Thursday, August 18, 2022

Indigenous youth film project turns the lens on nutrition and food security

Peer-Reviewed Publication

UNIVERSITY OF EAST ANGLIA

A unique initiative is helping Indigenous people in India exchange knowledge about locally available foods to improve dietary diversity – part of the UN Sustainable Development Goal related to food security and nutrition.

The project, coordinated by the University of East Anglia (UEA), is raising the visibility of the Santhal community, enabling the most marginalized to voice their own perspectives using cameras and filmmaking skills.

With support from UEA through the Global Research Translation Award entitled ‘Meeting the SDGs’ and a local NGO partner (PRADAN), 10 Santhal youth were trained to make films about locally available foods and other issues of concern.

The nearly 50 films they produced were broadcast on a YouTube channel and screened in their local villages. The group also took part in interviews and discussions with viewers who attended the screenings.

Prof Nitya Rao, professor of gender and development in UEA’s School of International Development, is the lead author of ‘Cameras in the hands of Indigenous youth: Participation, films and nutrition in India’, published today in Current Developments in Nutrition.

Prof Rao said: “These young filmmakers are voicing a critical issue, whether endemic malnutrition or vast deforestation, as a call to policy-makers for remedial action.

“The role of self-expression, especially for Indigenous communities, is important given their historical marginalization. By enabling their participation in governance and the political space, transformative change alongside improved health and nutritional outcomes will be more achievable.

“The use of the YouTube channel as a digital ‘space’ created by the participants gave them an opportunity to set the agenda where they can speak without interruption about their everyday needs and the challenges they confront.”

The young filmmakers are from the Jamui district of Bihar, among the worst-off districts in India for meeting the SDGs.

While residing near forests, where they have access to highly nutritious foods, these communities are nevertheless more vulnerable to food and nutrition insecurity compared to their rural counterparts. Forty-four per cent of indigenous children under the age of 5 years are stunted, 45 per cent are underweight and 27 per cent are wasted. Less than 6 per cent of young children, women and migrating men have a diet that fulfills their minimum nutritional requirements.

A majority of the films drew on intergenerational and Indigenous knowledge about edible plants, insects, and rodents; skills in foraging and preparing food; awareness of the benefits of the food; and sustainability issues across the traditional food systems.

The filmmakers initially focused on responding to community needs and showcasing Santhal cultural practices. Their later films began to reflect on aspects of their culture that needed to be preserved, revived, or modified. Audience reflection supported this process, identifying both strengths and gaps.

There were many suggestions for further films that could document other food items and recipes, especially those linked to health and nutrition.

An 18-year-old female filmmaker said: “My grandmother becomes very happy whenever I ask her about local food and culture. She says that during her childhood there were no phones or electronic media, or social media where she could have shared her knowledge. So it's a good thing that her granddaughter is trying to preserve what is their own by making films around the food they get from the forest and reach out to many people around the world.”

The project also sought to challenge unequal power relations between women and men in Santhal communities. While women are generally responsible for the collection and processing of all foods, it is important that men and upcoming generations learn about locally availably foods and preparation methods, as it has been shown that food security improves when nutrition information is provided to both male and female heads of households.

Prof Rao said: “Collective access to nutrition literacy is more effective than only women’s access to it.”

She cited a film that featured young boys hunting and cooking bamboo tree-dwelling rats [banwar], in which the filmmaker said: "Let us think if there are so many benefits in eating banwar, can women and girls not cook it in their home and eat it too?"

Prof Rao said: “The filmmakers have identified a gender discriminatory norm and through this film are attempting to reconstruct this cultural norm so that girls are not deprived of the benefits of this source of nutrition.

“As films are made, they challenge some of the biases and notions of ‘shame’, ‘backwardness’, or indeed ‘modernity’. In creating a more respectful dialogue between different actors, we empowered the most marginalized, giving them voice in a society where they generally remain unheard.”

The films have gained international recognition, with some being selected for the 2021 UN Food Systems Summit Youth Challenge and the Science Film Festival, with screenings across South Asia. Additionally they have been used by universities in India as teaching and learning resources.

Local media coverage about the Santhal youth filmmakers brought them to the attention of senior political leaders, illustrating the potential of this medium for reviving, but also modifying, Indigenous practices. 

