Browsing by Author "Middelkoop, Keren"
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- ItemOpen AccessAntiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods(Public Library of Science, 2011) Kranzer, Katharina; Lewis, James J; White, Richard G; Glynn, Judith R; Lawn, Stephen D; Middelkoop, Keren; Bekker, Linda-Gail; Wood, RobinBACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
- ItemOpen AccessBurden of new and recurrent tuberculosis in a major South African city stratified by age and HIV-status(Public Library of Science, 2011) Wood, Robin; Lawn, Stephen D; Caldwell, Judy; Kaplan, Richard; Middelkoop, Keren; Bekker, Linda-GailAim: To describe the burden of tuberculosis (TB) in Cape Town by calculating TB incidence rates stratified by age and HIV-status, assessing the contribution of retreatment disease and estimating the cumulative lifetime TB risk in HIV-negative individuals. METHODS: Details of TB cases were abstracted from the 2009 electronic TB register. Population denominators were estimated from census data and actuarial estimates of HIV prevalence, allowing calculation of age-specific and HIV-stratified TB notification rates. RESULTS: The 2009 mid-year population was 3,443,010 (3,241,508 HIV-negative and 201,502 HIV-positive individuals). There were 29,478 newly notified TB cases of which 56% were laboratory confirmed. HIV status was recorded for 87% of cases and of those with known HIV-status 49% were HIV-negative and 51% were positive. Discrete peaks in the incidence of non-HIV-associated TB occurred at three ages: 511/100,000 at 0-4 years of age, 553/100,000 at 20-24 years and 628/100,000 at 45-49 years with 1.5%, 19% and 45% being due to retreatment TB, respectively. Only 15.5% of recurrent cases had a history of TB treatment failure or default. The cumulative lifetime risks in the HIV-negative population of all new TB episodes and new smear-positive TB episodes were 24% and 12%, respectively; the lifetime risk of retreatment disease was 9%. The HIV-positive notification rate was 6,567/100,000 (HIV-associated TB rate ratio = 17). Although retreatment cases comprised 30% of the HIV-associated TB burden, 88% of these patients had no history of prior treatment failure or default. CONCLUSIONS: The annual burden of TB in this city is huge. TB in the HIV-negative population contributed almost half of the overall disease burden and cumulative lifetime risks were similar to those reported in the pre-chemotherapy era. Retreatment TB contributed significantly to both HIV-associated and non-HIV-associated TB but infrequently followed prior inadequate treatment. This likely reflects ongoing TB transmission to both HIV-negative and positive individuals.
- ItemOpen AccessChildhood tuberculosis infection and disease: A spatial and temporal transmission analysis in a South African township(2009) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Zwane, Eugene; Wood, RobinBackground. Tuberculosis (TB) remains a leading cause of South African mortality and morbidity. While adult TB arises from both recent and prior infection, childhood TB results from recent infection and reflects ongoing transmission occurring despite current TB control strategies. Setting. A South African community with high rates of TB and HIV disease. Outcomes. A Geographic Information System was used to spatially and temporally define the relationships between TB exposure, infection and disease in children <15 years of age, with exposure to adult HIV-positive and HIV-negative TB disease on residential plots between 1997 and 2007. Results. During the study period the annual adult TB notification rate increased from 629 to 2106/100,000 and <15yrs TB notification rate ranged between 664/100,000 and 1044/100,000. The mean exposure to adult TB for uninfected children, TB-infected, TB cases was 5.1%, 5.4% and 33% per annum and the mean number of adult smear-positive cases per exposed child was 1.0, 1.6 and 1.9 respectively. Acquisition of TB infection was not associated with HIV status of adult exposure TB case and 36% of child TB cases were diagnosed prior to the temporally closest adult case on their plot. Conclusions. Childhood infection and disease were quantitatively linked to infectious adult TB prevalence in an immediate social network. Childhood infection should be monitored in high burden settings as a marker of ongoing TB transmission. Improved knowledge of township childhood and adult social networks may also facilitate targeted active case finding, which may provide an adjunct to presently failing TB control strategies.
