Towards host-directed therapies for tuberculosis

Alimuddin Zumla¹, Markus Maeurer²; Host-Directed Therapies Network; Jeremiah Chakaya³, Michael Hoelscher⁴, Francine Ntoumi⁵, Roxana Rustomjee⁶, Cristina Vilaplana⁷, Dorothy Yeboah-Manu⁸, Voahangy Rasolof⁹, Paula Munderi¹⁰, Nalini Singh¹¹, Eleni Aklillu¹², Nesri Padayatchi¹³, Eusebio Macete¹⁴, Nathan Kapata¹⁵, Modest Mulenga¹⁶, Gibson Kibiki¹⁷, Sayoki Mfinanga¹⁸, Thomas Nyirenda¹⁹, Leonard Maboko²⁰, Alberto Garcia-Basteiro¹⁴, Niaina Rakotosamimanana⁹, Matthew Bates¹⁵, Peter Mwaba¹⁵, Klaus Reither²¹, Sebastien Gagneux²¹, Sarah Edwards²², Elirehema Mfinanga²³, Salim Abdulla²⁴, Pere-Joan Cardona⁷, James B W Russell²⁵, Vanya Gant²⁶, Mahdad Noursadeghi¹, Paul Elkington²⁷, Maryline Bonnet²⁸, Clara Menendez²⁹, Tandakha N Dieye³⁰, Bassirou Diarra³¹, Almoustapha Maiga³¹, Abraham Aseffa³², Shreemanta Parida², Christian Wejse³³, Eskild Petersen³³, Pontiano Kaleebu¹⁰, Matt Oliver³⁴, Gill Craig³⁵, Tumena Corrah³⁶, Leopold Tientcheu³⁷, Martin Antonio³⁷, Martin Rao², Timothy D McHugh³⁸, Aziz Sheikh³⁹, Giuseppe Ippolito⁴⁰, Gita Ramjee⁴¹, Stefan H E Kaufmann⁴², Gavin Churchyard⁴³, Andrie Steyn⁴⁴, Martin Grobusch⁴⁵, Ian Sanne⁴⁶, Neil Martinson⁴⁷, Rajhmun Madansein⁴⁸, Robert J Wilkinson⁴⁹, Bongani Mayosi⁵⁰, Marco Schito⁵¹, Robert S Wallis⁴³

