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Antimicrobial resistance is a growing threat to good health and well-being

Antimicrobial resistance is growing worldwide, rendering many "work horse" medicines ineffective. Without intervention, drug-resistant pathogens could lead to millions of deaths by 2050. Thankfully, companies like Pfizer are taking action.

Image courtesy of Pfizer.
  • Antimicrobial-resistant pathogens are one of the largest threats to global health today.
  • As we get older, our immune systems age, increasing our risk of life threatening infections. Without reliable antibiotics, life expectancy could decline for the first time in modern history.
  • If antibiotics become ineffective, common infections could result in hospitalization or even death. Life-saving interventions like cancer treatments and organ transplantation would become more difficult, more often resulting in death. Routine procedures would become hard to perform.
  • Without intervention, resistant pathogens could result in 10 million annual deaths by 2050.
  • By taking a multi-faceted approach—inclusive of adherence to good stewardship, surveillance and responsible manufacturing practices, as well as an emphasis on prevention and treatment—companies like Pfizer are fighting to help curb the spread.

Antibiotics have revolutionized healthcare.

With the advent of modern medicine, life threatening diseases such as smallpox, pertussis (whooping cough), tetanus (lockjaw) and measles have essentially been eradicated. More importantly, complicated procedures that increase our risk of infections—including plastic surgery, joint replacement, cancer treatments, and organ transplant, among others—have become routine because any resulting infection can be treated effectively.

But modern medicine depends on antibiotics to treat and cure many kinds of infections—infections that could impact anyone from the premature baby to the elderly. Unfortunately, antimicrobial resistance (AMR) has made some infections impossible and others increasingly difficult to treat, threatening the progress we have worked so hard to achieve.

AMR causes 700,000 deaths annually across the globe, a number projected to skyrocket to 10 million by 2050 without intervention.

What is antimicrobial resistance?

Antimicrobial drugs target the microorganisms that cause infection, such as bacteria, viruses, fungi, and parasites, and either kills them or inhibits their growth.

Anytime an antibiotic is used, either appropriately or inappropriately, the 30 trillion or more bacteria that live in or on our bodies undergo selective pressure to become resistant. Any that are sensitive to the antibiotic are killed, while those that remain are resistant or immune from the effects of that antibiotic. This is called AMR. Once a bacterial pathogen has reached a state of resistance to several types of antibiotics, it is colloquially referred to as a "superbug."

The consequences of AMR can be stated simply: Commonly used antibiotics are rendered ineffective against that pathogen. If an infection caused by resistant bacteria is treated by that antibiotic, the bacteria are unaffected, resulting in disease persistence, worsening of the infection and/or even death. Treatments for both minor and serious infections are compromised, surgeries and other routine procedures become riskier, and the treatment of diseases like pneumonia and tuberculosis becomes very complicated. For example, according to the World Health Organization, resistance in Klebsiella pneumoniae—a common intestinal bacterium that is a major cause of hospital-acquired infections, bloodstream infections, and infections in newborns and intensive-care unit patients—has spread to all regions of the world. In some countries, because of resistance, carbapenem antibiotics (often the "last resort" treatments) do not work in more than half of people treated for these types of infections. This results in prolonged hospitalization, increased medical costs and higher rates of death for infections that were easily treated only a few years ago.

"What's more, AMR is a truly global issue—it can affect anyone, of any age, in any country," Jill Inverso, Pfizer's Vice President of Global Medical Affairs and Anti-Infectives, told Big Think.

AMR causes 700,000 deaths annually across the globe, a number projected to skyrocket to 10 million by 2050 without intervention. The rise of resistant pathogens is causing many countries to accrue significantly higher healthcare costs due to longer duration of illness, additional tests, and the need for different medicines to treat patients.

And these costs add up. The World Bank Group estimates that AMR could reduce annual global gross domestic product from 1.1–3.8 percent depending on severity, with up to $10.8 trillion in additional health expenditures.

At Pfizer, we take this growing threat very seriously and are driven by our desire to protect global public health and address the medical needs of people suffering from infectious diseases.

Giving antimicrobial resistance a helping hand

The development of bacterial resistance to antibiotics is a natural process. Unlike almost every other class of drugs, antibiotics drive their own obsolescence by selecting antibiotic-resistant bacteria, even when used appropriately according to guidelines. When this happens, resistant bacteria survive and continue to multiply, causing the infection to worsen. These resistant bacteria can then also spread to other patients, causing new infections with these bacteria that are difficult to treat.

Overuse and misuse of antibiotics accelerates this process without providing any benefit to the patient. This happens when patients take a drug without need, do not finish their dose or stop taking the medication mid-course; it could also happen when a drug is either overprescribed or prescribed for the wrong duration/type of illness. All of these misuses create environments in which pathogens are exposed to drugs more often, allowing them to acclimate and breed resistance without any benefit to the patient.

Hence, antibiotics must be used wisely and sparingly.

