Is There a Hidden Burden of Disease as a Result of Epigenetic Epithelial-to-Mesenchymal Transition Following Chlamydia trachomatis Genital Tract Infection?

Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT's ability to promote EMT and to pinpoint the areas that merit further investigation.

What Can Serology Tell Us About the Burden of Infertility in Women Caused by Chlamydia?

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia's contribution to female infertility.

What Do Diagnoses of Pelvic Inflammatory Disease in Specialist Sexual Health Services in England Tell Us About Chlamydia Control?

BACKGROUND: Pelvic inflammatory disease (PID) is an outcome measure for the evaluation of chlamydia screening programs. We explore PID diagnoses in specialist sexual health services (SSHSs) in England to inform the evaluation of the National Chlamydia Screening Programme, which was implemented nationally in 2008. METHODS: We conducted descriptive analyses using data on diagnoses of PID-with and without Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC)-by age and year of birth, in SSHSs between 2009 and 2019 from the GUMCAD STI Surveillance System database. Rates were calculated per 100 000 females residing in England. RESULTS: CT screening activity peaked in 2010. The rates of all PID diagnoses decreased between 2009 and 2019 by 39%. CT-associated PID (CT-PID) declined by 58%, and nonspecific PID declined by 37%. GC-PID increased by 34%. CT-PID decreased across all age groups with the highest observed decline, 71%, in 15- to 19-year-olds. A dose-response relationship was observed between CT-PID rates and screening, with rates lowest in those with the greatest exposure to screening. CONCLUSIONS: There was a marked decline in diagnoses of CT-PID, and nonspecific PID, at SSHSs after the introduction of widespread chlamydia screening, whereas GC-PID diagnoses increased. This ecological trend was broadly consistent with what we would have expected to see if widespread screening reduced the incidence of chlamydia-associated PID (and of nonspecific PID), as has been observed in randomized controlled trials of screening.

High Plasmid Gene Protein 3 (Pgp3) Chlamydia trachomatis Seropositivity, Pelvic Inflammatory Disease, and Infertility Among Women, National Health and Nutrition Examination Survey, United States, 2013-2016.

BACKGROUND: Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Plasmid gene protein 3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA). METHODS: We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI ≥ 50 000; low-positive was MFI > 551-<50 000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (CI) were compared for women with chlamydial infection, self-reported PID, and infertility. RESULTS: Of 2339 women aged 18-39 years, 1725 (73.7%) had sera, and 1425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had lowpositive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]). Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab. CONCLUSIONS: High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection.

Evidence of changing sexual behaviours and clinical attendance patterns, alongside increasing diagnoses of STIs in MSM and TPSM.

BACKGROUND: Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS: We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS: Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION: Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

Human Immunodeficiency Virus Preexposure Prophylaxis Knowledge, Attitudes and Perceptions of Sexual Health Risk in an Age of Sexually Transmitted Infection Antimicrobial Resistance.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has helped reduce new HIV infections. However, bacterial sexually transmitted infections (STIs) have increased among PrEP users. We examined PrEP knowledge, access, and risk perceptions in an age of antimicrobial resistance (AMR). METHODS: An online anonymous survey was distributed to all cisgender men/transpersons who have sex with men attending a sexual health clinic in Bristol, United Kingdom (October 2018 to November 2019). Interviews with a sample identified at increased risk of HIV were analyzed thematically and integrated with survey data. RESULTS: Five hundred and seventy-eight (95%) of 617 cisgender men/transpersons who have sex with men survey respondents were HIV-negative/unknown, of these, 202 (34.9%) had ever used PrEP. Interviewees (n = 24) reported widespread awareness of and enthusiasm for PrEP. Among nonusers, 39% (146/376) were unaware how to access PrEP, and 27% (103/376) could not access PrEP through the national "impact" trial of whom 79% (81/103) were eligible. The PrEP was described as "life-changing," but expense was the main barrier to use. Sixty-two percent (358/578) of HIV-negative/unknown respondents on PrEP were more likely to have condomless anal intercourse with someone they thought was HIV-negative. Interviewees used PrEP with other risk-reduction strategies. Sexually transmitted infections were seen as "curable" and AMR rarely influenced risk perception or sexual decision making. CONCLUSIONS: The PrEP awareness was high, but purchase cost limited access. PrEP may increase condomless anal intercourse, but interviewees used PrEP as one of many risk-reduction tools. Reduced fear of HIV transmission and testing was highly valued. Sexually transmitted infection AMR was not seen as an immediate threat and did not influence risk perception or sexual decision making.

Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review.

