Month: January 2023

Categories : Diseases, Syndromes and Conditions PaediatricsTags :

In Depth: As Schools Open, will Measles Outbreaks get Worse?

On By ModernMedia

By Elri Voigt

In October last year, the National Institute for Communicable Diseases (NICD) alerted the public to a measles outbreak in Limpopo. Since then, four more provinces have reported outbreaks, and the number of positive cases in the country has climbed rapidly.

Last week’s measles report from the NICD indicated that between the first week of October 2022 and mid-week in the second week of January 2023, a total of 397 cases of measles were identified across the country. Of those, 382 cases were detected in five provinces – Limpopo 145, North West 125, Mpumalanga 79, Gauteng 18, and the Free State 15. These five provinces have all met the criteria for a measles outbreak (three or more cases in a district within a month).

The remaining 15 cases are spread around KwaZulu-Natal, Northern Cape, the Eastern Cape, and the Western Cape – none of which have so far met the criteria for an outbreak.

‘Biggest outbreak in 11 years’

Dr Kerrigan McCarthy, a pathologist from the Centre for Vaccines and Immunology at the NICD, tells Spotlight that this is the biggest outbreak in 11 years, surpassing the outbreak in 2017 when around 280 cases of measles were identified.

According to the NICD report, the total number of laboratory-confirmed measles cases and the total number of samples submitted for testing has decreased for the third consecutive week. However, McCarthy cautions that this apparent decline might actually be due to a decrease in the number of specimens sent to the NICD for testing, and not to the outbreak actually slowing down.

“The fact that we have seen a decrease in the number of positive cases could be attributed to the decrease in number of specimens that have been submitted, but there is a small possibility that it could represent a turnaround in the outbreak. However, a consensus amongst us in public health is that it is the former problem,” says McCarthy.

She adds that the true extent of this outbreak – and whether new cases have really declined or not – may only become clear in the next few weeks, as schools across the country resume activities.

While it isn’t possible to predict exactly where the outbreak is going, McCarthy says at the moment it is following a similar trend to the widespread measles outbreak that occurred just over a decade ago. “In 2009 to 2011 we had an outbreak of over 22 000 measles cases… and in fact, in that outbreak, we saw a similar pattern. The outbreak was declared in late 2009 and cases started increasing into December and then when the schools closed and December holidays happened, there was a lull in cases and then when the schools returned there was a massive increase in cases,” she says.

Fears of much larger outbreaks

In a Spotlight article published in July last year, Dr Haroon Saloojee, Professor and Head of the Division of Community Paediatrics at the University of the Witwatersrand, and other experts warned that low vaccination rates may lead to measles outbreaks of the type we are now seeing. Now they are concerned that things might get worse.

Saloojee agrees that it isn’t possible to predict exactly how this outbreak will behave. “There are obviously three possible outcomes,” he says, “An increase, levelling off, or decline. My fear and expectation [are] that the outbreak will continue to expand. There are more than a million unvaccinated children under five, and possibly about 2.5 million unvaccinated under 15 years.

“We should be greatly concerned. It is highly likely that the outbreak will extend beyond the five provinces and affect all provinces in the country,” he says.

He adds that children are protected from measles through vaccination and if 95% of children are vaccinated against measles, then this herd immunity will protect the 5% who are not vaccinated. But in South Africa, measles coverage is not at 95%.

“In South Africa, at best, about 80% of children are vaccinated [against measles]. The proportion is lower in some provinces. Thus, all children, but particularly unvaccinated children, are at risk of acquiring measles,” he says. “We haven’t had a serious problem [with] measles in South Africa for at least the last 20 years. But in other low- and middle-income countries, it is still one of the five major causes of child mortality.”

Mass measles immunisation campaign needed

Saloojee tells Spotlight the only way to curtail the outbreak at this point is through a national supplementary mass measles immunisation campaign.

