Chlamydia-infected Women Research Articles

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies.

Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.

Mycoplasma genitalium Coinfection in Women With Chlamydia trachomatis Infection.

We evaluated the prevalence of Mycoplasma genitalium coinfection in 302 chlamydia-infected women seen at a sexually transmitted disease clinic in Birmingham, AL. M genitalium coinfection was detected in 22 (7.3%). No participant characteristics predicted coinfection. Among coinfected women, M genitalium was detected again in 6 (28.6%) of 21 women returning for a 3-month follow-up visit after azithromycin treatment.

Stimulated peripheral blood mononuclear cells from chlamydia-infected women release predominantly Th1-polarizing cytokines

Chlamydia trachomatis infection (chlamydia) is the most prevalent sexually transmitted bacterial infection and causes significant reproductive morbidity in women. Little is known about how immunity to chlamydia develops in women, though animal models of chlamydia indicate that T-helper type 1 (Th1) responses are important for chlamydia clearance and protective immunity, whereas T-helper type 2 (Th2) responses are associated with persisting infection. In chlamydia-infected women, whether the predominant immune response is Th1- or Th2-polarizing remains controversial. To determine the cytokine profiles elicited by peripheral blood mononuclear cells (PBMCs) from chlamydia-infected women, we stimulated PBMCs with C. trachomatis elementary bodies and recombinant C. trachomatis Pgp3 and measured supernatant levels of select cytokines spanning Th1- and Th2-polarizing responses. We found that stimulated PBMCs from chlamydia-infected women secreted cytokines that indicate strong Th1-polarizing responses, especially interferon-gamma, whereas Th2-polarizing cytokines were expressed at significantly lower levels. In chlamydia-infected women, the predominant cytokine responses elicited on stimulation of PBMCs with C. trachomatis antigens were Th1-polarizing, with interferon-gamma as the predominant cytokine.

Tissue Specific Overexpression of Human Heat Shock Protein 70 in Mouse Oviduct Epithelium Reduces Chlamydia Induced Immunopathology

Abstract Chlamydia trachomatis genital infections lead to severe immunopathological consequences in the upper genital tract (UGT), including pelvic inflammatory disease and infertility, in a small subset of infected women. Heat shock protein 70 (Hsp70) is an evolutionarily conserved stress-induced protein and has been shown to exhibit significant cytoprotective and immunoregulatory activities. However, the role of Hsp70 in genital chlamydial pathologies had not been examined. Hsp70 transgenic (Hsp70 Tg) mice were created by injecting a villin promoter-driven human Hsp70 targeting vector into C57BL/6 oocytes. The villin promoter is active only in the epithelium of the mouse oviduct but not in other parts of the female mouse genital tract. Female, 6-8 week old, Hsp70 Tg and non-transgenic (NTG) littermates were infected intravaginally with 5×104 IFU of C. muridarum. Vaginal chlamydial shedding, bacterial burden in the upper genital tract including oviducts and uterine horns, Chlamydia-specific IFN-γ, TNF-α, and IL-17 production, and serum anti-Chlamydia antibody levels were comparable between NTG and Hsp70 Tg mice. However, at day 80 after inoculation, the incidence and severity of pathology in oviducts, not neighboring uterine horns, was significantly reduced in Hsp70 Tg mice compared to NTG mice. Given the highly polymorphic nature of hsp-70 gene and associated susceptibility to various inflammatory conditions, and the occurrence of immunopathology in only a subset of Chlamydia-infected women, these results also underscore the need to further evaluate the role of hsp-70 in chlamydial immunopathogenesis in the female upper reproductive tract.

IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage.

Genital Chlamydia trachomatis infections in women typically are asymptomatic and do not cause permanent upper genital tract (UGT) damage. Consistent with this presentation, type 2 innate and TH2 adaptive immune responses associated with dampened inflammation and tissue repair are elicited in the UGT of Chlamydia-infected women. Primary C. trachomatis infection of mice also causes no genital pathology, but unlike women, does not generate Chlamydia-specific TH2 immunity. Herein, we explored the significance of type 2 innate immunity for restricting UGT tissue damage in Chlamydia-infected mice, and in initial studies intravaginally infected wild-type, IL-10-/-, IL-4-/-, and IL-4Rα-/- mice with low-dose C. trachomatis inoculums. Whereas Chlamydia was comparably cleared in all groups, IL-4-/- and IL-4Rα-/- mice displayed endometrial damage not seen in wild-type or IL-10-/- mice. Congruent with the aberrant tissue repair in mice with deficient IL-4 signaling, we found that IL-4Rα and STAT6 signaling mediated IL-4-induced endometrial stromal cell (ESC) proliferation ex vivo, and that genital administration of an IL-4-expressing adenoviral vector greatly increased in vivo ESC proliferation. Studies with IL-4-IRES-eGFP (4get) reporter mice showed eosinophils were the main IL-4-producing endometrial leukocyte (constitutively and during Chlamydia infection), whereas studies with eosinophil-deficient mice identified this innate immune cell as essential for endometrial repair during Chlamydia infection. Together, our studies reveal IL-4-producing eosinophils stimulate ESC proliferation and prevent Chlamydia-induced endometrial damage. Based on these results, it seems possible that the robust type 2 immunity elicited by Chlamydia infection of human genital tissue may analogously promote repair processes that reduce phenotypic disease expression.

