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Tag: infectious diseases

  • Data Brief: One in Five Adults Unable to Isolate Sick Family Member During Disease Outbreak

    Data Brief: One in Five Adults Unable to Isolate Sick Family Member During Disease Outbreak

    Newswise — LOS ANGELESDec. 22, 2023 /PRNewswire/ — One-fifth of U.S. adults said that they would not be able to isolate a sick household member in a separate bedroom and bathroom in the case of an infectious disease outbreak, yet 75% believe that an infectious disease outbreak is moderately or highly likely to occur within the U.S. during the next year, according to a data brief issued by Heluna Health this week.

    The results come as part of a nationwide survey led by Jo Kay Ghosh, PhD, director of research and evaluation at Heluna Health.

    “While our overall results found moderate to high levels of outbreak preparedness among those surveyed, we identified areas of concern when it comes to people’s ability to isolate a sick family member, and their knowledge of how to use air filters in the home,” Ghosh said.

    One-fifth of those surveyed reported low knowledge of how to use or install high-efficiency air filters to reduce communicable disease spread.

    The survey also identified disparities in overall levels of household preparedness according to socioeconomic factors like age, race, ethnicity, education and income. Younger adults, those of Black or African American race, those of Hispanic ethnicity, those with less than a high school education and those with annual household incomes less than $35,000 reported being the least prepared for an outbreak.

    Blayne Cutler, MD, PhD, president and CEO of Heluna Health, said these results reinforce the importance of the organization’s mission.

    “Heluna Health is at the forefront of increasing equitable access to disease prevention, treatment, care and social resources,” Cutler said.

    The research was conducted by taking a survey of more than 4,000 adults in May 2023, immediately following the end of the COVID-19 public health emergency declaration. The survey assessed public opinions regarding risk for future outbreaks, preferred sources of outbreak information and preparedness for future outbreaks.

    The survey also asked about where participants seek information on how to cope with disease outbreaks. The most highly sought sources were government agencies, such as the Centers for Disease Control and Prevention or health departments; doctors or health systems; or television and news channels.

    For more information, visit www.helunahealth.org.

    Heluna Health

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  • Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

    Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

    Newswise — Immune cells play an active and intimate role in directing the growth of human lung tissue during development, researchers find, revolutionising our understanding of early lung development and the role of immune cells outside of immunity.

    The research offers new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory conditions account for almost 20 per cent of all deaths in children under five years worldwide1.

    The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This discovery raises questions about the potential role of immune cells in other developing organs across the body.

    Researchers from the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL’s European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.

    This study has created a first-of-its-kind immune cell atlas of the developing lung2. It is part of the international Human Cell Atlas3 initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.

    The findings, published today (15 December) in Science Immunology, will help shed light on the mechanisms behind childhood lung diseases.

    Immune cells make up a substantial portion of the airways and mature lungs, which have critical gas exchange and barrier functions, providing protection against infection of the respiratory tract. However, the roles of immune cells in the developing organ have remained unexplored compared to structural or lining cell types. Recent discoveries confirm the presence of immune cells in human lungs as early as five weeks into development4.

    To explore whether the immune system might influence how lungs grow, the team studied immune cells in early human lungs from 5 to 22 weeks of development. They used various techniques, including single-cell sequencing and experiments with lung cell cultures, to see if immune cells could affect lung cell development.

    They identified key regulators of lung development, including signalling molecule IL-1β and IL-13 that facilitate the coordination of lung stem cells differentiating into specialised mature cell types5.

    The researchers detected an infiltration of innate, followed by adaptive immune cells. Innate cells included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells and progenitor cells. With respect to adaptive immune cells, as well as T cells, both developing and mature B lineage cells were detected, indicating that the lung environment supports B cell development.

    The findings fundamentally change the understanding of the immune and epithelial interactions that are crucial for foetal lung maturation. They also suggest that early immune disturbances could manifest as paediatric lung disease.

    These new insights into mechanisms in early lung formation will also contribute to the development of new therapeutic approaches for regenerating damaged lung tissue and restoring lung function.

    Dr Peng He and Dr Jo Barnes, co-first authors of the study at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute, and UCL Division of Medicine respectively, said: “By adopting a focused strategy in mapping the immune system, we reveal a symbiotic relationship between immune cells and developing lungs. These detailed insights open the door to potential regenerative therapies in not only the lung, but in other vital human organs.”

    Dr Marko Nikolić, senior author of the study at UCL Division of Medicine and honorary consultant in respiratory medicine, said: “We now know immune-epithelial crosstalk is a feature of early lung development. This vital baseline of healthy lung development will help us understand what happens when lung developmental processes get disrupted, for example in preterm births, which can lead to respiratory deficiencies.”

    Dr Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, said: “The active participation of immune cells expands the possibilities for understanding and addressing impaired lung formation. What is super exciting about this mechanism is that it may well apply in other organ systems too.”

    Dr Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and Co-founder of the Human Cell Atlas, said: “If we are to fully understand the root causes of disease, we require a complete view of cells at all stages in the human body. This important contribution towards a comprehensive Human Cell Atlas will be a valuable reference for studying lung diseases.”

    ENDS

    Notes to Editors:

    1. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3147
    2. The researchers analysed human embryonic and foetal lung tissue between 5 and 22 weeks post-conception. Human embryonic tissue was provided by the Joint MRC/Wellcome Trust Human Developmental Biology Resource (www.hdbr.org)
    3. The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.
      The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 3,100 HCA members, from 98 countries around the world. https://www.humancellatlas.org
    4. https://www.cell.com/cell/fulltext/S0092-8674(22)01415-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867422014155%3Fshowall%3Dtrue
    5. Experimentation showed that IL-1β, a cytokine produced by immune cells, directly induced airway epithelial progenitor cells to differentiate into mature lung lining cells. They do this by decreasing SOX9 expression and proliferation, driving lung epithelial progenitor cells to stop self-renewal.

    Publication:
    J.L. Barnes et al. (2023) ‘Early human lung immune cell development and its role in epithelial cell fate.’ Science Immunology. DOI: 10.1126/sciimmunol.adf9988

    Funding:
    This research was supported by Wellcome. For full funding acknowledgements, please refer to the publication.

    Selected websites:

    About UCL (University College London)
    UCL was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world’s top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 39,000 students from 150 countries and over 12,500 staff. Our annual income is more than £1 billion. www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our YouTube channel YouTube.com/UCLTV

    The Wellcome Sanger Institute
    The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.

    Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.

    Find out more at www.sanger.ac.uk or follow us on Twitter, Instagram, FacebookLinkedIn 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, infectious disease and climate and health. https://wellcome.org/

    Wellcome Trust Sanger Institute

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  • ‘Long flu’ has emerged as a consequence similar to long COVID

    ‘Long flu’ has emerged as a consequence similar to long COVID

    BYLINE: Kristina Sauerwein

    Newswise — Since the COVID-19 pandemic began, extensive research has emerged detailing the virus’s ability to attack multiple organ systems, potentially resulting in a set of enduring and often disabling health problems known as long COVID. Now, new research from Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System indicates that people hospitalized with seasonal influenza also can suffer long-term, negative health effects, especially involving their lungs and airways.

    The new study comparing the viruses that cause COVID-19 and the flu also revealed that in the 18 months after infection, patients hospitalized for either COVID-19 or seasonal influenza faced an increased risk of death, hospital readmission, and health problems in many organ systems. Further, the time of highest risk was 30 days or later after initial infection.

    “The study illustrates the high toll of death and loss of health following hospitalization with either COVID-19 or seasonal influenza,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. “It’s critical to note that the health risks were higher after the first 30 days of infection. Many people think they’re over COVID-19 or the flu after being discharged from the hospital. That may be true for some people. But our research shows that both viruses can cause long-haul illness.”

    The findings are published Dec. 14 in The Lancet Infectious Diseases.

    The statistical analysis spanned up to 18 months post-infection and included a comparative evaluation of risks of death, hospital admissions and 94 adverse health outcomes involving the body’s major organ systems.

    “A review of past studies on COVID-19 versus the flu focused on a short-term and narrow set of health outcomes,” said Al-Aly, who treats patients within the VA St. Louis Health Care System and is an assistant professor of medicine at Washington University. “Our novel approach compared the long-term health effects of a vast array of conditions. Five years ago, it wouldn’t have occurred to me to examine the possibility of a ‘long flu.’ A major lesson we learned from SARS-CoV-2 is that an infection that initially was thought to only cause brief illness also can lead to chronic disease. This revelation motivated us to look at long-term outcomes of COVID-19 versus flu.

    “We wanted to know whether and to what degree people with flu also experience long-term health effects,” Al-Aly said. “The big answer is that both COVID-19 and the flu led to long-term health problems, and the big aha moment was the realization that the magnitude of long-term health loss eclipsed the problems that these patients endured in the early phase of the infection. Long COVID is much more of a health problem than COVID, and long flu is much more of a health problem than the flu.”

    However, the overall risk and occurrence of death, hospital admissions, and loss of health in many organ systems are substantially higher among COVID-19 patients than among those who have had seasonal influenza, Al-Aly said. “The one notable exception is that the flu poses higher risks to the pulmonary system than COVID-19,” he said. “This tells us the flu is truly more of a respiratory virus, like we’ve all thought for the past 100 years. By comparison, COVID-19 is more aggressive and indiscriminate in that it can attack the pulmonary system, but it can also strike any organ system and is more likely to cause fatal or severe conditions involving the heart, brain, kidneys and other organs.”

    The researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation’s largest integrated health-care delivery system. They evaluated information involving 81,280 patients hospitalized for COVID-19 at some point from March 1, 2020, through June 30, 2022, as well as 10,985 patients hospitalized for seasonal influenza at some point from Oct. 1, 2015, through Feb. 28, 2019.

    Patients represented multiple ages, races and sexes.

    Regarding both viruses, patient vaccination status did not affect results. Those in the COVID-19 cohort were hospitalized during the pre-delta, delta and omicron eras.

    During the overall 18-month study period, patients who had COVID-19 faced a 50% higher risk of death than those with seasonal influenza. This corresponded to about eight more deaths per 100 persons in the COVID-19 group than among those with the flu.

    Although COVID-19 showed a greater risk of health loss than seasonal influenza, infection with either virus carried significant risk of disability and disease. The researchers found COVID-19 exhibited increased risk of 68% of health conditions examined across all organ systems (64 of the 94 adverse health outcomes studied), while the flu was associated with elevated risk of 6% of health conditions (six of the 94) – mostly in the respiratory system.

    Also, over 18 months, COVID-19 patients experienced an increased risk of hospital readmission as well as admission to an intensive care unit (ICU). For every 100 persons in each group, there were 20 more hospital admissions and nine more ICU admissions in COVID-19 than flu.

    “Our findings highlight the continued need to reduce the risk of hospitalization for these two viruses as a way to alleviate the overall burden of health loss in populations,” Al-Aly said. “For both COVID-19 and seasonal influenza, vaccinations can help prevent severe disease and reduce the risk of hospitalizations and death. Optimizing vaccination uptake must remain a priority for governments and health systems everywhere. This is especially important for vulnerable populations such as the elderly and people who are immunocompromised.”

    In both COVID-19 and the flu, more than half of death and disability occurred in the months after infection as opposed to the first 30 days, the latter of which is known as the acute phase.

    “The idea that COVID-19 or flu are just acute illnesses overlooks their larger long-term effects on human health,” Al-Aly said. “Before the pandemic, we tended to belittle most viral infections by regarding them as somewhat inconsequential: ‘You’ll get sick and get over it in a few days.’ But we’re discovering that is not everyone’s experience. Some people are ending up with serious long-term health issues. We need to wake up to this reality and stop trivializing viral infections and understand that they are major drivers of chronic diseases.”

