Day: August 29, 2024

Categories : Immune System NeurologyTags : Leave a comment

How the Brain Protects Itself Against Herpes Simplex Virus

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Source: CC0

More than half of us are carriers of chronic herpesvirus infections. But even though the herpes simplex virus can infect nerve cells, it rarely causes serious infection of the brain. Researchers from Aarhus University have now discovered a key element of the explanation.

The researchers have discovered a previously unknown defence mechanism in the body that is the reason why herpes infection causes a serious and potentially fatal brain inflammation in only one out of 250 000 cases. The study has recently been published in the scientific journal Nature.

“The study has exciting perspectives because it gives us a better understanding of how the brain defends itself against viral infections,” says Professor Søren Riis Paludan from the Department of Biomedicine at Aarhus University. He is the article’s last author, a Lundbeck Foundation Professor and centre director of the Excellence Centre CiViA.

“We’ve discovered how our body prevents herpesvirus from entering into the brain, even though 50–80% of us are chronically infected with this particular virus. The idea behind CiViA is that we want to understand how the body fights infections without harming itself at the same time. The mechanism we’ve found doesn’t cause inflammatory reactions,” he says.

The answer lies in the protective TMEFF1 gene.

The brain uses a novel mechanism to keep the virus out

Many years of experimenting with the genome-wide CRISPR screening technology and development of mice that lacked the critical gene have finally convinced the researchers that TMEFF1 produces a protein that prevents herpesvirus from entering into nerve cells.   

The study in Nature is accompanied by another article describing two patients with brain inflammation caused by herpesvirus infection, called herpes encephalitic. In a collaborative study led by researchers in New York, the research group in Aarhus discovered that two children who developed herpes encephalitis were carrying a genetic defect that disabled the protective TMEFF1 gene.

“The new study is groundbreaking because it updates the basic understanding of immunity against viral infections,” explains Søren Riis Paludan.

 “This is interesting for immunologists because it illustrates that there are still many immunological mechanisms in the brain that we don’t know about. “The study is also relevant for neuroscience because it sheds light on how the brain, so to say, prevents unwanted visitors from intruding without causing harm to the brain itself, i.e. the neuronal cells,” he says.

May provide a better understanding of Alzheimer’s

Søren Riis Paludan hopes that the study is the first step towards revealing a completely new range of brain defence mechanisms. One of the tracks that the researchers will now investigate is what the discovery may mean for the development of dementia.

Research has already demonstrated a correlation between infection with herpesviruses and later development of Alzheimer’s disease.

“Perhaps our discovery of a new antiviral mechanism in the brain can help to clarify whether individual differences in this particular mechanism or similar mechanisms can give the virus access to the brain and accelerate neurodegenerative processes,” says Søren Riis Paludan.

Source: Aarhus University

Categories : Gastrointestinal UrogenitalTags : Leave a comment

Recurrent Chlamydia Results from Bacteria Settling in the Intestine

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Immunofluorescence staining of human gastric cells grown in a microplate and infected with Chlamydia trachomatis. Blue: cell nuclei, green: C. trachomatis, grey: actin. (Image: Pargev Hovhannisyan / Universität Würzburg)

A phenomenon is known from everyday clinical practice that can occur after successful antibiotic treatment: when people who have already been treated come to the doctor with a new chlamydia infection, they are often infected with exactly the same strains of bacteria as the previous infection.

“It is therefore reasonable to assume that the bacteria find a niche in the body where they are not yet vulnerable, that they form a permanent reservoir there and can become active again later,” says Professor Thomas Rudel, chlamydia expert and Head of the Chair of Microbiology at the Biocentre of Julius-Maximilians-Universität (JMU) Würzburg in Germany. This phenomenon is known as persistence. It is problematic because the chlamydia that persist in the body become increasingly resistant to antibiotics over time.

Intestinal Organoids Experimentally Infected with Chlamydia

Experiments on mouse models have shown that chlamydia can persist in the intestines of animals. In humans the bacteria also seem to make themselves at home there. This is reported by the research groups of Thomas Rudel and Sina Bartfeld in the journal PLOS Pathogens. Professor Bartfeld worked at JMU until 2021; she now heads the Department of Medical Biotechnology at Technische Universität Berlin.

The researchers identified the intestine as a niche with the help of artificial organs in miniature format, so-called organoids. These are structures produced in the laboratory from human intestinal cells that are very similar in structure and function to the model organ.

The teams from Würzburg and Berlin tried to infect the intestinal organoids with chlamydia. They discovered that the inner cell layer of the organoids is very resistant to the bacteria: the pathogens could only penetrate there if the cell epithelium was damaged. From the blood side, however, the chlamydia were able to infect very efficiently. “In this case, we repeatedly found the persistent forms of the bacteria, which can be clearly identified with their typical shape under the electron microscope,” says JMU researcher Pargev Hovhannisyan, first author of the publication.

