Protection of outbred mice against a vaginal challenge by a Chlamydia trachomatis serovar E recombinant major outer membrane protein vaccine is dependent on phosphate substitution in the adjuvant.

Chlamydia trachomatis is the most common bacterial sexually-transmitted pathogen for which there is no vaccine. We previously demonstrated that the degree of phosphate substitution in an aluminum hydroxide adjuvant in a TLR-4-based C. trachomatis serovar E (Ser E) recombinant major outer membrane protein (rMOMP) formulation had an impact on the induced antibody titers and IFN-γ levels. Here, we have extended these observations using outbreed CD-1 mice immunized with C. trachomatis Ser E rMOMP formulations to evaluate the impact on bacterial challenge. The results confirmed that the rMOMP vaccine containing the adjuvant with the highest phosphate substitution induced the highest neutralizing antibody titers while the formulation with the lowest phosphate substitution induced the highest IFN-γ production. The most robust protection was observed in mice vaccinated with the formulation containing the adjuvant with the lowest phosphate substitution, as shown by the number of mice with positive vaginal cultures, number of positive cultures and number of C. trachomatis inclusion forming units recovered. This is the first report showing that vaccination of an outbred strain of mice with rMOMP induces protection against a vaginal challenge with C. trachomatis.

Quarterly screening optimizes detection of sexually transmitted infections when prescribing HIV preexposure prophylaxis.

OBJECTIVE: The optimal screening frequency of sexually transmitted infections (STIs) for MSM and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with present guidelines recommending screening every 3-6 months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. DESIGN: The US PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami, and a community health center in Washington, DC. In all, 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. METHODS: The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every 6 versus every 3 months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. RESULTS: Among the participants, 50.9% had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to 3 months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. CONCLUSIONS: Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs, and decrease transmission.

Who is coming back for more chlamydia testing within non-specialist health services and where do they go? England, 2013-2016.

OBJECTIVES: To investigate patient demographics and venue type preferences within community settings associated with re-attendance for chlamydia testing. STUDY DESIGN: Data used for this analysis were obtained from the English National Chlamydia Screening Programme (NCSP) which focuses on prevention, control and treatment of chlamydia in sexually active under-25 year olds. A greater understanding of how young adults attend services helps to inform commissioners regarding where to focus resources within community settings. METHODS: Data from the Chlamydia surveillance system (CTAD) were used to count patient attendances at non-specialist sexual health services (SHSs) among 15-24-year-olds and monitor re-attendance for chlamydia testing within and between community services between 6 and 18 months of their first visit. RESULTS: From January 2013 to December 2016, 866,847 young people underwent 1,041,245 tests for chlamydia. Re-attendance for chlamydia testing was 20.1% (174,398/866,847). Re-attendance rate was 28.5% after a positive test and 19.5% after a negative test. For re-attenders, 64.2% used the same venue type for both visits. General practice (GP) and sexual and reproductive health services (SRH) were the most commonly re-attended services (31.0% and 30.6% respectively). CONCLUSIONS: Only one in five re-attended for chlamydia testing. Re-attendance was associated with having a positive result, accessibility and convenience. Patients are likely to return for testing to services they know. This should be considered by commissioners implementing new re-attendance guidance based on the NCSP.

Could Intensive Screening for Gonorrhea/Chlamydia in Preexposure Prophylaxis Cohorts Select for Resistance? Historical Lessons From a Mass Treatment Campaign in Greenland.

INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all classes of antimicrobials used against it. Current strategies to prevent the emergence of pan-resistance include increased gonorrhea screening in high-prevalence populations such as men who have sex with men taking HIV preexposure prophylaxis. By increasing antimicrobial exposure, others have argued that intensive screening may inadvertently promote the emergence of antimicrobial resistance. AIM/METHODOLOGY: To contribute to this discussion, we conducted a historical review of the effect of a mass gonorrhea treatment campaign in Greenland from 1965 to 1968 on the incidence of gonorrhea and antimicrobial resistance. We conducted a literature review using PubMed and Google Scholar to find relevant studies. Data on the incidence of gonorrhea, antimicrobial susceptibility, and antimicrobials dispensed were extracted and analyzed. RESULTS: Eight articles were found with relevant information. The cornerstone of the campaign involved the repeated treatment for all persons with a diagnosis of gonorrhea in the past 6 months as well as all remaining unmarried persons between 15 and 30 years of age. There was a small and temporary decline in the incidence of gonorrhea during the campaign. The campaign was, however, associated with an increase in the proportion of gonococci that were not susceptible to penicillin. Gonococcal incidence continued to climb after the campaign ended but did decline dramatically after reductions in risk behavior after the global AIDS epidemic. DISCUSSIONS: The mass gonorrhea treatment campaign in Greenland was associated with only a temporary decline in the incidence of gonorrhea. It was, however, followed by an increase in penicillin nonsusceptibility. Intense gonorrhea screening and treatment strategies should be aware of the risk of inducing antimicrobial resistance.

Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV pre-exposure prophylaxis.

OBJECTIVES: Rectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT). METHODS: From 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson's χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted. RESULTS: Of 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. CONCLUSION: Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.

Testing and Treatment After Adolescent Sexual Assault in Pediatric Emergency Departments.

OBJECTIVE: To examine rates of recommended of testing and prophylaxis for chlamydia, gonorrhea, and pregnancy in adolescents diagnosed with sexual assault across pediatric emergency departments (EDs) and to determine whether specialized sexual assault pathways and teams are associated with performance of recommended testing and prophylaxis. METHODS: In this retrospective study of 12- to 18-year-old adolescents diagnosed with sexual assault at 38 EDs in the Pediatric Hospital Information System database from 2004 to 2013, information regarding routine practice for sexual assault evaluations and presence and year of initiation of specialized ED sexual assault pathways and teams was collected via survey. We examined across-hospital variation and identified patient- and hospital-level factors associated with testing and prophylaxis using logistic regression models, accounting for clustering by hospital. RESULTS: Among 12,687 included cases, 93% were female, 79% were <16 years old, 34% were non-Hispanic white, 38% were non-Hispanic black, 21% were Hispanic, and 52% had public insurance. Overall, 44% of adolescents received recommended testing (chlamydia, gonorrhea, pregnancy) and 35% received recommended prophylaxis (chlamydia, gonorrhea, emergency contraception). Across EDs, unadjusted rates of testing ranged from 6% to 89%, and prophylaxis ranged from 0% to 57%. Presence of a specialized sexual assault pathway was associated with increased rates of prophylaxis even after adjusting for case-mix and temporal trends (odds ratio 1.46, 95% confidence interval 1.15 to 1.86). CONCLUSIONS: Evaluation and treatment of adolescent sexual assault victims varied widely across pediatric EDs. Adolescents cared for in EDs with specialized sexual assault pathways were more likely to receive recommended prophylaxis.

The forgotten link between sexual health and pregnancy.

Women presenting to midwives in pregnancy have one forgotten risk factor: sexually transmitted infections (STIs). Pregnant women have had unprotected sexual intercourse at least once. Statistics highlight the increasing prevalence of STIs, with women aged under 25 being at high risk due to reasons identified by the Department of Health (DH) (2012; 2013). Focusing on chlamydia in pregnancy, the risks to the neonate are severe. There are no health campaigns about safe sex in pregnancy, so women cannot access this information. The screening and education around STIs could be dramatically improved; women should be screened for chlamydia at booking, with this repeated if they have a new partner (which is a strong possibility as 50 per cent of pregnancies are unplanned). To increase awareness of this issue, further education for midwives is essential by collaborating with sexual health services and developing a referral pathway. Antenatal education about safe sex in pregnancy can then be introduced and health campaigns developed.

Water-filtered infrared a irradiation in combination with visible light inhibits acute chlamydial infection.

