses in men 18-30 years old between January 1, 2000 and December 31, 2003, living in 69 North Carolina counties. Risk behavior and demographic information for HIV-infected men enrolled in college were compared with HIV-infected male nonenrollees. Results:Of the 735 records available for review, 84 (11%) were college men. Eighty-seven percent of college men were African American and 92% were men who have sex with men (MSM) or men who have sex with men and women (MSM/W). Compared with noncollege men, college men were more likely to be African American (odds ratio 3.70, 95% CI = 1.86-7.54), to report meeting sex partners at bars or dance clubs (odds ratio 3.01, 95% CI = 1.77-5.10) or on the Internet/chat lines (odds ratio 4.95, 95% CI = 2.53-9.64), or to report use of “ecstasy” or club drugs (odds ratio 4.51, 95% CI = 1.15-15.40). Newly diagnosed HIV infection was found in men in 37 colleges located in North Carolina or surrounding states and a sexual partner network investigation linked 21 colleges, 61 students, and 8 partners of students. Conclusion:We describe an epidemic of HIV infection occurring in North Carolina college students, primarily involving African American MSM and MSM/W. College students represent an at-risk, accessible population, which deserves further HIV prevention interventions.

Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions

BackgroundSexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community.MethodsEight focus group discussions including 53 White, African American, and Latino youth (age 14–24) were conducted.ResultsPerceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information.ConclusionsFurther research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening.

Men who have sex with men and women: A unique risk group for HIV transmission on North Carolina college campuses

Objective: To better understand the role that men who have sex with men and women (MSM/W) play in the spread of HIV in young adults in North Carolina, we determined the prevalence of MSM/W among newly diagnosed HIV-infected men, compared social and behavioral characteristics of this group with MSM and MSW, and examined the sexual networks associated with HIV-infected college students among these groups. Methods: We reviewed state HIV surveillance records for all new diagnoses of HIV in males 18 to 30 years living in North Carolina between January 1, 2000, and December 31, 2004. Results: Of 1105 records available for review, 15% were MSM/W and 13% were college students. Compared with MSM, MSM/W were more likely to be enrolled in college, to report >10 sex partners in the year before diagnosis, or have sex partners who were also MSM/W. Sexual network analysis of the HIV-infected college students revealed that MSM/W occupied a central position. Of 20 individuals who described themselves as either MSW or abstinent at the time of their initial voluntary counseling and testing visit, 80% reported that they were either MSM or MSM/W during follow up. Discussion: MSM/W represent a unique risk group within the population of MSM that deserve further investigation. College MSM/W appear to occupy a unique, central place in the network of HIV-infected students.

Scabies and Pediculosis Pubis: An Update of Treatment Regimens and General Review

Ectoparasites continue to be a common cause of skin disease throughout the world. The present article dissects the epidemiological profile and treatment of both Sarcoptes scabiei variant hominis and pediculosis pubis.

Topical resiquimod 0.01% gel decreases herpes simplex virus type 2 genital shedding: A randomized, controlled trial

BACKGROUND Resiquimod, an investigational immune response modifier and Toll-like receptor (TLR) 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 (Th1)--acquired immune response. In animal models, induction of Th1-specific responses modifies experimental herpes simplex virus (HSV) infection. METHODS We conducted a randomized, double-blind, vehicle-controlled trial to assess the efficacy of resiquimod 0.01% gel for reducing human anogenital HSV-2 mucosal reactivation. Adults with genital HSV-2 applied resiquimod or vehicle topically to herpes lesions 2 times weekly for 3 weeks and then collected daily anogenital swabs for 60 days for HSV DNA polymerase chain reaction. Recurrences during the subsequent 7 months were treated with study gel. During the final treatment-free 60 days, participants again collected daily swabs to assess shedding. RESULTS The median lesion and shedding rates were lower for resiquimod compared with vehicle recipients during the initial sampling period (10% vs. 16% [P=.03] and 10% vs. 17% [P=.08], respectively) and during the final sampling period (3% vs. 22% [P<.001] and 10% vs. 26% [P=.009], respectively). Resiquimod did not influence recurrence length. CONCLUSIONS These findings suggest that the immunological control of HSV-2 reactivation and lesion clearance may differ and that TLR7 and TLR8 agonists can reduce the frequency of mucosal HSV-2 reactivation.