Prof Rao said: “This demonstrates the liberating aspect of the project where the participants had the opportunity to talk freely in their own language about their own perspectives and practices without fearing alienation by the dominant culture.”

‘Cameras in the hands of indigenous youth: Participation, films and nutrition in India’, published August 17 in Current Developments in Nutrition.

1 g cut in daily salt intake could ward off nearly 9 million cases of stroke/heart disease in China


...And save 4 million lives by 2030, modelling study suggests

Peer-Reviewed Publication

BMJ

A modest cut of just 1 g in daily salt intake could ward off nearly 9 million cases of heart disease and strokes and save 4 million lives by 2030, suggest the estimates of a modelling study published in the open access journal BMJ Nutrition Prevention & Health.

Salt intake in China is one of the highest in the world, averaging 11 g/day—over twice the amount recommended by the Chinese government. High salt intake drives up blood pressure and therefore the risk of cardiovascular disease, which accounts for 40% of all deaths in China every year.

The researchers set out to estimate the health gains that could be achieved by reducing salt intake across the nation, with the aim of helping to inform the development of a doable salt reduction programme.

They compiled the latest and most reliable figures for population size, salt intake, blood pressure and disease rates by region and age and then estimated the impact on cardiovascular health for 3 different approaches.

The first of these was a 1 g/day reduction in salt intake to be achieved within 1 year. The second was the WHO’s interim target of a 30% reduction by 2025—equivalent to a gradual reduction of 3.2 g/day. 

The third was reducing salt intake to less than 5 g/day by 2030, the target set by the Chinese government in its action plan for health and development, ‘Healthy China 2030’.

They then estimated the falls in systolic blood pressure—the higher number in a blood pressure reading that indicates the force at which the heart pumps blood around the body—and the subsequent risk of heart attacks/stroke and cardiovascular disease deaths.

Given that, on average, adults in China consume 11 g/day of salt, reducing this by 1 g/day should lower average systolic blood pressure by about 1.2 mmHg. And if this reduction were achieved in a year and sustained, some 9 million cases of heart disease and stroke could be prevented by 2030—4 million of them fatal. 

Keeping this up for another 10 years could add up to around 13 million cases of heart attack and strokes avoided—6 million of them fatal.

Achieving the WHO's interim target by 2025 would require a 3.2 g/day fall in salt intake. Were this to be maintained for another 5 years, a cumulative total of about 14 million cases of heart disease and strokes could be prevented by 2030—6 million of them fatal. 

And if kept up until 2040, the cumulative total could reach around 27 million cases, 12 million of them fatal. 

Achieving the ‘Healthy China 2030’ target  would require a 6 g/day reduction in salt intake, reducing average systolic blood pressure by just over 7 mmHg, adding up to 17 million cases of heart disease and strokes prevented—8 million of them fatal.

The benefits of a reduction in dietary salt intake would apply to men and women of all ages across China, say the researchers.

There might also be additional health benefits, which the lack of relevant data didn’t allow the researchers to estimate: these include secondary prevention of cardiovascular disease and reductions in cases of chronic kidney disease and stomach cancer, rates of which are already high or rising in China, they suggest.

“The Chinese government’s action plan ‘Healthy China 2030’ includes nutritional recommendations to reduce the intake of salt, sugar and oil. This modelling study shows that salt reduction alone could bring enormous health benefits to the entire population of China,”  say the researchers, adding that a 1 g daily reduction in intake “would be easily achievable.” 

But they highlight: “Our estimates rely on salt reductions to not only be achieved, but also sustained over time, which may be a great challenge given the fast-changing dietary patterns seen in China given its rapid urbanisation.”

They conclude: “The evidence for the substantial benefits of salt reduction in China is consistent and compelling. Achieving and sustaining population salt reduction in China could prevent millions of unnecessary cardiovascular events and deaths. Given the sheer size of the Chinese population, this would also bring major benefits to global health.”

“Modelling studies like this one provide an indicator of how specific dietary changes have the potential to alter the course of diet related disease,” comments Shane McAuliffe,  Science and Digital Communications Lead at the NNEdPro Global Centre for Nutrition and Health, which co-owns the journal.
 
“Given the established dose-response relationship between salt intake, systolic blood pressure and cardiovascular disease, reducing the intake of one of the highest global consumers would have a significant impact on population health—something that has already been achieved in other countries worldwide,” he adds.

