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How Can We Stop the Next Pandemic? We Asked an Epidemiologist

Scanning sewage for disease threats, vaccine safety, and the true origins of COVID-19. We discuss all these topics and more with Dr. David N. Fisman, an epidemiologist at the University of Toronto.

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Scanning sewage for disease threats, vaccine safety, and the true origins of COVID-19. We discuss all these topics and more with Dr. David N. Fisman, an epidemiologist at the University of Toronto.

It all started with something unimaginably tiny. In fact, if you could see the spiky coronavirus that causes COVID-19 floating midair, it would appear minuscule, even in comparison to the specks of dust floating alongside it. But that’s all it took, a submicroscopic, non-living pathogen to rock the world into chaos, to crash stock markets, to kill millions and to suffocate the world’s economies.

And, despite the panic and havoc the virus continues to cause worldwide – and its “novel” label – it is really nothing new. It has been, in fact, in nature all along, sitting there like a viral time bomb. And epidemiologists were expecting, even warning, that it – or at least something like it – could ignite the next pandemic.

“Most of our vulnerability comes from RNA viruses,” says Dr. David N. Fisman, an epidemiologist at the University of Toronto.

This includes coronaviruses, influenza viruses and a list of other bugs flagged by the World Health Organization as likely threats to mankind.

Why? RNA viruses, as opposed to DNA ones, says Fisman, “mutate and recombine readily, so they pose the greatest threat for novel diseases.”

Dr. DavidundefinedN. Fisman, a professor of epidemiology at the University of Toronto.

Fisman has watched the global COVID-19 outbreak unfold since the start. And he’s got lots of ideas on how to prevent the next pandemic. Both a medical doctor and a professor, Fisman teaches about the epidemiology of infectious diseases at the Dalla Lana School of Public Health in Canada. His research has focused on pneumonia and other epidemic diseases, such as certain intestinal infections and sexually transmitted disease. The Harvard-trained health expert also studies the mathematical modeling and simulation of viral outbreaks.

TheStreet has tapped Fisman for his views on the COVID crisis since weeks before it was officially declared an actual pandemic by the World Health Organization. But, here, he looks forward. Fisman discusses lessons learned, vaccine safety, the murky story of how SARS-CoV-2 jumped to people, and how to get ready for the next global outbreak that’s likely lurking around the corner.

The following exchange was conducted by email and has been lightly edited. It focuses mainly on viral threats and is planned as part of a series of an occasional series of interviews looking ways to prevent the next pandemic.

TheStreet: In my inbox recently was an email for a forum discussion by Harvard's T.H. Chan School of Public Health that began, "Fourteen months into an unprecedented, worldwide pandemic...."

But I don't think this pandemic was unprecedented, and, in the years prior, there was a lot of talk about the 1918 flu pandemic on its 100-year anniversary. SARS and MERS, two other dangerous coronaviruses, as well as Ebola and Zika, had also been in the news in the years prior. Still, most of the world, aside from Taiwan, Hong Kong and Singapore, really failed to act quickly with this virus, and really didn't seem to take it seriously at first. What do you think went wrong?

Fisman: I agree with you entirely in your rejection of this premise. Pandemics aren't a new thing at all. Epidemics and pandemics have been an important part of human history, and there are a lot of echoes of past responses to pandemics in our current situation. A paper by Dr. Peter Juni of St. Michael’s Hospital and colleagues does a wonderful job of showing that 2020 and 1918 are awfully similar. 

I think this feels like an aberration to us because – particularly in rich countries – we've grown very used to the idea that communicable diseases aren't something that can disrupt societies anymore. So, while this is just a repeat of the kind of event that's happened many times in human history, it's been a bit of a comeuppance, especially for wealthy Western countries. I think we've had a lot of competing interests and, frankly, some really bad governance. 

The countries that have done much better during this pandemic have been quick to identify it as an aerosol transmitted disease, have controlled their borders, have listened to science, and have been able to take collective action.