“There is only one option at this stage, as we are facing a crisis. A national supplementary immunisation campaign is warranted, despite its high cost and resource demands,” he says. “Such activities have already commenced in the affected provinces and will be extended to other provinces if the outbreak continues to spread. The aim of the campaign is to boost measles vaccine coverage to the 95% mark in the short term, so that herd immunity can kick in.”

How did we get here?

While such an immunisation campaign should help mitigate the current spread of measles, the question remains how a widespread outbreak could occur in the first place given South Africa’s well-established childhood immunisation programme.

“The outbreak was entirely predictable and preventable,” says Saloojee. “We have had similar outbreaks [about] every five years since 2000. Paradoxically, COVID delayed this outbreak, which should have happened in 2020 because the isolation measures protected against measles spread too.”

“However, we cannot run away from the fact that too few children receive all their routine vaccinations, and there is little being done to systematically change this such as stopping vaccine stockouts, and clinics and hospitals reducing missed opportunities to vaccinate eligible children,” he says. “If nothing is done, we can count on another outbreak in 2028.”

Countries across the world are reporting measles outbreaks, according to the CDC, which is being attributed to a disruption in services like routine immunisation because of the COVID pandemic. However, according to Saloojee, South Africa’s outbreak cannot be attributed exclusively to the pandemic disrupting services, instead, it is also due to years of suboptimal measles vaccine coverage.

Spotlight previously reported in-depth on results from the 2019 Expanded Programme on Immunisation (EPI) National Coverage survey, which showed that only around 77% (76.8%) of the children surveyed had received all fourteen age-appropriate vaccines from birth to 18 months. This includes the two doses of the measles vaccine.

Dr Lesley Bamford, a child health specialist in youth and school health at the National Department of Health, provided Spotlight with a table showing measles vaccination coverage per province between 2017 and 2022.

graph - Note that the data only includes vaccinations provided in the public sector, whilst the denominator includes all children in South Africa. Graph courtesy of Dr Lesley Bamford, National Department of HealthNote that the data only includes vaccinations provided in the public sector, whilst the denominator includes all children in South Africa. Graph courtesy of Dr Lesley Bamford, National Department of Health

According to the figures provided by Bamford, national coverage for the first dose of the measles vaccine has improved from 80% in 2017-2018 to 88% in 2021-2022. However, coverage for the second measles dose remained stuck in a narrow band from 77% to 80%, until 2021-2022, when it improved to 84% – still well below the 95% coverage required for herd immunity.

Expanded vaccination campaign

The NICD report shows the highest number of measles cases so far have been in the five to nine-year age group, which represents 40% of cases. 29% of cases were in the one to four age group and 17% in the 10 to 14-year age group. The remaining cases occurred in children younger than one year and those aged 15 and older.

According to McCarthy, based on the distribution of cases in these age groups, the NICD recommended to the National Department of Health that it extend its planned mass measles vaccination campaign to include children between six months and 15 years of age – which the Department has agreed to do.

Bamford tells Spotlight that a mass measles immunisation campaign had already been planned across all provinces for February 2023. But for the five provinces experiencing outbreaks, the timeline has since moved up. The four remaining provinces will still start their campaigns in February as planned.

“The target age group for that campaign has been extended. So, the initial plan was targeting children under 5 years of age and now in most provinces, it has been extended to include all children six months to 15 years of age,” she says.

Spokesperson for the National Department of Health, Foster Mohale confirms that all children between the ages of six months and 15 years, regardless of documentation, are eligible to receive their measles vaccination in the catch-up drive. “Most provinces have been vaccinating all children between 6 months and 15 years, with [or] without documents because diseases have no discrimination. So, we haven’t received any concern or report about non-vaccination of children without documentation,” he says.

Bamford adds that a measles incident management team has been established by the National Department of Health, which meets with the NICD and the provinces on a weekly basis.

She says Limpopo started its campaign in November, Mpumalanga and North West started in December, and Gauteng and the Free State started in January. The campaigns have so far been conducted mainly at primary healthcare clinics and outreach to ECD centres but now that the school year has resumed, children will also be vaccinated at schools.

