Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial operons, agf, saf, sti, and stc that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 x 10(5) CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 x 10(9) CFU of wild-type S. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a Salmonella vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, chi 9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the Streptococcus pneumoniae antigen PspA. Strains that constitutively expressed saf or stc elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying saf or stc deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent S. pneumoniae. Our results indicate that these fimbriae play important roles, as yet not understood, in Salmonella virulence and immunogenicity. IMPORTANCE Salmonella enterica is the leading cause of bacterial food-borne infection in the United States. S. Typhimurium is capable of producing up to 13 distinct surface structures called fimbriae that presumably mediate its adherence to surfaces. The roles of most of these fimbriae in disease are unknown. Identifying fimbriae produced during infection will provide important insights into how these bacterial structures contribute to disease and potentially induce protective immunity to Salmonella infection. We identified four fimbriae that are produced during infection. Deletion of all four of these fimbriae results in a significant reduction in virulence. We explored ways in which the expression of these fimbriae may be exploited for use in recombinant Salmonella vaccine strains and found that production of Saf and Stc fimbriae are important for generating a strong immune response against a vectored antigen. This work provides new insight into the role of fimbriae in disease and their potential for improving the efficacy of Salmonella-based vaccines.

Magister Public Health - MPH / Background: STIs are of major public health concern in developing countries, not least because they facilitate transmission of HIV, but also because they are important causes of mortality and morbidity among African populations, resulting in, among other things, adverse birth outcomes, neonatal and infant infections, ectopic pregnancy, anogenital cancer,infertility, pelvic inflammatory disease, and death. Thus, effective treatment needs to be prompt and accurate to control the spread, and morbidity and mortality of STIs. Even though syndromic approach to the management of STIs is effective, most evaluations have focused on syndromic STI management within STI clinics as opposed to research studies. Partner notification is an integral component of the syndromic approach and is aimed at preventing onward transmission of infection as well as re-infection. It includes informing sexual partners of infected people of their exposure, administering presumptive treatment, and providing advice about the prevention of future infection.Methods: This is a cross sectional descriptive study based on a retrospective review of STI data of study participants in KICoS aged 18 to 34 years. A non probability convenience sampling method was used to recruit study participants. A total of 1,277 participants were prescreened into KICoS of whom 847 were enrolled into this study. Data was collected using CAPI and ACASI questionnaires as well as Teleforms which was analysed in SAS for windows 9.1. Results: Syndromic prevalence of STIs was 5.7% while the aetiological prevalence was 32.8%.Risk factors to STI acquisition included, being female, having multiple sexual partners,having lower than tertiary education, using recreational drugs and being HIV. Agreement between the interviewing methods as well between the syndromic and laboratory diagnosis ranged from fair to substantial. This was also true for the agreement between laboratory and CAPI as well as between the laboratory and ACASI. Sensitivity was generally low while specificity was high. Uptake of contact tracing cards was high though with very low uptake of contact treatment with only 2.1% and 0.4% partners of the syndromically and aetiologically diagnosed participants coming for treatment.Conclusions: STI is a problem in this community and thus there should be more emphasis on risk reduction messages in patient education to mitigate the spread of STIs. The performance of syndromic management was very poor against the aetiological diagnosis thus there needs to further review the use of syndromic diagnosis of STIs in research settings. Partner tracing needs to be intensified since there was very poor partner treatment even with high uptake of contact cards.Acknowledgements: This study would have not been what it was without the immense support I received from many individuals all of whom cannot be mentioned here. I would however want to thank the Dr Wairimu Chege (Principal Investigator, KICoS) for her inspiration and encouragement. I would also like to thank my supervisor, Ernie Kunneke for going through this study with me repeated times including on a ride to the airport. On the same note I would also like to thank my lecturers and student administrators at the SOPH. My gratitude also goes to my colleagues Richard Ndivo, Sherri Pals and Eleanor McLellan-Lemal for all the support they accorded me throughout this research.I would also want to give my heartfelt gratitude to my family. My daughter Akinyi who used to type with me at night, her mother Auma for understanding my late nights up and finally to my Parents Mr and Mrs Gideon and Monica Otieno for understanding the importance of education and taking me to school through all the difficulties. Last but not least I would like to express my gratitude to the almighty God for having seen me through this process.