Affiliations

¹ 1] Division of Infection and Immunity at the University College London (UCL), London, UK and National Institute of Health Research's Biomedical Research Centre UCL Hospitals National Health Service Foundation Trust, Royal Free Campus, 2nd Floor, Rowland Hill Street, London NW3 2PF, UK. [2] Department of Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.
² Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet and Center for Allogeneic Stem Cell Transplantation, Karolinska Hospital, Hälsovägen, SE-14186 Stockholm, Sweden.
³ Kenya Medical Research Institute, Nairobi, Kenya.
⁴ Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), and DZIF German Centre for Infection Research, Munich, Germany.
⁵ Fondation Congolaise pour la Recherche Médicale, Brazzaville, Republic of Congo and Institute for Tropical Medicine, University of Tübingen, Germany.
⁶ Medical Research Council, Cape Town, South Africa.
⁷ Unitat de Tuberculosi Experimental Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i PujolEdifici Laboratoris de Recerca Can Ruti Campus, Barcelona, Spain.
⁸ Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
⁹ Mycobacteria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
¹⁰ Medical Research Council/Uganda Virus Research Institute, Research Unit on AIDS, Entebbe, Uganda.
¹¹ Inkosi Albert Luthuli Central Hospital and King DinuZulu Hospital, Durban, South Africa.
¹² Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
¹³ Centre for AIDS Prevention Research in South Africa (CAPRISA), SAMRC CAPRISA HIV -TB pathogenesis and treatment research unit, Durban, South Africa.
¹⁴ Centro de Investigação em Saude de Manhiça, Maputo, Mozambique.
¹⁵ UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
¹⁶ Tropical Diseases Research Centre, Ndola, Zambia.
¹⁷ Kilimanjaro Clinical Research Institute (KCRI), Kilimanjaro, Tanzania.
¹⁸ Muhimbili Medical Research Centre National Institute for Medical Research (NIMR), Dar es Salaam, Tanzania.
¹⁹ European Developing Countries Clinical Trials Partnership (EDCTP), Cape Town, South Africa; not officially a partner of this consortium but participated in the HDT-NET Cape Town launch.
²⁰ Mbeya Medical Research Centre, Mbeya, Tanzania.
²¹ Swiss Tropical and Public Health Institute, Basel, Switzerland.
²² Ethics and Governance, NIHR BRC at University College London Hospitals NHS Trust, London, United Kingdom.
²³ Ifakara Health Institute, Bagamoyo, Tanzania.
²⁴ Ifakara Health Institute, Dar-es-Salaam, Tanzania.
²⁵ Department of Internal Medicine, Connaught Hospital, College of Medicine and Allied Health Sciences, University of Sierra Leone, Sierra Leone.
²⁶ Department of Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.
²⁷ Respiratory Medicine department, Southampton University, Southampton, UK.
²⁸ Epicentre, IRD, Paris, France.
²⁹ ISGlobal, Barcelona Institute for Global health, Barcelona, Spain. Immunology Unit-Laboratoire Bactériologie Virologie, Le Dantec.
³⁰ Hospital, Laboratories of the National Blood Transfusion Center, Senegal.
³¹ SEREFO (HIV/TB Research and Training CenteHIV/TB Research and Training Center, FMOS, University of STT, Bamako, Mali.
³² Armaeur Hansen Resrach Institute (AHRI), Addis Ababa, Ethiopia.
³³ Department of Infectious Diseases, Aarhus University, Aarhus, Denmark.
³⁴ Results UK, London, United Kingdom.
³⁵ School of Health Sciences, City University London, City University, London, UK.
³⁶ Department of Infectious and Tropical Diseases, Northwick Park Hospital, London, UK.
³⁷ Medical Research Council, Banjul, Gambia.
³⁸ Division of Infection and Immunity at the University College London (UCL), London, UK and National Institute of Health Research's Biomedical Research Centre UCL Hospitals National Health Service Foundation Trust, Royal Free Campus, 2nd Floor, Rowland Hill Street, London NW3 2PF, UK.
³⁹ Centre of Medical Informatics, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.
⁴⁰ National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy.
⁴¹ HIV prevention Research Unit, MRC, Durban South Africa.
⁴² Max Planck Institute, Berlin, Germany.
⁴³ Aurum Institute, Johannesburg, South Africa.
⁴⁴ KwaZulu-Natal Research Institute for Tuberculosis &HIV, Nelson R. Mandela School of Medicine, K-RITH Tower Building, Durban, South Africa.
⁴⁵ Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, University of Amsterdam, Amsterdam, The Netherlands.
⁴⁶ Right to care, University of Witwatersrand, Johannesburg, South Africa.
⁴⁷ Public Health research Unit, Soweto, South Africa.
⁴⁸ Department of Cardiothoracic Surgery, University of KwaZulu Natal, Inkosi Albert Luthuli Central Hospital and King DinuZulu Hospital, Durban, South Africa.
⁴⁹ Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa and Francis Crick Institute Mill Hill Laboratory, London, UK.
⁵⁰ Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
⁵¹ Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, Arizona, USA.

PMID: 26184493
DOI: 10.1038/nrd4696

Free article

Towards host-directed therapies for tuberculosis

Alimuddin Zumla et al. Nat Rev Drug Discov. 2015 Aug.

Free article

. 2015 Aug;14(8):511-2.

doi: 10.1038/nrd4696. Epub 2015 Jul 17.