Because the provinces all started at different times, there is no specific timeline for the vaccination campaign to be completed, according to Bamford, but the expectation from the National Department is that all provinces will wrap up their campaigns by mid-February when the HPV vaccination campaign kicks off.

“We know that measles coverage is suboptimal, and that is why we were planning to run a campaign, but of course, that is the single biggest reason why we are now experiencing these outbreaks,” she says. “The only way really to stop measles outbreaks is to improve immunisation coverage.”

Republished from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : Medical Industry Medical Research & TechnologyTags :

A New Wave of Academia Spinouts is Shaking up Drug Development

On By ModernMedia
Photo from Pixabay

In recent times, new drug discoveries by independent large pharmaceutical companies have become increasingly rare, with almost 60% of new drugs discovered through mergers and acquisitions and drug licensing. Fortunately, an emerging trend of spinouts from academia and R&D investments heralds a promising shift in the industry’s interorganisational deal networks to improve research and development in the future. Researchers explore this new trend in Drug Discovery Today.

Launching a new drug in the market is risky, thanks to a low probability of success during the research and development (R&D) phase and the high costs involved. But through an improved understanding of disease biology, decision-making can be more streamlined through the effective use of scientific information.

With this in mind, researchers from Ritsumeikan University, Japan, led by Associate Professor Kota Kodama are uncovering how the trends in interorganisational deals in the pharmaceutical industry are changing to improve R&D productivity and drug discovery. “The network structure of innovation creation in the pharmaceutical industry has changed with the increasing emergence of start-up companies spinning out from academia and research institutions as players in the source of innovation,” explains Dr Kodama.

Their research suggests that the knowledge necessary for breakthrough innovation in drug discovery is more often than not obtained through alliance networks. Over the past decade, large research-based pharmaceutical companies have used research collaborations, innovation incubators, academic centres of excellence, public-private partnerships, mergers and acquisitions (M&As), drug licensing, and corporate venture capital funds as typical methods for external innovation. The researchers now aim to define the changes in the network structure and nature of such alliances that have occurred over the past decade to provide future strategic insights for industry and academic players involved in drug discovery.

Using data from the Cortellis Competitive Intelligence database, the researchers identified nearly 50 000 deals of various kinds related to pharmaceutical R&D across pharmaceutical, digital health software, animal drug, and medical device companies to uncover trends in the creation of new drugs for human use. They also studied the trends of 13 of the largest pharmaceutical companies with annual revenues of more than US$10 billion, who saw an improvement in their CAGR (compound annual growth rate) since 2015. The researchers noticed that the rising CAGR correlated to a significant change in M&A-related deals after 2015, indicating that M&A-related deals drive revenue growth for large pharmaceutical companies.

Furthermore, the number of organisations involved in interorganisational deals has been increasing yearly from 2012 to 2021. Although the number of organisations involved and the number of deals may be increasing, the density of the deal networks is decreasing annually, suggesting that networks are becoming more non-cohesive. The concentration of business relationships between organisations of certain areas in the network changed to dispersion around 2015, and new networks connecting different groups started to form after 2017. These trends are an important illustration of how the industry landscape is gradually evolving away from the traditional network in which large pharmaceutical companies drove drug discovery output. Now, interorganisational deals among more diverse players have become active and are driving R&D productivity for startups in biotechnology and pharmaceuticals.

A clear increase in the number of academia-owned spinouts of advanced technology and expansion of investment in start-ups is a positive sign. The emergence of new chemical modalities, such as biologics, oligonucleotides, and peptides that differ from traditional small molecule drug discovery indicate remarkable changes that have taken place over the past two decades. The trend of increased financing for start-up companies in personalised drug development is beneficial for patent creation and will positively impact innovation creation in the coming years.

“The presence of academia to support the technologies of these start-ups is becoming very important, and government and private support and investment in this area is boosting innovation. Our study shows that such medium- and long-term support may ultimately benefit the health and well-being of humankind,” concludes an optimistic Dr Kodama.