Rates of bacterial sexually transmitted infections (STIs) continue to rise, demanding treatments to be highly effective. However, curing infections faces significant challenges due to antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium and especially treating STIs at extragenital sites, particularly rectal chlamydia and oropharyngeal gonorrhoea. As no new antimicrobials are entering the market, clinicians must optimize the currently available treatments, but robust data are lacking on how the properties or pharmacokinetics of antimicrobials can be used to inform STI treatment regimens to improve treatment outcomes. This paper provides a detailed overview of the published pharmacokinetics of antimicrobials used to treat STIs and how factors related to the drug (tissue distribution, protein binding and t½), human (pH, inflammation, site of infection, drug side effects and sexual practices) and organism (organism load and antimicrobial resistance) can affect treatment outcomes. As azithromycin is commonly used to treat chlamydia, gonorrhoea and M. genitalium infections, and its pharmacokinetics are well studied, it is the main focus of this review. Suggestions are also provided on possible dosing regimens when using extended and/or higher doses of azithromycin, which appropriately balance efficacy and side effects. The paper also emphasizes the limitations of currently published pharmacokinetic studies including oropharyngeal gonococcal infections, where very limited data exist around ceftriaxone pharmacokinetics and its use in combination with azithromycin. In future, the different anatomical sites of infections may require alternative therapeutic approaches.

Phenotypic antimicrobial susceptibility testing of Chlamydia trachomatis isolates from patients with persistent or successfully treated infections.

Objectives: Antimicrobial susceptibility data for Chlamydia trachomatis are lacking. Methodologies for susceptibility testing in C. trachomatis are not well-defined, standardized or performed routinely owing to its intracellular growth requirements. We sought to develop an assay for the in vitro susceptibility testing of C. trachomatis isolates from two patient cohorts with different clinical outcomes. Methods: Twenty-four clinical isolates (11 from persistently infected and 13 from successfully treated patients) were overlaid with media containing two-fold serial dilutions of azithromycin or doxycycline. After incubation, aliquots were removed from the stock inoculum (SI) and each antimicrobial concentration for total RNA extraction, complementary DNA generation and real-time PCR. The MIC was defined as the lowest antimicrobial concentration where a 95% reduction in transcription was evident in comparison with the SI for each isolate. Results: MICs of azithromycin were comparable for isolates from the two patient groups (82% ≤ 0.25 mg/L for persistently infected and 100% ≤ 0.25 mg/L for successfully treated patients). Doxycycline MICs were at least two-fold lower for isolates from the successfully treated patients (53.9% ≤ 0.064 mg/L) than for the persistently infected patients (100% ≥ 0.125 mg/L) (P = 0.006, Fisher's exact test). Overall, 96% of isolates gave reproducible MICs when re-tested. Conclusions: A reproducible assay was developed for antimicrobial susceptibility testing of C. trachomatis. MICs of azithromycin were generally comparable for the two different patient groups. MICs of doxycycline were significantly higher in the persistently infected patients. However, interpretation of elevated MICs in C. trachomatis is extremely challenging in the absence of breakpoints, or wild-type and treatment failure MIC distribution data.

Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis.

BACKGROUND: There is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens. METHODS: The online databases PubMed and Medline were searched using terms "Mycoplasma genitalium", "macrolide" or "azithromycin" and "resistance" up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates. RESULTS: Eight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027). CONCLUSION: Azithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.

Cross-sectional study to evaluate Trichomonas vaginalis positivity in women tested for Neisseria gonorrhoeae and Chlamydia trachomatis, attending genitourinary medicine and primary care clinics in Bristol, South West England.

BACKGROUND: Highly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings. METHODS: Samples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests. RESULTS: T. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24/530, symptomatic) and 1.7% (27/1584, asymptomatic); in primary care 2.7% (94/3499, symptomatic) and 1.2% (41/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost £260 per positive case diagnosed compared with £716 using current microbiological tests. CONCLUSIONS: Aptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.

Mycoplasma genitalium Infection in Men.

Mycoplasmagenitalium is one of the major causes of nongonococcal urethritis (NGU) worldwide but an uncommon sexually transmitted infection (STI) in the general population. The risk of sexual transmission is probably lower than for Chlamydia trachomatis. Infection in men is usually asymptomatic and it is likely that most men resolve infection without developing disease. The incubation period for NGU caused by Mycoplasma genitalium is probably longer than for NGU caused by C. trachomatis. The clinical characteristics of symptomatic NGU have not been shown to identify the pathogen specific etiology. Effective treatment of men and their sexual partner(s) is complicated as macrolide antimicrobial resistance is now common in many countries, conceivably due to the widespread use of azithromycin 1 g to treat STIs and the limited availability of diagnostic tests for M. genitalium. Improved outcomes in men with NGU and better antimicrobial stewardship are likely to arise from the introduction of diagnostic M. genitalium nucleic acid amplification testing including antimicrobial resistance testing in men with symptoms of NGU as well as in their current sexual partner(s). The cost effectiveness of these approaches needs further evaluation. The evidence that M. genitalium causes epididymo-orchitis, proctitis, and reactive arthritis and facilitates human immunodeficiency virus transmission in men is weak, although biologically plausible. In the absence of randomized controlled trials demonstrating cost effectiveness, screening of asymptomatic men cannot be recommended.

