Researchers have tested a newly developed vaccine that could confer long-term protection against allergic asthma, reducing the severity of its symptoms.
Their research in animals has been published in the journal Nature Communications.
Asthma affects 340 million worldwide. It is a chronic disease of the air passages characterised by inflammation and narrowing of the airways in response to allergens such as dust mites. Symptoms of asthma include shortness of breath, cough, and wheezing.
Exposure to dust mites and other allergens leads to the production of antibodies called immunoglobulin E (IgE) and type 2 cytokines (such as interleukin-4 (IL-4) and IL-13) in the airways. This leads to a cascade of reactions resulting in hyperresponsiveness of the respiratory tract, excessive mucus production, and eosinophilia (when there are too many eosinophils, a type of white blood cell, in the airways).
Currently, inhaled corticosteroids are the gold standard for controlling asthma — but in the case of severe asthma, this treatment is not enough. Then, it is necessary to use therapeutic monoclonal antibodies that target IgE or the IL-4 and IL-13 pathways. These are costly treatments, however, requiring long-term or even lifelong administration of injections.
To solve this, the researchers developed a conjugate vaccine, called a kinoid, by coupling the recombinant cytokines IL-4 and IL-13 with a carrier protein called CRM197 (a non-pathogenic mutated form of the diphtheria toxin, used in many conjugate vaccines).
The preclinical results from animal models demonstrate that this vaccine induces the sustained production of antibodies specifically directed against IL-4 and IL-13. The vaccine was so effective that six weeks after the first injection of the conjugate vaccine, 90% of the mice presented high levels of antibodies. Over one year after primary immunisation, 60% of them still had antibodies capable of neutralising IL-4 and IL-13 activity.
The vaccine was also shown to strongly reduce levels of IgE, eosinophilia, mucus production and airway hyperresponsiveness in a model of dust mite allergic asthma. This study therefore suggests both the prophylactic and therapeutic efficacy of the vaccine in this model of asthma and no adverse effects were observed in the animals. The next step for the researchers will be to test these findings in a clinical trial setting.
Journal information: Eva Conde et al, Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice, Nature Communications (2021). DOI: 10.1038/s41467-021-22834-5
An innovative early cardiac rehabilitation intervention customised for the individual improved physical function, frailty, quality of life, and depression in hospitalised heart failure patients.
These findings were published in the New England Journal of Medicine and also presented at the American College of Cardiology’s 70th Annual Scientific Session.
“Designing earlier and more personalised individual-specific approaches to heart failure rehab shows great promise for improving outcomes for this common but complex condition that is one of the leading causes of hospitalisation for older adults,” said National Institute on Aging (NIA) Director Richard J Hodes, MD. “These results mark encouraging progress on a path to better overall quality of life and physical function for the millions of older Americans who develop heart failure each year.”
The study team was led by Dalane W Kitzman, MD, professor of cardiovascular medicine and geriatrics/gerontology at Wake Forest School of Medicine, Winston-Salem, North Carolina, and they followed 349 clinical trial participants with heart failure enrolled in “A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients” (REHAB-HF). On average, participants had five comorbidities that reduced of function — diabetes, obesity, high blood pressure, lung disease or kidney disease.
In an earlier pilot study, Kitzman and colleagues found striking deficits in strength, mobility and balance, along with the expected loss of endurance in older patients with acute heart failure, who were mostly fail or pre-fail. The team decided to focus on improving patients’ physical function, weakened already by chronic heart failure and age, and which was worsened by the traditional cardiac hospital experience involving lots of bedrest and resulting in loss of functions often persisting after discharge.
To address this. The REHAB-HF team designed earlier and more customised exercise programs focusing on improving balance, strength, mobility and endurance. They also began REHAB-HF during a patient’s hospital stay when possible rather than the usual six weeks post-discharge. After discharge, participants shifted to outpatient sessions three times per week for three months.
Compared to a control group getting usual cardiac rehab care, REHAB-HF participants showed significant gains in measures of physical functioning and overall quality of life, including tests for lower extremity function and mobility, and a six-minute walk test. Self-perception of their health status and depression improved in surveys compared to pre-trial baselines. Over 80% of REHAB-HF participants reported they were still doing their exercises six months after study completion.