    Washington University in St. Louis

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  • Boosting engagement in heterosexual men may reduce HIV in Uganda

    Boosting engagement in heterosexual men may reduce HIV in Uganda

    Newswise — A study looking at 15 years of HIV transmission and suppression in Uganda reveals how closing gender gaps in treatment could slash infection rates.

    Providing more heterosexual men with easy access to HIV treatment and care could help to suppress the virus and rapidly cut transmission to their female partners, shows a new study published in Nature Microbiology.

    The research, led by scientists from Imperial College London and the Rakai Health Sciences Program in Uganda, analysed 15 years of data from 2003-2018, during which the US President’s Emergency Plan For AIDS Relief (PEPFAR) has delivered an extensive programme of HIV/AIDS testing, prevention, and treatment.

    This included distributing Antiretroviral Therapy (ART) drugs, which supress the virus so a person is no longer infectious. The analysis shows that the PEPFAR program and other services have greatly reduced new infections among young women and heterosexual men, but that reductions were less substantial in women aged 25 and above.

    This is thought to be because women are more likely to reach viral suppression through uptake and effective use of HIV treatment, preventing them from passing HIV to their male partners, but that the same is not true the other way around.

    Gender disparity

    The analysis showed that the number of women reaching and maintaining undetectable (non-transmissible) levels of HIV infection were 1.5 to 2 times higher than men across all ages by the year 2018. The analysis shows that had men reached the same levels of virus suppression as women, around half the new infections that occurred between 2016 and 2018 could have been avoided.

    The team also reconstructed transmission networks based on the genetic code of the virus from thousands of participants, which confirmed that overall, the proportion of transmissions from men is increasing and is now at 63% of all transmissions in the area – even though a greater number of women are living with HIV than men.

    The team say the disparity could be because men need to travel for work, that clinics are closed when they are back home, or for other reasons, including social stigma.

    Dr Oliver Ratmann, senior author of the study from the Department of Mathematics at Imperial, said: “In this evolving battle against HIV, it is critical we adapt our strategies, bridge gaps in care, and ensure that individuals, regardless of their gender, have access to the lifesaving benefits of ART.

    “It is important to design services in a way that everybody who would like to use them is able and feels empowered to do so. By routinely monitoring the changing dynamics of the epidemic and striving for equity in HIV care, we can move closer to the ultimate goal of controlling and, one day, eliminating HIV transmission.”

    Dr Kate Grabowski, a co-author of the study from the Johns Hopkins School of Medicine, added: “The continued success of the President’s Emergency Plan for AIDS Relief (PEPFAR) in reducing infections and saving lives is crucial for ending HIV transmission. With United States Congress currently evaluating PEPFAR funding, our evidence strongly supports the program’s efficacy and provides a clear roadmap to ending the pandemic through enhanced HIV treatment coverage, particularly among men.”

    Closing the gap in transmission

    The team used data from the Rakai Community Cohort Study (RCCS) in southern Uganda, a region where more than 9% of adults are living with HIV – approximately 20 times higher than in the US. Since 2003, a period predating the widespread availability of ART in Africa, RCCS has enrolled nearly 37,000 individuals, tracking changes in HIV infection as new interventions came on board.

    The analysis tracked evolving heterosexual HIV epidemic dynamics in 36 communities over a 15-year span of RCCS surveillance data, including records of new infections, deep sequence HIV genomic data, HIV treatment uptake, viral suppression, and behavioural information.

    Analyses in earlier years showed that the highest number of new HIV cases in southern Uganda was among adolescent girls and young women aged 15-24 years. In more recent years tracked in the new study, women 25-34 years old have become a new focal group, experiencing a slower decline in new infections than other age groups. This is alongside a significant difference in the declines in new infections between men and women, with those among boys and men declining much faster.

    To estimate the likely impact of getting men to the same level of viral suppression, the team applied statistical models based on the data about transmission dynamics. The resulting projections indicate that closing the viral suppression gap in men could have effectively halved rates of new infections among women and eliminated gender disparities in acquiring HIV.

    Dr Joseph Kagaayi, previous director of the Rakai Health Sciences program and senior co-author of the study, said: “Our study findings emphasise the importance of addressing disparities in ART uptake and viral suppression between men and women. By doing so, we can not only reduce HIV infections among women but also work towards closing the gender gap in HIV transmission. Achieving these goals will require concerted efforts, informed policies, and strengthened healthcare services.”

    Imperial College London

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  • Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

    Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

    Newswise — Viruses have limited genetic material—and few proteins—so all the pieces must work extra hard. Zika is a great example; the virus only produces 10 proteins. Now, in a study published in the journal PLOS Pathogens, researchers at Sanford Burnham Prebys have shown how the virus does so much with so little and may have identified a therapeutic vulnerability.

    In the study, the research team showed that Zika’s enzyme—NS2B-NS3—is a multipurpose tool with two essential functions: breaking up proteins (a protease) and dividing its own double-stranded RNA into single strands (a helicase).

    “We found that Zika’s enzyme complex changes function based on how it’s shaped,” says Alexey Terskikh, Ph.D., associate professor at Sanford Burnham Prebys and senior author of the paper. “When in the closed conformation, it acts as a classic protease. But then it cycles between open and super-open conformations, which allows it to grab and then release a single strand of RNA—and these functions are essential for viral replication.”

    Zika is an RNA virus that’s part of a family of deadly pathogens called flaviviruses, which include West Nile, dengue fever, yellow fever, Japanese encephalitis and others. The virus is transmitted by mosquitoes and infects uterine and placental cells (among other cell types), making it particularly dangerous for pregnant women. Once inside host cells, the virus re-engineers them to produce more Zika.

    Understanding Zika on the molecular level could have an enormous payoff: a therapeutic target. It would be difficult to create safe drugs that target the domains of the enzyme needed for protease or helicase functions, as human cells have many similar molecules. However, a drug that blocks Zika’s conformational changes could be effective. If the complex can’t shape-shift, it can’t perform its critical functions, and no new Zika particles would be produced.

    An efficient machineResearchers have long known that Zika’s essential enzyme was composed of two units: NS2B-NS3pro and NS3hel. NS2B-NS3pro carries out protease functions, cutting long polypeptides into Zika proteins. However, NS2B-NS3pro’s abilities to bind single-stranded RNA and help separate the double-stranded RNA during viral replication were only recently discovered.

    In this study, the researchers leaned on recent crystal structures and used protein biochemistry, fluorescence polarization and computer modeling to dissect NS2B-NS3pro’s life cycle. NS3pro is connected to NS3hel (the helicase) by a short amino acid linker and becomes active when the complex is in its closed conformation, like a closed accordion. The RNA binding happens when the complex is open, whereas the complex must transition through the super-open conformation to release RNA.

    These conformational changes are driven by the dynamics of NS3hel activity, which extends the linker and eventually “yanks” the NS3pro to release RNA. NS3pro is anchored to the inside of the host cell’s endoplasmic reticulum (ER)—a key organelle that helps shepherd cellular proteins to their appropriate destinations—via NS2B and, while in the closed conformation, cuts up the Zika polypeptide, helping generate all viral proteins.

    On the other side of the linker, NS3hel separates Zika’s double-stranded RNA and conveniently hands a strand over to NS3pro, which has positively charged “forks” to grab on to the negatively charged RNA.

    “There’s a very nice groove of positive charges,” says Terskikh. “So, RNA just naturally follows that groove. Then the complex shifts to the closed conformation and releases the RNA.”

    As NS3hel reaches forward to grab the double-stranded RNA, it pulls the complex with it; however, since the NS3pro is anchored in the ER membrane, and the linker can only extend so far, the complex snaps into the super-open conformation and releases RNA. The complex then relaxes back to the open conformation, ready for a new cycle.

    Meanwhile, when NS3pro detects a viral polypeptide to cut, it forces the complex into the closed conformation, becoming a protease. The authors call this process “reverse inchworm,” because grabbing and releasing the single-stranded RNA resembles inchworm movements, but backward with the jaws (the protease) trailing behind.

    In addition to providing a possible therapeutic target for Zika, this detailed understanding could be applied to other flaviviruses, which share similar molecular machinery.

    “Versions of the NS2B-NS3pro complex are found throughout the flaviviruses,” says Terskikh. “It could potentially constitute a whole new class of drug targets for multiple viruses.”

    ###

    Additional authors include Sergey A. Shiryaev, Piotr Cieplak, Anton Cheltsov and Robert C. Liddington.

    This study was supported by grants from the National Institutes of Health (5R21AI134581 and R01 NS105969).

    Sanford Burnham Prebys

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  • No antibiotics worked, so this woman turned to a natural enemy of bacteria to save her husband's life | CNN

    No antibiotics worked, so this woman turned to a natural enemy of bacteria to save her husband's life | CNN



    CNN
     — 

    In February 2016, infectious disease epidemiologist Steffanie Strathdee was holding her dying husband’s hand, watching him lose an exhausting fight against a deadly superbug infection.

    After months of ups and downs, doctors had just told her that her husband, Tom Patterson, was too racked with bacteria to live.

    “I told him, ‘Honey, we’re running out of time. I need to know if you want to live. I don’t even know if you can hear me, but if you can hear me and you want to live, please squeeze my hand.’

    “All of a sudden, he squeezed really hard. And I thought, ‘Oh, great!’ And then I’m thinking, ‘Oh, crap! What am I going to do?’”

    What she accomplished next could easily be called miraculous. First, Strathdee found an obscure treatment that offered a glimmer of hope — fighting superbugs with phages, viruses created by nature to eat bacteria.

    Then she convinced phage scientists around the country to hunt and peck through molecular haystacks of sewage, bogs, ponds, the bilge of boats and other prime breeding grounds for bacteria and their viral opponents. The impossible goal: quickly find the few, exquisitely unique phages capable of fighting a specific strain of antibiotic-resistant bacteria literally eating her husband alive.

    Next, the US Food and Drug Administration had to greenlight this unproven cocktail of hope, and scientists had to purify the mixture so that it wouldn’t be deadly.

    Yet just three weeks later, Strathdee watched doctors intravenously inject the mixture into her husband’s body — and save his life.

    Their story is one of unrelenting perseverance and unbelievable good fortune. It’s a glowing tribute to the immense kindness of strangers. And it’s a story that just might save countless lives from the growing threat of antibiotic-resistant superbugs — maybe even your own.

    “It’s estimated that by 2050, 10 million people per year — that’s one person every three seconds — is going to be dying from a superbug infection,” Strathdee told an audience at Life Itself, a 2022 health and wellness event presented in partnership with CNN.

    “I’m here to tell you that the enemy of my enemy can be my friend. Viruses can be medicine.”

    sanjay pkg vpx

    How this ‘perfect predator’ saved his life after nine months in the hospital

    During a Thanksgiving cruise on the Nile in 2015, Patterson was suddenly felled by severe stomach cramps. When a clinic in Egypt failed to help his worsening symptoms, Patterson was flown to Germany, where doctors discovered a grapefruit-size abdominal abscess filled with Acinetobacter baumannii, a virulent bacterium resistant to nearly all antibiotics.

    Found in the sands of the Middle East, the bacteria were blown into the wounds of American troops hit by roadside bombs during the Iraq War, earning the pathogen the nickname “Iraqibacter.”

    “Veterans would get shrapnel in their legs and bodies from IED explosions and were medevaced home to convalesce,” Strathdee told CNN, referring to improvised explosive devices. “Unfortunately, they brought their superbug with them. Sadly, many of them survived the bomb blasts but died from this deadly bacterium.”

    Today, Acinetobacter baumannii tops the World Health Organization’s list of dangerous pathogens for which new antibiotics are critically needed.

