Host Directed Therapies TB Clinical Trials Network
An international effort spearheaded by Prof. Markus Maeurer (LabMed, KI) and Prof. Alimuddin Zumla (University College London) to bring together various academic and clinical partners across the globe with a great interest in implementing novel host-directed therapies for the treatment of clinical tuberculosis.
The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR-TB, and those with co-morbidity of TB with HIV and NCDs, in sub-Saharan Africa is unacceptable [1-5]. New innovations for shortening duration of therapy, improving treatment outcomes, preventing relapse, reducing drug resistance, and preventing long term lung damage, are urgently required [2,3,6]. The TB drug pipeline remains sparse [4,6]. A broad of range of Host Directed Therapies (HDT) now provide hope for improving treatment outcomes and reducing duration of therapy [7-15]. These require evaluation in randomized, placebo-controlled clinical trials(RCTs) as adjuncts to current TB treatment regimens.
The objectives of HDT-NET
1. To evaluate in RCTs a range of Adjunct Host Directed Therapies (see list) for:
- Shortening duration of treatment for:
- drug sensitive TB (DS-TB).
- multi-/extensively drug resistant TB (MDR-TB/XDR-TB).
- Improving treatment outcomes (mortality/morbidity) for MDR/XDR-TB patients.
- Improving treatment outcomes for specific clinical conditions associated with tissue injury:
- HIV co-infected individuals with DS-TB and MDR/XDR-TB.
- TB pericarditis.
- Miliary TB and TB meningitis.
- TB-associated Immune Reconstitution inflammatory syndrome (IRIS).
- Preventing recurrence of TB or relapse or TB drug resistance.
- Reducing excessive lung inflammation and preventing long term lung matrix destruction and complications.
- Improving treatment outcomes of people with co-morbidities such as NCDs (eg diabetes COAD, any cancers, NIDs. This will create a more holistic approach for high quality care. HDT could also benefit cancer services in Africa.
2. To develop high quality clinical trials and laboratory infrastructure at all African partner sites irrespective of current capabilities
This will include staffing, infrastructure, facilities for cell and culture, immunology, mycobacteriology including drug sensitivity testing, diagnostics, data entry/storage, protocol harmonization, communication, biobanking, end user involvement, ethics, continuing professional development, and networking with other trials consortia.
3. To produce a high calibre cadre of African researchers (scientists, health and laboratory personnel) who will be suitably empowered to take leadership and conduct of high quality research and clinical trials.
At each site, a range of postdocs, PhDs, Masters and Diploma students will bementored closely aligned to the design and development of clinical trials, cohorts and biobanks. The multidisciplinary consortium will allow for access to a broader range of expertise training and supervision, wider knowledge and resource acquisition and enable trials of other PRDs to be hosted in each country.
Alimuddin Zumla, Salim Abdulla, Eleni Akililu, Martin Antonio, Abraham Aseffa, Matthew Bates, Maryline Bonnet, Pere-Joan Cardona, Jeremiah Chakaya, Gavin Churchyard, Tumena Corrah, Gill Craig, Bassirou Diarra, Tandakha N Dieye, Sarah Edwards, Paul Elkington, Sebestian Gagneux, Vanya Gant, Albert Garcia-Basteiro, Martin Grobusch, Richard Hafner, Michael Hoelscher, Giuseppe Ippolito, Pontiano Kaleebu, Nathan Kapata, Stefan Kaufmann, Gibson Kibiki, Eusebio Macete, Bruce Macrae, Almoustapha Maiga, Rajhmun Mandansein, Neil Martinson, Bongani Mayosi, Leonard Mboko, Tim McHugh, Clara Menendez,Sayoki Mfinanga, Elirehema Mfinanga, Emma Morris, Modest Mulenga, Paula Munderi, Peter Mwaba, Maddy Noursadeghi, Francine Ntoumi, Thomas Nyirenda, Matt Oliver, Nesri Padayatchi, Eskild Petersen, Shreemanta Parida, Niaina Rakotosamimanana, Gita Ramjee, Voahangy Rasolof, Klaus Reither, James BW Russell, Roxana Rustomjee, Ian Sanne, Aziz Sheik, Nalini Singh, Andrie Steyn, Leopold Tientcheu, Cristina Vilaplana, Robert S. Wallis, Christian Wejse, Robert J Wilkinson, Dorothy Yeboah-Manu, Markus Maeurer.
Tuberculosis—advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.
Robert S Wallis, Markus Maeurer, Peter Mwaba, Jeremiah Chakaya, Roxana Rustomjee, Giovanni Battista Migliori, Ben Marais, Marco Schito, Gavin Churchyard, Soumya Swaminathan, Michael Hoelscher, Alimuddin Zumla
The Lancet Infectious Diseases, Volume 16, No. 4, e34–e46, April 2016
Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.
Alimuddin Zumla, Martin Rao, Robert S Wallis, Stefan H E Kaufmann, Roxana Rustomjee, Peter Mwaba, Cris Vilaplana, Dorothy Yeboah-Manu, Jeremiah Chakaya, Giuseppe Ippolito, Esam Azhar, Michael Hoelscher, Markus Maeurer, for Host-Directed Therapies Network consortium.
The Lancet Infectious Diseases, Volume 16, No. 4, e47–e63, April 2016
Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates.
Clin. Infect. Dis. 2015 Nov;61(9):1432-8
Towards host-directed therapies for tuberculosis.
Nat Rev Drug Discov 2015 Aug;14(8):511-2
Cellular therapy in tuberculosis.
Int. J. Infect. Dis. 2015 Mar;32():32-8
Host-directed therapies for tuberculous pericarditis.
Int. J. Infect. Dis. 2015 Mar;32():30-1
Host-directed therapy: tuberculosis vaccine development.
Lancet Respir Med 2015 Mar;3(3):172-3
Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.
Lancet Infect Dis 2014 Nov;14(11):1136-1149
Progress in tuberculosis vaccine development and host-directed therapies--a state of the art review.
Lancet Respir Med 2014 Apr;2(4):301-20
Inflammation and tuberculosis: host-directed therapies.
J. Intern. Med. 2015 Apr;277(4):373-87
New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects.
Lancet Infect Dis 2014 Apr;14(4):327-40
Advances in the development of new tuberculosis drugs and treatment regimens.
Nat Rev Drug Discov 2013 May;12(5):388-404