Category: Diseases, Syndromes and Conditions

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Red Blood Cell Abnormalities May Trigger Lupus

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A new study revealed that lupus may be triggered by a defective process in the development of red blood cells (RBCs) which leaves mitochondria remnants. The study was published in Cell.

The researchers found that in a number of lupus patients, maturing red blood cells fail to get rid of their mitochondria, which are normally excluded from red blood cells. This abnormal retention of mitochondria can trigger the cascade of immune hyperactivity characteristic of this disease.

“Our findings support that red blood cells can play a really important role in driving inflammation in a subgroup of lupus patients. So this adds a new piece to the lupus puzzle, and could now open the door to new possibilities for therapeutic interventions,” said the study’s senior author, Dr Virginia Pascual, the Drukier Director of the Gale and Ira Drukier Institute for Children’s Health and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine

Lupus is a chronic disorder with no cure that features intermittent and sometimes debilitating attacks by the immune system on the body’s own healthy tissues, including skin, joints, hair follicles, heart and kidneys. A common underlying factor in lupus is the abnormally elevated production of immune-activating proteins called type I interferons. Treatments aim to suppress immune activity, including interferon-driven inflammation.

Previous research found defective mitochondria in the immune cells of lupus patients. In the current study, the researchers focussed on red blood cells, which should lack mitochondria. Many lupus patients had red blood cells with detectable levels of mitochondria, and more common in patients with worse symptoms. By contrast, healthy controls had no mitochondria-containing red blood cells.

Lead author of the study, Dr. Simone Caielli, assistant professor of immunology research at the Drukier Institute and the Department of Pediatrics at Weill Cornell Medicine, then studied how human red blood cells normally get rid of mitochondria as they mature, as prior studies had mainly examined this in mice, and why this process could be defective in lupus patients.

Subsequent experiments showed these abnormal red blood cells cause inflammation. Normally, when red blood cells age or display signs of damage they are removed by macrophages, with binding antibodies helping removal. When the macrophages ingest them, the mitochondrial DNA in the red blood cells triggers a powerful inflammatory pathway called the cGAS/STING pathway, in turn driving type I interferon production. These findings show that “those lupus patients with mitochondria-containing red blood cells and evidence of circulating anti-RBC antibodies had higher interferon signatures compared to those who didn’t,” Dr Caielli said.

The researchers are now investigating how the mitochondria is retained in these cells. Identifying lupus patients with these cells could help predict when they are likely to undergo lupus flares and to develop therapies.

Source: Weill Cornell Medicine

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Marburg Virus Detected in Guinea

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Colourised scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange). Credit: NIAID

Guinea’s health authority announced the first detection of the Marburg virus in the country, which is also the first case in West Africa.

Marburg, a haemorrhagic fever-causing virus related to Ebola, killed more than 200 people in Angola in 2005, the deadliest recorded outbreak. Laboratory tests of samples taken from a now-deceased patient turned out positive for the Marburg virus.

The patient had sought treatment at a local clinic in the southern prefecture of Gueckedou, and a medical team had been sent to investigate the case.  Cases of the 2021 Ebola outbreak in Guinea occurred in Gueckedou, as well as the 2014–2016 West Africa outbreak were initially detected.

“We applaud the alertness and the quick investigative action by Guinea’s health workers. The potential for the Marburg virus to spread far and wide means we need to stop it in its tracks,” said Dr Matshidiso Moeti, World Health Organization (WHO) Regional Director for Africa. “We are working with the health authorities to implement a swift response that builds on Guinea’s past experience and expertise in managing Ebola, which is transmitted in a similar way.”

Contact tracing efforts are underway, and health authorities are launching education and awareness programmes on the disease. 

Four high-risk contacts, including a healthcare worker, have been identified, as well as 146 others who could be at risk, according to expert Dr Krutika Kuppalli, who spoke to the BBC. A team of WHO experts is on the ground helping to investigate the case and aiding the national health authority’s emergency response.

Cross-border surveillance is also being enhanced to quickly detect any cases, with neighbouring countries on alert. The Ebola control systems in place in Guinea and in neighbouring countries are proving crucial to the emergency response to the Marburg virus.

Marburg is transmitted to people from fruit bats and spreads among humans through direct contact of body fluids.

Illness begins abruptly, with high fever, severe headache and malaise. Within seven days, severe haemorrhagic signs appear in many patients. Case fatality rates are high, ranging from 24% to 88% in past outbreaks depending on virus strain and case management.