- ItemOpen AccessDecreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township(BioMed Central Ltd, 2014) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Lee, Namee; Wood, RobinBACKGROUND: Tuberculosis (TB) transmission rates are exceptionally high in endemic TB settings. Adolescence represents a period of increasing TB infection and disease but little is known as to where adolescents acquire TB infection. We explored the relationship between residential exposure to adult TB cases and infection in children and adolescents in a South African community with high burdens of TB and HIV. METHODS: TB infection data were obtained from community, school-based tuberculin skin test (TST) surveys performed in 2006, 2007 and 2009. A subset of 2007 participants received a repeat TST in 2009, among which incident TB infections were identified. Using residential address, all adult TB cases notified by the community clinic between 1996 and 2009 were cross-referenced with childhood and adolescent TST results. Demographic and clinic data including HIV status were abstracted for TB cases. Multivariate logistic regression models examined the association of adult TB exposure with childhood and adolescent prevalent and incident TB infection. RESULTS: Of 1,100 children and adolescents included in the prevalent TB infection analysis, 480 (44%) were TST positive and 651 (59%) were exposed to an adult TB case on their residential plot. Prevalent TB infection in children aged 5-9 and 10-14 years was positively associated with residential exposure to an adult TB case (odds ratio [OR]:2.0; 95% confidence interval [CI]: 1.1-3.6 and OR:1.5; 95% CI: 1.0-2.3 respectively), but no association was found in adolescents [greater than or equal to]15years (OR:1.4; 95% CI: 0.9-2.0). HIV status of adult TB cases was not associated with TB infection (p=0.62). Of 67 previously TST negative children, 16 (24%) converted to a positive TST in 2009. These incident infections were not associated with residential exposure to an adult TB case (OR: 1.9; 95% CI: 0.5-7.3). CONCLUSIONS: TB infection among young children was strongly associated with residential exposure to an adult TB case, but prevalent and incident TB infection in adolescents was not associated with residential exposure. The HIV-status of adult TB cases was not a risk factor for transmission. The high rates of TB infection and disease among adolescents underscore the importance of identifying where infection occurs in this age group.
- ItemOpen AccessThe effect of HIV and an Antiretroviral treatment programme on Tuberculosis transmission, incidence and prevalence in a South African Township(2011) Middelkoop, KerenThis doctoral work aimed to describe the epidemiology of TB in a high HIV and TB prevalent community from 1997 to 2008, and to assess the effect of HIV and a highly active antiretroviral therapy (HAART) programme on the TB epidemic in this setting.
- ItemOpen AccessEpidemiology of HIV-1 subtypes among men who have sex with men in Cape Town, South Africa(2013) Middelkoop, Keren; Myer, Landon; Bekker, Linda-GailThere are few data describing the HIV epidemic among men who have sex with men (MSM) in South Africa, and thus little information is available to inform appropriate public health response strategies for this high-risk group. One such existing knowledge gap is an understanding of HIV transmission patterns between different MSM communities and between MSM and the heterosexual population. Studies in the early 1990s identified two independent HIV-1 epidemics in Cape Town: a predominantly subtype B epidemic among white MSM and the mainly subtype C epidemic among the predominantly black heterosexual epidemic. While the heterosexual epidemic remains primarily due to subtype C virus, few recent HIV-1 subtype data are available for MSM in South Africa. This study examined circulating HIV-1 subtypes among MSM in Cape Town.
