Browsing by Author "Maeurer, M."
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Item Blue Skies research is essential for ending the Tuberculosis pandemic and advancing a personalized medicine approach for holistic management of Respiratory Tract infections.(Elsevier, 2022) Ntoumi, F.; Petersen, E.; Mwaba, P.; Aklillu, E.; Mfinanga, S.; Yeboah-Manu, D.; Maeurer, M.; Zumla, A.Objectives: Investments into ‘Blue Skies’ fundamental TB research in low- and middle-income countries (LMICs) have not been forthcoming. We highlight why blue skies research will be essential for achieving global TB control and eradicating TB. Methods: We review the historical background to early TB discovery research and give examples of where investments into basic science and fundamental ‘blue skies research’ are delivering novel data and ap- proaches to advance diagnosis, management and holistic care for patients with active and latent TB in- fection. Findings: The COVID-19 pandemic has shown that making available adequate funding for priority invest- ments into ‘Blue skies research’ to delineate scientific understanding of a new infectious diseases threat to global health security can lead to rapid development and rollout of new diagnostic platforms, treat- ments, and vaccines. Several advances in new TB diagnostics, new treatments and vaccine development are underpinned by basic science research. Conclusions: Blue Skies research is required to pave the way for a personalized medicine approach for management of TB and other Respiratory Tract Infections and preventing long-term functional disability. Transfer of skills and resources by wealthier nations is required to empower researchers in LMICs countries to engage in and lead Blue Skies research.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 Learning from epidemiological, clinical, and immunological studies on Mycobacterium africanum for improving current understanding of host–pathogen interactions, and for the development and evaluation of diagnostics, host-directed therapies, and vaccines for tuberculosis(International Journal of Infectious Diseases, 2017-03) Zumla, A.; Otchere, I.D.; Mensah, G.I.; Asante-Poku, A.; Gehre, F.; Maeurer, M.; Bates, M.; Mwaba, P.; Ntoumi, F.; Yeboah-Manu, D.Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host–pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)–those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host–M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB. © 2016 The Author(s)Item 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 Taking forward the World TB Day 2016 theme 'Unite to End Tuberculosis' for the WHO Africa Region(International Journal of Infectious Diseases, 2016-05) Ntoumi, F.; Kaleebu, P.; Macete, E.; Mfinanga, S.; Chakaya, J.; Yeboah-Manu, D.; Bates, M.; Mwaba, P.; Maeurer, M.; Petersen, E.; Zumla, A.Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100 000 population-more than double the global average of 133 per 100 000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480 000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190 000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is 'Unite to End TB'. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host-Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. © 2016.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 therapiesItem World TB Day 2022: Revamping and Reshaping Global TB Control Programs by Advancing Lessons learnt from the COVID-19 pandemic(Elsevier, 2022) Petersen, E.; Al-Abri, S.; Chakaya, J.; Goletti, D.; Parolina, L.; Wejse, C.; Mucheleng’anga, L.A.; Al Khalil, S.; Yeboah-Manu, D.; Chanda-Kapata, P.; Nasiri, M.J.; Lungu, P.S.; Maeurer, M.; Tiberi, S.; Ntoumi, F.; Battista-Migliori, G.; Zumla, A.