National survey data designed to delineate clinician perspectives on the indications to hospitalize adolescents for pelvic inflammatory disease indicate that clinicians endorse care consistent with the Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines but that there is less agreement on the social factors that may impair an adolescent's ability to self-care in the outpatient setting.

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.

BACKGROUND:

Vaginal douching (VD) is a common practice among married women all over the world specially those in the Middle East. It is used for personal hygiene or for other aesthetic reasons in many countries. The current study investigates the prevalence of VD among patients with vulvovaginitis in Egypt. It also compares the reproductive health hazards among women performing routine VD with those using external hygiene. It also investigates why, and how women practice this douching.

METHODS:

A cross sectional observational study was conducted in a tertiary university affiliated hospital in Assiut, Egypt. An interview administered questionnaire was administered to 620 women by two trained clinic nurse. Women presented to the outpatient clinic and diagnosed to have any type of vaginal infections were approached for participation. The principle outcome was the history of preterm labor in women who routinely performed VD versus those who did not (upon which sample size was estimated). Other outcome measures were the types of vaginal infections, and reproductive implications comprising, ectopic pregnancy, abortion and pelvic inflammatory disease (PID).

RESULTS:

The participants were predominantly multiparas from semi-urban background and middle socioeconomic level. Considering VD as a religious duty and a kind of personal cleanliness were the most common reasons for performing VD in 88.9% and 80.6% of the studied population, respectively. History of preterm labor was reported in 19.2% versus 11.9% (p=0.048), while history of PID in 13.2% versus 6.0% (p=0.008) in women performing VD compared to those not performing this habit, respectively. There were no significant differences between the two groups as regard the history of ectopic pregnancy or the number of previous abortions.

CONCLUSION:

Vaginal douching is a prevalent practice in Egypt and has traditional and religious roots within the community. There are many misbeliefs around this habit in Egypt. Vaginal douching increases certain reproductive health hazards especially preterm labor and PID. Much effort and awareness campaigns are needed to increase women awareness about health hazards of this incorrect practice and to limit its use.

Mycoplasma genitalium is a significant sexually transmitted pathogen, causing up to 25% of cases of non-gonococcal urethritis in men and is strongly associated with cervicitis and pelvic inflammatory disease in women. Currently, the usual first-line treatment is with the macrolide antibiotic, azithromycin, but an increasing incidence of treatment failure over the last five years suggests emergence of resistance. Mutations responsible for macrolide resistance have been found in the 23S rRNA gene (23S rDNA) in numerous M. genitalium populations. A second-line antibiotic, the fluoroquinolone moxifloxacin, was thought to be a reliable alternative when azithromycin failed, but recent studies have identified mutations in the genes, parC and gyrA, that may confer fluoroquinolone resistance.The aim of this study was to determine the prevalence of antibiotic resistance in M. genitalium in Sydney, Australia, by detection of relevant mutations in 23S rDNA, parC and gyrA. M. genitalium-positive DNA extracts of specimens, collected from patients attending sexual health clinics in Sydney, were tested by PCR amplification and DNA sequence alignment. The 186 specimens tested included 143 initial patient specimens, and 43 second, or subsequent, specimens from 24 patients. We identified known macrolide resistance-associated mutations in 23S rDNA of 43%, and mutations potentially associated with fluoroquinolone resistance in parC or gyrA sequences of 15%, of initial patient samples. These findings support anecdotal clinical reports of azithromycin and moxifloxacin treatment failures in Sydney. Our results indicated that further surveillance is needed and testing and treatment protocols for M. genitalium infections may need to be reviewed.

The "silent epidemic" of Chlamydia trachomatis threatens to cause reproductive damage and infertility in many of the 50 million women who acquire it each year. Female reproductive tract infection has more recently been linked to stillbirth and premature delivery. Innate immune cells and mediators appear to be the primary players in pathogenesis, with neutrophils playing a prominent role in disease development. Although adaptive antibody and CD4 T cell responses appear primarily protective, these responses are inefficient. Infections are frequently chronic as a result, and when infection is diagnosed and treated with appropriate antibiotics, repeated infection is the rule. The lack of acute symptoms in many infected individuals contributes to the high prevalence of chlamydial infection. Although chronic sequelae are relatively rare in men, and many women sustain infection without developing pelvic inflammatory disease or chronic sequelae, the extremely high prevalence of chlamydial infection leads to significant morbidity and healthcare costs. A vaccine is urgently needed to prevent infection, but given the difficulties of inducing a CD4 T cell memory response that can home quickly to the genital tract, induction of sterilizing immunity may not be possible. A vaccine that prevents disease by lowering bacterial burden and dampening production of tissue-damaging responses may be possible. Until an efficacious vaccine is developed, screening and treatment programs appear to be the best method of disease prevention.

