It was a sweltering August day when Sebastian DeLeon’s parents first started worrying about him. The family was on vacation in Orlando, Florida, and the 16-year-old part-time camp counselor wasn’t doing well. He was tired, sensitive to light, and had a two-day headache that no over-the-counter drug could shake. Concerned, his parents checked him into the Florida Hospital for Children. Doctors assumed DeLeon was just having a migraine, but the pain grew so bad he couldn’t even stand to be touched.
It was the dead of summer in Florida and Sebastian had been swimming in a body of freshwater east of Fort Lauderdale just a few days earlier, on August 5. On a hunch, Dr. Dennis Hernandez ordered a spinal fluid test. The results confirmed the doctors’ worst fears: DeLeon had contracted Naegleria fowleri, commonly known as the “brain-eating amoeba.”
If you’ve splashed in a warm body of freshwater recently—anything from a swimming hole in North Carolina or Texas to geothermal pools in the Grand Tetons or California—chances are you frolicked in the home turf of an amoeba that kills 97 percent of the people it infects. N. fowleri is a microscopic single-celled organism native to the warm, fresh waters of the Americas and Australia; it usually feeds on harmless bacteria present in freshwater muck. Human infections are exceedingly rare, but when N. fowleri is inhaled through the nose, the amoeba will ravenously eat away at the neurons and astrocytes that make up a person’s brain. Only six victims out of more than 140 on record have ever survived infection.
This nightmarish trait is why, on the afternoon of August 14, Michael MacLaughlan was barreling through Orlando traffic in only his pajamas. N. fowleri was responsible for four deaths last summer, and Michael’s father, Todd, runs a small drug company called Profounda Inc. that had recently secured the rights to distribute a treatment that just might stop the amoeba in its path. That Sunday in August, Todd MacLaughlan got a call from the Florida Hospital for Children. A teenage boy—DeLeon—had tested positive for N. fowleri, the pharmacist told him. How fast could he get his drug to the hospital?
Every hour counts when you’re trying to stop this deadly invader. Luckily for DeLeon, Profounda is based in Orlando, and the company had a supply of the drug on hand. From the initial call to delivering the meds, “the whole process took 25 minutes,” Todd MacLaughlan says. DeLeon become survivor number six, and he has no lasting side effects three months after his hospitalization. The drug, called miltefosine, it seemed, had saved the day.
Not every patient is as lucky as DeLeon, though. Today, Todd MacLaughlan is grappling with a frustrating element of our fragmented health care system: though we have a potential cure for an infection, getting it into doctor’s hands in time requires overcoming a daunting number of hurdles. For example, rather than distributing the treatment to all the hospitals across the country, MacLaughlan has to deal with each health care provider individually. And because there are only a half dozen victims per year (and a $48,000 price tag on the treatment), hospitals are hesitant to stock a drug they may never use. To top it all off, even though DeLeon survived after receiving miltefosine, it's difficult to prove the drug saved his life without clinical trials. All this points to frightening reality: if the amoeba finds its way into your brain next summer, chances are MacLaughlan won’t be able to get his potentially lifesaving drug to you in time.
The disease caused by the brain-eating amoeba—officially called primary amebic meningoencephalitis (PAM)—is exceptionally rare and uniquely terrifying. There have only been around 150 confirmed cases of PAM in the U.S. in the past 54 years and, until recently, almost no one survived. Until 2013, only two people on record had ever pulled through PAM.
The organism is almost cruel in the victims it selects, too. Since warmer water temps are ideal for N. fowleri, almost all PAM patients are children or young adults who had been splashing away the dog days of summer. “It’s a horrible disease. It’s just so sad,” says Francine Marciano-Cabral, a professor of microbiology at the Virginia Commonwealth University who has spent her career studying N. fowleri. “The parents really suffer.”
For the last 30 years, doctors have treated patients by pumping them full of antibiotics and anti-fungals, then inducing a medical coma to lower the body temperature. The goal was to make the brain as uninhabitable as possible for the amoeba. It worked only once, in the 1978 case, on a California teenager who probably had a less virulent strain of the amoeba.
When DeLeon showed up at the Florida Hospital for Children in Orlando this summer, doctors were already familiar with N. fowleri. Florida is a hotbed for the amoeba, and they’d seen a patient die from the infection a few years earlier. Even with the delivery of miltefosine, DeLeon’s doctors were far from confident. “I told them to say anything they wanted to tell their child because I didn't know if he would wake up,” Dr. Humberto Liriano told attendees at a medical conference last month.
Miltefosine emerged as a potential cure in 2013. For years, the Centers for Disease Control and Prevention had been testing existing drugs on N. fowleri, but they’d had little luck. In 2007, researchers came across a seemingly unremarkable drug from West Germany. In the 1980s it had been used, experimentally, to fight cancer; today it is only approved to treat Leishmaniasis, a tropical disease caused by sandfly bites. But when miltefosine was let loose in a petri dish swarming with squirming amoebas, the drug killed the free standing organisms dead.
While they weren’t completely sure of miltefosine’s efficacy—it’s hard to run human trials on a drug for a rare, deadly disease—the CDC’s lab experiments suggested the treatment could halt the amoeba’s pillage in human brains, too, says Jennifer Cope, a physician and epidemiologist with the CDC. The drug wasn’t available in the U.S., so in 2013 the CDC got special approval to acquire the treatment from abroad and began stockpiling it in their Atlanta headquarters.