TheStreet: This pandemic really seemed to highlight was a lack of understanding of viral diseases, and that appeared to make people want to put this novel one in a familiar box: the flu or SARS or even the common cold. People seemed surprised that SARS-CoV-2 could be infectious before symptoms appear, that it could have such a long incubation time, and that it could leave many apparently unharmed, while killing and causing severe and sometimes lasting illness in others. But should we have been surprised? Shouldn't all of these been considered as possibilities from the start, instead of relying on airport temperature taking and assuming the virus wouldn't spread beyond Hubei?

Fisman: Again, I concur entirely. Most diseases have a wide spectrum in terms of virulence; pre-symptomatic transmission was something the Chinese were talking about early on. Pre-symptomatic transmission is a factor that really helps determine whether a disease can be controlled, and also, again, implies aerosol transmission of a respiratory disease. We are still struggling with these concepts institutionally in North America. If you can't accept science on how a disease spreads, you're not going to be able to control it.

TheStreet: Looking ahead to preventing or containing the next pandemic, it seems both ideas should be considered, right? So, let's start with surveillance. Talk about some ways world health authorities can boost surveillance to spot the next pandemic?

Fisman: I think we already have some interesting surveillance systems in place that work quite well. ProMED, which is a global email list server on infectious diseases, flagged COVID back around December 2019 or January 2020; they have a history of being out early on other diseases like SARS-1 and MERS. 

Something that's been interesting here in Canada is that web-crawler-based surveillance systems, that were leaned on by WHO and developed in Canada, were actually defunded prior to the pandemic. That's a bit of a scandal here right now, and it's not really clear who gave the order to pull the plug on that alert system, called GPHIN. It makes sense to me that we'd scale stuff like that back up.

An interesting surveillance tool that's really coming into its own during this pandemic is wastewater and sewage surveillance. It is proving to be sensitive and specific for epidemic activity, and one could imagine that being scaled up into a global network for surveillance of priority pathogens. There are already global research networks that look at pathogens in sewage.

One kind of surveillance activity whose role is a bit more questionable after this pandemic is construction of repositories of virulent pathogens gathered from the wild. I think we'll see where we land on the natural emergence vs. lab accident question in Wuhan, but if this pandemic does turn out to be the result of an accidental release from a lab that was engaged in collecting and possibly modifying coronaviruses, that kind of work is really going to have to be looked at carefully after the pandemic. In my opinion, it should be looked at regardless, because even if this was a pandemic that resulted from emergence of the virus in nature, exactly the same thing can happen with accidental lab release.

TheStreet: So, we know these novel diseases ... usually come from wild animals or insects that carry disease, right? We also know that some places, such as China, the world's second largest economy, has been a source of several recent outbreaks: SARS, COVID-19 and bird influenzas H5N1 and H7N9. What are some ways to prevent these types of viral outbreaks from occurring at the source? How much pressure should the world be putting on places like China -- whether this was from a lab or natural spillover -- and how much should it be helping places like Guinea and Sierra Leone or even Mexico and poorer places that are also sources of outbreaks?

Fisman: Yes, around 75% of "novel" emerging infectious diseases happen at the human-animal interface. The drivers of that phenomenon are complex and include how we produce food, including both industrial food production and consumption of bushmeat, increasing sprawl of cities into wilderness areas, and climate and environmental change. This is a paper from 15 years ago from EcoHealth Alliance, a group that's now somewhat in the headlines because of the possibility of lab origins of the current pandemic. 

In China, whatever the origin of SARS-2, it's clear that live animal markets and the trade in wild animals for food create potential vulnerability. Cross species transmission and viral recombination in stressed animals in crowded conditions. But industrial food production and sprawl also create vulnerability. And while economic development for poorer countries is a real positive, transportation infrastructure means that new diseases can move much more quickly from formerly isolated rural areas to global hubs. This happened with Ebola in 2015. So, it's almost the definition of a wicked problem, where you need people who understand economic development, ecology, climate change, food production, and infectious diseases putting their heads together on how to mitigate risk.

