Tag: 13/1/26

Categories : VaccinesTags :

World-first Single-dose Dengue Vaccine Approved in Brazil

On By ModernMedia
Red blood cells and serum separate after spinning in a centrifuge in the UVM Vaccine Testing Center. (Photo: Andy Duback)

The world’s first single-dose vaccine to prevent dengue fever has been approved for licensure in one of the largest countries affected by the disease, following 16 years of research contributions by scientists at the University of Vermont (UVM) Vaccine Testing Center, in partnership with the US National Institutes of Health (NIH) and the Johns Hopkins Bloomberg School of Public Health (JHSPH). 

Dengue is the most common mosquito-borne disease worldwide, with nearly half the world’s population living in places with the risk of dengue. Along with high fever and severe muscle and bone pain, the virus can lead to shock, bleeding, and death. With more than 100 million cases reported annually, dengue poses a growing risk throughout the globe. Brazil recorded 5.9 million cases of dengue and more than 6000 deaths in 2024.

The new vaccine has now been licensed for use in Brazil under the name Butantan-TV. On November 26 the Instituto Butantan, a biologic research centre in São Paulo, announced that the vaccine will be incorporated into Brazil’s national immunisation program. Additional global approvals are anticipated as the vaccine is developed through other pharmaceutical partners including Merck and the Serum Institute of India.

In addition to the vaccine approval, a promising new antiviral medication designed to prevent infection and illness in individuals exposed to dengue virus will now advance, thanks to clinical trials at the UVM Vaccine Testing Center and JHSPH. The findings were published in the November 26 issue of the New England Journal of Medicine (NEJM).

“These milestones represent a turning point in global dengue prevention and treatment,” said UVM Vaccine Testing Center founder Beth Kirkpatrick, M.D., professor and chair of the Department of Microbiology and Molecular Genetics at the Robert Larner, M.D. College of Medicine at the University of Vermont. “We are proud of the role UVM has played in advancing science that will save lives worldwide.”

Kirkpatrick served as principal investigator for the umbrella research funding award that supported early-stage clinical trials and immunology research on the vaccine at UVM. Kirkpatrick and colleagues began studying the candidate tetravalent (four-serotype) dengue vaccine in 2009 in collaboration with leaders in the dengue field: JHSPH professor Anna Durbin, M.D., and NIH virologist Steven Whitehead, Ph.D. Whitehead and colleagues at the NIH designed the candidate vaccine. Since 2009, more than 27 clinical trials have been conducted at UVM and JHSPH to develop this vaccine, yielding many major scientific and immunologic insights. 

At UVM, the new dengue antiviral treatment investigation was led by Kristen Pierce, MD, co-director of the Vaccine Testing Center and professor of medicine, and by Durbin’s team at JHSPH. About 80 volunteers participated in clinical trials at the two sites. 

The volunteers were randomly assigned to receive either the treatment or a placebo prior to receiving a dose of a mild strain of dengue virus. The study data published in NEJM showed that the treatment, an oral pan-dengue small molecular antiviral called Mosnodenivir, inhibits replication of dengue virus and prevents infection. An oral antiviral drug would be extremely useful during outbreaks and could be utilized by travelers and persons who are not able to receive a vaccine. 

Categories : Gastrointestinal Lab Tests and ImagingTags :

New Optical Tool Lights up IBD Biomarkers

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A test that rapidly detects signs of inflammatory bowel disease (IBD) in stool samples could improve future diagnosis and monitoring of the condition, a study suggests.

Microscopy images of colon tissue samples from IBD patients under remission (left) and with active disease (right). Granzyme A, indicated by green fluorescence, is elevated in the intestinal tract of IBD patients with active disease. Credit: Emily Thompson.

Scientists have developed a tool to measure the activity of a molecule linked to gut inflammation within faecal samples. The optical tool, known as a luminescent reporter, lights up when it detects the molecule, with higher readouts indicating increased activity and inflammation.

The new technique could boost the accuracy of stool sample tests for IBD, reducing the need for invasive, expensive procedures, experts say.

Gut inflammation

IBD is a chronic illness where the body’s immune system mistakenly attacks the digestive tract, leading to long-lasting inflammation. Diagnosis and monitoring of the condition often rely on colonoscopies, where a small camera is used to examine the gut.

Current IBD stool tests measure general markers of inflammation, such as the protein calprotectin, so a positive result requires further investigation to confirm the source. 

University of Edinburgh researchers studied gut tissue from IBD patients and identified high levels of an enzyme – a molecule that speeds up chemical reactions in cells – called granzyme A (GzmA) in inflamed gut tissue compared with non-inflamed tissues. 

Enzyme activity

GzmA is released by T cells; in IBD, T cells mistakenly see the gut as a threat and become overactive, which can lead to tissue damage and inflammation.

The research team developed a luminescent reporter to measure the activity of GzmA in stool samples. The reporter tool was tested on 150 samples from both IBD and healthy patients. 

Combining the new reporting tool with the current common testing of faecal calprotectin levels was more successful in identifying IBD in patients than using faecal calprotectin scores alone.

