Breast and cervical cancer are leading causes of female cancer morbidity and mortality in Sub-Saharan Africa (SSA). Despite the high burden of disease, women’s knowledge of evidence-based risk factors and symptoms remains low. To adequately address the apparent knowledge deficits, the underlying knowledge in communities needs to be measured, so as to identify important gaps and contextually address them. To date, cancer knowledge in SSA has been measured using either prompted or unprompted question formats, yielding varying knowledge scores. However, there has been little exploration on the impact of using either question format for assessing disease awareness. This study sought to measure the differences in breast and cervical cancer risk factors and symptoms knowledge reported through prompted and unprompted questions, in South Africa (SA) and Uganda (UG). This was a descriptive cross-sectional study drawing on data collected during validation of an interviewer administered questionnaire (African Woman’s Awareness of Cancer - AWACAN) measuring breast and cervical cancer awareness in SSA. The sample included 139 women recruited from public sector primary health care facilities in two urban districts, Gulu (UG) and Cape Town (SA). Descriptive statistics were used to summarize participant’s socio-demographic characteristics and knowledge about breast and cervical cancer. Composite knowledge scores were calculated by adding up the number of correct responses per individual. The Wilcoxon Singed Rank test was used to compare differences between unprompted and prompted knowledge scores. Regression analyses were used to measure the relationship between unprompted and prompted knowledge. The median age of study participants was 42 years. The majority of women had not completed secondary education (57%) and were unemployed (64%). Unprompted knowledge was considerably lower than prompted knowledge for all breast and cervical cancer risk factors and symptoms. Median scores for unprompted knowledge of breast cancer risk factors (0) and symptoms (1) were significantly lower than for prompted at 6 and 14 respectively. Similarly, the median scores for unprompted knowledge of cervical cancer risk factors (0) and symptoms (1) were lower than prompted knowledge at 6 and 9 respectively. The difference between prompted and unprompted knowledge was least for classical breast and cervical cancer symptoms. For instance, the well-known breast cancer symptom ‘lump in the breast’ was recalled by 57% and 96% with unprompted and prompted questioning respectively. Unprompted questioning identified additional risk lay beliefs such as, ‘itching of the breast’. Combined use of unprompted and prompted questions provides more insight on breast and cervical cancer knowledge patterns in SSA. The low unprompted knowledge scores reported here demonstrate the need for health education interventions to improve knowledge of established breast and cervical cancer risk factors and whilst addressing any predominant lay beliefs about the disease in SSA. This dissertation is divided into three parts. Part A consists of the study protocol outlining the rational for undertaking this study as well as the proposed research methodology. Part B is the literature review that gives a summary of existing literature on the use of prompted and unprompted questions in measuring cancer knowledge thereby providing context for this study. Part C is a journal ready manuscript presenting the results and discussion of study findings.

The World Health Organisation (WHO) recommends the introduction of at least one single dose of inactivated polio vaccine (IPV) in routine immunisation schedules to mitigate the risk of a polio virus type 2 reintroduction or re-emergence. As a result, there has been an increased demand and concurrent supply shortages of IPV worldwide resulting in poor access to IPV. With the phasing out of the oral polio vaccine and the pursuit of global eradication of polio, ensuring an adequate supply of IPV is of paramount importance. One of the strategies to improve access is the use of the fractional dose because of its dose sparing and cost reduction properties. This mini-dissertation presents a research protocol (Section A), scoping review (Section B) and journal formatted manuscript (Section C) for a systematic review and meta-analysis of fractional dose compared to standard dose inactivated polio vaccination in children. Section A describes the rationale for the review, eligibility criteria, the search strategy and methods for data extraction and analysis. Section B is a scoping review that details the journey towards eradication of polio, the current state of IPV demand and supply and further explains the rationale for performing the systematic review. Section C is a manuscript that gives the results of the review after performing the methods outlined in Section A. The results showed that as the number of IPV doses increased the seroconversion rates for fractional dose and full dose IPV approximated each other such that at three doses the rates were similar. In conclusion, there is no difference in seroconversion between three doses of fractional dose IPV and three doses of full dose IPV. With the current IPV shortages, using fractional dose IPV instead of the full dose IPV can stretch supplies and possibly lower the cost of polio vaccination.