    “It’s something of a bacterial kleptomaniac. It’s really good at stealing antimicrobial resistance genes from other bacteria,” Strathdee said. “I started to realize that my husband was a lot sicker than I thought and that modern medicine had run out of antibiotics to treat him.”

    With the bacteria growing unchecked inside him, Patterson was soon medevaced to the couple’s hometown of San Diego, where he was a professor of psychiatry and Strathdee was the associate dean of global health sciences at the University of California, San Diego.

    “Tom was on a roller coaster — he’d get better for a few days, and then there would be a deterioration, and he would be very ill,” said Dr. Robert “Chip” Schooley, a leading infectious disease specialist at UC San Diego who was a longtime friend and colleague. As weeks turned into months, “Tom began developing multi-organ failure. He was sick enough that we could lose him any day.”

    Patterson's body was systemically infected with a virulent drug-resistant bacteria that also infected troops in the Iraq War, earning the pathogen the nickname

    After that reassuring hand squeeze from her husband, Strathdee sprang into action. Scouring the internet, she had already stumbled across a study by a Tbilisi, Georgia, researcher on the use of phages for treatment of drug-resistant bacteria.

    A phone call later, Strathdee discovered phage treatment was well established in former Soviet bloc countries but had been discounted long ago as “fringe science” in the West.

    “Phages are everywhere. There’s 10 million trillion trillion — that’s 10 to the power of 31 — phages that are thought to be on the planet,” Strathdee said. “They’re in soil, they’re in water, in our oceans and in our bodies, where they are the gatekeepers that keep our bacterial numbers in check. But you have to find the right phage to kill the bacterium that is causing the trouble.”

    Buoyed by her newfound knowledge, Strathdee began reaching out to scientists who worked with phages: “I wrote cold emails to total strangers, begging them for help,” she said at Life Itself.

    One stranger who quickly answered was Texas A&M University biochemist Ryland Young. He’d been working with phages for over 45 years.

    “You know the word persuasive? There’s nobody as persuasive as Steffanie,” said Young, a professor of biochemistry and biophysics who runs the lab at the university’s Center for Phage Technology. “We just dropped everything. No exaggeration, people were literally working 24/7, screening 100 different environmental samples to find just a couple of new phages.”

    While the Texas lab burned the midnight oil, Schooley tried to obtain FDA approval for the injection of the phage cocktail into Patterson. Because phage therapy has not undergone clinical trials in the United States, each case of “compassionate use” required a good deal of documentation. It’s a process that can consume precious time.

    But the woman who answered the phone at the FDA said, “‘No problem. This is what you need, and we can arrange that,’” Schooley recalled. “And then she tells me she has friends in the Navy that might be able to find some phages for us as well.”

    In fact, the US Naval Medical Research Center had banks of phages gathered from seaports around the world. Scientists there began to hunt for a match, “and it wasn’t long before they found a few phages that appeared to be active against the bacterium,” Strathdee said.

    Dr. Robert

    Back in Texas, Young and his team had also gotten lucky. They found four promising phages that ravaged Patterson’s antibiotic-resistant bacteria in a test tube. Now the hard part began — figuring out how to separate the victorious phages from the soup of bacterial toxins left behind.

    “You put one virus particle into a culture, you go home for lunch, and if you’re lucky, you come back to a big shaking, liquid mess of dead bacteria parts among billions and billions of the virus,” Young said. “You want to inject those virus particles into the human bloodstream, but you’re starting with bacterial goo that’s just horrible. You would not want that injected into your body.”

    Purifying phage to be given intravenously was a process that no one had yet perfected in the US, Schooley said, “but both the Navy and Texas A&M got busy, and using different approaches figured out how to clean the phages to the point they could be given safely.”

    More hurdles: Legal staff at Texas A&M expressed concern about future lawsuits. “I remember the lawyer saying to me, ‘Let me see if I get this straight. You want to send unapproved viruses from this lab to be injected into a person who will probably die.’ And I said, “Yeah, that’s about it,’” Young said.

    “But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together,” Young added.

    “It was like the parting of the Red Sea — all the paperwork and hesitation disappeared.”

    The purified cocktail from Young’s lab was the first to arrive in San Diego. Strathdee watched as doctors injected the Texas phages into the pus-filled abscesses in Patterson’s abdomen before settling down for the agonizing wait.

    “We started with the abscesses because we didn’t know what would happen, and we didn’t want to kill him,” Schooley said. “We didn’t see any negative side effects; in fact, Tom seemed to be stabilizing a bit, so we continued the therapy every two hours.”

    Two days later, the Navy cocktail arrived. Those phages were injected into Patterson’s bloodstream to tackle the bacteria that had spread to the rest of his body.

    “We believe Tom was the first person to receive intravenous phage therapy to treat a systemic superbug infection in the US,” Strathdee told CNN.

    “And three days later, Tom lifted his head off the pillow out of a deep coma and kissed his daughter’s hand. It was just miraculous.”

    Patterson awoke from a coma after receiving an intravenous dose of phages tailored to his bacteria.

    Today, nearly eight years later, Patterson is happily retired, walking 3 miles a day and gardening. But the long illness took its toll: He was diagnosed with diabetes and is now insulin dependent, with mild heart damage and gastrointestinal issues that affect his diet.

    “He isn’t back surfing again, because he can’t feel the bottoms of his feet, and he did get Covid-19 in April that landed him in the hospital because the bottoms of his lungs are essentially dead,” Strathdee said.

    “As soon as the infection hit his lungs he couldn’t breathe and I had to rush him to the hospital, so that was scary,” she said. “He remains high risk for Covid but we’re not letting that hold us hostage at home. He says, ‘I want to go back to having as normal life as fast as possible.’”

    To prove it, the couple are again traveling the world — they recently returned from a 12-day trip to Argentina.

    “We traveled with a friend who is an infectious disease doctor, which gave me peace of mind to know that if anything went sideways, we’d have an expert at hand,” Strathdee said.

    “I guess I’m a bit of a helicopter wife in that sense. Still, we’ve traveled to Costa Rica a couple of times, we’ve been to Africa, and we’re planning to go to Chile in January.”

    Patterson’s case was published in the journal Antimicrobial Agents and Chemotherapy in 2017, jump-starting new scientific interest in phage therapy.

    “There’s been an explosion of clinical trials that are going on now in phage (science) around the world and there’s phage programs in Canada, the UK, Australia, Belgium, Sweden, Switzerland, India and China has a new one, so it’s really catching on,” Strathdee told CNN.

    Some of the work is focused on the interplay between phages and antibiotics — as bacteria battle phages they often shed their outer shell to keep the enemy from docking and gaining access for the kill. When that happens, the bacteria may be suddenly vulnerable to antibiotics again.

    “We don’t think phages are ever going to entirely replace antibiotics, but they will be a good adjunct to antibiotics. And in fact, they can even make antibiotics work better,” Strathdee said.

    In San Diego, Strathdee and Schooley opened the Center for Innovative Phage Applications and Therapeutics, or IPATH, in 2018, where they treat or counsel patients suffering from multidrug-resistant infections. The center’s success rate is high, with 82% of patients undergoing phage therapy experiencing a clinically successful outcome, according to its website.

    Schooley is running a clinical trial using phages to treat patients with cystic fibrosis who constantly battle Pseudomonas aeruginosa, a drug-resistant bacteria that was also responsible for the recent illness and deaths connected to contaminated eye drops manufactured in India.

    And a memoir the couple published in 2019 — “The Perfect Predator: A Scientist’s Race to Save Her Husband From a Deadly Superbug” — is also spreading the word about these “perfect predators” to what may soon be the next generation of phage hunters.

    VS Phages Sanjay Steffanie

    How naturally occurring viruses could help treat superbug infections

    “I am getting increasingly contacted by students, some as young as 12,” Strathdee said. “There’s a girl in San Francisco who begged her mother to read this book and now she’s doing a science project on phage-antibiotic synergy, and she’s in eighth grade. That thrills me.”

    Strathdee is quick to acknowledge the many people who helped save her husband’s life. But those who were along for the ride told CNN that she and Patterson made the difference.

    “I think it was a historical accident that could have only happened to Steffanie and Tom,” Young said. “They were at UC San Diego, which is one of the premier universities in the country. They worked with a brilliant infectious disease doctor who said, ‘Yes,’ to phage therapy when most physicians would’ve said, ‘Hell, no, I won’t do that.’

    “And then there is Steffanie’s passion and energy — it’s hard to explain until she’s focused it on you. It was like a spiderweb; she was in the middle and pulled on strings,” Young added. “It was just meant to be because of her, I think.”

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  • Bacteria, stay out!

    Bacteria, stay out!

    Hospital germs and pathogens are not always transmitted directly from person to person. They can also spread via germ-contaminated surfaces and objects.

    Empa, Swiss Federal Laboratories for Materials Science and Technology

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  • WHO’s new COVID guidelines see fewer patients requiring hospitalization

    WHO’s new COVID guidelines see fewer patients requiring hospitalization

    Most patients are unlikely to develop severe disease or die if they get the current variants of COVID-19 as immunity levels have climbed given higher levels of vaccination.

    That’s according to the World Health Organization, which updated its COVID-19 guidelines on Friday for the 13th time.

    The guidelines highlight that fewer patients will require hospitalization as they are more likely to have non-severe COVID.

    “The new ‘moderate risk’ category now includes people previously considered to be high risk including older people and/or those with chronic conditions, disabilities, and comorbidities of chronic disease,” the agency said in a statement.

    People who are immunosuppressed remain at higher risk, however, with an estimated hospitalization rate of 6%. But people who are older than 65 years old, those with conditions like obesity, diabetes and/or chronic conditions including chronic obstructive pulmonary disease, kidney or liver disease, cancer, people with disabilities and those with comorbidities of chronic disease are at moderate risk, with an estimated hospitalization rate of 3%.

    And patients who belong to neither of those groups are at low risk of hospitalization, at an estimated rate of just 0.5%. Most people are now considered low-risk, said the WHO.

    The agency continues to recommend the use of Paxlovid for anyone at high or moderate risk of hospitalization. The antiviral developed by Pfizer Inc.
    PFE,
    -1.20%

    is still the best choice for most eligible patients, given its therapeutic benefits, ease of use and fewer concerns about potential harms.

    In cases where Paxlovid is not available, the WHO recommends molnupiravir, an antiviral developed by Merck
    MRK,
    -1.11%
    ,
    or remdesivir, an antiviral developed by Gilead Sciences Inc.
    GILD,
    +0.92%

    Read now: Pfizer to more than double price of its COVID antiviral once drug moves to commercial market

    “For people at low risk of hospitalization, WHO does not recommend any antiviral therapy. Symptoms like fever and pain can continue to be managed with analgesics like paracetamol,” said the agency.

    The WHO said it recommends against the use of a new antiviral called VV116 for patients, apart from those who are enrolled in clinical trials.

    That oral antiviral is being developed by Junshi Biosciences and Vigonvita in China.

    It issued a warning against the use of ivermectin for people with non-severe COVID. The drug used to treat parasites in animals proved highly controversial during the pandemic when many people were persuaded by fraudulent research and online misinformation that it was an effective treatment.

    From the archive: ‘You will not believe what I’ve just found.’ Inside the ivermectin saga: a hacked password, mysterious websites and faulty data.

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  • Bats Could Hold the Secret to Better, Longer Human Life

    Bats Could Hold the Secret to Better, Longer Human Life

    In Linfa Wang’s ideal world, all humans would be just a bit more bat-like.

    Wang, a biochemist and zoonotic-disease expert at Duke-NUS Medical School, in Singapore, has no illusions about people flapping about the skies or echolocating to find the best burger in town. The point is “not to live like a bat,” Wang told me, but to take inspiration from their very weird physiology in order to boost the quality, or even the length, of human life. They might not look it, but bats, Wang said, are “the healthiest mammals on Earth.”

