Fungus Immune To Drugs Quietly Sweeps The Globe; The Next Pandemic, How Plagues Really Work

Fungus Immune To Drugs Quietly Sweeps The Globe; The Next Pandemic, How Plagues Really Work
     The title above comes from Matt Richtel and Andrew Jacobs’s April 7, 2019, front-page article in the New York Times. They have a lengthy article about a mysterious new bug/fungus that “is quietly sweeping the globe,” and is resistant to antibiotics. I refer you to their article for additional background material. “The germ, a fungus called Candida auris, preys on people with weakened immune systems,” they wrote. “Over the past five years,” they note, “it has hit a neonatal unit in Venezuela, swept through a hospital in Spain, forced a prestigious medical center in Britain to shut down its intensive care unit, and taken root in India, Pakistan, and South Africa.” 
     “Recently, Candida auris reached New York, New Jersey, and Illinois, prompting the Federal Center for Disease Control and Prevention (CDC) to add it to a list of germs deemed an ‘urgent threat,” Mr. Richtel and Mr. Jacobs wrote. A patient who was diagnosed with the fungus at New York’s Mount Sinai Hospital in May of 2017, “died ninety days later in the hospital; but, C. auris did not. It was everywhere in his room, so invasive that the hospital needed special cleaning equipment; and, had to rip out some of the ceiling and floor tiles to eradicate it.”
     “Everything was positive — the walls, the bed, the doors, the curtains, the sink, the phones, the whiteboard, the poles, and the pump,” said Dr. Scott Lorin, the hospital’s president. “The mattress, the bed rails, the canister holes, the window shades, the ceiling, everything in the room was positive,” she told the NYTs.
     “C. auris is so tenacious in part,” Mr. Richtel and Mr. Jacobs note, “because it is impervious to major anti-fungal medications, making it a new example of one of the world’s most intractable health care threats: the rise of drug resistant infections.”  Dr. Lynn Sosa, Connecticut’s Deputy State Epidemiologist, told the NYTs that she now sees C. auris as “the top” threat among resistant infections. “It is pretty much unbeatable, and difficult to identify,” she said.
     “Nearly half the patients who contract C. auris, die within 90 days,” according to the CDC; and, its origin remains a medical mystery. “It’s a creature from the Black Lagoon,” said Dr. Tom Chiller, who heads the fungal branch at the CDC, which is spearheading a global detective effort  to find a treatment’s, and stop the infection,” Mr. Richtel and Mr. Jacobs wrote.
     “In the U.S. 587 cases of people having contracted C. auris have been reported, with 300 of those in New York, 104 in New Jersey, and 144 in Illinois,” according to the CDC. The earliest known case diagnosed in the U.S. occurred in New York, in May of 2013, a woman who was in her early 60s from the United Arab Emirates — though the NYTs said she was probably not the first person in the U.S. to contract the disease.
The Next Pandemic; How Plagues Really Work
     Not mentioned in the article was how infectious, or not, this fungus is. It would seem for now, mostly resigned to those with weakened/compromised immune systems.  Thank goodness for that, as 50 percent lethality would put it on par with the Black Plague of the 1300s and the Spanish flu outbreak in 1918. “According to the evolutionary epidemiologist Paul W Ewald, of the University of Louisville, the most dangerous infectious diseases are almost always not animal diseases freshly broken into the human species; but, diseases adapted over time: smallpox, malaria, tuberculosis, leprosy, typhus, yellow fever, polio. In order to adapt to the human species, a germ needs to cycle among people — from person to person. In each iteration strain,” wrote Wendy Orent, author of The Next Pandemic: How Plagues Really Work,”  “the strains best adapted to transmission, will be the ones that spread. So, natural selection will push circulating strains toward more and more effective transmission, and therefore, towards increasing adaptation to human hosts. This process necessarily takes place among people.”
     “One mysterious, ancient outbreak, the Great Plague of Athens, shows how deadly epidemics unroll in time,” Ms Orent suggests. “The [Athens] Plague, — said to have been caused by typhus, measles, small pox, or Ebola, depending on whom you ask — exploded in Athens in the summer of 430 BCE, during the early days of the Peloponnesian War, an [epic] 27 year struggle between Athens and Sparta over hegemony in the Hellenic world. Pericles, the de facto leader of Athens — who pushed for war, developed a defensive strategy that proved fatal, to him; and, as many as a third of Athenian citizens. He insisted on bringing all citizens — people who lived in towns and the rural areas outside the city — into Athens, leaving the rest of the city-state to be ravaged by the invading Spartans. The Athenian Long Walls ran down to the separate ports of Piraeus and Phaleron, each of which lay about four miles from the city of Athens proper. Thus, sealed off, fronting only on the sea, Athenians could shelter safely Pericles argued, until the Peloponnesian War.”

