Yellow fever
Hidden TB Risk In Treating Autoimmune And Inflammatory Diseases
Scientists have identified how a protein used to treat autoimmune and inflammatory diseases can weaken the body's defense against tuberculosis (1✔ ✔Trusted SourceTuberculosis - World Health Organization (WHO)Go to source). (TB) While TB is the leading cause of mortality from infectious disease in the world, the deaths represent just 5 percent of infections with Mycobacterium tuberculosis (Mtb). Mtb spreads through the air and usually infects the lungs. Researchers have long known that an acquired deficiency of "tumour necrosis factor" (TNF) can raise the risk of developing TB. Upending long-held assumptions about the immune system, the study, published in the journal Nature, revealed that a lack of TNF incapacitates a specific immune process in the lungs, leading to severe illness. 'Mycobacterium #tuberculosis, the sneaky culprit behind #TB, has been around for centuries, quietly wreaking havoc. Despite advancements in medicine, it continues to be a global health challenge. #lunghealth ' Jean-Laurent Casanova, from Rockefeller University in the US, said that TNF protects the lungs against TB. But otherwise, it plays "a limited role in inflammation and immunity. "The study focussed on recurring TB infections experienced by two people in Colombia -- a 28-year-old woman and her 32-year-old cousin. Both were repeatedly hospitalised with significant lung conditions. Both initially responded well to anti-TB antibiotics."Yet even though their immune systems functioned normally they became sick again within a year. The team conducted a whole-exome sequencing on the two, as well as a genetic analysis of their respective parents and relatives to probe their recurring TB infections.
The two were found to be the only members of their extended family with a mutation in the TNF gene, which failed to function. As a result, the patient's alveolar macrophages, located in their lungs, were overrun with Mtb. The team noted that the lack of TNF in alveolar macrophages makes people susceptible to airborne TB (Mtb).
The discovery solves a long-standing mystery about why TNF inhibitors, which are used to treat autoimmune and inflammatory diseases, raise the chances of contracting TB. Without TNF, a key part of the defence against it is defunct, said the team.Reference:
Tackling Global Tuberculosis: WHO And MSF-led Propose EndTB Treatments
The African Union's health agency Africa said200,000 doses of the drugmaker's vaccine were to be deployed in Africa - Copyright GETTY IMAGES NORTH AMERICA/AFP/File SCOTT OLSON
The World Health Organisation (WHO), in a bid to reduce cases of tuberculosis (TB) infection, is recommending the wider use of shorter and effective treatment regimens studied through a programe called endTB. This should help improve care for people with drug-resistant TB worldwide.
The WHO recommendation is based on the results of a Doctors Without Borders/Médecins Sans Frontières' (MSF) endTB clinical trial. This was a multi-year study aimed at finding more tolerable drug regimens for millions of people living with TB worldwide.
According to Pharmaceutical Microbiology Resources: "TB is a bacterial infection spread through inhaling tiny droplets from the coughs or sneezes of an infected person. Here, TB is spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected."
The study is based on new regimens comprised of all-oral medicines and a much shorter treatment duration of nine months compared to 18. These have been shown to be at least as effective as conventional regimens for patients with multidrug-/rifampicin-resistant TB (MDR-/RR-TB).
The data indicates that easier and shorter treatment options are key to encouraging adherence and effective treatment. Adherence is especially critical for infectious diseases like TB that, if left untreated, can spread to others. MDR-TB is particularly difficult to treat because it is resistant to the two most powerful first-line antibiotics typically used, rifampicin and isoniazid.
Mycobacterium tuberculosis (Public Health Image Library, NIAID, Image ID: 18139)Testing the new regime
The WHO-recommended endTB regimens were studied in seven countries between 2017 and 2023 in collaboration with Partners In Health (PIH) and Interactive Research and Development (IRD) and funding from Unitaid.
The endTB clinical trial was launched seven years ago to find shorter, more tolerable, injection-free treatments for people with MDR-TB/RR-TB using combinations of drugs including bedaquiline and delamanid. Bedaquiline and delamanid were the first new TB drugs developed in almost 50 years since pharmaceutical companies did not see the value in creating medicines for a disease that predominately affects poorer communities.
MSF carried out the endTB clinical trial along with another TB trial called TB PRACTECAL because the pharmaceutical industry failed to do so. Both trials have found better treatments for people with TB and influenced WHO recommendations and guidelines.
Big pharma
The pharmaceutical industry, despite significant public financing, has only brought new drugs to market. They have not informed the use of these drugs in regimens. It has been left to non-governmental organisations to conduct controlled trials to inform practical use of, and innovations with, novel products.
Two of the newly-WHO-recommended MDR-TB/RR-TB regimens include delamanid. However, Japanese pharmaceutical corporation Otsuka—through its exclusive licensee Viatris—keeps the price of delamanid excessively high, limiting people's access.
MSF has repeatedly called on Otsuka and Viatris to stop blocking price-lowering generics from entering the market and to immediately share delamanid with every company interested in making more affordable quality-assured generic versions of this lifesaving TB drug.
TB Under The Sea: A Marine Sponge Microbe Provides Insights Into The Evolution Of Tuberculosis
image:
Mycobacterium spongiae under the microscope
view moreCredit: Pidot and team at the Doherty Institute
TB remains one of the world's deadliest infectious diseases, yet the origins of M. Tuberculosis are still not fully understood.
In a new study published in PLOS Pathogens, research led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) details the newly identified bacterium, Mycobacterium spongiae, found in a marine sponge collected near Cooktown, Queensland.
Often referred to as 'chemical factories', marine sponges are a valuable source of bioactive compounds with potent anticancer, antibacterial, antiviral and anti-inflammatory properties. While studying a sponge specimen for its chemical-producing bacteria, researchers at the University of Queensland found a bacterium that puzzled them.
The sample was sent to the Doherty Institute, where the team conducted extensive analyses of the genes, proteins and lipids of M. Spongiae. They discovered that it shares 80 per cent of its genetic material with M. Tuberculosis, including some key genes associated with the bacteria's ability to cause disease. However, the researchers found that, unlike M. Tuberculosis, M. Spongiae does not cause disease in mice, making it non-virulent.
The University of Melbourne's Dr Sacha Pidot, a Laboratory Head at the Doherty Institute and co-lead author of the paper, said it was an exciting and important find.
"We were astounded to discover that this bacterium is a very close relative of M. Tuberculosis," said Dr Pidot.
"This finding provides new insights into the evolution of M. Tuberculosis, suggesting that these pathogens may have originated from marine mycobacteria."
The University of Melbourne's Professor Tim Stinear, a Laboratory Head at the Doherty Institute and co-lead author of the paper, said that that this new knowledge is an important building block for future research.
"While there is more work to be done in this space, this discovery is a valuable piece in the puzzle of understanding how TB came to be such a serious disease," said Professor Stinear.
"Our findings could help find weak links in M. Tuberculosis to inform the development of new strategies such as vaccines to prevent and combat tuberculosis."
Additional information:
Data/statistical analysis
Article TitleMarine sponge microbe provides insights into evolution and virulence of the Tubercle bacillus
Article Publication Date29-Aug-2024
COI StatementThe authors declare they have no conflict of interest.
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