- ItemOpen AccessFeatures of recently transmitted HIV-1 clade C viruses that impact antibody recognition: implications for active and passive immunization(Public Library of Science, 2016) Rademeyer, Cecilia; Korber, Bette; Seaman, Michael S; Giorgi, Elena E; Thebus, Ruwayhida; Robles, Alexander; Sheward, Daniel J; Wagh, Kshitij; Garrity, Jetta; Carey, Brittany R; Gao, Hongmei; Greene, Kelli M; Tang, Haili; Bandawe, Gama P; Marais, Jinny C; Diphoko, Thabo E; Hraber, Peter; Tumba, Nancy; Moore, Penny L; Gray, Glenda E; Kublin, James; McElrath, M Juliana; Vermeulen, Marion; Middelkoop, Keren; Bekker, Linda-Gail; Hoelscher, Michael; Maboko, Leonard; Makhema, Joseph; Robb, Merlin L; Karim, Salim Abdool; Karim, Quarraisha Abdool; Kim, Jerome H; Hahn, Beatrice H; Gao, Feng; Swanstrom, Ronald; Morris, Lynn; Montefiori, David C; Williamson, CarolynAuthor Summary: Vaccine and passive immunization prophylactic trials that rely on antibody-mediated protection are planned for HIV-1 clade C epidemic regions of southern Africa, which have amongst the highest HIV-1 incidences globally. This includes a phase 2b trial of passively administered monoclonal antibody, VRC01; as well as a phase 3 trial using the clade C modified version of the partially efficacious RV144 vaccine. The extraordinary diversity of HIV-1 poses a major obstacle to these interventions, and our study aimed to determine the implications of viral diversity on antibody recognition. Investigations using our panel of very early viruses augment current knowledge of vulnerable targets on transmitted viruses for vaccine design and passive immunization studies. Evidence of antigenic drift with viruses becoming more resistant over time suggests that these prevention modalities will need to be updated over time and that combinations of antibodies will be necessary to achieve coverage in passive immunization studies. We further show that it may be more difficult to obtain protection in the genetically diverse clade C epidemic compared to RV144 where the epidemic is less diverse, although it should be noted that the correlates of infection risk are yet to be defined in the clade C setting.
- ItemOpen AccessForce of tuberculosis infection among adolescents in a high HIV and TB prevalence community: a cross-sectional observation study(BioMed Central Ltd, 2011) Middelkoop, Keren; Bekker, Linda-Gail; Liang, Hua; Aquino, Lisa; Sebastian, Elaine; Myer, Landon; Wood, RobinBACKGROUND: Understanding of the transmission dynamics of tuberculosis (TB) in high TB and HIV prevalent settings is required in order to develop effective intervention strategies for TB control. However, there are little data assessing incidence of TB infection in adolescents in these settings. METHODS: We performed a tuberculin skin test (TST) and HIV survey among secondary school learners in a high HIV and TB prevalence community. TST responses to purified protein derivative RT23 were read after 3 days. HIV-infection was assessed using Orasure(R) collection device and ELISA testing. The results of the HIV-uninfected participants were combined with those from previous surveys among primary school learners in the same community, and force of TB infection was calculated by age. RESULTS: The age of 820 secondary school participants ranged from 13 to 22 years. 159 participants had participated in the primary school surveys. At a 10 mm cut-off, prevalence of TB infection among HIV-uninfected and first time participants, was 54% (n = 334/620). HIV prevalence was 5% (n = 40/816). HIV infection was not significantly associated with TST positivity (p = 0.07). In the combined survey dataset, TB prevalence was 45% (n = 645/1451), and was associated with increasing age and male gender. Force of infection increased with age, from 3% to 7.3% in adolescents [greater than or equal to]20 years of age. CONCLUSIONS: We show a high force of infection among adolescents, positively associated with increasing age. We postulate this is due to increased social contact with infectious TB cases. Control of the TB epidemic in this setting will require reducing the force of infection.
