Chlamydial infection and spatial ascension of the female genital tract : a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata–partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

Effect of female sex hormones on Chlamydia trachomatis growth and gene expression

Transmissible diseases are re-emerging as a global problem, with Sexually Transmitted Diseases (STDs) becoming endemic. Chlamydia trachomatis is the leading cause of bacterially-acquired STD worldwide, with the Australian cost of infection estimated at $90 - $160 million annually. Studies using animal models of genital tract Chlamydia infection suggested that the hormonal status of the genital tract epithelium at the time of exposure may influence the outcome of infection. Oral contraceptive use also increased the risk of contracting chlamydial infections compared to women not using contraception. Generally it was suggested that the outcome of chlamydial infection is determined in part by the hormonal status of the epithelium at the time of exposure. Using the human endolmetrial cell line ECC-1 this study investigated the effects of C. trachomatis serovar D infection, in conjunction with the female sex hormones, 17β-estradiol and progesterone, on chlamydial gene expression. While previous studies have examined the host response, this is the first study to examine C.trachomatis gene expression under different hormonal conditions. We have highlighted a basic model of C. trachomatis gene regulation in the presence of steroid hormones by identifying 60 genes that were regulated by addition of estradiol and/or progesterone. In addition, the third chapter of this thesis discussed and compared the significance of the current findings in the context of data from other research groups to improve our understanding of the molecular basis of chlamydial persistence under hormonal different conditions. In addition, this study analysed the effects of these female sex hormones and C. trachomatis Serovar D infection, on host susceptibility and bacterial growth. Our results clearly demonstrated that addition of steroid hormones not only had a great impact on the level of infectivity of epithelial cells with C.trachomatis serovar D, but also the morphology of chlamydial inclusions was affected by hormone supplementation.

Effects of inoculating dose on the kinetics of Chlamydia muridarum genital infection in female mice

Chlamydia trachomatis infections have been implicated in problems such as pelvic inflammatory disease and infertility in females. Although there are some studies examining the kinetics of ascending infection, there is limited information on the kinetics of pathology development and cellular infiltrate into the reproductive tissues in relation to the effects of inoculating dose, and a better understanding of these is needed. The murine model of female genital tract Chlamydia muridarum infection is frequently used as a model of human C. trachomatis reproductive tract infection. To investigate the kinetics of ascending genital infection and associated pathology development, female BALB/c mice were intravaginally infected with C. muridarum at doses ranging from 5102 to 2.6106 inclusion forming units. We found that the inoculating dose affects the course of infection and the ascension of bacteria, with the highest dose ascending rapidly to the oviducts. By comparison, the lowest dose resulted in the greatest bacterial load in the lower reproductive tract. Interestingly, we found that the dose did not significantly affect inflammatory cell infiltrate in the various regions. Overall, this data show the effects of infectious dose on the kinetics of ascending chlamydial infection and associated inflammatory infiltration in BALB/c mice.

Female genital mutilation : Australian law, policy and practical challenges for doctors

As long ago as 1994, the Family Law Council accepted it was likely that female genital mutilation (FGM) was being conducted in Australia. In 2010, doctors and hospitals reported that it is being conducted and that they are seeing female patients who have experienced FGM. It is impossible to obtain precise data about the extent to which it is performed in Australia, but data indicates that FGM is a relevant issue for Australian medical practitioners. The medical profession has an interest in this topic because its members may be asked to conduct FGM, advise those considering it, or treat female patients with effects from the practice. This article provides a background on the practice of FGM, explains the relevant Australian law, considers whether the current legal prohibition on FGM is justified, and discusses the practical challenges facing individual practitioners and the profession. To inform further discussions about methods of responding to demand for FGM, reference is made to strategies being promoted in African nations to abolish this cultural practice.

A comparison of the effects of a chlamydial vaccine administered during or after a C. muridarum urogenital infection of female mice

There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract

Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.

Female genital mutilation : legal, attitudinal and practical reform

Female genital mutilation (FGM) is a cultural practice common in many Islamic societies. It involves the deliberate, non-therapeutic physical modification of young girls’ genitalia. FGM can take several forms, ranging from less damaging incisions to actual removal of genitalia and narrowing or even closing of the vagina. While often thought to be required by religion, FGM both predates and has no basis in the Koran. Rather, it is a cultural tradition, motivated by a patriarchal social desire to control female bodies to ensure virginity at marriage (preserving family honour), and to prevent infidelity by limiting sexual desire. In the USA and Australia in 2010, peak medical bodies considered endorsing the medical administration of a ‘lesser’ form of FGM. The basis for this was pragmatic: it would be preferable to satisfy patients’ desire for FGM in medically-controlled conditions, rather than have these patients seek it, possibly in more severe forms, under less safe conditions. While arguments favouring medically-administered FGM were soon overcome, the prospect of endorsing FGM illuminated the issue in these two Western countries and beyond. This paper will review the nature of FGM, its physical and psychological health consequences, and Australian laws prohibiting FGM. Then, it will scan recent developments in Africa, where FGM has been made illegal by a growing number of nations and by the Protocol to the African Charter on Human and Peoples’ Rights 2003 (the Maputo Protocol), but is still proving difficult to eradicate. Finally, based on arguments derived from theories of rights, health evidence, and the historical and religious contexts, this paper will ask whether an absolute human right against FGM can be developed.