With no direct treatments for the virus, supportive care, including rehydration with oral or intravenous fluids, and treatment of specific symptoms, improves survival. There are evaluations underway for potential treatments, including blood products, immune therapies and drug therapies.

One experimental antiviral compound being tested works by preventing viral particles from ‘budding off’ of infected cells.

Source: WHO

Categories : Diseases, Syndromes and Conditions Mental HealthTags :

Severe Atopic Dermatitis Threatens Mental Health

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Photo by Romina Farías on Unsplash
Photo by Romina Farías on Unsplash

A US study showed that adults with atopic dermatitis (AD) had a higher burden of disease than those with other chronic diseases. Even mild dermatitis can negatively affect quality of life (QoL), increasing risk of anxiety, depression, and suicide.

Persistent itching and skin pain can disrupt sleep, leading to poor work or study performance. In moderate to severe disease, oozing, crusting lesions can lead to stigmatisation social isolation. More adults are affected than previously thought, with some 16.5 million adults in the US estimated to have AD.

In a study of 1278 patients using the US web-based Growth from Knowledge (GfK) panel, 60.1% had mild disease, 28.9% had moderate AD, and 11% had severe AD. Patients with more severe disease had higher scores on the dermatology life quality index and on the hospital anxiety and depression scale (HADS) when compared with controls.

This indicates “a worse impact on quality of life and an increased likelihood of anxiety or depression,” the researchers wrote in the Journal of Investigative Dermatology. “Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.”

Quality of life threatened
A pair of studies in patients from the GfK panel reinforce these findings. The first, with 602 patients, showed that AD carried a “profound” disease burden, based on a comparison of patient-oriented AD measures between patients with and without AD. Those with moderate and severe AD had lower mean mental health scores compared with those who had mild disease, and lower QoL compared with patients with other chronic disorders.

“We recommend that clinicians incorporate QoL assessments in clinical practice to determine disease burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbance,” wrote Jonathan I Silverberg, MD, PhD, MPH, of George Washington University, and colleagues in the Annals of Allergy, Asthma and Immunology.

A subsequent study in 2137 patients from the GfK Knowledge Panel found that 40% of patients with AD had a higher prevalence of anxiety or depression in the previous 12 months compared with 17.5% of adults without AD. The researchers concluded that anxiety and depression were driven primarily by disease severity, and were heavily underdiagnosed.

Breaking the ‘vicious cycle’
AD can be life-threatening in some patients, warned the authors of a systematic review and meta-analysis of AD studies. The combination of pruritus, visible skin lesions, social isolation, depression, and anxiety likely sets up a “vicious cycle,” according to the authors.

This “may result in suicidal ideation, suicide attempts, and even completed suicide,” they reported in the Journal of the American Academy of Dermatology.

The investigators found a positive and significant association between AD in adulthood and depression, anxiety, and suicidal ideation, regardless of where the patients lived. And while only a few studies examined the risk of completed suicide, the majority showed a positive association, the authors said. A positive association between AD and depression in children was also identified.

They advised that “depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” adding: “Because AD disease improvement appears to reduce these risks, this should be a priority.”

Better systemic and topical AD therapies are improving the QoL of patients. “It is important to recognise that improvement of AD often results in improvements in symptoms of depression and anxiety, as these mental health symptoms are caused or worsened by the AD,” Dr Silverberg told MedPage Today. “We already have data for dupilumab and the JAK inhibitors that show improvements of HADS scores and other patient-reported outcome measures of mental health.”

Robert Sidbury, MD, MPH, of the University of Washington School of Medicine in Seattle said, “relatively recent literature suggests screening for depression is particularly important for kids with AD, especially those with severe disease.”

AD affects children of all ages, including the very young, and more than 50% of children with AD are diagnosed by age 1 year, he noted.”Dupilumab has been the most effective new available therapy to date by far,” Dr Sidbury told MedPage Today. “Pipeline drugs, particularly the JAK inhibitors like upadacitinib  show tremendous promise.”

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags :

Host Genes Can Hinder H. Pylori Eradication

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Helicobacter pylori is a strong risk factor for gastric cancer and other gastrointestinal disorders, and efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs) often fail.

A new study has linked this eradication failure with genetic variations that increase the activity of the CYP2C19 enzyme, which metabolises first-generation PPIs.

These so-called ‘fast metabolisers’ may prevent PPIs from suppressing gastric acid production, which is necessary for successful H. pylori eradication.