“These findings will inform choices of heart failure rehabilitation strategies that could lead to better physical and emotional outcomes,” said Evan Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology. “Tailored interventions like REHAB-HF that target heart failure’s related decline in physical abilities can result in real overall benefits for patients.”
The study did not show significant differences in related clinical events including rates of hospital readmission for any reason or for heart-failure related rehospitalizations. The research team plans to further explore that and other issues through future expansions of REHAB-HF into larger and longer-term trials with broader participant subgroups.
Journal information: Kitzman et al. Rehabilitation Intervention in Older Patients with Acute Heart Failure with Preserved versus Reduced Ejection Fraction. New England Journal of Medicine. 2021 May 16 doi: 10.1056/NEJMoa2026141.
Long working hours led to 745 000 deaths from stroke and ischaemic heart disease in 2016, a 29% increase from 2000, according to a report by the World Health Organization and the International Labour Organization.
Published in Environment International, this is the first global analysis of the loss of life and health associated with working long hours. The global analysis drew on 37 studies on ischaemic heart disease with over 768 000 participants and 22 studies on stroke with more than 839 000 participants. The WHO and ILO estimate that, in 2016, 398 000 people died from stroke and 347 000 from heart disease as a result of having worked at least 55 hours a week. Between 2000 and 2016, the number of deaths from heart disease due to working long hours rose by 42%, and those from stroke by 19%.
This burden of work-related disease is particularly significant in men (72% of deaths were males), people living in the Western Pacific and South-East Asia regions, and middle-aged or older workers. Most of these deaths were among people aged 60-79 years, who had worked for 55 hours or more per week between the ages of 45 and 74 years.
Long work hours are now known to cause about one-third of the total estimated work-related burden of disease, and so is now the risk factor with the largest occupational disease burden. This shifts thinking towards a relatively new and more psychosocial occupational risk factor to human health.
Compared to a 35-40 hour work week, a 55 hour or more work week is associated with an estimated 35% higher risk of a stroke and a 17% higher risk of dying from ischaemic heart disease, concluded the study.
Increasing numbers of people are working long hours, currently standing at 9% of the world’s population. Even more people are being put at risk of work-related disability and early death by this trend.
This report comes just as the COVID pandemic is feeding a trend towards increased work hours. In China, 18 health workers died from overwork-related illnesses in the pandemic.
“The COVID pandemic has significantly changed the way many people work,“ said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Teleworking has become the norm in many industries, often blurring the boundaries between home and work. In addition, many businesses have been forced to scale back or shut down operations to save money, and people who are still on the payroll end up working longer hours. No job is worth the risk of stroke or heart disease. Governments, employers and workers need to work together to agree on limits to protect the health of workers.”
“Working 55 hours or more per week is a serious health hazard,” added Dr Maria Neira, Director, Department of Environment, Climate Change and Health, at the WHO. “It’s time that we all, governments, employers, and employees wake up to the fact that long working hours can lead to premature death”.
The WHO pointed out the following actions that governments, employers and workers can take protect workers’ health:
governments can introduce, implement and enforce laws, regulations and policies that ban mandatory overtime and ensure maximum limits on working time;
bipartite or collective bargaining agreements between employers and workers’ associations can arrange working time to be more flexible, while at the same time agreeing on a maximum number of working hours;
employees could share working hours to ensure that numbers of hours worked do not climb above 55 or more per week.
Journal information: Pega, F., et al. 2021. Global, regional, and national burdens of ischemic heart disease and stroke attributable to exposure to long working hours for 194 countries, 2000–2016: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury. Environment International, p.106595.
One South African man, who, like many South Africans, suffered from COVID-related anxiety, is looking to set a running world record as he runs along the South African coastline in order raise funds for a mental health charity.
The lockdown was hard on millions of South African, including restauranteur Henry Cock. It forced the closure of his restaurants, leaving his employees without income. But even before the stresses of lockdown, he had been suffering from severe anxiety, and in 2019 had started seeing a therapist.