New therapeutic strategies are needed to overcome drawbacks in treatment of infections with intracellular bacteria. Chlamydiaceae are Gram-negative bacteria implicated in acute and chronic diseases such as abortion in animals and trachoma in humans. Water-filtered infrared A (wIRA) is short wavelength infrared radiation with a spectrum ranging from 780 to 1400 nm. In clinical settings, wIRA alone and in combination with visible light (VIS) has proven its efficacy in acute and chronic wound healing processes. This is the first study to demonstrate that wIRA irradiation combined with VIS (wIRA/VIS) diminishes recovery of infectious elementary bodies (EBs) of both intra- and extracellular Chlamydia (C.) in two different cell lines (Vero, HeLa) regardless of the chlamydial strain (C. pecorum, C. trachomatis serovar E) as shown by indirect immunofluorescence and titration by subpassage. Moreover, a single exposure to wIRA/VIS at 40 hours post infection (hpi) led to a significant reduction of C. pecorum inclusion frequency in Vero cells and C. trachomatis in HeLa cells, respectively. A triple dose of irradiation (24, 36, 40 hpi) during the course of C. trachomatis infection further reduced chlamydial inclusion frequency in HeLa cells without inducing the chlamydial persistence/stress response, as ascertained by electron microscopy. Irradiation of host cells (HeLa, Vero) neither affected cell viability nor induced any molecular markers of cytotoxicity as investigated by Alamar blue assay and Western blot analysis. Chlamydial infection, irradiation, and the combination of both showed a similar release pattern of a subset of pro-inflammatory cytokines (MIF/GIF, Serpin E1, RANTES, IL-6, IL-8) and chemokines (IL-16, IP-10, ENA-78, MIG, MIP-1α/ß) from host cells. Initial investigation into the mechanism indicated possible thermal effects on Chlamydia due to irradiation. In summary, we demonstrate a non-chemical reduction of chlamydial infection using the combination of water-filtered infrared A and visible light.

Treatment and prevention of ophthalmia neonatorum.

QUESTION: In my office I occasionally see neonates with conjunctivitis. What are the current recommendations for ocular prophylaxis at birth? Do topical antibiotics alone provide adequate treatment of neonatal conjunctivitis? When is systemic therapy indicated? ANSWER: All infants should receive ocular prophylaxis at birth to prevent gonococcal ophthalmia. Neonates presenting with signs of conjunctivitis should have a conjunctival swab sent for Gram stain and culture. If Gram-negative diplococci are present on the Gram stain results, the infants and their parents should be treated immediately for presumed gonorrhea. Infants with chlamydial infection should be treated with oral antibiotics. Most of all other forms of bacterial conjunctivitis can be treated with topical antibiotics, with the exception of Pseudomonas infection. Infants should be followed during their treatment and upon completion of therapy to ensure resolution of symptoms. For cases in which sexually transmitted bacteria are implicated, the mothers and their sexual partners should be treated.

Chlamydial infections in Chinese livestock.

The occurrence and impact of chlamydial infections in Western livestock is well documented in the international literature, but less is known aboutthese infections in livestock in the People's Republic of China. China's livestock production and its share in the global market have increased significantly in recent decades. In this review, the relevant English and Chinese literature on the epidemiology of chlamydial infections in Chinese livestock is considered, and biosecurity measures, prophylaxis and treatment of these infections in China's livestock are compared with Western practices. Chlamydial infections are highly prevalent in Chinese livestock and cause important economic losses, as they do in the rest of the world. Surveillance data and diagnostic results of abortion outbreaks in cattle, sheep and goats highlight the importance of virulent chlamydial infections in China's major ruminant species in many of China's provinces, autonomous regions and municipalities. Data from many of China's provincial divisions also indicate the widespread presence of chlamydial infections in industrially reared swine across the country. Less is known about chlamydial infections in yak, buffalo and horses, but available reports indicate a high prevalence in China's populations. In these reports, chlamydiosis was related to abortions in yak and pneumonia in horses. In Western countries, chlamydial infections are principally treated with antibiotics. In China, however, traditional medicine is often used in conjunction with antibiotics or used as an alternative treatment.

