Browsing by Author "Kirchner, H. L."
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- ItemEffect of Ascaris Lumbricoides specific IgE on tuberculin skin test responses in children in a high-burdensetting : a cross-sectional community-based study(BioMed Central, 2012-09) Van Soelen, Nelda; Mandalakas, Anna M.; Kirchner, H. L.; Walzl, Gerhard; Grewal, Harleen M. S.; Jacobsen, Marc; Hesseling, Anneke C.ABSTRACT:M.tuberculosis (M.tb) is associated with enhanced T helper cell type 1 (Th1) immune responses while helminth infection is associated with T helper cell type 2 (Th2) immune responses. Our aim was to investigate whether helminth infection could influence the ability to generate an appropriate Th1 immune response that is characterized by a positive tuberculin skin test (TST), in M.tb exposed children.MethodsWe completed a community-based, cross sectional household contact tracing study, using matched enrolment of HIV negative children with and without documented household M.tb exposure. We documented demographics, clinical characteristics, HIV status, M.tb exposure (using a standard contact score) and M.tb infection status (TST > = 10 mm). Ascaris lumbricoides-specific IgE was used as proxy for Ascaris infection/exposure.ResultsOf 271 children (median age 4 years (range: 4 months to 15 years)) enrolled, 65 participants (24%) were serum positive for Ascaris IgE. There were 168 (62%) children with a documented household tuberculosis contact and 107 (40%) were (TST) positive overall.A positive TST was associated with increasing age (Odds Ratio (OR) =1.17, p < 0.001), increasing M.tb contact score (OR = 1.17, p < 0.001), previous tuberculosis treatment (OR = 4.8, p = 0.06) and previous isoniazid preventive treatment (OR = 3.16, p = 0.01). A visible bacillus Calmette-Guérin (BCG) scar was associated with reduced odds of being TST positive (OR = 0.42, p = 0.01).Ascaris IgE was not associated with TST status in univariate analysis (OR = 0.9, p = 0.6), but multivariable logistic regression analysis suggested an inverse association between Ascaris IgE status and a positive TST (OR = 0.6, p = 0.08), when adjusted for age, and M.tb contact score. The addition of an age interaction term to the model suggested that the age effect was stronger among Ascaris IgE positive children; the effect of being Ascaris IgE positive significantly reduced the odds of being TST positive amongst younger children while this effect weakened with increasing age.ConclusionsOur preliminary findings highlight a high prevalence of both Ascaris exposure/infection and M.tb infection in children in an urban setting. Helminth exposure/infection may reduce the immune response following M.tb exposure when controlling for epidemiological and clinical covariates. These findings might be relevant to the interpretation of immunological tests of M.tb infection in children.
- ItemNovel application of NIH case definitions in a paediatric tuberculosis contact investigation study(International Union Against Tuberculosis and Lung Disease, 2015-04) Wiseman, C. A.; Mandalakas, A. M.; Kirchner, H. L.; Gie, R. P.; Schaaf, H. Simon; Walters, E.; Hesseling, A. C.; Paediatrics and Child HealthBACKGROUND: International (National Institutes of Health [NIH]) case definitions have been proposed for paediatric tuberculosis (TB) diagnostic studies. The relevance of these definitions for contact tracing studies is unknown. METHODS: We developed case definitions for a community-based contact tracing diagnostic study. We compare disease certainty using protocol-defined and NIH case definitions and describe TB disease spectrum and severity. RESULTS: There were 111 potential disease episodes in 109 (21% human immunodeficiency virus [HIV] infected) of 1093 children enrolled. Based on NIH definitions, there were 8 confirmed, 12 probable, 17 possible and 3 unlikely TB and 2 non-TB episodes. Using protocol case definitions, there were 23 episodes of confirmed, 36 probable, 27 possible and 0 unlikely TB and 21 non-TB. Of 111 potential episodes, 69 were unclassifiable using the NIH definition, while 4 were unclassifiable using the protocol definition. Agreement between definitions was 0.30 (95%CI 0.23-0.38). There were 62 episodes (72%) of non-severe and 24 (28%) of severe TB. CONCLUSIONS: The NIH definition had limited applicability to household contact studies, despite the wide spectrum of disease observed. Further research is needed to develop case definitions relevant to different research settings, including contact investigation to capture the wide spectrum of paediatric TB in clinical research.