    That thought might be tough to square with bats’ recent track record. In the past three decades—from 1994, when Hendra virus jumped to humans, to 2019, when SARS-CoV-2 emerged—at least half a dozen of the most devastating viral epidemics known to have recently leapt into people from wildlife have had their likeliest origins in bats. But bats themselves rarely, if ever, seem to fall ill. Ebola, Nipah, Marburg, and various coronaviruses don’t appear to trouble them; some bats can survive encounters with rabies, which, left untreated in humans, has a near 100 percent fatality rate. “They’ve evolved mechanisms to limit the damage of disease,” says Emma Teeling, a bat biologist at University College Dublin, who collaborates with Wang.

    The creatures’ apparent ability to defy death goes even beyond that. Some nectar-devouring species spend years spiking their blood-sugar levels high enough to send a human into a hyperglycemic coma—and yet, those bats never seem to develop what we’d call diabetes. Others have been documented surviving up to 41 years in the wild—nearly 10 times as long as mammals of their size are generally expected to live—all the while avoiding cancer and fertility dips.

    Wang and Teeling, along with several colleagues, were recently awarded a $13 million grant by the European Research Council to try to better understand the biology behind these batty abilities—and how it might help other creatures. (And they’re certainly not the only ones trying to find out.) Wang’s team, as he likes to cheerfully boast, has already put some of his ideas to the test by genetically engineering a healthier, more disease-tolerant “bat-mouse.” He and his colleagues are still years away from creating any sort of bat person, but they are confident that this line of thinking could one day inform new treatments for humans—to combat diabetes, to temper infectious diseases, maybe even to extend the life span.

    The key to bats’ health seems to be flight, or at least the effects that evolving flight has had on the bat body. Flight, for all its perks, is one of the most energetically taxing transportation options: When bats fly, their metabolism can rev up to 15 to 16 times above its resting state; their heart rate may soar above 1,000 beats per minute; their body temperature can exceed 105 degrees Fahrenheit, effectively plunging the animals into an epic fever state. Put all of that on virtually any other mammal, and their body would likely be overwhelmed by the blaze of extreme inflammation, the toxic by-products of their metabolism effectively rending cells apart.

    To cope with this self-destructive form of locomotion, bats have evolved two essential safeguards. First, they are extraordinarily good at maintaining bodily Zen. Even when pushed into extreme forms of exertion, bat bodies don’t get all that inflamed—maybe in part because they lack some of the molecular machinery that kicks those systems into gear. Which means that bats simply rack up less damage when their bodies get stressed. And for any damage that does occur, bats have a second trick: Their cells appear to be unusually efficient at cleanup and repair, rapidly stitching back together bits of torn-up DNA.

    Those strategies, Wang and Teeling told me, haven’t just made flight a breeze for bats. They also mitigate other types of bodily harm. Cancer tends to unfurl after errors appear in particular parts of our genetic code. And, molecularly speaking, aging is basically what happens to the body as it accumulates a lifetime of cellular wear and tear. In a sense, stress is simply stress: The root causes of these chronic health issues overlap with the greatest taxes of flight. So the solutions that keep a bat body running smoothly in the air can address problems throughout its lifetime. While humans get worse at repairing damage with age, bats’ ability improves, Teeling told me.

    All of this can also help explain why bats are such hospitable hosts for pathogens that can kill us. Many of the most dangerous cases of infectious disease are driven by the body’s overzealous inflammatory response; that reaction can pose a greater threat than any damage that a pathogen itself might do to cells. Many of our defenses are like bombs set off on our home turf—capable of killing invaders, yes, but at great cost to us. Bats have such a high threshold for igniting inflammation that many viruses seem able to inhabit their tissues without setting off that degree of destruction. In laboratory experiments, bats have been dosed with so much virus that their tissues end up chock-full—clocking some 10 million units of Ebola virus per milliliter of serum, or 10 million units of the MERS coronavirus per gram of lung——and researchers were still unable to discern serious problems with the bats’ health. Bats and their viruses have, in effect, struck “an immunological detente,” says Tony Schountz, a bat immunologist at Colorado State University.

    Such astronomical levels of virus aren’t a bat’s preferred state. Bat bodies also happen to be very good at tamping down viral replication up front. Part of the reason seems to be that, in certain bat species’ bodies, parts of their antiviral defense system “are always on,” Wang told me. “I call them ‘battle ready.’” So when a pathogen does appear, it knocks up against a host that is already teeming with powerful proteins, ready-made to block parts of the viral life cycle, hindering the microbe from spinning out of control.

    The catch here is that the viruses have wised up to bats’ tricks—and evolved to be more forceful as they attempt to infiltrate and replicate inside of, and then spread between, those well-defended cells. And that bat-caliber offense can be excessive in a human that lacks the same shields, says Cara Brook, a disease ecologist at the University of Chicago. That might help explain why so many bat viruses hit us so hard.. Couple that show of force with our difficulties reining in our own inflammation, and what might have been a trivial infection for a bat can turn into utter chaos for a person.

    One of Wang’s primary ideas for dealing with this kind of host-pathogen mismatch is to use drugs to make our inflammatory responses a bit more muted—that is, a bit more bat-like. That option is especially intriguing, he told me, because it could also lower the risk of autoimmunity, maybe even forestall aging or certain kinds of chronic metabolic disease. His bat-mouse, which was engineered to express a particular inflammation-suppressing bat gene, is an experiment with that principle, and it seemed to fare better against flu, SARS-CoV-2, even gout crystals.

    But the idea of muffling inflammation isn’t exactly new: Our medical armamentarium has included steroids and other immune-system-modulating drugs for decades. All have their limits and their drawbacks, and a treatment specifically inspired by bats would likely be subject to the same caveats, says Arinjay Banerjee, a virologist and bat immunologist at the University of Saskatchewan. Inflammation, as damaging as it can be, is an essential defense. Any drug that modifies it—especially one taken long-term—must avoid the hurt of too much while skirting the risk of not enough. And ultimately, humans just aren’t bats. Plop a bat’s defense into a human body, and it might not work in the way researchers expect, says Hannah Frank, a bat immunologist at Tulane University. To truly see bat-like benefits in people, chances are, we’d need more than one treatment turning more than one physiological dial, Banerjee told me.

    As much as researchers are learning about bats, the gaps in their knowledge are still huge. What’s observed in one of the more than 1,400 species of bats may not hold true for another. Plus, bat physiology is distinct enough from ours that no one really can precisely say what optimal health for them looks like, Frank told me. Although bats rarely die from their viruses, those infections may be still taking a toll in ways that researchers have yet to appreciate, Brook told me. Bats aren’t the only intriguing virus-carriers, either. Rodents, too, haul around a lot of deadly pathogens without falling sick, as Schountz points out. Nor are they the only mammals that live at extremes. Naked mole rats withstand low-oxygen conditions underground; seals must cope with organ-crushing pressures when they dive. Like flight, those adaptations may have rejiggered immunity in yet untold ways.

    Certainly, though, bats have more to offer us than many people give them credit for. In the aftermath of a Hendra virus outbreak in Australia, years ago, “we even had a politician say, Let’s bomb the bats,” Wang told me. The start of the coronavirus pandemic, too, ignited calls for bat cullings; some animals were even reportedly burned out of roosts. “I still don’t want a bat as a pet,” Wang told me. But if his findings keep panning out, maybe someday people will associate bats less with the diseases we don’t want to get from them, and more with the healthy traits we do.

    Katherine J. Wu

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  • This city never slept. But with China tightening its grip, is the party over? | CNN Business

    This city never slept. But with China tightening its grip, is the party over? | CNN Business

    Editor’s Note: Sign up for CNN’s Meanwhile in China newsletter which explores what you need to know about the country’s rise and how it impacts the world.


    Hong Kong
    CNN
     — 

    As the scattered patrons hop from one deserted bar to the next, it’s hard to believe the near-empty streets they are zigzagging down were once among the most vibrant in Asia.

    It is Thursday evening, a normally busy night, but there are no crowds for them to weave through, no revelers spilling onto the pavements and no need for them to wait to be seated. At some of the stops on this muted bar crawl, they are the only ones in the room.

    It wasn’t always this way. It might seem unlikely from this recent snapshot, but Hong Kong was once a leading light in Asia’s nightlife scene, a famously freewheeling neon-lit city that never slept, where East met West and crowds would spill from the bars throughout the night and long into the morning – even on a weekday.

    Such images were beamed around the world in 1997, when Britain handed over sovereignty of its prized former colony to China, and locals and visitors alike welcomed in the new era with a 12-hour rave featuring Boy George, Grace Jones, Pete Tong and Paul Oakenfold.

    China’s message at the time was that even if change was coming to Hong Kong, its spirit of “anything goes” would be staying put. The city was promised a high degree of autonomy for the next 50 years and assured that its Western ways could continue. Or, as China’s then leader Deng Xiaoping put it: “Horses will still run, stocks will still sizzle and dancers will still dance.”

    And for long after the British departed, the dancing did indeed continue. Hong Kong retained not only the spirit of capitalism, but many other freedoms unknown in the rest of China – not just the gambling on horse races that Deng alluded to, but political freedoms of the press, speech and the right to protest. Even calls for greater democracy were tolerated – at least, for a time.

    But little more than halfway into those 50 years, Deng’s promise now rings hollow to many. Spasms of mass protests – against “patriotic education” legislation in 2012, the Occupy Central movement in 2014 and pro-democracy demonstrations in 2019 – led China to restrict civil liberties with a sweeping National Security Law. Hundreds of pro-democracy figures have since been jailed and tens of thousands of residents have headed for the exits.

    That crackdown and Hong Kong’s fading freedoms have been well-documented, but it is only more recently that a less-reported knock-on effect of China’s crackdown has started to emerge: In the streets and the bars, the trendy clubs and Michelin-starred restaurants, the city that never slept has begun to doze.

    Nightlife in the city has become a pale shadow of its heyday as a regional rest and relaxation magnet, when its reputation rested on it being easier to navigate than Japan, less boring than Singapore and freer than mainland China.

    Now, apparently in tandem with the diminishing political freedoms, business in the city’s once-thriving bars is drying up. And while some argue over whether politics or Covid is at fault, few dispute that something needs to be done.

    Bars earned about $88.9 million in the first half of 2023, 18% less than the $108.5 million brought in during the same period in 2019, according to official data.

    In an effort to arrest the decline, the Hong Kong government has launched a “Night Vibes” campaign featuring bazaars at three waterfront areas, splurged millions on a recent fireworks show to celebrate China’s National Day and reintroduced a dragon dance, lit by incense sticks, in its neighborhood of Tai Hang.

    Those efforts have attracted a mixture of criticism and mockery – with many pointing out the irony of the campaign’s opening ceremony featuring two white lions, a color associated in Chinese culture with funerals. Meanwhile, the bazaars have been interrupted by a mix of typhoons and security concerns over the use of fireworks.

    Still, Hong Kong’s Chief Executive John Lee insists the events are a success, saying at least 100,000 people have checked out the bazaars and that 460,000 tourists from mainland China visited for National Day. And the white lions? Officials say they were “fluorescent.”

    A Hong Kong government spokesman told CNN this week that the activities were “well-received by local residents and tourists”. A recent Hong Kong Wine & Dine Festival brought in 140,000 patrons and shopping malls supporting the Night Vibes campaign said they had seen “growth in visitor flow and turnover,” he added.

    A man walks past a closed bar along a near-empty street in the Soho area of Hong Kong.

    There are some who point the finger solely at Covid.

    “It’s obvious that it’s worse than before. This is the side effect of Covid, which has changed the way of life,” said Gary Ng, an economist with French investment bank Natixis.

