Indian-made 'freeze-free' vaccine carrier to undergo field trials

Agencies
February 9, 2018

New Delhi, Feb 9: This week, the first commercially available freeze-free vaccine carrier will begin introductory field trials in Nepal. This follows the World Health Organisation (WHO) announcement that the Indian-made carrier using PATH's "Freeze-Safe" reference design passed WHO Performance, Quality, and Safety (PQS) laboratory tests for User Independent Freeze Prevention, which prequalifies it for use in global immunisation programs.

This is the first low-cost carrier innovation available to address the widespread and long-standing problem of vaccines freezing in the cold chain during the "last mile" of outreach to infants and children.

Currently in low - and middle - income countries, health workers carry millions of temperature-sensitive vaccines next to ice packs inside vaccine carriers to reduce heat exposure, but this risks freezing the vaccines if ice packs are not conditioned (carefully warmed to around 0°C).

Freezing can irreversibly compromise vaccine potency, resulting in inadequate protection from disease for people receiving vaccines. When health workers suspect temperature damage, the vaccine or medication is often discarded - at great cost to health care programs.

PATH's breakthrough solution mitigates the risk of vaccines being damaged by freezing or heat in carriers and eliminates the step of conditioning ice packs, reducing health worker burden. Frozen ice packs can be inserted immediately into the carrier thanks to a built-in barrier that shields the vaccines from reaching negative temperatures and excessive heat.

Many of the newer vaccines that protect children and infants from life-threatening diseases and infections, such as for human papillomavirus, pneumonia, and rotavirus, are freeze sensitive and cost far more than other vaccines. In 2015, the United Nations Children's Fund (UNICEF) procured approximately USD 1.7 billion worth of vaccines for immunization programs, of which more than USD 1.2 billion were freeze sensitive.

"Our priority is maintaining vaccine potency for the millions of people living in remote communities. In the future, vaccine carriers that prevent freezing will become the new standard for immunization programs," said Pat Lennon, who leads the cold chain team at PATH.

In order to rapidly accelerate introduction of this innovation, PATH put the Freeze-Safe reference design into the public domain for any manufacturer to use in their vaccine carrier products.

PATH staff in Seattle and New Delhi, India, has provided technical advice to three product manufacturers who have adopted the technology. India-based AOV International's product AFVC46 is the first carrier to receive WHO-PQS approval and will be available for purchase through the UNICEF Supply Division catalog.

"The Freeze-Safe vaccine carrier is a great example of Indian industry helping solve a global public health challenge. This 'Made in India' freeze-preventive vaccine carrier can help health workers in India and globally to administer lifesaving vaccines that do not freeze and could help save millions of lives," said Neeraj Jain, Country Director of PATH's India country program.

PATH estimates that more than 2 million new and replacement carriers will be needed by 2020 for the 73 Gavi-member countries. To accelerate scale-up of the Freeze-Safe innovation, PATH is conducting field trials, supporting efforts to integrate the carriers into existing health systems, and working with manufacturers as well as adapting the innovation for use in other cold chain equipment.

"Vaccine carriers that prevent vaccines from freezing while in transit and yet are low cost and easy to use can save millions of children's lives. These are exactly the type of cutting-edge solutions we need to immunize every child," said Dr. Benjamin Schreiber, Deputy Immunization at UNICEF.

PATH has worked to advance technologies, policies, and programs to address vaccine freezing issues across the supply chain from formulation to the last mile since 1996, and on the Freeze-Safe innovation since 2012. This work aligns with UNICEF; Gavi, the Vaccine Alliance; and WHO strategies to maintain vaccine potency and improve immunization cost efficiencies and coverage.

This project was made possible with support from the Bill & Melinda Gates Foundation.

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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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International New York Times
July 7,2020

The coronavirus can stay aloft for hours in tiny droplets in stagnant air, infecting people as they inhale, mounting scientific evidence suggests.

This risk is highest in crowded indoor spaces with poor ventilation, and may help explain superspreading events reported in meatpacking plants, churches and restaurants.

It’s unclear how often the virus is spread via these tiny droplets, or aerosols, compared with larger droplets that are expelled when a sick person coughs or sneezes, or transmitted through contact with contaminated surfaces, said Linsey Marr, an aerosol expert at Virginia Tech.

Follow latest updates on the Covid-19 pandemic here

Aerosols are released even when a person without symptoms exhales, talks or sings, according to Marr and more than 200 other experts, who have outlined the evidence in an open letter to the World Health Organization.

What is clear, they said, is that people should consider minimizing time indoors with people outside their families. Schools, nursing homes and businesses should consider adding powerful new air filters and ultraviolet lights that can kill airborne viruses.

What does it mean for a virus to be airborne?

For a virus to be airborne means that it can be carried through the air in a viable form. For most pathogens, this is a yes-no scenario. HIV, too delicate to survive outside the body, is not airborne. Measles is airborne, and dangerously so: It can survive in the air for up to two hours.

For the coronavirus, the definition has been more complicated. Experts agree that the virus does not travel long distances or remain viable outdoors. But evidence suggests it can traverse the length of a room and, in one set of experimental conditions, remain viable for perhaps three hours.

How are aerosols different from droplets?

Aerosols are droplets, droplets are aerosols — they do not differ except in size. Scientists sometimes refer to droplets fewer than 5 microns in diameter as aerosols. (By comparison, a red blood cell is about 5 microns in diameter; a human hair is about 50 microns wide.)

From the start of the pandemic, the WHO and other public health organizations have focused on the virus’s ability to spread through large droplets that are expelled when a symptomatic person coughs or sneezes.

These droplets are heavy, relatively speaking, and fall quickly to the floor or onto a surface that others might touch. This is why public health agencies have recommended maintaining a distance of at least 6 feet from others, and frequent hand washing.