Periodical antibiotic treatment for the control of gonococcal and chlamydial infections among sex workers in Benin and Ghana: a cluster-randomized placebo-controlled trial.

BACKGROUND: In resource-poor settings, control of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among female sex workers (FSWs) is difficult. We sought to determine whether periodical antibiotic treatment (PAT) might be effective in controlling these infections among West African FSWs. Secondary objectives were to determine the impact of PAT on human immunodeficiency virus (HIV) incidence among FSWs and on NG/CT prevalence among their clients. METHODS: Cluster-randomized, double-blind, placebo-controlled trial among FSW communities in Benin and Ghana. Within each of 9 pairs of clusters of FSW communities, one was allocated to receive, during 9 months, a monthly antibiotic (alternatively ciprofloxacin or azithromycin, n = 296 FSWs) and the other a placebo (n = 340 FSWs). Prevalence of NG/CT infections was measured at 3-month intervals using the polymerase chain reaction. HIV status was determined at the beginning and at the end of the study. RESULTS: After adjusting for age, HIV status, duration of prostitution, price per intercourse and condom use, and accounting for prevalence at enrollment and cluster-pairing effect, prevalence ratios (intervention vs. placebo) of NG infection were 0.77 (P = NS), 1.07 (P = NS), and 0.49 (P = 0.05) at the first, second, and third follow-up visits, respectively. PAT neither reduced significantly CT prevalence or HIV incidence among FSWs nor NG/CT prevalence among their clients. CONCLUSION: The only beneficial impact of PAT was on the prevalence of gonococcal infections among FSWs 9 months after the beginning of the intervention. Although PAT could be more effective in other circumstances, for instance, in the early stages of a program for FSWs, it can not be recommended at present as a routine strategy to control cervical infections among FSWs.

Effects of baicalin on Chlamydia trachomatis infection in vitro.

Baicalin has emerged as a promising agent for the therapy of infectious diseases due to the increasing number of pathogenic microbial strains resistant to several antibiotics. In this study, we investigated the inhibitory activity of baicalin on Chlamydia infection in vitro. We found that baicalin blocked the infection of HeLa cells in vitro when added to the infected cells. In order to shed light on the inhibitory effects of baicalin on the Chlamydia-infected cells, the expression of RFX5 and Chlamydia protease-like activity factor (CPAF) mRNAs and proteins in the Chlamydia-infected cells were examined using Western blot and real-time RT-PCR analysis. The results demonstrated that RFX5 and CPAF were upregulated and downregulated, respectively, by baicalin. Because CPAF is responsible for degrading RFX5, it is suggested that CPAF is a primary target of baicalin and plays an important role in downregulating RFX5. In conclusion, our findings demonstrated that baicalin can effectively inhibit Chlamydia Trachomatis in HeLa cells and therefore can be considered a potential agent for the therapy of infectious diseases caused by C. trachomatis.

Chlamydia trachomatis in Tasmania 2001-2007: rising notification trends.

OBJECTIVES: To investigate trends in notification rates of Chlamydia trachomatis in Tasmania, Australia, by population sub-groups, from 1 January 2001 to 31 December 2007. METHODS: An enhanced surveillance dataset was used to supplement case notifications. Rates based on age group were analysed by sex, geographic region, indigenous status, sexual exposure, reason for testing and healthcare provider. RESULTS: In all age groups, the notification rate increased steeply. The highest rates were seen in the ages 15-24 years; this age group represented 15% of the population but accounted for 74% of the chlamydial notifications. The increased rates in females aged 15-24 years and males 15-19 years in Tasmania were larger than the increases observed nationally. Rates were consistently higher in urban areas. Females were more likely to have been tested as a result of screening, and males were more likely to have been tested when presenting with symptoms or as a result of contact tracing. The majority of cases reported sexual exposure with opposite sex partners only. CONCLUSIONS: This study highlights the increasing significance of chlamydial infection as a public health issue, the gender differences in health-seeking behaviour, and the discrepancies in testing patterns. These findings will assist with the design of health promotion programs.

