Browsing by Author "Tameris, Michele"
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- 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 AccessEngaging adolescents in TB and clinical trial research through drama(BioMed Central, 2016-04-01) Schmidt, Bey-MarrieAbstract Background: The South African Tuberculosis Vaccine Initiative is based in Worcester where tuberculosis (TB) is endemic, and incidence rates are amongst the highest nationally. In high TB burden settings after an early childhood peak, incidence rates start to rise again in adolescents, therefore they are an important target group for tuberculosis vaccine research. In 2012, learners from a local school developed a one-off theatrical production out of an educational comic book Carina’s Choice, developed by the South African Tuberculosis Vaccine Initiative in 2010. A Wellcome Trust International Engagement grant allowed for this one-off production to be further developed, with input from university students and staff, and rolled out to schools in the Worcester area as an engagement and education intervention. Methods: Focus group feedback was used to identify key messages and to develop the play’s script. Qualitative methods were used to collect and analyse relevant data. Interviews were conducted with learner-actors, pre- and post-focus group feedback was obtained from a sample of school-going adolescents, and pre- and post-questionnaires were administered to adolescent audience members. Results: From the pre-drama focus group discussions, topics such as TB symptoms, stigma and transmission were identified as areas that needed attention. After the performances, adolescents showed improved knowledge on the identified topics and they discussed TB prevention measures. They highlighted transmission of TB during pregnancy as a further topic to be addressed in future iterations of the drama. Although stigma is a difficult phenomenon to interpret, post-drama participants understood that TB transmission could occur in all individuals. Learner-actors agreed with focus group participants that the play could impact the wider community if it were rolled out. Feedback from the South African Tuberculosis Vaccine Initiative staff verified that recruitment for an upcoming trial was facilitated by the preparedness that the play provided in recruitment areas. The study showed that before and after evaluations provide data on the usefulness of the play as an education tool. Conclusions: Theatre, presented and motivated by adolescent peers, can raise awareness of TB, and assist clinical trial preparedness and further engagement between trial staff and their trial community.
- ItemOpen AccessAn evaluation of the impact of performing arts on the knowledge of Tuberculosis and Clinical Research in adolescents in selected high schools in the Boland Overberg region, Western Cape(2016) De Kock, Marwou; Tameris, Michele; Baxter, VeronicaBackground: There is a high incidence of Mycobacterium tuberculosis (M tb) infection and active Tuberculosis (TB) disease among adolescents in high TB burden countries, such as South Africa (SA), which indicates that clinical trials assessing vaccine-induced protection are critical in this age group. In educating adolescents regarding TB and clinical trials it is important to ensure that this population has received some relevant prior information if they are approached for clinical research, as well as for the benefits to their own health. Method: Applied theatre was used to educate and inform adolescents to improve their knowledge about TB and clinical research. The script used was based on a young mother's decision to enroll her baby as a participant in a TB vaccine trial and the questions asked by her family and the community. The story played itself out in public transport, a local clinic and the participants' household, using singing, dancing and rap in the local dialect. The message was visually delivered by actors from the Worcester Senior Secondary (WSS) School's drama class in an adolescent-friendly format to learners. A pre-performance multiple choice knowledge survey was completed by the study population before they watched the play and approximately seven days after the play the same knowledge survey was completed as a post-test. Results: Of the total study population 4.56% of the adolescents had had TB previously and 39.15 % had been involved in TB research. A high number of the adolescents (97. 7 0 %) had heard about TB and 78. 39 % indicated that they heard about TB at school. The majority of adolescents knew that TB is contagious: 82.92 % in pre-and 97.26 % in post-test. The results for mode of prevention (covering your mouth when coughing / sneezing) in the pre-test for all the schools were above 9 1.28 %. In all tested schools combined there was a slight knowledge increase from pre-to post-test that TB is curable. There was a significant knowledge improvement (P=0.009) for the question: "TB can easily be cured if you take your treatment?" Reassuringly, 9 4.84 % (pre-test) and 9 2.78 % (post-test) indicated that they would consult a medical doctor or go to the clinic if they thought they had TB. Clinical research knowledge did not improve. Conclusion: Using applied theatre to sensitize a rural adolescent population to TB-related clinical research was a novel approach to educate and convey sensitive information to potential study participants. Through theatre, SATVI raised awareness and established strong partnerships with the Department of Basic Education (DoE), school principals, teachers and adolescents as well as indirectly with their parents. It created a platform to engage with the adolescents as well as sensitizing them for a future clinical trial.
- 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 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 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.