     “The normal population of the [ancient] city [Athens] was around 150,000. Scholars estimate that 200,000 – 250,000 farmers and townsmen; and, their families, came streaming in, bringing everything they could carry with them — down to the woodwork of their farmhouse walls. But, Pericles made no provision for the newcomers, who were used to their country manors, their quiet towns, their open fields,” Ms. Orent elegantly writes. A few had homes, or relatives within the walls. But, most had no where to go, and huddled in stifling huts, or tents flung up in the narrow spaces between the walls. The crowded encampments were ripe for a virulent infection,” she writes.

“Physicians and attendants died quickly, and the only people who could care for the sick, were survivors immune to further infection.”

“The infection came from the sea,” Ms. Orent notes, “the portal that Pericles had left open to feed the Athenian people and bring in enough money to keep the war effort alive. The Athenian historian Thucydides tells us that the disease originated in Ethiopia, travelled northward into Egypt, and Libya, moved across the Mediterranean to the island of Lemnos, and on to Athens. ‘There was no record of the disease being so virulent anywhere else, or causing so many deaths as it did in Athens,’ wrote Thucydides; and, we have no reason to doubt him. This is a critical bit of information,” Ms. Orent contends. “It tells us,” she argues, “that The Great Plague evolved: it became much more lethal in the great refuge camp of wartime that Athens had become. Thucydides continued: “People in perfect health, suddenly began to have burning feelings in the head; their eyes became red and inflamed; inside their mouths, there was bleeding from the throat and tongue, and the breath became unnatural and unpleasant. The next symptoms were sneezing and hoarseness of voice, and before long, the pain settled on the chest and was accompanied by coughing. Next, the stomach was affected, with stomach-aches; and, with vomiting of every kind of bile that has been given a name by the medical profession, and this being accompanied by great pain and difficulty. In most cases, there were attacks of ineffectual retching, producing violent spasms; this sometimes ended with this stage of the disease, but sometimes continued long afterwards.”

“Thucydides goes on to describe rashes, delirium, mental confusion and, among the survivors, blackened, dead tissue on the extremities and sometimes blindness. This was a highly transmissible, virulent, systemic disease. Physicians and attendants died quickly, and the only people who could care for the sick — were survivors immune to further infection.”

 Ms. Orent concludes that “the Athenian plague shows how a disease of mild to moderate virulence can heat up in what we can only call a ‘disease factory’ — a place where the sick are trapped together with well, causing infection to spread with wildfire. If the Athenian infection was typhus, the most likely culprit,” Ms. Orent argues, “it would normally be spread by the human body louse and its infected faeces. There must have been body lice among the Athenian squatters.” she observes. Usually, just scratching lice bites, thus digging louse faeces inadvertently into the skin, causes transmission. But, in crowded conditions, transmission of typhus can be more direct. For instance,” she notes, “in the Serbian prison camps of World War I, where typhus was rampant, transmission through the air – possibly caused by aerosolized louse faeces — was known to occur. The right conditions, in other words, can cause the short-term evolution of a louse-borne disease into something explosive.”

“As Ewald has shown,” she writes, “a similar evolutionary process gave rise to the 1918 flu, propelled by the trench-warfare system of the Western Front. In the Spring of 1918, a first wave of mild flu broke out in the U.S.; and, spread across the country to the troop ships loading for Europe. From those ships, the infection spread into the trenches, where it swiftly heated up to deadly virulence in the disease factory conditions of the Front: the trenches, the trains, the trucks moving the wounded and the sick together, where virus from the people immobilized by illness was able, over and over, to infect the well. The whole system was a giant viral delivery service. The disease left the Western Front by several ports and exploded across the planet, killing about 2.5 percent of those it infected — and, it infected hundreds of millions.”

“This predatory influenza was not caused by some random combination of bird flu genes, as the new plague paranoia predicts. Both the Athenian plague and the 1918 flu evolved in predictable Darwinian fashion,” Ms. Orent writes. “Germs that ravage the body more swiftly, and effectively, will out-compete milder strains. If those lethal strains have repeated access to fresh hosts, the brakes on virulence are off, and deadly disease evolves and spreads.”