Clinical Studies and Further Experiments Must Follow

Transferred to the human organism, this would mean that chlamydia infection with subsequent persistence can only occur with difficulty via the inner side of the intestine, but very easily via the blood. However, whether this actually happens in the human body has yet to be confirmed in clinical studies, says Thomas Rudel.

The next step for Thomas Rudel and Sina Bartfeld is to to find out whether the chlamydia select certain cell types for their persistence – no easy task, as the intestine consists of hundreds of different cell types. But perhaps it is also factors from the surrounding tissue that trigger persistence. These and other details are now to be investigated.

Source: University of Würzburg

Categories : CancerTags : Leave a comment

Breakthrough Collaboration between Public and Private Sectors Points the Way for National Health

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Photo by Anna Shvets

As debate rages around the feasible application of NHI on a national scale, seemingly ad infinitum, the escalating cancer crisis in South Africa underscores the need for immediate action on the ground. Recent reports shed light on the distressing reality that individuals diagnosed with cancer, dependent on an overburdened public health system, often face extended waiting periods or impossible distances that prevent them from accessing life-saving treatment.

Yet in the Northern Cape, a remarkable success story has quietly unfolded over the last five years, impacting the lives of hundreds of cancer patients and demonstrating that the way to bring better health to the public on a macro scale may be to focus on practical micro solutions that, once proven, can be replicated around the country.

It arises out of a collaboration between the Northern Cape Department of Health, Kimberley’s Robert Mangaliso Sobukwe Hospital and private sector oncology service provider, Icon Oncology, with the shared goal of delivering the best possible care for patients needing radiotherapy services – which were previously far from home.

Jennifer Fuller, Regional Manager for Icon Oncology explains: “The average radiotherapy treatment journey spans between two to six weeks. Previously, the profound socio-economic and psycho-social toll of Northern Cape patients traveling far from their homes and families was immeasurable. During this period there was no radiation facility in the province, so patients had to travel to Bloemfontein for treatment. We collaborated with the Department of Health to treat radiation patients here in the Northern Cape. The result is a true example of how government and the private sector can work together when there is a shared focus on patient outcomes.”

Today, the province provides transport from far-off areas for treatment at Icon’s radiotherapy facility in Kimberley. If needed, accommodation is provided by the RMS Hospital for the duration of the radiotherapy treatment, which can sometimes last for six weeks.

Watch the video on Icon Oncology’s success story in the Northern Cape

Since the implementation of the project in October 2019, 511 cancer patients have completed radiation treatment. Previously all these patients would have had to travel to Bloemfontein to receive treatment. 

“It’s a major success”, says Dr Alastair Kantani, Clinical Manager for hospital services in the Northern Cape. “It’s actually more than a success; it’s a lifesaving partnership. Personally, as a clinician, I’m proud of the fact that we, as a tertiary hospital, can give access to therapy services. Since this partnership, we’ve saved a lot of lives.”

Dr Esme Olivier, acting CEO of Robert Mangaliso Sobukwe Hospital says, “For me this collaboration between Icon and the Department of Health, specifically this hospital, is one of the best things that could happen for the sake of our oncology patients.”

“This is truly a complete collaboration” adds Fuller. “It shows that it can work – and I do believe that this can be replicated further into other provinces.”

Dr Olivier agrees: “I would really encourage every province to get involved with this. Even if they have their own radiation therapy units, just the collaboration and the expertise that Icon brings on board – they can even assist with nursing, whatever need there is that is not immediately available in public hospitals.”

Governance is key and monthly meetings are held between the two management teams to discuss patient experience, statistics, billing and other operational matters.

“This has resulted in continuous improvement of the project delivery over the past five years.  This sharing of responsibility has led to the development of a very strong relationship and the interdependence has meant both parties have worked hard to make sure it works,” says Dr Olivier.

How it works – the patient journey:

  • The patient journey starts at the tertiary state facility, Robert Mangaliso Sobukwe Hospital, where the resident oncologist will consult with the patient once diagnosed by a surgeon or radiologist.  If radiotherapy is indicated, the patient is referred to the Icon Radiotherapy unit in Kimberley.

  • A planning CT-scan is done by an Icon radiotherapist at Robert Magaliso Sobukwe Hospital
  • The treating oncologist and the Icon planning department, draws a plan on the CT-scan to determine the dose and area of radiotherapy that the patient will receive, using a sophisticated, state of the art planning system. The oncologist can access Icon’s planning system remotely and can do this work from anywhere.
  • This constitutes a 15 min radiotherapy session every day on Icon’s linear accelerator, until the required dose is delivered, and treatment is completed. 

