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Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

Mycoplasma genitalium is associated with acute and chronic urethritis in men. Existing data on infection in women are limited and inconsistent but suggest that M.genitalium is associated with urethritis, cervicitis, pelvic inflammatory disease, and possibly female infertility. Data are inconclusive regarding the role of M.genitalium in adverse pregnancy outcomes and ectopic pregnancy. Available data suggest that azithromycin is superior to doxycycline in treating M. genitalium infection. However, azithromycin-resistant infections have been reported in 3 continents, and the proportion of azithromycin-resistant M.genitalium infection is unknown. Moxifloxacin is the only drug that currently seems to uniformly eradicate M. genitalium.Detection of M.genitalium is hampered by the absence of a commercially available diagnostic test. Persons with persistent pelvic inflammatory disease or clinically significant persistent urethritis or cervicitis should be tested for Af.genitalium, if possible. Infected persons who have not previously received azithromycin should receive that drug. Persons in whom azithromycin therapy fails should be treated with moxifloxicin.

The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.

Cervicitis is one of the major health problems amongst women caused by infection of various pathogens including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) as well as human papillomavirus (HPV), and persistent cervical inflammation is one of the etiologic agents of cervical cancer. Toll-like receptors (TLRs) play an important role in the recognition and subsequent elimination of these pathogens. Variations in the Toll-like receptor genes influence susceptibility to pathogens as well as disease progression independently. Ten single nucleotide polymorphisms, five each of TLR4 and TLR9 genes were analyzed among 130 cervicitis patients and 150 controls either using polymerase chain reaction-restriction fragment length polymorphism or allele specific-PCR. T. vaginalis infection was found at the highest frequency (30.7%) as compared to C. trachomatis (1.5%), N. gonorrhoeae (2.3%) and HPV (4.6%) infections in cervicitis patients. TLR4 rs11536889 CC (age-adjusted OR, 2.469 [95% CI, 1.499 to 4.065]; p < 0.001) and TLR9 rs187084 TC (age-adjusted OR, 2.165 [95% CI, 1.267-3.699]; p = 0.005) genotypes showed the higher distribution in cervicitis patients compared to controls. In addition, TLR4 rs11536889 C allele was shown to increase the risk of cervicitis (age-adjusted OR, 1.632 [95% CI, 1.132 to 2.352]; p = 0.009) compared to controls. The TLR4 haplotype GCA (OR, 0.6 [95% CI, 0.38-0.95]; p = 0.0272) and TLR9 haplotype GTA (OR, 1.99 [95% CI, 1.14-3.48]; p = 0.014) were found to be associated with decreased and increased risk of cervicitis respectively. TLR4 and TLR9 polymorphisms, as well as haplotypes were shown to modulate the cervicitis risk.

Health consequences of sexually transmitted diseases disproportionately affect women, making it important to determine whether newly emerged pathogens cause sequelae. Although the pathogenic role of Mycoplasma genitalium in male urethritis is clear, fewer studies have been conducted among women to determine its pathogenic role in the female reproductive tract. Pelvic inflammatory disease (PID) is an important cause of infertility and ectopic pregnancy, and Chlamydia trachomatis and Neisseria gonorrhoeae are recognized microbial causes. Emerging data demonstrate an association between M. genitalium and PID, and limited data suggest associations with infertility and preterm birth, yet the attributable risk for female genital tract infections remains to be defined. Further investigations are needed to better define the impact of M. genitalium on women's reproductive health. Importantly, prospective studies evaluating whether screening programs and targeted treatment of M. genitalium improve reproductive outcomes in women are necessary to guide public health policy for this emerging pathogen.

Background. Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group. Methods. Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial. Results. HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3–7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines. Conclusions. Elevated genital concentrations of HIV target cell–recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.