Source: Ritsumeikan University.

Categories : Addiction ExerciseTags :

Running away from Life’s Stresses: The Phenomenon of Exercise Addiction

On By ModernMedia
Photo by Quino Al on Unsplash

Recreational running offers a lot of physical and mental health benefits – but some people can develop exercise dependence, a form of addiction to physical activity which can cause health issues. Shockingly, signs of exercise dependence are common even in recreational runners. A study published in Frontiers in Psychology investigated whether the concept of escapism can help us understand the relationship between running, well-being, and exercise dependence.

“Escapism is an everyday phenomenon among humans, but little is known regarding its motivational underpinnings, how it affects experiences, and the psychological outcomes from it,” said Dr Frode Stenseng of the Norwegian University of Science and Technology, lead author of the paper.

Running to explore or to evade?

“Escapism is often defined as ‘an activity, a form of entertainment, etc. that helps you avoid or forget unpleasant or boring things.” In other words, many of our everyday activities may be interpreted as escapism,” said Stenseng. “The psychological reward from escapism is reduced self-awareness, less rumination, and a relief from one’s most pressing, or stressing, thoughts and emotions.”

Escapism can restore perspective, or it can act as a distraction from problems that need to be tackled. Escapism which is adaptive, seeking out positive experiences, is referred to as self-expansion. Meanwhile maladaptive escapism, avoiding negative experiences, is called self-suppression. Effectively, running as exploration or as evasion.

“These two forms of escapism are stemming from two different mindsets, to promote a positive mood, or prevent a negative mood,” said Stenseng.

Escapist activities used for self-expansion have more positive effects but also more long-term benefits. Self-suppression, by contrast, tends to suppress positive feelings as well as negative ones and lead to avoidance.

Self-suppression associated with exercise dependence

The team recruited 227 recreational runners, half men and half women, with widely varying running practices. They were asked to fill out questionnaires which investigated three different aspects of escapism and exercise dependence: an escapism scale which measured preference for self-expansion or self-suppression, an exercise dependence scale, and a satisfaction with life scale designed to measure the participants’ subjective well-being.

The scientists found that there was very little overlap between runners who favoured self-expansion and runners who preferred self-suppression modes of escapism. Self-expansion was positively related with well-being, while self-suppression was negatively related to well-being. Self-suppression and self-expansion were both linked to exercise dependence, but self-suppression was much more strongly linked to it. Neither escapism mode was linked to age, gender, or amount of time a person spent running, but both affected the relationship between well-being and exercise dependence. Whether or not a person fulfilled criteria for exercise dependence, a preference for self-expansion would still be linked to a more positive sense of their own well-being.

Although exercise dependence corrodes the potential well-being gains from exercise, it seems that perceiving lower well-being may be both a cause and an outcome of exercise dependency: the dependency might be driven by lower well-being as well as promoting it.

Similarly, experiencing positive self-expansion might be a psychological motive that promotes exercise dependence.

“More studies using longitudinal research designs are necessary to unravel more of the motivational dynamics and outcomes in escapism,” said Stenseng. “But these findings may enlighten people in understanding their own motivation, and be used for therapeutic reasons for individuals striving with a maladaptive engagement in their activity.”

Source: Frontiers

Categories : NeurologyTags :

Not all Memories Lost to Sleep Deprivation are Gone Forever

On By ModernMedia
Sleeping man
Photo by Mert Kahveci on Unsplash

Sleep deprivation is bad for memorisation, something which still doesn’t deter many med students from late night cramming. Researchers however have discovered that memories learned during sleep deprivation is not necessarily lost, it is just difficult to recall. Publishing in the journal Current Biology, the researchers have found a way to make this ‘hidden knowledge’ accessible again days after studying whilst sleep-deprived using optogenetic approaches and the asthma drug roflumilast.

