Tag: 6/5/24

Categories : Respiratory DiseasesTags :

SA’s Flu Rates Anticipated to Return to Pre-COVID-19 Levels

On By ModernMedia
Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID

By Elri Voigt for Spotlight

COVID-19-related factors resulted in several years of lower-than-normal rates of the flu, but experts say that is now something of the past. As this year’s flu season gets under way, Elri Voigt asks several local experts what their expectations are, which flu vaccines are available this year, and whether we should be concerned about new strains of bird flu.

While most people who get the flu experience only mild to moderate symptoms, some can get severe symptoms and even die, especially the very young and the old. As Spotlight previously reported, the influenza virus causes around 11 000 deaths per year in South Africa, with around 40 000 people hospitalised.

Dr Sibongile Walaza, a medical epidemiologist and the Head of Epidemiology at the Centre for Respiratory Disease and Meningitis at the National Institute for Communicable Diseases (NICD), says that it is difficult to predict what a flu season will look like beforehand.

Nicole Jennings, spokesperson for the South African Pharmaceutical company Pharma Dynamics, agrees. “Influenza is a global disease and the spread of the virus in other parts of the world can influence the trajectory of flu seasons in different regions. For now, it’s too early to make any predictions,” she says.

It is difficult to predict the trajectory of flu seasons ahead of time, Jennings says, because of a “complex interplay” of factors, including the fact that influenza viruses are constantly mutating. This makes it difficult to accurately predict which strains of the influenza virus will dominate and how they will behave.

“The level of immunity in the population can also vary from year to year due to factors, such as vaccination rates, previous exposure to similar strains and so forth,” she adds. “However, surveillance efforts, modelling and ongoing research conducted by the NICD can help the public to prepare for the cold and flu season as best possible.”

NICD guidelines published in April 2023 already stated that since the COVID-19 pandemic, there have been some changes in the timing of flu transmission.

The transmission reduction strategies – like masking and social distancing – during the pandemic had an impact on the rates of flu transmission and the duration of the flu season between 2020 to 2022, according to Dr Jocelyn Moyes, a medical epidemiologist at the Centre for Respiratory Disease and Meningitis at the NICD.

Back to normal?

Although the numbers were still much lower, it appears that the winter flu season’s peak had started to return to levels seen pre-COVID-19 in 2022 and 2023, Walaza confirms.

“In 2023, the flu season was a little bit longer than we’d seen before [COVID-19], but it started on time. So, in terms of the timing, it was similar to what we would see before COVID-19,” she says.

When exactly the winter flu season starts each year varies, Walaza says, but on average it can start anytime from the third week of April and can circulate until August. It has been known to go on longer though.

At the time of the interview, the NICD had only detected sporadic cases of flu but had not yet seen the sustained uptick in transmission which usually signals the start of the flu season. The latest surveillance data published by the NICD indicate that 108 cases of influenza had been detected so far this year. The real number of flu cases will be much higher since most cases of flu are not diagnosed.

This year’s vaccines

Walaza explains that the flu vaccine is updated each year based on the World Health Organization’s (WHO) recommendations. This is to ensure it provides protection against evolving influenza viruses seen in global surveillance programmes.

Photo by National Cancer Institute

Flu shots used in South Africa are inactivated influenza vaccines. This means they do not contain live virus and cannot cause flu.

In the public healthcare sector, the government this year procured the trivalent vaccine which protects against three strains of the influenza virus – two influenza A strains (H1N1pdm 2009 and H3N2) and one influenza B strain (known as the B/Victoria), Walaza says. These jabs should be in public health clinics by the first week of May.

In the private healthcare sector, she says a trivalent and a quadrivalent vaccine are available. The quadrivalent shot includes protection against a second influenza B strain (B/Yamagata), but that strain has not been seen circulating in a few years. These flu shots are already available in the private healthcare sector.

The level of protection provided by the flu shot varies and generally it ranges in effectiveness against infection from about 30% to 60%, according to Walaza, but importantly it protects against severe illness.

How effective this year’s flu shot will be depends on which influenza strain or strains circulate in the country. “The hope is that if an individual gets infected by any of those strains [in the vaccine], then that individual is protected or has some level of protection [against these strains] and will have some protection against severe illness” she says.

However, she adds, it’s difficult to predict how effective this year’s flu shot will be against preventing someone from getting the flu or experiencing symptoms of the flu. This is because there is always the chance that the strains which do circulate this season are different from the ones in the vaccine or have mutated so the shot becomes less effective.

Should we worry about bird flu?

At the start of April, the WHO reported that one case of avian influenza A (H5N1), one of the avian/bird flu viruses, had been detected in a person in the United States after they had come into contact with a cow who was presumed to be infected. This was the second human case of influenza A (H5N1) detected in that country, and the first case of a person being infected with this strain after coming into contact with a non-avian species.