China meets Serbia as genetic testing applications goes global | BGI Perspectives

Business Announcement

BGI GENOMICS

Screenshot of WHO Director-General Dr Tedros' tweet 

IMAGE: SCREENSHOT OF WHO DIRECTOR-GENERAL DR TEDROS ADHANOM GHEBREYESUS’ TWEET THANKING THE WHO SCIENCE COUNCIL FOR ITS INAUGURAL REPORT view more 

CREDIT: WHO TWITTER PAGE

"Genomic technologies are driving some of the most ground-breaking research happening today. Yet the benefits of these tools will not be fully realized unless they are deployed worldwide. Only through equity, can science reach its full potential impact and improve health for everyone, everywhere," said Dr. Soumya Swaminathan, WHO Chief Scientist

As post-pandemic recovery speeds up, there is increasing realization about the value of genomic technology applications in confronting infectious diseases, cancers, and other chronic diseases. But how exactly can these tools become more accessible worldwide? 

This requires the contributions of professionals such as BGI Genomics Field Applications Support engineer and project leader Grace Xu who has spent over two-thirds of her time supporting clients since the start of the COVID-19 pandemic in February 2020. She joins us to share her unique perspective after 22 months away from home at Serbia, Saudi Arabia and Australia.  

Spending over half of her time overseas since Feb 2020

Xu returned to China in June 2022, after spending eight months in Serbia helping to train a local team at the country's first genome sequencing center at the Serbian Genome Sequencing and Bio-informatics Center. There are strict quality control standards, and the local team is benchmarked against the sequencing results that a more established team at another location is churning out. 

This center has a COVID-19 sequencing line. In addition, there are three other sequencing product lines focusing on non-invasive prenatal testing (NIPT), whole exome sequencing (WES) and whole genome sequencing (WGS). 

This is Xu's third trip overseas. She spent four months in Australia and ten months in Saudi Arabia. In total, she spent around 22 months overseas since COVID-19 started in February 2020. 

"I actually spent more than two-thirds of my time overseas since February 2020 but it was a time of great personal and professional growth for myself as I got to lead teams overseas and learn from our clients. My family was very encouraging even when I missed home and that kept me going as well," Xu said. 

Looking back, Xu noticed that her team's work depends on where we are at in terms of global COVID-19 response. For Serbia, COVID-19 control is still important but there is great interest to realize other important genomic applications as well. 

The bond of friendship between Serbia and China 

BGI Genomics had implemented a Huoyan lab project  that focused on COVID-19 testing though Xu was not involved in it, but she met some members of the Serbian team that were involved in that work. 

This proved useful as Serbia invested in the construction and infrastructure of this Center as per their requirements since these team members understood the safety aspect of the work very well. 

As this Center is located within the University of Belgrade, "Our Serbian counterparts are extremely qualified with many of them holding doctorate degrees and asking very good questions," Xu said. "It is no surprise that this Center is setting new milestones such as being the first NIPT facility in the country." 

NIPT is suitable for screening advanced pregnancy, twin pregnancy, and pregnancies with a history of trisomy, high risk of aneuploidy, contraindications for invasive procedures, or in-vitro fertilization.  

There is a close bond of friendship between Serbia and China. "Outside the laboratories, we often receive 'ni hao(hello in Chinese)' greetings and hear 'Thank you for helping out during the pandemic' from ordinary folks," Xu said. 

"The Center staff also organized a one-day city tour for the BGI Genomics team when we wrapped up our work and getting ready to return to China," Xu said. 

Dr. Jelena Begovic, Director of the Serbian Genome Sequencing and Bio-informatics Center: "We are working closely with stakeholders from various fields, to provide affordable, secure and ethical access to this technology. I also hope that we will continue to collaborate more deeply with BGI in the development of the BIO4 campus in Belgrade."

"In the post-pandemic era, Serbia is proactively accelerating access to genomics for the public. I am encouraged to hear Dr. Jelena's comments and see that the WHO's Science Council call for equitable expansion of genomics," Xu said. 

BGI Genomics is aligned with Serbia and WHO's objectives and shares a commitment to make genomics applications more available, affordable and accessible. 