    And few would dispute that Covid took its toll. During the pandemic, Hong Kong made a virtue of cleaving closely to a mainland Chinese-style zero-tolerance approach that, though not quite as draconian, was still extreme enough to send large numbers of expatriates heading for the exit, with many of them decamping to rival Asian cities like Singapore, Thailand and Japan.

    Hong Kong, where incoming travelers faced weeks in quarantine and restaurant tables were limited to two customers, was suddenly the boring one and Singapore – in a telling comparison – the more lively.

    Under Hong Kong’s pandemic restrictions, live music was all but banned in small venues for more than 650 days.

    But others say Hong Kong is in denial and that its nightlife problems go much deeper than the pandemic. Other places have recovered, they say, why not Hong Kong?

    These observers note the city’s response to Covid should itself be seen through the lens of the city’s ever disappearing freedoms.

    Months before the virus emerged, China had been tightening its grip on Hong Kong in response to pro-democracy protests that had spread throughout the city.

    It introduced restrictions on freedoms – such as of expression and of the press – which were supposedly guaranteed at the time of the handover.

    Songs and slogans perceived as linked to the protests were outlawed, memories of past protests scrubbed from the internet, sensitive films censored and newspaper editors charged with sedition and colluding with foreign forces.

    The government has maintained that legal enforcement is necessary for Hong Kong to restore stability and prosperity and stop what China says is “foreign forces” from meddling in the city.

    “We strongly disapproved of and firmly rejected those groundless attacks, slanders and smears against the HKSAR on the protection of such fundamental rights and freedoms in Hong Kong,” a spokesman said, referring to Hong Kong’s official name, in a reply to CNN.

    But, the critics hit back, none of that lends itself to an atmosphere where people will want to sit back, relax and shoot the breeze.

    “People may feel like they have to self-censor when having a chat at restaurants or bars because, who knows who may be listening. They may as well stay home for the same chat where they feel safe,” said Benson Wong, one of the hundreds of thousands who have left Hong Kong.

    Wong, a former associate professor who specialized in local politics, said he used to enjoy eating out at dai pai dongs – open-air stalls selling Cantonese classics and (usually) plenty of beer – where patrons once talked freely about everything from celebrity gossip to politics.

    Now though, he said, “one won’t feel happy if they have to watch everything they say.”

    A man sits inside a bar in Lan Kwai Fong, Hong Kong's renowned nightlife hub.

    Whether it was Covid or the crackdown, or some combination of the two, an exodus of middle-class Hong Kongers and affluent expats has taken place in recent years.

    Last year, the city saw a net outflow of 60,000 residents, its third drop in as many years, taking the number of usual residents down to 7.19 million as of the end of 2022 — a drop of almost 144,000 from the end of 2020.

    Tens of thousands of them are Hong Kongers who have taken up special visas and pathways to citizenship offered by Western countries such as Britain, Canada and Australia in the wake of China’s crackdown.

    But there has also been a steady drip of departures from the expat population that, like a post-colonial hangover, had remained in the city long after Britain’s departure. They were largely professionals in finance and law with a reputation for working hard and partying even harder, regardless of the politics.

    Local media is now awash with reports of banking and law firms relocating their offices, in part or full, to rival financial hubs such as the no-longer-boring Singapore.

    Unfortunately for bar and restaurant owners, the two demographics leaving are among their biggest customers.

    “The expats have relocated, as well as [Hong Kongers] with a higher income. Their departure of course will have an impact,” said Ng, from Natixis.

    Increasingly, these two groups are being replaced by people from mainland China, who now account for more than 70% of the 103,000 work or graduate visas granted since 2022, according to the Immigration Department. The newly dominant migrants, economists point out, tend to have very different spending habits.

    Yan Wai-hin, an economics lecturer at the Chinese University of Hong Kong, said the city’s previously robust nightlife was propped up largely by a base of expats and middle-class locals steeped in the time-honored drinking culture of enjoying a nice cold one after a long day.

    “The makeup of the population is different now,” Yan said. “Now we have more immigrants from the mainland, and they tend to love to go back to mainland China to spend instead.”

    At Hong Kong’s most famous nightlife district, Lan Kwai Fong, the music may be fading, but it hasn’t stopped completely.

    The area was long synonymous with jam-packed streets of revelers who would spill out from the bars as the air filled with the sounds of boisterous chatter, clinking glasses and dance music blasting away late into the night.

    But during a recent visit by CNN, there was little to distinguish the area from any other street.

    People stand and drink in Lan Kwai Fong in 2017, back when the place was still pumping.

    “It has been very challenging so far and it has not got back to normal by a long shot,” said Richard Feldman, who runs the gay bar Petticoat Lane at the California Tower in Lan Kwai Fong.

    The chairman of the Soho Association, who has been running businesses in the city for more than three decades, Feldman said business was slightly better between Friday and Saturday than weekdays and shops with a good reputation have been less affected.

    But across the board, he too said the number of Western faces were dwindling in what was once a favored expat haunt.

    “It was a mix of expats and local professionals who would go out for drinks and a late night dance. But that demographic has eased quite a bit in the past year,” said another bar owner Becky Lam. “We are getting more mainland customers.”

    Lam, joint founder of a number of Hong Kong bars and restaurants, including wine bar Shady Acres in Central, said while mainland Chinese were willing to spend, they tended to gravitate towards restaurants rather than bars and were less likely to stay out late.

    On a weekday, she said, the bars she runs have been getting only half of the customers compared to pre-pandemic days.

    “They’ll settle for the Happy Hours and that’s it. We are not talking about 2 a.m. to 3 a.m.,” she said.

    There are other problems gnawing away at the nightlife sector.

    “People’s habits have changed since Covid, as many are so used to staying at home watching TV and Netflix,” Feldman said.

    During the pandemic, Hong Kong imposed a lengthy ban on bars and dine-in services to stem social gatherings, in what many saw as a nod to mainland China’s “zero-Covid” strategy.

    This affected shops and malls, which shortened their business hours due to the lack of customers. In many cases, those shortened hours have now become the new normal, with some shops now closing as early as 9 p.m. as opposed to the pre-Covid standard of 10:30 p.m.

    Lan Kwai Fong during its heyday in 2017

    Also conspiring against the city’s nightlife is a strong Hong Kong dollar compared to the Chinese yuan, which affects how both Hong Kongers and potential tourists spend their money.

    “People from the mainland are less likely to come here to shop, while people in Hong Kong are going to Shenzhen to spend their money,” said Marco Chan, head of research at real estate and investment firm CBRE.

    While mainland tourists now think twice about coming to Hong Kong, many Hongkongers have been spending their weekends in mainland China, where many services come at a fraction of the price, Chan said.

    Known as the “Godfather of Lan Kwai Fong,” Allan Zeman – the entrepreneur who turned the small square in Hong Kong’s Central district into a renowned nightlife hub – cuts a more optimistic figure than most and insists business is not as bad as it appears.

    He estimates mainland Chinese customers now account for 35% of the patrons in Lan Kwai Fong and says they are big spenders.

    Allan Zeman, chairman of Lan Kwai Fong Group, says mainland Chinese tourists are still spending generously.

    “They’ll go up to a club, like the California Tower on the roof, and they’ll spend like 400,000 to 550,000 Hong Kong dollars ($51,000 to $70,000) just for drinks,” he said.

    His take is that it is Hong Kong’s strong currency and a relative lack of incoming flights compared to the pre-Covid era that are stalling the city’s comeback. “I think it’s temporary,” he said.

    But bar owner Lam said Hong Kong needs to reexamine its regulatory approach, if it is to thrive at night once more.

    Lam pointed to a drive in recent years by the authorities to remove the city’s famous neon lights in the name of safety as an example of the current misguided approach, saying Hong Kong’s most defining nighttime icons were being dismantled one sign at a time.

    She also said her bar, Shady Acres, had been told to serve customers only indoors and shut all doors and windows after 9 p.m. as part of its licensing requirement.

    “These kinds of hurdles are really big in Hong Kong,” Lam said. “But I look at our neighboring cities like Bangkok, Shanghai and Taipei. These cities have an exciting nightlife as they really make it late night fun with music, street art and late night dining.”

    Feldman, of Petticoat Lane, had another suggestion. “Hong Kong used to be a far more international destination. Now it is a domestic destination,” he said.

    The city, said Feldman, should “do everything it can to attract people not only from China but from all over the world.”

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  • IBD patients at risk of serious infection, even when disease is mild

    IBD patients at risk of serious infection, even when disease is mild

    Newswise — Inflammatory bowel disease (IBD) is an independent risk factor for serious infection, even at very low levels of gastrointestinal inflammation. This has been shown by a study at the University of Gothenburg.

    IBD is an umbrella term for chronic inflammatory bowel diseases, with a population prevalence of around 0.5%. The main types of IBD are ulcerative colitis and Crohn’s disease. Unlike irritable bowel syndrome (IBS), IBD results in visible damage to the intestinal mucous membrane.

    IBD is characterized by intermittent symptoms. Periods of high disease activity are sometimes followed by longer periods of low or no activity. However, the extent to which IBD patients with low disease activity are also at increased risk of serious infections, including sepsis, has been unclear.

    The current study, published in the journal Clinical Gastroenterology and Hepatology, included data on 55,626 individuals diagnosed with IBD. ‘Serious infections’ referred to infections requiring hospitalization.

    The difference between healed and unhealed

    The results show that during periods of low disease activity but active gastrointestinal inflammation, known as microscopic inflammation, there was an increased risk of being affected by serious infections compared to periods of microscopically healed intestinal mucosa.

    In the case of microscopic inflammation, the number of serious infections was 4.62 per 100 people per year. The corresponding figure for microscopically healed mucosa was 2.53. This corresponded to a 59% relative risk increase for residual microscopic gastrointestinal inflammation, on adjusting the results for various confounders.

    Interestingly, the results held true even after adjusting for the prescribed IBD medications, and were otherwise similar regardless of age group, sex, and level of education.

    The study’s first-named and corresponding author is Karl Mårild, an associate professor in pediatrics at the University of Gothenburg’s Sahlgrenska Academy and a consultant at the Gastrointestinal and Liver Clinic at Queen Silvia’s Children’s Hospital in Gothenburg.

    Healing provides important protection

    “We have shown that even during periods of microscopic intestinal inflammation, IBD patients have an increased risk of serious infections, including sepsis, compared to periods when they have a microscopically healed mucosa,” he explains. “This is also true for patients who appear to have low-active disease in clinical terms, but who have microscopic intestinal inflammation beneath the surface.

    “The results indicate that achieving a fully healed intestinal mucosa in IBD may reduce the risk of serious infections. This is important, as serious infections currently contribute toward increased morbidity and mortality in both children and adults with IBD.”

    The results from the study are based on data from a national cohort (ESPRESSO) with information from Swedish health registers, and from the quality register for IBD (SWIBREG) on people in Sweden diagnosed with IBD between 1990 and 2016. This information was linked to data from microscopic intestinal examinations of patients with IBD.

    University of Gothenburg

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  • Specific gut bacteria increase risk of severe malaria

    Specific gut bacteria increase risk of severe malaria

    BYLINE: Jackie Maupin

    Newswise — INDIANAPOLIS—Indiana University School of Medicine researchers have identified multiple species of bacteria that, when present in the gut, are linked to an increased risk of developing severe malaria in humans and mice. Their findings, recently published in Nature Communications, could lead to the development of new approaches targeting gut bacteria to prevent severe malaria and associated deaths.

    Malaria is a life-threatening infectious disease caused by parasites transmitted through the bite of infected mosquitoes. According to the World Health Organization’s latest World Malaria Report, an estimated 619,000 people died from malaria globally in 2021, with 76% of those deaths occurring in children age 5 or younger. 

