Epidemiology and pathophysiology of vascular thrombosis in ...
Lung Pathogen May Spread Between People Less Than Previously Thought
A little-known bacterium — a distant cousin of the microbes that cause tuberculosis and leprosy — is emerging as a public health threat capable of causing severe lung infections among vulnerable populations, those with compromised immunity or reduced lung function.
Recent research found that various strains of the bacterium Mycobacterium abscessus were genetically similar, stoking fears that it was spreading from person to person.
But a new study by Harvard Medical School researchers published May 22 in PNAS, calls those findings into question, offering an alternative explanation behind the genetic similarity of clinical clusters. This suggests that the pathogen may not be that prone to person-to-person transmission after all.
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Subscribe for FREE "Our findings make a strong case for a different explanation behind the observed genetic similarities across strains," said study senior author Maha Farhat, the Gilbert S. Omenn Associate Professor of Biomedical Informatics at HMS and a pulmonary disease expert at Massachusetts General Hospital. Farhat conducted the work in collaboration with Eric Rubin's lab at the Harvard T.H. Chan School of Public Health.The results, Farhat added, argue against direct person-to-person transmission in clinical settings and instead point to M. Abscessus infections being acquired from the home or other environmental exposures.
In addition to having implications for the precautions that hospitals take to prevent outbreaks, it's an important new clue into the behavior of a relatively unknown pathogen that poses serious risks for vulnerable populations.
The research not only contributes to the understanding of M. Abscessus transmission, but also suggests scientists should be cautious about assuming human transmission when they see genetic similarities in pathogens more generally, said study first author Nicoletta Commins, who conducted the research as a doctoral candidate at HMS and is now a postdoctoral fellow at the Broad Institute.
"Our results certainly do not refute the possibility of person-to-person transmission of Mycobacterium abscessus in some cases, and more research is needed to inform best clinical practice for vulnerable patients," she said. "However, our work supports a model in which person-to-person transmission may not be as common as it is sometimes suggested to be."
M. Abscessus is a hardy microbe highly resistant to antibiotics and can infect the lungs of immunocompromised people. While it doesn't pose a threat to most healthy individuals, it can cause severe infection in those with suppressed immunity or people with compromised lung function such as patients with cystic fibrosis, a genetic condition marked by recurrent lung infections and lung scarring. Notably, patients with CF who become infected with this organism become ineligible for lifesaving lung transplants.
The earlier study that sounded the alarm about person-to-person transmission was based on genetic sequencing of M. Abscessus samples obtained from cystic fibrosis patients at clinics in the United States, Australia, and Europe, including the United Kingdom. Researchers found few genetic mutations across the samples — a possible sign that the pathogen was spreading directly between humans.
For many pathogens such as TB, for example, recent person-to-person transmission leads to only a few or no mutations between any pair of samples simply because the pathogen does not have much time to acquire genetic mutations, Farhat explained.
"Understandably, observing the genetic similarity between M. Abscessus samples caused a great deal of anxiety and fear around how these organisms could be transmitting," she said.
Clinicians, especially in clinics that treat cystic fibrosis patients, began taking extra precautions to avert transmission. However, follow-up investigations failed to find supporting evidence that human-to-human transmission was happening, raising questions about other possible explanations for the genetic similarities across samples.
Farhat's team set out to investigate a hypothesis that the samples appeared genetically similar because the pathogen was evolving at a very slow rate.
"We thought, yeah, you observed a small number of mutations, but we don't know how quickly these mutations are acquired, she explained. "It may be slower than we think, and links between samples that appear recent may not be.'"
The scientists first used a large dataset of M. Abscessus genomes to create a "tree of life," a kind of genetic family tree for the bacterium.
They looked at branches of the tree with clusters of genetically similar strains, then tried to calculate their evolutionary rate. They found that these genetically similar clusters were evolving around 10 times more slowly than typical M. Abscessus strains.