Management of non-gonococcal urethritis.

Non-gonococcal urethritis (NGU), or inflammation of the urethra, is the most common treatable sexually transmitted syndrome in men, with approximately 20-50 % of cases being due to infection with Chlamydia trachomatis and 10-30 % Mycoplasma genitalium. Other causes are Ureaplasma urealyticum, Trichomonas vaginalis, anaerobes, Herpes simplex virus (HSV) and adenovirus. Up to half of the cases are non-specific. Urethritis is characterized by discharge, dysuria and/or urethral discomfort but may be asymptomatic. The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear. An excess of mononuclear leucocytes in the smear indicates a viral etiology. In patients presenting with symptoms of urethritis, the diagnosis should be confirmed by microscopy of a stained smear, ruling out gonorrhea. Nucleid acid amplifications tests (NAAT) for Neisseria gonorrhoeae, C. trachomatis and for M. genitalium. If viral or protozoan aetiology is suspected, NAAT for HSV, adenovirus and T. vaginalis, if available. If marked symptoms and urethritis is confirmed, syndromic treatment should be given at the first appointment without waiting for the laboratory results. Treatment options are doxycycline 100 mg x 2 for one week or azithromycin 1 gram single dose or 1,5 gram distributed in five days. However, azithromycin as first line treatment without test of cure for M. genitalium and subsequent Moxifloxacin treatment of macrolide resistant strains will select and increase the macrolide resistant strains in the population. If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment. If positive in test of cure, moxifloxacin 400 mg 7-14 days is indicated. Current partner(s) should be tested and treated with the same regimen. They should abstain from intercourse until both have completed treatment. Persistent or recurrent NGU must be confirmed with microscopy. Reinfection and compliance must be considered. Evidence for the following recommendations is limited, and is based on clinical experience and guidelines. If doxycycline was given as first therapy, azithromycin five days plus metronidazole 4-500 mg twice daily for 5-7 days should be given. If azithromycin was prescribed as first therapy, doxycycline 100 mg x 2 for one week plus metronidazole, or moxifloxacin 400 mg orally once daily for 7-14 days should be given.

Time to manage Mycoplasma genitalium as an STI: but not with azithromycin 1 g!

PURPOSE OF REVIEW: Mycoplasma genitalium is a sexually transmitted infection that causes significant morbidity in men and women and is a co-factor in HIV transmission. However, commercial diagnostic tests are not generally available for M. genitalium and sub-optimal treatment is often given. We review the literature on the burden of infection, how it may present in clinical practice and the effectiveness of current treatment regimens. RECENT FINDINGS: In-vivo and in-vitro data strongly suggest that M. genitalium is an important cause of urethritis, cervicitis, pelvic inflammatory disease and potentially asymptomatic proctitis. Studies now consistently demonstrate suboptimal eradication rates with the current treatment regimens recommended first line for the treatment of nongonococcal urethritis. Concurrently, there has been a rapid emergence of antibiotic resistance in M. genitalium, with macrolide resistance now appearing to be endemic in some centres, and quinolone resistance is beginning to emerge. SUMMARY: In the absence of specific M. genitalium diagnostic and antimicrobial resistance testing, azithromycin 1 g should not be used for the management of patients with symptomatic disease potentially caused by M. genitalium. This review offers an alternative evidence-based approach to managing such patients that should, theoretically, reduce the risk of the development of antimicrobial resistance.

An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England.

OBJECTIVES: To estimate the costs and benefits of clinical pathways incorporating a point of care (POC) nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea in genitourinary medicine (GUM) clinics compared with standard off-site laboratory testing. METHOD: We simulated 1.2 million GUM clinic attendees in England. A simulation in Microsoft Excel was developed to compare existing standard pathways of management for chlamydia and gonorrhoea with a POC NAAT. We conducted scenario analyses to evaluate the robustness of the model findings. The primary outcome was the incremental cost-effectiveness ratio. Secondary outcomes included the number of inappropriate treatments, complications and transmissions averted. RESULTS: The baseline cost of using the point of POC NAAT was £103.9 million compared with £115.6 million for standard care. The POC NAAT was also associated with a small increase of 46 quality adjusted life years, making the new test both more effective and cheaper. Over 95 000 inappropriate treatments might be avoided by using a POC NAAT. Patients receive diagnosis and treatment on the same day as testing, which may also prevent 189 cases of pelvic inflammatory disease and 17 561 onward transmissions annually. DISCUSSION: Replacing standard laboratory tests for chlamydia and gonorrhoea with a POC test could be cost saving and patients would benefit from more accurate diagnosis and less unnecessary treatment. Overtreatment currently accounts for about a tenth of the reported treatments for chlamydia and gonorrhoea and POC NAATs would effectively eliminate the need for presumptive treatment.