"There is much that we could do together with Serbia especially in terms of early detection of diseases such as HPV which might lead to cervical cancer. We look forward to working with our Serbian friends at this Center in the future," Xu said.  

About the Serbian Genome Sequencing and Bio-informatics Center

The Serbian Genome Sequencing and Bio-informatics Center, located within the Institute of Molecular Genetics and Genetic Engineering (IMGGE), seeks to develop and enhance its genomic analysis, whole exome sequencing (WES) and whole genome sequencing (WGS) capabilities. Serbia has invested in the construction and infrastructure of this Center while BGI Genomics has donated equipment such as a genomic sequencer and sent a team of five Chinese technical experts to train their Serbian counterparts over eight months.

About BGI Genomics

BGI Genomics, headquartered in Shenzhen China, is the world's leading provider of genomic sequencing and proteomic services. We enable scientists and researchers to reach their full potential by providing them with fully integrated genomic sequencing, proteomic services, and high-quality solutions across a range of applications. Our services cover more than 100 countries and regions, involving more than 2,300 medical institutions.

CAPTION

BGI Genomics’ Grace Xu training her Serbian counterparts

CREDIT

BGI Genomics


CAPTION

The BGI Genomics team at the Serbian Genome Sequencing and Bio-informatics Center, Grace Xu is third from left

CREDIT

BGI Genomics

How hepatitis E tricks the immune system

Medicine

Peer-Reviewed Publication

RUHR-UNIVERSITY BOCHUM

Daniel Todt, Eike Steinmann and Toni Luise Meister (left to right) 

IMAGE: DANIEL TODT, EIKE STEINMANN AND TONI LUISE MEISTER (LEFT TO RIGHT) LOOK AT THE IMAGE OF A CELL INFECTED WITH THE HEPATITIS E VIRUS. THE CAPSID PROTEIN CAN BE SEEN IN GREEN, THE CELL NUCLEUS IN BLUE. view more 

CREDIT: © ABTEILUNG FÃœR MOLEKULARE UND MEDIZINISCHE VIROLOGIE

Advantages and disadvantages of mutations

Antibodies are an important defence mechanism against viral infections in our body. They specifically bind mostly to surface proteins of viruses to render it harmless. But, viruses have developed strategies to evade this neutralisation. During an infection with the hepatitis E virus, random mutations often give rise to virus variants that can coexist within an infected person. The antiviral agent Ribavirin, which many chronically infected patients receive, can even increase the formation of such variants.

The research team took a closer look at eight capsid protein variants from samples of chronically infected patients treated with ribavirin in the laboratory. The team wanted to know: Do the genetic changes bring advantages or disadvantaged for the virus? Do they influence the virus’ ability to replicate or its infectivity?

„While seven of the investigated mutations behaved exactly like the wild type virus, we found differences in one mutant,” reports Toni Luise Meister. This mutation affects the capsid protein, which is essential for packaging the viral particles. “The viruses with this mutation are assembled incorrectly, are probably smaller than the wild type virus, and the capsid protein does not accumulate in the cell,” describes Daniel Todt. These particles are not infectious, but are correctly recognised and bound by antibodies of the immune system. “This could be an advantage for the virus. These defective particles could potentially catch antibodies, so that there are no longer enough to neutralise correctly assembled, infectious virus particles,” speculates Eike Steinmann.

Hepatitis E

The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Around 70,000 people die from the disease every year. After the first documented epidemic outbreak in 1955 to 1956, more than 50 years passed before researchers took a closer look at the issue. Acute infections usually heal on their own in individuals with an intact immune system. In patients with reduced or suppressed immune systems, such as organ transplant recipients or HIV-infected patients, HEV can become chronic. HEV is also particularly threatening for pregnant women.

Genomics empowers vaccine makers to tackle shapeshifting bacteria

Peer-Reviewed Publication

WELLCOME TRUST SANGER INSTITUTE

A pioneering genomic surveillance study has provided the clearest picture yet of the arms race between Streptococcus pneumoniae, the bacterium responsible for a range of illnesses such as pneumonia and meningitis, and the vaccines designed to protect against the most dominant types. A strain called GPSC10 was found to be a particular threat, due to its increased virulence, ability to transform its structure to evade vaccines and its resistance to several common antibiotics.

