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I Cured My Superbug Infection But We Can't Count On Homegrown Remedies

I woke up one morning with the side of my face purple and my ear swollen to more than twice its normal size. I'll never forget the look on the face of the attending infectious disease physician when he told me I needed immediate emergency surgery to evacuate the site. That surgery consisted of cutting out and cauterizing the infected tissue behind my ear and a sizable portion of my earlobe and scalp, along with 50 stitches across four layers to piece the remains back together.

When the culture came back days later, it confirmed I was suffering from a bacterial "superbug," a pathogen that evolved to resist traditional antibiotics due to a phenomenon called antimicrobial resistance, or AMR. The infection was relentless. That first day was just the beginning of the nightmarish process of being an AMR patient. The infection continually returned. I needed more than a dozen additional surgeries with long courses of antibiotics that eradicated my gut flora – all with no resolution in sight.

Credit: Courtesy

Credit: Courtesy

I was a pacemaker manufacturer sales rep at the time, making daily rounds to help patients get the lifesaving devices they need. The superbug I contracted, Klebsiella aerogenes, is often found in hospitalized patients but uncommon in skin. I almost certainly picked this superbug up while working, likely doing something as innocuous as touching the wrong table in the wrong room, followed by my own scalp.

And so could you. Hospitals are prime breeding grounds for superbugs. In fact, superbugs were associated with nearly 173,000 American deaths in 2019, making AMR the third leading cause of death from disease in the United States behind heart disease and cancer.

In the end, I solved my own problem. After years of research on the chemistry equipment and second-hand machinery I installed in my kitchen and garage, I devised a first-of-its-kind antimicrobial ointment that can eliminate superbugs in wounds and shows no known resistance. Thanks to my one-man team, a credit line and the Food and Drug Administration help desk, it's now FDA-cleared and working miracles for others, and I am CEO of a company that works every day to bring this solution to more patients.

But as a society, we can't count on home-grown solutions to what could be a species-ending problem.

Since the introduction of antibiotics in the 20th century, bacteria have been evolving to resist them. It's really very simple: we want to kill them, and they want to live. Every use of an antimicrobial gives the target pathogens a chance to survive and come back stronger, rendering existing treatments less effective.

Bacteria evolve quickly. It can take about twenty minutes for a new generation to emerge. We are one bad-luck mutation away from a problem we're currently powerless to stop.

Antimicrobial stewardship programs -- which inform clinicians about appropriate antimicrobial use -- are critical. But COVID-19 erased years of progress. Early on, well-intended doctors prescribed antibiotics to gravely ill patients to ward off secondary infections. Meanwhile, surges in hospitalizations led resistant hospital-onset infections to jump 15% in 2020.

We need a steady supply of novel antimicrobials to have any hope of beating back superbugs. Nearly 5 million people died globally in 2019 in connection with antibiotic resistance, and AMR overall could kill 10 million people annually worldwide by 2050.

The problem is that under sound stewardship protocols, doctors should prescribe new antibiotics only when older ones won't work -- lest the bugs more quickly develop resistance to the new medicines. That means sales will be low. Under these circumstances, manufacturers can't recoup their research and development costs. This broken ecosystem is the main reason behind the exodus in investment toward novel antimicrobial R&D.

We must repair the disconnect between public health needs and private investment.

Fortunately, we know how to solve this problem: change the incentives. We did the same thing successfully to encourage new rare diseases treatments, which likewise would never generate enough sales to justify the development expense. The speedy response to COVID-19 also shows what we're capable of when incentives align with need.

The answer for the broken antimicrobials market is a plan called the Pasteur Act, which was recently reintroduced in Congress. The legislation would establish an alternative payment model whereby the government enters into contracts with antimicrobial developers to pay upfront for access to however much, or little, of the new treatment federal programs need. Patients will gain access to critically needed medications while antimicrobial innovators are assured a return on their investment.

Superbugs are a natural feature of evolution. More are coming. It would be a shame if we're not wise enough as a species to take readily available steps to keep them in check.

Bradley Burnam of Atlanta is a superbug survivor and the founder and CEO of Turn Therapeutics. His story is featured in the new documentary "HOLOBIOME." He will be among the panelists discussing microbes and the future of infectious disease Saturday at the Atlanta Science Festival.

New Study Finds That Persistent COVID-19 Infections Are Surprisingly Common

A study from the University of Oxford reveals that a significant number of COVID-19 infections persist for over a month, potentially contributing to the emergence of new variants and Long COVID symptoms. Analysis of over 90,000 participants found that up to 0.5% of infections could last 60 days or more, with some infections showing high mutation rates.