    IU School of Medicine’s Nathan Schmidt, PhD, an associate professor of pediatrics with the Ryan White Center for Pediatric Infectious Disease and Global Health and the Herman B Wells Center for Pediatric Research, said previous efforts to combat the disease have led to several advancements in malaria treatment and prevention, including new vaccines and antimalarial drugs, insecticides to manage mosquito populations and improved health care processes. However, he said new developments are desperately needed because the gains made in decreasing malaria-related deaths between the early 2000s and late 2010s have plateaued over the last five years.

    “This plateau highlights the need for novel approaches to prevent malaria-related fatalities,” said Schmidt, whose research lab is focused on investigating this global health crisis and its critical impact on children. “Presently, there are no approaches that target gut microbiota. Therefore, we believe that our approach represents an exciting opportunity.”

    In a pivotal 2016 article published in PNAS, Schmidt and his colleagues made a groundbreaking discovery in their experimental models: the gut microbiota has the capability to influence the severity of malaria. This revelation ignited their determination to pinpoint the precise microorganisms, called “Bacteroides,” within the intestinal tract that orchestrate this effect. 

    In their latest study, the researchers found mice harboring particular species of Bacteroides were notably associated with an elevated risk of severe malaria. A similar correlation was also observed in the intestinal tracts of children afflicted with severe malaria.

    Most of the Schmidt lab’s research has been conducted using mouse models of malaria. Thanks to collaboration with several colleagues in the field, the research team was able to extend its observations by studying approximately 50 children with malaria in Uganda. They plan to continue their clinical observations by working with a cohort of over 500 children with malaria. 

    This collaboration was made possible by the joint efforts of Chandy John, MD, MS, of IU School of Medicine; Ruth Namazzi, MB ChB, MMEd, of Makerere University; and Robert Opoka, MD, MPH,  of Global Health Uganda. Together, they are evaluating how severe malaria may affect child neurodevelopment by studying children from households with a history of severe malaria. While these children may not display any symptoms of illness, some carry the malaria parasite in their blood, allowing researchers to explore risk factors associated with the development of severe malaria, including variations observed in the microbiome.

    “Dr. Namazzi, Dr. Opoka and I aren’t experts in the microbiome, so we collaborated with Nathan [Schmidt] on this part of the study since he is an expert,” said John, who is the Ryan White Professor of Pediatrics at IU School of Medicine. “I believe Nathan’s findings are important because they point to the possibility that certain bacteria or combinations of bacteria in the gut may predispose a child to severe malaria. This opens the way to thinking about how we might alter those combinations in the gut to try to protect children from severe malaria.”

    In addition to studying the expanded cohort in Uganda, Schmidt and his team will also collaborate with researchers in Malawi and Mali to get a broader sense of trends present between gut microbiota and malaria across Africa. 

    “Beyond our efforts to assess the contribution of gut bacteria towards severe malaria in diverse African populations, we have initiated pre-clinical efforts to target gut bacteria that cause susceptibility to severe malaria,” Schmidt said. “Our long-term aspiration is to move a treatment into the clinic.”

    About Indiana University School of Medicine

    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

    Indiana University

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  • What If There’s a Secret Benefit to Getting Asian Glow?

    What If There’s a Secret Benefit to Getting Asian Glow?

    At every party, no matter the occasion, my drink of choice is soda water with lime. I have never, not once, been drunk—or even finished a full serving of alcohol. The single time I came close to doing so (thanks to half a serving of mulled wine), my heart rate soared, the room spun, and my face turned stop-sign red … all before I collapsed in front of a college professor at an academic event.

    The blame for my alcohol aversion falls fully on my genetics: Like an estimated 500 million other people, most of them of East Asian descent, I carry a genetic mutation called ALDH2*2 that causes me to produce broken versions of an enzyme called aldehyde dehydrogenase 2, preventing my body from properly breaking down the toxic components of alcohol. And so, whenever I drink, all sorts of poisons known as aldehydes build up in my body—a predicament that my face announces to everyone around me.

    By one line of evolutionary logic, I and the other sufferers of so-called alcohol flush (also known as Asian glow) shouldn’t exist. Alcohol isn’t the only source of aldehydes in the body. Our own cells also naturally produce the compounds, and they can wreak all sorts of havoc on our DNA and proteins if they aren’t promptly cleared. So even at baseline, flushers are toting around extra toxins, leaving them at higher risk for a host of health issues, including esophageal cancer and heart disease. And yet, somehow, our cohort of people, with its intense genetic baggage, has grown to half a billion people in potentially as little as 2,000 years.

    The reason might hew to a different line of evolutionary logic—one driven not by the dangers of aldehydes to us but by the dangers of aldehydes to some of our smallest enemies, according to Heran Darwin, a microbiologist at New York University. As Darwin and her colleagues reported at a conference last week, people with the ALDH2*2 mutation might be especially good at fighting off certain pathogens—among them the bug that causes tuberculosis, or TB, one of the greatest infectious killers in recent history.

    The research, currently under review for publication at the journal Science, hasn’t yet been fully vetted by other scientists. And truly nailing TB, or any other pathogen, as the evolutionary catalyst for the rise of ALDH2*2 will likely be tough. But if infectious disease can even partly explain the staggering size of the flushing cohort—as several experts told me is likely the case—the mystery of one of the most common mutations in the human population will be one step closer to being solved.

    Scientists have long been aware of aldehydes’ nasty effects on DNA and proteins; the compounds are carcinogens that literally “damage the fabric of life,” says Ketan J. Patel, a molecular biologist at the University of Oxford who studies the ALDH2*2 mutation and is reviewing the new research for publication in Science. For years, though, many researchers dismissed the chemicals as the annoying refuse of the body’s daily chores. Our bodies produce them as part of run-of-the-mill metabolism; the compounds also build up during infection or inflammation, as byproducts of some of the noxious chemicals we churn out. But then aldehydes are generally swept away by our molecular cleanup systems like so much microscopic trash.

    Darwin and her colleagues are now convinced that the chemicals deserve more credit. Dosed into laboratory cultures, aldehydes can kill TB within days. In previous research, Darwin’s team also found that aldehydes—including ones produced by the bacteria themselves—can make TB ultra sensitive to nitric oxide, a defensive compound that humans produce during infections, as well as copper, a metal that destroys many microbes on contact. (For what it’s worth, the aldehydes found in our bodies after we consume alcohol don’t seem to much bother TB, Darwin told me. Drinking has actually been linked to worse outcomes with the disease.)

    The team is still tabulating the many ways in which aldehydes are exerting their antimicrobial effects. But Darwin suspects that the bugs that are vulnerable to the chemicals are dying “a death by a thousand cuts,” she told me at the conference. Which makes aldehydes more than worthless waste. Maybe our ancestors’ bodies wised up to the molecules’ universally destructive powers—and began to purposefully deploy them in their defensive arsenal. “It’s the immune system capitalizing on the toxicity,” says Joshua Woodward, a microbiologist at the University of Washington who has been studying the antibacterial effects of aldehydes.

    Specific cells show hints that they’ve caught on to aldehydes’ potency. Sarah Stanley, a microbiologist and an immunologist at UC Berkeley, who has been co-leading the research with Darwin, has found that when immune cells receive certain chemical signals signifying infection, they’ll ramp up some of the metabolic pathways that produce aldehydes. Those same signals, the researchers recently found, can also prompt immune cells to tamp down their levels of aldehyde dehydrogenase 2—the very aldehyde-detoxifying enzyme that the mutant gene in people like me fails to make.

    If holstering that enzyme is a way for cells to up their supply of toxins and brace for inevitable attack, that could be good news for ALDH2*2 carriers, who already struggle to make enough of it. When, in an extreme imitation of human flushers, the researchers purged the ALDH2 gene from a strain of mice, then infected them with TB, they found that the rodents accumulated fewer bacteria in their lungs.

    The buildup of aldehydes in the mutant mice wasn’t enough to, say, render them totally immune to TB. But even a small defensive bump can make for a massive advantage when combating such a deadly disease, Russell Vance, an immunologist at UC Berkeley who’s been collaborating with Darwin and Stanley on the project, told me. Darwin is now curious as to whether TB’s distaste for aldehyde could be leveraged during infections, she told me—by, for instance, supplementing antibiotic regimens with a side of Antabuse, a medication that blocks aldehyde dehydrogenase, mimicking the effects of ALDH2*2.

    Tying those results to the existence of ALDH2*2 in half a billion people is a larger leap, several experts told me. There are clues of a relationship: Darwin and Stanley’s team found, for instance, that in a cohort from Vietnam and Singapore, people carrying the mutation were less likely to have active cases of TB—echoing patterns documented by at least one other study from Korea. But Daniela Brites, an evolutionary geneticist at the Swiss Tropical and Public Health Institute, told me that the connection still feels a little shaky. Other studies that have searched for genetic predispositions to TB, or resistance to it, she pointed out, haven’t hit on ALDH2*2—a sign that any link might be weak.

    The team’s general idea could still pan out. “They are definitely on the right track,” Patel told me. Throughout most of human history, infectious diseases have been among the most dramatic influences over who lives and who dies—a pressure so immense that it’s left obvious scars on the human genome. A mutation that can cause sickle cell anemia has become very common in parts of the African continent because it helps guard people against malaria.

    The story with ALDH2*2 is probably similar, Patel said. He’s confident that some infectious agent—perhaps several of them—has played a major role in keeping the mutation around. TB, with its devastating track record, could be among the candidates, but it wouldn’t have to be. A few years ago, work from Woodward’s lab showed that aldehydes can also do a number on the bacterial pathogens Staphylococcus aureus and Francisella novicida. (Darwin and Stanley’s team have now shown that mice lacking ALDH2 also fare better against the closely related Francisella tularensis.) Che-Hong Chen, a geneticist at Stanford who’s been studying ALDH2*2 for years, suspects that the culprit might not be a bacterium at all. He favors the idea that it’s, once again, malaria, acting on a different part of our genome, in a different region of the world.

    Other tiny perks of ALDH2*2 may have helped the mutation proliferate. As Chen points out, it’s a pretty big disincentive to drink—and people who abstain (which, of course, isn’t all of us) do spare themselves a lot of potential liver problems. Which is another way in which the consequences of my genetic anomaly might not be so bad, even if at first flush it seems more trouble than it’s worth.

    Katherine J. Wu

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  • How mosquito-controlling bacteria might also enhance insect fertility

    How mosquito-controlling bacteria might also enhance insect fertility

    Newswise — A new study reveals biological mechanisms by which a specific strain of bacteria in the Wolbachia genus might enhance the fertility of the insects it infects—with potentially important implications for mosquito-control strategies. Shelbi Russell of the University of California Santa Cruz, US, and colleagues report these findings in the open access journal PLOS Biology on October 24th.

    Different strains of Wolbachia bacteria naturally infect a number of different animals worldwide, such as mosquitos, butterflies, and fruit flies. Wolbachia can manipulate the fertility of their hosts through a specific biological mechanism that aids the spread of Wolbachia within host populations. In recent years, people have harnessed that mechanism in strategies to deliberately infect mosquitos with a specific Wolbachia strain, reducing targeted mosquito populations and thereby potentially reducing the spread of human viruses carried by mosquitos, such as dengue or Zika.

    Research in fruit flies suggests that that same strain, which is native to fruit flies, may also enhance insect fertility, with potentially important implications for mosquito control. Evidence suggests that biological processes involving the fruit-fly protein meiotic-P26 (“mei-P26″), which is essential for fruit-fly reproduction, may underlie this enhanced fertility. However, these processes have remained unclear.