Mucopurulent cervicitis (MPC) is a clinical syndrome characterized by mucopurulent discharge from the cervix and other signs of inflammation. This was a phase III, multicenter study designed to evaluate the effectiveness of placebo versus empiric antibiotic treatment for clinical cure of MPC of unknown etiology at 2-month follow-up. Unfortunately, enrollment was terminated because of low accrual of women with cervicitis of unknown etiology, but important prevalence and outcome data were obtained. Five hundred seventy-seven women were screened for MPC. Women with MPC were randomized to the treatment or placebo arm of the study, and the 2 arms were evaluated based on the etiology, clinical cure rates, adverse events (AEs), and rates of pelvic inflammatory disease. One hundred thirty-one (23% [131/577]) screened women were found to have MPC. Eighty-seven were enrolled and randomized. After excluding women with sexually transmitted infections and other exclusions, 61% (53/87) had cervicitis of unknown etiology. The overall clinical failure rate was 30% (10/33), and the clinical cure rate was only 24% (8/33). Rates were not significantly different between the arms. There were 24 gastrointestinal AEs in the treatment arm compared with 1 AE in the placebo arm. More than half of the cases of MPC were of unknown etiology. Clinical cure rates for the placebo and treatment arms were extremely low, with most women concluding the study with a partial response. Gastrointestinal AEs were higher in the treatment arm.

To determine the association between Mycoplasma genitalium infection and female reproductive tract syndromes through meta-analysis, English-language, peer-reviewed studies were identified via PubMed, Embase, Biosis, Cochrane Library, and reference review. Two reviewers independently extracted data. Random-effects models were employed to calculate summary estimates, between-study heterogeneity was evaluated using I2 statistics, publication bias was assessed via funnel plots and the Begg and Egger tests, and methodologic quality was rated. Mycoplasma genitalium infection was significantly associated with increased risk of cervicitis (pooled odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.35–2.04]), pelvic inflammatory disease (pooled OR, 2.14 [95% CI, 1.31–3.49]), preterm birth (pooled OR, 1.89 [95% CI, 1.25–2.85]), and spontaneous abortion (pooled OR, 1.82 [95% CI, 1.10–3.03]). Risk of infertility was similarly elevated (pooled OR, 2.43 [95% CI, .93–6.34]). In subanalyses accounting for coinfections, all associations were stronger and statistically significant. Testing of high-risk symptomatic women for M. genitalium may be warranted.

Clinical diagnoses of cervicitis and pelvic inflammatory disease (PID) are often subjective, and not all are associated with sexually transmitted infections (STI). Presumptive treatment for these syndromes may lead to unnecessary antibiotics in those subsequently found to be STI-negative. We investigated patient and clinician characteristics associated with accurately diagnosing bacterial STI-positive cervicitis and PID. We quantified the amount of unnecessary antibiotics prescribed in STI-negative cases. A cross-sectional study of 243 cervicitis and 179 PID patients presenting to Sydney Sexual Health Centre between January 2020 and 2023 was conducted. Patient demographics, sexual behaviours, symptoms, examination, results and clinician type were extracted from electronic medical records. A total of 70 cervicitis (28.8%) and 28 PID (15.6%) patients were bacterial-STI positive. Age <25 years (aOR 2.78, 95% CI 1.25-6.25, P < 0.001) was associated with bacterial STI-positive cervicitis; presence of endocervical mucopurulent discharge on examination (aOR 6.05, 95% CI 2.20-16.68, P < 0.001) and current use of contraception (aOR 7.69, 95% CI 2.13-25.00, P = 0.002) were associated with bacterial STI-positive PID. For cervicitis, there were 139 doxycycline, 11 azithromycin and 5 ceftriaxone courses that were given to STI-negative patients. For PID, there were 148 doxycycline, 7 azithromycin and 152 ceftriaxone courses that were given to STI-negative patients. This study identified several characteristics that predicted STI-positive cervicitis and PID. However, none predicted STI-positivity with high degrees of confidence. Presumptive treatment leads to significant unnecessary antibiotic use, but ceftriaxone may have additional coverage beyond gonorrhoea. Rapid molecular point-of-care testing should be trialled to reduce unnecessary antibiotics for these syndromes - starting with cervicitis.

Background Cervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions. Case presentation A 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae . There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms. Conclusion Herpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment.