Marshfield Clinic studies rare illness

Blastomycosis only kills some people

Early in 2008, Scott Magrecke started to act strangely.

The Wausau man would sometimes stare off into space, lose track of conversations or forget where he was, said his wife, Sally.

Then one day in late spring, Sally Magrecke went to work, leaving Scott home with her 2year-old daughter. She called him from her job, and he didn’t answer. Worried, she called her mother-in-law, who went to the couples’ home. Scott was

passed out on the couch.

He spent the next two and a half weeks in hospitals in Wausau and Madison, life draining slowly away as doctors tried to figure out why. On Father’s Day that year, doctors told Scott he had blastomycosis.

He would survive, but the disease left him with brain damage and a life that would never be the same.

Blastomycosis is a sometimes deadly disease caused by a fungus called blastomyces. It’s an organism that’s been found in its natural environment only a handful of times. It can react with a human body in a variety of ways, making it difficult to diagnose and treat. Blastomyces lives in wet, swampy areas that often have decaying vegetation. That makes Wisconsin one of blastomyces’ hot spots in the world.

Much remains unknown about the fungal disease. But a team of Marshfield Clinic scientists hopes to solve one of blastomycosis’ biggest mysteries. Jennifer Meece, a blasto scientist with the Marshfield Clinic Research Institute, Dr. Holly Frost, a pediatrician at Marshfield Clinic-Minocqua Center, and Jennifer Anderson, a senior research associate at the Institute, are working on a study designed to ascertain whether, and which, genetic factors play a role in how a person reacts to a blasto infection.

If the study is a success, the results could help shorten, focus and customize the blastomycosis treatment process. That has the potential to save lives and diminish long-term effects of the disease.

Their study was spawned by a simple question: Why?

A ‘treacherous’ bug

Even in Wisconsin, one of the places the disease is most prevalent, the cases of blasto are sporadic. There were 455 reported cases of blastomycosis in Wisconsin between 2011 and 2015, the most recent records available, according to the state Department of Health Services. Of those, 48 deaths were attributed to the disease, almost 1 in 100 patients.

Experts estimate that only about half of all blastomycosis infections are reported. Many people who breath in the spores get only mildly ill or don’t get sick at all, underscoring one of the disease’s mysteries.

A person first gets sick from blasto by

breathing in microscopic spores of blastomyces. The spores lodge themselves in the lungs’ alveoli, the tiny sacs where oxygen gets absorbed into the blood stream and carbon dioxide is exhausted. The spores can react to their new environment in a variety of ways.

The spores can lay dormant for months. Sometimes the body’s immune systems kills them. Other times, the spores thrive in their new warm, moist home in a human body and transform into a yeast. The yeast wreaks havoc on the host. Sometimes the infection spreads from lungs to other parts of the body such as the skin, bones or organs. Or, as in Scott Magrecke’s case, the brain.

“The thing about blasto is that it looks like a lot of things,” Meece said. “It’s complicated by the fact that it presents differently to different people . ... The bug itself is sort of treacherous in many ways . ... So much about blastomycosis remains unknown and seemingly random, from who is susceptible, to what exactly spurs an outbreak,” Meece said.

A genetic study

For doctors who deal directly with patients, there are many, many unanswered questions, Frost said.

Most people who know about blasto generally understand it to be a disease that hits the lungs, causing flu-like symptoms. So when it shows up in a different way, such as Magrecke’s case when it struck his brain, it can take a long time to diagnose.

“Sometimes a patient suffers a bone fracture from the infection, and it is discovered at that time,” Frost said.

The Marshfield Clinic study aims to establish whether a person with a certain genetic profile might be more successful in staving off blasto illnesses or whether a person’s genes make him or her more predisposed to serious effects.

The study will scrutinize the genetic factors of 350 people who have been diagnosed with blastomycosis. The team will look at those factors, confirm what kind of blasto the patient had and record how the patient responded.