So far, the risk to the general public is low, according to the WHO.

“Since the virus [avian influenza A (H5N1)] has not acquired mutations that facilitate transmission among humans and based on available information the WHO assesses the public health risk to the general population posed by this virus to be low and for occupationally exposed persons, the risk of infection is considered low-to-moderate,” the WHO statement said.

There are many subtypes of influenza A viruses, Moyes tells Spotlight, and avian influenzas are similar to human influenza A viruses. And so, she explains, there is always a possibility that these viruses mutate, enabling them to infect humans, or more importantly develop the ability to transmit effectively from one person to another. This could potentially cause a pandemic.

She tells Spotlight that over the last decade sporadic cases of human avian influenza have been described related to global outbreaks in birds. These cases have all been in people who have had very close contact – usually during the culling process – with sick birds. She advises that people involved in the management of avian influenza outbreaks take precautions, such as using appropriate personal protective equipment to prevent infection.

When asked whether people in South Africa need to be concerned about a potential bird flu outbreak, Walaza says so far, no cases of bird flu infection in humans – even during the recent widespread outbreaks in birds – have been identified in the country. But it is something that the NICD is aware of and surveillance for human cases during outbreaks of bird flu in the country is being conducted.

“What’s important though to note is that even when cases have been detected [in other countries] the risk of person-to-person transmission is extremely low,” she adds.

Launch of Cough Watch SA

Walaza tells Spotlight that most of the data gathered by the NICD on influenza is from surveillance in healthcare facilities, which means that not all cases of influenza are necessarily identified.

To gather additional data, the NICD is in the process of rolling out an additional digital surveillance system to detect influenza cases, called Cough Watch SA. This online web application allows the public to report influenza symptoms.

People who sign up are asked to provide basic demographic data like age and postal code. Participants will then be sent a weekly prompt asking if they’ve had any flu symptoms. If they have had symptoms, according to Walaza, then they will be asked to provide more information. This data will then be linked to the NICD database where it will be compared to other surveillance data to see if the platform could serve as an early warning system for a flu outbreak.

Cough Watch SA will be launched in the week of 7 May, says Moyes, who urged the public to help keep an eye on flu by signing up.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : Immune System Metabolic DisordersTags :

Experimental Type 1 Diabetes Drug Shields Pancreas Cells from Immune System Attack

On By ModernMedia
A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0

An experimental monoclonal antibody drug called mAb43 appears to prevent and reverse the onset of clinical type 1 diabetes in mice, in some cases lengthening the animals’ lifespan, report scientists at Johns Hopkins Medicine.

The drug is unique, according to the researchers, because it targets insulin-making beta cells in the pancreas directly and is designed to shield those cells from attacks by the body’s own immune system cells. The drug’s specificity for such cells may enable long-term use in humans with few side effects, say the researchers. Monoclonal antibodies are made by cloning, or making identical replicas of, an animal (including human) cell line.

The findings, published in Diabetes, raise the possibility of a new drug for type 1 diabetes, an autoimmune condition which has no cure or means of prevention. Unlike type 2 diabetes, in which the pancreas makes too little insulin, in type 1 diabetes, the pancreas makes no insulin because the immune system attacks the pancreatic cells that make it.

The lack of insulin interferes with the body’s ability to regulate blood sugar levels.

According to Dax Fu, PhD, associate professor of physiology at the Johns Hopkins University School of Medicine and leader of the research team, mAb43 binds to a small protein on the surface of beta cells, which dwell in clusters called islets. The drug was designed to provide a kind of shield or cloak to hide beta cells from immune system cells that attack them as “invaders.” The researchers used a mouse version of the monoclonal antibody, and will need to develop a humanised version for studies in people.

For the current study, the researchers gave 64 non-obese mice bred to develop type 1 diabetes a weekly dose of mAb43 via intravenous injection when they were 10 weeks old. After 35 weeks, all mice were non-diabetic. One of the mice developed diabetes for a period of time, but it recovered at 35 weeks, and that mouse had early signs of diabetes before the antibody was administered.

In five of the same type of diabetes-prone mice, the researchers held off giving weekly mAb43 doses until they were 14 weeks old, and then continued dosages and monitoring for up to 75 weeks. One of the five in the group developed diabetes, but no adverse events were found, say the researchers.

In the experiments in which mAb43 was given early on, the mice lived for the duration of the monitoring period of 75 weeks, compared with the control group of mice that did not receive the drug and lived about 18-40 weeks.