 “Looking at epidemics, and pandemics through this evolutionary lens makes it clear that the most important condition necessary for the evolution of virulent, transmissible disease is the existence of a disease factory. Without social conditions that allow the evolution of virulent, transmissible disease, deadly outbreaks are unlikely to emerge,” Ms. Orent says.

“Deadliness itself, isn’t all that uncommon: SARS, or severe acute respiratory syndrome, which terrorized China in 2002 and 2003, killed ten percent of its victims; Ebola kills 60-90 percent; untreated rabies kills close to 100 percent, as does pneumonic plague, caused by Yersinia pestis, the bacterial agent of The Black Death, the worst pandemic in human history. But, to be both deadly, and efficiently transmissible — requires exacting circumstances,” Ms. Orent observes. Even the Black Death — though to originally have come from Central Asian marmots — must have evolved in a chain of human-to-human transmission, to become as lethally effective as it was.”

“Fighting existing pathogens is more urgent than hunting for possible new ones — less exciting, but more likely to ease real suffering in the world.”

“So, what is wrong with listening to the drumbeat, to the endless calls to protect ourselves against the coming plague — against Ebola from Africa to bird flu from Asia? Is it possible that a huge pandemic could erupt from some as-yet unknown pathogen? Is apocalypse lurking out there, among rats, or monkeys, or bats or flying squirrels, or birds? The Black Death shows that you can never say never: there might be an animal pathogen out there that, under the right circumstances, can evolve and maintain both virulence and transmissibility among humans as well as animals.”

“The Central African Monkey Pox virus (so-called because it was first identified in macaques in 1958) has dangerous attributes: like smallpox virus it is often deadly, and it’s also a ‘sit-and-wait pathogen,’ in Ewald’s terms — highly durable in the outside environment. Yet the evolution of monkey-pox into a human disease such as smallpox seems, at this point, unlikely: some strains of monkey-pox have transmitted from person-to-person for several iterations, but, the chains of transmission have easily been broken; and, the evolutionary processed stops in its tracks,” Ms. Orent wrote.

“Instead, people continue to die of human-adapted disease,” Ms. Orent adds. “Malaria kills more than one million children annually. Tuberculosis, in its ugliest, drug-resistant forms, is well-entrenched worldwide. Polio, despite our noblest efforts, continues to cripple and kill children. Fighting existing pathogens seems more urgent than hunting for possible new ones — less exciting, but more likely to ease real suffering in the world.”

      Ms. Orent ends on this note. “If The Great Plagues Of Athens tells us anything,” she notes, “it is to avoid social conditions that allow pathogens to evolve to great virulence and transmissibility. Preventing disease factories — trench-like warfare conditions, crowded hospitals, enormous refugee camps — is our best protection. While alarmists among us wait for the plague to pounce out of the jungle, it is far more likely to come from inside us, our disease factories, and our social world.”
The Next Pandemic – When, Not If
     David Quammen, author of “Spillover: Animal Infections And The Next Human Pandemic,” wrote every pandemic begins small. Early indicators can be subtle and ambiguous. When the Next Big One arrives, spreading across oceans and continents like the sweep of nightfall, causing illness and fear, killing thousands or maybe millions of people, it will be signaled first by quiet, puzzling reports from faraway places — reports to which disease scientists and public health officials, but few of the rest of us, pay close attention.”
     “Every new disease outbreak starts, he writes, “as a mystery, and among the first things to be solved is the question of source. In most cases, the answer is wildlife. Sixty percent of our infectious diseases fall within this category, caused by viruses or other microbes known as zoonoses. A zoonosis is an animal infection transmissible to humans. Another bit of special lingo: reservoir host. That’s the animal species in which the zoonotic bug resides endemically, inconspicuously, over time. Some unsuspecting person comes in contact with an infected monkey, ape, rodent or wild goose — or maybe just with a domestic duck that has fed around the same pond as the wild goose — and a virus achieves transcendence, passing from one species of host into another. The disease experts call that event a spillover.”

     “We can’t detach ourselves from emerging pathogens either by distance or lack of interest,” he concludes. “The planet is too small. We’re like the light heavyweight boxer Billy Conn, stepping into the ring with Joe Louis in 1946: we can run, but we can’t hide.”

Interesting and thoughtful articles. The increase prevalence and emergence of antibiotic-resistant infections is certainly a very worrisome, unfolding “train-wreck.” We definitely need to incentivize pharmaceutical companies to explore and develop a new generation of antibiotic medicines — or, we will indeed be heading down a path that Pericles did — so many, many years ago. V/R, RCP

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