“That’s what we’re hoping to clear up with this study: Who is likely to be the sickest? Who are the ones who will be less affected?” Frost said. “If we can find genetic variations that indicated which people respond severely to this disease, it could speed up diagnoses and allow doctors to treat it earlier.”

For example, in cases of blasto such as Scott

Magrecke’s, doctors could use the genetic makeup of the patient and of the blasto to determine the most effective medications to use. They could make that diagnosis more quickly, which hopefully would minimize the long-term damage of the disease.

‘Why would somebody die?’

Meece has been focused on blastomycosis for years, and it started with a short encounter in the autopsy room of Saint Joseph’s Hospital, now known as the Marshfield Medical Center.

She was with Dr. Kurt Reed, a noted pathologist, Meece’s mentor and the reason she came to work for the Marshfield Clinic. Meece remembers Reed peering into a microscope that had multiple eyepieces, a kind often used in science classrooms. He asked her to look.

Meece looked into the lenses and saw blueish, blobby growths. “It was broad-based, budding yeast,” Meece said. She was looking at blasto, an organism that is somewhere between a plant and an animal, and it had killed a young, otherwise healthy man.

Reed looked up at Meece, and said, “This just doesn’t make sense. Why would somebody die from this?”

It’s a question that has gripped Meece ever since. “Blasto is like my passion,” she said.

Frost is similarly focused on the disease. She grew up in Rhinelander, where, she said, “We hear a lot about blasto.”

At the same time, blastomycosis is not a top priority in the medical world as a whole. The disease has not received intense study or attention because outside of the upper Midwest and certain parts of Canada, it is relatively rare.

“My comment to (Meece) was out of a real sense of frustration,” Reed said recently in a phone interview from his home in Fort Atkinson. “We would see these young people dying of blasto, and an older person would survive. We don’t really understand what is going on. Is it the person, or is it the bug?”

When it does get diagnosed, doctors “tend to err on the side of caution,” Frost said. “We’ll tend to overtreat and over-follow-up. And some of the medications have pretty significant side effects.”

The genetic information coming from the study could mean that doctors could better understand how blasto will affect individual patients. A lesser course of treatment could be prescribed if a person has a better genetic ability to naturally fight the disease off.

Blasto survivor is different, but ‘here’

Magrecke underwent weeks of intravenous injections of the antifungal medication Amphotericin B, which is commonly used for severe blasto infections or for cases that have spread beyond the lungs. According to the U.S. National Library of Medicine, Amphotericin should be used only on life-threatening infections.

Side effects include diarrhea, weight loss, pain in muscles, bones or joints and lack of energy. More serious effects of the medication include blisters or hives, wheezing or difficulty breathing.

The medication helped Magrecke overcome blastomycosis, but the disease has left permanent damage.

“He has memory loss. He can’t hear out of his left ear,” Sally Magrecke said. “Sometimes he gets super depressed. He can’t stay focused for a long time.”

Her husband used to play softball six days a week. Now he can’t run.

“It’s different,” Sally Magrecke said of their post-blasto lives. “But we make it the best we can. He’s here.”

Frost and Meece said their study is just one step in the long-term battle to conquer blastomycosis.

“It’s not the be-all or end-all,” Meece said. “This is a pilot study.”

If results are promising, the researchers hope to expand the study and delve deeper.

“We can look at our populations, such as races or ethnicities,” Meece said.

Frost, who recently took a research position at the University of Colorado but will continue her work on the project, sees other areas worthy of study, including scrutinizing whether blasto affects children differently from adults and searching for easier and noninvasive ways to test for the infection.

Meanwhile, the researchers continue to recruit people for the study. So far researchers have been testing about 250 people, with about 100 more to go. Meece estimates that the recruiting of test subjects should be complete by December.

“It will take several weeks to crunch the numbers,” Meece said. Sophisticated medical software programs will scrutinize millions of genetic factors to look for trends or similarities in the way people reacted to blasto.

Meece estimated that the researchers should have results from the study sometime in the spring of 2018.