- ItemOpen AccessHigh prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing: a cross-sectional population based sero-survey in South Africa(Public Library of Science, 2011) Kranzer, Katharina; van Schaik, Nienke; Karmue, Unice; Middelkoop, Keren; Sebastian, Elaine; Lawn, Stephen D; Wood, Robin; Bekker, Linda-GailObjectives: To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test. METHODS: A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model. RESULTS: 1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3-73.6) had previously had an HIV test and 37.5% (34.6-40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3-25.3) with peak prevalence of 41.8% (35.8-47.8) in women aged 25.1-35 years and 37.5% (26.7-48.3) in men aged 25.1-45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5-12.1) overall and 4.5% (2.3-6.6), 8.0% (CI 3.9-12.0) and 20.0% (13.2-26.8) in individuals who had their most recent HIV test within 1, 1-2 and more than 2 years prior to the survey. CONCLUSION: The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed.
- ItemOpen AccessIndoor social networks in a South African township: potential contribution of location to tuberculosis transmission(Public Library of Science, 2012) Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Morrow, Carl; Middelkoop, Keren; Mark, Daniella; Lawn, Stephen DBACKGROUND: We hypothesized that in South Africa, with a generalized tuberculosis (TB) epidemic, TB infection is predominantly acquired indoors and transmission potential is determined by the number and duration of social contacts made in locations that are conducive to TB transmission. We therefore quantified time spent and contacts met in indoor locations and public transport by residents of a South African township with a very high TB burden. METHODS: A diary-based community social mixing survey was performed in 2010. Randomly selected participants (n = 571) prospectively recorded numbers of contacts and time spent in specified locations over 24-hour periods. To better characterize age-related social networks, participants were stratified into ten 5-year age strata and locations were classified into 11 types. RESULTS: Five location types (own-household, other-households, transport, crèche/school, and work) contributed 97.2% of total indoor time and 80.4% of total indoor contacts. Median time spent indoors was 19.1 hours/day (IQR:14.3-22.7), which was consistent across age strata. Median daily contacts increased from 16 (IQR:9-40) in 0-4 year-olds to 40 (IQR:18-60) in 15-19 year-olds and declined to 18 (IQR:10-41) in ≥45 year-olds. Mean daily own-household contacts was 8.8 (95%CI:8.2-9.4), which decreased with increasing age. Mean crèche/school contacts increased from 6.2/day (95%CI:2.7-9.7) in 0-4 year-olds to 28.1/day (95%CI:8.1-48.1) in 15-19 year-olds. Mean transport contacts increased from 4.9/day (95%CI:1.6-8.2) in 0-4 year-olds to 25.5/day (95%CI:12.1-38.9) in 25-29 year-olds. CONCLUSIONS: A limited number of location types contributed the majority of indoor social contacts in this community. Increasing numbers of social contacts occurred throughout childhood, adolescence, and young adulthood, predominantly in school and public transport. This rapid increase in non-home socialization parallels the increasing TB infection rates during childhood and young adulthood reported in this community. Further studies of the environmental conditions in schools and public transport, as potentially important locations for ongoing TB infection, are indicated.
