Browsing by Author "Mahomed, Hassan"
- ItemOpen AccessThe candidate TB vaccine, MVA85A, induces highly durable Th1 responses(Public Library of Science, 2014) Tameris, Michele; Geldenhuys, Hennie; Luabeya, Angelique KanyKany; Smit, Erica; Hughes, Jane E; Vermaak, Samantha; Hanekom, Willem A; Hatherill, Mark; Mahomed, Hassan; McShane, Helen; Scriba,Thomas JBACKGROUND: Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis ( M.tb ). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone. METHODS: We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011. RESULTS: Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA−CCR7+ central memory or CD45RA−CCR7− effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination. CONCLUSION: MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.
- ItemOpen AccessChildhood mortality in the Boland Overberg region(2007) Moyo, Sizulu; Mahomed, Hassan; Groenewald, Pam; Hawkridge, AnthonyThe aim of this thesis is to characterise the profile of infant, childhood and adolescent mortality in three adjancent district municipalities in the Boland region of the Western Cape Province of South Africa.
- ItemOpen AccessComparison of mantoux and tine tuberculin skin tests in BCG-vaccinated children investigated for tuberculosis(Public Library of Science, 2009) Pan, Wenli; Matizirofa, Lyness; Workman, Lesley; Hawkridge, Tony; Hanekom, Willem; Mahomed, Hassan; Hussey, Gregory; Hatherill, MarkBackground: Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result. Methodology/Principal Findings: 1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result. Conclusions/Significance: The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.
- ItemOpen AccessCOVID-19 and the Gaping Wounds of South Africa’s Suboptimal Immunisation Coverage: An Implementation Research Imperative for Assessing and Addressing Missed Opportunities for Vaccination(2021-06-23) Nnaji, Chukwudi A; Wiysonge, Charles S; Lesosky, Maia; Mahomed, Hassan; Ndwandwe, DuduzileDespite South Africa’s substantial investments in and efforts at ensuring universal access to immunisation services, progress has stalled and remains suboptimal across provinces and districts. An additional challenge is posed by the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has disrupted immunisation services globally, including in South Africa. While there is growing evidence that missed opportunities for vaccination (MOV) are a major contributor to suboptimal immunisation progress globally, not much is known about the burden and determinants of MOV in the South African context. Herein, we make a case for assessing MOV as a strategy to address current immunisation coverage gaps while mitigating the adverse impacts of the COVID-19 pandemic on immunisation services. We illustrate a practical implementation research approach to assessing the burden of MOV among children in primary care settings; for understanding the factors associated with MOV; and for designing, implementing, and evaluating context-appropriate quality improvement interventions for addressing missed opportunities. Such efforts are vital for building health system resilience and maintaining immunisation programme capacity to optimally deliver essential health services such as routine childhood immunisation, even during pandemics.
- ItemOpen AccessEvaluation of Xpert® MTB/RIF assay in induced sputum and gastric lavage samples from young children with suspected tuberculosis from the MVA85A TB vaccine trial(Public Library of Science, 2015) Bunyasi, Erick Wekesa; Tameris, Michele; Geldenhuys, Hennie; Schmidt, Bey-Marrie; Luabeya, Angelique Kany Kany; Mulenga, Humphrey; Scriba, Thomas J; Hanekom, Willem A; Mahomed, Hassan; McShane, HelenObjective Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert ® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. METHODS: We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ 2 test; and Wilson's score method to calculate sensitivity and specificity. RESULTS: 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. CONCLUSION: Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum and gastric lavage to justify selection of one sampling method over the other, in young children with suspected pulmonary TB. Trial Registration ClinicalTrials.gov NCT00953927
- ItemOpen AccessThe incidence of tuberculosis in adolescents in the context of proposed TB vaccine trials(2013) Mahomed, Hassan; Ehrlich, Rodney; Hussey, Gregory; Verver, Suzanne[Background] Tuberculosis (TB) is a significant global health problem and the development of new TB vaccines is one strategy proposed to address this scourge. Adolescents are a potential target group for new TB vaccines. Limited data are available in the scientific literature on the epidemiology of TB in adolescents. This thesis aimed to add substantial data on adolescent TB epidemiology through a cohort study of TB infection and disease in adolescents in a high burden setting. Such data will support clinical trials of new TB vaccines in adolescents but the knowledge gained will also be of value for TB Control Programmes. [Methods] Adolescents aged 12-18 years were recruited from 11 high schools in the rural town of Worcester and surrounding areas of the Western Cape Province of South Africa. They were screened at baseline for latent TB infection using both the tuberculin skin test (TST) and an interferon gamma release assay, the QuantiFERON® TB Gold (in-tube) assay (QFT). They were also screened for TB disease using an algorithm composed of a set of screening tests. They were followed up for at least two years for