Early Diagnosis of Subclinical Multidrug-Resistant Tuberculosis
- Luca Richeldi, MD, PhD;
- Katie Ewer, BSc;
- Monica Losi, BSc;
- David M. Hansell, MD;
- Pietro Roversi, MD;
- Leonardo M. Fabbri, MD; and
- Ajit Lalvani, MRCP, DM
- From University of Modena and Reggio Emilia and Azienda Ospedaliera Policlinico di Modena, Modena, Italy; University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and Royal Brompton Hospital, London, United Kingdom.
Abstract
Background: Tuberculosis control hinges on prompt diagnosis of active cases and screening of contacts by tuberculin skin testing. Rapid blood tests for Mycobacterium tuberculosis infection are a new alternative to the tuberculin skin test, but whether they improve clinical outcomes is unknown.
Objective: To describe how a novel T-cell–based test for M. tuberculosis infection helped diagnose tuberculosis in an asymptomatic, immunosuppressed adult with a negative result on a tuberculin skin test.
Design: Case report.
Setting: Household contact.
Patients: Asymptomatic man receiving maintenance azathioprine therapy for Crohn disease whose wife had multidrug-resistant pulmonary tuberculosis.
Measurements: Enzyme-linked immunospot (ELISPOT) assay, computed tomography, and bronchoalveolar lavage cultures.
Results: The man had a negative tuberculin skin test result and a positive ELISPOT assay result. High-resolution computed tomography of the chest showed consolidation with early cavitation. Bronchoalveolar lavage and culture confirmed multidrug-resistant tuberculosis.
Limitations: This single case report is a proof of concept and is not a formal evaluation of clinical utility.
Conclusions: A positive ELISPOT assay result helped diagnose subclinical active tuberculosis in an immunosuppressed patient with a false-negative tuberculin skin test result. Large prospective studies that compare benefits and costs of this alternative to tuberculin skin testing are needed.
Article and Author Information
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Acknowledgments: The authors thank Patrizia Marchegiano (Azienda Ospedaliera Policlinico di Modena, Modena, Italy) for helping with the organization of the study and Giulio Ferrario and Andrea Gori (University of Milano, Milan, Italy) for restriction fragment length polymorphism typing. The authors also thank Peter Barnes (Center for Pulmonary and Infectious Disease Control, Tyler, Texas), Anna M. Marata (CeVEAS, Modena, Italy), and Giovanni B. Migliori (Tradate, Italy) for their helpful comments.
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Grant Support: By the Wellcome Trust (London, United Kingdom) and the Azienda Ospedaliera Policlinico di Modena (Modena, Italy). Ajit Lalvani is a Wellcome Senior Research Fellow in clinical science.
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Potential Financial Conflicts of Interest:Consultancies: A. Lalvani (Oxford Immunotec Ltd.); Stock ownership or options (other than mutual funds): A. Lalvani (Oxford Immunotec Ltd.); Patents received, patents pending, and royalties: A. Lalvani (patents filed by the University of Oxford since 1996 relating to T-cell–based diagnosis); Patents pending: K. Ewer (named as inventor on a patent application relating to the application of the RD-1–based ELISPOT assay); Other: The University of Oxford owns stock in Oxford Immunotec Ltd.
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Requests for Single Reprints: Ajit Lalvani, MRCP, DM, Nuffield Department of Clinical Medicine, University of Oxford, Level 7, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; e-mail, ajit.lalvani{at}ndm.ox.ac.uk.
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Current Author Addresses: Drs. Richeldi, Roversi, and Fabbri and Ms. Losi: Policlinico di Modena, via del Pozzo 71, 41100 Modena, Italy.
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Ms. Ewer and Dr. Lalvani: John Radcliffe Hospital, Level 7, Oxford OX3 9DU, United Kingdom.
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Dr. Hansell: Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom.
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Author Contributions: Conception and design: L. Richeldi, K. Ewer, A. Lalvani.
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Analysis and interpretation of the data: L. Richeldi, K. Ewer, M. Losi, D.M. Hansell, A. Lalvani.
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Drafting of the article: L. Richeldi, K. Ewer, A. Lalvani.
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Critical revision of the article for important intellectual content: L. Richeldi, K. Ewer, D.M. Hansell, M. Losi, A. Lalvani.
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Final approval of the article: L. Richeldi, K. Ewer, M. Losi, D.M. Hansell, P. Roversi, L.M. Fabbri, A. Lalvani.
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Provision of study materials or patients: A. Lalvani.
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Statistical expertise: K. Ewer.
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Obtaining of funding: L.M. Fabbri, A. Lalvani.
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Administrative, technical, or logistic support: M. Losi, P. Roversi, L.M. Fabbri, A. Lalvani.
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Collection and assembly of data: L. Richeldi, K. Ewer, M. Losi, D.M. Hansell, P. Roversi, A. Lalvani.
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