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Study Shows Undernourishment Increases Risk Of TB
NIAID Undernourished household members are at triple the risk of developing tuberculosis (TB) disease after exposure, but not necessarily increased risk of infection with Mycobacterium tuberculosis, the bacterium that causes TB, according to a study today in Clinical Infectious Diseases.
The study, based on body mass index (BMI), was conducted among household contacts (HHCs) of people with TB diagnosed within 2 months of the study date. The study took place in India, which had roughly 25% of the world's TB cases in 2022 and a high prevalence of undernutrition.
Of the 857 HHCs enrolled, 239 (27.9%) had a BMI of 18.5 kilograms per meter of height squared or less, which is considered underweight. The median age was 29 years, and 59% of contacts were female. The average follow-up time was 24 months.
All cases linked to severe undernutritionThere were 18 new TB cases during follow-up, the authors said, and 10 cases were among contacts with a BMI of 18.5 or less. Four participants in the study developed early TB disease, all of whom were severely malnourished, with a BMI of less than 16, and 4 cases were excluded because they occurred within 1 week of enrollment and within 2 weeks of the index patients' diagnosis.
The researchers estimated a hazard ratio of 3.16 (95% confidence interval, 1.25 to 8.02) for TB disease in undernourished household contacts.
"The insight that undernourished individuals are at increased risk of progression, not infection is crucial for developing and refining transmission models of TB and for targeting interventions to mitigate the impact of undernutrition on the TB pandemic," concluded the authors.
The insight that undernourished individuals are at increased risk of progression, not infection is crucial for developing and refining transmission models of TB.
"Our findings should prompt TB programs to promptly provide adequate rations for the entire household to prevent TB disease among household contacts in addition to TB preventive therapy," said first author Pranay Sinha, MD, assistant professor of medicine at Boston University, in a university news release.
Undernourished Household Members At Higher TB Risk Post-Exposure
In a recent study tracking household contacts (individuals residing in the same dwelling) of tuberculosis (TB) patients, researchers discovered that undernourished contacts were three times more likely to develop TB disease. Interestingly, the study did not observe a higher likelihood of undernourished contacts testing positive for TB infection compared to well-nourished individuals. () Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB), has a unique ability to lay dormant within individuals for extended periods before becoming active and causing severe illness. The immune system plays a crucial role in controlling the bacteria and maintaining dormancy. Decades of epidemiological research have connected undernutrition to TB, suggesting that undernourished individuals, often experiencing a weakened immune system referred to as nutritionally acquired immune deficiency (N-AIDS), are at a heightened risk of TB disease. However, the precise reasons behind this increased susceptibility remain unclear. 'Undernourished household members face a heightened risk of developing #TB following exposure. #tuberculosis' "Are they more likely to become infected with the TB germ? Or are their immune systems unable to contain the germ resulting in severe disease? This fundamental question is important to answer as it can guide how we can best protect undernourished individuals who form a key and vulnerable population in the fight against TB," explained corresponding author Pranay Sinha, MD, assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine.The researchers, which included investigators from both U.S. And Indian institutions (which are part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India consortium), identified nearly 900 household contacts of persons who were newly diagnosed with TB, screening them to make sure they did not have TB disease at enrollment.
They then followed these contacts to see if they developed TB disease for up to four years. Those who had a negative TB infection test at enrollment were retested to see if it had turned positive. The researchers then compared the rate of TB disease and TB infection between undernourished household contacts and well-nourished household contacts.
According to the researchers, these findings have clinical implications. "It is not by increasing infection, instead, it is by failing to contain the infection when it happens. Fortunately, undernutrition is a modifiable risk factor. Our findings should prompt TB programs to promptly provide adequate rations for the entire household to prevent TB disease among household contacts in addition to TB preventive therapy," adds Sinha.Reference:
Trinity Researchers Uncover New Reasons To Target Neutrophils For Tuberculosis Therapy
Trinity researchers uncover new reasons to target neutrophils for tuberculosis therapy
New research that improves our understanding of how tuberculosis infection causes lung damage and how we might prevent this, has been published by a team of Trinity College Dublin scientists at St. James's Hospital in the International Journal of Molecular Sciences. [Tuesday, 16th April 2024]
Tuberculosis is the biggest infectious killer in the world, causing 1.2 million deaths every year. In common with other pneumonia types, tuberculosis can destroy the human lung as a result of excessive inflammation. One of the greatest drivers of this excessive inflammation is an immune cell called the neutrophil, which paradoxically plays an important protective role during early infection. However, like a double-edged sword, overactive neutrophils can cause lung tissue damage in established tuberculosis disease. Researchers wanted to know more about how tuberculosis infection drives this damage.
Using cell models of infection, the team examined the cross-talk between two lung immune cells: the macrophage and the neutrophil. These cells contrive to cause lung disease in the setting of tuberculosis. The group found that macrophages infected with Mycobacterium tuberculosis, the bacteria that causes tuberculosis, could directly activate neutrophils, heighten their metabolism, and lead to the production of Neutrophil Extracellular Traps (or NETs). NETs are known to drive type 1 interferons, the proteins that are harbingers of severe tuberculosis disease. These events also detain the damaging neutrophil cells in the lung where further insult can occur.
By dissecting out these pathways of human disease, the group has improved our understanding of how we might target inflammatory neutrophils in lung disease. Simple measures like administering steroids to tuberculosis patients might diminish destructive neutrophil activity, and spare the lung.
This work provides scientific plausibility for using anti-neutrophil directed therapies in tuberculosis treatment alongside antibiotics. As the rate of antibiotic resistant tuberculosis infections are constantly increasing, finding alternative ways to treat patients is now vitally important.
PhD student Dearbhla Murphy, lead author of the paper said:
"We're really excited about this work as it shows the importance of investigating how macrophages and neutrophils interact and the significance of this interaction during tuberculosis infection. Studying how neutrophils are influenced by other cells can help us identify druggable targets to help develop new therapies for tuberculosis. This is especially important as the number of antibiotic-resistant tuberculosis cases are rising every year and novel therapies are desperately needed to overcome this."
Professor Joseph Keane, Clinical Medicine, Trinity College Dublin and St James's Hospital, said:
"Targeting the neutrophil is one of the hottest topics in tuberculosis research. This mechanistic research encourages the development of therapies that will limit lung damage in this important infection."
Read: you can view the complete paper Human Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis in theInternational Journal of Molecular Sciences here: https://www.Mdpi.Com/1422-0067/25/5/2898
This research was funded by the Royal City of Dublin Hospital Trust and the Health Research Board.
Ends
JournalInternational Journal of Molecular Sciences
Method of ResearchExperimental study
Subject of ResearchPeople
Article TitleHuman Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis
Article Publication Date1-Mar-2024
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