incident TB and the predictive value of the baseline TST and QFT for incident TB disease was compared. Demographic, socio-economic and clinical predictive factors for latent TB infection prevalence at enrolment and for incident TB disease during follow up were determined. A survey of attitudes to participation in TB vaccine clinical trials in a subset of adolescents from these schools was also conducted. Both studies had ethics approval. Standard scientific statistical techniques were used to analyse the data. [Results] Fifty eight percent (6363) of the target population of 10,492 adolescents were recruited into the main cohort study. A prevalence of latent TB infection amongst the study participants at enrolment of 55% (TST) and 51% (QFT) was found. Predictive factors for latent infection were: being of black or mixed race origin compared to being of white or indian origin, older age (>15 years), previous household TB contact, low parental income and low education status of the parents. The TST and QFT were found to have good agreement (% agreement 84.8%, kappa [κ] = 0.70, 95%CI 0.68–0.71) in contrast to certain studies in other settings. A baseline prevalence of TB disease of 3/1000 was found in adolescents. While the TST and QFT were sensitive predictors of the presence of TB disease, none of the screening tests evaluated (TB related symptoms, recent household contact, TST or QFT) had high positive predictive values (all less than 2%) making these tests impractical for routine use. Given the imperative for screening in TB vaccine trials, these data are important for deciding on choice of screening tests in a clinical trial setting. Both the TST and QFT were found to be predictive of the onset of TB and were equally predictive. An incidence of bacteriologically confirmed active TB of 0.45/100 (95% confidence interval 0.29-0.72) person years (pyrs) was found in this cohort. Using different definitions of active TB, the rate varied from 0.31-0.59/ 100 pyrs. Risk factors gleaned at baseline that were predictive of the onset of TB disease were: being of black or mixed race origin, maternal education of primary school or less or unknown, evidence of latent infection (positive TST or QFT) and absence of a BCG scar. Knowledge of TB was fair amongst adolescents but willingness to participate in TB vaccine trials varied depending on the procedures involved. [Limitations] Important limitations were as follows. The data presented are likely to underestimate the true prevalence and incidence of TB amongst adolescents in general since adolescents not at school are likely to have higher rates of TB than those attending school. On the other hand TB rates amongst those recruited are likely to have been higher than those not agreeing to participate since participation rates were higher in poorer schools than in more affluent schools. Chest radiographs as a screening tool for TB could not be evaluated because this method of screening was excluded for logistical reasons. The number of TB cases is likely to have been underestimated since smear screening was the main method of case detection and smear negative culture positive TB cases would have been missed. [Application of results] A range of data was obtained through these analyses which will be very useful for planning TB vaccine trials in adolescents and also for TB Control Programmes. Since data were collected in a high TB burden setting, the findings are mainly generalisable to such settings rather than low burden settings. Nevertheless, efficacy trials of new TB vaccines are likely to be carried out in high TB burden settings making these results highly relevant to TB vaccine efficacy trial planning. Policy with respect to the use of interferon gamma release assays will be informed by this data given that it is a relatively new diagnostic modality. Knowledge of the baseline prevalence of TB disease and the utility of different screening tools amongst healthy adolescents would help the design and costing of screening approaches to be used in TB vaccine clinical trials which include adolescents. The data on the prevalence of latent TB infection will assist with the selection of TB vaccine candidates for this target group will be of value given that certain vaccines are designed to target those with latent infection. These data will also support planning where latent TB infection is an exclusion criterion such as in safety trials. TB incidence rates can be used to plan samples sizes for efficacy trials. The comparison of the TST and QFT with respect to prevalence of latent TB infection and predictive value for TB disease provide evidence for policies on the use of these tools in clinical trials and for TB Control Programmes in high burden settings. The fact that these measures showed good agreement and were equally predictive of the onset of TB disease, suggest that the QFT need not replace the TST in current routine practice. However, the two tests may be used interchangeably to equal effect. The knowledge and attitudes of adolescents towards participation in TB vaccine trials provides some guidance with respect to what to expect when approaching this group for recruitment purposes. In summary, the prevalence of latent TB infection, the prevalence and incidence of TB disease and predictive factors for latent infection and disease as well as the knowledge and attitudes of adolescents towards participating in TB vaccine trials are described in this thesis. The application of these results to TB vaccines trials and potential value in TB Control Programmes is discussed.
