TY - JOUR
T1 - Improving treatment outcomes for MDR-TB - Novel host-directed therapies and personalised medicine of the future
AU - Rao, M.
AU - Ippolito, G.
AU - Mfinanga, S.
AU - Ntoumi, F.
AU - Yeboah-Manu, D.
AU - Vilaplana, Cristina
AU - Zumla, Alimuddin
AU - Maeurer, M.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Clinical studies
KW - Host-directed therapies
KW - Immunotherapy
KW - Multidrug-resistant tuberculosis
KW - Personalised medicine
U2 - 10.1016/j.ijid.2019.01.039
DO - 10.1016/j.ijid.2019.01.039
M3 - Article
C2 - 30685590
SN - 1201-9712
VL - 80
SP - S62-S67
JO - International Journal of Infectious Diseases
JF - International Journal of Infectious Diseases
ER -