Objective: The objective of this study was to describe the prevalence of sexually transmitted co-infections and assess factors associated with a single infection and co-infections. Methods: A total of 388 women were included in this study. At enrollment of the EVRI trial women were tested for five STIs: Human papilloma virus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus-2 (HSV-2) and Treponema pallidum. Prevalence of STI infections and proportion of women with different combinations of co-infections were calculated. Factors associated with single infection and STI co-infection were assessed using a polytomous logistic regression model and odds ratio (OR) and 95% confidence intervals (95% CI) were reported as the measure of association. Results: Prevalence of a single STI and concurrent STI co-infections were high. Prevalence of chlamydia was 33%, syphilis 6%, HSV-2 46% and HPV 71%. The most common STI co-infection pattern was HPV-HSV (32%), followed by HPV-chlamydia (17%). The odds of single STI compared to no STIs was significantly lower for women who had education level of grade 7 compared to women who had some college or technical education (OR 0.16, 95% CI: 0.03-0.79).The odds of a single STI compared to no STIs were significantly higher (OR 3.02, 95% CI: 1.05-8.64) and the odds of concurrent STIs compared to no infection were significantly higher (OR 3.86, 95% CI: 1.42-10.48) for women with three or more lifetime partners compared to one life time partner. Conclusions: STIs, single and multiple concurrent infections, are common among this cohort of South African women. These results strengthen the recommendation that STI screening and treatment needs to be a component of multiple intervention strategies among high-risk women residing in communities with high STI prevalence.

Introduction: Oil/gas communities across Northeastern British Columbia are experiencing rapid in-migration of young, primarily male workers in response to an economic ‘boom’ in the oil/gas sectors. Accompanying the ‘boom’ has been a rise in rates of sexually transmitted infections (STIs) among young people, with Chlamydia rates among youth in the Northeast exceeding the provincial average by 22%. Previous research indicates that socio-cultural and structural determinants of youth sexual behaviour and access to STI testing are important for understanding youth sexual health disparities – and represent key targets for STI prevention efforts. No other research has explored STIs in this rapidly developing, under-resourced context. Therefore, objectives of this thesis were to: (1) Examine how socio-cultural and structural features related to the oil/gas ‘boom’ affect the sexual behaviour of young people in Fort St. John (FSJ), BC; (2) Gather the perspectives of youth and their service providers on the socio-cultural and structural barriers to STI testing in FSJ; (3) Develop recommendations to improve the accessibility of STI testing. Results: Participants identified 4 main ways in which the socio-cultural and structural conditions created by the ‘boom’ affect sexual behaviours, fuelling the spread of STIs in FSJ: mobility of oil/gas workers; binge partying; high levels of disposable income; and gendered power dynamics. As well, 5 key barriers to STI testing among youth were identified: limited opportunities for access; geographic inaccessibility; local social norms; limited information; and negative interactions with providers. Discussion: These data indicate that the conditions fostered by the ‘boom’ in FSJ exacerbate sexual health inequalities among young people. They can be more widely contextualized as an example of the unintended – but not unexpected – health and social implications of a resource-extraction ‘boom’, illustrating the fallacy of ‘development’ as representing uniformly positive ‘progress’. Recommended actions include STI prevention and testing service delivery models that incorporate a locally tailored public awareness campaign, outreach to oil/gas workers, condom distribution, expanded clinic hours and drop-in appointments, specialized training for health care providers, and intersectoral partnerships between public health, non-profit organizations, and industry. An ongoing knowledge translation internship has been undertaken to implement some of these recommendations. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