The study, published today (16 August) in Lancet Microbe, was led by the Wellcome Sanger Institute, National Reference Center for Pneumococci, France, and Hospital Sant Joan de Deu, Spain, as part of the Global Pneumococcal Sequencing (GPS) project. The findings demonstrate the value of genomic surveillance to inform vaccine design and highlight the challenge posed by ‘shapeshifting’ strains like GPSC10.

Streptococcus pneumoniae, also known as the pneumococcus, is a bacterial pathogen that causes diseases ranging from ear infections through to pneumonia, septicaemia and meningitis. It is responsible for around nine million global infections annually, with elderly adults and children particularly susceptible. More than 300,000 children die from pneumococcal infection each year, mainly in low- and middle-income countries (LMICs)1.

Since 2000, a series of pneumococcal conjugate vaccines (PCVs) have been deployed that have targeted S. pneumoniae serotypes responsible for most disease cases in infants2, resulting in a reduction in disease worldwide. Currently, PCV-13 targets 13 serotypes and PCVs targeting up to 25 serotypes are in development. However, there are more than 100 distinct serotypes, and they can affect children and adults in different ways. Knowing which serotypes to target with the PCVs, and what the likely impact will be on disease and the wider pneumococcal population, is vitally important when designing effective global vaccination strategies.

Through the work of the GPS project since 2011, a picture of the S. pneumoniae serotypes in circulation has been built up that allows trends in the bacterial population to be identified. One serotype, 24F, has been on the rise, as documented by the National Reference Center for Pneumococci, France and many other countries such as Canada, Denmark, Germany, Israel, Italy, Japan, Lebanon, Norway, Spain, and UK.

In this new study, scientists from the Wellcome Sanger Institute performed whole-genome sequencing on 419 samples of S. pneumoniae serotype 24F, collected from individuals in France between 2003 and 2018 by the National Reference Center for Pneumococci (NRCP) and Association Clinique et Therapeutique Infantile du Val-de-Marne (ACTIV), and on 91 pneumococcal serotype 24F isolates collected from individuals in Spain by the Hospital Sant Joan de Deu. To provide a global comparison, an international collection of other S. pneumoniae genomes were added from the Global Pneumococcal Sequencing (GPS) project database.

Dr Stephanie Lo, first author of the study from the Wellcome Sanger Institute, said: “In a microbiology lab, classifying strains and testing for drug resistance are time consuming and resource intensive. Whole genome sequencing can now reliably infer serotype and antibiotic resistance profiles, identify where outbreaks might be occurring and track which strains mediate serotype replacement. So it’s one test that can answer a lot of different questions.”

Analysis showed that 24F was present in many countries largely due to the spread of three strains: GPSC10, GPSC16 and GPSC206. One strain in particular, GPSC10, was responsible for the rapid increase in 24F in France around four years following the introduction of PCV-13. It was found to have high disease potential and be resistant to multiple antibiotic treatments.

These findings support recent research that showed that GPSC10 drove the increase in 24F after the introduction of PCV-13 in Spain, and that 24F is one of the most frequent causes of pneumococcal disease in children in different countries. In India, the country estimated to have the largest burden of pneumococcal disease, researchers have predicted that GPSC10 has the potential to evade PCV-13. These and other studies from GPS partners across the globe are collected in an issue of Microbial Genomics.

Perhaps the biggest concern arising from the study was GPSC10’s ability to express 17 different serotypes, only six of which are included in current PCV vaccines.

Dr Emmanuelle Varon, a senior author of the study from the National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil, France, said: “The Streptococcus pneumoniae strain GPSC10 is something of a shapeshifter, able to express a wide range of serotypes and multidrug resistance patterns. Surveillance on pneumococcal disease, such as that implemented in France since 2001, is our best tool to evaluate the impact of vaccine policies and will allow us to detect the emergence of other non-vaccine serotypes.”

To some extent, the evolutionary arms race between pathogens and vaccine makers is inevitable. If one strain dies out because it has been targeted by a vaccine, other strains may rise to take its place. A strain may also evolve sufficiently that vaccines cease to be effective against it. The important thing is that vaccine makers and public health organisations have the best information with which to keep pace and, ultimately, to save lives.