Researchers say the ability to identify gut-specific inflammation is a step forward for IBD diagnosis, but caution further research is needed before it can be used in a clinical setting.

Spin-out company

The tool will form part of the assets of a new company in the process of spinning out of the University of Edinburgh, called IDXSense, supported by Edinburgh Innovations, the University’s commercialisation service. 

The technique could also support the development of personalised IBD treatments in the future, with the ability to rapidly and accurately monitor gut inflammation levels in response to different therapies, experts say.

Source: The University of Edinburgh

Categories : GeneticsTags :

Two Wrongs Make a Right: How Two Harmful Variants Can Counteract Each Other

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Photo by Sangharsh Lohakare on Unsplash

In a groundbreaking study published in the Proceedings of the National Academy of Sciences (PNAS), scientists at Pacific Northwest Research Institute (PNRI) have overturned a long-held belief in genetics: that inheriting two harmful variants in the same gene always worsens disease. Instead, the team found that, in many cases, two harmful variants can actually restore normal protein function.

The research focused on a human enzyme called argininosuccinate lyase (ASL), which plays a critical role in removing toxic ammonia from the body. Variants in ASL that decrease its activity cause one of the urea cycle disorders, a set of rare and potentially life-threatening metabolic diseases.

By experimentally measuring the functional impact of several thousand individual variants and variant combinations, PNRI researchers discovered that over 60% of pairs that were individually damaging could, together, bring enzyme activity back to healthy levels.

“This work shows that genetic variants don’t act independently in many important cases,” said Michelle Tang, PhD, PNRI Staff Scientist and lead author of the study. “For a defined group of genes, the default assumptions we use to predict disease risk simply don’t hold.”

This phenomenon is known as intragenic complementation. It occurs when damage caused by one variant is offset by another variant in a different part of the same protein. The mechanism was first proposed in 1964 by Francis Crick and Leslie Orgel, but until now had not been tested systematically or shown to be common or predictable at scale.

The study was led by scientists in the Dudley Lab at PNRI, in collaboration with clinicians and researchers at Children’s National Hospital, St. Jude Children’s Research Hospital, George Mason University, and the University of Washington.

To make these interactions predictable, the research team developed an AI-based model that accurately forecasted whether two variants would restore protein function. The model achieved nearly 100% accuracy in predicting intragenic complementation in ASL as well as in a second human enzyme, fumarase, suggesting these rules apply broadly across the human genome.

“We’ve shown that, in many cases, two damaging variants can work together to restore protein function,“ said Aimée Dudley, PhD, PNRI Senior Investigator who led the study. “This kind of genetic interaction is not an isolated exception, but a widespread and underappreciated way that variants can interact, especially in rare disease contexts.”

The researchers estimate that approximately 4% of human genes have the structural features that allow this type of interaction. For these genes, standard genetic predictions can overestimate disease risk, particularly for people who carry two different variants in the same gene.

Source: Pacific Northwest Research Institute

Categories : Diet and Nutrition PaediatricsTags :

Major Study Highlights Benefits – and Risks – of Plant-based Diets in Children

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Photo by cottonbro studio

Vegetarian and vegan diets can support healthy growth when carefully planned with appropriate supplementation, finds a major new meta-analysis – the most comprehensive study to-date of plant-based diets in children.

A team of researchers, from Italy, USA and Australia, analysed data from over 48 000 children and adolescents worldwide who followed different dietary patterns, examining health outcomes, growth and nutritional adequacy. They found that vegan and vegetarian diets can be nutrient-rich and support healthy growth, but also carry a risk of deficiencies if key nutrients are not obtained through fortified foods or supplements.

The peer-reviewed study, published in Critical Reviews in Food Science and Nutrition, also suggests that plant-based diets may offer additional health benefits for children – including improved cardiovascular risk profiles – compared with omnivorous diets that include meat, fish and other animal-derived foods.

This large meta-analysis is the most comprehensive study to date of plant-based diets in children under 18 years of age, examining data from 59 studies across 18 countries. It compared lacto-ovo-vegetarian (which include dairy products and eggs, but exclude meat, fish and poultry) and vegan diets (which exclude all animal-derived foods) with omnivorous diets across a wide range of nutritional and health outcomes in 7280 lacto-ovo-vegetarians, 1289 vegans and 40 059 omnivores.

The study found that vegetarian children consumed more fibre, iron, folate, vitamin C and magnesium than omnivores, but they had lower intakes of energy, protein, fat, vitamin B12 and zinc. While evidence on vegan diets was more limited, similar patterns emerged.

“Notably, vitamin B12 didn’t reach adequate levels without supplementation or fortified foods, and calcium, iodine and zinc intakes were often at the lower end of recommended ranges, making them important nutrients to consider for children on plant-based diets,” explains the study co-author Dr Jeannette Beasley, an Associate Professor in the Departments of Nutrition and Food Studies and Medicine at New York University.

“Vegan children, in particular, had especially low calcium intake.”

Health benefits

Despite these risks, both vegan and vegetarian children displayed more favourable cardiovascular health profiles than omnivores, with lower total and low-density lipoprotein (LDL) cholesterol – the “unhealthy” form of cholesterol.

