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Eur Respir J. 2018 Nov 8;52(5). pii: 1801089. doi: 10.1183/13993003.01089-2018. Print 2018 Nov.

Can we predict tuberculosis cure? What tools are available?

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Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Dept of Epidemiology and Preclinical Research, Rome, Italy
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LJI), La Jolla, CA, USA.
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Dept of Pathology, University of Cape Town, Cape Town, South Africa.
National Institute for Public Health and the Environment (RIVM), Utrecht, The Netherlands.
Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, HSR, Division of Immunology and Infectious Diseases Milan, Milan, Italy.
Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Dept of Epidemiology and Preclinical Research, Rome, Italy.
Tuberculosis and Hepatitis Programme, FIND, Geneva, Switzerland.
Dept of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.


Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of "cure". Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests.

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Conflict of interest statement

Conflict of interest: D. Goletti reports personal fees from Qiagen, Quidel and Janssen, outside the submitted work. Conflict of interest: C.S. Lindestam Arlehamn has nothing to disclose. Conflict of interest: T.J. Scriba reports two pending patents of blood transcriptomic signatures of risk. Conflict of interest: R. Anthony reports grants from FIND to study the utility of IP-10 for treatment monitoring, outside the submitted work. Conflict of interest: D.M. Cirillo reports an unrestricted grant from QIAGEN to research the use of Quantiferon plus to predict outcome, and grants from JANSSEN on the establishment of Bedaquiline DST as SRL, outside the submitted work. Conflict of interest: T. Alonzi has nothing to disclose. Conflict of interest: C.M. Denkinger reports that FIND is a non-for-profit foundation, whose mission is to find diagnostic solutions to overcome diseases of poverty in LMICs. It works closely with the private and public sectors and receives funding from some of its industry partners. It has organisational firewalls to protect it against any undue influences in its work or the publication of its findings. All industry partnerships are subject to review by an independent scientific advisory committee or another independent review body, based on due diligence, TTPs and public sector requirements. FIND catalyses product development, leads evaluations, takes positions, and accelerates access to tools identified as serving its mission. It provides indirect support to industry (e.g. access to open specimen banks, a clinical trial platform, technical support, expertise, laboratory capacity strengthening in LMICs) to facilitate the development and use of products in these areas. FIND also supports the evaluation of prioritised assays and the early stages of implementation of WHO-approved (guidance and PQ) assays using donor grants. In order to carry out test validations and evaluations, has product evaluation agreements with several private sector companies for the diseases FIND works in which strictly define its independence and neutrality vis-a-vis the companies whose products get evaluated, and describes roles and responsibilities. Conflict of interest: F. Cobelens has nothing to disclose.

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