    To investigate, Russell and colleagues bred fruit flies with various defects affecting mei-P26—resulting in reduced fruit-fly fertility—and examined what happened when they then infected the flies with the fruit-fly-native Wolbachia strain.

    They found that Wolbachia infection restored fertility in fruit flies with various mei-P26 defects, enabling them to produce more offspring than uninfected flies. Further experiments revealed how Wolbachia may restore fertility by mitigating certain perturbing effects of mei-P26 defects on specific genes and proteins, thereby resolving problems with the stem cells that produce fruit fly eggs and sperm.

    In additional experiments, Wolbachia infection also enhanced the fertility of fruit flies without mei-P26 defects, resulting in higher egg lay and hatch rates.

    These findings help to resolve the mystery of how this particular Wolbachia strain enhances fruit-fly fertility. Further research will be needed to better understand these effects and their potential implications for strategies that employ this strain to control mosquito populations.

    Russell adds, “Wolbachia endosymbionts exist at high infection frequencies in many host populations, despite exhibiting weak gene drive systems and unobserved impacts on host fitness. Here, we show that the wMel strain of Wolbachia is able to rescue and reinforce host fertility, demonstrating their capacity to function as a beneficial symbiont.”

    #####

    In your coverage, please use this URL to provide access to the freely available paper in PLOS Biologyhttp://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002335

    Press-only preview: https://plos.io/3tudL1r

     

    Image Caption: mei-P26 mutant Drosophila melanogaster ovariole infected with wMel bacterial symbionts. DNA is stained in red, anti-Vasa protein is stained blue, and anti-Hu-li tai shao ring canal protein is stained cyan.

    Image Credit: Shelbi Russell (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

    Image URL: https://plos.io/459VWBV

    Citation: Russell SL, Castillo JR, Sullivan WT (2023) Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host. PLoS Biol 21(10): e3002335https://doi.org/10.1371/journal.pbio.3002335

    Author Countries: United States

    Funding: This work was supported by the UC Santa Cruz Chancellor’s Postdoctoral Fellowship and the NIH (R00GM135583 to SLR; R35GM139595 to WTS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Competing interests: The authors have declared that no competing interests exist.

    PLOS

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  • The mechanism of tuberculosis infection via cord-like bacterial aggregates.

    The mechanism of tuberculosis infection via cord-like bacterial aggregates.

    Newswise — The ability of Mycobacterium tuberculosis (MTB), a serious respiratory infection, to form snake-like cords was first noted nearly 80 years ago. In a study published October 20 in the journal Cell, investigators report the biophysical mechanisms by which these cords form and demonstrate how several generations of dividing bacteria hang together to create these structures that enable resistance to antibiotics.

    “Our work clearly showed that cord formation is important for infection and why this highly ordered architecture might be important for pathogenesis,” says senior author Vivek Thacker (@DrVivekThacker), who led the work at the Global Health Institute at École Polytechnique Fédérale de Lausannen (EPFL) in Switzerland and is now based at the Department of Infectious Diseases at Heidelberg University in Germany.

    The study used a unique combination of technologies to address the role of MTB cord formation. One was a lung-on-chip model, which allowed the researchers to get a direct look at “first contact” between MTB and host cells at the air-liquid interface in the lungs. This revealed that cord formation is prominent in early infection. The researchers also used a mouse model that develops pathologies mimicking human tuberculosis, allowing them to obtain tissue that could be studied using confocal imaging and confirming that cording also occurs early in infection in vivo.

    The work yielded several new findings about how these cords interact with and compress the cell nucleus, how this compression affects the immune system and connections between host cells and epithelial cells, and how cord formation affects the alveoli in the lungs. The study also revealed how these cords retain their structural integrity and how they increase tolerance to antibiotic therapy.

    “There is an increasing understanding that these mechanical forces influence cellular behavior and responses, but this aspect has been overlooked since traditional cell culture models do not recapitulate the mechanical environment of a tissue,” says Melanie Hannebelle (@MelanieHanneb), formerly at EPFL’s Global Health Institute and now at Stanford University. “Understanding how forces at the cellular and tissue level or crowding at the molecular level affects cell and tissue function is therefore important to develop a complete picture of how biosystems work.”

    “By thinking of MTB in infection as aggregates and not single bacteria, we can imagine new interactions with host proteins for known effectors of MTB pathogenesis and a new paradigm in pathogenesis where forces from bacterial architectures affect host function,” says Thacker.

    Future research will focus on understanding whether cord formation enables new functionality to known effectors of MTB pathogenesis, many of which are located on the MTB cell wall. In addition, it will look at the consequence of tight-packing on the bacteria within the clump and how this may lead to a protective effect against antibiotics.

    “Antibiotic therapy is the mainstay of treatment for tuberculosis infections, but therapeutic regimens are long and complicated, with an increasing threat of drug resistance,” says Richa Mishra, the other first author who is currently at EPFL’s Global Health Institute. “There is a recognized need for host-directed therapies or therapies that inhibit specific virulence mechanisms that can shorten and improve antibiotic therapy.”

    Cell Press

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  • Pfizer gets FDA green light for new shot that can streamline teenagers’ vaccinations

    Pfizer gets FDA green light for new shot that can streamline teenagers’ vaccinations

    Pfizer Inc.
    PFE,
    -1.73%

    said Friday that the U.S. Food and Drug Administration has approved the first five-in-one vaccine designed to protect teenagers and young adults against meningococcal disease. 

    The new Pfizer shot, Penbraya, protects against the five most common subgroups of meningococcal disease, a rare but serious and potentially fatal illness that most often affects babies and teenagers. 

    Penbraya “has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots,” Annaliesa Anderson, Pfizer senior vice president and head of vaccine research and development, said in a statement. 

    The U.S. Centers for Disease Control and Prevention currently recommends that all 11- to 12-year-olds get a meningococcal vaccine protecting against four of the subgroups — A, C, W and Y — and get a booster dose of the same vaccine type at age 16. Teenagers and young adults age 16 to 23 may also get a meningococcal B vaccine, the CDC says, particularly if they’re at increased risk due to other health conditions. 

    The complex vaccination schedule has weighed on uptake of the meningococcal shots, and the COVID-19 pandemic may have compounded the problem, as many families missed routine appointments when vaccinations were due, researchers say. Among teenagers who were born in 2008 — who were due for their routine adolescent vaccinations as the pandemic was raging in 2020 — uptake of meningococcal and other recommended vaccines declined, according to CDC research. Only about 60% of the 17-year-olds surveyed by the CDC last year had received both recommended doses of the ACWY vaccine, and fewer than 30% had received at least one dose of the meningococcal B vaccine. 

    The new Pfizer shot combines components of a meningococcal group B vaccine and an ACWY vaccine. 

    A CDC immunization advisory committee is set to meet Oct. 25 to discuss recommendations for the use of Penbraya in teenagers and young adults, Pfizer said. 

    The green light for Penbraya gives Pfizer the edge in its race with GSK
    GSK,
    +0.54%
    ,
    which is also working on a five-in-one meningococcal shot. GSK earlier this year released positive late-stage clinical-trial results for that vaccine. 

    The FDA approval of Pfizer’s shot caps a rocky week for the pharmaceutical giant, which late last Friday cut $9 billion from its full-year revenue guidance due to reduced COVID sales expectations and announced a cost-cutting program designed to deliver savings of at least $3.5 billion. Pfizer executives said on a call with analysts Monday that development of combination respiratory vaccines, such as those that provide COVID and flu protection in one shot, remains a focus for the company, in part because they can help boost vaccine uptake.

    Pfizer shares were down 1.7% Friday and have dropped 40% in the year to date, while the S&P 500
    SPX
    has gained 10%.

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  • Johns Hopkins Study Supports Potential for Injectable ‘Chemical Vaccine’ For Malaria Using Atovaquone

    Johns Hopkins Study Supports Potential for Injectable ‘Chemical Vaccine’ For Malaria Using Atovaquone

    Newswise — Johns Hopkins researchers looking to develop a long-acting, injectable malaria preventive using atovaquone have shown in a new study that resistance may not be the challenge scientists thought it was, particularly when using atovaquone as a malaria preventive. Malaria parasites in infected patients being treated with atovaquone tend to develop a resistance to the drug. Because of this, atovaquone by itself is not used as a malaria treatment nor has not been seen as a strong candidate for use as a preventive.

    The study, led by a team of researchers at the Johns Hopkins Malaria Research Institute and the Johns Hopkins University School of Medicine, in conjunction with colleagues at the University of Liverpool, was published online October 12 in Nature Communications. The Malaria Research Institute is based at the Johns Hopkins Bloomberg School of Public Health.

    In their study, the researchers found that the same genetic mutation that renders malaria parasites resistant to atovaquone in patients also destroys the parasite’s ability to live within mosquito hosts—meaning atovaquone-resistant malaria parasites would not be transmissible. The researchers concluded that atovaquone, despite concerns over resistance, holds promise as a long-acting, injectable “chemical vaccine” that could prevent infection in malaria-endemic areas.

    “These findings should reduce concerns about the transmission of atovaquone resistance with atovaquone therapy, particularly when it is used as a chemical vaccine,” says study senior author Theresa Shapiro, MD, PhD, professor of Clinical Pharmacology in the Johns Hopkins University School of Medicine and professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Bloomberg School.

    Malaria continues to be a major global health burden. According to the World Health Organization, the mosquito-borne parasitic disease afflicted nearly a quarter of a billion people in 2021, killing more than 600,000. Researchers generally agree that, despite the impact of insecticides and other malaria control measures, and the recent development of a malaria vaccine, new approaches against this deadly parasitic pathogen are needed.

    One new approach, described by Shapiro and colleagues at the University of Liverpool in a 2018 preclinical study, would use an injectable, slow-release formulation of atovaquone to provide vaccine-like protection for weeks at a time. Atovaquone is generally considered safe for long-term use even at higher doses, and has the further advantage that it interrupts the malaria life-cycle in human hosts even at the pre-symptomatic stage, when the parasite is developing in liver cells.

    However, when atovaquone is used not as a preventive but as a treatment for symptomatic malaria infection, it often fails due to the emergence of genetically acquired resistance. Shapiro notes that by the time an infection is symptomatic, it involves billions of individual malaria organisms, and in this vast population it is likely that a resistance mutation will appear, if only by random genetic variation. Under atovaquone treatment, parasites with this mutation will come to dominate the infection. Because of the resistance problem, atovaquone is used to treat malaria only in combination with another antimalarial called proguanil.

    Resistance should be much less likely when using atovaquone as a preventive in people who are malaria-free, Shapiro says. The drug in such cases would be acting against a far smaller number of individual parasites that are only in the early, liver-infection stage.

    “In fact, there are no reported cases of atovaquone resistance when the drug has been given prophylactically,” she says.

    Nevertheless, fear of resistance has left a cloud over the drug’s use even as a preventive. Indeed, there have been concerns that the mutation, once it emerged—for example, in a large population treated prophylactically with atovaquone—could spread via human-to-mosquito-to-human transmission.

    In the study, Shapiro’s team examined the resistance problem, focusing on a key resistance mutation, cytochrome-b Y268S, that has been found in clinical investigations involving the major malaria parasite of concern, Plasmodium falciparum. The researchers confirmed that P. falciparum parasites carrying this mutation are thousands of times less susceptible to atovaquone, compared to unmutated parasites.

    However, the scientists also found that the Y268S mutation, while it enables P. falciparum to survive in human hosts being treated with atovaquone, essentially destroys its ability to live within its Anophelesmosquito hosts. This means that atovaquone-resistant mutant parasites cannot spread via transmission from humans to mosquitoes and back again—as the researchers demonstrated using mosquitoes and a P. falciparum-infectable mouse model. For the study, the mice were engrafted with human liver cells and human red blood cells.