Preventive screening of women who use complementary and alternative medicine providers.

BACKGROUND: Many women use complementary and alternative medicine (CAM). Although CAM use has been associated with reductions in conventionally recommended pediatric preventive care (e.g., vaccination), little is known about associations between CAM use and receipt of recommended preventive screening in women. METHODS: Using Washington State insurance data from 2000 to 2003, the authors generated clustered logistic regression models, examining associations between provider-based CAM use and receipt of screening tests for Chlamydia trachomatis, breast cancer, and cervical cancer: (1) contrasting women who used CAM providers only (alternative use) and women who used both conventional and CAM providers (complementary use) with women who used conventional care only and (2) testing associations between screening and use of four specific CAM provider types-naturopathic physicians, chiropractors, massage therapists, and acupuncturists. RESULTS: Both alternative and complementary use was associated with reduced Chlamydia screening. Cancer screening increased with complementary use but decreased with alternative use of CAM. Use of naturopathy was associated with decreased mammography, whereas all four CAM therapies were positively associated with Papanicolaou testing. CONCLUSIONS: When used in conjunction with conventional care, use of provider-based CAM may signal high interest in various types of health-promoting behavior, including cancer screening. Negative associations between CAM and Chlamydia screening and between naturopathy and mammography require additional study. Interventions with CAM providers and their patients, aimed at improving rates of conventionally recommended screening, might encourage greater focus on preventive care, an important task when CAM providers serve as women's only contact with the healthcare system.

A summary of preclinical topical microbicide rectal safety and efficacy evaluations in a pigtailed macaque model.

BACKGROUND: There is widespread recognition of the potential promise of vaginal microbicides as a tool to combat global human immunodeficiency virus/acquired immunodeficiency syndrome and sexually transmitted infections epidemics, and candidate product development has maintained a rapid pace in recent years; however, rectal microbicide development has received less attention. As it is likely that commercial products developed for vaginal use will also be used rectally, there is a clear need to assess the safety and efficacy of candidate microbicide products specifically in the rectal compartment. METHODS: We have developed a standardized protocol for preclinical rectal safety and (chlamydial) efficacy assessment of topical microbicide candidates in a nonhuman primate model. We evaluated a total of 12 test compounds for rectal safety (via rectal pH, microflora, and rectal lavage) and 1 compound for efficacy against rectal chlamydial infection. RESULTS: In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the rectal environment. We also outline the specific criteria used to recommend products move into preclinical rectal efficacy trials or be recommended for reformulation to the product developer. In summary, we observed significant adverse effects in 2 products. The single product that underwent efficacy evaluation was not observed to be protective against rectal chlamydial infection. CONCLUSIONS: A preclinical safety and efficacy model is critical to promoting rectal microbicide development, which will ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.

A summary of preclinical topical microbicide vaginal safety and chlamydial efficacy evaluations in a pigtailed macaque model.

BACKGROUND: The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials. METHODS: We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the cervicovaginal environment. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer. RESULTS: Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection. CONCLUSIONS: The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.

Preclinical safety and efficacy assessments of dendrimer-based (SPL7013) microbicide gel formulations in a nonhuman primate model.

Three gel formulations (1%, 3%, and 5% [wt/wt]) of SPL7013, a dendrimer known to have antiviral (anti-human immunodeficiency virus and anti-herpes simplex virus) activities, completed a range of preclinical tests in the pigtailed macaque models for vaginally and rectally applied topical microbicide safety assessments. The vaginal safety profile of the 3% SPL7013 gel formulation was equal to that of the 1% formulation but was superior to that of the 5% formulation. The 3% SPL7013 gel was further evaluated for rectal safety and for antichlamydial efficacy with cervical challenge with Chlamydia trachomatis. This first-generation dendrimer-based product was shown to be safe to the vaginal and rectal microenvironments with repeated daily use. However, a single intravaginal application of the 3% (wt/wt) SPL7013 gel did not provide protection from the acquisition of cervical chlamydial infection.