Legal, cultural and practical developments in responding to female genital mutilation : can an absolute human right emerge?

Female genital mutilation (FGM) is a cultural practice involving the deliberate, non-therapeutic physical modification of young girls’ genitalia. FGM can take several forms, ranging from smaller incisions, to removal of the clitoris and labia, and narrowing or even closing of the vagina. FGM predates and has no basis in the Koran, or any other religious text. Rather, it is a cultural tradition, particularly common in Islamic societies in regions of Africa, motivated by a patriarchal society’s desire to control female bodies and lives. The primary reason for this desire for control is to ensure virginity at marriage, thereby preserving family honour, within a patriarchal social structure where females’ value as persons is intrinsically connected to, and limited to, their worth as virgin brides. Recent efforts at legal prohibition and practical eradication in a growing number of African nations mark a significant turning point in how societies treat females. This shift in cultural power has been catalysed by a concern for female health, but it has also been motivated by an impulse to promote the human rights of girls and women. Although FGM remains widely practiced and there is much progress yet to be made before its eradication, the rights-based approach which has grown in strength embodies a marked shift in cultural power which reflects progress in women’s and children’s rights in the Western world, but which is now being applied in a different cultural context. This chapter reviews the nature of FGM, its prevalence, and health consequences. It discusses recent legal, cultural and practical developments, especially in African nations. Finally, this chapter raises the possibility that an absolute human right against FGM may emerge.

Circulating immunoglobulin A- and immunoglobulin G-secreting hybridoma cells in peripheral blood preferably migrate to female genital tracts. The role of sex hormones

Antigen-specific circulating immunoglobulin-secreting cells (ISC) migrate to various secondary and tertiary lymphoid tissues. To understand the migration of the cells into the genital tract and its regulation by sex hormones, spleen-derived SG2 hybridoma cells secreting immunoglobulin G2b (IgG2b) and Peyer's patch-derived PA4 hybridoma cells secreting polymer IgA were labelled with (3) H-TdR, and intravenously injected into syngeneic mice of both sexes. Using flow cytometry, surface molecular markers of plasma cells, CD38 and CD138, and adhesion molecules, CD49d, CD162, and CD11a were found to be positive in SG2 and PA4 cells, but CD62L, alpha4beta7 and CD44 were not expressed on these cells. The relative distribution indexes (RDIs) of the cells in genital tract and other tissues were measured. The means of RDIs of SG2 and PA4 cells in female genital tissues were 6.5 and 4.5 times as many as the means in male genital tissues, respectively. The treatment of ovariectomized mice with beta-oestradiol significantly increased the RDIs of PA4 cells in cervix and vagina, but decreased the RDIs of SG2 cells in vagina, horn of uterus, uterus and rectum (P <0.05). Progesterone treatment increased the RDIs of PA4 cells in vagina and rectum (P <0.05). The treatment with testosterone significantly increased the RDIs of SG2 and PA4 cells in epididymis and accessory sex glands (P <0.05). These results demonstrate that the female genital tract is the preferable site for the migration of circulating hybridoma cells to the male genital tract, and sex hormones play an important role in regulation of the migration of circulating ISC to genital tracts.

Beyond a "woman's problem" : the role of relationship processes in female genital pain

Female genital pain is a prevalent condition that can disrupt the psychosexual and relational well-being of affected women and their romantic partners. Despite the intimate context in which the pain can be elicited (i.e., during sexual intercourse), interpersonal correlates of genital pain and sexuality have not been widely studied in comparison to other psychosocial factors. This review describes several prevailing theoretical models explaining the role of the partner in female genital pain: the operant learning model, cognitive-behavioral and communal coping models, and intimacy models. The review includes a discussion of empirical research on the interpersonal and partner correlates of female genital pain and the impact of genital pain on partners’ psychosexual adjustment. Together, this research highlights a potential reciprocal interaction between both partners’ experiences of female genital pain. The direction of future theoretical, methodological, and clinical research is discussed with regard to the potential to enhance understanding of the highly interpersonal context of female genital pain

Sexual blinging of women : Alice Walker's african character tashi and issue of female genital cutting

This thesis provides a reading of the different forms of representation that can be attributed to the character Tashi, the protagonist of the novel Possessing the Secret of Joy (1992), written by the African American writer Alice Walker. Before this work Tashi had already appeared in two previous novels by Walker, first, in The Color Purple (1982) and then, as a mention, in The Temple of My Familiar (1989). With Tashi, the author introduces the issue of female circumcision, a ritual Tashi submits herself to at the beginning of her adult life. The focus of observation lies in the ways in which the author’s anger is transformed into a means of creative representation. Walker uses her novel Possessing the Secret of Joy openly as a political instrument so that the expression “female mutilation” (term used by the author) receives ample attention from the media and critics in general. The aim of this investigation is to evaluate to what extent Walker’s social engagement contributes to the development of her work and to what extent it undermines it. For the analysis of the different issues related to “female genital cutting”, the term I use in this thesis, the works of feminist critics and writers such as Ellen Gruenbaum, Lightfoot-Klein, Nancy Hartsock, Linda Nicholson, Efrat Tseëlon and the Egyptian writer and doctor Nawal El Saadawi will be consulted. I hope that this thesis can contribute as an observation about Alice Walker’s use of her social engagement in the creation of her fictional world.