As with so many people faced with the unexpected hardships of lockdown, he came up with a way to help his employees. He aimed to raise R80 000 for them through a innovative campaign, which involved Cock ‘running the Comrades Marathon’ — consisting of some 6000 laps up and down his own passageway to make up the 90km.
Though no less a gruelling undertaking than doing it outdoors, this turned out to be more successful than anticipated.
“In the end, we managed to raise R120 000,” he related. “It took eleven hours. Eleven hours of running back and forth across a 15-metre passage with just a few short breaks to eat and rest my legs,” he said.
With only his walls to look at during his hours of running, the 34-year-old had time to think about helping out others in light of the mental health challenges he himself had experienced.
Cock has started the ‘Mentally Aweh’ campaign to raise funds for South African Depression and Anxiety Group (SADAG), an organisation that provides free counselling to thousands of South Africans on a daily basis. His inspiration was the Terry Fox Initative, started by Canadian Terry Fox, who attempted to run across that vast country to raise funds for cancer research, though he passed away before he could complete it.
“I will be running the length of the South African coastline, from Kosi Bay in KwaZulu-Natal to Vioolsdrift near the Namibia border, to raise awareness for mental health and raise R6 million for the South African Depression and Anxiety Group,” Cock told Health-e News.
And the unmet need is vast. As he explained on his fundraising page, only a shocking 0.89% of the uninsured South African population has access to free mental health care.
Call volumes doubled since lockdown
SADAG senior counsellor Fatima Seedat said that call volumes had doubled since the start of lockdown.
“We used to receive 600 calls a day. When we entered the pandemic, with lockdown, we were getting over 1200 calls a day. That’s excluding the emails we receive, the SMSes received, and the WhatsApp messages that we receive on a daily basis. We have had around 500,000 calls since lockdown until now.”
Because it is toll free, SADAG’s phone bill runs up to R120 000 each month, so Cock’s mission to raise R6 million will help greatly.
“It is an absolutely amazing initiative,” said Seedat. “Henry is an inspiration for standing up for mental health, because that alone breaks a lot of barriers and boundaries.”
Mental health in South Africa
A third of South Africans will experience a mental health issue during their lifetime, according to SADAG. Depression and anxiety are also considered as mental illnesses, and are much more common than believed.
Cock endured his own mental strain during the lockdown; financial uncertainty, the ending of a long-term relationship, and the illness of a family member all set off his battle with anxiety.
“I was in a very bad space last year, like a very bad space. I was struggling. You get to a point when you’re an anxiety sufferer that you just think this is normal. You just think that this state of being is normal, but it’s not normal,” he said.
This is a pattern that Alexa Scher, a clinical psychologist in private practice, often sees.
“I think there is a lot under the surface that blocks people from actually saying, you know what, I’m not okay. We are usually scared to acknowledge and admit that and notice that in ourselves, so it can creep in invisibly, and then all of a sudden, you’re crying all the time, and then you think, ‘Oh, yeah, maybe this isn’t actually normal.’”
She advised that one should seek help when their state of mind begins to impact their ability to function.
Free help is available
While Cock was able to seek help, the majority of South Africans cannot access mental health treatment, which is why he is trying to help SADAG.
The organisation operates the only suicide crisis line in the country, and also has a 24-hour toll-free telephonic, SMS, and WhatsApp lines.
“We reach people not only in your urban areas, but deep rural areas. People are really in need of help in rural areas because there are not many resources available. So we try to help as many people as we can, by reaching out to everyone,” Seedat explained.
SADAG has about 200 volunteers working in shifts, and all go through a screening process.
While Cock will hit the road solo, and does feel a certain pressure to succeed within the 133 days, he said he is using his emotions to motivate himself.
“I channel all of that energy into days when I’m feeling down or feeling bad. I remind myself that I’m not doing it just for me — I’m doing it to raise awareness for these people that really struggle and don’t have access to the same resources that I do,” he said.
“No matter how dark it is, it’s important to remember that you’re not alone. Reach out. You’ll be surprised how much help you actually receive if you just ask.”
Henry Cock’s journey can be followed on Instagram at @cock.henry.