Includes bibliographical references / The Substance Use Risk Profile Scale (SURPS) is a relatively new questionnaire that assesses individual personality risk for substance-related problems. Preliminary findings have indicated that the SURPS is a useful measure for identifying characteristics predisposing some individuals to alcohol and other drug (AOD) use. High levels of hopelessness, anxiety sensitivity, sensation seeking, and impulsivity are each associated with specific patterns of substance use caused by underlying motivational susceptibilities. Furthermore, incorporating these traits into tailored prevention and treatment efforts have shown value in other countries. The present study enrolled a community sample in Cape Town, South Africa and asked respondents about their demographics, history of AOD use, personality as measured by the SURPS, and other mental health indicators. This information was used to identify personality risks in the local population and validate the utility of the SURPS for the first time in Sub-Saharan Africa. Results found that sensation seekers had a significantly higher risk for alcohol, tobacco, cannabis, cocaine, and hallucinogen use compared to other personality groups and controls. As expected, respondents demonstrating anxiety sensitivity also showed high-risk use of alcohol, but less high-risk illicit drug use . Finally, the hopelessness group exhibited a higher risk for opioid use but overall, hopelessness and impulsivity had little impact on concurrent substance use, which contrasts with other literature. Unlike findings from mostly European and North American samples that indicate generalizability, this study did not find structural or concurrent validity for the SURPS. This provides evidence against it being adopted as a culturally appropriate assessment tool in a diverse South African population.

Master of Health Sciences (MSc)

Background: Prevention of unplanned pregnancy is a crucial aspect of preventing mother-to-child HIV transmission (PMTCT). However, we have little understanding of how HIV status and antiretroviral therapy (ART) may influence pregnancy planning. There are few data on pregnancy planning in HIV-infected South African women, and no comparative data with HIV-uninfected women. Methods: We conducted a cross-sectional study of 2105 pregnant women (1512 HIV-infected; 593 HIV-uninfected) ages 18-44 making their first antenatal clinic visit at a primary-level health care facility in Gugulethu, Cape Town. All women completed structured questionnaires including the London Measure of Unplanned Pregnancy (LMUP), a 6-item scale that categorizes pregnancies into planned, ambivalent and unplanned. Analyses examined LMUP results across 4 groups of participants: HIV-infected established on ART; known HIV-infected but not currently on ART; newly diagnosed HIV-infected; and HIV-uninfected. Results: Overall, the mean age was 29 years (SD: 5.63), 43% of women were married or cohabiting and 20% were nulliparous. The LMUP performed well across all groups (Cronbach's α=0.84). Levels of unplanned pregnancy were higher in HIV-infected versus HIV-uninfected women (50% vs. 33%, p<0.001); and highest in women not on ART. Overall, 69% of women reported contraceptive use in the year before pregnancy; this was strongly associated with unplanned pregnancy (p<0.001). Compared to HIV-uninfected women, HIV-infected women had significantly higher odds of unplanned pregnancy, even after adjusting for age, parity and cohabiting status. The odds were greatest among women newly-diagnosed with HIV and previously diagnosed but not on ART (OR: 1.43; 95% CI: 1.05-1.94 and OR: 1.56; 95% CI: 1.13-2.15, respectively). Increased parity and age <24 years were also associated with unplanned pregnancy (OR 1.83; 95% CI: 1.24-2.74 and OR 1.42; 95% CI: 1.25- 1.60 respectively). Conclusions: These data indicate high levels of unplanned pregnancy in a high HIV prevalence setting, highlighting missed opportunities for family planning and counselling services for HIVpositive women. Possible explanations for the high level of unplanned pregnancy observed include contraceptive failure and/or misuse thereof. Therefore, women living with HIV require additional support to avoid unplanned, particularly those who are younger and have one or more children.

