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Fungal Invasion May Drive Some Pancreatic Cancers

By EJ Mundell
HealthDay Reporter

FRIDAY, Oct. 4, 2019 (HealthDay News) — Fungi living in the gut can move into the pancreas, triggering changes to normal cells that can result in cancer, a new study suggests.

The finding could advance the prevention and treatment of pancreatic cancer, which is usually fatal because it’s often detected too late. The disease has been in the news lately because “Jeopardy!” host Alex Trebek is waging a battle against an advanced form of the illness.

The new research focuses on a particular form of the cancer, called pancreatic ductal adenocarcinoma, which can be fatal within two years.

While the exact causes of pancreatic cancer remain unclear, the American Cancer Society has long recognized that viruses, bacteria and parasites can help spur pancreatic tumors, the authors of the new study noted.

But fungi haven’t been shown to play a role — until now.

“While past studies from our group have shown that bacteria travel from the gut to the pancreas, our new study is the first to confirm that fungi, too, make that trip, and that related fungal population changes promote tumor inception and growth,” study co-author Dr. George Miller said in a news release from NYU Langone Health.

Miller is co-leader of the Tumor Immunology Research Program at Perlmutter Cancer Center at NYU Langone Health, in New York City.

Pancreatic ductal adenocarcinoma is cancer of the tube in the pancreas where digestive juices drain into the intestines. This exchange causes fungal populations in the gut and pancreas — the “mycobiome” — to become abnormal, the NYU team explained. That change may cause pancreatic cells to turn malignant.

In the new study, the researchers first looked at fungal transfer from the gut to the pancreas in mice that already had pancreatic tumors.

In those experiments, the researchers found that treating the rodents with an antifungal drug shrunk the weight of tumors from between 20% to 40% over 30 weeks.

Investigating further, the team catalogued the species of fungi in the poop of mice with or without pancreatic cancer. They even tagged the fungi with “glowing” proteins to watch the microbes travel from the gut to the pancreas.

Continued

Certain patterns emerged, with some populations of fungal species increasing at a far higher rate in the cancerous pancreases versus the non-cancerous ones.

One such cancer-linked species is called Malassezia.

“We have long known that Malassezia fungi — generally found on the skin and scalp — are responsible for dandruff and some forms of eczema, but recent studies have also linked them to skin and colorectal cancer,” study senior co-author Deepak Saxena noted in the news release.

“Our new findings add evidence that Malassezia is abundant in pancreatic tumors as well,” said Saxena, who is professor of basic science and craniofacial biology at NYU College of Dentistry. Pancreatic cancers in the mice grew about 20% faster when Malassezia was allowed to grow unchecked, the team noted.

The researchers theorized that fungi spur growth of the cancer by affecting immune system mechanisms that lead to abnormal tissue growth.

Study co-first author Smruti Pushalkar, a research scientist at NYU College of Dentistry, added, “Moving forward, one goal for our team is to determine which species are most relevant to cancer, as doing so could guide future attempts to slow tumor growth with targeted antifungal medications, and to avert side effects.”

The results of the study add evidence to the theory that fungi increase the risk for cancer by activating an ancient part of the immune system, the researchers said. This immune response fights infections but also increases cell growth as the infection is cured. Past studies have shown that aggressive tissue growth can cause cancer when it’s combined with genetic flaws.

The report was published Oct. 2 in the journal Nature.

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Sources

SOURCE:Nature,  news release, Oct. 2, 2019

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13 Cases of ‘Superbug’ Fungal Infection in U.S.

FRIDAY, Nov. 4, 2016 — Federal health officials say 13 cases of a potentially deadly, drug-resistant fungal infection have been reported in the United States.

Four of those cases ended in death, but health officials said it’s not clear if the deaths were due to the infection or the patients’ underlying health conditions.

Candida auris fungal infection is emerging as a health threat worldwide, and it appears to spread in hospitals and other health care facilities, according to the U.S. Centers for Disease Control and Prevention.

“We need to act now to better understand, contain and stop the spread of this drug-resistant fungus,” CDC Director Dr. Tom Frieden said in an agency news release. “This is an emerging threat, and we need to protect vulnerable patients and others.”

Of the 13 U.S. cases reported between May 2013 and August 2016, seven are described in the CDC’s Nov. 4 Morbidity and Mortality Weekly Report. The other six remain under investigation.

The seven cases described in the report occurred in four states: Illinois, Maryland, New Jersey and New York. All of the patients had serious underlying medical conditions and had been hospitalized an average of 18 days when diagnosed with C. auris infection.

Four patients died, the CDC said, but whether the fungal infection was the direct cause of the deaths remains unclear.