Spatial analysis and mapping of sexually transmitted diseases to optimise intervention and prevention strategies

Objective: We analysed and mapped the distribution of four reportable sexually transmitted diseases, chlamydial infection/non-gonococcal urethritis (chlamydial infection), gonorrhoea, primary and secondary syphilis (syphilis), and HIV infection, for Wake County, North Carolina, to optimise an intervention. Methods: We used STD surveillance data reported to Wake County, for the year 2000 to analyse and map STD rates. STD rates were mathematically represented as a spatial random field. We analysed spatial variability by calculating and modelling covariance functions of random field theory. Covariances are useful in assessing spatial patterns of disease locally and at a distance. We combined observed STD rates and appropriate covariance models using a geostatistical method called kriging, to predict STD rates and associated prediction errors for a grid covering Wake County. Final disease estimates were interpolated using a spline with tension and mapped to generate a continuous surface of infection. Results: Lower incidence STDs exhibited larger spatial variability and smaller neighbourhoods of influence than higher incidence STDs. Each reported STD had a clustered spatial distribution with one primary core area of infection. Core areas overlapped for all four STDs. Conclusions: Spatial heterogeneity within STD suggests that STD specific prevention strategies should not be targeted uniformly across Wake County, but rather to core areas. Overlap of core areas among STDs suggests that intervention and prevention strategies can be combined to target multiple STDs effectively. Geostatistical techniques are objective, population level approaches to spatial analysis and mapping that can be used to visualise disease patterns and identify emerging outbreaks.

A Phase III Equivalence Trial of Azithromycin versus Benzathine Penicillin for Treatment of Early Syphilis

BACKGROUND Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy. METHODS This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly. RESULTS A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints. CONCLUSIONS In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.

Delayed presentation to clinics for sexually transmitted diseases by symptomatic patients. A potential contributor to continuing STD morbidity.

Objective: To determine the proportion of symptomatic patients attending public sexually transmitted disease (STD) clinics who fail to seek care within 7 days of the onset of STD symptoms and their self‐reported reasons for delays in obtaining care. Design: Interviewers administered 23‐item questionnaire to a cross section of STD clinic clients between April and September 1995. Setting: Five urban STD clinics in the United States (Birmingham, AL; St Paul, MN; San Francisco CA; Seattle, WA; and Raleigh, NC). Results: Of 1,621 patients with genitourinary symptoms, over one third (35% of men, 37% of women) presented to STD clinics only after 1 week or more of symptoms. Men with genital warts (73%) or with nongonococcal urethritis (23.1%) or symptomatic men who were recent contacts to sex partners with STDs were significantly more likely to delay clinic attendance more than a week than men with gonorrhea (6.5%, p < 0.001 for each). Overall 43.8% of women receiving specific clinical diagnoses other than genital warts delayed clinic attendance for more than 1 week. When asked why they delayed clinic attendance, respondents were most likely to respond that they had hoped their symptoms would “go away” (48.5% of men and 49.4% of women who waited a week or more before seeking care). Conclusion: A substantial proportion of patients with genitourinary symptoms attending public STD clinics delay seeking care for a week or more, increasing their likelihood of complications and of transmission of infection to others. Interventions to promote more timely clinic attendance may help reduce STD morbidity in the United States.

Development and Validation of a PCR-Based Enzyme-Linked Immunosorbent Assay with Urine for Use in Clinical Research Settings To Detect Trichomonas vaginalis in Women

ABSTRACT Trichomonas vaginalis infection is highly prevalent worldwide and is associated with poor birth outcomes and enhanced human immunodeficiency virus transmission. Traditional detection methods rely on microscopic examination of vaginal specimens (wet mount) and culture, which can be insensitive and time-consuming. More than 3,000 women attending two sexually transmitted disease clinics were enrolled in this cross-sectional study to evaluate urine-based PCR for detection of T. vaginalis using a combined reference standard of wet mount and culture from vaginal swab. The prevalence of trichomoniasis in the population was 16.7% (502 of 3,009 women) using the reference standard. PCR with urine combined with agarose gel-based detection was 66.9% sensitive and 98.3% specific compared to the reference standard. Detection of PCR products using an unlabeled enzyme-linked immunosorbent assay (ELISA) improved the sensitivity to 86.4%, but specificity fell to 86.1%. Using a digoxigenin-labeled ELISA for detection of amplified T. vaginalis DNA from urine, the sensitivity and specificity of the PCR improved to 90.8 and 93.4%, respectively, compared to wet mount or culture from vaginal swabs. For clinical research settings in which vaginal specimens are not available and culture conditions are not feasible, urine-based PCR-ELISA may be useful for the detection of trichomoniasis in women.