Margaret Hoffman

The Prevalence and Identification of Risk Factors for NIDDM in Urban Africans in Cape Town, South Africa

OBJECTIVE To determine the prevalence of NIDDM and associated risk factors in urban Africans in Cape Town, South Africa. RESEARCH DESIGN AND METHODS With a three-stage, proportional, stratified, random cluster method, we sampled 1000 Africans, > 30 yr of age, living in African residential areas in Cape Town. We assessed glucose tolerance with a 75-g oral glucose tolerance test, according to World Health Organization criteria, and obtained anthropometric and demographic data. RESULTS The response rate was 79%. The prevalence of NIDDM was 8.0% (confidence interval 5.8–10.3%), age-adjusted to world population figures and that of impaired glucose tolerance, 7.0% (confidence interval 4.9–9.1%). Multivariate analysis indicated that increased age (odds ratio 4.18), upper-segment fat distribution (odds ratio 2.94), proportion of life spent in an urban area (odds ratio 2.32), and obesity (odds ratio 2.31) were significant independent risk factors for NIDDM. In contrast, sex, family history, alcohol intake, and physical activity were not independent risk factors. Only increased age (odds ratio 4.06) was a significant risk factor for impaired glucose tolerance. CONCLUSIONS The prevalence of NIDDM in urban Africans in Cape Town, South Africa, is moderately high, and considerably higher than previous reports from Africa. The association of NIDDM with urbanization has important implications in view of the large-scale urbanization occurring in southern Africa.

Intimate Partner Violence: Prevalence and Risk Factors for Men in Cape Town, South Africa

This study examined the prevalence of and risk factors for intimate partner physical violence against women. Interviews were conducted with a sample of 1,378 men working in Cape Town municipalities. An average of 42.3% (95% CI: 39.6, 44.8) reported physical violence against a partner of the last 10 years, and 8.8% (95% CI: 7.3, 10.3) reported physical violence in the past year. After adjustment for age, occupational group, and race, the factors associated with use of violence against partners of the last 10 years were having no post-school training (OR = 2.10), witnessing parental violence in childhood (OR = 1.87), involvement in fights at work (OR = 2.73) and in communities (OR = 1.54), drug use (OR = 1.99), problem alcohol use (OR = 1.98), perceiving hitting women to be acceptable (OR = 4.54), frequent conflict (OR = 2.40), women’s alcohol use (OR = 2.25), conflict about sex (OR = 2.16), and conflict about his infidelity (OR = 2.81). The study shows that ideas supportive of gender inequality and normative use of violence in different settings are major underlying factors for men’s violence against partners.

Sexual violence against intimate partners in Cape Town: prevalence and risk factors reported by men

OBJECTIVE To describe the prevalence of and risk factors for the perpetration of sexual violence by men against female intimate partners. METHODS A cross-sectional study was conducted on 1368 randomly selected men working in three Cape Town municipalities. The men were interviewed with the aid of a questionnaire on current sexual partners in the preceding 10 years, personal and relationship characteristics and the use of violence against their partners. RESULTS The perpetration of sexual violence against intimate partners in the past 10 years was reported by 15.3% of the men. After adjustment for sociodemographic circumstances, the factors associated with such violence were involvement in physical conflict outside the home, problematic alcohol use, having more than one current partner and abusing partners verbally. While having frequent conflict with partners was important for the risk of sexual violence, only two types of conflict sources were significantly associated with this risk, namely conflict over sexual refusal and conflict when men perceived their authority to be undermined. CONCLUSION Sexual violence in intimate relations was common. The risk of being sexually violent was associated with the use of violence to solve problems in other settings, having more than one current partner, alcohol abuse and verbally abusing a partner. It was also associated with particular types of conflict stemming from ideas of male sexual entitlement and dominance. Prevention programmes that focus on gender relations and non-violent conflict resolution for men and youths may be useful in combating such sexual violence.