Authors

Affiliations

¹ 1] Division of Infection and Immunity at the University College London (UCL), London, UK and National Institute of Health Research's Biomedical Research Centre UCL Hospitals National Health Service Foundation Trust, Royal Free Campus, 2nd Floor, Rowland Hill Street, London NW3 2PF, UK. [2] Department of Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.
² Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet and Center for Allogeneic Stem Cell Transplantation, Karolinska Hospital, Hälsovägen, SE-14186 Stockholm, Sweden.
³ Kenya Medical Research Institute, Nairobi, Kenya.
⁴ Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), and DZIF German Centre for Infection Research, Munich, Germany.
⁵ Fondation Congolaise pour la Recherche Médicale, Brazzaville, Republic of Congo and Institute for Tropical Medicine, University of Tübingen, Germany.
⁶ Medical Research Council, Cape Town, South Africa.
⁷ Unitat de Tuberculosi Experimental Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i PujolEdifici Laboratoris de Recerca Can Ruti Campus, Barcelona, Spain.
⁸ Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
⁹ Mycobacteria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
¹⁰ Medical Research Council/Uganda Virus Research Institute, Research Unit on AIDS, Entebbe, Uganda.
¹¹ Inkosi Albert Luthuli Central Hospital and King DinuZulu Hospital, Durban, South Africa.
¹² Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
¹³ Centre for AIDS Prevention Research in South Africa (CAPRISA), SAMRC CAPRISA HIV -TB pathogenesis and treatment research unit, Durban, South Africa.
¹⁴ Centro de Investigação em Saude de Manhiça, Maputo, Mozambique.
¹⁵ UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
¹⁶ Tropical Diseases Research Centre, Ndola, Zambia.
¹⁷ Kilimanjaro Clinical Research Institute (KCRI), Kilimanjaro, Tanzania.
¹⁸ Muhimbili Medical Research Centre National Institute for Medical Research (NIMR), Dar es Salaam, Tanzania.
¹⁹ European Developing Countries Clinical Trials Partnership (EDCTP), Cape Town, South Africa; not officially a partner of this consortium but participated in the HDT-NET Cape Town launch.
²⁰ Mbeya Medical Research Centre, Mbeya, Tanzania.
²¹ Swiss Tropical and Public Health Institute, Basel, Switzerland.
²² Ethics and Governance, NIHR BRC at University College London Hospitals NHS Trust, London, United Kingdom.
²³ Ifakara Health Institute, Bagamoyo, Tanzania.
²⁴ Ifakara Health Institute, Dar-es-Salaam, Tanzania.
²⁵ Department of Internal Medicine, Connaught Hospital, College of Medicine and Allied Health Sciences, University of Sierra Leone, Sierra Leone.
²⁶ Department of Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.
²⁷ Respiratory Medicine department, Southampton University, Southampton, UK.
²⁸ Epicentre, IRD, Paris, France.
²⁹ ISGlobal, Barcelona Institute for Global health, Barcelona, Spain. Immunology Unit-Laboratoire Bactériologie Virologie, Le Dantec.
³⁰ Hospital, Laboratories of the National Blood Transfusion Center, Senegal.
³¹ SEREFO (HIV/TB Research and Training CenteHIV/TB Research and Training Center, FMOS, University of STT, Bamako, Mali.
³² Armaeur Hansen Resrach Institute (AHRI), Addis Ababa, Ethiopia.
³³ Department of Infectious Diseases, Aarhus University, Aarhus, Denmark.
³⁴ Results UK, London, United Kingdom.
³⁵ School of Health Sciences, City University London, City University, London, UK.
³⁶ Department of Infectious and Tropical Diseases, Northwick Park Hospital, London, UK.
³⁷ Medical Research Council, Banjul, Gambia.
³⁸ Division of Infection and Immunity at the University College London (UCL), London, UK and National Institute of Health Research's Biomedical Research Centre UCL Hospitals National Health Service Foundation Trust, Royal Free Campus, 2nd Floor, Rowland Hill Street, London NW3 2PF, UK.
³⁹ Centre of Medical Informatics, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.
⁴⁰ National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy.
⁴¹ HIV prevention Research Unit, MRC, Durban South Africa.
⁴² Max Planck Institute, Berlin, Germany.
⁴³ Aurum Institute, Johannesburg, South Africa.
⁴⁴ KwaZulu-Natal Research Institute for Tuberculosis &HIV, Nelson R. Mandela School of Medicine, K-RITH Tower Building, Durban, South Africa.
⁴⁵ Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, University of Amsterdam, Amsterdam, The Netherlands.
⁴⁶ Right to care, University of Witwatersrand, Johannesburg, South Africa.
⁴⁷ Public Health research Unit, Soweto, South Africa.
⁴⁸ Department of Cardiothoracic Surgery, University of KwaZulu Natal, Inkosi Albert Luthuli Central Hospital and King DinuZulu Hospital, Durban, South Africa.
⁴⁹ Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa and Francis Crick Institute Mill Hill Laboratory, London, UK.
⁵⁰ Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
⁵¹ Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, Arizona, USA.

PMID: 26184493
DOI: 10.1038/nrd4696

Abstract

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

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References

1. Nat Rev Drug Discov. 2013 May;12(5):388-404 - PubMed
1. PLoS Pathog. 2014 Feb 20;10(2):e1003946 - PubMed
1. Lancet Respir Med. 2015 Mar;3(3):220-34 - PubMed
1. DNA Cell Biol. 2015 Apr;34(4):228-42 - PubMed
1. Nat Rev Immunol. 2015 Apr;15(4):255-63 - PubMed

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Towards host-directed therapies for tuberculosis

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Towards host-directed therapies for tuberculosis

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