Analysing 57 studies from 11 countries, the researchers found that the failure rate of H. pylori eradication more than doubled in people with a version of the CYP2C19 gene that increased its metabolic activity. Their results were published in Gastroenterology.

However, CYP2C19 variants were not linked to eradication failure if the fast metabolisers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolised by the enzyme or which bypass CYP2C19 metabolism.

Further well-designed studies are needed to determine whether eradication rates could be improved with higher or more frequent dosages of first-generation PPIs to people with the fast metaboliser gene variant, noted the paper’s corresponding author, Shailja Shah, MD, MPH.
“Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.

Source: Vanderbilt University

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Nerve Damage Observed as Liver Disease Progresses

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Photo by National Cancer Institute on Unsplash

Using an innovative 3D imaging technology, researchers at Karolinska Institutet have discovered that a part of the liver’s autonomic nervous system undergoes severe degeneration in non-alcoholic fatty liver disease.

The study showed that the degeneration of nerves is correlated with the severity of liver pathology. The findings are being published in the journal Science Advances.

With a global prevalence of about 25 percent, non-alcoholic fatty liver disease is the most common hepatic disorder. Approximately one third of all fatty liver cases progress to steatohepatitis, a severe disease seriously affecting the entire metabolism.

In the current paper, researchers explore the nervous system in fatty liver using volume immuno-imaging and light sheet microscopy ― a novel imaging technique, which together offers large-scale 3D visualisation with cellular resolution. According to the study, this technology can reveal even early, minor or hidden structural impairments of the liver.

“Now we know that nerves in the liver have multiple subtle regulatory roles” says Csaba Adori, researcher at the Department of Neuroscience, who led the study. “Their role, however, may be more essential during the fight-or-flight response or when subjected to metabolic challenges. Degeneration of liver sympathetic nerves and abnormal operation of the remaining nerve fibres in the fatty liver could compromise all these functions, which may contribute to further aggravation of the disease, as part of a vicious cycle.”

According to the study, changes in liver innervation are already underway in the early stages of fatty liver disease. As it progresses to more severe steatohepatitis, these impairments become a significant degradation of the nerves. The nerve pathology is also similar in mouse models of fatty liver and in human fatty liver samples. The team hopes this will open new avenues for  the treatment of steatohepatitis and portal hypertension, through targeting the liver sympathetic nervous system.

Source: Karolinska Institutet

Categories : COVID Diseases, Syndromes and ConditionsTags :

A Report of Two Sequential Cases of Facial Palsy after COVID Vaccines

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The case of a patient who experienced two facial palsies, both immediately after receiving the Pfizer-BioNTech vaccine, strongly suggests that they are linked to the vaccine, wrote in the journal BMJ Case Reports.

The case report of two separate unilateral facial nerve palsies, where muscles on one side of the face become weak or paralysed, occurring shortly after each dose of a COVID vaccine, is the first in medical literature.

“The occurrence of the episodes immediately after each vaccine dose strongly suggests that the Bell’s palsy was attributed to the Pfizer-BioNTech vaccine, although a causal relationship cannot be established,” the authors said.

Single episodes of unilateral facial nerve palsies were reported in the initial clinical trials of Pfizer-BioNTech, Moderna and Oxford/Astra Zeneca and there have been subsequent case reports.

In phase 3 trials, four cases of facial palsy of unknown cause (Bell’s palsy) were reported in volunteers who received the Pfizer-BioNTech mRNA vaccine and none in the placebo group, and three cases were reported in volunteers who received the Moderna mRNA vaccine compared with one in the placebo group. Three cases of facial nerve palsy were also reported in volunteers who received the Oxford/AstraZeneca vaccine, and there were three cases in the placebo group.

This case report describes a 61-year-old Caucasian male with no previous history of facial nerve palsy who experienced an episode of Bell’s palsy on the right side of his face five hours after receiving his first dose of the Pfizer-BioNTech vaccine, and a more severe episode of Bell’s palsy on the left side of his face two days after receiving the second dose. The patient had a high BMI, hypertension, hypercholesterolaemia and type 2 diabetes.

After the first episode, the patient went to the emergency department, with incomplete eye closure and no forehead movement and was diagnosed with Bell’s palsy. Blood tests and a CT head scan revealed no pathologies and he was discharged with a course of steroids, and the right-sided facial nerve palsy completely resolved.