    “Testing the mutant parasites for their ability to infect humanized mice is the best in vivo assay we have short of using humans, and strongly supports the inability of drug-resistant parasites to be transmitted by mosquitoes,” says Photini Sinnis, MD, deputy director at the Johns Hopkins Malaria Research Institute and one of the paper’s senior authors.

    The findings suggest that a “chemical vaccine” strategy for protecting people from malaria with atovaquone remains viable and should continue to be investigated. Shapiro and colleagues are collaborating with Andrew Owen, PhD, a professor at the University of Liverpool, and his team to complete preclinical studies and launch a Phase I trial. Owen is principal investigator for LONGEVITY, an international project funded by Unitaid that aims to translate long-acting medicines for malaria and other diseases that disproportionately affect people in low- and middle-income countries.

    “Many advances in malaria medicines that have started at small scale for the protection of travelers, later see wider use in endemic areas where they are most needed—and this may be the path atovaquone takes as a chemical vaccine,” Shapiro says.

    The study’s first author was Victoria Balta, PhD, a graduate student working with coauthor David Sullivan, MD, a professor in the Bloomberg School’s Department of Molecular Microbiology and Immunology.

    Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito” was co-authored by Victoria A. Balta, Deborah Stiffler, Abeer Sayeed, Abhai Tripathi, Rubayet Elahi, Godfree Mlambo, Rahul Bakshi, Amanda Dziedzic, Anne Jedlicka, Elizabeth Nenortas, Keyla Romero-Rodriguez, Matthew Canonizado, Alexis Mann, Andrew Owen, David Sullivan, Sean Prigge, Photini Sinnis and Theresa Shapiro.

    Funding was provided by Unitaid (2020-38-LONGEVITY); the Johns Hopkins Malaria Research Institute and Bloomberg Philanthropies; and the National Institutes of Health (R01AI132359, R01AI1095453, T32AI138953).

    Disclosures
    Johns Hopkins co-authors Rahul P. Bakshi, Godfree Mlambo, Theresa A. Shapiro, Abhai K. Tripathi, and co-author Andrew Owen of the University of Liverpool, are co-inventors on PCT/GB2017/ 051746 (Atovaquone long-acting injectable formulation).

    Additional author disclosures appear in the Competing interests section at the end of the paper, which is open access.

    # # #

    Johns Hopkins Bloomberg School of Public Health

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  • UM School of Medicine Researchers Provide First Statewide Prevalence Data on Two New Emerging Pathogens in Healthcare Settings

    UM School of Medicine Researchers Provide First Statewide Prevalence Data on Two New Emerging Pathogens in Healthcare Settings

    Newswise — University of Maryland School of Medicine (UMSOM) researchers conducted a statewide survey of all patients on breathing machines in hospitals and long-term care facilities and found that a significant percentage of them harbored two pathogens known to be life-threatening in those with compromised immune systems. One pathogen, Acinetobacter baumannii, was identified in nearly 31 percent of all patients on ventilators to assist with their breathing; Candida auris was identified in nearly 7 percent of patients on ventilators, according to the study which was published this week in the Journal of the American Medical Association.  

    They conducted the study with colleagues at the Maryland Department of Health and presented their findings at this week’s Infectious Disease Society of America annual meeting in Boston.

    “We found patients in long-term care facilities, like skilled nursing homes, were more likely to be colonized with these pathogens than those getting treated in hospitals,” said study leader Anthony Harris, MD, MPH, Professor of Epidemiology & Public Health at UMSOM and infectious disease specialist at University of Maryland Medical Center. “We were the first in the nation to get a statewide survey of all ventilated patients, and I think it points to the stringency of the infection control programs in place in the state of Maryland and the excellent collaboration between the University of Maryland and the State Health Department.”

    Both A. baumannii and C. auris have been highlighted by the federal Centers for Disease Control and Prevention (CDC) as emerging pathogens that present a global health threat. C. auris is a fungus that spreads within and among local healthcare facilities–usually in those hospitalized and on breathing machines (ventilators). Older people with weakened immune systems are particularly susceptible to this infection, which resists treatment with common anti-fungal medications. A. baumannii, a bacteria, also poses a threat to these same types of  patients and has become very resistant through the years to treatment with most  antibiotics.

    To conduct the study, Dr. Harris and his colleagues obtained culture swabs from all 482 patients receiving mechanical ventilation in Maryland healthcare facilities between March and June of this year. All eligible healthcare facilities, 51 in total, participated in the survey. They identified A. baumannii from at least one patient in one-third of the acute care hospitals and from 94 percent of the long-term care facilities. They identified C. auris in nearly 5 percent of hospitalized patients and in 9 percent of patients in long-term care facilities.

    “Testing positive, however, does not mean that patients have symptoms or active infections that are potentially life-threatening,” said study co-author J. Kristie Johnson, PhD, Professor of Pathology at UMSOM whose lab did the A. baumannii testing for the study. “But knowing which patients are colonized with these pathogens can help contain their spread to other patients.”

    Over the course of 2022, state and local health departments around the country reported 2,377 clinical cases, according to the CDC, nearly five times the number infections in 2019, which was less than 500 cases. Maryland alone had 46 cases in 2022. While these infections don’t normally pose much of health risk to hospital workers, they pose a significant risk of death in patients with weakened immune systems. Often the infections can be spread from patient to patient by health care workers carrying the germs on their hands, equipment or clothing.

    “There is a need for more health care facilities nationwide to be aware of the extent of the problem through surveillance testing,” Dr. Harris said. Certain measures can be implemented to help reduce spread of these pathogens including more stringent use of disposable gloves and gowns between patients and the use of chlorhexidine bathing of the critically ill to disinfect their skin.

    “Emerging pathogens that are resistant to available therapeutics present a growing challenge in our country, especially with a projected increased growth in our aging population entering long term care facilities,” said UMSOM Dean Mark Gladwin, MD, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM.  “Nearly half of patients who contract C. auris infections die within 90 days, according to the CDC, and this pathogen is now found in nearly 50 states. This is why it is critical for these surveillance studies to be conducted nationwide, not just in Maryland.”

    UMSOM faculty members Lisa Pineles, MA, Lyndsay O’Hara, PhD, Leigh Smith, MD, and Indira French, MS, were co-authors on this study. The study was funded by a grant from the CDC (1U54CK000450-01).

    About the University of Maryland School of Medicine

    Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $500 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2023, the UM School of Medicine is ranked #10 among the 92 public medical schools in the U.S., and in the top 16 percent (#32) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

    University of Maryland School of Medicine

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  • Prior infections and vaccinations affect COVID-19 mutation vulnerability, per study.

    Prior infections and vaccinations affect COVID-19 mutation vulnerability, per study.

    Newswise — A person’s immune response to variants of SARS-CoV-2, the virus that causes COVID-19, depends on their previous exposure – and differences in the focus of immune responses will help scientists understand how to optimise vaccines in the future to provide broad protection.

    A new study has found that people differ in how vulnerable they are to different mutations in emerging variants of SARS-CoV-2.

    This is because the variant of SARS-CoV-2 a person was first exposed to determines how well their immune system responds to different parts of the virus, and how protected they are against other variants.

    It also means that the same COVID-19 vaccine might work differently for different people, depending on which variants of SARS-CoV-2 they have previously been exposed to and where their immune response has focused.

    The discovery underlies the importance of continuing surveillance programmes to detect the emergence of new variants, and to understand differences in immunity to SARS-CoV-2 across the population.

    It will also be important for future vaccination strategies, which must consider both the virus variant a vaccine contains and how immune responses of the population may differ in their response to it.

    “It was a surprise how much of a difference we saw in the focus of immune responses of different people to SARS-CoV-2. Their immune responses appear to target different specific regions of the virus, depending on which variant their body had encountered first,” said Dr Samuel Wilks at the University of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, first author of the report.

    He added: “Our results mean that if the virus mutates in a specific region, some people’s immune system will not recognize the virus as well – so it could make them ill, while others may still have good protection against it.”

    The research, published today in the journal Science, involved a large-scale collaboration across ten research institutes including the University of Cambridge and produced a comprehensive snapshot of early global population immunity to COVID-19.

    Researchers collected 207 serum samples – extracted from blood samples – from people who had either been infected naturally with one of the many previously circulating SARS-CoV-2 variants, or who had been vaccinated against SARS-CoV-2 with different numbers of doses of the Moderna vaccine.

    They then analysed the immunity these people had developed, and found significant differences between immune responses depending on which variant a person had been infected with first.

    “These results give us a deep understanding of how we might optimise the design of COVID-19 booster vaccines in the future,” said Professor Derek Smith, Director of the University of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, senior author of the report.

    He added: “We want to know the key virus variants to use in vaccines to best protect people in the future.”

    The research used a technique called ‘antigenic cartography’ to compare the similarity of different variants of the SARS-CoV-2 virus. This measures how well human antibodies, formed in response to infection with one virus, respond to infection with a variant of that virus. It shows whether the virus has changed enough to escape the human immune response and cause disease.

    The resulting ‘antigenic map’ shows the relationship between a wide selection of SARS-CoV-2 variants that have previously circulated. Omicron variants are noticeably different from the others – which helps to explain why many people still succumbed to infection with Omicron despite vaccination or previous infection with a different variant.

    Immunity to COVID-19 can be acquired by having been infected with SARS-CoV-2 or by vaccination. Vaccines provide immunity without the risk from the disease or its complications. They work by activating the immune system so it will recognise and respond rapidly to exposure to SARS-CoV-2 and prevent it causing illness. But, like other viruses, the SARS-CoV-2 virus keeps mutating to try and escape human immunity.

    During the first year of the pandemic, the main SARS-CoV-2 virus in circulation was the B.1 variant. Since then, multiple variants emerged that escaped pre-existing immunity, causing reinfections in people who had already had COVID.

    “The study was an opportunity to really see – from the first exposure to SARS-CoV-2 onwards – what the basis of people’s immunity is, and how this differs across the population,” said Wilks.

    University of Cambridge

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  • It’s October and it’s not too late to get a flu shot

    It’s October and it’s not too late to get a flu shot

    BYLINE: Eric Gorton, media relations coordinator

    HARRISONBURG, Va. — About a month into flu season JMU professor Suzanne Grossman says it is not too late to get a flu shot.

    “I get the flu shot every year and I usually get that sometime in October,” she said.

    As the months get colder viruses spread rapidly, said Grossman, a professor of health sciences who teaches a class on infectious diseases. “This means people are closer together, which increases the likelihood that the virus will spread and also because it’s cooler outside, we’re not opening windows and having better ventilation, which can also increase the spread of the virus,” she said.

    In addition to flu and the common cold, COVID cases are on the rise. Grossman said the newest vaccine is effective against the latest subvariant and is recommended for people who have not had the virus or the shot in the last two months.

    When talking about vaccine effectiveness Grossman offered, “They’re especially effective in preventing against severe illness as well as hospitalization and death. So, people who are vaccinated might still get ill with COVID or the flu but the illness that they get will likely be much less severe than if they hadn’t been vaccinated against the flu or COVID.” 

    There’s no vaccine for the common cold, but there are measures to help protect against it. Grossman suggests washing hands, covering your nose and mouth when coughing or sneezing, and wearing a mask if you must go out.

    Audio of Grossman’s comments is here: https://www.dropbox.com/scl/fi/qwaq5zalj5prw0nyvbtxx/230929-Grossman-update-clips.wav?rlkey=hzhksgw0tswsuml0r5mmoud12&dl=0

    A transcript of her comments is here: https://www.dropbox.com/scl/fi/axexlmnb551et5tk1qurw/230928-Grossman-transcript-flu-season.docx?rlkey=st8inzpracnnd17ivskgw6o5k&dl=0

     

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    James Madison University

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