The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.

Feasibility of Chlamydia trachomatis screening and treatment in pregnant women in Lima, Peru: a prospective study in two large urban hospitals

ObjectivesChlamydia trachomatis, which is asymptomatic in most women, causes significant adverse effects for pregnant women and neonates. No programmes conduct antenatal screening in Latin America. We determined chlamydia prevalence, feasibility...

Characteristics and predictors of women who obtain rescreening for sexually transmitted infections using the www.iwantthekit.org screening programme.

Professional organizations recommend rescreening chlamydia-infected women. The iwantthekit Internet-screening programme offered rescreening opportunities by using iwantthekit. Mailed, home-collected vaginal swabs were tested for chlamydia, gonorrhoea, and trichomoniasis by nucleic acid amplification tests. Demographics and risk behaviours of repeat users were determined from questionnaires. Predictors of repeat users were measured in a matched case-control study. Of 1747 women, 304 (17%), who used iwantthekit, indicated they had used the kit previously. Mean age was 24.7 ± 5.7 years and 69% were African-American. Repeat iwantthekit users were more likely to be aged ≥ 20 years (OR=2.10); were more likely to have been treated for a sexually transmitted infection (OR=2.32); less likely to drink alcohol before sex (OR=0.63); and to never use condoms (OR=0.43). Of repeat users, 84.2% had a negative prior test and 15.8% had a positive. At current test, 13.2% were infected. Previous trichomoniasis was associated with current trichomoniasis (p<0.05). The iwantthekit may offer rescreening opportunities for previously infected women.

Timing of progression from Chlamydia trachomatisinfection to pelvic inflammatory disease: a mathematical modelling study

BackgroundPelvic inflammatory disease (PID) results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia) might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection.MethodsWe develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT) and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT.ResultsThe predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13%) in both processes.ConclusionsThe findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

Does CCR5 gene-D32 deletion protect C.trachomatis infected Indian women from tubal pathology?

Deletion in chemokine receptor CCR5 gene is reported to prevent development of tubal pathology among Dutch Caucasian C. trachomatis infected women. Hence, a pilot study was undertaken, to evaluate the involvement of CCR5 gene in tubal pathology among Indian women with or without Chlamydia infection. Three hundred women with or without Chlamydia infection and with different reproductive manifestations were screened for CCR5 gene using a standardized PCR. Only 6 C. trachomatis infected women without tubal block had heterozygous deletion for this gene. The rest had wild type CCR5 gene, that includes fertile women infected and non infected; infertile women infected and non infected with and without tubal block as well as infected women with history of recurrent spontaneous abortions. The study indicates no role of heterozygous CCR5 D32 gene deletion in prevention of tubal pathology in Chlamydia infected Indian women. Only 2% heterozygous deletion in CCR5 gene is observed in the studied population.

Can E-Technology Through the Internet be Used as a New Tool to Address the Chlamydia trachomatis Epidemic by Home Sampling and Vaginal Swabs?

The Internet provides patients, as well as clinicians with immediate, confidential access to information about sexually transmitted diseases (STDs).1,2 Young individuals are avid users of the Internet and usage has been considered to be a risk factor for STDs.3–7 Data indicate that there are 246,402,574 North American Internet users.8

The incidence of pelvic inflammatory disease in untreated women infected with Chlamydia trachomatis: a structured review

Because of the long-term consequences of pelvic inflammatory disease (PID), the cost-effectiveness of Chlamydia trachomatis screening depends in part on the incidence of PID in untreated, chlamydia-infected women. The aim of this study was to evaluate the original research assessing the incidence of PID following C. trachomatis infection. We conducted a thorough search of the literature and selected all available prospective cohort studies. Six studies had original data: the incidence of PID varied from 0% (97.5% confidence interval [CI] 0-12%) during one year of follow-up of 30 women to 30% (95% CI 12-54%) during 50 days of follow-up of 20 women. Studies that included asymptomatic women in other settings reported a lower incidence than those that evaluated women in sexually transmitted disease clinics. In conclusion, no study was of a size or quality to answer our research question definitively. Investigators and clinicians planning chlamydia-screening programmes need to be cognizant of the inconclusive incidence data.