University of Groningen neuroscientist Robbert Havekes and his team have extensively studied how sleep deprivation affects memory processes. “We previously focused on finding ways to support memory processes during a sleep deprivation episode,” says Havekes. However, in his latest study, his team examined whether amnesia as a result of sleep deprivation was a direct result of information loss, or merely caused by difficulties retrieving information. “Sleep deprivation undermines memory processes, but every student knows that an answer that eluded them during the exam might pop up hours afterwards. In that case, the information was, in fact, stored in the brain, but just difficult to retrieve.”

Priming the hippocampus

To find out, the researchers selectively introduced optogenetic proteins into neurons that are activated during a learning experience, enabling recall of a specific experience by shining a light on the cells. “In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area in the brain where spatial information and factual knowledge are stored,” says Havekes.

First, the genetically engineered mice were given a spatial learning task in which they had to learn the location of individual objects, a process heavily reliant on neurons in the hippocampus. The mice then had to perform this same task days later, but this time with one object moved to a new location. The mice that were deprived of sleep for a few hours before the first session failed to detect this spatial change, which suggests that they cannot recall the original object locations. “However, when we reintroduced them to the task after reactivating the hippocampal neurons that initially stored this information with light, they did successfully remember the original locations,” says Havekes. “This shows that the information was stored in the hippocampus during sleep deprivation, but couldn’t be retrieved without the stimulation.”

Memory problems

The molecular pathway set off during the reactivation is also targeted by the drug roflumilast, which is used by patients with asthma or COPD. Havekes says: “When we gave mice that were trained while being sleep deprived roflumilast just before the second test, they remembered, exactly as happened with the direct stimulation of the neurons.” Since roflumilast is approved for use in humans and can enter the brain, this may lead to testing to see if it can recover ‘lost’ memories for humans..

It might be possible to stimulate the memory accessibility in people with age-induced memory problems or early-stage Alzheimer’s disease with roflumilast,” says Havekes. “And maybe we could reactivate specific memories to make them permanently retrievable again, as we successfully did in mice.” If a subject’s neurons are stimulated with the drug while they try and ‘relive’ a memory, or revise information for an exam, this information might be reconsolidated more firmly in the brain. “For now, this is all speculation of course, but time will tell.”

Source: University of Groningen.

Categories : Ageing Cardiovascular DiseaseTags :

Common Hypertension Drug Extends Lifespan in Animal Studies

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Old man
Photo by Kindel Media on Pexels

Researchers have found that, in animal studies, the hypertension drug rilmenidine can extend lifespan and slow ageing. Published in Aging Cell, the findings show that animals treated with rilmenidine at young and older ages increases lifespan and improves health markers by mimicking the effects of caloric restriction.

They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.

With side-effects being rare and non-severe, unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed antihypertensive has potential for future translatability.

A caloric restriction diet has thus far proved to be the most robust anti-ageing intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-ageing strategy.

Professor João Pedro Magalhães, who led the research whilst at the University of Liverpool and is now based at the University of Birmingham, said: “With a global ageing population, the benefits of delaying ageing, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”

Source: University of Liverpool. 

Categories : Hospitals Medical IndustryTags :

Health Care Integration Sees Ballooning Costs for Minor Care Benefit

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Photo by Andrea Piacquadio on Unsplash

Over the past few decades, health care integration has absorbed physician practices and hospitals into large health systems, a practice which was heralded as the way to cut health care costs and boosting quality of care.

But integrated health systems appear to be failing on both fronts, according to the results of a new US study published in JAMA. For patients in health systems, care is only marginally improved while costs are significantly higher compared to those at independent practices or hospitals.

In the US, health systems have grown exponentially in size and market share through mergers and acquisitions of physician practices and hospitals and the joining of separate health systems.

Proponents of consolidation have argued over the years that physicians and hospitals working together in integrated, coordinated systems provide better patients care while being more efficient than independent physician practices and hospitals. This would drive quality of care up while keeping spending steady and even driving costs down.

“One of the key arguments for hospital mergers and practice acquisition was that health systems would deliver better-value care for patients. This study provides the most comprehensive evidence yet that this isn’t happening,” said study first author Nancy Beaulieu at Harvard Medical School.

