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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.

New Transmission Route For An Old Disease

Over the past few days, the number of cases with acute diarrhoea has been increasing gradually in the community. Most patients have experienced severe watery stools more than a dozen times within several hours. Moreover, it has been noted that these watery stools have been seen one after another among family members at intervals of a few days. On June 16 last year, the first case of cholera was officially reported at Shukraraj Tropical and Infectious Disease Hospital, meaning cholera may appear and spread anytime and anywhere in the coming days.

Cholera is an acute diarrhoeal illness caused by the bacterium Vibrio cholerae. Two serogroups O1 and O139 (out of more than 200 serogroups) produce cholera-toxin and can cause severe life-threatening diarrhoeal illness; and are found to be associated with widespread outbreaks worldwide. Serogroup O1 is further divided into three serotypes known as "Ogawa", "Inaba" and "Hikojima". It has two biotypes "El tor" and "Classical". Serogroup O1, Ogawa serotype and biotype El tor are found to be responsible for most of the frequent cholera outbreaks in Nepal.

Researchers believe that the Classical biotype is extinct, since cases related to it have not been reported or documented in the past several years. It is, however, worth mentioning here that for the first time, I have reported the Classical biotype having been discovered in cholera patients during the 2012 study in Nepal. Previous studies have shown that the Classical biotype is likely to cause more severe diseases compared to the El tor biotype. Thus, the Nepal study has thrown up a question regarding the existence of the Classical biotype of vibrio cholera, and this requires further investigation. A study conducted by a Japan-Nepal research team analysed sewage water from various locations of Kathmandu Valley in 2008 (June to September) and found multiple serotypes and biotypes of cholera, and warned of possible diarrhoeal outbreaks due to lack of safe drinking water and personal hygiene.

In 2015, for the first time, I identified/observed cholera in admitted patients who had been consuming jar water—a new but unexpected route of transmission of cholera infection. Jar water is generally thought to be clean, safe and ready to drink, and is now becoming the most common drinking water in Nepal. A couple of years ago, the Nepal Academy of Science and Technology (NAST) did surveillance on the commercial jar and bottled water sold in the market, and found medically harmful coliform bacteria which are responsible for diarrhoeal outbreaks each year. Based on this information, it is most likely that the residents of Kathmandu Valley are consuming contaminated drinking water causing diarrhoeal illnesses that may potentially increase in the coming days as the bottled water sold in the market is not being checked by the concerned authorities.

Cholera can be fatal within hours if left untreated. In 2021, a cholera outbreak occurred in Krishnanagar Municipality, Kapilvastu district where four people out of the 885 cases died of diarrhoea. All four patients did not reach health care facilities or were unable to receive proper treatment on time, meaning severe cholera can rapidly reach fatal levels if not treated promptly. In 2022, the first cholera patient admitted to our hospital showed symptoms after consuming uncooked food. These symptoms included severe watery stools and vomiting (multiple episodes), approximately 6-8 hours after eating. Cholera symptoms can appear within a few hours and as late as five days after eating or drinking contaminated food or water.

Profuse watery stool (rice-water stools), vomiting, abdominal or leg cramps, and restlessness are the main symptoms of severe cholera. Cholera can cause severe dehydration that can lead to kidney failure, shock and in the worst case, death. Severe cholera can be seen in 10-20 percent of the patients. Some studies have shown a relationship between blood type O and severe cholera. An asymptomatic cholera patient can spread bacteria up to 10 days after infection. Laboratory confirmation by culture or polymerase chain reaction (PCR) method of the clinically suspected cases or positive rapid diagnostic test (RDT) is needed to confirm a cholera outbreak.

Observation of cholera outbreak during the past nine-year period (2010-19) showed an interesting but unexpected shifting seasonal trend in Nepal. In 2010, a cholera outbreak occurred in the third week of August. Now it has been appearing earlier in April. Currently, the reason for the shifting seasonal trend of cholera in Nepal is not well known or studied; however, some studies pointed to global warming as a cause of this shifting trend. Based on this observation, a cholera outbreak may occur anytime, anywhere and spread rapidly around the country in the coming days. Thus, proper surveillance of commercially bottled water needs to be conducted by the concerned authorities immediately.

Besides preventive measures, vaccines can be considered as another option to mitigate severe cholera. Currently, the World Health Organisation (WHO) has made recommendations on the use of three pre-qualified oral cholera vaccines (Dukoral, Shanchol and Euvicol), especially in areas that have a high risk of cholera transmissions or outbreaks. Unfortunately, vaccines against cholera are not readily available at health care centres as cholera outbreaks occur almost every year in Nepal. In fact, most of the Nepali people are not even aware of the availability of these cholera vaccines, further spreading outbreaks around the country. Thus, the government of Nepal must initiate and provide cholera vaccines in sectors with a high possibility of an outbreak, especially in populated areas or cities.

To sum up, cholera is a severe diarrhoeal illness, and it can be fatal if not treated within hours. Over the last few years, bottled water has become more common in Nepal. Unfortunately, it has also become one of the main routes of cholera transmission in our country. 

Health Ministry Warns Airborne Diseases Could Become Disease X

Jakarta (ANTARA) - The Indonesian Ministry of Health has warned that various airborne diseases have the potential to become Disease X, which could trigger future pandemics.

"Global diseases are usually transmitted through the air, and it is difficult to prevent them compared to transmission through blood or water. It is impossible for people to stop breathing," stated Siti Nadia Tarmizi, the head of the ministry's communication and public services bureau, in Jakarta on Wednesday.

Tarmizi mentioned that one of the diseases that can be transmitted through the air is influenza, similar to COVID-19, which triggered a global pandemic.

"That's why influenza always has the potential to become a pandemic. We do not have a cure for all types of influenza yet. The most possible way to deal with it is through vaccination," Tarmizi explained.

In addition to influenza, she also mentioned several other potential candidates for Disease X, categorized as zoonoses, which are diseases transmitted from animals to humans, such as Ebola, acute hepatitis, and monkeypox.

"Like Ebola, it has been speculated to become a global outbreak for several years, but it hasn't reached that stage yet," she remarked.

Tarmizi explained that Disease X is a term adopted by the World Health Organization (WHO) in February 2018 to represent hypothetical diseases that are not yet known but have the potential to cause future pandemics.

During the 76th World Health Assembly meeting in Geneva, Switzerland, on May 22, the WHO drew attention to the possibility of the emergence of Disease X .

Tarmizi stated that Disease X is caused by unknown pathogens in humans, such as viruses, bacteria, or fungi, with no known treatment.

The term Disease X has been used by the WHO since 2018 for unknown diseases. One year later, COVID-19 emerged as a new pandemic.

"The current readiness is for anticipating and preparing the whole country. The problem is, we still do not know the drug to cure it or the trigger that starts it all," she concluded.

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