Correctly diagnosing pelvic inflammatory disease (PID) using noninvasive clinical criteria remains challenging. Current guidelines for initiating treatment, based on minimal criteria (sensitive but not specific), are justified for public health purposes but inadequate and misleading for scientific purposes. Previous research on the link between the intrauterine device (IUD) and PID was controversial and subject to many limitations. Even today, these limitations still exist and include uncertainty of the PID diagnosis, unfair contraceptive comparisons, selection and diagnostic bias, and confounding. For example, IUD users are on heightened alert for PID relative to users of other methods. In addition, IUD users with pelvic pain may be more likely to seek physician consultation and consequently receive a PID diagnosis (true-positive or false-positive). Confounding factors such as higher coital frequency, multiple sexual partners, and low condom use may explain any finding that shows a higher PID rate among IUD users compared with other contraceptive users. Good evidence on how or whether the IUD changes the etiology of PID is lacking. In the past 10 years, use of the intrauterine device in the United States has increased markedly. Thus today, researchers may now have sufficient population-level exposure (IUD use) and disease (PID) to search for a connection and repeat past mistakes. Any new findings using observational research should be interpreted with caution. More rigorous research designs may not be pragmatic or feasible.

: Many U.S. health care providers remain reluctant to prescribe intrauterine devices (IUDs) to teenagers as a result of concerns about serious complications. This study examined whether 15-19-year-old IUD users were more likely to experience complications, failure, or early discontinuation than adult users aged 20-24 years and 25-44 years and whether there were differences in these outcomes between users of levonorgestrel-releasing intrauterine systems and copper IUDs.: A retrospective cohort study was conducted using health insurance claims obtained from a private insurance company of 90,489 women who had an IUD inserted between 2002 and 2009. Logistic regression models were used to estimate the odds of experiencing complications, method failure, or early discontinuation within 12 months of insertion by age group and type of IUD inserted.: Serious complications, including ectopic pregnancy and pelvic inflammatory disease, occurred in less than 1% of patients regardless of age or IUD type. Women aged 15-19 years were more likely than those aged 25-44 years to have a claim for dysmenorrhea (odds ratio [OR] 1.4, confidence interval [CI] 1.1-1.6), amenorrhea (OR 1.3, CI 1.1-1.5), or normal pregnancy (OR 1.4, CI 1.1-1.8). Overall, early discontinuation did not differ between teenagers and women aged 25-44 years (13% compared with 11%, P>.05). However, use of the levonorgestrel-releasing intrauterine system was associated with fewer complications and less early discontinuation than the copper IUD in all age groups.: The IUD is as appropriate for teenagers to use as it is for older women, with serious complications occurring infrequently in all groups. The levonorgestrel-releasing intrauterine system may be a better choice than the copper IUD as a result of lower odds of complications, discontinuation, and failure.: II.

ABSTRACT

STING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ligand remains unknown. In this report, we provide evidence that Chlamydia synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite not previously identified in Gram-negative bacteria, and that this metabolite is a prominent ligand for STING-mediated activation of IFN responses during infection. We used primary mouse lung fibroblasts and HEK293T cells to compare IFN-β responses to Chlamydia infection, c-di-AMP, and other type I IFN-inducing stimuli. Chlamydia infection and c-di-AMP treatment induced type I IFN responses in cells expressing STING but not in cells expressing STING variants that cannot sense cyclic dinucleotides but still respond to cytoplasmic DNA. The failure to induce a type I IFN response to Chlamydia and c-di-AMP correlated with the inability of STING to relocalize from the endoplasmic reticulum to cytoplasmic punctate signaling complexes required for IFN activation. We conclude that Chlamydia induces STING-mediated IFN responses through the detection of c-di-AMP in the host cell cytosol and propose that c-di-AMP is the ligand predominantly responsible for inducing such a response in Chlamydia-infected cells. IMPORTANCE This study shows that the Gram-negative obligate pathogen Chlamydia trachomatis, a major cause of pelvic inflammatory disease and infertility, synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite that thus far has been described only in Gram-positive bacteria. We further provide evidence that the host cell employs an endoplasmic reticulum (ER)-localized cytoplasmic sensor, STING (stimulator of interferon [IFN] genes), to detect c-di-AMP synthesized by Chlamydia and induce a protective IFN response. This detection occurs even though Chlamydia is confined to a membrane-bound vacuole. This raises the possibility that the ER, an organelle that innervates the entire cytoplasm, is equipped with pattern recognition receptors that can directly survey membrane-bound pathogen-containing vacuoles for leaking microbe-specific metabolites to mount type I IFN responses required to control microbial infections.

Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide and leads to serious pathological sequelae in the upper genital tract (UGT) including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several components of the host immune responses have been shown to contribute to the UGT pathology following genital chlamydial infection. We have shown recently that CD8(+) T cells induce the chlamydial UGT pathology via the production of TNF-α. However, those studies did not determine whether the pathology is mediated by bystander or antigen-specific CD8(+) T cells. In this study, we compared chlamydial clearance and UGT pathology in OT-1 transgenic mice and the corresponding C57BL/6J wild-type mice following primary intravaginal Chlamydia muridarum infection. All CD8(+) T cells in the OT-1 mice respond only to the Ova 257-264 peptide and are incapable of responding to other antigenic epitopes including those of Chlamydia. OT-1 mice displayed vaginal chlamydial clearance comparable to the wild-type animals. However, both oviduct and uterine horn pathology were minimal in the OT-1 mice compared with the high degree of pathology observed in the wild-type animals. These results strongly suggest that Chlamydia-specific, not bystander, CD8(+) T cells mediate the UGT pathological sequelae following genital chlamydial infection.