Multicomponent Strategies to Prevent SARS-CoV-2 Transmission - Nine Overnight Youth Summer Camps, United States, June-August 2021.

Most U.S. overnight youth camps did not operate during the summer of 2020 because of the COVID-19 pandemic* (1). Several that did operate demonstrated that multiple prevention strategies, including pre- and postarrival testing for SARS-CoV-2, the virus that causes COVID-19, masking, and physical distancing helped prevent the introduction and spread of COVID-19; in contrast, camps that relaxed prevention strategies, such as requiring a single prearrival test without subsequent testing, experienced outbreaks (2-4). The availability of COVID-19 vaccines for persons aged ≥12 years enabled implementation of an additional prevention strategy that was not available in summer 2020. This study assessed the number of COVID-19 cases and potential secondary spread among 7,173 staff members and campers from 50 states, 13 countries, and U.S. military overseas bases at nine independently operated U.S. summer youth camps affiliated with the same organization. The camps implemented multiple prevention strategies including vaccination, testing, podding (cohorting), masking, physical distancing, and hand hygiene during June-August 2021. Vaccination coverage was 93% among eligible persons aged ≥12 years.† All staff members (1,955) and campers (5,218) received site-specific, protocol-defined screening testing, which included prearrival testing and screening tests during the camp session (38,059 tests). Screening testing identified six confirmed COVID-19 cases (one in a staff member and five in campers) by reverse transcription-polymerase chain reaction (RT-PCR) testing (screening test positivity rate = 0.02%). Three additional cases (in two staff members and one camper) were identified based on symptoms and were confirmed by RT-PCR testing. Testing for SARS-CoV-2, isolation, and quarantine in a population with high vaccination coverage resulted in no known secondary transmission of SARS-CoV-2 identified during camp. Implementation of multicomponent strategies is critical for prevention of COVID-19 outbreaks in congregate settings, including overnight youth camps.

Assessment of adherence to product dosing in a pilot microbicide study.

OBJECTIVES: To determine whether applicator staining could be incorporated into a microbicide study as a marker of adherence. GOAL: To test whether observers could identify intravaginally inserted applicators and compare the observers' ratings to subjects' self reports. STUDY DESIGN: Subjects participating in a 14-day microbicide trial to assess the safety of 0.5% PRO 2000 or matched placebo gel returned used and unused applicators. Each applicator was individually dyed or batched and immersed in a 0.4% trypan blue waterbath. Masked observers rated the applicators as intravaginally inserted or not; results were compared to subjects' self-reports. To determine if the dye would allow observers to differentiate whether applicators had been filled before intravaginal insertion, staff either filled applicators and discarded gel ex vivo or asked volunteers to intravaginally insert applicators without gel and mixed these with a random sampling of used and unused study samples. RESULTS: 358 of 360 applicators were returned; 306 were reported to have been vaginally inserted and 52 unused. Observers agreed with the participant's self reports in 98-99% of cases. No differences were observed between applicators stained individually or in batches. The ability to distinguish between applicators that were presumed to have been used properly, intravaginally inserted without gel, filled with gel and emptied ex vivo, or unused ranged from 76 to 87%. CONCLUSIONS: Staining of applicators is accurate, inexpensive, and correlated well with self-report in a study of short duration. This method could prove useful in assessing adherence to product dosing in future microbicide trials.

PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity.

OBJECTIVE: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity. DESIGN AND METHODS: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21. RESULTS: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus). CONCLUSION: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity.

Stage of change behavioral assessment tool fails to predict the prevalence of chlamydia in an urban adolescent health clinic.

STUDY OBJECTIVE: Strategies to reduce STI among adolescents and young adults have failed to consistently demonstrate effectiveness. A universal approach may not be appropriate because individuals are at different stages with respect to self-management behaviors. Thus, the Stage of Change Transtheoretical Model has been advocated. This study was conducted to determine whether staging could be accomplished in an urban adolescent clinic and whether it provides a tool to predict STI risk. DESIGN: Participants were interviewed and staged according to a standardized instrument with respect to sexual risk behaviors and contraceptive use. SETTING: Urban adolescent health clinic. PARTICIPANTS: 103 females (ages 18-24). INTERVENTIONS: A physical examination and diagnostic tests for syphilis, HSV, HCV, chlamydia, gonorrhea and HPV were performed. MAIN OUTCOME MEASURES: Stages for behaviors to reduce STI risk and to utilize contraception and STI prevalence. RESULTS: 78% of the participants were in the three earliest stages of behavior (precontemplative, contemplative, and ready for action) with respect to condom use for STI prevention; conversely only 47% were in early stages with respect to birth control practices. Of the participants tested, 12/81 (15%) had chlamydial infection detected by molecular techniques, whereas no participants had gonorrhoeae. Among the subset tested for HPV DNA, 18/45 (40%) were positive. The diagnostic behavior stage for STI prevention did not correlate with the presence of chlamydia. CONCLUSIONS: A staging instrument can be implemented into adolescent health clinic practice, but cannot be used as a risk assessment tool for the presence of chlamydia. Additionally females are more likely to protect themselves against pregnancy than against an STI.

PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.

BACKGROUND: Microbicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing to clinical trials on the basis of activity observed in vitro and in animal models. However, no data demonstrate activity of microbicides after application in humans. This study was designed to determine the antiviral activity in cervicovaginal lavage (CVL) samples collected after intravaginal application of 0.5% PRO 2000 gel (Indevus). METHODS: A randomized, double-blind study was conducted to assess the anti-HIV and anti-herpes simplex virus (HSV) activity of PRO 2000 in CVL samples obtained at screening (48 hours before) and 1 hour after application of study or placebo gel. HeLa cells or human macrophages were inoculated with CVL samples spiked with replication-defective HIV containing a luciferase indicator gene and pseudotyped with an R5 envelope. Human cervical epithelial cells were inoculated with CVL samples and challenged with HSV-2(G), and the virus titer was then determined. RESULTS: CVL samples obtained after application of PRO 2000 gel significantly inhibited HIV and HSV infection by at least 1000-fold, compared with CVL samples obtained at screening (P < .001). There were no differences in cytokine levels between the drug and placebo groups. CONCLUSIONS: PRO 2000 gel (0.5%) is sufficiently bioavailable and retains substantial antiviral activity after intravaginal application. This strategy provides a mechanism for testing the efficacy of a microbicide before embarking on large-scale clinical trials.

Cervicovaginal secretions contribute to innate resistance to herpes simplex virus infection.

Defining and preserving the innate antiviral activity found in cervicovaginal secretions is critical. Cervicovaginal lavage (CVL) samples were obtained from 20 healthy women and evaluated for anti-herpes simplex virus (HSV) activity. CVL samples reduced HSV-2 yields by 23-fold (median), and the anti-HSV activity of CVL samples correlated with the concentration of human neutrophil peptides (HNP)-1-3. Both CVL samples and HNP-1-3 interacted with virus and prevented entry after binding. Substantially less protective activity was observed in CVL samples obtained from 20 human immunodeficiency virus--infected subjects, but the addition of CVL samples from healthy subjects enhanced the antiviral activity. The significance of the innate activity was further demonstrated by showing that CVL samples prevented murine genital herpes. Fourteen of 15 mice were protected from genital herpes if they were challenged with HSV-2 pretreated with CVL samples from healthy subjects. In contrast, all 15 mice challenged with untreated HSV-2 died. These findings are evidence that cervicovaginal secretions contribute to innate resistance to HSV-2 and identify defensins as contributors to this activity.