Two patients had been treated in the same hospital or long-term care facility and had nearly identical fungal strains. This suggests that C. auris can be spread within health care facilities, investigators said.

In June, the CDC issued a clinical alert about the global emergence of C. auris. It requested that laboratories report cases and send patient samples to state and local health departments and the CDC.

Since then, CDC has been investigating reports of C. auris with several state and local health departments. Further investigations of possible cases are expected as awareness of the infection increases.

Without specialized laboratory testing, C. auris infection is easily misidentified as another type of Candida infection, the report said. This means patients may not receive appropriate treatment.

Also, 71 percent of the C. auris strains from U.S. patients had some resistance to antifungal drugs, the agency noted. This makes it difficult to treat.

While the strains in the U.S. patients were related to strains in South Asia and South America, none of the patients had traveled to or had direct links to those regions. This means they likely acquired their infections locally, according to the CDC.

“It appears that C. auris arrived in the United States only in the past few years,” said Dr. Tom Chiller, chief of the CDC’s Mycotic Diseases Branch.

“We’re working hard with partners to better understand this fungus and how it spreads so we can improve infection control recommendations and help protect people,” he added.

For now, the CDC recommends vigilant daily and post-discharge disinfection of infected patients’ rooms.

More information

The U.S. Centers for Disease Control and Prevention has more on C. auris.

Posted: November 2016

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Valley Fever Fungal Infection on Rise in Southwest

THURSDAY March 28, 2013 — Cases of a fungal lung infection called Valley Fever increased sharply in several southwestern states since the late 1990s, according to a report released Thursday.

In Arizona, California, Nevada, New Mexico and Utah, the number of cases climbed from less than 2,300 in 1998 to more than 22,000 in 2011, the U.S. Centers for Disease Control and Prevention found.

During that time, Arizona and California had the largest average increases in Valley Fever incidence, at 66 percent and 31 percent per year, respectively.

Valley Fever (Coccidioidomycosis) is caused by inhaling a fungus called Coccidioides, which lives in the soil in southwestern states. Not everyone who is exposed to the fungus gets sick, but those who do become ill typically have flu-like symptoms that can last for weeks or months.

More than 40 percent of patients who get sick may require hospitalization, with an average cost of nearly $ 50,000 per visit. And research has shown that 75 percent of those who get sick miss work or school for about two weeks, the CDC said.

Between 1998 and 2011, nearly 112,000 cases of Valley Fever were reported in 28 states and Washington, D.C., but 66 percent of the cases were in Arizona, 31 percent were in California, 1 percent were in Nevada, New Mexico and Utah, and about 1 percent were in all other states combined.

More research is needed to determine what is causing the increase in Valley Fever and how to reduce its effects, the CDC said. Possible reasons could be population growth, weather changes that could affect where the fungus grows and how much of it is circulating, or changes in the way the disease is detected and reported to the CDC.

“Valley Fever is causing real health problems for many people living in the southwestern United States,” Dr. Tom Frieden, director of the CDC, said in an agency news release. “Because fungus particles spread through the air, it’s nearly impossible to completely avoid exposure to this fungus in these hardest-hit states. It’s important that people be aware of Valley Fever if they live in or have traveled to the southwest United States.”

Doctors and patients need to be aware that the symptoms of Valley Fever are very similar to flu or pneumonia symptoms, the CDC said. A lab test is the only way to diagnosis Valley Fever.

Not everyone who gets Valley Fever requires treatment, but early diagnosis and treatment are important for those at risk for the more severe forms of the disease. Those at higher risk for severe disease include people of Asian descent (particularly Filipino), blacks, pregnant women and people with weakened immune systems, according to the CDC website.

More information

The American Lung Association has more about Valley Fever.

Posted: March 2013

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Fungal Meningitis Patients: A Long Road to Recovery

Dec. 26, 2012 — Johnnie McKee thought she was out of the woods.

McKee, a 72-year-old grandmother of four from Bethpage, Tenn., was one of nearly 14,000 people who found out this fall that they’d been exposed to tainted medications made by the now shuttered New England Compounding Center.

In her case, the threat came from a steroid shot that she’d had on Sept. 7 to relieve some nagging back pain.

“We got a letter. We were told that if we could make it 28 days, that we’d be clear,” says Fred McKee, her husband of 51 years. “We watched it and worried about it,” says Fred, his voice filling with emotion.

But Johnnie felt fine. She didn’t have any of the symptoms they were told to look for — headaches, nausea, fever.

The waiting period passed, and she felt good enough to get back to her yard, which she had always tended with great care. “She mowed the lawn,” says Fred.