Growth and body composition measures indicated that children on plant-based diets tended to be leaner than omnivores: vegetarian children were slightly shorter and lighter, with lower body mass index (BMI), fat mass and bone mineral content. Vegan children also had shorter stature and lower BMI scores.

“Our analysis of current evidence suggests that well-planned and appropriately supplemented vegetarian and vegan diets can meet nutritional requirements and support healthy growth in children,” states lead-author Dr Monica Dinu, who focuses on exploring how nutrition shapes health and well-being at the Department of Experimental and Clinical Medicine, at the University of Florence, in Italy.

Parents: take an informed approach

Plant based diets remain entirely achievable for children and can offer environmental advantages as well as health benefits. The authors stress that families should not be discouraged from choosing vegetarian or vegan diets for ethical, environmental or health reasons. Instead, they recommend that parents approach these diets with informed planning and, where possible, seek support from clinicians such as dietitians and paediatric health professionals. With attention to a few key nutrients, these diets can fully meet children’s needs during periods of rapid growth while reducing nutritional risks.

“We hope these findings offer clearer guidance on both the benefits and potential risks of plant-based diets, helping the growing number of parents choosing these diets for health, ethical or environmental reasons,” Dr Dinu adds.

More research needed, but balance is key

The authors also emphasise the need for clear, evidence-based guidance to support families with planning healthy plant-based diets for children, who may have higher nutritional needs during periods of rapid growth and development.

However, the researchers caution that these results are limited by the cross-sectional design of most included studies, variability in methods and populations, and challenges in accurately assessing children’s dietary intake.

“In conclusion,” says fellow co-author Dr Wolfgang Marx, from the Food & Mood Centre, at Deakin University, Australia, “while well-planned vegetarian and vegan diets are nutritionally adequate and beneficial for adults, there is far less clarity about their suitability for children – leading to inconsistent or even conflicting advice for parents.

“Our findings suggest that a balanced approach is essential, with families paying close attention to certain nutrients – particularly vitamin B12, calcium, iodine, iron and zinc – to ensure their children get everything they need to thrive.”

Source: Taylor & Francis

Categories : Cancer Lab Tests and ImagingTags :

Diagnostic Breast MRI may be Unnecessary for Some Patients with Early-stage Breast Cancer

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Adding breast magnetic resonance imaging (MRI) to a diagnostic mammogram did not reduce five-year cancer recurrence rates for patients with stage I/II hormone receptor (HR)-negative breast cancer, according to researchers at The University of Texas MD Anderson Cancer Center. 

The Phase III Alliance A011104/ACRIN6694 trial found that five-year locoregional recurrence rates were 6.8% in patients who received an MRI as part of a diagnostic work-up and 4.3% in those who did not. These data were presented today at the San Antonio Breast Cancer Symposium (SABCS) by principal investigator Isabelle Bedrosian, MD, professor of Breast Surgical Oncology (Abstract GS2-07).

“We have long assumed that finding more breast cancer on an MRI and removing it with surgery would help lower the chance of a patient’s cancer coming back,” Bedrosian said. “When you look at our findings alongside earlier trials, the message is clear: adding MRI before surgery doesn’t improve results for patients – and may not have to be used as a standard part of the diagnostic process.”

No additional MRI benefit in this group

The trial enrolled 319 patients between 2014 and 2018 with newly diagnosed stage I or II HR-negative breast cancer. These patients were eligible for lumpectomy and did not have germline BRCA1/2 mutations, bilateral breast cancer or a history of prior breast cancer. All patients had undergone diagnostic mammography with or without ultrasound prior to trial enrolment.  Patients were randomly assigned to undergo additional imaging by breast MRI (161 patients) or to receive no further imaging (158 patients).

Not only did breast MRI not impact five-year recurrence rates, but there were also not significant differences between groups for five-year distant recurrence-free survival nor overall survival. 

A small subset of patients with tumour subtypes (HR- HER2+ and HR-HER2-) and those over the age of 50 at diagnosis also showed no benefit to MRI.

Pre-op MRI not finding anything important

Breast MRI is a common part of the diagnostic evaluation because it can reveal cancer that mammography might not detect. However, the evidence that it improves surgical outcomes for patients has been limited.

“We believe the reason MRI did not reduce recurrence rates may be twofold,” Bedrosian said. “It is possible that MRI didn’t uncover many lesions that mammography hadn’t already found, or perhaps identifying and surgically removing those additional lesions was not important to reducing risk of the cancer coming back. It’s possible that in the group that did not receive MRI, radiation and chemotherapy effectively treated the occult areas of disease”. 

Experts are now analysing how often breast MRI identified additional lesions in the trial population to better understand why breast MRI did not impact oncologic outcomes.

Study limitations 

Limitations included that most patients involved in the trial had breast cancer that hadn’t spread to their lymph nodes, which may partly explain why recurrence rates were low overall. Despite being open to women of all ages, the study enrolled mostly older women who may have been less likely to benefit from breast MRI.