ORCID Profile
0000-0003-3070-6154
Current Organisations
Africa Health Research Institute
,
University of Washington
,
University of Cape Town
,
University College London
,
University of KwaZulu-Natal
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Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.VACCINE.2016.06.077
Abstract: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia. Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis. Result from 98 BCG-immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-γ(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups. Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity.
Publisher: American Thoracic Society
Date: 15-08-2015
Publisher: Elsevier BV
Date: 06-2016
Publisher: Public Library of Science (PLoS)
Date: 25-10-2011
Publisher: Springer Science and Business Media LLC
Date: 08-04-2011
DOI: 10.1038/NRI2960
Abstract: Currently there are no sufficiently validated biomarkers to aid the evaluation of new tuberculosis vaccine candidates, the improvement of tuberculosis diagnostics or the development of more effective and shorter treatment regimens. To date, the detection of Mycobacterium tuberculosis or its products has not been able to adequately address these needs. Understanding the interplay between the host immune system and M. tuberculosis may provide a platform for the identification of suitable biomarkers, through both unbiased and targeted hypothesis-driven approaches. Here, we review immunological markers, their relation to M. tuberculosis infection stages and their potential use in the fight against tuberculosis.
Publisher: American Thoracic Society
Date: 15-01-2012
Publisher: Oxford University Press (OUP)
Date: 05-10-2017
Publisher: American Thoracic Society
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 08-2018
Publisher: Public Library of Science (PLoS)
Date: 19-07-2012
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
DOI: 10.1038/S41598-020-65043-8
Abstract: Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying in iduals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood s les collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2018
Publisher: Oxford University Press (OUP)
Date: 08-2008
DOI: 10.1111/J.1574-6976.2008.00118.X
Abstract: The Bacille Calmette-Guérin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifying BCG strains with superior protection would have a dramatic effect on tuberculosis control at a population level: a small increment in protection provided by BCG immunization will prevent large numbers of cases of severe tuberculosis and deaths, particularly in children.
Publisher: American Academy of Pediatrics (AAP)
Date: 2009
Abstract: OBJECTIVE. We wished to compare the sensitivity of an enzyme-linked immunospot assay (T-SPOT.TB Oxford Immunotec, Oxford, United Kingdom) and the tuberculin skin test for the detection of tuberculosis infection in very young children being evaluated for active tuberculosis in a rural community setting. METHODS. Children with a history of exposure to tuberculosis and children presenting to a local clinic or hospital with symptoms suggesting tuberculosis were admitted to a dedicated case verification ward. T-SPOT.TB testing was performed, and children were evaluated with a clinical examination, a tuberculin skin test, chest radiographs, and cultures of induced sputum and gastric lavage specimens. The diagnosis was determined by using a clinical algorithm. RESULTS. A total of 243 children (median age: 18 months) were recruited, of whom 214 (88%) had interpretable T-SPOT.TB results. Children ≥12 months of age were more likely than younger children to have positive T-SPOT.TB results, whereas tuberculin skin test results were unaffected by age. The sensitivity of the T-SPOT.TB was no better than that of the tuberculin skin test for culture-confirmed tuberculosis (50% and 80%, respectively) and was poorer for the combined group of culture-confirmed and clinically probable tuberculosis (40% and 52%, respectively). For the 50 children clinically categorized as not having tuberculosis, the specificity of both the T-SPOT.TB and the tuberculin skin test was 84%. CONCLUSIONS. For young children presenting in a community setting after exposure to tuberculosis or with symptoms suggesting tuberculosis, T-SPOT.TB cannot be used to exclude active disease. The sensitivity of this assay may be impaired for very young children.
Publisher: Public Library of Science (PLoS)
Date: 16-04-2019
Publisher: Public Library of Science (PLoS)
Date: 18-07-2019
Publisher: Elsevier BV
Date: 05-2017
Publisher: Frontiers Media SA
Date: 13-04-2018
Publisher: American Thoracic Society
Date: 04-2022
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 05-2014
Publisher: American Thoracic Society
Date: 04-2013
Publisher: American Society for Microbiology
Date: 08-2009
DOI: 10.1128/CVI.00111-09
Abstract: Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa ( n = 56), The Gambia ( n = 26), and Uganda ( n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in % of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity.
Publisher: Frontiers Media SA
Date: 05-04-2019
Publisher: Springer Science and Business Media LLC
Date: 06-12-2018
DOI: 10.1038/S41467-018-07635-7
Abstract: New biomarkers of tuberculosis (TB) risk and disease are critical for the urgently needed control of the ongoing TB pandemic. In a prospective multisite study across Subsaharan Africa, we analyzed metabolic profiles in serum and plasma from HIV-negative, TB-exposed in iduals who either progressed to TB 3–24 months post-exposure (progressors) or remained healthy (controls). We generated a trans-African metabolic biosignature for TB, which identifies future progressors both on blinded test s les and in external data sets and shows a performance of 69% sensitivity at 75% specificity in s les within 5 months of diagnosis. These prognostic metabolic signatures are consistent with development of subclinical disease prior to manifestation of active TB. Metabolic changes associated with pre-symptomatic disease are observed as early as 12 months prior to TB diagnosis, thus enabling timely interventions to prevent disease progression and transmission.
Publisher: Public Library of Science (PLoS)
Date: 10-09-2013
Publisher: Wiley
Date: 04-08-2009
Publisher: Elsevier BV
Date: 04-2014
Location: United States of America
Location: United States of America
Location: South Africa
Location: South Africa
Location: South Africa
Location: United Kingdom of Great Britain and Northern Ireland
Location: South Africa
Location: South Africa
No related grants have been discovered for Willem Hanekom.