- ItemOpen AccessInvestigating the socio-economic and epidemiological risk factors associated with TB transmission in a high TB and HIV burdened community in Cape Town, South Africa(2018) Tadokera, Rabecca; Middelkoop, Keren; Bekker, Linda-GailBackground: While several studies have studied the associations between biological factors such as HIV-status with TB transmission or clustering, our understanding of the associations between TB transmission and socio-economic risk factors for TB remains incomplete. More studies are required to enhance our understanding, and hence inform targeted interventions to curb TB transmission, particularly in high burden communities. This study aimed to explore the associations between TB transmission and socio-economic risk factors in one such high TB and HIV burdened community. Methods: A cross-sectional molecular epidemiology study was conducted among adult TB patients resident in a geographically well-defined peri-urban township of Cape Town between 2001 and 2010. Following informed consent, clinical and demographic data were extracted from TB registers and clinical folders. Additional socio-economic data were collected using interviewer-administered questionnaires that were designed to capture data on TB history, TB contacts, socio-economic conditions such as occupation, income level, educational level, sexual behaviour, sexual history in addition to other social and demographic data. M.tb isolates from TB patients were previously analysed using IS6110-based RFLP. Strains with <6 copies of IS6110 (low bandwidth strains) are known to be poorly differentiated and so were excluded from analysis. Composite variables were generated for the social and economic factors using a scoring algorithm to create a "social score" and an "economic score". Data was analysed using StataCorp version 12 software. Bivariate associations and adjusted binary logistic regression analyses were performed to determine associations between TB transmission and the social/economic score in addition to other risk factors that were studied. Results: Of the 509 participants who had complete data available, 352 (69%) were classified as clustered while the remaining 157 participants (31%) were classified as non-clustered. Our analysis showed that clustered cases were more likely to have stayed for a longer period in the study community, (OR=1.06, C.I: 1.02 to 1.10, p=0.006). Clustered cases were also more likely to have stayed in the same house for longer, (median=3 years vs. 2 years, p=0.06) and to live in more crowded conditions as shown by the size of the house and number of rooms used for sleeping (p=0.038). While the evidence was weak, there was a tendency towards a positive association between a high social score and clustering (OR=1.39, C.I: 0.94; 2.03, p=0.08). Conversely, there was a moderate negative association between a high economic score and clustering (OR=0.69, C.I: 0.45; 1.06, p=0.09). Conclusions: While the association between poverty (poor socio-economic status) and TB transmission is not new, the association between TB transmission and prolonged stay within a high burdened community that we report in this study is novel. Our findings further suggest that even in poorer communities there is a "sliding-scale of poverty", with individuals at the lower end of the economic scale being at greater risk for acquiring TB infection and that targeted interventions to address TB transmission in such high burdened communities may be required.
- ItemOpen AccessLipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria(BioMed Central Ltd, 2012) Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Middelkoop, Keren; Vogt, Monica; Kreiswirth, Barry; Lawn, StephenBACKGROUND:Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert(R) MTB/RIF assay. RESULTS: 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of [greater than or equal to] 200, 100-199, 50-99, and < 50 cells/mul, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.
- ItemOpen AccessPrevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study(Multidisciplinary Digital Publishing Institute, 2022-03-16) Middelkoop, Keren; Walker, Neil; Stewart, Justine; Delport, Carmen; Jolliffe, David A.; Nuttall, James; Coussens, Anna K.; Naude, Celeste E.; Tang, Jonathan C. Y.; Fraser, William D.; Wilkinson, Robert J.; Bekker, Linda-Gail; Martineau, Adrian R.Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6–11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July–September vs. January–March 10.69, 95% CI 5.02 to 22.77; aOR for October–December vs. January–March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01–1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03–1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January–March to 22.8% in July–September.
- ItemOpen AccessSocio-behaviour challenges to phase III HIV vaccine trials in sub-Saharan Africa(2005) Smit, Joalida; Middelkoop, Keren; Myer, Landon; Lindegger, Graham; Swartz, Leslie; Seedat, Soraya; Tucker, Tim; Wood, Robin; Bekker, Linda-Gail; Stein, Dan JBackground: A number of countries in sub-Saharan Africa are preparing for HIV vaccine efficacy trials. Social and behavioural factors related to HIV transmission require examination in each setting where these trials are considered. As part of this, several countries have also recently begun preparatory research investigating relevant social and behavioural issues. There is a need for a review of the literature to help focus such research efforts in Sub-Saharan Africa. Objective: To examine key social and behavioural issues that may impact on the conduct of HIV vaccine efficacy trials in sub-Saharan Africa. Design: Literature review Methods: Major databases (PubMed, PsychInfo, EBSCOhost, and AIDSline) were searched for literature that discussed social and behavioural issues related to HIV vaccine trials. Three areas are highlighted as being particularly significant for HIV vaccine research: (1) willingness to participate in future HIV vaccine efficacy trials, (2) retention of participants in studies, and (3) sexual risk reporting during trials. For each of these topics, major findings from both developed and developing countries are described and avenues for further research are discussed. Results: There are few data from Sub-Saharan Africa regarding willingness to participate in HIV vaccine trials. Data on participant retention rates varies widely, and maintaining large cohorts of individuals within Phase III trials presents an important challenge. In addition, the possible impact of trial participation on sexual disinhibition, and response bias on sexual risk-reporting remain as issues for HIV vaccine trials in African contexts. Conclusions: Social and behavioural research forms an important part of preparations for HIV vaccine efficacy trials, and there is a clear need for more research of this type in Sub-Saharan Africa. Innovative approaches are required to address issues such as willingness to participate in vaccine research, participant retention during efficacy trials, and the accurate reporting by participants of sexual risk behaviours.
