SUNScholar - Browsing by Author "Bekker, Linda-Gail"

Browsing by Author "Bekker, Linda-Gail"

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Burden of new and recurrent tuberculosis in a major South African city stratified by age and HIV-status
(Public Library of Science, 2011-10-10) Wood, Robin; Lawn, Stephen D.; Caldwell, Judy; Kaplan, Richard; Middelkoop, Keren; Bekker, Linda-Gail
Aim 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.
High human papillomavirus (HPV) prevalence in South African adolescents and young women encourages expanded HPV vaccination campaigns
(Public Library of Science, 2018-01-02) Mbulawa, Zizipho Z. A.; Van Schalkwyk, Cari; Hu, Nai-Chung; Meiring, Tracy L.; Barnabas, Shaun; Dabee, Smritee; Jaspan, Heather; Kriek, Jean-Mari; Jaumdally, Shameem Z.; Muller, Etienne; Bekker, Linda-Gail; Lewis, David A.; Dietrich, Janan; Gray, Glenda; Passmore, Jo-Ann S.; Williamson, Anna-Lise
The objectives of the study were to investigate prevalence of cervical human papillomavirus (HPV) genotypes to inform HPV vaccination strategy in South Africa and to study factors associated with HPV prevalence. Sexually active, HIV-negative women, aged 16–22 years recruited from Soweto (n = 143) and Cape Town (n = 148) were tested for cervical HPV and other genital infections. Overall HPV prevalence was 66.7% (194/291) in young women. Cape Town women were more likely to have multiple HPV infections than the Soweto women (48.0%, 71/148 versus 35.0%, 50/143 respectively, p = 0.033) and probable HR-HPV types (34.5%, 51/148 versus 21.7%, 31/143 respectively, p = 0.022). The most frequently detected HPV types were HPV-16 (11.7%), HPV-58 (10.3%), HPV-51 (8.9%), HPV-66 (8.6%), HPV-18 and HPV-81 (7.6% each). HPV types targeted by the bivalent HPV vaccine (HPV-16/18) were detected in 18.6% (54/291) of women, while those in the quadrivalent vaccine (HPV-6/11/16/18) were detected in 24.7% (72/291) of women; and those in the nonavalent vaccine (HPV-6/11/16/18/31/33/45/52/58) were detected in 38.5% (112/291) of women. In a multivariable analysis, bacterial vaginosis remained significantly associated with HPV infection (OR: 4.0, 95% CI: 1.4–12.6). Women were more likely to be HPV positive if they had received treatment for STI during the past 6-months (OR: 3.4, 95% CI: 1.1–12.4) or if they had ever been pregnant (OR: 2.3, 95% CI: 1.1–5.5). Compared to women who reported only one sexual partner, those with increased number of lifetime sex partners were more likely to have HPV (4–10 partners: OR: 2.9, 95% CI: 1.1–8.0). The high prevalence of HPV types targeted by the nonavalent HPV vaccine encourages the introduction of this vaccine and catch-up HPV vaccination campaigns in South Africa. The high burden of BV and concurrent STIs also highlights the need to improve the prevention and appropriate management of sexually-acquired and other genital tract infections in South African youth.
High 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, 2011-09-28) Kranzer, Katharina; Van Schaik, Nienke; Karmue, Unice; Middelkoop, Keren; Sebastian, Elaine; Lawn, Stephen D.; Wood, Robiin; Bekker, Linda-Gail
Objectives 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.
The impact of mass media interventions on tuberculosis awareness, health-seeking behaviour and health service utilisation : a systematic review protocol
(BMJ Publishing Group, 2014-12) Nglazi, Mweete D.; Bekker, Linda-Gail; Wood, Robin; Shey, Muki S.; Uthman, Olalekan A.; Wiysonge, Charles S.