HIV and pre-neoplastic and neoplastic lesions of the cervix in South Africa: a case-control study

BackgroundCervical cancer and infection with human immunodeficiency virus (HIV) are both major public health problems in South Africa. The aim of this study was to determine the risk of cervical pre-cancer and cancer among HIV positive women in South Africa.MethodsData were derived from a case-control study that examined the association between hormonal contraceptives and invasive cervical cancer. The study was conducted in the Western Cape (South Africa), from January 1998 to December 2001. There were 486 women with invasive cervical cancer, 103 control women with atypical squamous cells of undetermined significance (ASCUS), 53 with low-grade squamous intraepithelial lesions (LSIL), 50 with high-grade squamous intraepithelial lesions (HSIL) and 1159 with normal cytology. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression.ResultsThe adjusted odds ratios associated with HIV infection were: 4.4 [95% CI (2.3 – 8.4) for ASCUS, 7.4 (3.5 – 15.7) for LSIL, 5.8 (2.4 – 13.6) for HSIL and 1.17 (0.75 – 1.85) for invasive cervical cancer. HIV positive women were nearly 5 times more likely to have high-risk human papillomavirus infection (HR-HPV) present compared to HIV negative women [OR 4.6 (95 % CI 2.8 – 7.5)]. Women infected with both HIV and high-risk HPV had a more than 40 fold higher risk of SIL than women infected with neither of these viruses.ConclusionHIV positive women were at an increased risk of cervical pre-cancer, but did not demonstrate an excess risk of invasive cervical cancer. An interaction between HIV and HR-HPV infection was demonstrated. Our findings underscore the importance of developing locally relevant screening and management guidelines for HIV positive women in South Africa.

Impact of Mucosal Inflammation on Cervical Human Immunodeficiency Virus (HIV-1)-Specific CD8 T-Cell Responses in the Female Genital Tract during Chronic HIV Infection

ABSTRACT The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8+ T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8+ T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-α, IL-1β, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

BackgroundCervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy.MethodsA cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology.ResultsThe median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU.ConclusionWomen initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women

BackgroundCervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-α gene polymorphism in South African women with cervical cancer compared to control women.MethodsIncluded in our study were women with histologically proven cancer of the cervix (n = 244) and hospital-based controls (n = 228). All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G) polymorphism in the promoter region of TNF-α was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups.ResultsIn this study we observed no association between the distribution of -308 TNF-α polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X2 = 2.26). In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-α. However, the frequency of the rare high-producing allele -308A of TNF-α was significantly lower in the South African population when compared to Caucasians and Chinese population groups.ConclusionWe demonstrated no association between -308 TNF-α polymorphism and the risk of cervical cancer among two South African ethnic population groups. However, as the distribution of the -308A TNF-α was notably different between the control groups of South Africa and other population groups this result suggests that ethnic disparity may influence the levels of TNF-α produced.

Genital Human Papillomavirus Prevalence and Human Papillomavirus Concordance in Heterosexual Couples Are Positively Associated with Human Immunodeficiency Virus Coinfection

This study examined the concordance of genital human papillomavirus (HPV) infection in 254 heterosexually active couples and the impact of HIV coinfection. Genital HPV detection was significantly more common among HIV-infected women than among HIV-seronegative women (99 [68%] of 145 women vs. 33 [31%] of 107 women; P < .001); similarly, HPV detection was significantly more common among HIV-infected men than among HIV-seronegative men (67 [72%] of 93 and 65 [43%] of 150 men, respectively; P < .001). HIV-seronegative male partners of HIV-infected women had a significantly greater prevalence of HPV infection than did HIV-seronegative male partners of HIV-seronegative women (38 [58%] of 65 men vs. 27 [32%] of 85 men; P = .001), indicating that HIV coinfection in one partner has a significant impact on the prevalence of HPV genital infection in the other partner. HPV concordance between couples was associated with HIV infection status (P < .001, by Pearsons chi2 test) and was significantly higher among HIV-infected couples than among HIV-seronegative couples. Type-specific sharing of HPV was associated with HIV concordance status (P = .024). HIV-seronegative couples were more likely to share 1 HPV type and were unlikely to share >1 type, whereas HIV-infected or HIV-discordant couples were more likely to share >1 HPV type. Women with a high HPV load frequently shared HPV types with their male partners, suggesting that a high HPV load may play a role in HPV transmission between partners. In conclusion, HIV coinfection in one or both sexually active partners increased HPV prevalence and HPV type-specific concordance.

Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer

Background The failure of specific types of human papillomaviruses (HPV) to raise effective immune responses may be important in the pathogenesis of cervical cancer, the second most common cancer in South African women. Polymorphisms of a number of cytokine genes have been implicated in inducing susceptibility or resistance to cancers caused by infectious agents owing to their role in determining host immune response. Polymorphisms of IL-10 and IFN-γ genes are believed to influence the expression and/or secretion levels of their respective cytokines. Methods and Results In this study, women with histologically proven cancer of the cervix (n = 458) and hospital-based controls (n = 587) were investigated for bi-allelic -1082 (A/G) polymorphisms of IL-10 and the bi-allelic +874(A/T) polymorphisms of IFN-γ. In addition, the distributions of the allelic frequencies were stratified in both the African and mixed race population groups of South Africa. We found striking differences in the allele distribution of IFN-γ (X2 = 0.02) among the two ethnic groups. A significant increase in the allele distribution of the IFN-γ AA genotype was found in the African group compared to the mixed population group (OR, 0.5; 95% CI, 0.2–1.0). For IL-10 there were no significant allelic differences between the two South African ethnic groups. Furthermore, when the ethnic groups were combined the IL-10 allelic frequencies in the combined South African data were similar to those observed in an Oriental population from Southern China and in an Italian population. However, the allele frequencies of the IFN-γ genotype among the two South African ethnic groups were different when compared to an Italian Caucasoid group. While crude analysis of these data showed both statistically significantly increased and diminished risks of cervical cancer among high producers of INF-γ and low producers of IL-10 respectively, these associations were no longer significant when the data were adjusted for confounding factors. Conclusion These findings demonstrate a clear correlation between ethnicity and IFN-γ polymorphism across different population groups. However, these differences in ethnicity and gene polymorphisms in the aforementioned cytokines are suggested not to influence the development of invasive cervical cancer but may represent an important susceptibility biomarker for other diseases and should be explored further.

Determinants of Sexual Activity and Its Relation to Cervical Cancer Risk among South African Women

BackgroundInvasive cervical cancer is the commonest cause of cancer morbidity and mortality in South African women. This study provides information on adult womens sexual activity and cervical cancer risk in South Africa.MethodsThe data were derived from a case-control study of hormonal contraceptives and cervical cancer risk. Information on age of sexual debut and number of lifetime sexual partners was collected from 524 incident cases and 1541 hospital controls. Prevalence ratios and adjusted prevalence ratios were utilised to estimate risk in exposures considered common. Crude and adjusted relative risks were estimated where the outcome was uncommon, using multiple logistic regression analysis.ResultsThe median age of sexual debut and number of sexual partners was 17 years and 2 respectively. Early sexual debut was associated with lower education, increased number of life time partners and alcohol use. Having a greater number of sexual partners was associated with younger sexual debut, being black, single, higher educational levels and alcohol use. The adjusted odds ratio for sexual debut < 16 years and ≥ 4 life-time sexual partners and cervical cancer risk were 1.6 (95% CI 1.2 – 2.2) and 1.7 (95% CI 1.2 – 2.2), respectively.ConclusionLower socio-economic status, alcohol intake, and being single or black, appear to be determinants of increased sexual activity in South African women. Education had an ambiguous effect. As expected, cervical cancer risk is associated with increased sexual activity. Initiatives to encourage later commencement of sex, and limiting the number of sexual partners would have a favourable impact on risk of cancer of the cervix and other sexually transmitted infections