An important additional step forward would involve phase I and II trials for vaccines against animal diseases that we know have the potential to jump the species barrier and create a future pandemic: Nipah, Crimean-Congo, Rift Valley Fever, MERS, avian influenza viruses. Having vaccines at least partially developed when a future pandemic unfolds would avoid our current predicament of making vaccines from zero, while fighting a pandemic.

TheStreet: And then, climate change. In the U.S., at least, that's been a huge source of controversy. But aside from its other problems, it can actually contribute to the risk of pandemics, right? Explain.

Fisman: Climate change impacts communicable diseases in a few different ways. In terms of pandemics, I think it's more likely that both climate change and pandemics share upstream drivers in human economic activity and environmental degradation. There's some science-fiction-sounding stuff around defrosting permafrost and viral release, but that's really beyond my pay grade in terms of whether or not that's a threat. The big issues with climate change are: Warmer surface waters are clearly increasing risk of some waterborne diseases – cholera, non-cholera vibrios; increase in fly density has the potential to increase food-borne disease broadly; increased mosquito biting rates at warmer temperatures increases transmission risk for malaria and arboviral diseases like yellow fever and dengue; and diseases like Lyme disease have greater range. Also, disrupted ecology has the potential to increase the risk of zoonotic disease and we are probably seeing this with tularemia in Europe already. And, of course, human migration via desertification, increased sea levels, and war, will predictably have knock-on effects on communicable disease, for example, by increasing refugee and migrant populations.

TheStreet: We also the importance of public health messaging. We really seemed to witness a failure of public health messaging during this pandemic, not just in the U.S. but elsewhere, too. We still have people who don't even believe COVID is real. What are some ways to deal with this? 

Fisman: This is tough stuff. I think clear risk communication, as well as transparency and telling people what they can do to protect themselves, are core public health competencies, but not everyone is great at this part of the job. I remember Dr. Julie Gerberding, who was the Centers for Disease Control and Prevention's director under President George W. Bush, as being a particularly excellent risk communicator, but I'm a big fan of the current director, Dr. Rochelle Walensky, too.

Some of the muddle comes from emerging information being at odds with existing medical dogma. Zeynep Tufekci, an associate professor at the University of North Carolina's School of Information and Library Science, has written about how that's really disrupted messaging on aerosol transmission of COVID-19, where physicians and public health continue to insist that this is a disease that only transmits at short range, which is untrue.

Lastly, we have to deal with a real torrent of misinformation and disinformation, much of it pushed by hostile actors, likely including foreign intelligence services. We have open societies and social media provides tremendous ability to reach and target people. This is article is pretty interesting on some of the weirdness with Great Barrington.

TheStreet: Finally, we seem to have been both lucky and well positioned to have come up with what appear to be really good vaccines for COVID-19 so quickly. But I'm wondering about the PR campaign around them that seems to dismiss any problems associated with them. ... Should governments be more upfront about potential risks, but focus instead on much greater benefits of the vaccines' use during a pandemic? I mean, there's a reason people don't get smallpox vaccines, for example, when there is no risk of infection anymore, and that's partly because the risk of that vaccine outweighs the zero risk of the disease right now. But if that were to reemerge, certainly the vaccine would be far more preferable.

Fisman: We don't use smallpox vaccine anymore because that disease is eradicated, but your larger point about risk-benefit is important and we're seeing that play out right now with the AstraZeneca  (AZN) - Get Report vaccine and vaccine-induced thrombotic thrombocytopenia risk (which is a type of blood clotting along with a simultaneous low blood platelet count). As you say, it's tough to do "phase 4" safety surveillance, because it's hard to assign causality to bad things that happen after vaccines. But the VITT signal was picked up quickly for AZN and the quantitative risk analysis says that in a country like Canada, where we have lots of mRNA vaccine, it doesn't make sense to use AZN. But this is really tricky messaging: Vaccines are very safe, but we hold them to a higher standard than most health interventions, and we're discontinuing use because of safety. I agree: That's tricky. So far, the mRNA vaccines do seem to be remarkably safe and effective, but they're new, so we have to carry on with surveillance

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International

Are We Falling As Rome Did?