Two days after his second shot, he developed a more severe left-sided facial nerve palsy. The symptoms included dribbling, difficulty swallowing and again, incomplete left eye closure. He went to the emergency department, where he was again prescribed a course of steroids. He was also referred to an emergency Ear Nose and Throat clinic, which continued the steroids and referred him to ophthalmology.

The authors reported that the patient is almost back to normal. “The patient has been advised to discuss future mRNA vaccines with the GP on a case-by-case basis, taking into account risk versus benefit of having each vaccine,” they said.

Bell’s palsy is believed to be related to facial nerve inflammation and oedema from viral infection. In 2004 the inactivated intranasal influenza vaccine was shown to significantly increase the risk of Bell’s palsy and was discontinued. Increased incidence of Bell’s palsy has also been seen following administration of other influenza and meningococcal vaccines. The annual incidence is 15 to 20 per 100 000 and the lifetime risk is 1 in 60, with an 8% to 12% recurrence rate.

While most cases of Bell’s palsy recover on their own over time, the symptoms can cause significant temporary disability, affecting facial expression and eating and drinking. Risk factors for the condition include diabetes, obesity, hypertension, pregnancy, pre-eclampsia and upper respiratory disease.

Source: EurekAlert!

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Untreated Sewage is a Driver of Antibiotic Resistance

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Photo by Jordan Opel on Unsplash
Photo by Jordan Opel on Unsplash

Contamination of urban lakes, rivers and surface water by human waste is creating pools of ‘superbugs’ in Low- and Middle-Income Countries (LMIC), according to new research. However, improving access to clean water, sanitation and sewerage infrastructure could help to improve public health.

For the study, researchers studied bodies of water in urban and rural sites in three areas of Bangladesh: Mymensingh, Shariatpur and Dhaka. In comparison to rural settings, they detected more antibiotic resistant faecal coliforms in urban surface water , consistent with reports of such bacteria in rivers across Asia. Their findings were published in mSystems.

Lead author Willem van Schaik, Professor of Microbiology and Infection at the University of Birmingham, commented: “The rivers and lakes of Dhaka are surrounded by highly-populated slums in which human waste is directly released into the water. The presence of human gut bacteria links to high levels of antibiotic resistance genes, suggesting that such contamination is driving the presence of these ‘superbugs’ in surface water.

“Interventions aimed at improving access to clean water, sanitation and sewerage infrastructure may thus be important to reduce the risk of antimicrobial resistance spreading in Bangladesh and other LMICs. While levels of antibiotic resistance genes are considerably lower in rural than in urban settings, we found that antibiotics are commonly used in fish farming and further policies need to be developed to reduce their use.”

Infections from antibiotic-resistant bacteria are on the rise globally, but the clinical issues posed by these bacteria are particularly alarming in LMICs, with significant morbidity and mortality. As in other LMICs, multidrug-resistant E. coli has a relatively high prevalence in healthy humans in Bangladesh.

With a population of around 16 million people, Dhaka’s population density ranks among the highest of any megacity, but less than 20% of its households have a sewerage connection.

Urban surface waters in Bangladesh are particularly rich in antibiotic resistance genes, the researchers discovered, with a higher number of them associated with plasmids — vehicles of genetic exchange among bacteria — indicating that they are more likely to spread through the population.

Antibiotic-resistant bacteria that colonise the human gut can be passed into rivers, lakes and coastal areas through the release of untreated wastewater, the overflow of pit latrines during monsoon season or by practices such as open defecation.

Such contaminated environments are often used for bathing, for the washing of clothes and food utensils, thereby risking human gut colonisation by antibiotic-resistant bacteria.

The researchers from the University of Birmingham and the International Centre for Diarrhoeal Disease Research, Bangladesh called for further research to quantify the drivers of antibiotic resistance in surface waters in Bangladesh.

Source: University of Birmingham

Journal information: McInnes, R.S., et al. (2021) Metagenome-Wide Analysis of Rural and Urban Surface Waters and Sediments in Bangladesh Identifies Human Waste as a Driver of Antibiotic Resistance. mSystems. doi.org/10.1128/mSystems.00137-21.

Categories : Diseases, Syndromes and Conditions Injury & TraumaTags :

New Biomarker for Soft Tissue Infections

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This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Photo by CDC on Unsplash
This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Image by CDC on Unsplash

Researchers have identified a new and very promising biomarker for bacterial soft tissue infections, which previously lacked one. 