Today, these systems are responsible for a large proportion of the medical care delivered in the US, some employing thousands of physicians. But despite their impact on population health and the economy, little is known about the actual performance of integrated health organisations, the study authors noted.

A lack of detailed data on performance and scale is a key obstacle. The current analysis is believed to be the first comprehensive national study to compare outcomes between patients receiving care within health systems and outside of them, including patients with private insurance as well as traditional Medicare, which is the US health insurance system for those over 65 or which certain disabilities or conditions. 

The analysis included a total of 580 health systems, accounting 40% of physicians and 84% of general acute care hospital beds. Academic and large nonprofit systems accounted for a majority of system physicians (80%) and system hospital beds (64%).

System hospitals were larger than hospitals than nonsystem ones, with 67% of system hospitals having more than 100 beds, while only 23% of nonsystem hospitals having more than 100 beds. System physician practices were also more likely to have more than 100 physicians compared with nonsystem practices (74% vs 12%). Integrated systems delivered primary care to 41% of traditional Medicare beneficiaries.

As for quality and cost of care delivered within systems, patients with primary care physicians in health systems reported slightly better satisfaction and overall care experience than patients of independent physicians.

This is the case even though many patients with nonsystem primary care providers also receive some of their care in hospitals or specialist practices that are part of a health system. However, care in systems came at a much higher price, contributing to higher overall spending on health care, the research showed.

Prices for services from physicians and hospitals within health systems were significantly higher than for independent healthcare, the study found. Physician services delivered within health systems cost between 12% and 26% more, compared with independent practices. System-based hospital services cost an average of 31% more than care delivered by independent hospitals.

Small differences in quality combined with large differences in cost of care suggests that health systems have not, on average, realised their potential for better care at equal or lower cost, the researchers said.

Members of the research team have compiled a database from various sources to help characterise these health systems and to link claims data with information on health care providers in and out of health systems. The database, housed at NEBR, will be made available for free to other researchers in the near future.

“There’s no question that large, sophisticated health systems have benefits over independent systems,” said study author David Cutler, Harvard economic professor. “Big systems tend to be less vulnerable to economic downturns and they can provide specialised care that would be difficult to maintain in smaller systems. But the hoped-for cost savings benefits of integrated health systems have not yet materialised.”

Source: Harvard Medical School

Categories : Paediatrics Respiratory DiseasesTags :

More Physical Activity Linked to Fewer Respiratory Infections in Children

On By ModernMedia
Boys running
Photo by Margaret Weir on Unsplash

A study of 104 children wearing pedometers to monitor daily activity showed that higher levels of physical activity are associated with reduced susceptibility to upper respiratory tract infections such as the common cold. Reporting the findings in Pediatric Research, the researchers suggest reduced inflammatory cytokines and improved immune responses as a possible mechanism.

Wojciech Feleszko, Katarzyna Ostrzyżek-Przeździecka and colleagues measured the physical activity levels and symptoms of upper respiratory tract infections of children aged between four and seven years in the Warsaw city region between 2018 and 2019. Participants wore a pedometer armband 24 hours a day for 40 days to measure their activity levels and sleep duration. For 60 days, parents used daily questionnaires to report their children’s symptoms of upper respiratory tract infections, such as coughing or sneezing. On a second questionnaire, parents reported their children’s vaccinations, participation in sport, whether they had siblings, and their exposure to smoking and pet hair.

The authors found that as the average daily number of steps taken by children throughout the study period increased by 1000, the number of days that they experienced symptoms of upper respiratory tract infections decreased by an average of 4.1 days. Additionally, children participating in three or more hours of sport per week tended to experience fewer days with respiratory tract infection symptoms than those not regularly participating in sports.