Are We Falling As Rome Did?

Authored by Julie Ponese via The Epoch Times,

3, 2, 1… Timber! A Philosopher’s Take on the Collapse of Our…

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Are We Falling As Rome Did?

Authored by Julie Ponese via The Epoch Times,

3, 2, 1... Timber! A Philosopher’s Take on the Collapse of Our Civilization

The clock seems to be ticking.

Growing disparities in wealth, a housing and gas crisis, transhumanism galloping over the horizon, heroized incivility, and the constant threat of viruses, the “cures” for which may be worse than the diseases. Global politics feels eerily apocalyptic these days and, in our own little worlds, many of us are so lost, so unmoored from the comforts of our pre-pandemic lives, that we don’t know which end is up or what the future will hold. Investigative journalist Trish Wood recently wrote that we are living the fall of Rome (though it’s being pushed on us as a virtue).

I wonder, are we falling as Rome did? Is it possible that our civilization is on the verge of collapse? Not imminent collapse, perhaps, but are we taking the initial steps that civilizations before ours took before their eventual downfalls? Will we suffer the fates of the Indus, the Vikings, the Mayans, and the failed dynasties of China?

As a philosopher, I need first to understand what we mean by “civilization” and what it would mean for that thing to collapse.

This is a significant conceptual hurdle. “Civilization” (from the Latin civitas, meaning a body of people) was first used by anthropologists to refer to a “society made up of cities” (Mycenae’s Pylos, Thebes, and Sparta, for example). Ancient civilizations were typically non-nomadic settlements with concentrated complexes of persons who divided labor. They had monumental architecture, hierarchical class structures, and significant technological and cultural developments.

But just what is our civilization? There isn’t a tidy line between it and the next in the way the Mayans’ and the Greeks’ coexistence was defined by the ocean between them. Is the concept of Western civilization—rooted in the culture that emerged from the Mediterranean basin over 2,000 years ago—still meaningful, or has globalization made any distinction between contemporary civilizations meaningless? “I am a citizen of the world,” wrote Diogenes in the fourth century B.C. But of course, his world wasn’t quite as vast as our own.

Now for the second issue: civilization collapse. Anthropologists typically define it as a rapid and enduring loss of population, socio-economic complexity, and identity.

Will we suffer a mass loss of population or socio-economic complexity? Perhaps. But that isn’t what concerns me. What I really worry about is our loss of identity. I worry that we’ve lost the plot, as they say, and that with all our focus on the ability of science to save us, we’ve lost our ideals, our spirit, our reasons for being. I worry we are suffering what Betty Friedan called “a slow death of the mind and spirit.” I worry that our nihilism, our façadism, our progressivism are incurring a debt that we may not be able to pay.

As the eminent anthropologist Sir John Glubb wrote (pdf), “The life-expectation of a great nation, it appears, commences with a violent, and usually unforeseen, outburst of energy, and ends in a lowering of moral standards, cynicism, pessimism and frivolity.”

Think of a civilization as the top step on a staircase, with each stair below having fallen away. Western civilization today is built largely on the foundational ideals of ancient Greece and Rome that endure long after their physical structures and governments disappeared. But they endure because we find them meaningful. They endure through literature and art and conversation and ritual. They endure in how we marry, how we write about one another, and how we care for our sick and aging.

One lesson history tries to teach us is that civilizations are complex systems—of technology, economics, foreign relations, immunology, and civility—and complex systems regularly give way to failure. The collapse of our civilization is almost certainly inevitable; the only questions are when, why, and what will replace us.

But this brings me to another point. Early in its usage, anthropologists started using “civilization” as a normative term, distinguishing “civilized society” from those who are tribal or barbaric. Civilizations are sophisticated, noble, and morally good; other societies are uncivilized, backward, and unvirtuous.

But the old distinction between civilization and barbarism has taken on a new form in the 21st century. It is from within our own “civilized” culture that emerges an inversion of the concepts of civility and brutishness. It is our leaders, our journalists, and our professionals who ignore the standards of rational discourse, who institutionalize hatred and incite division. Today, it is the elites who are the true barbarians among us.