Fighting the resistance

WHO calls AMR an "increasingly serious threat to global public health" and one that "requires action across all government sectors and society." Its widespread growth is threatening the United Nations General Assembly's Sustainable Development Goal of Good Health and Well-Being.

Companies like Pfizer are heavily committed to the fight against AMR, taking action across a variety of areas such as surveillance, stewardship, and prevention and treatment.

On the surveillance front, Pfizer is proud to sponsor one of the largest AMR surveillance programs in the world, the Antimicrobial Testing Leadership and Surveillance (or ATLAS). ATLAS monitors real-time changes in bacterial resistance and tracks these trends in real-time. Gathering information from more than 760 hospitals across 73 countries in many underserved areas, ATLAS has generated 14 years of continuous global data on bacteria. Researchers and healthcare professionals can access ATLAS's data—free of charge—to study resistance trends, even in emerging market countries like Africa, Asia, and Latin America.

"At Pfizer, we take this growing threat very seriously," Inverso added, "and are driven by our desire to protect global public health and address the medical needs of people suffering from infectious diseases."

Pfizer also encourages good stewardship practices and supports education and training programs to help ensure patients receive the correct antibiotic only if needed, at the right dose and for the right duration.

"We believe that everybody can play a part in AMR stewardship by not taking an antibiotic unless provided by a healthcare professional, sticking to antibiotic regimens when prescribed, and keeping their vaccinations up to date," said Inverso. She added, "Vaccines are administered to help prevent infections from happening in the first place, thereby reducing the need for antibiotic usage that can lead to the development of resistance."

To date, several studies have demonstrated the beneficial role vaccines play in the reduction of AMR, such as reducing the use of antibiotics by preventing bacterial infections which may, in turn, prevent antimicrobial resistant infections from developing. Pfizer is committed to continue the development of new, innovative vaccines to help prevent infectious diseases globally.

We believe that everybody can play a part in AMR stewardship by not taking an antibiotic unless provided by a healthcare professional, sticking to antibiotic regimens when prescribed, and keeping their vaccinations up to date.

Given this, we should ask ourselves the following:

  • Have I ever not finished an antibiotic given to me by my doctor?
  • Have I ever used an antibiotic given to someone else?
  • Am I up-to-date on my vaccinations that prevent infections that would need antibiotics?
  • Have I ever demanded an antibiotic for myself or a child that the doctor thought was caused by a virus?
  • Have I ever saved antibiotics given to me for one infection and used it at a different time?

The key takeaway? AMR is a pervasive, growing threat that cannot be tamed without the collective efforts of government, industry, health systems, society and others. Working together, we may have a fighting chance.

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Chronic stress and captive orcas

A new study lays out the case for the damaging effects of stress on orcas living in tanks.

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  • There are currently around 60 orcas living in concrete tanks globally.
  • Orcas' brain structures and behaviors strongly suggest smart, emotional, self-aware beings.
  • The study provides compelling evidence that the stresses inherent in captivity do damage to these naturally free-roaming cetaceans.

A study, "The harmful effects of captivity and chronic stress on the well-being of orcas (Orcinus orca)" recently published in Journal of Veterinary Behavior is the product of a unique collaboration of experts in marine mammal science, veterinary science, internal medicine and psychiatry. It makes the case for a careful consideration of the impacts of chronic stress on captive orcas, at least 60 of whom are currently in captivity. Most have spent years or decades of their lives in these conditions. 56.7% of these orcas were born in captivity, with 26 captured young. (Orcas are actually the third most commonly confined cetaceans — there are even more bottlenose dolphins and beluga whales held in tanks.)

The study explains how the continual, oppressive stress inherent to a captive orca's life is unhealthy and should be more thoughtfully addressed. Study lead author biopsychologist Lori Marino tells Big Think in an email:

"Our review shows that intelligence, complexity, and awareness are characteristics that make an animal more — not less — vulnerable to the effects of captivity. That seems counterintuitive because a lot of people think that the more mental resources you have the better you are able to cope with various situations. But it is also the case that the more mental capacity you have the greater your needs in order to thrive and the more extreme the impact of living in an artificial environment, that is, an environment outside your adaptive envelope."

While skeptics may consider it a leap to assume that orcas are intelligent and emotional enough to suffer the ill effects of stress, Marino responds, "That would be a claim in search of evidence. Stress is a common phenomenon in all mammals and many other organisms. The effects of chronic stress have been well-studied in mice, rats, dogs, etc." The study provides ample evidence that orcas are exceptionally intelligent, feeling creatures in any event.

The orca brain

Image source: FineShine/Shutterstock

The orca brain exhibits neurobiological traits that are considered prerequisites for complex psychology, emotion, and behavior:

  • a large brain size
  • an expanded neocortex
  • a well-differentiated cortical cytoarchitecture
  • an elaborated limbic system.

Even more important than sheer brain size is its size in relation to an animal's body. This is captured as the organism's encephalization quotient, or EQ. Says the study, "Odontocetes, and in particular Delphinoidea [the superfamily to which orcas belong], are the most highly encephalized nonhuman taxonomic group known … except modern humans."