Coming just days after a third wave was officially declared in Gauteng, and months of delays, frustration and confusion, South Africa’s COVID vaccination programme is at last rolling out on Monday.
The vaccination programme will start off mostly on old age homes, at 87 sites across 9 provinces.
Fanned out across nine provinces and 87 sites, healthcare workers and those licensed to administer vaccines will start the mammoth task, which will kick off mostly at old age homes.
Those who are registered and eligible will receive a vaccination date and site to visit where they will either receive the once-off Johnson and Johnson vaccination – or the first dose of the Pfizer vaccine with another to be taken a fortnight later.
A vaccine site such as a pharmacy may charge up to R354.75 per dose of Pfizer, and R330 for a dose of Johnson and Johnson, according to a memo released by the department of health.
Additionally, a R70 fee for administering the vaccine will be billed to the recipient’s health insurance company or the government if uninsured.
The programme will also cover the hundreds of thousands of healthcare workers who have not yet received their vaccinations.
Health Minister Zweli Mkhize, health MECs and other representatives described their plans for the nation on Sunday night.
Dr Mkhize is under no illusion about what lies ahead and what it will take to get it all done.
“Five million senior citizens are targeted to be completed by the end of June, provided that the supply of vaccines flow as anticipated.”
To put this into context, that’s just 44 days for this target to be met and given some of the setbacks experienced during the Sisonke implementation study, the government will face many sceptics.
“We know that everyone has been very anxious to know what will happen and how we will start to vaccinate our most vulnerable citizens and then move onto vaccinating the general population,” Dr Mkhize said.
According to the minister, over 1.2 million senior citizens have registered to be inoculated thus far. Officials are also hoping to vaccinate an additional 700 000 health workers during this time.
Text messages are being sent out to citizens aged 60 years and over, to get help them prepare.
As the campaign begins, there should be over 975 000 doses of Pfizer vaccines in stock, which have stringent, ultra-cold storage requirements.
Dr Mkhize emphasised that Monday or this week is not open to all senior citizens 60 year and above, rather that old age homes will be the priority.
“We recommend that as many people as possible register beforehand. We will not accommodate people walking into the vaccination sites, the program has been designed to avoid long queues, that’s why we want to keep people on going in based on the message inviting them for vaccination.”
However, some provinces with smaller populations,such as Mpumalanga and the North West, have stated they would try to accommodate senior citizens who would have travelled long distances to vaccination sites.
Dr Mkhize underscored the difficulty of conducting such a programme.
“This is just to know how many vaccines you will get out of a vial and how you draw out the requisite amount, to allow us a few days to iron out teething problems and we expect there will be many teething problems so we are expected to start slow.”
In a letter in the journal Science, eighteen scientists from world-leading research institutions are urging their colleagues to dig deeper into the origins of the coronavirus responsible for the global pandemic.
They argue that there is still not enough evidence to rule out the possibility that the SARS-CoV-2 virus escaped from a lab in China, and they call for a “proper investigation” into the matter.
“We believe this question deserves a fair and thorough science-based investigation, and that any subsequent judgment should be made on the data available,” said Dr. David Relman, professor of microbiology and immunology at Stanford University who helped pen the letter.
They were motivated partly by the March 30 publication of a report commissioned by the World Health Organization that sought to discover the origin of the SARS-CoV-2 virus.
The report’s authors, jointly credited to the WHO and China, ranked each of four possible scenarios on a scale from “extremely unlikely” to “very likely.” After assessing evidence provided by the Chinese team members, the authors concluded the probability that the virus jumped from animal to humans via an intermediary animal was “likely to very likely,” while an accidental laboratory release was deemed “extremely unlikely.”
Other potential pathways the investigators considered were a direct jump from animal to human without an intermediate host (“possible to likely”) and transmission from the surface of frozen food products (“possible”).
“We’re reasonable scientists with expertise in relevant areas,” Relman said, “and we don’t see the data that says this must be of natural origin.”
Ravindra Gupta, a professor of clinical microbiology at the University of Cambridge who signed the letter, said he would like to review lab notes from scientists working at the Wuhan Institute of Virology, and see a list of viruses used at the institute over a five-year period.