Next, they used computer modeling to determine whether the genetic similarities could be explained by the relatively small population size of these bacteria. But even when they simulated extreme population sizes, the result didn't change. This was an indicator that the high genetic similarity is best explained by a slower evolutionary rate.
Finally, researchers conducted experiments to see how fast different strains of M. Abscessus evolved to develop resistance when exposed to antibiotics in the lab. They found that the genetically similar strains evolved much more slowly than other strains.
"These are three separate lines of evidence supporting this idea that these clustered isolates of Mycobacterium abscessus are evolving at a slower rate," Farhat said.
In addition to reducing concern about person-to-person transmission, the findings provide new insight into a poorly understood pathogen.
In particular, the results offer clues about how a bug found primarily in the environment adapts and changes after it enters the human body — information that could help scientists eventually understand how to prevent and treat infections.
Farhat is now planning follow-up studies that would compare bacteria in the environment with samples taken from patients, to better understand why certain patients become infected.
Reference: Bryant JM, Grogono DM, Rodriguez-Rincon D, et al. Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium. Science. 2016;354(6313):751-757. Doi: 10.1126/science.Aaf8156
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Aggressive Lung Pathogen May Not Be Prone To Person-to-person Transmission
A little-known bacterium -; a distant cousin of the microbes that cause tuberculosis and leprosy -; is emerging as a public health threat capable of causing severe lung infections among vulnerable populations, those with compromised immunity or reduced lung function.
Recent research found that various strains of the bacterium, Mycobacterium abscessus, were genetically similar, stoking fears that it was spreading from person to person.
But a new study by Harvard Medical School researchers published May 22 in PNAS, calls those findings into question, offering an alternative explanation behind the genetic similarity of clinical clusters. This suggests that the pathogen may not be that prone to person-to-person transmission after all.
Our findings make a strong case for a different explanation behind the observed genetic similarities across strains."
Maha Farhat, study senior author, the Gilbert S. Omenn Associate Professor of Biomedical Informatics at HMS and a pulmonary disease expert at Massachusetts General Hospital
Farhat conducted the work in collaboration with Eric Rubin's lab at the Harvard T.H. Chan School of Public Health.
The results, Farhat added, argue against direct person-to-person transmission in clinical settings and instead point to M. Abscessus infections being acquired from the home or other environmental exposures.
In addition to having implications for the precautions that hospitals take to prevent outbreaks, it's an important new clue into the behavior of a relatively unknown pathogen that poses serious risks for vulnerable populations.
The research not only contributes to the understanding of M. Abscessus transmission, but also suggests scientists should be cautious about assuming human transmission when they see genetic similarities in pathogens more generally, said study first author Nicoletta Commins, who conducted the research as a doctoral candidate at HMS and is now a postdoctoral fellow at the Broad Institute.
"Our results certainly do not refute the possibility of person-to-person transmission of Mycobacterium abscessus in some cases, and more research is needed to inform best clinical practice for vulnerable patients," she said. "However, our work supports a model in which person-to-person transmission may not be as common as it is sometimes suggested to be."
M. Abscessus is a hardy microbe highly resistant to antibiotics and can infect the lungs of immunocompromised people. While it doesn't pose a threat to most healthy individuals, it can cause severe infection in those with suppressed immunity or people with compromised lung function such as patients with cystic fibrosis, a genetic condition marked by recurrent lung infections and lung scarring. Notably, patients with CF who become infected with this organism become ineligible for lifesaving lung transplants.
The earlier study that sounded the alarm about person-to-person transmission was based on genetic sequencing of M. Abscessus samples obtained from cystic fibrosis patients at clinics in the United States, Australia, and Europe, including the United Kingdom. Researchers found few genetic mutations across the samples -; a possible sign that the pathogen was spreading directly between humans.
For many pathogens such as TB, for example, recent person-to-person transmission leads to only a few or no mutations between any pair of samples simply because the pathogen does not have much time to acquire genetic mutations, Farhat explained.