Taking a cue from Walt Whitman, who thought his own 19th century America was waning, “We had best look our times and lands searchingly in the face, like a physician diagnosing some deep disease.”

If our civilization collapses, it won’t be because of an outside attack, like Bedouin charging in from the desert. It will be because of those among us who, like parasites, destroy us from within. Our civilization may collapse and it could be due to any number of factors—war, the economy, natural disasters—but the silent killer, the one that may get us in the end, is our own moral catastrophe.

The ultimate problem, therefore, is not interpersonal; it’s inner-personal. If our civilization is collapsing, it’s because something in each of us is collapsing. And we need to rebuild ourselves first, brick by brick, if we are to have a chance of rebuilding ourselves together.

Tyler Durden Wed, 09/28/2022 - 22:20

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Economics

DryEyeRhythm: A reliable, valid, and non-invasive app to assess dry eye disease

Dry eye disease (DED) is a condition characterized by an array of different symptoms, including dryness, ocular discomfort, fatigue, and visual disturbances….

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Dry eye disease (DED) is a condition characterized by an array of different symptoms, including dryness, ocular discomfort, fatigue, and visual disturbances. This condition has become increasingly common in recent years owing to an aging society, increased screen time, and a highly stressful social environment. There are about 1 billion people, worldwide, who have DED. Undiagnosed and untreated DED can lead to a variety of symptoms, including ocular fatigue, sensitivity to light, lower vision quality, and a lower quality of life. Given the widespread prevalence of the condition, this can further lead to reduced work productivity and economic loss.

Credit: Juntendo University

Dry eye disease (DED) is a condition characterized by an array of different symptoms, including dryness, ocular discomfort, fatigue, and visual disturbances. This condition has become increasingly common in recent years owing to an aging society, increased screen time, and a highly stressful social environment. There are about 1 billion people, worldwide, who have DED. Undiagnosed and untreated DED can lead to a variety of symptoms, including ocular fatigue, sensitivity to light, lower vision quality, and a lower quality of life. Given the widespread prevalence of the condition, this can further lead to reduced work productivity and economic loss.

 

Despite the obvious disadvantages of DED, a large portion of the population remains undiagnosed, which ultimately leads to increased disease severity. DED is currently diagnosed through a series of questionnaires and ocular examinations (which can be invasive). But this method of diagnosis is not ideal. DED examinations do not always correspond with  patients’ subjective DED symptoms. Furthermore, non-invasive and non-contact dry eye examinations are required in the COVID-19 pandemic. These flaws point to a need for a simple, reliable, and accessible screening method for DED to improve diagnosis and prognosis of the disease.

 

To answer this need, a research group, led by Professor Akira Murakami and Associate Professor Takenori Inomata of the Juntendo University Graduate School of Medicine, developed a smartphone application called DryEyeRhythm. “DryEyeRhythm leverages the cameras in smartphones to measure users’ blink characteristics and determine maximum blink interval (MBI)—a substitute for tear film breakup time, an important diagnostic criterion of DED,” explains Associate Prof. Inomata. “The app also administers Ocular Surface Disease Index (OSDI) questionnaires, which are also a crucial component of DED diagnosis.

 

To validate the usefulness of the app, the research team conducted a prospective, cross-sectional, observational, single-center study, the results of which have been published in

The Ocular Surface (available online on 25 April 2022 and published in volume 25 in July 2022).

 

For their study, the team recruited 82 patients, aged 20 years or older, who visited the ophthalmology outpatient clinic at the Juntendo University Hospital between July 2020 and May 2021. The participants completed the Japanese version of the OSDI questionnaire (J-OSDI) and underwent examinations for MBI, both via the app and via other analysis techniques.