In bacterial soft tissue infections, rapid diagnosis is crucial in reducing the risk of severe injury or amputation. Vague symptoms and a varied patient presentations increase the risk of misdiagnosis.The study, by  Researchers at Karolinska Institutet in Sweden  and other research institutions, and published in the Journal of Clinical Investigation, may have implications for both diagnosis and treatment.

Last author Anna Norrby-Teglund, Professor, Department of Medicine, Karolinska Institutet, said: “There are currently no tools for safe, rapid diagnosis in life-threatening soft tissue infections. Our findings are consequently very interesting as the biomarkers identified are possible candidates for improved diagnostics. The results are also relevant for individualised treatment in the future.”

Necrotising soft tissue infections (NSTI) are bacterial infections which are characterised by rapid tissue degradation. Such infections, often caused by streptococci, while relatively uncommon, are extremely serious. In most cases they necessitate intensive care and can quickly become life-threatening.

Extensive surgery, intravenous antibiotics are often required to prevent the infection from spreading, and amputation may be required in extreme situations. Many patients also develop sepsis, which further complicates the course of the condition.

Early, correct diagnosis is crucial to save lives and avoid amputation, but this is complicated by factors such as vague symptoms including vomiting, fever and severe pain, as well as the heterogeneous group of patients. Despite recommendations for surgical evaluation in suspected NSTI, there is a considerable risk of misdiagnosis.

Currently, various laboratory tests, including white blood cell counts, are used as diagnostic tools, but suffer from low sensitivity. NSTI-specific biomarkers are therefore needed. The condition is classified into four types depending on the infecting organism.

Researchers at Karolinska Institutet, Haukeland University Hospital, Norway, and Copenhagen University Hospital, Denmark, have now been able to identify biomarkers specific to different patient groups with soft tissue infections.

Using machine learning, the researchers analysed 36 soluble factors in blood plasma from the 311 NSTI patients included in the international INFECT study. Control groups included patients with suspected NSTI and sepsis, respectively.

The analyses showed a new biomarker that accurately identifies patients with tissue necrosis.

“The new biomarker, thrombomodulin, proved to be superior to the laboratory parameters used clinically today. The analyses also identified biomarkers for patients with soft tissue infection caused by different types of bacteria, as well as patients who developed septic shock,” said first author Laura Palma Medina, researcher at the Department of Medicine, Karolinska Institutet (Huddinge).

Source: Karolinska Institutet

Journal information: Palma Medina, L.M., et al. (2021) Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections. Journal of Clinical Investigation. doi.org/10.1172/JCI149523.

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New Insights into Gum Disease and Inflammatory Response

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Photo by Caroline LM on Unsplash
Photo by Caroline LM on Unsplash

A team of researchers has identified how different people respond to the accumulation of dental plaque, helping us understand the vulnerability of some to serious conditions that lead to tooth loss and other problems. 

The study was led by University of Washington researchers and recently published in the journal Proceedings of the National Academy of Sciences (PNAS). 

Buildup of plaque, the sticky biofilm covering teeth and gums, can induce gingivitis, or gum inflammation if left unchecked. Gingivitis, in turn, can lead to periodontitis, a serious infection that can damage and destroy the gum and bones supporting teeth. As well as causing tooth loss, this chronic inflammation can also trigger heart disease, diabetes, cancer, arthritis, and bowel diseases.

The researchers also discovered a range of inflammatory responses to oral bacterial accumulation. When bacteria build up on tooth surfaces, it generates inflammation as the body responds. Two known major oral inflammation phenotypes were known: a high or strong clinical  response and a low clinical response. The team identified a third phenotype, which they dubbed ‘slow’: a delayed strong inflammatory response in the wake of the bacterial buildup.

The study also found that subjects with low clinical response also showed a low inflammatory response for a variety of inflammation signals.  “Indeed, this study has revealed a heterogeneity in the inflammatory response to bacterial accumulation that has not been described previously,” said Dr Richard Darveau of the UW School of Dentistry, one of the study’s authors.

Study co-author Dr Jeffrey McLean said, “We found a particular group of people that have a slower development of plaque as well as a distinct microbial community makeup prior to the start of the study.” The authors wrote that understanding the variations in gum inflammation could help screen for higher periodontitis risk. In addition, it is possible that this variation in the inflammatory response among the human population may be related to the susceptibility to other chronic bacterial-associated inflammatory conditions such as inflammatory bowel disease.