- ItemOpen AccessTB transmission is associated with prolonged stay in a low socio-economic, high burdened TB and HIV community in Cape Town, South Africa(2020-02-10) Tadokera, Rebecca; Bekker, Linda-Gail; Kreiswirth, Barry N; Mathema, Barun; Middelkoop, KerenAbstract Background While several studies have assessed the associations between biological factors and tuberculosis (TB) transmission, our understanding of the associations between TB transmission and social and economic factors remains incomplete. We aimed to explore associations between community TB transmission and socio-economic factors within a high TB-HIV burdened setting. Methods We conducted a cross-sectional molecular epidemiology study among adult patients attending a routine TB clinic. Demographic and clinical data were extracted from TB registers and clinical folders; social and economic data were collected using interviewer-administered questionnaires; Mycobacterium tuberculosis isolates were genotyped and classified as clustered/non-clustered using IS6110-based Restriction Fragment Length Polymorphism. Composite “social” and “economic” scores were generated from social and economic data. Data were analyzed using StataCorp version 15.0 software. Stratified, bivariable analyses were performed using chi-squared. Wilcoxon signed rank tests; univariable and multivariable logistic regression models were developed to explore associations in the social, economic, traditional and composite TB risk factors with TB transmission. Results Of the 505 patient Mtb strains, 348(69%) cases were classified as clustered and 157(31%) were non-clustered. Clustered cases were more likely to have lived longer in the study community, (odds ratio [OR] = 1.05, 95% Confidence interval [C.I]:1.02–1.09, p = 0.006); in the same house (OR = 1.04, C.I: 0.99–1.08, p = 0.06); and had increased household crowding conditions (i.e fewer rooms used for sleeping, OR = 0.45, C.I:0.21–0.95, p = 0.04). Although a higher proportion of clustered cases had a low economic score, no statistically significant association was found between clustering and either the economic score (p = 0.13) or social score (p = 0.26). Conclusions We report a novel association between Mtb transmission and prolonged stay within a high burdened community. Transmission was also associated with fewer rooms for sleeping in a household. Increased social interaction and prolonged residence in a high burdened community are important factors linked to Mtb transmission, possibly due to increased probability of higher effective contact rates. The possible importance of degrees of poverty within low socio-economic setting warrants further study.
- ItemOpen AccessThe association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review(BioMed Central, 2017-12-15) Hyle, Emily P; Mayosi, Bongani M; Middelkoop, Keren; Mosepele, Mosepele; Martey, Emily B; Walensky, Rochelle P; Bekker, Linda-Gail; Triant, Virginia Aackground: Sub-Saharan Africa (SSA) has confronted decades of the HIV epidemic with substantial improvements in access to life-saving antiretroviral therapy (ART). Now, with improved survival, people living with HIV (PLWH) are at increased risk for non-communicable diseases (NCDs), including atherosclerotic cardiovascular disease (CVD). We assessed the existing literature regarding the association of CVD outcomes and HIV in SSA. Methods: We used the PRISMA guidelines to perform a systematic review of the published literature regarding the association of CVD and HIV in SSA with a focus on CVD surrogate and clinical outcomes in PLWH. Results: From January 2000 until March 2017, 31 articles were published regarding CVD outcomes among PLWH in SSA. Data from surrogate CVD outcomes (n = 13) suggest an increased risk of CVD events among PLWH in SSA. Although acute coronary syndrome is reported infrequently in SSA among PLWH, limited data from five studies suggest extensive thrombus and hypercoagulability as contributing factors. Additional studies suggest an increased risk of stroke among PLWH (n = 13); however, most data are from immunosuppressed ART-naïve PLWH and thus are potentially confounded by the possibility of central nervous system infections. Conclusions: Given ongoing gaps in our current understanding of CVD and other NCDs in PLWH in SSA, it is imperative to ascertain the burden of CVD outcomes, and to examine strategies for intervention and best practices to enhance the health of this vulnerable population.
