Browsing by Author "Mfinanga, S."
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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 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 Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania(Journal of Clinical Microbiology, 2021) Mbelele, P.M.; Mpolya, E.A.; Sauli, E.; Mtafya, B.; Ntinginya, N.E.; Addo, K.K.; Kreppel, K.; Mfinanga, S.; Phillips, P.P.J.; Gillespie, S.H.; Heysell, S.K.; Sabiiti, W.; Mpagama, S.G.Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component, despite the drug class’ purported bactericidal activity early in treatment. We tested whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDRTB regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable M. tuberculosis 16S rRNA in sputum for estimation of colony forming units per ml (eCFU/ml). M. tuberculosis killing rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. Thirty-seven patients produced 296 serial sputa and received treatment as follows: 13 patients received an injectable bedaquiline-free reference regimen, 9 received an injectable bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen, and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/ pyrazinamide/ethambutol (RHZE). Compared to the adjusted M. tuberculosis killing of 20.17 (95% confidence interval [CI] 20.23 to 20.12) for the injectable bedaquiline-free reference regimen, the killing rates were 20.62 (95% CI 21.05 to 20.20) log10 eCFU/ml for the injectable bedaquiline-containing regimen (P=0.019), 20.35 (95% CI 20.65 to 20.13) log10 eCFU/ml for the all-oral bedaquiline-based regimen (P=0.054), and 20.29 (95% CI 20.78 to 10.22) log10 eCFU/ml for the RHZE regimen (P=0.332). Thus, M. tuberculosis killing rates from sputa were higher among patients who received bedaquiline but were further improved with the addition of an injectable aminoglycoside.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 Tuberculosis, HIV/AIDS and Malaria Health Services in sub-Saharan Africa – A Situation Analysis of the Disruptions and Impact of the COVID-19 Pandemic(Elsevier, 2022) Chanda-Kapata, P.; Ntoumi, F.; Kapata, N.; Lungu, P.; Mucheleng'anga, L.A.; Chakaya, J.; Tembo, J.; Himwaze, C.; Ansumana, R.; Asogun, D.; Mfinanga, S.; Nyasulu, P.; Mwaba, P.; Yeboah-Manu, D.; Zumla, A.; Nachega, J.B.Background: The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries’ health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. Methods: In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. Results: The COVID-19 pandemic resulted in disruptions of routine health services and diversion of al- ready limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. Conclusions: Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa’s economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.Item Tuberculosis, HIV/AIDS and Malaria Health Services in sub-Saharan Africa – A Situation Analysis of the Disruptions and Impact of the COVID-19 Pandemic(Elsevier, 2022) Chanda-Kapata, P.; Ntoumi, F.; Kapata, N.; Lungu, P.; Mucheleng’anga, L.A.; Chakaya, J.; Tembo, J.; Himwaze, C.; Ansumana, R.; Asogun, D.; Mfinanga, S.; Nyasulu, P.; Mwaba, P.; Yeboah-Manu, D.; Zumla, A.; Nachega, J.B.Background: The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries’ health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. Methods: In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. Results: The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. Conclusions: Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa’s economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.