A elevada variabilidade genética do HIV tipo 1 e a seleção de mutações de resistência às drogas antirretrovirais tem representado um enorme desafio para o sucesso dos esquemas terapêuticos. Muitos estudos têm demonstrado que há padrões específicos de mutações para cada um dos subtipos de HIV-1. Os padrões do subtipo B são os mais bem definidos em função de sua presença majoritária nas epidemias da Europa e Estados Unidos. Contudo, a prevalência dos subtipos não-B, assim como a das formas recombinantes, tem aumentado significativamente em várias regiões. No Brasil, onde os subtipos B e F, e em alguns estados, também o C, coexistem, a presença de recombinantes BF vem ganhando destaque. Os objetivos deste trabalho foram comparar a região da protease do recombinante BF e do subtipo F puro quanto à possível presença de substituições diferentes, analisar o perfil mutacional e a covariação de mutações associadas ao tratamento e ao uso de inibidores específicos na protease do HIV-1 subtipo F e avaliar a reversão de mutações que já haviam sido selecionadas e a seleção de novas mutações após a troca do esquema terapêutico / The high genetic variability of HIV type 1 and the selection of antiretroviral resistance mutations have represented an enormous challenge to therapeutic schema success. Many studies have demonstrated that there are specific mutations patterns for each of the HIV-1 subtypes. Subtype B mutation profiles are the best studied due to its high presence in Europe and USA epidemics. However, prevalence of non-B subtypes, as well as recombinant forms, has been significantly increasing in many regions. In Brazil, where subtypes B and F, and in some states also C, have been co-circulating, BF recombinants are commonly found. The aims of this work were to compare protease region of BF recombinants to pure subtype F to search for different amino acid substitutions; analyzing mutation profile and co-variation of related-to-treatment mutations; verifying the relationship between the presence of groups of mutations and the use of specific antiretroviral drugs; and evaluating the selection of new mutations after changing therapeutic schema

A elevada variabilidade genética do HIV tipo 1 e a seleção de mutações de resistência às drogas antirretrovirais tem representado um enorme desafio para o sucesso dos esquemas terapêuticos. Muitos estudos têm demonstrado que há padrões específicos de mutações para cada um dos subtipos de HIV-1. Os padrões do subtipo B são os mais bem definidos em função de sua presença majoritária nas epidemias da Europa e Estados Unidos. Contudo, a prevalência dos subtipos não-B, assim como a das formas recombinantes, tem aumentado significativamente em várias regiões. No Brasil, onde os subtipos B e F, e em alguns estados, também o C, coexistem, a presença de recombinantes BF vem ganhando destaque. Os objetivos deste trabalho foram comparar a região da protease do recombinante BF e do subtipo F puro quanto à possível presença de substituições diferentes, analisar o perfil mutacional e a covariação de mutações associadas ao tratamento e ao uso de inibidores específicos na protease do HIV-1 subtipo F e avaliar a reversão de mutações que já haviam sido selecionadas e a seleção de novas mutações após a troca do esquema terapêutico / The high genetic variability of HIV type 1 and the selection of antiretroviral resistance mutations have represented an enormous challenge to therapeutic schema success. Many studies have demonstrated that there are specific mutations patterns for each of the HIV-1 subtypes. Subtype B mutation profiles are the best studied due to its high presence in Europe and USA epidemics. However, prevalence of non-B subtypes, as well as recombinant forms, has been significantly increasing in many regions. In Brazil, where subtypes B and F, and in some states also C, have been co-circulating, BF recombinants are commonly found. The aims of this work were to compare protease region of BF recombinants to pure subtype F to search for different amino acid substitutions; analyzing mutation profile and co-variation of related-to-treatment mutations; verifying the relationship between the presence of groups of mutations and the use of specific antiretroviral drugs; and evaluating the selection of new mutations after changing therapeutic schema