"Understandably, observing the genetic similarity between M. Abscessus samples caused a great deal of anxiety and fear around how these organisms could be transmitting," she said.
Clinicians, especially in clinics that treat cystic fibrosis patients, began taking extra precautions to avert transmission. However, follow-up investigations failed to find supporting evidence that human-to-human transmission was happening, raising questions about other possible explanations for the genetic similarities across samples.
Farhat's team set out to investigate a hypothesis that the samples appeared genetically similar because the pathogen was evolving at a very slow rate.
"We thought, yeah, you observed a small number of mutations, but we don't know how quickly these mutations are acquired, she explained. "It may be slower than we think, and links between samples that appear recent may not be.'"
The scientists first used a large dataset of M. Abscessus genomes to create a "tree of life," a kind of genetic family tree for the bacterium.
They looked at branches of the tree with clusters of genetically similar strains, then tried to calculate their evolutionary rate. They found that these genetically similar clusters were evolving around 10 times more slowly than typical M. Abscessus strains.
Next, they used computer modeling to determine whether the genetic similarities could be explained by the relatively small population size of these bacteria. But even when they simulated extreme population sizes, the result didn't change. This was an indicator that the high genetic similarity is best explained by a slower evolutionary rate.
Finally, researchers conducted experiments to see how fast different strains of M. Abscessus evolved to develop resistance when exposed to antibiotics in the lab. They found that the genetically similar strains evolved much more slowly than other strains.
"These are three separate lines of evidence supporting this idea that these clustered isolates of Mycobacterium abscessus are evolving at a slower rate," Farhat said.
In addition to reducing concern about person-to-person transmission, the findings provide new insight into a poorly understood pathogen.
In particular, the results offer clues about how a bug found primarily in the environment adapts and changes after it enters the human body -; information that could help scientists eventually understand how to prevent and treat infections.
Farhat is now planning follow-up studies that would compare bacteria in the environment with samples taken from patients, to better understand why certain patients become infected.
Source:
Journal reference:
Commins, N., et al. (2023) Mutation rates and adaptive variation among the clinically dominant clusters of Mycobacterium abscessus. PNAS. Doi.Org/10.1073/pnas.2302033120.
What Are The Early Signs Of COPD?
Early signs of chronic obstructive pulmonary disease (COPD) include a chronic cough, increased mucus, and tiredness. Knowing which symptoms to look out for at home can help a person know when to visit a doctor for tests.
COPD is the term for a group of lung diseases that tend to worsen over time. Examples of these conditions include emphysema and chronic bronchitis.
COPD obstructs a person's airways, making it difficult to breathe. It is a progressive condition, meaning it tends to worsen over time. Without treatment, COPD can be life threatening.
According to the World Health Organization (WHO), the Global Burden of Disease Study estimated that COPD caused 3.23 million deaths worldwide in 2019. Additionally, health experts estimate around 16 million people in the United States have the disease.
This article describes the early signs and symptoms of COPD and how it gets worse. It also covers when to speak with a doctor.
The Global Initiative for Chronic Obstructive Lung Disease's COPD Gold Guidelines can help doctors assess whether a person has COPD according to the nature and degree of their symptoms, their history of symptom progression, and the presence of additional medical diagnoses that might cause or worsen their symptoms.
Additionally, the guidelines classify the severity of airflow limitation in COPD according to forced expiratory volume (FEV). FEV is how much air a person can push out of their lungs in 1 second during a spirometry test. The lower the value, the more breathing difficulties an individual has. Health experts grade the severity of airflow limitation using four categories:
However, the organization also recognizes that assessment of airflow limitation alone is not sufficient, as health experts now know COPD affects more than a person's ability to breathe. With this in mind, a full medical examination by a doctor can best determine whether an individual has COPD and the degree of the disease's severity.
In its early stages, COPD symptoms may be so mild that the individual does not notice them. The symptoms and severity of COPD can also vary from person to person.