Next, the researchers, including postdoctoral fellows Devi Kasinathan and Zheng Guo, looked more closely at the mice that received mAb43 and used a biological marker called Ki67 to see if beta cells were multiplying in the pancreas. They said, after treatment with the antibody, immune cells retreated from beta cells, reducing the amount of inflammation in the area. In addition, beta cells slowly began reproducing.

“mAb43 in combination with insulin therapy may have the potential to gradually reduce insulin use while beta cells regenerate, ultimately eliminating the need to use insulin supplementation for glycaemic control,” says Kasinathan.

The research team found that mAb43 specifically bound to beta cells, which make up about 1% or 2% of pancreas cells.

Another monoclonal antibody drug, teplizumab, received US Food and Drug Administration approval in 2022. Teplizumab binds to T cells, making them less harmful to insulin-producing beta cells. The drug has been shown to delay the onset of clinical (stage 3) type 1 diabetes by about two years, giving young children who get the disease time to mature and learn to manage lifelong insulin injections and dietary restrictions.

“It’s possible that mAb43 could be used for longer than teplizumab and delay diabetes onset for a much longer time, potentially for as long as it’s administered,” says Fu.

Source: John Hopkins Medicine

Categories : ExerciseTags :

Time-restricted Eating and High-intensity Exercise Might Work Together to Improve Health

On By ModernMedia
Photo by Malvestida on Unsplash

Combining time-restricted eating with high-intensity functional training may improve body composition and cardiometabolic parameters more than either alone, according to a study published May 1, 2024 in the open-access journal PLOS ONE by Ranya Ameur and Rami Maaloul from the University of Sfax, Tunisia, and colleagues.

Changes in diet and exercise are well-known ways to lose weight and improve cardiometabolic health. However, finding the right combination of lifestyle changes to produce sustainable results can be challenging. Prior studies indicate that time-restricted eating (which limits when, but not what, individuals eat) and high-intensity functional training (which combines intense aerobic and resistance exercise) may be beneficial and easier for individuals to commit to long term.

In a new study, researchers investigated the impact of time-restricted eating and high-intensity functional training on body composition and markers of cardiometabolic health such as cholesterol, blood glucose, and lipid levels. 64 women with obesity were assigned to one of three groups: time-restricted eating (diet only), high-intensity functional training (exercise only), or time-restricted eating plus high-intensity functional training (diet + exercise). Participants following the time-restricted eating regimen ate only between 8:00 am and 4:00 pm. Those in the functional training groups worked out three days per week with an instructor.

After 12 weeks, all three groups had significant weight loss and decreases in waist and hip circumference. Likewise, all groups showed favorable changes in lipid and glucose levels.

Some differences were seen between groups. For example, fat-free mass (a combination of lean mass and skeletal muscle mass) and blood pressure improved in the diet + exercise and exercise groups but did not change in the diet-only group.

Participants in the diet + exercise group generally experienced more profound changes in body composition and cardiometabolic parameters than either diet or exercise alone.

The researchers noted that this is a relatively small study, and it is difficult to tease out the contributions of specific exercise routines or of time-restricted eating and calorie reduction since both groups reduced their calorie intake. However, they note that combining time-restricted eating with high-intensity functional training might show promise in improving body composition and cardiometabolic health.

The authors add: “Combining time-restricted eating with High Intensity Functional Training is a promising strategy to improve body composition and cardiometabolic health.”

Provided by PLOS

Categories : Environmental EffectsTags :

Not Just Sunlight – Individual Factors Influence Vitamin D Production

On By ModernMedia
Photo by Michele Blackwell on Unsplash

A new study from Trinity College Dublin sheds light on the complexities of achieving optimal vitamin D status across diverse populations. The study, which was recently published in the journal Clinical Nutrition, showed that individual factors like age, sex and body mass index significantly affected vitamin D levels generated from sunlight exposure.

Despite substantial research on the determinants of vitamin D, levels of vitamin D deficiency remain high. Dr Margaret M. Brennan, Research Assistant, Department of Public Health and Primary Care, School of Medicine, Trinity College and first author, said:

“We hope this work can highlight the significant differences in vitamin D levels among different ethnic groups at northern latitudes and contribute to efforts to address the long-standing population health issue of vitamin D deficiency.”

The authors analysed data from half a million participants from the United Kingdom (UK,) and for each person, they calculated the individualised estimate of ambient ultraviolet-B (UVB) level, which is the wavelength of sunlight that induces vitamin D synthesis in the skin.

A comprehensive analysis of key determinants of vitamin D and their interactions revealed novel insights. The first key insight is that ambient UVB emerges as a critical predictor of vitamin D status, even in a place like the UK, which receives relatively little sunlight. The second is that age, sex, body mass index (BMI), cholesterol level, and vitamin D supplementation significantly influence how individuals respond to UVB. For example, as BMI and age increase, the amount of vitamin D produced in response to UVB decreases.