- ItemOpen AccessInflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response(2014-06-09) Matsumiya, Magali; Harris, Stephanie A; Satti, Iman; Stockdale, Lisa; Tanner, Rachel; O’Shea, Matthew K; Tameris, Michelle; Mahomed, Hassan; Hatherill, Mark; Scriba, Thomas J; Hanekom, Willem A; McShane, Helen; Fletcher, Helen AAbstract Background Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration ClinicalTrials.gov number NCT00953927
- ItemOpen AccessIsolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis(Public Library of Science, 2006) Hatherill, Mark; Hawkridge, Tony; Whitelaw, Andrew; Tameris, Michele; Mahomed, Hassan; Moyo, Sizulu; Hanekom, Willem; Hussey, GregoryObjective To evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community. METHODS: Children were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001-2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis . RESULTS: Mycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5-7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31-50), compared to 67% (95% CI 58-76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9-12). Compared to those with culture-proven M. tuberculosis , children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0-0.76). Children with NTM were older (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04). DISCUSSION: NTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation.
- ItemOpen AccessMissed Opportunities for Vaccination and Associated Factors among Children Attending Primary Health Care Facilities in Cape Town, South Africa: A Pre-Intervention Multilevel Analysis(2022-05-16) Nnaji, Chukwudi A; Wiysonge, Charles S; Adamu, Abdu A; Lesosky, Maia; Mahomed, Hassan; Ndwandwe, DuduzileDespite the substantial efforts at ensuring universal access to routine immunisation services among children in South Africa, major gaps in immunisation coverage remain. This study assessed the magnitude of missed opportunities for vaccination (MOV) and associated factors among children aged 0–23 months attending primary health care (PHC) facilities in Cape Town. We used multilevel binomial logistic regression models to explore individual and contextual factors associated with MOV, with children aged 0–23 months at Level 1, nested within PHC facilities (Level 2). A total of 674 children and their caregivers were enrolled. MOV prevalence was 14.1%, ranging from 9.1% to 18.9% across sub-districts. Dose-specific MOV prevalence was highest for the second dose of measles vaccine (9.5%) and lowest for the first dose of rotavirus vaccine (0.6%). The likelihood of a child experiencing MOV was significantly associated with caregivers’ low level of education (Odds ratio (OR) = 3.53, 95% credible interval (CrI): 1.13–11.03), recent receipt of immunisation messages (OR = 0.46, 95%CrI: 0.25–0.87), shared immunisation decision making by both parents (OR = 0.21, 95%CrI: 0.07–0.62) and health facility staff number (OR = 0.18, 95%CrI: 0.06–0.61). The burden of MOV among children in Cape Town is influenced by individual and contextual factors, which provide important opportunities for quality improvement and broader strategies to improve routine immunisation service delivery.
- ItemOpen AccessThe predictive value of a QuantiFERON conversion in the development of active tuberculosis disease in adolescents(2011) Machingaidze, Shingai; Mahomed, HassanThis study is an extension of a prospective epidemiological study of TB disease and infection in adolescents in the Worcester and surrounding areas in the Western Cape carried out from 2005 to 2009, in which 6363 participants were enrolled from local public schools. In this follow-on study, a subset of adolescents who were identified to have converted their QFT status during the original study will be followed up and observed for the occurrence of active TB disease over a period of two years. A similar sized, random sample of participants identified to have a QFT status that remained negative throughout the original study will be used as the control group.