However, because the disease is progressive, symptoms often worsen over time. The early signs and symptoms of COPD can include the below.
Chronic coughA persistent or chronic cough is often one of the first symptoms of COPD. A person may experience a chesty cough that does not go away on its own.
Doctors generally consider a cough that lasts for longer than 8 weeks to be chronic.
Coughing is a protective mechanism that typically occurs in response to irritants, such as inhaled cigarette or tobacco smoke, getting into the lungs. Coughing also helps remove phlegm, or mucus, from the lungs.
However, if a person has an ongoing cough, this may signify a problem with their lungs.
Excess mucus productionProducing too much mucus can also be an early symptom of COPD. Mucus is essential for keeping the airways moist, and it also captures germs and irritants that get into the lungs.
When a person inhales an irritant, their body produces more mucus, which can lead to coughing. Smoking is a very common cause of excess mucus production and coughing.
Long-term exposure to irritants can damage the lungs and lead to COPD. Other lung irritants can include:
The obstruction of the air passages can make it more difficult for a person to breathe, which can lead to shortness of breath, another common symptom of COPD.
At first, shortness of breath may only occur after exercise, but it can worsen over time. Some people cope with their breathing difficulties by becoming less active, which can lead to them becoming less physically fit.
A person with COPD needs to exert extra effort to breathe. This exertion can result in lower energy levels and feeling tired all the time.
Because their lungs are not functioning as well as they should, people with COPD are more likely to experience chest infections, including the common cold, flu, and pneumonia.
Other symptoms of COPD include:
A person with a COPD diagnosis may experience flare-ups, which are also known as COPD exacerbations, when symptoms suddenly worsen. Triggers of COPD flare-ups can include chest infections and exposure to cigarette smoke and other lung irritants.
Exacerbations may begin as mild, but they can become very serious quickly without prompt medical care. Early warning signs of a COPD flare-up may include:
A person who experiences any of the above symptoms regularly should speak with a doctor. Anyone who experiences signs of COPD exacerbation should also consult their doctor as soon as possible.
Even if people are not sure they have COPD, a healthcare professional can usually distinguish between COPD and other diseases. Early diagnosis of COPD can allow individuals to receive treatment sooner, which can help slow the progression of the disease before it becomes severe or life threatening.
The most common cause of COPD is smoking cigarettes or other tobacco products. According to the National Heart, Lung, and Blood Institute, up to 75% of people with COPD either smoke or have smoked. However, long term exposure to other irritants or harmful fumes may also cause or contribute to the condition.
Genetics may also increase the risk of developing COPD. For example, people with a deficiency in a protein called alpha-1 antitrypsin may be more likely to develop the condition, especially if they smoke or have regular exposure to other lung irritants.
The signs and symptoms of COPD most often start in people aged 40 years or older.
Getting a COPD diagnosis begins with a medical exam. Doctors usually start by asking the individual about their symptoms and medical history, including whether or not they smoke and if they have had exposure to any lung irritants.
They may also perform a physical examination and check for wheezing or other signs of lung problems.
To confirm their diagnosis, a healthcare professional may order some tests, such as:
COPD is a common condition. However, some people mistake its symptoms for the normal signs of aging, which can mean they do not get a diagnosis. Without treatment, COPD can become progressively worse over time.
COPD can be a significant cause of disability. An individual with severe COPD may struggle with day-to-day tasks, such as climbing a flight of stairs or standing for prolonged periods to cook a meal. Flare-ups and complications can also severely impact a person's health and quality of life.
There is no cure for COPD, but early diagnosis and treatment can greatly improve a person's outlook. Appropriate treatment and lifestyle changes can relieve symptoms and slow or halt the progression of the condition.
Treatment options include medications, oxygen therapy, and pulmonary rehabilitation. Lifestyle changes involve engaging in regular exercise, eating a nutritious diet, and stopping smoking.
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