Then, on Oct. 8, the pain hit like a bolt of lightning at the base of her spine. “It was just excruciating pain,” says Fred. Their surgeon told them to drive to the emergency room at St. Thomas Hospital in Nashville, where doctors had started to treat a wave of patients who were battling a rare type of fungal meningitis, an infection of the brain and spinal cord.

“There were three criteria they looked for to determine if you have fungal meningitis, and she met all three,” Fred says.

Still, he says, they didn’t worry. But that may have been because they didn’t understand what was coming.

“I don’t think we really realized that we were really getting into a two- to three-month hospitalization period and a six-month-to-a-year complete recovery,” he says.

An Outbreak Without Precedent

Since the outbreak began, 620 people have been infected and 39 have died in 19 states. No one has been cured.

“As far as we know, no one has been taken off medicines, and we wouldn’t recommend that now; it’s still too early,” says Tom M. Chiller, MD, MPH, deputy chief of the Mycotic Diseases Branch at the CDC in Atlanta.

Many hope they are on the road to recovery, but no one can tell them when it will end.

Experts say they’ve never seen these kind of fungal infections, much less this many cases.

“It’s very difficult for the doctors and the patients because we can’t say, ‘Well, just two more weeks of this and it will be over.’ What we’re saying is that we’re going to keep treating you. We’re going to keep caring for you, and when the experts tell us we can stop, we’re going to do that,” says William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.

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More Drug Shortages in Fungal Meningitis Aftermath

Nov. 2, 2012 — Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.

Ameridose — the sister firm of the NECC, the compounding pharmacy whose tainted products are at the heart of the outbreak — has shut down, and at the FDA’s urging recalled the more than 2,000 products it sold nationwide. The FDA yesterday admitted that these actions will worsen the ongoing shortage of six important drugs hospitals need to help critically ill patients.

Currently, 226 drugs are in short supply. Last year, 99% of U.S. hospitals reported drug shortages. And these are important drugs, says Joseph Hill, director of federal legislative affairs for the American Society of Health-System Pharmacists.

“In the last five years we have seen a significant spike in the number and severity of shortages,” Hill says. “It is really alarming when you look at the classes of drugs involved: cancer drugs, heart drugs, pain drugs, and anesthetics. Imagine not being able to perform an emergency surgery.”

Compounding pharmacies do not make most of the drugs that are in shortage. But they make an increasing number of them, says David Miller, RPh, CEO of the International Academy of Compounding Pharmacists (IACP).

“What we have seen is on a large scale, important drugs being in shortage — and not for short periods, but in the months-to-years range,” Miller says. “Compounding pharmacies help with that. Now, instead of filling short-term needs, compounding pharmacies are being looked to on a larger scale.”

How many compounding pharmacies are doing this? The FDA does not know.

“We do not have this data,” says FDA public information officer Sarah Clark-Lynn via email.

“It is important to note that compounded drugs can serve an important public health need if a patient has a particular medical need that cannot be met with an FDA-approved drug,” Clark-Lynn says. “Compounded drugs that are prepared improperly pose potential health risks to the patients who take them. When such compounding occurs on a large scale, more patients are exposed to those risks.”

Compounding Pharmacy Safety

It’s impossible for a hospital running out of crucial drugs to know if a compounder is safe, says Michael Cohen, RPh, president of the Institute for Safe Medication Practices (ISMP).

“I cannot to this day clearly see anything that articulates what pharmacies are provided with the oversight to ensure that they’re making these drugs safely and what pharmacies are not,” Cohen testified before the FDA’s September 2011 workshop on drug shortages.

A full year before the fungal meningitis outbreak, Cohen warned the panel that unsterile drugs made by compounders already had caused infections and deaths — and that the oversight needed to prevent future disasters was “not happening.”

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New Warnings in Fungal Meningitis Outbreak

Oct. 15, 2012 — More patients — not just those who got steroid shots — will be getting calls from their doctors warning them they might have a dangerous fungal infection.

The FDA now suspects fungal contamination is possible in all of the supposedly sterile products made by the New England Compounding Pharmacy (NECC) on or after May 21, 2012. People who got shots of any of these medicines — particularly those given during eye treatments or heart surgery — are at risk.

There’s already one possible case of fungal meningitis in a patient who received a different NECC steroid product (triamcinolone acetonide) than the three lots of methylprednisolone known to have infected patients.

Two people who received an NECC heart medication during transplant surgeries have fungal infections. The heart drug is called cardioplegic solution and is used to temporarily stop the heart during open heart surgery.

It’s not clear whether those infections came from the NECC drug or something else. So far, there have been no reported cases of eye infections linked to NECC products.