Recent research conducted by the University of Oxford has found that a high proportion of SARS-CoV-2 infections in the general population lead to persistent infections lasting a month or more. The findings have been published in the journal Nature.

It has long been thought that prolonged COVID-19 infections in immunocompromised individuals may have been the source of the multiple new variants that arose during the coronavirus pandemic and seeded successive waves of infection, including the Alpha and Omicron variants. But until now, the prevalence of persistent COVID-19 infections in the general population and how the virus evolves in these situations remained unknown.

Study Methodology and Findings

To investigate this, the researchers used data from the Office for National Statistics Covid Infection Survey (ONS-CIS), which tested participants approximately monthly. Of the 90,000+ participants, 3,603 provided two or more positive samples between November 2020 to August 2022 where the virus was sequenced. Of these, 381 individuals tested positive for the same viral infection over a period of a month or longer. Within this group, 54 individuals had a persistent infection that lasted at least two months. The researchers estimate that between one in a thousand to one in 200 (0.1-0.5%) of all infections may become persistent, and last for at least 60 days.

In some cases, individuals remained infected with viral variants that had gone extinct in the general population. In contrast, the researchers found that reinfection with the same variant was very rare, likely due to the host developing immunity to that variant and the variant reducing in frequency to very low levels after a few months.

Insights into Viral Dynamics and Long-COVID

Of the 381 persistent infections, 65 had three or more PCR tests taken over the course of their infection. Most (82%) of these individuals demonstrated rebounding viral dynamics, experiencing high, then low, then high viral load dynamics. According to the researchers, this demonstrates that the virus can maintain the ability to actively replicate during prolonged infections.

In the study, people with persistent infections were 55% more likely to report having Long COVID symptoms more than 12 weeks since the start of the infection than people with more typical infections.

Certain individuals showed an extremely high number of mutations, including mutations that define new coronavirus variants, alter target sites for monoclonal antibodies, and introduce changes to the coronavirus spike protein. However, most individuals did not harbor a large number of mutations, suggesting that not every persistent infection will be a potential source for new concerning variants.

Co-lead author of the study Dr Mahan Ghafari (Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford) said: 'Our observations highlight the continuing importance of community-based genomic surveillance both to monitor the emergence and spread of new variants, but also to gain a fundamental understanding of the natural history and evolution of novel pathogens and their clinical implications for patients.'

Co-lead author Dr Katrina Lythgoe (Department of Biology and Pandemic Sciences Institute, University of Oxford) said: 'Although the link between viral persistence and Long Covid may not be causal, these results suggest persistent infections could be contributing to the pathophysiology of Long Covid. Indeed, many other possible mechanisms have been suggested to contribute to Long Covid including inflammation, organ damage, and microthrombosis.'

Reference: "Prevalence of persistent SARS-CoV-2 in a large community surveillance study" by Mahan Ghafari, Matthew Hall, Tanya Golubchik, Daniel Ayoubkhani, Thomas House, George MacIntyre-Cockett, Helen R. Fryer, Laura Thomson, Anel Nurtay, Steven A. Kemp, Luca Ferretti, David Buck, Angie Green, Amy Trebes, Paolo Piazza, Lorne J. Lonie, Ruth Studley, Emma Rourke, Darren L. Smith, Matthew Bashton, Andrew Nelson, Matthew Crown, Clare McCann, Gregory R. Young, Rui Andre Nunes dos Santos, Zack Richards, Mohammad Adnan Tariq, Roberto Cahuantzi, Wellcome Sanger Institute COVID-19 Surveillance Team, COVID-19 Infection Survey Group, The COVID-19 Genomics UK (COG-UK) Consortium, Jeff Barrett, Christophe Fraser, David Bonsall, Ann Sarah Walker and Katrina Lythgoe, 21 February 2024, Nature.DOI: 10.1038/s41586-024-07029-4

Temperature, Humidity May Drive Future Transmission Of Parasitic Worm Infections

UNIVERSITY PARK, Pa. — As climate changes, temperature isn't the only factor to influence the spread of infectious diseases. Humidity plays a role, too, according to new research published this week (Feb. 25) in Ecology Letters. The international team, led by Penn State researchers, developed a model to examine how parasitic worms, specifically species that infect livestock and wildlife, respond to changes in temperature and humidity and how those variables may shape the risk of infection and the development of new hot spots in the future. The findings, which may suggest similar behavior among worms that infect humans, could guide improvements in livestock management and public health interventions in endemic areas.