Introduction: Tuberculosis (TB) is a serious public health problem in many parts of the world. Strategies to curb the spread of TB must match the multifaceted nature of the epidemic. The use of mass media is one of the important strategies in communicating behavioural change in relation to TB prevention and the treatment. However, the benefits of this intervention are unclear. We, therefore, plan to conduct a systematic review on the effects of mass media interventions on TB awareness, health-seeking behaviour and health service utilisation. Methods: and analysis We will preferably include randomised controlled trials (RCTs) in this systematic review. However, non-randomised studies will be included if there is an inadequate number of RCTs. We will perform electronic searches in PubMed, Scopus and other databases, along with manual searches. Articles written (or translated) in English and French and published between 1 January 1980 and 31 October 2013 will be eligible for inclusion in this review. The primary outcomes will be TB knowledge, attitudes and awareness, healthcare-seeking behaviour and service utilisation. The secondary outcomes will include stigma and discrimination against people with TB and the costs of the interventions. We will investigate clinical and statistical heterogeneity and pool studies judged to be clinically and statistically homogeneous. Relative risks will be calculated for dichotomous outcomes and mean differences for continuous outcomes, both with their corresponding 95% CIs. Ethics: and dissemination The systematic review will use data that is not linked to individuals. The review findings may have implications for clinical practice and future research, and will be disseminated electronically and in print through peer-reviewed publications.
Indoor social networks in a South African township : potential contribution of location to tuberculosis transmission
(Public Library of Science, 2012-06-29) Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Morrow, Carl; Middelkoop, Keren; Mark, Daniella; Lawn, Stephen D.
Background 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.
Intra- and inter-clade cross-reactivity by HIV-1 gag specific T-cells reveals exclusive and commonly targeted regions : implications for current vaccine trials
(Public Library of Science, 2011-10-12) Zembe, Lycias; Burgers, Wendy A.; Jaspan, Heather B.; Bekker, Linda-Gail; Bredell, Helba; Stevens, Gwynneth; Gilmour, Jill; Cox, Josephine H.; Fast, Patricia; Hayes, Peter; Vardas, Eftyhia; Williamson, Carolyn; Gray, Clive M.
ENGLISH ABSTRACT: The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-c Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p,0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities.
Lipoarabinomannan in urine during tuberculosis treatment : association with host and pathogen factors and mycobacteriuria
(BioMed Central, 2012-02) Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Middelkoop, Keren; Vogt, Monica; Kreiswirth, Barry N.; Lawn, Stephen D.
Microbial function and genital inflammation in young South African women at high risk of HIV infection
(BMC (part of Springer Nature), 2020-11-21) Alisoltani, Arghavan; Manhanzva, Monalisa T.; Potgieter, Matthys; Balle, Christina; Bell, Liam; Ross, Elizabeth; Iranzadeh, Arash; du Plessis, Michelle; Radzey, Nina; McDonald, Zac; Calder, Bridget; Allali, Imane; Mulder, Nicola; Dabee, Smritee; Barnabas, Shaun; Gamieldien, Hoyam; Godzik, Adam; Blackburn, Jonathan M.; Tabb, David L.; Bekker, Linda-Gail; Jaspan, Heather B.; Passmore, Jo-Ann S.; Masson, Lindi
Background: Female genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile; however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium, or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations. Results: A total of 3186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p < 0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women 9 weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT inflammation in an independent sample of ten women. Conclusions: Both the presence of specific microbial taxa in the FGT and their properties and activities are critical determinants of FGT inflammation. Our findings support those of previous studies suggesting that peptidoglycan is directly immunosuppressive, and identify a possible avenue for biotherapeutic development to reduce inflammation in the FGT.
Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment : a systematic review
(BioMed Central, 2013-12-02) Nglazi, Mweete D.; Bekker, Linda-Gail; Wood, Robin; Hussey, Gregory D.; Wiysonge, Charles S.