Professor Lina Zgaga, Associate Professor of Epidemiology, Department of Public Health and Primary Care, School of Medicine, Trinity College and the principal investigator, said:

“We believe our findings have significant implications for the development of tailored recommendations for vitamin D supplementation. Our study underscores the need to move away from a one-size-fits-all approach towards personalised strategies for optimising vitamin D status.”

Source: Trinity College Dublin

Categories : Cancer VaccinesTags :

mRNA Cancer Vaccine Unleashed on Glioblastomas in First Human Trial

On By ModernMedia
Photo by Anna Shvets

In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at the University of Florida quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumour.

The results mirror those in 10 pet dog patients suffering from naturally occurring brain tumours whose owners approved of their participation, as they had no other treatment options, as well as results from preclinical mouse models. Next, the researchers will test the treatment in a Phase 1 paediatric clinical trial.

This breakthrough, published in Cell, represents a potential new way to recruit the immune system to fight notoriously treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID vaccines, but with two key differences: use of a patient’s own tumour cells to create a personalised vaccine, and a newly engineered complex delivery mechanism within the vaccine.

“Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions,” said senior author Elias Sayour, MD, PhD, a UF Health paediatric oncologist who pioneered the new vaccine, which like other immunotherapies attempts to “educate” the immune system that a tumour is foreign. “And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would.”

Among the most impressive findings was how quickly the new method, delivered intravenously, spurred a vigorous immune-system response to reject the tumour, said Sayour, principal investigator of the RNA Engineering Laboratory within UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy and a UF Health Cancer Center and McKnight Brain Institute investigator who led the multi-institution research team.

“In less than 48 hours, we could see these tumours shifting from what we refer to as ‘cold’ – immune cold, very few immune cells, very silenced immune response – to ‘hot,’ very active immune response,” he said. “That was very surprising given how quick this happened, and what that told us is we were able to activate the early part of the immune system very rapidly against these cancers, and that’s critical to unlock the later effects of the immune response.”

Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. Current standard of care involves surgery, radiation and some combination of chemotherapy.

The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. That trial was conducted with owners’ consent in collaboration with the UF College of Veterinary Medicine. Dogs offer a naturally occurring model for malignant glioma because they are the only other species that develops spontaneous brain tumors with some frequency, said Sheila Carrera-Justiz, DVM., a veterinary neurologist at the UF College of Veterinary Medicine who is partnering with Sayour on the clinical trials. Gliomas in dogs are universally terminal, she said.

After treating pet dogs that had spontaneously developed brain cancer with personalised mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

In a cohort of four patients, RNA was extracted from each patient’s own surgically removed tumour, and then messenger RNA, or mRNA was amplified and wrapped in the newly designed high-tech packaging of biocompatible lipid nanoparticles, to make tumour cells “look” like a dangerous virus when reinjected into the bloodstream and prompt an immune-system response. The vaccine was personalised to each patient with a goal of getting the most out of their unique immune system.

“The demonstration that making an mRNA cancer vaccine in this fashion generates similar and strong responses across mice, pet dogs that have developed cancer spontaneously and human patients with brain cancer is a really important finding, because oftentimes we don’t know how well the preclinical studies in animals are going to translate into similar responses in patients,” said Duane Mitchell, M.D., PhD, director of the UF Clinical and Translational Science Institute and the UF Brain Tumor Immunotherapy Program and a co-author of the paper. “And while mRNA vaccines and therapeutics are certainly a hot topic since the COVID pandemic, this is a novel and unique way of delivering the mRNA to generate these really significant and rapid immune responses that we’re seeing across animals and humans.”

While too early in the trial to assess the clinical effects of the vaccine, the patients either lived disease-free longer than expected or survived longer than expected. The 10 pet dogs lived a median of 139 days, compared with a median survival of 30 to 60 days typical for dogs with the condition.

The next step will be an expanded Phase I clinical trial to include up to 24 adult and paediatric patients to validate the findings. Once an optimal and safe dose is confirmed, an estimated 25 children would participate in Phase 2, said Sayour.

Despite the promising results, the authors said one limitation is continued uncertainty about how best to harness the immune system while minimising the potential for adverse side effects.

“I am hopeful that this could be a new paradigm for how we treat patients, a new platform technology for how we can modulate the immune system,” Sayour said. “I am hopeful for how this could now synergise with other immunotherapies and perhaps unlock those immunotherapies. We showed in this paper that you actually can have synergy with other types of immunotherapies, so maybe now we can have a combination approach of immunotherapy.”

Source: University of Florida