ABSTRACT Synthetic oligonucleotides containing CpG motifs in specific sequence contexts have been shown to induce potent immune responses. We have evaluated mucosal administration of two immunostimulatory sequence (ISS)-containing phosphorothioate-stabilized oligonucleotides for antiherpetic efficacy in animal models. The ISS oligonucleotides, suspended in phosphate-buffered saline, were tested in mouse and guinea pig vaginal models of herpes simplex virus type 2 (HSV-2) infection. For comparison, groups of untreated, non-ISS oligonucleotide-treated, and acyclovir-treated animals also were monitored. The results indicated that vaginal epithelial application of ISS (up to 6 h after viral inoculation) with mice lethally challenged with HSV-2 delayed disease onset and reduced the number of animals that developed signs of disease ( P = 0.003). ISS application significantly increased survival rates over those of controls ( P = 0.0014). The ISS also impacted an established infection in the guinea pig model of HSV-2 disease. A single administration of ISS (21 days after viral inoculation) significantly reduced the frequency and severity of HSV-2 lesions compared to results with non-ISS oligonucleotide-treated and untreated guinea pigs ( P < 0.01). HSV-2 is shed from the vaginal cavity of the guinea pig in the absence of lesions, similar to the case with humans. As an additional indication of ISS efficacy, the magnitude of viral shedding also was significantly reduced in ISS-treated animals ( P < 0.001). These effects appeared to be immunologically mediated, since ISS had no direct effect on HSV-2 replication in vitro using standard plaque assays. These data suggest that ISS may be useful in the treatment and control of genital herpes in humans.
Objective. The Children’s Hospitals in Africa Mapping Project survey was developed and implemented to assess the readiness of hospitals in sub-Saharan African to respond to emergencies, epidemics, and pandemics affecting children. Methods. This sub-study analyzed 56 survey questions that characterized the hospitals and assessed resources for diagnosis, treatment, and prevention of community-acquired infections and healthcare-associated infections (HAIs). Results. Twenty-four sites were recruited and 20 (from 15 countries) completed the survey in 2018 to 2019. Overall, 90% to 100% of sites reported that diagnostic assays were available for malaria, tuberculosis, and HIV. Periodic shortages of antibiotics, antimalarial drugs, and vaccines were reported by 45%, 25%, and 20% of sites, respectively. Sites reported formal programs for infection prevention and control (79%), monitoring HAIs (17%), and antimicrobial stewardship (53%). Conclusions. Opportunities to improve care for hospitalized African children were identified. These included resources for HAI surveillance and antimicrobial stewardship which can facilitate epidemic and pandemic preparedness.
Background:The degree of effectiveness of condom use in preventing the transmission of herpes simplex virus 2 (HSV-2) is uncertain.To address this issue, we performed a large pooled analysis. Methods:We identified prospective studies with individual-level condom use data and laboratory-defined HSV-2 acquisition.Six studies were identified through a review of publications through 2007: 3 candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational sexually transmitted infection (STI) incidence study, and a behavioral STI intervention study.Study investigators provided us individual-level data to perform a pooled analysis.Effect of condom use was modeled using a continuous percentage of sex acts during which a condom was used and, alternatively, using absolute numbers of unprotected sex acts.
The prevalence of herpes genitalis (genital herpes) has increased markedly over the past three decades. The most common cause is infection with the herpes simplex virus type 2 (HSV-2), but it can also occur as a result of HSV-1 infection. Herpes genitalis can cause substantial psychosexual as well as physical morbidity and, in immunocompromised individuals, such as those who are HIV-positive, HSV infection can result in severe disease with progressive and extensive lesions. The natural history of herpes genitalis and the pathways of infection are now well known; however, the factors associated with reactivation have yet to be fully defined. A number of management approaches with antiviral medications are commonly used, including episodic and suppressive treatments. For episodic therapy, the duration of both lesions and symptoms, as well as the proportion of aborted episodes, are the most important measures of efficacy. For suppressive therapy, the time to first recurrence and frequency of recurrences over time are the most important clinical measures of antiviral benefit. Regarding the duration of episodic regimens, comparisons of 1-, 2- and 3-day antiviral courses with standard 5-day regimens show similar benefits on healing and relief of symptoms, with the obvious improvement in convenience, economy and compliance. In HIV-positive patients, antiherpes therapy has proved effective in speeding healing of lesions and reducing subclinical shedding, and can be used to treat genital HSV-2 infections in this group. Suppressive antiviral therapy has been shown to decrease the risk of HSV transmission in heterosexual couples. New approaches to the prevention of HSV infection, including vaccines and topical microbicides, are under investigation.
In Brief Background Because topical microbicides designed to prevent the spread of sexually transmitted diseases may be applied frequently, it is important to ensure product safety as well as efficacy. A murine model was developed to test for induction of inflammatory responses following application of candidate microbicides. Goal A comparison was made of the induction of inflammation following vaginal application of detergent-based and sulfated polymer–based microbicides. Study Design Vaginal leukocytes were collected, identified, and quantified following microbicide application to detect the entry of inflammatory leukocytes into the vaginal lumen. Results Large numbers of neutrophils and macrophages entered the vaginal lumen following a single application of detergent-based microbicides. No significant increase in vaginal leukocytes was detected following a single or repeated application of sulfated polymer–based microbicides. Conclusion Application of sulfated polymer–based microbicides was less likely to result in inflammatory responses than was application of detergent-based compounds. This murine model should prove useful as part of a screening process to prioritize candidate microbicides before clinical trial. A murine model was used to detect and quantify inflammatory responses in the vaginal mucosa following application of candidate microbicides. Significant inflammatory responses were detected following application of detergent-based but not sulfated polymer-based microbicides.