Purpose. To identify correlates of combined hormonal contraception and condom use (dual method use) compared with no methods, condoms only or hormonal contraception only. Data are from a baseline assessment of 335 youth (52% female) enrolled in an intervention trial. Multinomial logistic regression identified theory-based factors associated with dual method use. At last intercourse 47% of respondents used dual methods, 29% condom only, 14% hormonal contraception only, and 10% no methods. No method users were less likely than dual-method users to feel “dirty” about pregnancy, to have ask about historical condom use, to have more than two partners, to view condom use as normative for boys and more likely to perceive pregnancy risk as remote. Hormonal-contraception-only users were more likely to have sex weekly and perceive sex as pleasurable for girls, and less likely to view condom use as normative for boys and to ask a partner to use a condom. Condom-only users were more likely to perceive pregnancy chance as remote, and less likely to have more than two partners and to want peers to think they were virgins. Interventions should include benefits of dual methods while counseling about the negative impact of STI and unplanned teen pregnancy.

Background: The burden of Sexually transmitted infections (STIs) is high globally. The World Health Organisation (WHO) recommends syndromic management of these STIs, based on presentation with signs and symptoms, in resource-limited countries. Due to this syndromic approach, there is little current data on STI prevalence, including asymptomatic STIs, in high risk populations. Methods: We reviewed secondary data collected as part of the screening procedures of 6 clinical trials between 2012 and 2017 in Cape Town, South Africa. These trials recruited populations of different sexual orientation and gender, mostly key populations at risk of HIV and STI acquisition. Routine screening for STI symptoms and testing for Chlamydia, Gonorrhoea, Trichomonas, Syphilis and HIV was performed for all of the studies at screening/enrollment. Results: A total of 639 participants were screened; 411 (64.3%) self-identifying as female, 198 (31%) males, 29 (4.5%) transgender women and 01 (0.2%) transvestite. Median age was 20 years (IQR: 18-24), with the 15-24-year age category contributing 77% to the cohort. Laboratory testing diagnosed 239 (37.4%) people with STI infections in this cohort; only 28 (11.7%) people were symptomatic. 119 (88.8%) of Chlamydial, 64 (82.1%) of Gonorrhoeal, 23 (92%) of Trichomonal and 31(79.5%) of Syphilis infections elicited no signs and/or symptoms. Conclusion: A vast majority of STIs in this high-risk population were asymptomatic. Laboratory testing of causal organism was more reliable in diagnosing STIs than the use of signs and/or symptoms as recommended by WHO.

Sexual and gender politics inform relational expectations surrounding sexual experiences of Peruvian transgender women (TW) and men who have sex with men (MSM). We used the framework of sexual role strain, or incongruence between preferred sexual role and actual sexual practices, to explore potential conflicts between personally articulated identities and externally defined norms of gender and sexuality and its potential to increase HIV/STI risk. Cross-sectional individual- and dyad-level data from 766 TW and MSM in Lima, Peru were used to assess the partnership contexts within which insertive anal intercourse was practiced despite receptive role preference (receptive role strain), and receptive anal intercourse practiced despite insertive role preference (insertive role strain). Sexual role strain for TW was more common with non-primary partners, while for MSM it occurred more frequently in the context of a primary partnership. Receptive role strain was more prevalent for TW with unknown HIV status (reference: without HIV) or pre-sex drug use (reference: no pre-sex drug use). For homosexual MSM, receptive role strain was more prevalent during condomless anal intercourse (reference: condom-protected) and with receptive or versatile partners (reference: insertive). Among heterosexual or bisexual MSM, insertive role strain was more prevalent with insertive or versatile partners (reference: receptive), and less prevalent with casual partners (reference: primary). Our findings suggest TW and MSM experience different vulnerabilities during sexual role negotiation with different partner-types. Future studies should explore the impact of sexual role strain on condom use agency, HIV/STI risk, and discordances between public and private presentations of gender and sexual orientation. / National Institutes of Health / Revisión por pares