Higher activity levels at the beginning of the study were associated with fewer days with respiratory tract infection symptoms during the following six weeks. Among 47 children, with 5668 average daily steps during the first two weeks of the study period, the combined number of days during the following six weeks that these children experienced upper respiratory tract infection symptoms was 947. However, among 47 children whose initial average daily steps numbered 9368, the combined number of days during the following six weeks that these children experienced respiratory symptoms for was 724. Upper respiratory tract infection symptoms were not associated with sleep duration, siblings, vaccinations, or exposure to pet hair or smoking.

The authors speculate that higher physical activity levels could help reduce infection risk in children by reducing levels of inflammatory cytokines and by promoting immune responses involving T-helper cells. They also suggest that skeletal muscles could release small extracellular vesicles that modulate immune responses following exercise. However, they caution that future research is needed to investigate these potential mechanisms in children. In addition, since this was an observational study, causality could not be established.

Source: EurekAlert!

Categories : COVIDTags :

Hybrid Immunity Offers Greatest Protection against COVID

On By ModernMedia
Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

Analysing data from controlled studies throughout the world, researchers discovered that people with hybrid immunity – from both full vaccination and prior infection – are the most protected against severe illness and reinfection. The study, published in The Lancet Infectious Diseases, will aid public policy-makers in planning the optimal timing of vaccinations.

Researchers from University of Calgary teamed up with World Health Organization (WHO) experts to answer the question of how well protected people are from combinations of vaccinations, boosters and prior infection.

“The results reinforce the global imperative for vaccination,” says Dr Niklas Bobrovitz, first author on the study. “A common question throughout the pandemic was whether previously infected people should also get vaccinated. Our results clearly indicate the need for vaccination, even among people that have had COVID.”

The global emergence and rapid spread of the Omicron variant required scientists and policy-makers to reassess population protection against Omicron infection and severe disease. In the study, investigators were able to look at immune protection against Omicron after a prior SARS-CoV-2 infection, vaccination or hybrid immunity.

“Protection against hospitalisation and severe disease remained above 95 per cent for 12 months for individuals with hybrid immunity,” says Dr Lorenzo Subissi, PhD, a technical officer with WHO and senior author on the study. “We know more variants are going to emerge. The study shows, to reduce infection waves, vaccinations could be timed for rollout just prior to expected periods of higher infection spread, such as the winter season.”

The systematic review and meta-analysis found that protection against Omicron infection declines substantially by 12 months, regardless of prior infection, vaccinations or both, which means vaccination is the best way to periodically boost protection and to keep down levels of infection in the population. In total, 4268 articles were screened and 895 underwent full-text review – a difficult task before the assistance of experts in health informatics.

“This study demonstrates the power of machine translation. We were able to break through language barriers; most of the time, systematic reviews aren’t done in every language, they are limited to one or two,” says Dr Tyler Williamson “These former BHSc classmates, along with the large diverse team they brought together, have emerged as global leaders in SARS-CoV-2 research and delivered decision-grade evidence to the world.”

While the findings demonstrate that vaccination along with a prior infection carries the most protection, the scientists warn against intentional exposure to the virus.

“You should never try to get COVID,” says Bobrovitz. “The virus is unpredictable in how it will affect your system. For some, it can be fatal or send you to hospital. Even if you have a mild infection, you risk developing long COVID.”

The group says the next phase of this research would be to investigate how the bivalent vaccine performs against severe disease.

Findings from the study complement data on the SeroTracker dashboard which monitors studies and news reports to track seroprevalence data – the percentage of people in a population who have antibodies against the novel coronavirus. The website aggregates serology data from studies and news reports in different populations, and built-in filters allow users to compare seroprevalence levels between countries, occupations, and demographic groups.

Source: University of Calgary

Categories : Uncategorized

Low Dietary Potassium can Cause Direct Kidney Injury

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

It is well known that diets with a high sodium-to-potassium ratio are linked to poor cardiovascular outcomes. To date, most attention has mostly focused on high sodium, but low potassium is also a culprit in cardiovascular disease. Now, research published in Cell Reports has revealed that low dietary potassium also causes direct kidney injury.