“The Northern Cape initiative exemplifies the potential inherent in bridging the gap between public and private healthcare sectors. It showcases how collaboration can transcend obstacles and provide specialised healthcare services and treatment to all citizens. As the country grapples with the challenges and concerns raised by the National Health Insurance (NHI) Bill, this collaborative achievement stands as a testament that the seemingly daunting task of implementing universal healthcare coverage can indeed be navigated. We must commend the vision of the Northern Cape DoH, management from the Robert Mangaliso Sobukwe Hospital and all other stakeholders who have made this project such a success,” explains Dr Ernst Marais, COO of Icon Oncology. 

“It is through collaborations like this one, that we excel in providing the best possible treatment to our patients. Like Hellen Keller said: ‘Alone we can do so little, but together we can do so much’,” concludes Dr Olivier.

Categories : Healthcare Politics and RegulationsTags : Leave a comment

Slow Growth in Health Spending in Sub-Saharan Africa Projected to 2050

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Slow growth in health sector spending is projected in Sub-Saharan Africa as reported in a study published in the open access journal, PLOS Global Public Health. The decline is expected to continue to 2050, according to Angela E Apeagyei and researchers at the Institute for Health Metrics and Evaluation, University of Washington, Seattle, and is driven by tepid growth in the share of government spending that is allocated to health and reductions in development assistance for health.

The research analyses data from databases covering development assistance for health, global health spending and gross domestic spending (GDP) per capita as well as an expected health spending database which provides projected health spending data to 2050. It finds that except for central and eastern Europe and Central Asia, around the world total health spending is expected to rise as a share of GDP, but in Sub-Saharan Africa (except in southern sub-Sahara Africa) it is expected to decrease.

Beyond the challenge of a low prioritisation of the health sector in the government budget, another major driver of this decline is a reduction in development assistance for health. The Millennium Development Goals led to a period of growth in health funding, and development assistance for health grew on average 11.1% annually from 2000 until 2015. It has since dropped to just 4.6% and was particularly hit by the global economic issues caused by the COVID pandemic and subsequent economic shocks such as the war in Ukraine. Although government spending on health in Sub-Saharan Africa has increased, and is expected to continue to rise, the gap left by decreases in development assistance will not be met.

Without improvements, this trend will pose a significant challenge to meeting health-related Sustainable Development Goals and the African Union’s Africa Agenda 2063. The authors hope that their analysis will help policymakers understand future health spending patterns and can translate the insights into tangible actions that can help navigate the region’s complex economic and health challenges.

The authors add: “For countries in sub-Saharan Africa, the projected growth in donor and government funding for health is expected to be significantly lower compared to countries in other regions. This worrying trend underscores the need to prioritise innovative financing strategies to strengthen health systems in line with the region’s economic growth and the broader health needs of its population.”

Provided by PLOS

Categories : AntibioticsTags : Leave a comment

Bacteria able to Overcome Cost of Vancomycin Resistance in Lab Setting

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Compensatory mutations enabled vancomycin resistance to persist through several generations

Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

Staphylococcus aureus has the potential to develop durable vancomycin resistance, according to a study published August 28, 2024, in the open-access journal PLOS Pathogens by Samuel Blechman and Erik Wright from the University of Pittsburgh, USA.

Despite decades of widespread treatment with the antibiotic vancomycin, vancomycin resistance among the bacterium S. aureus is extremely uncommon – only 16 such cases have reported in the US to date. Vancomycin resistance mutations enable bacteria to grow in the presence of vancomycin, but they do so at a cost. Vancomycin-resistant S. aureus (VRSA) strains grow more slowly and will often lose their resistance mutations if vancomycin is not present. The reason behind vancomycin’s durability and the potential for VRSA strains to further adapt have not been adequately explored.

In this study, researchers took four VRSA strains and grew them in the presence and absence of vancomycin to see how the strains would evolve. They found that strains grown in the presence of vancomycin developed additional mutations in the ddl gene, which has previously been associated with vancomycin dependence. These mutations enabled VRSA strains to grow faster when vancomycin was present. Unlike the original strains, which quickly lost vancomycin resistance, the evolved strains maintained resistance through several generations, even when vancomycin was no longer present.

The study shows that durability of vancomycin susceptibility to date should not be taken for granted. The trade-off that often comes with vancomycin resistance can be overcome if the bacteria is allowed to grow in the presence of vancomycin. As antibiotic resistance continues to grow as a public health threat, studies like this underscores the importance of developing new antibiotics.

The authors add: “The superbug MRSA has been held off by the antibiotic vancomycin for decades. A new study shows we will not be able to count on vancomycin forever.”

Provided by PLOS