Professor Stephen Bentley, a senior author of the study from the Wellcome Sanger Institute, said: “It’s exciting that genomic surveillance now allows us to have a real impact on improving pneumococcal vaccines and, most importantly, helping to reduce the number of children who die from related illnesses in low- and middle-income countries. The whole Global Pneumococcal Survey consortium should also be proud of the huge collaborative effort that has gone into generating these data.”

ENDS

Contact details:
Dr Matthew Midgley
Press Office
Wellcome Sanger Institute
Cambridge, CB10 1SA
Phone: 0044 1223 494856
Email: press.office@sanger.ac.uk

Notes to Editors:

For more information on S. pneumoniae and pneumococcal disease, see the CDC website.

A serotype is a group of strains that share similar biological features, usually on the cell surface. In S. pneumoniae, the serotype is determined by properties of the capsule that surrounds the bacterium, protecting it from attack by the host immune system. A vaccine designed to target a certain serotype is able to disrupt all the strains that belong to it.

Publication:

Stephanie W. Lo and Kate Mellor et al. (2022). Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study. Lancet Microbe. DOI: https://doi.org/10.1016/S2666-5247(22)00158-6

 

Funding:

This research was funded by the Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention (CDC).

Selected websites:

The Global Pneumococcal Sequencing (GPS) project

The mission of the GPS is to establish a worldwide genomic surveillance network for Streptococcus pneumoniae to provide evidence for pneumococcal disease control by building a decentralised system for local data generation and analysis that will be sustainable into the future. https://www.pneumogen.net/gps/

The Wellcome Sanger Institute
The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast – we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at www.sanger.ac.uk or follow us on TwitterFacebookLinkedIn and on our Blog.

About Wellcome

Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, global heating and infectious diseases. https://wellcome.org

Disclaimer: AA

Dearth of high quality monkeypox guidelines may be hampering care globally

What’s available too often out of date, lacking sufficient detail, not inclusive and contradictory

Peer-Reviewed Publication

BMJ

A dearth of high quality, up to date clinical guidance on monkeypox may be hampering effective and safe treatment of the infection around the world, concludes a review of what’s available to guide patient care and published in the open access journal BMJ Global Health.

Existing guidance, such as it is, too often lacks sufficient detail, fails to include different groups, and is contradictory, say the researchers.

Since the first human case of monkeypox infection was identified in 1970 in the Democratic Republic of Congo, it has mostly been reported in Central and Western African countries. 

The ongoing outbreak in 2022 is the first to affect several non-endemic countries, with 257 confirmed cases in 23 countries reported, as of 26 May 2022. 

The infection is mild in most cases, but younger children may be at higher risk of severe infection. And while the death rate is usually low, evidence from Africa suggests it can be fatal in up to 10% of cases, particularly in younger children.

Complications include painful pustules, secondary infections, bronchopneumonia, encephalitis (brain swelling), keratitis (inflammation of the eye’s surface) and psychological symptoms.

Monkeypox in people is spread through direct contact, such as from bodily fluids and respiratory droplets, indirectly from contaminated surfaces, and vertically from a mother to her fetus through the placenta. 

Even when the evidence base is limited, clinical guidelines are important for informing and standardising the best available care for patients around the world, and for enabling further research to identify new treatments, say the researchers.

They therefore set out to assess the availability, quality, scope and inclusivity of available international clinical guidance on the treatment and supportive care of patients with monkeypox infection.

They searched 6 major research databases for relevant content published up to mid October 2021, plus the ‘grey literature’---policy documents, newsletters, reports, for example, published up to May 2022—in several languages.

They found 14 relevant guidelines. Most were of low quality according to the Appraisal of Guidelines for Research and Evaluation II (AGREE) system, scoring an average of 2 out of a possible 7. And most lacked detail and covered only a narrow range of topics.

There was little provision for different risk groups: only 5 (36%) provided any advice for children; and only 3 (21%) provided advice for pregnant women or for people living with HIV. 

Treatment guidance was mostly limited to advice on antivirals and wasn’t consistent: 7 guidelines advised cidofovir, 4 of which specified this only for severe infection; just 4 (29%) advised tecovirimat, and 1 (7%) brincidofovir. 

More recent guidance, including from the World Health Organization, recommends the use of tecovirimat rather than cidofovir.

