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Int J Infect Dis. 2019 Mar;80S:S62-S67. doi: 10.1016/j.ijid.2019.01.039. Epub 2019 Jan 24.

Improving treatment outcomes for MDR-TB - Novel host-directed therapies and personalised medicine of the future.

Author information

1
ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal. Electronic address: martin.rao@research.fchampalimaud.org.
2
National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy. Electronic address: giuseppe.ippolito@inmi.it.
3
National Institute of Medical Research Muhimbili, Dar es Salaam, Tanzania. Electronic address: gsmfinanga@yahoo.com.
4
University Marien NGouabi and Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Institute for Tropical Medicine, University of Tübingen, Germany. Electronic address: ffntoumi@hotmail.com.
5
Department of Bacteriology, Noguchi Memorial Institute for Medical Research, Accra, Ghana. Electronic address: dyeboah-manu@noguchi.ug.edu.gh.
6
Experimental Tuberculosis Unit (UTE), Fundació Institut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona (UAB), Badalona, Catalonia, Spain. Electronic address: cvilaplana@gmail.com.
7
Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. Electronic address: a.zumla@ucl.ac.uk.
8
ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal; Department of Oncology and Haematology, Krankenhaus Nordwest, Frankfurt am Main, Germany. Electronic address: markus.maeurer@fundacaochampalimaud.pt.

Abstract

Multidrug-resistant TB (MDR-TB) is a major threat to global health security. In 2017, only 50% of patients with MDR-TB who received WHO-recommended treatment were cured. Most MDR-TB patients who recover continue to suffer from functional disability due to long-term lung damage. Whilst new MDR-TB treatment regimens are becoming available, conventional drug therapies need to be complemented with host-directed therapies (HDTs) to reduce tissue damage and improve functional treatment outcomes. This viewpoint highlights recent data on biomarkers, immune cells, circulating effector molecules and genetics which could be utilised for developing personalised HDTs. Novel technologies currently used for cancer therapy which could facilitate in-depth understanding of host genetics and the microbiome in patients with MDR-TB are discussed. Against this background, personalised cell-based HDTs for adjunct MDR-TB treatment to improve clinical outcomes are proposed as a possibility for complementing standard therapy and other HDT agents. Insights into the molecular biology of the mechanisms of action of cellular HDTs may also aid to devise non-cell-based therapies targeting defined inflammatory pathway(s) in Mtb-driven immunopathology.

KEYWORDS:

Biomarkers; Clinical studies; Host-directed therapies; Immunotherapy; Multidrug-resistant tuberculosis; Personalised medicine

PMID:
30685590
DOI:
10.1016/j.ijid.2019.01.039
[Indexed for MEDLINE]
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