Effect of time since exposure to Chlamydia trachomatis on chlamydia antibody detection in women: a cross-sectional study.

OBJECTIVES: To investigate what factors influence the detection of Chlamydia trachomatis antibody following genital tract infection. METHODS: One hundred and sixty-four women with a previous history of C trachomatis infection contributed to an earlier report on the performance of chlamydia antibody ELISA assays. We undertook further analysis to explore how chlamydia antibody assay sensitivity changes with time since infection. RESULTS: Chlamydia antibody was detected in more women soon after the last detection of chlamydia at the lower genital tract than at later times. This holds true for all tests, but the Anilabsystems IgG EIA, Medac pELISA plus ELISA and the Savyon SeroCT-IgG ELISA were less sensitive than the pgp3 ELISA and the Anilabsystems microimmunofluorescence (MIF) assay at all time points except during current infection. Fall in seropositivity in women generally occurred in the early weeks and months following the last episode of chlamydia infection. There was no clear pattern of further reduction in seropositivity after 6 months. Multiple previous episodes were associated with increased seropositivity in the pgp3 assay (two or more vs one, OR 19, p<0.001) and other tests, but the effect was significantly smaller for the Anilabs, Medac and SeroCT MOMP peptide ELISAs, but not for the MIF assay. CONCLUSIONS: Chlamydia antibody detection decreases with time since infection and this is most apparent in the first 6 months. In women who have had more than one infection, antibody remained detectable longer for all tests, but this was more marked for the pgp3 ELISA and MIF assay.

Can we improve partner notification rates through expedited partner therapy in the UK? Findings from an exploratory trial of Accelerated Partner Therapy (APT).

OBJECTIVES: To develop two new models of expedited partner therapy for the UK, and evaluate them for feasibility, acceptability and preliminary outcome estimates to inform the design of a randomised controlled trial (RCT). METHODS: Two models of expedited partner therapy (APTHotline and APTPharmacy), known as 'Accelerated Partner Therapy' (APT) were developed. A non-randomised comparative study was conducted of the two APT models and routine partner notification (PN), in which the index patient chose the PN option for his/her partner(s) in two contrasting clinics. RESULTS: The proportion of contactable partners treated when routine PN was chosen was 42/117 (36%) and was significantly higher if either APT option was chosen: APTHotline 80/135 (59%), p=0.003; APTPharmacy 29/44 (66%) p=0.001. However, partner treatment was often achieved through other routes. Although 40-60% of partners in APT groups returned urine samples for sexually transmitted infection (STI) testing, almost none accessed HIV and syphilis testing. APT options appear to facilitate faster treatment of sex partners than routine PN. Preferences and recruitment rates varied between sites, related to staff satisfaction with existing routine PN; approach to consent; and possibly, characteristics of local populations. CONCLUSIONS: Both methods of APT were feasible and acceptable to many patients and led to higher rates of partner treatment than routine PN. Preferences and recruitment rates varied greatly between settings, suggesting that organisational and cultural factors may have an important impact on the feasibility of an RCT and on outcomes. Mindful of these factors, it is proposed that APT should now be evaluated in a cluster RCT.

Immunity and vaccines against sexually transmitted Chlamydia trachomatis infection.

PURPOSE OF REVIEW: The aim is to review recent findings on immunity and vaccine development to Chlamydia trachomatis. RECENT FINDINGS: There is increasing knowledge on the interactions between C. trachomatis and infected host cells. During genital infection the organism avoids generating protective immunity but immune responses to a number of chlamydial proteins have been associated with reproductive tract pathology. Various vaccine and adjuvant preparations have been tried experimentally. Information generated by proteomics and complex studies of serological and T-lymphocyte immune responses points to novel vaccine candidates. SUMMARY: C. trachomatis, an obligate intracellular bacterium, is the commonest sexually transmitted infection worldwide and is associated with reproductive pathology. To develop rational vaccines it is necessary to understand the complex lifecycle of the organism, the host immune response to infection and how these relate to disease. Infection does not prevent re-infection and antibiotic treatment prevents antibody production at a population level. It remains unclear what type of immune response would be sufficient to prevent infection and/or re-infection. Although the prevalence and demographics of infection and the severity of disease associations suggest that it would be desirable, there is no vaccine currently available. A number of studies have identified novel vaccine candidates.