- ItemOpen AccessThe epidemiology of Chronic Non-Communicable Diseases (NCDS) and NCD risk factors in adolescents & youth living with HIV in Cape Town, South Africa(2021) Kamkuemah, Monika; Oni, Tolullah; Middelkoop, KerenIntroduction: South Africa, like many other low- and middle-income countries (LMIC), is currently undergoing an epidemiological transition with a growing burden of noncommunicable diseases (NCDs) co-occurring with an existent burden of infectious diseases like human immunodeficiency virus (HIV). South Africa continues to have the biggest HIV epidemic globally, and adolescents and young people, especially young women, bear a disproportionate burden of HIV in the country. Adolescents and youth living with HIV (AYLHIV) face an elevated NCD risk resulting from chronic immune activation, psychosocial factors and the complications of long-term antiretroviral therapy (ART). However, there is data paucity on the intersection of NCDs and HIV in adolescents in South Africa and Africa. This thesis aims to contribute to the limited evidence base in LMIC settings by investigating NCD multimorbidity and risk factors in AYLHIV within a context of epidemiological transition and urbanisation. Objectives: This aim is achieved by fulfilling the following research objectives: 1. To investigate the extent to which NCD comorbidity (prevention, screening and management) is incorporated within existing adolescent HIV primary healthcare services in Cape Town, South Africa. 2. To estimate the prevalence of common NCDs and their known cardiometabolic, respiratory and behavioural risk factors in AYLHIV residing in peri-urban Cape Town. 3. To determine individual, household, social and neighbourhood level factors associated with obesity in AYLHIV. Methods: I conducted a narrative literature review to inform the development of a conceptual framework for investigating the intersection of adolescence developmental theory with NCDs and HIV. The emergent concepts were explored from an over-arching socioecological viewpoint, drawing on life course epidemiology and epidemiological transition theories. I conducted a cross-sectional quantitative study in nine primary care facilities across peri-urban Cape Town. The study was conducted in two parts. The first part of the study was comprised of data collected from 491 medical records of AYLHIV accessing HIV care in these facilities. The second part of the study sought to investigate the epidemiology of NCDs and NCD risk factors and to assess multilevel factors associated with abdominal obesity (the primary outcome). I recruited 176 eligible AYLHIV to participate in the study with primary data (on NCDs and NCD risk factors) collected from 92 participants during routine clinic visits between March and December 2019. Results: The findings from the 491 patient medical records reviewed demonstrated limited attention to NCD comorbidity prevention, screening and treatment within adolescent HIV primary care services. Only 62% of patient folders had documented anthropometric measurements, 59% had documented blood pressure measurements, and less than 11% of patient folders reviewed had any NCD health promotion documented. Among the 92 participants recruited for primary data collection, 76% were female. More than a quarter (27%) were not in education, employment or training; 70% lived in food-insecure households, and 44% were multidimensionally poor. At the individual level, a high prevalence of NCDs was found, particularly elevated blood pressure and hypertension (20% and 5% respectively), overweight/obesity (36%), central obesity (37%), and depressive symptoms (43%). With respect to NCD risk factors, 69% reported engaging in sufficient physical activity (79% of males and 66% of females), and 49% reported three or more hours of sedentary behaviour per day. However, unhealthy dietary practices were common, with only 27% eating fresh fruit, 52% eating vegetables and 33% eating whole grains daily. On the other hand, 29% drank sugar-sweetened beverages, and 33% ate sweets and cakes daily, while 42% skipped breakfast regularly. Furthermore, nutritional knowledge was low, especially