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The Effect of Deworming on Tests of Tuberculosis Infection in Children With Recent Tuberculosis Exposure: A Randomized Controlled Trial

Van der Zalm, Marieke M. MD, PhD; van Soelen, Nelda MD, MPH, MBA; Mandalakas, Anna M. MD, PhD; Jacobsen, Marc PhD; Detjen, Anne K. MD; Marx, Florian M. MD, MSc; Grewal, Harleen M. S. MD, PhD; Cotton, Mark F. MD, PhD; Walzl, Gerhard MD, PhD; Hesseling, Anneke C. MD, PhD

The Pediatric Infectious Disease Journal: June 2016 - Volume 35 - Issue 6 - p 622–627
doi: 10.1097/INF.0000000000001115
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Background: Helminth infestations are associated with T-helper cell type 2 (Th2) immune responses, leading to suppression of Th1 responses required to control Mycobacterium tuberculosis infection. We hypothesized that deworming after documented M. tuberculosis exposure might improve Th1 immune responses.

Methods: This was a randomized controlled trial comparing the effect of early versus delayed (after 3 months) deworming on tuberculin skin testing (TST) and Quantiferon-Gold-in-tube responses among children from a setting with a known high burden of M. tuberculosis and helminth co-infection in Cape Town, South Africa. Children aged 6 to 15 years with documented M. tuberculosis exposure were enrolled. Ascaris lumbricoides status was measured by Ascaris-specific IgE and stool microscopy.

Results: A total of 250 children (mean age, 9.6 years) were enrolled; 11.9% (27/227) were Ascaris stool microscopy positive and 54.2% (135/249) were Ascaris stool and/or IgE positive (Ascaris status). In univariable analysis, deworming at enrollment was not associated with a negative TST at 3 months (odds ratio, 0.61; 95% confidence interval, 0.35–1.07; P = 0.08). In stratified analysis, children with a positive Ascaris status were more likely to be TST negative at 3 months if dewormed early (odds ratio, 0.49; 95% confidence interval, 0.23–1.04; P = 0.06). In multivariable analysis, deworming was not associated with TST status (adjusted odds ratios, 0.62; 95% confidence interval, 0.34–1.10; P = 0.10). There was no association between deworming and Quantiferon-Gold-in-tube status.

Conclusions: Deworming in children with recent M. tuberculosis exposure is associated with a trend toward a negative TST result. Timing of deworming might influence interpretation of TST in settings with high burdens of tuberculosis and helminths.

Supplemental Digital Content is available in the text.

From the *Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Stellenbosch, South Africa; Section on Global and Immigration Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Duesseldorf, Germany; §The International Union Against Tuberculosis and Lung Disease, Paris, France; Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin, Berlin, Germany; Division of Global Health Equity, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; **Faculty of Medicine and Dentistry, Department of Clinical Science, University of Bergen, Bergen, Norway; ††Department of Microbiology, Haukeland University Hospital, Bergen, Norway; ‡‡FAM-CRU, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa; and §§Immunology Research Group, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for TB Research, Faculty of Medicine and Health Sciences, Division of Molecular Biology and Human Genetics, Stellenbosch University, Stellenbosch, South Africa.

Accepted for publication December 1, 2015.

G.W. and A.C.H. contributed equally to this study.

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Norwegian Programme for Development, Research and Education (NUFU).

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Marieke M. Van der Zalm, MD, PhD, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Stellenbosch, South Africa. E-mail: mariekevdzalm@sun.ac.za

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