When Peter Redweik’s physicians finally realized that his splitting headaches, slurred speech and stumbling gait were caused by cryptococcal meningitis — a severe inflammation of his brain caused by a fungal infection — they prescribed amphotericin B. The medication causes such awful side effects — kidney damage, anemia, nausea, seizures — that doctors call it “amphoterrible” and usually reserve it for life-threatening infections. Redweik had picked up a fungal infection, probably during a visit to Vancouver Island in mid-2016, and there was little doubt he now was near death: He was crashing into walls when he tried to walk and vomiting frequently.

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“He was probably within a day or two of dying when he got to the hospital,” said Redweik’s wife, Joyce.

Redweik was hospitalized from August to October while doctors blasted the fungus in his system with amphotericin. He lost his hearing and went blind in one eye from the pressure of swelling on critical nerves. His kidneys were damaged by the medication. He couldn’t walk or even swallow, receiving nutrition through a feeding tube in his nose. A former competitive weightlifter, Redweik, who was 58 years old at the time, lost 63 pounds.

But after six weeks, the amphotericin seemed to have killed the fungus. Laboratory cultures of Redweik’s spinal fluid began to run clear. He started relearning how to walk, swallow and take care of himself. On Oct. 17, he went home to continue recuperating, and a few weeks later, he attended his daughter’s wedding, even walking a few steps down the aisle with her.

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Four days later, though, while sitting on a couch at his home in Arizona, Redweik passed out. At a Tucson hospital, he complained of pain in his eye sockets. The pressure in his brain had soared, and a surgeon there installed a shunt in his head that routed the excess cerebrospinal fluid into his abdomen.

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But soon, his ability to walk regressed and he lapsed into near-unconsciousness. More amphotericin seemed like the only choice. Yet cultures of his spinal fluid showed definitively the fungus was dead. What good would another round of “amphoterrible” do?

Stumped by Redweik’s continuing severe illness, his doctor tracked down a specialist in fungal diseases at the National Institutes of Health who said he knew of cases like Redweik’s. Peter Williamson, chief of the translational mycology section at the National Institute of Allergy and Infectious Diseases, had a hunch about how to treat Redweik. But Redweik needed to come to the NIH’s clinical center, the research hospital for severely ill patients where Williamson worked. Only then was Redweik’s condition identified and treated, saving his life.

Unbearable headaches

When his crushing headaches began in the spring of 2017, Redweik gobbled over-the-counter painkillers and eventually visited the emergency room near his Green Valley, Arizona, home. There he received a common diagnosis for people in hot, dry climates: dehydration.

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He and Joyce didn’t believe it. Redweik had once developed a blood clot in his calf, and they were concerned he had another in his head. They wanted an MRI, but the wait to see a neurologist was four to six months, and Redweik was starting a new job in Plano, Texas, leaving ahead of Joyce, who would join him later.

There, his condition worsened. The headaches were nearly unbearable and had spread down his neck. He began throwing up two or three times a day, and his gait was unsteady.

“It was like I was intoxicated,” Redweik recalled. “I couldn’t walk steadily. I was hoping people weren’t watching. It was like I was going to work drunk.”

During a visit a few weeks later, Joyce Redweik found her husband confused and disoriented. By August, Peter Redweik was falling down when he tried to walk. He needed a wheelchair. He finally got in to see a neurologist and had an MRI exam.

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There was no blood clot. But given his condition, Redweik was admitted to the hospital, where tests revealed cryptococcal meningitis, which, left untreated, can be fatal. He began therapy with amphotericin.

The Redweiks had spent their adult lives in the deserts of Arizona and Nevada, so it was unusual that Peter was infected by a fungus, Cryptococcus gattii, that thrives in a wet, temperate, forested climate. But they had visited Vancouver Island, which had such a climate, the year before, so perhaps that was where Peter was exposed.

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With dangerous pressure building up in his brain, Redweik endured painful lumbar punctures to drain cerebrospinal fluid every few days. Eventually, that procedure was replaced by a lumbar drain installed in his lower back that siphoned off the fluid when the pressure grew too high.

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After six weeks, laboratory cultures of Redweik’s spinal fluid were negative. The amphotericin had finally killed the fungus, and he began relearning how to walk, swallow and take care of himself.

During the AIDS epidemic, fungal diseases infected hundreds of thousands of people whose weakened immune systems could not ward off cryptococcosis and pneumocystis pneumonia. With the development of powerful medications to control HIV, the virus that causes AIDS, very few cases now occur.

According to the NIH’s Williamson, only about 3,000 people are infected by the cryptococcus fungus each year. About 1,000 are HIV patients, another 1,000 are people with suppressed immune systems such as transplant recipients, and 1,000 are previously healthy people like Redweik. About a third of the 3,000 die.

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When Redweik collapsed on his couch and was taken to the hospital again with what seemed like a relapse, his doctors were puzzled. Lab cultures of his spinal fluid showed no evidence of live fungus, but he still showed symptoms of severe meningitis. One test might be wrong, but not several. Should they ignore the results and try to kill the fungus again?

In a search for that answer, one of Redweik’s physicians found Williamson’s name online and contacted him.

According to Williamson, a subset of the previously healthy patients suffer an autoimmune reaction after the fungus is killed: a post-infectious inflammatory response syndrome, or PIIRS. It is not unlike the inflammatory response that has produced long covid in some people.

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Williamson was confident that Redweik was one of those patients and his immune system still considered the fungus a threat. It had amped up the various cells that attack invaders, focusing on tiny particles of the fungus — proteins it had released and cell walls that still remained in Redweik’s system after the cryptococcus was vanquished.

That is what unleashed another round of inflammation and the new symptoms, Williamson theorized.

Redweik was declining quickly when he arrived at the NIH, and Williamson put him on large doses of the steroid methylprednisolone to suppress the immune response, along with the antifungal fluconazole in case the cryptococcus fungus somehow flourished again.

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It may be that microscopic particles of the fungus were still in Redweik’s brain, triggering swelling and pressure akin to his meningitis as the immune system attacked, according to Williamson. Or perhaps antibodies were able to travel to areas of the brain and produce generalized inflammation, he said.

“It is so counterintuitive,” Williamson said. Doctors “treat again with amphotericin because they don’t know.” But “it’s the delay in diagnosis and the inflammatory response that kills you,” he said. “It’s the edema [swelling] that kills you.”

After about three days, Redweik began to respond to the steroids and his symptoms started to fade.

The technology available at the NIH hospital for monitoring his immune response was critical to saving him, Williamson said. Advanced flow cytometry allowed doctors to rapidly identify the immune cells in Redweik’s spinal fluid and confirm Williamson’s diagnosis that he was suffering an immune response to the dead fungus, not a recurrence of the disease.

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After three weeks at the NIH, Redweik went through rehab again and returned home.

Today he still has difficulty hearing, he remains blind in his right eye, and his legs are numb below the knees, he said. With Stage 3 kidney disease caused by the amphotericin, he may one day need dialysis.

But even with those deficits, Redweik has regained his weight and resumed the retired life he and Joyce had planned. After more than 50 years together, the couple is grateful for that.