with respect to healthy food choices and dietdisease relationships. Risky behaviours were also prevalent with 30% current smokers (48% males and 25% females) and 41% alcohol use in the past month (58% males versus 36% females), with binge drinking most commonly reported in the youngest age group < 18 years (55%). Significantly more malesreported lifetime use of any illicitsubstances(53% versus 30% for females), with cannabis the most frequently reported substance used (23% lifetime prevalence). Beyond individual-level risk factors, household-level factors were also explored. More than half (58%) reported the death of one or both parents, while 47% reported a biological parent as their primary caregiver. Parental level factors were largely positive, with participants reporting high levels of positive parenting and parental supervision. However, 35% lived in informal dwellings, 38% did not have access to piped water inside their dwelling and 62% experienced thermal discomfort in winter. Community experiences revealed a mixed picture, with 61% of participants exposed to high levels of community violence, while participants largely reported high neighbourhood belonging and low levels of stigma. Multilevel regression was conducted to investigate the factors associated with abdominal obesity at different socio-ecological levels. All models were adjusted for sex and age. Statistically significant individual-level risk factors that were associated with higher odds of abdominal obesity were skipping breakfast (OR= 5.42; 95% confidence interval (CI): 1.32 – 22.25) and absence from school or work (OR= 3.06; 95% CI: 1.11 – 8.40), while daily whole grain consumption (OR= 0.20; 95% CI: 0.05 – 0.71) and weekly moderate-intensity physical activity (OR = 0.24; 95% CI: 0.06 – 0.92) were associated with lower odds of abdominal obesity. At the household- and community levels, experiencing thermal discomfort was associated with increased odds of obesity (OR= 4.42; 95% CI: 1.43 – 13.73), while higher anticipated stigma was associated with reduced odds of obesity (OR= 0.58; 95% CI: 0.33 – 1.00). The features of the built and food environment that were associated with reduced odds of abdominal obesity in AYLHIV were land-use mix diversity (OR= 0.52; 95% CI: 0.27 – 0.97), access to recreational places (OR= 0.37; 95% CI: 0.18 – 0.74), higher perceived pedestrian and traffic safety (OR= 0.20; 95% CI: 0.05 – 0.80), and having a non-fast-food restaurant within walking distance (OR= 0.30; 95% CI: 0.10 – 0.93). Conclusion: These results indicate an existent burden of NCDs and NCD risk factors in urban AYLHIV. Beyond the NCD risk attributable to HIV and ART, these multiple risk factors coupled with early initiation of high-risk behaviours like smoking and harmful alcohol use further increase NCD risk. Despite high NCD comorbidity and risk, evidence shows little to no integration of health services and limited responsiveness with regards to NCD health promotion. These findings underscore a missed opportunity in multimorbidity prevention. Overall, these findings highlight the need for a comprehensive, integrated approach for AYLHIV to both prevent and manage NCD multimorbidity within primary care. This integrated approach should include mental health assessment and screening for weight status, abdominal obesity and blood pressure to identify comorbid NCDs early and intervene to improve NCD outcomes. Additionally, risk factor screening should be incorporated into HIV care to prevent NCD multimorbidity. Screening should include early identification of the most common NCD risk factors (insufficient physical activity, poor dietary practices, smoking, alcohol use and binge drinking, particularly in male adolescents and younger age groups). These findings also highlight the need for intervention at various levels of the socio-ecological framework through multisectoral interventions in the social and built environments. Finally, this thesis contributes an evidence base to inform the development of integrated and intersectoral models of care to address the colliding epidemics of HIV and NCDs in young people in LMIC settings.