Additionally, the researchers found a novel protective response by the body, triggered by plaque accumulation, that can save tissue and bone during inflammation. This mechanism, which was apparent among all three phenotypes, utilises white blood cells known as neutrophils. In the mouth, they act something like cops on the beat, patrolling and regulating the bacterial population to maintain a stable condition known as healthy homeostasis.

In this instance, plaque is not a villain. To the contrary, the researchers said that the proper amount and makeup of plaque supports normal tissue function. Studies in mice have also shown that plaque also provides a pathway for neutrophils to migrate from the bloodstream through the gum tissue and into the crevice between the teeth and gums.

When healthy homeostasis exists and everything is working right, the neutrophils promote colonization resistance, a low-level protective inflammatory response that helps the mouth fend off an excess of unhealthy bacteria and resist infection. At the same time, the neutrophils help ensure the proper microbial composition for normal periodontal bone and tissue function.

The researchers’ findings underscore why dentists preach the virtues of regular brushing and flossing, which prevent too much plaque buildup. “The idea of oral hygiene is to in fact recolonise the tooth surface with appropriate bacteria that participate with the host inflammatory response to keep unwanted bacteria out,” Dr Darveau explained. The bacteria start repopulating the mouth’s surfaces spontaneously and almost immediately afterward, Dr Darveau said.

Source: University of Washington School of Dentistry

Journal information: Bamashmous, S., et al. (2021) Human variation in gingival inflammation. PNAS. doi.org/10.1073/pnas.2012578118.

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Nose Drops of ‘Friendly’ Bacteria Protects Against Meningitis

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Photo by Mathilde Langevin on Unsplash
Photo by Mathilde Langevin on Unsplash

Researchers have shown that nose drops of genetically modified ‘friendly’ bacteria protect against a form of meningitis.

The study, published in the journal Science Translational Medicine, was led by Professor Robert Read and Dr Jay Laver from the NIHR Southampton Biomedical Research Centre and the University of Southampton, and is the first of its kind.

The researchers spliced a gene into a harmless bacteria type, which enabled it to remain in the nose for longer than normal, triggering an immune response. Then, via nose drops, they administered these altered bacteria into the noses of healthy volunteers. The results showed a strong immune response against bacteria that cause meningitis and long-lasting protection.

Meningitis protection

Meningitis occurs in people of all age groups but affects mainly infants, young children and the elderly. Meningococcal meningitis, a bacterial form of the disease, can lead to death in as little as four hours after symptom onset.

Around 10% of adults carry Neisseria meningitidis in the back of their nose and throat without any signs or symptoms. In certain people however, it can invade the bloodstream, potentially leading to life-threatening conditions including meningitis and septicaemia.

The ‘friendly’ bacteria Neisseria lactamica also lives in some people’s noses naturally. By occupying the nose, it denies a foothold to its close relative N. meningitidis.

Boosted immune response

The study is an extension of the team’s previous work aiming to exploit this natural phenomenon. Nose drops of N. lactamica in that previous study prevented N. meningitidis from settling in 60% of participants. The team sought to improve on this.

They gave N. lactamica one of N. meningitidis’ key weapons; by giving it the gene for a ‘sticky’ surface protein that grips the cells lining the nose.
Those modified bacteria managed to remain longer and produced a stronger immune response. From at least 28 days, most participants (86%) still carried it at 90 days, it caused no adverse symptoms.

This is a promising find for this new way of preventing life-threatening infections, without drugs, especially in the face of growing antimicrobial resistance.

Dr Jay Laver, Senior Research Fellow in Molecular Microbiology at the University of Southampton, commented: “Although this study has identified the potential of our recombinant N. lactamica technology for protecting people against meningococcal disease, the underlying platform technology has broader applications.

“It is theoretically possible to express any antigen in our bacteria, which means we can potentially adapt them to combat a multitude of infections that enter the body through the upper respiratory tract. In addition to the delivery of vaccine antigens, advances in synthetic biology mean we might also use genetically modified bacteria to manufacture and deliver therapeutics molecules in the near future.”

Prof Read, Director of the NIHR Southampton Biomedical Research Centre said: “This work has shown that it is possible to protect people from severe diseases by using nose drops containing genetically modified friendly bacteria. We think this is likely to be a very successful and popular way of protecting people against a range of diseases in the future.”

Source: University of Southampton

Journal reference: Laver, J.R., et al. (2021) A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage. Science Translational Medicine. doi.org/10.1126/scitranslmed.abe8573.