Individuals infected with HIV through heterosexual contact made up 24% (9,578) of all new infections in the United States. Female sex workers are at increased risk of getting HIV and other sexually transmitted infections (STI) because they may be more likely to participate in risky sexual behaviors including sex with multiple partners and condom-less anal/vaginal sex. Guided by the syndemic theory, the purpose of this study was to explore the relationships between social and structural factors (homelessness, substance use, immigration status, and use of healthcare) and risky sexual behaviors (condom-less vaginal sex and multiple sex partners) among female sex workers while controlling for age and sexual violence. This study was conducted using a quantitative research approach with a correlational method. Multiple linear regression statistical testing was performed using data from 534 participants from the National HIV Behavioral Surveillance study. Immigration status was not significantly associated with condom-less vaginal sex or multiple sex partners. However, homelessness and substance use were positively associated with condom-less vaginal sex and multiple sex partners. In addition, utilization of healthcare was negatively associated with condom-less vaginal sex. The results from this study can increase awareness and knowledge of challenges and barriers among female sex workers living in Illinois. In addition, the results of this study may contribute to establishing baseline epidemiology of this population and guidelines on addressing the factors associated with unsafe sexual behaviors that can potentially lead to HIV and other STIs.

SAMMANFATTNING Bakgrund De senaste åren har antalet fall av klamydia, Humant immunbristvirus (HIV), gonorré och syfilis ökat i Sverige. Vad gäller klamydia och gonorré har den största ökningen skett bland ungdomar och unga vuxna som är i åldern 15-24 år. Effektiva förebyggande insatser existerar i nuläget, men antalet fall av ovanstående sexuellt överförbara infektioner (STI) fortsätter att öka. Syfte Syftet var att beskriva det förebyggande arbetet med att förhindra sexuellt överförbara infektioner bland ungdomar och unga vuxna i åldrarna 15-24 år i en storstad. Metod Studien utgick från kvalitativa intervjuer med en deskriptiv ansats. Vid två intervjuer medverkade två personer från verksamheterna vilket resulterade i att nio personer intervjuades vid sju intervjutillfällen. Inklusionskriterierna för att få medverka i studien var att respondenterna arbetade inom professionella verksamheter som arbetade förebyggande mot STI hos ungdomar och unga vuxna. Sju intervjuer genomfördes. Resultat Resultatet redovisades utifrån ett antal huvudkategorier med tillhörande underkategorier. I det förebyggande arbetet med att förhindra spridning av STI var utbildning, information och att ständigt aktualisera ämnet tre centrala begrepp. Bland annat använde verksamheterna sig av metoder så som utåtriktad verksamhet, massmedia, kondomutdelning och personliga möten för att nå målgrupperna. Resultatet visade även brister som respondenterna ansåg fanns i det förebyggande arbetet och vad respondenterna ansåg behövde utvecklas inom området. Slutsats När föreliggande studie gjordes fanns ett flertal aktörer som arbetade med att på olika sätt hålla frågan om STI på dagordningen. Skolan visade sig ha en betydande roll i mötet med ungdomar och unga vuxna. Sex- och samlevnadsundervisningen i skolan var en viktig grund för ungdomar och unga vuxnas sexuella hälsa samt levnadsvanor. För att förändra ungdomar och unga vuxnas sexuella riskbeteenden krävdes inte bara en större kunskap utan också en förändring av beteenden i praktiken.

ABSTRACT The Ministry of Health in South Africa has launched massive campaigns to try and prevent the spread of HIV/AIDS. However, South Africa still has more people infected with HIV/AIDS than any other country in the world. This has led to government and health care planners re-evaluating neglected traditional health systems as potential contributors to health care delivery. This report highlights some areas where traditional healers can play a role in the prevention of HIV/AIDS as told by traditional healers themselves. In discussing these roles, the report raises the need for supportive government policy. Up to now government policies on HIV/AIDS have relied largely on biomedical explanations of illness and ignored other popular explanations. This poses a serious problem in a country like South Africa, where a large proportion of the population consults traditional healers first before consulting the medical sector. Such policies also impact on collaborative measures between the two sectors. Thus far, almost all prevention programmes are run by clinics with very little interaction with other sectors. The report then goes on to discuss the perceptions on HIV/AIDS as discussed by traditional healers. In so doing, the report begins to touch on the role of traditional practices that relates to sexual behaviour in HIV/AIDS prevention. As custodians of traditional culture, traditional healers have a huge role to play in re-inventing such practices in a manner that raises awareness about HIV/AIDS and at the same time preventing the spread of the disease.