- ItemOpen AccessSerum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A(2014-12-03) Tanner, Rachel; Kakalacheva, Kristina; Miller, Ellen; Pathan, Ansar A; Chalk, Rod; Sander, Clare R; Scriba, Tom; Tameris, Michelle; Hawkridge, Tony; Mahomed, Hassan; Hussey, Greg; Hanekom, Willem; Checkley, Anna; McShane, Helen; Fletcher, Helen AAbstract Background There is an urgent need for improved vaccines to protect against tuberculosis. The currently available vaccine Bacille Calmette-Guerin (BCG) has varying immunogenicity and efficacy across different populations for reasons not clearly understood. MVA85A is a modified vaccinia virus expressing antigen 85A from Mycobacterium tuberculosis which has been in clinical development since 2002 as a candidate vaccine to boost BCG-induced protection. A recent efficacy trial in South African infants failed to demonstrate enhancement of protection over BCG alone. The immunogenicity was lower than that seen in UK trials. The enzyme Indoleamine 2,3-dioxygenase (IDO) catalyses the first and rate-limiting step in the breakdown of the essential amino acid tryptophan. T cells are dependent on tryptophan and IDO activity suppresses T-cell proliferation and function. Methods Using samples collected during phase I trials with MVA85A across the UK and South Africa we have investigated the relationship between vaccine immunogenicity and IDO using IFN-γ ELISPOT, qPCR and liquid chromatography mass spectrometry. Results We demonstrate an IFN-γ dependent increase in IDO mRNA expression in peripheral blood mononuclear cells (PBMC) following MVA85A vaccination in UK subjects. IDO mRNA correlates positively with the IFN-γ ELISPOT response indicating that vaccine specific induction of IDO in PBMC is unlikely to limit the development of vaccine specific immunity. IDO activity in the serum of volunteers from the UK and South Africa was also assessed. There was no change in serum IDO activity following MVA85A vaccination. However, we observed higher baseline IDO activity in South African volunteers when compared to UK volunteers. In both UK and South African serum samples, baseline IDO activity negatively correlated with vaccine-specific IFN-γ responses, suggesting that IDO activity may impair the generation of a CD4+ T cell memory response. Conclusions Baseline IDO activity was higher in South African volunteers when compared to UK volunteers, which may represent a potential mechanism for the observed variation in vaccine immunogenicity in South African and UK populations and may have important implications for future vaccination strategies. Trial registration Trials are registered at ClinicalTrials.gov; UK cohort NCT00427830 , UK LTBI cohort NCT00456183 , South African cohort NCT00460590 , South African LTBI cohort NCT00480558 .
- ItemOpen AccessTB incidence in an adolescent cohort in South Africa(Public Library of Science, 2013) Mahomed, Hassan; Ehrlich, Rodney; Hawkridge, Tony; Hatherill, Mark; Geiter, Lawrence; Kafaar, Fazlin; Abrahams, Deborah Ann; Mulenga, Humphrey; Tameris, Michele; Geldenhuys, HennieBACKGROUND: Tuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa. METHODS: We recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment. RESULTS: A total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29-0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis. CONCLUSION: The adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease.
- ItemOpen AccessThe tuberculin skin test versus QuantiFERON TB Gold® in predicting tuberculosis disease in an adolescent cohort study in South Africa(Public Library of Science, 2011) Mahomed, Hassan; Hawkridge, Tony; Verver, Suzanne; Abrahams, Deborah; Geiter, Lawrence; Hatherill, Mark; Ehrlich, Rodney; Hanekom, Willem A; Hussey, Gregory DSetting This study was conducted in a high tuberculosis (TB) burden area in Worcester, South Africa, with a notified all TB incidence rate of 1,400/100,000. Main Objective To compare the predictive value of a baseline tuberculin skin test (TST) with that of the QuantiFERON TB Gold (In-tube) assay (QFT) for subsequent microbiologically confirmed TB disease among adolescents. METHODS: Adolescents aged 12-18 years were recruited from high schools in the study area. At baseline, blood was drawn for QFT and a TST administered. Participants were followed up for up to 3.8 years for incident TB disease (median 2.4 years). RESULTS: After exclusions, 5244 (82.4%) of 6,363 adolescents enrolled, were analysed. The TB incidence rate was 0.60 cases per 100 person years (pyrs) (95% CI 0.43-0.82) for baseline TST positive (≥5 mm) participants and 0.64 cases per 100 pyrs (95% CI 0.45-0.87) for baseline QFT positive participants. TB incidence rates were 0.22 per 100 pyrs (0.11-0.39) and 0.22 per 100 pyrs (0.12-0.38) among those with a negative baseline TST and QFT respectively. Sensitivity for incident TB disease was 76.9% for TST and 75.0% for QFT (p = 0.81). Positive predictive value was 1.4% for TST and 1.5% for QFT. CONCLUSION: Positive TST and QFT tests were moderately sensitive predictors of progression to microbiologically confirmed TB disease. There was no significant difference in the predictive ability of these tests for TB disease amongst adolescents in this high burden setting. Therefore, these findings do not support use of QFT in preference to TST to predict the risk of TB disease in this study population.