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While tuberculosis (TB) has become relatively rare in Germany and other industrialised nations, around ten million people contract the bacterial infection every year, especially in resource-poorer countries of Southeast Asia, Africa and the Western Pacific region. This means that TB is currently the infectious disease that causes the most deaths worldwide. To mark World Tuberculosis Day, which is celebrated annually on 24 March, we would like to present some examples from research in recent months of the German Center for Infection Research on the treatment, diagnosis and monitoring of treatment success and the spread of antibiotic-resistant tuberculosis.
According to the World Health Organisation (WHO), around 1.6 million people die from an infection with Mycobacterium tuberculosis every year, including 240,000 children. The challenges in combating the disease and containing its global spread include the lack of effective vaccines and medication against TB as well as the increased emergence of multidrug-resistant tuberculosis pathogens. The prognosis and monitoring of the success of individual treatments also pose major problems for the medical profession.
Treating tuberculosis when antibiotics no longer work
A research team led by infectious disease specialist Dr Jan Rybniker at University Hospital Cologne and the DZIF, together with partners from France, has identified novel, antibiotically active molecules that target M. tuberculosis and make it less pathogenic for humans. In addition, some of the substances may enable renewed treatment with available antibiotic medications—including against strains of the pathogen that have already developed resistance.
You can find the press release on the study here: https://www.dzif.de/en/treating-tuberculosis-when-antibiotics-no-longer-work
New active agent for the treatment of tuberculosis
Together with international colleagues, researchers from the DZIF Clinical Tuberculosis Unit (DZIF ClinTB) at the Research Center Borstel, Leibniz Lung Center have shown that the novel active substance ganfeborole exhibits clinical activity in patients and could be a promising candidate for the safe and effective treatment of pulmonary tuberculosis. Ganfeborol belongs to a new class of antibiotics—the so-called "leucyl-tRNA synthetase inhibitors"—which prevent the formation of new important proteins in the bacteria and thus inhibit the growth of pathogens.
You can find more information on the new active agent here: https://www.dzif.de/en/new-active-agent-treatment-tuberculosis
Leibniz active agent of the year 2023 is a tuberculosis antibiotic candidate
The drug candidate BTZ-043 has a novel mechanism of action and belongs to a new class of substances. The active agent discovered at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) has been developed since 2014 in collaboration with the Tropical Institute at LMU University Hospital Munich and Hapila GmbH in Gera in the framework of the DZIF and the InfectControl 2020 consortium, among others. BTZ-043 was named Leibniz Drug of the Year 2023.
The press release on the Leibniz Active Ingredient of the Year 2023 can be found here: https://www.dzif.de/en/leibniz-active-agent-year-2023-tuberculosis-antibiotic-ca...
A new dawn in the fight against Tuberculosis
UNITE4TB—an international public-private partnership aiming to accelerate the development of innovative tuberculosis treatments—has announced the start of its Phase IIb/c clinical trial programme in November 2023. UNITE4TB's innovative Phase IIb/c trials will test 14 combinations of nine existing drugs and two newly developed drug candidates (BTZ-043 and GSK656). The aim is to develop treatment regimens that can further improve the treatment of multidrug-resistant (MDR) and drug-sensitive TB. The DZIF and the LMU University Hospital Munich, a member institution of the DZIF, play a central role in the UNITE4TB consortium.
You can find out more about the new UNITE4TB clinical trials here: https://www.dzif.de/en/new-dawn-fight-against-tuberculosis
Identifying and combating new antibiotic resistance in tuberculosis early on
The antibiotic bedaquiline was approved in 2014 specifically for the treatment of multidrug-resistant TB and has been an important component of successful TB therapy ever since. However, some pathogen strains have already developed resistance to this active agent. The mutations in the genetic material of the bacteria that mediate this resistance have not yet been fully known. Using evolutionary biology methods, international researchers led by scientists from the Research Center Borstel, Leibniz Lung Center and the DZIF have succeeded in classifying new and previously unknown resistance mutations. In future, this knowledge can be used in molecular diagnostics to provide patients with tailored antibiotic therapy.