Inflammation on liquid-based cervical cytology: can leukocytes be used to triage for Chlamydia trachomatis testing?

The study was undertaken to investigate whether leukocytes on liquid-based cervical cytology can predict Chlamydia trachomatis infection. A retrospective case-control study of females under 30 years examined the association between leukocytes on liquid-based cervical cytology and C. trachomatis infection. Smears from chlamydia-infected women had an average of 30.7 leukocytes and a median of 25.4 leukocytes per high-powered field (hpf), whereas smears from controls had an average of 11.5 leukocytes and a median of 7.1 leukocytes per hpf. The median leukocyte to epithelial cell ratio among infected women was 1.4 vs 0.6 in the controls (P < .05). No clear cutpoint of leukocytes to epithelial cells was identified that could serve to detect the maximal number of infected women while minimizing the testing of uninfected women. There is an association between inflammation on liquid-based cervical cytology and C. trachomatis infection. However, assessing for leukocytes cannot be recommended as a triage for chlamydia screening, as there is great overlap in inflammation among infected and uninfected women.

A comparison of amoxicillin and erythromycin for asymptomatic Chlamydia trachomatis infection in pregnancy

Chlamydia trachomatis is recognized as the most common sexually transmitted disease among women of reproductive age. Diagnosis and treatment of chlamydia-infected women before delivery are prudent and cost-effective means of preventing prenatal and neonatal complications of chlamydia infection. Currently recommended medications for pregnant women include erythromycin amoxicillin and azithromycin. A randomized cohort trial was carried out between October 2003 and March 2004 at Shiraz University of Medical Sciences. It included 92 pregnant women receiving care at 2 prenatal clinics who had been found IgM-and IgG-positive for Chlamydia trachomatis by the ELISA method. The women were randomly divided into 3 groups. (excerpt)

Chlamydia and other sexually transmitted bacterial infections

Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. In Western Europe, the prevalence of gonorrhoea has decreased by more than 95% since the 1970ies; "tripper" and syphilis are essentially confined to high-risk groups while genital chlamydial infections affect people of all social classes, but information about chlamydia is still scarce in many European countries. Clinically genital chlamydial infections resemble gonorrhoea (dysuria, discharge, irregular bleeding, dyspareunia, perihepatitis) and may be mistaken for appendicitis. However, Chlamydia trachomatis persists longer and more often asymptomatic than Neisseria gonorrhoeae in the urogenital tract of men and women. About 20% of all chlamydia infected women suffer from partial or complete tubal occlusion. Chlamydia trachomatis is the leading cause of female infertility, but most of these women never experienced any clinical sign of pelvic inflammatory disease. Since particle concentrations are often very low in urine and cervical secretions only DNA-amplification tests, e.g. PCR or LCR, exhibit sufficient sensitivity for direct detection Chlamydia trachomatis. While Neisseria gonorrhoeae is eradicated by single-shot treatment with commonly used antibiotics like penicillins or cephalosporins Chlamydia trachomatis affords treatment for at least 10 days with doxycyline or macrolides. Partner treatment is essential to avoid reinfections. Condoms not only protect against HIV, but also against chlamydia, gonorrhoea and syphilis.

Completeness of and duration of time before treatment after screening women for Chlamydia trachomatis infections.

To assess the proportion of women with verified treatment after positive screening tests for C. trachomatis infection and to evaluate the duration of time until treatment. Retrospective cohort analysis linking the date of a positive genital C. trachomatis test with the documented date of treatment. Family planning, sexually transmitted disease, obstetrical/gynecologic, adolescent, and walk-in clinics in Philadelphia from March 1, 1994 through December 31, 1995. Included 4,158 women with screening tests positive for C. trachomatis. Documented treatment of chlamydia-infected women and duration of time between initial clinic visit and therapy. Over a 21-month period, 4,158 women had endocervical screening tests positive for C. trachomatis. Twenty-four percent of these women were treated presumptively (on the day of specimen collection), with sexually transmitted disease clinics yielding the highest percentage (70.9%) of presumptively treated patients. Of the 3,143 chlamydia-positive women not treated presumptively, treatment was subsequently verified in 96.2%. The median interval between screening and treatment was 21 days. Private adolescent clinics had the lowest median interval of 14 days between screening and treatment, whereas public family planning clinics showed the largest median screening to treatment interval of 26 days. Large-scale screening programs in public health settings can bring nearly all C. trachomatis-infected patients to treatment. However, new strategies are needed to shorten the duration of time before treatment of selected subsets of women who screen positive for C. trachomatis.