That summer, a 12-year-old girl in Arkansas showed up in the ER with what, to most folks, would have seemed like relatively common symptoms: headache, nausea, vomiting, drowsiness. But a particularly thorough lab tech examined the girl’s cerebral spinal fluid and spotted amoebas. Doctors called the CDC immediately; miltefosine was couriered to the hospital. Miraculously, the girl lived.
It’s impossible to know what exactly saved the girl’s life, Cope says. She’d also been treated with the antifungals and antibiotics that American physicians have been using on PAM patients for decades. But still, the girl was first American to survive the amoeba in 35 years. “That put miltefosine on the map,” Cope says.
Getting the drug to patients was proving difficult, however. No American company had the rights to manufacture or distribute miltefosine in the U.S. and the CDC still needed special approval to acquire and store the foreign drug. As a result, the CDC was stockpiling miltefosine in Atlanta and flying it to hospitals whenever the amoeba reared its head. The next patient to get miltefosine, a 14-year-old boy in Texas, did not survive. An 8-year-old in Texas who received the drug several days after symptoms appeared managed to hold on, but suffered lasting brain damage. Time was of the essence in treating the amoeba, it was clear, and miltefosine was arriving too late.
Jordan Smelski, an 11-year old from Orlando, and his parents, Steve and Shelly, had gone on vacation to Costa Rica in June 2014. On the trip, Jordan went swimming in natural hot springs. When they returned to Florida, “things went downhill very quickly,” Steve Smelski says. Doctors thought Jordan had viral meningitis—a much more common condition, Cope says, and a typical misdiagnosis—and watched as he declined for several days. Finally, they tested for N. fowleri. Spinal fluid samples confirmed that Jordan had PAM and the CDC rushed a shipment of miltefosine from its headquarters in Atlanta. It arrived at the hospital two hours after he died. “Jordan was case number 134 in the U.S.,” says Steve.
Cases like the Jordan’s are why Michael MacLaughlan didn’t take the time to change out of his pajamas when he got the call from his dad. But the next patient might not be so lucky. “Had [DeLeon] gone to a different hospital or been in Miami, things would have been different,” Todd MacLaughlan, Profounda’s CEO, says.
Todd’s company secured the U.S. marketing and distribution rights for miltefosine from a Canadian manufacturer in the spring of 2016. Profounda is now the main American source for miltefosine, marketed by the company as Impavido. But his company faces the same frustrating reality that hampered the CDC’s efforts: Miltefosine, even if you call it Impavido, doesn’t do patients in Louisiana or Texas or California any good if it's stockpiled in Orlando. Although MacLaughlan has only had the rights to the drug for a few months, he’s already seen patients die because they couldn’t get access to the treatment fast enough.
MacLaughlan has a plan, though: he wants to provide hospitals across the country with supplies of miltefosine and only charge the facilities if the drug is used. “They never use it, they never have to pay,” he says. (The drug costs $16,000 per course and most patients will require three or so doses—a total bill that’s comparable to the cost of the current batch of anti-fungals used to fight PAM.)
So far, though, convincing hospitals to take his offer has been difficult. “We’ll have it in nine hospitals by the end of this week,” MacLaughlan said in early October, after three months of negotiation with hospitals across the country. “But that’s nine out of the hundred thousand hospitals in the US.” Even at Orlando’s Florida Hospital for Children, discussions dragged on for months.
“I don’t understand it,” MacLaughlan says. “I think the resistance is apathy. It’s a rare disease. ‘We’ve never seen it before, so we don’t need it,’ hospitals think. ‘And it is expensive. If we need it and still have time, we’ll call [Profounda] and they can fly it to us.’ But how many minutes would you like an amoeba to eat your brains before they treat it?"
For most hospitals, stocking miltefosine probably isn’t on the top of administrators’ to-do list, given that PAM only affects a handful of people a year. It doesn't help that the disease is understudied, underfunded, and little understood, says the Virginia Commonwealth University’s Marciano-Cabral, who’s spent her own money to keep her lab running. Although there’s “not a precedent for this,” Cope says, the CDC is supporting Profounda in its efforts. But it doesn’t really surprise her that hospitals aren’t champing at the bit to get access. “It’s a scary disease, but fortunately it’s not a common one,” she says. “When something doesn’t affect a lot of people, it can be tough to get funding.”
Although it’s winter now and the amoeba is dormant across America, MacLaughlan knows he has just months to secure deals and get the drug into hospitals before the summer, when waters warm up and people start going for afternoon dips. “If you don’t have miltefosine, you die. It may not be the cure-all, but I’d want if I had the amoeba,” he says.
Steve Smelski and his wife have dedicated themselves to helping MacLaughlan. After Jordan’s death, the couple started a foundation to spread awareness and educate doctors about PAM. Getting miltefosine into hospitals, Steve says, is one of their key goals and this winter they'll be pushing for more widespread adoption. “We’re trying to get people to realize they need it in every hospital pharmacy,” he says. In the fight against N. fowleri, time is of the essence and, as Steve says, “you have no idea how much time you have left.”