Background: Mobile phone text messaging (SMS) has the potential to promote adherence to tuberculosis treatment. This systematic review aims to synthesize current evidence on the effectiveness of SMS interventions in improving patients’ adherence to tuberculosis treatment. Methods: We searched electronic databases (PubMed, EMBASE, Science Citation Index), reference lists of relevant articles, conference proceedings, and selected websites for eligible studies available by 15 February 2013; regardless of language or publication status. Two authors independently screened selected eligible studies, and assessed risk of bias in included studies; resolving discrepancies by discussion and consensus. Results: We identified four studies that compared the outcomes of the SMS intervention group with controls. Only one of the four studies was a randomized controlled trial. This was conducted in Argentina and the SMS intervention did not significantly improve adherence to tuberculosis treatment compared to self-administration of tuberculosis treatment (risk ratio [RR] 1.49, 95% confidence intervals [CI] 0.90 to 2.42). One of the non-randomized studies, conducted in South Africa, which compared SMS reminders to directly observed therapy short course (DOTS) reported similar rates of tuberculosis cure (62.35% vs. 66.4%) and treatment success (72.94% vs. 69.4%). A second study from South Africa, utilized SMS reminders when patients delayed in opening their pill bottles and reported increased tuberculosis cure (RR 2.32, 95% CI 1.60 to 3.36) and smear conversion (RR 1.62, 95% CI 1.09 to 2.42) rates compared to DOTS. In the third non-randomized study, conducted in Kenya, use of SMS reminders increased rates of clinic attendance on scheduled days compared to standard care (RR 1.56, 95% CI 1.06 to 2.29). Using the GRADE approach, we rate the quality of the evidence as low, mainly because of the high risk of bias and heterogeneity of effects across studies. Conclusions: This systematic review indicates that there is a paucity of high-quality data on the effectiveness of SMS interventions for improving patients’ adherence to tuberculosis treatment. The low quality of the current evidence implies that further studies (in particular randomized trials) on the subject are needed. In the interim, if the intervention is implemented outside research settings an impact evaluation is warranted.
Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay : a prospective study
(Public Library of Science, 2011-07-26) Lawn, Stephen D.; Brooks, Sophie V.; Kranzer, Katharina; Nicol, Mark P.; Whitelaw, Andrew; Vogt, Monica; Bekker, Linda-Gail; Wood, Robin
Background: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. Methods and Findings: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/μl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). Conclusions: In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. © 2011 Lawn et al.
Socio-behaviour challenges to phase III HIV vaccine trials in Sub-Saharan Africa
(Makerere University Medical School, 2005-09) Smit, Joalida; Middelkoop, Keren; Myer, Landon; Lindegger, Graham; Swartz, Leslie; Seedat, Soraya; Tucker, Tim; Wood, Robin; Bekker, Linda-Gail; Stein, Dan J.
Background: 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.
TB transmission is associated with prolonged stay in a low socio-economic, high burdened TB and HIV community in Cape Town, South Africa
(BMC (part of Springer Nature), 2020-02-10) Tadokera, Rebecca; Bekker, Linda-Gail; Kreiswirth, Barry N.; Mathema, Barun; Middelkoop, Keren
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 chisquared. 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 nonclustered. 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.
Tuberculosis control has failed in South Africa : time to reappraise strategy
(Health and Medical Publishing Group (HMPG), 2011) Wood, Robin; Lawn, Stephen D.; Johnstone-Robertson, Simon; Bekker, Linda-Gail
South Africa's rate of tuberculosis (TB) has increased over the last 20 years, to now having the third-highest TB burden in the world. The TB control programme has primarily focused on effective case management of passively presenting TB cases, and progress has been recorded towards international treatment targets. While outcomes for notified TB cases have improved, this strategy failed to contain the TB epidemic. South Africa has the highest per capita annual risk of TB disease of comparably sized countries globally, and its communities have extremely high TB transmission rates. The rates of TB infection of children and adolescents are now similar to those reported 100 years ago in Europe long before chemotherapy became available. High rates of HIV testing of TB patients in Cape Town allows analysis of TB notification data stratified by age, type of TB and HIV status, and a better understanding of TB epidemiology. TB infection prevalence data from Cape Town communities allow estimation of the prevailing force of TB infection and, together with TB notification and prevalence data, the effective number of secondary infections and case finding proportions can be estimated. This better understanding of the major drivers of the TB epidemic allows reasons to be identified for failure of the present strategy. New control strategies can also be identified, that must be accompanied by novel TB control targets.

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