Browsing by Author "Ippolito, G."
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Item The global dynamics of diabetes and tuberculosis: the impact of migration and policy implications(International Journal of Infectious Diseases, 2017-03) Girardi, E.; Sañé Schepisi, M.; Goletti, D.; Bates, M.; Mwaba, P.; Yeboah-Manu, D.; Ntoumi, F.; Palmieri, F.; Maeurer, M.; Zumla, A.; Ippolito, G.The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB. © 2017 The AuthorsItem Improving treatment outcomes for MDR-TB - Novel host-directed therapies and personalised medicine of the future(International Journal of Infectious Diseases, 2019-03) Rao, M.; Ippolito, G.; Mfinanga, S.; Ntoumi, F.; Yeboah-Manu, D.; Vilaplana, C.; Zumla, A.; Maeurer, M.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.Item Latent TB Infection (LTBI) – Mycobacterium tuberculosis pathogenesis and the dynamics of the granuloma battleground(International Journal of Infectious Diseases, 2019-02) Rao, M.; Ippolito, G.; Mfinanga, S.; Ntoumi, F.; Yeboah-Manu, D.; Vilaplana, C.; Zumla, A.; Maeurer, M.Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from whom new active TB cases will arise. Understanding the spatio-temporal dynamics of host immune responses in LTBI granulomas is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities – where local chronic inflammation leads to immunopathology – can help provide insights into the biological pathways at play in LTBI granulomas. Translational studies using patient material as well as LTBI+ donor-derived tissue samples are instrumental in understanding the various components of granuloma dynamics, immunological landscapes therein and how this could help to identify therapeutic targets. Deep sequencing technologies may aid to decipher the genetic changes in lung granuloma and blood samples from LTBI+ individuals associated with progression to active TB disease. This may lead to advancement of development of targeted Host-Directed Therapies (HDTs) and their evaluation as adjunct TB therapies for improving treatment outcomes for LTBI and pulmonary TB. Keywords: latent tuberculosis infection, granuloma, mutations, immune landscape, host-directed therapiesItem Taking forward the Stop TB Partnership and World Health Organization Joint Theme for World TB Day March 24th 2018 — “Wanted: Leaders for a TB-Free World. You can make history. End TB”(International Journal of Infectious Diseases, 2018-03) Tiberi, S.; Petersen, E.; Maeurer, M.; Ntoumi, F.; Yeboa-Manu, D.; Mwaba, P.; Vilaplana, C.; Dar, O.; Bates, M.; Corrah, T.; Rao, M.; Kapata, N.; Azhar, E.I.; Memish, Z.A.; Mfinanga, S.; Aseffa, A.; Ippolito, G.; Migliori, G.B.; Zumla, A.Item Towards host-directed therapies for tuberculosis(Nature Reviews Drug Discovery, 2015-08) Wejse, C.; Petersen, E.; Kaleebu, P.; Oliver, M.; Craig, G.; Corrah, T.; Tientcheu, L.; Antonio, M.; Rao, M.; McHugh, T.D.; Sheikh, A.; Zumla, A.; Maeurer, M.; Chakaya, J.; Hoelscher, M.; Ntoumi, F.; Rustomjee, R.; Vilaplana, C.; Yeboah-Manu, D.; Rasolofo, V.; Munderi, P.; Singh, N.; Aklillu, E.; Padayatchi, N.; Macete, E.; Kapata, N.; Mulenga, M.; Kibiki, G.; Mfinanga, S.; Nyirenda, T.; Maboko, L.; Garcia-Basteiro, A.; Rakotosamimanana, N.; Bates, M.; Mwaba, P.; Reither, K.; Gagneux, S.; Edwards, S.; Mfinanga, E.; Abdulla, S.; Cardona, P.-J; Russell, J.B.W.; Gant, V.; Noursadeghi, M.; Elkington, P.; Bonnet, M.; Menendez, C.; Dieye, T.N.; Diarra, B.; Maiga, A.; Aseffa, A.; Parida, S.; Ippolito, G.; Ramjee, G.; Kaufmann, S.H.E.; Churchyard, G.; Steyn, A.; Grobusch, M.; Sanne, I.; Martinson, N.; Madansein, R.; Wilkinson, R.J.; Mayosi, B.; Schito, M.; Wallis, R.S.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