You can find out more about the classification of antibiotic resistance here: https://www.dzif.de/en/identifying-and-combating-new-antibiotic-resistance-tuber...
New tool makes it easier to diagnose tuberculosis in children
Every year, around 240,000 children worldwide die from TB. This makes the disease one of the ten most common causes of death in children under the age of five. One of the main reasons for this is that the disease is often not diagnosed correctly or in good time, particularly in resource-poor regions. A new diagnostic tool, which an international research consortium led by DZIF researchers Laura Olbrich and Norbert Heinrich from the Tropical Institute of the LMU University Hospital Munich has tested in five countries as part of a large-scale study, may now bring important progress.
Details on the new TB diagnostics tool can be found here: https://www.dzif.de/en/new-tool-makes-it-easier-diagnose-tuberculosis-children
When (new) drugs don’t work: Mozambique faces alarming multidrug-resistant tuberculosis epidemic
With one of the highest TB incidences (368 cases/100,000 inhabitants) in the African region, Mozambique is severely affected by the TB epidemic. The uncontrolled transmission of multidrug-resistant TB strains in Mozambique and other parts of Africa poses an enormous challenge for TB control in the 21st century. Researchers from an international consortium led by DZIF scientists at the Research Center Borstel, Leibniz Lung Center investigated multidrug-resistant TB strains and found a high proportion of resistance to two key drugs in current treatment regimens. The study underlines the importance of effective diagnosis and TB surveillance based on comprehensive molecular biology methods such as sequencing technologies.
You can find the press release on the study here: https://www.dzif.de/en/when-new-drugs-dont-work-mozambique-faces-alarming-multid...
DZIF tuberculosis researchers help Ukrainian partner university
Due to the war in Ukraine, maintaining classes for students at the V. N. Karazin Kharkiv National University and other universities in the country is a major challenge. As part of the online lecture series "Tuberculosis and other Infectious Diseases" launched by DZIF scientist Prof Christoph Lange and the DZIF ClinTB team, leading scientists from Germany, Denmark, Austria, Switzerland and the USA are teaching medical students in Ukraine about tuberculosis, HIV, COVID-19 and viral hepatitis.
You can find more information about the international online lecture series here: https://www.dzif.de/en/dzif-tuberculosis-researchers-help-ukrainian-partner-univ...
PD Dr. Jan Rybniker
University Hospital Cologne
jan.rybniker@uk-koeln.de
Dr. Maja Reimann
Research Center Borstel Leibniz Lung Center
mreimann@fz-borstel.de
Prof. Dr. Michael Hoelscher
LMU University Hospital Munich
hoelscher@lrz.uni-muenchen.de
Prof. Dr. Stefan Niemann
Research Center Borstel Leibniz Lung Center
sniemann@fz-borstel.de
Dr. Laura Olbrich
LMU University Hospital Munich
olbrich@lrz.uni-muenchen.de
Dr. Norbert Heinrich
LMU University Hospital Munich
heinrich@lrz.uni-muenchen.de
Prof. Dr. Dr. h.c. Christoph Lange
Research Center Borstel Leibniz Lung Center
clange@fz-borstel.de
https://doi.org/10.1016/j.chembiol.2023.12.007
https://doi.org/10.1038/s41591-024-02829-7
https://doi.org/10.1016/S2666-5247(23)00002-2
https://doi.org/10.1016/S1473-3099(23)00491-7
https://doi.org/10.1016/S1473-3099(23)00498-X
https://www.dzif.de/en/world-tuberculosis-day-24-march-2024-under-motto-yes-we-c... Press release of the German Center for Infection Research on the World Tuberculosis Day on 24 March
World Tuberculosis Day 2024
WHO/Global Tuberculosis Programme
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World Tuberculosis Day 2024
WHO/Global Tuberculosis Programme
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