While cidofovir and brincidofovir are active against pox viruses in laboratory studies, there are few data on how well they treat pox viruses in people, added to which they are only authorised for use in certain countries, note the researchers.

None of the guidelines detailed optimal dose, timing or length of treatment. And only one guideline provided recommendations on supportive care and the treatment of complications. 

All 14 guidelines recommended vaccination as post-exposure prophylaxis (PEP), but not all of them were up to date on the newer generation vaccines. And PEP guidance for different risk groups was limited and at times contradictory.

The researchers acknowledge that understanding of the monkeypox virus is still evolving, which may account for some of the variability in recommendations they found.

But they say: “Even with a limited evidence base, clinical management guidelines are important tools for guiding decision-making and to reduce risk of inappropriate treatments.” 

They add: “The lack of clarity between guidelines creates uncertainty for clinicians treating patients with [monkeypox] which may impact patient care.”

And they conclude: Our study highlights a need for a rigorous framework for producing guidelines ahead of epidemics and a recognised platform for rapidly reviewing and updating guidance during outbreaks, as new evidence emerges. 

“Human [moneypox] is providing a challenge even in high-resource settings with well-resourced healthcare systems. The lack of guidelines may especially impact clinics with limited previous experience in managing patients with [monkeypox]. 

Given the recent global publicity surrounding monkeypox, this is an opportune moment to harness interest and investment in further research to make sure that everyone is given the best treatment, they say.

UBC researchers discover ‘weak spot’ across major COVID-19 variants

Peer-Reviewed Publication

UNIVERSITY OF BRITISH COLUMBIA

Cryo-electron microscopy reveals how the VH Ab6 antibody fragment (red) attaches to the vulnerable site on the SARS-CoV-2 spike protein (grey) to block the virus from binding with the human ACE2 cell receptor (blue). 

IMAGE: CRYO-ELECTRON MICROSCOPY REVEALS HOW THE VH AB6 ANTIBODY FRAGMENT (RED) ATTACHES TO THE VULNERABLE SITE ON THE SARS-COV-2 SPIKE PROTEIN (GREY) TO BLOCK THE VIRUS FROM BINDING WITH THE HUMAN ACE2 CELL RECEPTOR (BLUE). view more 

CREDIT: DR. SRIRAM SUBRAMANIAM, UBC

Researchers at the University of British Columbia have discovered a key vulnerability across all major variants of the SARS-CoV-2 virus, including the recently emerged BA.1 and BA.2 Omicron subvariants.

The weakness can be targeted by neutralizing antibodies, potentially paving the way for treatments that would be universally effective across variants.

The findings, published today in Nature Communications, use cryo-electron microscopy (cryo-EM) to reveal the atomic-level structure of the vulnerable spot on the virus’ spike protein, known as an epitope. The paper further describes an antibody fragment called VH Ab6 that is able to attach to this site and neutralize each major variant. 

“This is a highly adaptable virus that has evolved to evade most existing antibody treatments, as well as much of the immunity conferred by vaccines and natural infection,” says Dr. Sriram Subramaniam (he/him), a professor at UBC’s faculty of medicine and the study’s senior author. “This study reveals a weak spot that is largely unchanged across variants and can be neutralized by an antibody fragment. It sets the stage for the design of pan-variant treatments that could potentially help a lot of vulnerable people.”

Identifying COVID-19 master keys

Antibodies are naturally produced by our bodies to fight infection, but can also be made in a laboratory and administered to patients as a treatment. While several antibody treatments have been developed for COVID-19, their effectiveness has waned in the face of highly-mutated variants like Omicron.

“Antibodies attach to a virus in a very specific manner, like a key going into a lock. But when the virus mutates, the key no longer fits,” says Dr. Subramaniam. “We’ve been looking for master keys — antibodies that continue to neutralize the virus even after extensive mutations.”

The ‘master key’ identified in this new paper is the antibody fragment VH Ab6, which was shown to be effective against the Alpha, Beta, Gamma, Delta, Kappa, Epsilon and Omicron variants. The fragment neutralizes SARS-CoV-2 by attaching to the epitope on the spike protein and blocking the virus from entering human cells.