 

The study revealed that the J-OSDI collected with DryEyeRhythm showed good internal consistency. Moreover, the app-based questionnaire and MBI yielded significantly higher discriminant validity. The app also showed good positive and negative predictive values, with 91.3% and 69.1%, respectively. The area under the Receiver operating characteristic (ROC) curve—a measure of clinical sensitivity and specificity—for the concurrent use of the app-based J-OSDI and MBI was also high, with a value of 0.910. These results demonstrate that the app is a reliable, valid, and moreover non-invasive, instrument for assessing DED.

 

Non-contact and non-invasive DED diagnostic assistance, like the kind provided by DryEyeRhythm, could help facilitate the early diagnosis and treatment of patients, as well as, DED treatment through telemedicine and online medical care,” says Associate Prof. Inomata. The research team plans to further validate its results by conducting a multi-institutional collaborative study in the future. They are also planning to obtain medical device approval and insurance reimbursement for the smartphone application.

 

The development of DryEyeRhythm is crucial step forward toward the management of DED and improving vision and quality of life among the population.


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Spread & Containment

A rapid, highly sensitive method to measure SARS-CoV-2 in wastewater

Wastewater-based epidemiology (WBE) has been shown to be an excellent means of understanding the spread of SARS-CoV-2 in communities. It is now used in…

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Wastewater-based epidemiology (WBE) has been shown to be an excellent means of understanding the spread of SARS-CoV-2 in communities. It is now used in multiple areas across the world to track the prevalence of the virus, serving as a proxy for determining the status of COVID-19. Of particular importance is that WBE can be used to estimate the prevalence of COVID-19, including asymptomatic cases. However, one of the major drawbacks of WBE for SARS-CoV-2 has been that the traditional method was not very sensitive, and low viral loads could not be reliably detected.

Credit: Hiroki Ando, et al. Science of the Total Environment. August 8, 2022

Wastewater-based epidemiology (WBE) has been shown to be an excellent means of understanding the spread of SARS-CoV-2 in communities. It is now used in multiple areas across the world to track the prevalence of the virus, serving as a proxy for determining the status of COVID-19. Of particular importance is that WBE can be used to estimate the prevalence of COVID-19, including asymptomatic cases. However, one of the major drawbacks of WBE for SARS-CoV-2 has been that the traditional method was not very sensitive, and low viral loads could not be reliably detected.

A team of scientists from Hokkaido University and Shionogi & Co, Ltd., have developed a simple, rapid, highly sensitive method for the detection of SARS-CoV-2 in wastewater. The method, EPISENS-S, which does not require specialised equipment, was described in the journal Science of the Total Environment.

During the COVID-19 pandemic, Japan has had the lowest number of cases per capita. Thus, the viral loads in sewage have also been lower, and much more difficult to evaluate using established WBE methods—due to their low sensitivity. Prior work by the research team showed that the SARS-CoV-2 virus was associated with solids in sewage, so they focused on developing a method to analyse the solid phase of wastewater.

The method they developed, EPISENS-S, involves centrifuging collected wastewater samples to separate all the solids in the samples. The solids were then treated with a commercially available kit to extract all the RNA; the RNA was then reverse transcribed and amplified to obtain a substantial amount of DNA copies. A separate set of samples was subjected to treatment with polyethylene glycol followed by RNA extraction and reverse transcription to synthesize DNA: the method that is currently widely implemented in Japan. The DNA obtained from each of these methods was subjected to quantitative PCR (qPCR).

The team found that the EPISENS-S method is approximately 100 times more sensitive than the polyethylene glycol method. They used EPISENS-S to conduct a long-term analysis of wastewater from two sewage treatment plants in Sapporo city, and found that there was a high correlation between changes in RNA concentrations in the collected samples and changes in the number of reported cases in the city. EPISENS-S can also detect and quantify the Pepper mild mottle virus (PMMoV), which is associated with fecal matter and is used as an internal control.

EPISENS-S provides a way to track COVID-19 cases that are asymptomatic, as well as those that have not been clinically confirmed. In addition, it has great potential to continue tracking the prevalence of SARS-CoV-2 as vaccination rates increase. Finally, EPISENS-S could also be adapted to track other viral diseases with low infection numbers and viral loads.


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