"We need to understand how climate change can affect the future of these infections," said Isabella Cattadori, professor of biology at Penn State and senior author of the study. "Are they going to get worse? Are they going to shift into different habitats and create new hotspots? Will they mutate and develop into more pathogenic infections?"

Parasitic worms, specifically soil-transmitted helminths, are common and infect roughly 25% of the global human population, according to the World Health Organization. They're also a major source of infection in animals, causing large economic loss to the livestock industry. Yet, Cattadori said, studies on climate and infections typically look at diseases carried by vectors like mosquitoes and ticks.

"There isn't much attention on helminth infections because they're not as threatening as vector-borne diseases, and people tend to underestimate the importance of worm infections," Cattadori said, further explaining that most studies focus on temperature, and few consider other climate-related variables, like humidity, as drivers of infection.

The lifecycle of soil-transmitted helminths has two phases — a free-living stage as eggs and larvae in the environment and an adult stage inside the host. Researchers sought to understand how the free-living stages were affected by climate. They reviewed current scientific literature to gather data on the effect of temperature and relative humidity on helminth egg and larval stages of nine species of helminth that commonly infect livestock and wildlife. These species were then divided into two groups depending on where they reside in their host: worms that live in the stomach and worms that live in the intestines.

Based on this information, they developed a mathematical model to describe how helminth hatching, development and mortality of each helminth group responds to temperature and humidity. They then applied this model to look at historical and future projections of infection risk under different climate change scenarios across Southern, Central and Northern Europe. For future projections, they considered short-term, from 2041 to 2060, and long-term, from 2081 to 2100, scenarios.

"We didn't just look at correlation or linear relationships between variables. We disentangled how each component of the free-living stages is affected by climatic conditions, developing a mechanistic understanding of how helminths respond to these environmental stressors," said Chiara Vanalli, postdoctoral scholar at Penn State and lead author of the study, which she conducted as a graduate student in Cattadori's lab. "This is essential for understanding what might happen in the future."

The study is one of the first, Cattadori said, to look at the interaction between multiple climate variables across multiple parasitic worm species to understand how these factors may alter the seasonal profile of disease transmission, as well as when and where these patterns might arise.

Researchers discovered that not all parasite species behave the same way. Those that reside in the host's intestines were strongly affected by temperature, reaching the highest risk of infection at 50 degrees Fahrenheit. On the other hand, helminths that reside in the stomach responded strongly to humidity, reaching their peak when humidity was 80% or higher. When researchers looked at the seasonality in these patterns across Europe, they found that historically, infection risk has one or two peaks in the spring and summer for the intestinal group and one peak for the stomach group. However, in the future, they expect these peaks may change.

"The intensity of these peaks and the way they shift will depend on location and specific climatic conditions as well as helminth species type," Vanalli said. A two-season trend, with one peak in spring and one in fall, is expected to intensify for intestinal helminths while stomach helminths may be more likely to maintain the summer peak, especially at northern regions.

Researchers also considered how spatial distribution may change too. Historically, infection risk is low in Northern Europe. However, when researchers looked into the future, they found that infection hot spots will shift north, facilitated by increasingly milder climate in central and northern regions while southern regions will undergo more extreme temperature and drier conditions. Over the long-term, Scandinavian countries are projected to experience the greatest risk among both groups of helminths, up to an increase of 100% for the intestinal species and 55% for the stomach species compared to the rest of the continent. What's more, the drastic increase in infection risk at mid-to-high latitudes may likely intensify the risk of co-infection since multiple species of helminths could thrive together.

With a better understanding of how animals are exposed to these infections and potential changes in the future, the findings could lead to the development of better livestock management and preventative control strategies, the researchers said. The dynamics described by the researchers could also shed light on the potential risk for human health because some of the family groups studied include parasites that also affect humans.

"We need to start thinking about how to adapt our strategies to a world where climate is changing," Cattadori said.

Cattadori is also affiliated with the Center for Infectious Disease Dynamics in the Penn State Huck Institutes of the Life Sciences. Other authors on the paper are Marino Gatto, Lorenzo Mari and Renato Casagrandi, all faculty in the Department of Electronics, Information and Bioengineering at Politecnico di Milano.

Funds from the Huck Institutes of the Life Sciences and the Eberly College of Science supported this work.

Article Title

Helminth ecological requirements shape the impact of climate change on the hazard of infection

Article Publication Date

25-Feb-2024

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