Using in vitro and in vivo approaches, Andrew Terker, MD, PhD, and colleagues demonstrated that the injury effects depend on the Kir4.2 potassium channel in kidney proximal tubule cells. First, they reduced dietary potassium levels to determine changes in kidney injury markers, and then lowered blood potassium levels to confirm that it indeed drove kidney injury.

Efflux of potassium from the cells caused intracellular acidosis and activated the enzyme glutaminase. This increased enzyme activity contributed to kidney injury, leading to hypertrophy, inflammation and fibrosis. They found that deleting Kir4.2 or glutaminase protected proximal tubule cells from injury in both cell culture and animal models. 

The findings identify Kir4.2 and glutaminase as mediators of low potassium-related kidney injury and potential therapeutic targets. The findings also suggest that the standard practice of recommending excessive restriction of dietary potassium for patients with chronic kidney disease could unintentionally contribute to disease progression in certain settings

Source: Vanderbilt University

Categories : COVIDTags :

How SARS-CoV-2 Evolved Past its Own Weaknesses

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Image from Pixabay

New research suggests that the first pandemic-accelerating mutation in the SARS-CoV-2 virus evolved as a way to correct vulnerabilities that were caused by the mutation that started the SARS-CoV-2 pandemic.

Published in Science Advances, this new evidence addresses important biological questions about two key mutations in the virus’ surface spike protein, say the researchers. It suggests that a spike protein mutation called D614G, which emerged a few months after the virus began spread among humans, was not an adaptation to humans. Instead, the mutation was an adaptation to the major changes that happened in the spike gene just before the pandemic, changes which allowed spread via respiratory transmission.

“This study has revealed that the first two genetic alterations in the evolution of the spike protein in SARS-CoV-2 are connected by their function, and this knowledge can improve our understanding of how the spike protein works and how the virus evolves, with important implications for vaccine design and effectiveness of COVID antibodies,” says Stephen Gould, professor of biological chemistry at the Johns Hopkins University School of Medicine, whose lab was studying the basic biology of the virus’s spike protein when the study began.

The initial mutation in the virus, Gould says, is known by scientists as the “furin cleavage site insertion mutation.”

Research by other scientists across the world has shown that this mutation enabled the virus’s spike protein to be cut and primed it for rapid infection of cells lining the airway.

While this initial mutation was essential in helping SARS-CoV-2 efficiently slip into human cells, the mutation’s effects weren’t all good, says Gould, as it cut the spike protein structure into two separate pieces.

According to Gould, this change disrupted other functions of the spike protein, creating evolutionary pressure for a second mutation to correct the disrupted functions of the spike protein while keeping the initial mutations’ rapid infection benefits .

In early 2020, researchers from the University of Toronto discovered a subsequent SARS-CoV-2 mutation, called D614G; however, its precise function was not known.

Gould, first author and graduate student Chenxu Guo, and the research team set out to understand the D614G mutation and its effect.

Working with dozens of blood samples from patients with COVID-19 hospitalized in April 2020 at the Johns Hopkins Hospital, Gould’s team isolated antibodies for the spike protein from the patients’ blood samples. Then, they used these antibodies to track the location of spike proteins in human cells genetically engineered to produce the spiky surface molecules.

They found that the D614G mutation redirects the spike protein and pulls the virus from the surface of human cells into a tiny compartment within the cell called a lysosome, which the spike protein reprograms into storage containers that are used to release infectious virus particles from the cell.

In addition, the D614G mutation caused a three-fold drop in the abundance of spike proteins at the cell surface.

“With less spike protein on the surface of virus-infected cells, it may be more difficult for the immune system to identify and kill those virus-containing cells,” says Gould.

The researchers caution that the study does not provide information about the still-debated origins of the virus. However, their work suggests that the two mutations likely arose in rapid succession.

The researchers are new examining whether spike protein mutations in more recent virus strains affect spike protein trafficking, studying the identity of the human proteins that deliver spike proteins to lysosomes, and researching how spike proteins convert lysosomes into compartments that release more virus.

Source: John Hopkins Medicine