Orcas also have the most highly convoluted, or folded, neocortical surface of all mammals including humans, and their ratio of neocortical surface to brain weight also exceeds the human brain's, suggesting an organ well-suited to higher-order functions.

Among a range of other clues presented by the study that suggest orcas are highly intelligent creatures are these:

  • Areas associated in the human brain with high-level cognitive and social functions including attention, prediction, social awareness, and empathy are all highly developed in orcas.
  • Orcas have a well-integrated mammalian limbic system that supports having emotions, memory, motivation, reasoning, learning, and abstraction.

Supporting behaviors

Image source: Willyam Bradberry /Shutterstock

Observations of orca behavior richly supports the implications of their neurobiological structures. Marino says, "Free-ranging orcas live in tightly-knit social groups that are necessary during their long juvenile periods and afterwards. They support each other, help each other when in trouble, and grieve each other. Mothers and calves are very tightly bonded. In some groups, male orcas stay with their mom their whole life and if mom dies [the male offpsring] may go into a deep depression and die as well. Family and social group are everything."

Orcas also demonstrate culture, with vocalizations and even hunting methods unique within groups and passed from generation to generation.

"Orcas at Punta Norte, Argentina, hunt sea lion and elephant seal pups by beaching themselves and capturing the pups, typically in the surf zone," according to the study.

Captivity morbidities

Image source: Peter Etchells/Shutterstock

In the wild, free-ranging female orcas live an average of 46 years — some live as long as 90 years — and males 31 years, or as long as 50-60 years. Captive orcas rarely live more than 30 years, with many dying in their teens or 20s. Their medical histories can be difficult to access due to facilities' desire for confidentiality. Nonetheless, some morbidities, or causes of death, have become clear over time.

One review from 1979 identified infectious disease as the culprit behind the death of 17 captive North American orcas who'd died since 1965 prior to the report's writing. The new study cites publicly available documentation revealing that between 1971 and 2017, SeaWorld parks alone have experienced 35 documented orca deaths, and that, "When causes of death were available, the most commonly implicated conditions were viral, bacterial and fungal infections, gastrointestinal disease, and trauma."

Infections such as these may not in and of themselves have necessarily been lethal, but when combined with orcas' "weakened immune system, chronic exposure to chemical irritants or trauma to the skin, excessive or improper use of antimicrobials, and an imbalance in the microbiota of the body or environment (which may exist in tanks)," they become deadly. Common fungal infections may also especially dangerous in this context "as a result of long-term and aggressive antibiotic treatment, overtreatment of water for purity, or both." The same is true for untreated dental infections.

Another frequent cause of orca death: gastrointestinal ulceration — ulcers — caused by prolonged exposure to stress.

The destructive power of stress

Image source: eldeiv/Shutterstock

"Importantly, the poor health and short lifespans of captive orcas are most clearly understood as connected elements in a cycle of maladaptiveness to the conditions of captivity that involves behavioral abnormalities, physical harm and vulnerability to disease."

The paper shows, says Marino, that "when you examine the totality of the welfare findings for captive orcas the whole picture fits best within a larger common framework of evidence on how stress effects captive animals. We know that, when confined, other animals show the same kinds of behavioral and physiological abnormalities that captive orcas do. This is not mysterious or even controversial. It is basic science."

Marino cites as especially damaging the manner in which captivity prevents orcas from making social connections. Tanks also deprive them of places to retreat, making conflicts inescapable even temporarily. Finally, captive orcas are likely to become bored and chronically demotivated by the frustration over their loss of autonomy.

The study also notes physical effects brought on by long-term stress, including:

  • the release of too much cortisol by the hypothalamus-pituitary-adrenal, or HPA, axis, causing elevated blood sugar, suppression of the immune system, as well as metabolism and blood pressure issues.
  • alterations of the hippocampus, amygdala, and prefrontal cortex due to prolonged stress, potentially leading to Increased anxiety, post-traumatic stress, cognitive impairment, depression, and mood dysregulation.
  • organ degradation in response to unrelenting stress.
  • a loss of natural sensory information, about which, says the study, "a growing body of research has found that exposure to excessive or unnatural levels or types of acoustic input can cause a number of impacts to cetaceans, including but not limited to … accelerated aging, suppression of the immune response, as well as premature hearing loss."

A valuable conversation

Marino explains why it was important to conduct this study, saying, "My co-authors and I wrote this review to bring all of the available information on captive orca well-being together in one place and to suggest that we might all best be able to understand the effects of captivity within a very familiar and well-researched model of how chronic stress effects all organisms. We want this paper to be a catalyst for dialogue and further scientific exploration based on data as to how we can better understand who orcas are and how we can identify the important elements needed in a captive environment for them to thrive."

The Whale Sanctuary Project is hosting a free public webinar to discuss the study and the effects of stress on captive orcas with three of the study's authors Tuesday, July 14, 2020.

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