The discovery is the latest from a longstanding and productive collaboration between Dr. Subramaniam’s team at UBC and colleagues at the University of Pittsburgh, led by Drs. Mitko Dimitrov and Wei Li. The team in Pittsburgh has been screening large antibody libraries and testing their effectiveness against COVID-19, while the UBC team has been using cryo-EM to study the molecular structure and characteristics of the spike protein.

Focusing in on COVID-19’s weak points

The UBC team is world-renowned for its expertise in using cryo-EM to visualize protein-protein and protein-antibody interactions at an atomic resolution. In another paper published earlier this year in Science, they were the first to report the structure of the contact zone between the Omicron spike protein and the human cell receptor ACE2, providing a molecular explanation for Omicron’s enhanced viral fitness.

By mapping the molecular structure of each spike protein, the team has been searching for areas of vulnerability that could inform new treatments.

“The epitope we describe in this paper is mostly removed from the hot spots for mutations, which is why it’s capabilities are preserved across variants,” says Dr. Subramaniam. “Now that we’ve described the structure of this site in detail, it unlocks a whole new realm of treatment possibilities.”

Dr. Subramaniam says this key vulnerability can now be exploited by drug makers, and because the site is relatively mutation-free, the resulting treatments could be effective against existing—and even future—variants.

“We now have a very clear picture of this vulnerable spot on the virus. We know every interaction the spike protein makes with the antibody at this site. We can work backwards from this, using intelligent design, to develop a slew of antibody treatments,” says Dr. Subramaniam. “Having broadly effective, variant-resistant treatments would be a game changer in the ongoing fight against COVID-19.”

IV nutrition risks becoming the norm for athletes, despite no evidence it works

Used to be considered treatment of ‘last resort’. ‘Food first’ and ‘no needle’ messages need to be amplified, urge experts

Peer-Reviewed Publication

BMJ

Intravenous (IV) nutrition, which used to be considered a treatment of ‘last resort’, is threatening to become the norm for competitive athletes, despite no scientific evidence that it works or that it is safe, warn experts in an editorial, published online in the British Journal of Sports Medicine.

‘Food first’ and ‘no needle’ messages need to be amplified among all athletes and their support teams to stop this trend in its tracks, they urge.

The authors, who regularly interact with professional team players in European and American leagues and their support teams, have become increasingly aware of the practice.

And while it’s not known exactly how common it is, anecdotally, some players are hooked up to IV nutrition drips as often as every week as part of a pre- or post-game routine, they say. 

So-called ‘drip bars’ and concierge IV nutrition services claim to boost health and performance, restore hydration, and speed up recovery, offering a menu of B vitamins, amino acids, glutathione, vitamin C and electrolytes, and potentially boosting levels beyond any therapeutic range.

Although easily accessible, these services seem to have escaped regulatory oversight, nor is there any guidance on their use for players or practitioners, point out the authors.

The principle of reducing needle use in sport and a ‘food first’ approach is taught in sports nutrition courses around the world, and a ban on needle use by athletes at the Olympic Games, except for appropriate medical use, and where a therapeutic use exemption (TUE) is obtained, has been in place for all recent Games, they highlight.

IV nutrition drips have traditionally been reserved for serious clinical conditions, such as anaemia, symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in a desert, for example. But they are now being used for tiredness, fatigue, or recovery, say the authors.

“But the evidence is sparse and not supportive. We are aware of just two studies assessing vitamin injections in otherwise healthy participants, neither of which yielded an effect for the injection group,” note the authors.

And these drips are not free of risk, potentially interfering with the body’s power houses of detoxification and immunity—the liver and gut microbes—they add.

“Bypassing these mechanisms appears foolhardy unless there is a significant clinical rationale,” they write, adding that IV drips also carry risks of infection at the needle site and of blood clots.

Too much vitamin B6 is associated with peripheral neuropathy, while athletes regularly receiving IV iron risk liver disease, they point out.

“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they write. 

“More than this is the reputational risk to sport if it is normalised for athletes to regularly partake in self-directed IV [nutrition] use with a worrying shift away from what ‘works’ (according to scientific standards), to that which is unproven. 

“Furthermore, some athletes risk an anti-doping violation by participating in self-directed IV [nutrition] use.”

Figures on the prevalence of IV nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of IV nutrition use, say the authors.

“The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams to avoid what was previously a ‘last resort’ treatment becoming normal without scientific evidence of benefit,” they warn.