Cost-Effectiveness of Chlamydial Screening

Cost-Effectiveness of Chlamydial Screening

Chlamydia trachomatis and febrile complications of postpartum tubal ligation

OBJECTIVE: Our goal was to determine whether chlamydia-infected women have a higher rate of febrile complications after postpartum tubal ligation. STUDY DESIGN: Cross-sectional analysis of 1447 women tested for chlamydial infection within 2 weeks of delivery and who underwent postpartum tubal ligation was performed. Subjects were identified with the Regenstrief Institute for Health Care database. Infected subjects were compared with uninfected subjects for incidence of fever not explained by nongynecologic sources. RESULTS: Women infected with Chlamydia trachomatis at delivery were more likely to experience febrile postoperative complications after tubal ligation (p <0.0001, relative risk 9.5, 95% confidence interval 4.5 to 20.1). CONCLUSION: Women undergoing postpartum tubal ligation may benefit from prompt diagnosis and preoperative treatment of chlamydial infection. (Am J Obstet Gynecol 1997;176:100-2.)

Prevalence of genital Chlamydia trachomatis infection among women in a Swedish primary health care area.

The objective of this study was to estimate the prevalence of genital chlamydial infection in an unselected population of young women by offering a screening investigation to all women between the ages of 15 and 34 in a primary health care area. Specimens were taken from both the urethra and the cervix in all participating women, and data regarding the participants' symptoms, sexual habits, contraceptive use and socioeconomic factors were also collected. The specimens were analyzed with a primary enzyme immunoassay (Syva MikroTrak) and a confirmatory direct immunofluorescence test (Syva MikroTrak). A total of 543 women were invited to the study and 374 women (68.9%) participated. 10/374 women (2.7%) were chlamydia positive and only 2 of these 10 chlamydia infected women were less than 25 years of age. The chlamydia infected women had positive tests either from the urethra (4 women) or from the cervix (6 women), and in no case the tests were positive from both locations. No statistically significant differences between the chlamydia positive and negative women were found concerning any clinical or anamnestic factor.

Clueing in on Chlamydia

It can be as sneaky as an ingrown toenail and as innocuous-seeming as the common cold. It infects more people in the United States than any other sexually transmitted disease, yet it ranks as one of the least familiar of those rarely divulged afflictions. It leads to infertility in more than 20,000 women in the United States each year, but many of them won't discover they have had the disease until they try to get pregnant. The bacterium responsible for this trickery, Chlamydia trachomatis, has managed to escape much of the public recognition it deserves for its role in female infertility. Yet scientific studies conducted over the last decade have consistently shown that about 75 percent of women who cannot get pregnant because of a fallopian tube blockage also test positive for chlamydia antibodies, indicating past or present infection, notes H. Hunter Handsfield, an epidemiologist at the University of Washington in Seattle. Scientists have also begun to blame chlamydia for a dramatic rise in ectopic, or tubal, pregnancies over the past two decades. This dangerous complication of early pregnancy occurs when the fertilized egg becomes wedged within a fallopian tube instead of making its way to the uterus, where it belongs. When the misplacement becomes apparent, physicians must remove the fetus and repair any damaged tissue. Otherwise, the growing fetus may burst through the fragile tubean emergency that can cause massive blood loss and send the mother into physiological shock. Last December, the Centers for Disease Control reported that more than 88,000 women in the United States developed ectopic pregnancies in 1987 a nearly fourfold increase over the 1970 rate. Ectopic pregnancy now ranks as the leading cause of pregnancy-related death among women in the first trimester. Although other sexually transmitted diseases can also cause ectopic pregnancy, the rising numbers appear inextricably linked with chlamydia, asserts A. Eugene Washington, an epidemologist and gynecologist at the University of California, San Francisco. Chlamydia may be responsible for as much as 50 to 80 percent of the increase in ectopic pregnancies, he says. But scientists might avert the infection's tragic reproductive effects if new avenues of research live up to their early promise. Investigators have begun to unravel the basic biology of how chlamydia causes such lasting problems, and in doing so they have uncovered links to a class of proteins with mysterious connections to other diseases such as leprosy and tuberculosis. Eventually, such work may suggest ways to refine the clinical diagnosis of chlamydia, and may even yield the first effective vaccine against the disease. Another facet of this research could produce a test that would offer women with a history of chlamydia a way to gauge their risk of infertility or ectopic pregnancy, and would assist physicians in determining which of these patients need more extensive testing to detect hidden damage resulting from the infection. Findings emerging from this work already offer clues to help explain why so many chlamydia-infected women experience no symptoms.