The WHO report documents a meeting between its investigators and several members of the institute, including lab director Yuan Zhiming, who gave the joint team a tour of the facility.
At the meeting, representatives of WIV refuted the possibility that SARS-CoV-2 could have leaked from the lab, noting that none of the three SARS-like viruses cultured in the laboratory are closely related to that virus.
They also pointed out that blood samples obtained from workers and students in a research group led by Shi Zhengli, a WIV virologist who studies SARS-like coronaviruses that originate in bats, contained no SARS-CoV-2 antibodies, which would indicate a current or past infection.
However, Relman said that, as a scientist, more than this thirdhand account was needed for him to exclude the possibility of of an accidental laboratory leak.
“Show us the test you used: What was the method? What were the results and the names of the people tested? Did you test a control population?” Relman said. “On all accounts, it was not an adequate, detailed kind of presentation of data that would allow an outside scientist to arrive at an independent conclusion.”
WHO Director General Tedros Adhanom Ghebreyesus was similarly cautious about the report’s findings.
“Although the team has concluded that a laboratory leak is the least likely hypothesis, this requires further investigation, potentially with additional missions involving specialist experts, which I am ready to deploy,” he said in an address to WHO member states on March 30. “Let me say clearly that, as far as WHO is concerned, all hypotheses remain on the table.”
Michael Worobey, who studies viruses at the University of Arizona to better understand pandemics, also signed the letter. From the beginning of the pandemic, he considered that it was either an escape from a lab or natural transmission from animal to human. His stance is still unchanged.
“There just hasn’t been enough definitive evidence either way,” he said, “so both of those remain on the table for me.”
Worobey works in his own lab with a grad student who collects viruses from bats in the wild, and he’s considered how this kind of work could introduce new pathogen to humans.
“As someone who does this, I’m very aware of the opening that creates for new viruses to get close to humans, and so I think that’s another reason I take this seriously,” he said. “I’m concerned about it in my own work.”
SARS-CoV-2 has been shown not to be a laboratory construct genetically modified to make it more transmissible to humans, Worobey said. But an unmodified virus could have been brought into the lab and then moved into humans.
“I’ve seen no evidence that I can look at and say, ‘Oh, OK, this certainly refutes the accidental lab origin and makes it virtually 100% certain that it was a natural event,'” he said. “Until we’re at the stage, both possibilities are viable.”
Scientists said there was one piece of conclusive evidence that would indicate the virus had indeed spread to humans through a natural event—the discovery of the wild animals in whom the virus originated.
Akiko Iwasaki, a professor of immunobiology and epidemiology at Yale University, noted that the WHO report mentioned the testing of more than 80 000 animal samples collected across China. None of those tests turned up a SARS-CoV-2 antibody or snippet of the virus’ genetic material before or after the SARS-CoV-2 outbreak in China.
“However, it is possible that an animal reservoir was missed and further investigation may reveal such evidence,” said Iwasaki, another signatory to the letter.
David Robertson, the head of viral genomics and bioinformatics at the University of Glasgow had not signed the letter, saying he didn’t understand the point.
“Nobody is saying that a lab accident isn’t possible—there’s just no evidence for this beyond the Wuhan Institute of Virology being in Wuhan,” he said, adding that viruses naturally jump from animals to humans all the time.
Although he agreed with the authors of the letter that it was essential to find the origins of SARS-CoV-2 to prepare for the next pandemic, “wasting time investigating labs is a distraction from this,” he said.
Relman disagrees.
“If it turns out to be of natural origin, we’ll have a little bit more information about where that natural reservoir is, and how to be more careful around it in the future,” he said. “And if it’s a laboratory, then we’re talking about thinking much more seriously about what kinds of experiments we do and why.”
The letter’s authors noted that in this time of anti-Asian sentiment in some countries, it was Chinese doctors, scientists, journalists and citizens who shared with the world crucial information about the spread of the virus.
“We should show the same determination in promoting a dispassionate, science-based discourse on this difficult but important issue,” they wrote. Source: Medical Xpress
Journal information: Jennifer Sills et al. Investigate the origins of COVID-19, Science (2021). DOI: 10.1126/science.abj0016
