Chlamydia trachomatis is a human pathogen of the genital tract and ocular epithelium. It is an obligate intracellular parasite with a unique biphasic development cycle. C.trachomatis infection is the most common bacterial sexually transmitted disease in industrialized nations. Its ability to cause chronic disease makes it a serious economic burden and health threat to developed and developing countries. Although treatable, approximately 70% of C.trachomatis infections are asymptomatic, potentially leading to the development of chronic sequelae. Furthermore, chlamydial genital tract infection has been associated with an increased risk of cervical cancer and human immunodeficiency virus infection. Consequently, the development of an efficacious vaccine is the most convenient, potentially reliable and cost effective option to control chlamydial infection and disease complications. Anti-chlamydial protective immunity is essentially mediated by a T helper, type 1 (Th1), response that is dependent upon the presentation of antigen via major histocompatibility (MHC) class II molecules. While antibody secreting cells are not critical components of the primary effector response, they have been shown to be important for clearance of re-infection. Thus an ideal vaccine would be one capable of inducing both a strong Th1 T cell response and a strong mucosal antibody response. Currently there are very few efficacious vaccine candidates that have been identified and characterized. More specifically, there is only a limited number of known T cell antigens processed and presented by the human leukocyte antigen (HLA) class II molecules. This type of antigen is going to be essential to the development of an efficacious chlamydial vaccine. In this study we have identified a number of unique vaccine candidates using a novel in silico approach. In an attempt to overcome HLA polymorphism the whole chlamydial genome was screened for proteins containing epitopes predicted to bind multiple HLA class II molecules (i.e. predicted ‘promiscuous’ T cell epitopes). A wide range of HLA class II molecules were used in this screen to identify vaccine antigens that could potentially offer broad and ethnically balanced population coverage. This analysis identified a number of novel targets and was validated by the identification of a known chlamydial T cell epitope. A selection of these target proteins was cloned, expressed and purified. Recombinant protein was screened against serum samples from patients with both acute and chronic chlamydial infections. Two novel targets, hypothetical protein CT425 and ribonucleotide reductase small chain protein (NrdB) were identified as being immunoreactive. The in vivo protective efficacy of NrdB was analyzed using a mouse model. CD4+ T cells were harvested from NrdB immunized mice and adoptively transferred to naïve mice, which were subsequently infected at the genital site. NrdB immunization was found to confer a CD4+ T cell driven degree of protection similar to that seen with CD4+ T cells primed from a live challenge. The adjuvants and route of immunization used ensured immunological responses were initiated at both the systemic and local sites of infection. Immunization elicited a predominant Th1 response with primed T cells producing high levels of interferon gamma, an essential requirement for the development of an efficacious chlamydial vaccine. Furthermore, high titres of antigen specific IgG and IgA were produced following immunization, with sera derived antibodies demonstrating neutralization properties. NrdB is a highly conserved chlamydial protein with an essential role in the replication of chlamydiae and could play a central role in a multi-subunit vaccine against chlamydial genital tract infections.

This thesis presents data on two separate areas relevant to the prevention of HIV and sexually transmitted infection (STI) transmission in homosexual men. These data arise from the community-based Health in Men (HIM) cohort of HIV-negative homosexual men in Sydney. First, the association of circumcision status with HIV and STIs was examined. Older age, ethnicity and country of birth were demographic factors independently associated with circumcision status. Self-report was a valid measure of circumcision status in this population. Overall, being circumcised was associated with a non-significant reduced risk of HIV seroconversion in the HIM cohort (HR 0.76, 95% CI 0.41-1.41, p=0.381). Among the one-third of participants predominantly practising the insertive role in anal intercourse (AI), being circumcised was associated with a significantly reduced risk of HIV infection (HR 0.15, 95% CI 0.03-0.80, p=0.026). Circumcised HIM participants also had a lower risk of incident syphilis (HR 0.35, 95% CI 0.15-0.84, p=0.019), however circumcision status had no significant effect on the remainder of prevalent and incident STIs examined. Second, risk factors for pharyngeal gonorrhoea and chlamydia were investigated. The BD ProbeTec nucleic acid amplification test (NAAT) had a positive predictive value (PPV) for pharyngeal gonorrhoea diagnosis of only 30.4% (95% CI 25.2-36.1%) when compared to a previously validated NAAT targeting the gonococcal porA pseudogene. Pharyngeal gonorrhoea was common in HIM, mostly occurred without concurrent anogenital infection and may frequently spontaneously resolve. Infection was independently associated with younger age (p-trend=0.001), higher number of male partners (p-trend=0.002), contact with gonorrhoea (p<0.001) and insertive oro-anal sex with casual partners (p-trend=0.044). Pharyngeal chlamydia was less common but a high prevalence/incidence ratio suggested that infection may persist in the pharynx for long periods. Pharyngeal chlamydia was independently associated with receptive penile-oral sex with casual partners (p-trend=0.009). In conclusion, circumcision may have a role as an HIV prevention intervention among the subgroup of homosexual men who predominantly practise insertive rather than receptive AI. Regular screening of the pharynx including a validated supplemental NAAT for gonorrhoea diagnosis may prevent much transmission to anogenital sites, whereas chlamydia occurs too infrequently in the pharynx to recommend routine screening in homosexual men.

Good sexual and reproductive health is fundamental to the overall health status of Māori communities. In 2001, the Ministry of Health reported that New Zealand was facing a Chlamydia epidemic. This epidemic has not abated as rates of Chlamydia have increased significantly in the past five years, with disproportionately high rates in young Māori women compared to non-Māori women. Despite significant sexual health disparities, young Māori have had limited opportunities to participate in research focussed on sexual health and voice their opinions and concerns on sexual health issues. This qualitative descriptive study has used a Māori inquiry paradigm and approached the research from a Kaupapa Māori perspective. The primary research question asked what the knowledge, attitudes and reported behaviours of young urban Māori women were in regards to sexual health and in particular, the sexually transmitted infection Chlamydia. Secondary aims were to ascertain the sources of information used and accessibility of sexual health services, as well as identifying resilience factors associated with protection against Chlamydia infection. The data was collected from semi-structured interviews with 16 young Māori women living in the Auckland region. Data analysis involved the inductive approach of categorical content analysis to identify major categorical themes to answer the specific questions posed. The main conclusion was that there are a number of barriers to accessing quality sexual health information and services for young Māori women. Participants’ level of knowledge varied reflecting their personal experiences and many were unaware that Chlamydia is asymptomatic and that delayed diagnosis can lead to fertility problems. The main sources of sexual health information accessed were whānau, peers, school, and contact with health professionals. Racism was identified as one of the barriers to sexual healthcare services. The young women expressed a clear preference for sexual health services to be delivered by Māori. Most importantly, for sexual health interventions to be successful it is essential that Māori communities, including young people and their whānau, are an integral part of creating positive solutions. Resilience factors that may help protect young women from contracting chlamydia characteristic of this group were having a strong connection with a caring adult or friend and parents who viewed sexuality as a normal part of adolescent development. In addition, having a positive Māori cultural identity with an ability to understand bicultural differences was strongly associated with participants accessing sexual healthcare services despite identified barriers.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 7 uppsatser.

Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available online through Digital Dissertations.

Thesis (Ph. D.)--University of Washington, 1990. / Vita. Includes bibliographical references (leaves [525]-545).