But some experts have said for months that infected people also are releasing aerosols when they cough and sneeze. More important, they expel aerosols even when they breathe, talk or sing, especially with some exertion.

Scientists know now that people can spread the virus even in the absence of symptoms — without coughing or sneezing — and aerosols might explain that phenomenon.

Because aerosols are smaller, they contain much less virus than droplets do. But because they are lighter, they can linger in the air for hours, especially in the absence of fresh air. In a crowded indoor space, a single infected person can release enough aerosolized virus over time to infect many people, perhaps seeding a superspreader event.

For droplets to be responsible for that kind of spread, a single person would have to be within a few feet of all the other people, or to have contaminated an object that everyone else touched. All that seems unlikely to many experts: “I have to do too many mental gymnastics to explain those other routes of transmission compared to aerosol transmission, which is much simpler,” Marr said.

Can I stop worrying about physical distancing and washing my hands?

Physical distancing is still very important. The closer you are to an infected person, the more aerosols and droplets you may be exposed to. Washing your hands often is still a good idea.

What’s new is that those two things may not be enough. “We should be placing as much emphasis on masks and ventilation as we do with hand washing,” Marr said. “As far as we can tell, this is equally important, if not more important.”

Should I begin wearing a hospital-grade mask indoors? And how long is too long to stay indoors?

Health care workers may all need to wear N95 masks, which filter out most aerosols. At the moment, they are advised to do so only when engaged in certain medical procedures that are thought to produce aerosols.

For the rest of us, cloth face masks will still greatly reduce risk, as long as most people wear them. At home, when you’re with your own family or with roommates you know to be careful, masks are still not necessary. But it is a good idea to wear them in other indoor spaces, experts said.

As for how long is safe, that is frustratingly tough to answer. A lot depends on whether the room is too crowded to allow for a safe distance from others and whether there is fresh air circulating through the room.

What does airborne transmission mean for reopening schools and colleges?

This is a matter of intense debate. Many schools are poorly ventilated and are too poorly funded to invest in new filtration systems. “There is a huge vulnerability to infection transmission via aerosols in schools,” said Don Milton, an aerosol expert at the University of Maryland.

Most children younger than 12 seem to have only mild symptoms, if any, so elementary schools may get by. “So far, we don’t have evidence that elementary schools will be a problem, but the upper grades, I think, would be more likely to be a problem,” Milton said.

College dorms and classrooms are also cause for concern.

Milton said the government should think of long-term solutions for these problems. Having public schools closed “clogs up the whole economy, and it’s a major vulnerability,” he said.

“Until we understand how this is part of our national defense, and fund it appropriately, we’re going to remain extremely vulnerable to these kinds of biological threats.”

What are some things I can do to minimize the risks?

Do as much as you can outdoors. Despite the many photos of people at beaches, even a somewhat crowded beach, especially on a breezy day, is likely to be safer than a pub or an indoor restaurant with recycled air.

But even outdoors, wear a mask if you are likely to be close to others for an extended period.

When indoors, one simple thing people can do is to “open their windows and doors whenever possible,” Marr said. You can also upgrade the filters in your home air-conditioning systems, or adjust the settings to use more outdoor air rather than recirculated air.

Public buildings and businesses may want to invest in air purifiers and ultraviolet lights that can kill the virus. Despite their reputation, elevators may not be a big risk, Milton said, compared with public bathrooms or offices with stagnant air where you may spend a long time.

If none of those things are possible, try to minimize the time you spend in an indoor space, especially without a mask. The longer you spend inside, the greater the dose of virus you might inhale.

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Agencies
July 7,2020

The World Health Organization (WHO) is reviewing a report that suggested its advice on the novel coronavirus needs updating after some scientists told the New York Times there was evidence the virus could be spread by tiny particles in the air.

The WHO says the Covid-19 disease spreads primarily through small droplets, which are expelled from the nose and mouth when an infected person breaths them out in coughs, sneezes, speech or laughter and quickly sink to the ground.

In an open letter to the Geneva-based agency, 239 scientists in 32 countries outlined the evidence they say shows that smaller exhaled particles can infect people who inhale them, the newspaper said on Saturday.

Because those smaller particles can linger in the air longer, the scientists - who plan to publish their findings in a scientific journal this week - are urging WHO to update its guidance, the Times said.

"We are aware of the article and are reviewing its contents with our technical experts," WHO spokesman Tarik Jasarevic said in an email reply on Monday to a Reuters request for comment.

The extent to which the coronavirus can be spread by the so-called airborne or aerosol route - as opposed to by larger droplets in coughs and sneezes - remains disputed.

Any change in the WHO's assessment of the risk of transmission could affect its current advice on keeping one-metre physical distancing. Governments, which also rely on the agency for guidance policy, may also have to adjust public health measures aimed at curbing the spread of the virus.

"Especially in the last couple of months, we have been stating several times that we consider airborne transmission as possible but certainly not supported by solid or even clear evidence," Benedetta Allegranzi, the WHO's technical lead for infection prevention and control, was quoted as saying in the New York Times.

WHO guidance to health workers, dated June 29, says that SARS-CoV-2, the virus that causes Covid-19, is primarily transmitted between people through respiratory droplets and on surfaces.

But airborne transmission via smaller particles is possible in some circumstances, such as when performing intubation and aerosol-generating procedures, it says.

Medical workers performing such procedures should wear heavy-duty N95 respiratory masks and other protective equipment in an adequately ventilated room, the WHO says.

Officials at South Korea's Centers for Disease Control said on Monday they were continuing to discuss various issues about Covid-19, including the possible airborne transmission. They said more investigations and evidence were needed.

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