“At this point in FDA’s investigation, the sterility of any injectable drugs, including ophthalmic drugs that are injectable or used in conjunction with eye surgery, and cardioplegic solutions produced by NECC, are of significant concern, and out of an abundance of caution, patients who received these products should be alerted to the potential risk of infection,” the FDA today warned in a statement.

The CDC now has two reports of fungal infections in patients who received NECC steroid shots in the knee, hip, shoulder, or elbow.

Including these cases, 214 people in 15 states got fungal infections traced to NECC products. Fifteen patients have died.

Today’s warning applies only to sterile drugs delivered by injections. “At this time,” the FDA notes, the warning does not include NECC products applied as lotions, creams, eye drops, or suppositories. Before shutting down operations, the NECC offered more than 2,100 different products for sale in all 50 states.

The FDA advises doctors that they may get a lot of calls from patients and to use their judgment about who is at risk.

Symptoms of Fungal Infection, Fungal Meningitis

People who received injections of NECC drugs should be alert for symptoms of fungal infection:

  • Fever
  • Swelling
  • Increasing pain, redness, or warmth at injection site
  • Changes in vision (if injection was in the eye)
  • Pain, redness, or discharge from the eye (if injection was in the eye)
  • Chest pain (if drug was used during heart surgery)
  • Drainage from the surgical site (infection within the chest, if drug was used during heart surgery)

Symptoms of fungal meningitis may be very mild at first. They may include slight weakness, slightly worse pain, or a mild headache. Other symptoms include fever, headache, stiff neck, nausea and vomiting, sensitivity to light, and altered mental status. 

The CDC warns patients who received suspect medications to be alert for:

  • New or worsening headache
  • Fever
  • Sensitivity to light
  • Stiff neck
  • New weakness or numbness in any part of your body
  • Slurred speech
  • Increased pain, redness, or swelling at your injection site

While most patients with infections developed symptoms one to four weeks after infection, the CDC remains unsure how long those who received suspect medications should be on the alert.

The FDA has extended its investigation to include Ameridose, another Massachusetts compounding pharmacy owned by some of the same people who own the NECC. So far, no Ameridose products have been linked to fungal meningitis.

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Fungal Meningitis Q&A

Oct. 12, 2012 — More people have been stricken with fungal meningitis that’s been linked to contaminated steroid shots sold by a compounding pharmacy in Massachusetts.

So far, 184 people in 12 states have the rare meningitis, the CDC said on Friday. One person has an infected ankle after receiving one of the steroid shots. Fourteen people have died.

Health officials expect those numbers to rise.

Before the outbreak dominated news headlines, most people had never even heard of fungal meningitis.

WebMD reached out to experts in fungal diseases to get answers to common questions about fungal meningitis.

What is meningitis?

Meningitis involves swelling and irritation of the meninges, the membranes that cover the brain and spinal cord.

In most cases, these membranes become inflamed in response to a viral or bacterial infection. But certain drugs can also cause meningitis, as can cancer.

How is fungal meningitis different than the viral or bacterial types?

“First of all it’s very rare, so we don’t have a lot of experience with it,” says Luis Ostrosky-Zeichner, MD, an infectious disease expert and director of the laboratory of mycology research at the University of Texas Health Science Center in Houston.

In fungal meningitis, fungal organisms like mold or yeast invade the cerebral spinal fluid, the clear fluid that bathes the brain and spinal cord. They also invade the brain’s blood vessels, which can cause strokes.

“With bacterial and viral meningitis, they’re relatively common and physicians know how to recognize them,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville, Tenn. Schaffner has treated some of the patients involved in the outbreak.

Before the current outbreak, only doctors who treated people with very low immune systems, such as patients with HIV or those who were treated with immunity-suppressing medications, would see cases of fungal meningitis.

Is fungal meningitis contagious?

No. According to the CDC, the infection can’t be passed from person to person.

What are the symptoms of fungal meningitis?

They are largely the same as the symptoms of bacterial or viral meningitis: headache, fever, chills, a stiff neck, and “just feeling very badly,” Schaffner says.

But they may be slow to develop and mild.

“The speed at which people get sick is very different,” says Benjamin Park, MD, medical officer at the Mycotic Diseases Branch of the CDC.

Unlike bacterial and viral forms of meningitis, which tend to develop within hours, fungal meningitis “creeps up on you,” Park says.

“People who have gotten infected, they’ve had somewhat milder symptoms than you would expect,” says Park.

Park says nearly everyone who has gotten sick has had a headache, for example, but the headache wasn’t the worst-kind-you’ve-ever-had-in-your-life variety, as often comes with bacterial or viral meningitis.

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