The spot under Lauren Hart's left eye looked like a bug bite but it didn't go away.
Instead, it started to swell.
And it kept swelling, even after an ophthalmologist prescribed antibiotics and told the 11-year-old from Millington, Tenn., to come back in two days.
Lauren was back in the office the next day.
She was sent to Le Bonheur Children's Medical Center in Memphis, where a biopsy was performed on the inflamed area of her face.
That's when Lauren learned what she was up against.
She had been exposed to Pythium insidiosum, a rare but deadly pathogen found naturally in the environment. Most people who come in contact with the pathogen never get sick, but it can cause death if left untreated. Only a handful of people in the United States have been diagnosed with Pythiosis, the disease caused by the pathogen, in the last 100 years.
Leonel Mendoza, an MSU associate professor of biomedical laboratory diagnostics, is one of the few Pythium insidiosum experts in the country, which thrusts him into the national and international spotlight whenever a new case emerges.
Mendoza developed and patented the only known treatment alternative to surgery and has spent much of the last four months working with doctors in Tennessee to get Lauren well.
"This is an unusual disease," he said. "You can imagine that when something like this happens, there would only be a few who would know about it."
An unknown killer
Not much is known about Pythiosis, partly due to its medical rarity: Only about five people have been diagnosed with the disease in the United States during the last century, and another five cases likely were misdiagnosed as some other disease, Mendoza said.
The pathogen is more commonly found in animals, particularly horses and dogs. Thailand has the highest number of diagnosed human cases, at nearly 100.
Because Pythiosis cases are so rare, the disease doesn't warrant many federal research grants, Mendoza said, which perpetuates the disease as one of little societal importance.
"People are not familiar with this disease," said Mendoza, who said it has been "difficult" trying to secure funding from the National Institutes of Health for his Pythium insidiosum research. "Most researchers will go with more mainstream diseases."
What is known is the way it attacks the human immune system. The pathogen is typically found in soil and wet environments.
Mendoza believes all humans come in contact with it, but most people already are resistant to its effects. Those who get sick, he said, likely have a slight difference in their immune systems that makes them susceptible.
Pythium insidiosum can enter the body through a cut and can spread to other tissues, including the arteries.
The affected tissues become inflamed, and the disease can produce ulcers and skin loss. In children, the most commonly affected area is near the eye, possibly because it is transferred there through rubbing or scratching.
The disease can spread as rapidly as 24 hours after contact.
"It's a killer," Mendoza said. "If you are not treated, you will die."
That's what he doesn't want to happen to Lauren.
The swelling under her eye was first noticed on July 10, said Lauren's mother, Karen Yarbrough. Lauren was admitted to the hospital 11 days later.
Since then, she has been in and out of the hospital. There's still a lot of swelling around her face, and Yarbrough said her daughter is in a lot of pain.
"I didn't know how in the world she got it," she said. "I never heard of it, and nobody around her had ever heard of it. We were just in shock."
Infectious disease specialists in Memphis treated a Pythiosis patient prior to Lauren, which helped them suspect the disease in her case, said Sandra Arnold, assistant professor of pediatrics in the infectious diseases division at the University of Tennessee Health Science Center.
Arnold has worked with Lauren since late July.
She said officials at the Centers for Disease Control and Prevention referred her colleagues to Mendoza, who diagnosed Pythiosis after examining Lauren's tissue sample. Arnold and Mendoza began communicating via telephone and e-mail almost daily about Lauren's condition.
"None of us here might ever have heard of Pythium if it wasn't for this other patient because it's so rare," Arnold said.
Mendoza's method
A native of Costa Rica, Mendoza was teaching microbiology at a veterinary school there when he found the disease in seven horses. At the time, no one was really studying it.
In 1989, the first human case was diagnosed in Thailand, followed by a young boy in Texas a year later.
"That's when we knew we had it here too," said Mendoza, whose background is in human medicine. "What caught my attention was that no one was looking at this disease.
"I was becoming somebody who knew a lot about this disease."
The only method available to treat a Pythiosis patient was a drastic operation. Surgery wasn't a practical option.
"You don't want to remove the entire eye of the little girl," Mendoza said.
He began to look at Pythiosis in animals, knowing information he gained could be applied to humans.
Mendoza adapted a treatment method previously only used in animals called immunotherapy. MSU holds the patent for the human version, with Mendoza as the principal investigator.
The Food and Drug Administration approved its use in humans on a one-time basis specifically to treat Lauren because it has not been used in the United States before now, Mendoza said.
The treatment has been used before in humans in Thailand, as a last resort.
In immunotherapy, proteins are injected in the patient's bloodstream in hopes that the immune system will quickly respond to a particular area, taking the pathogen by surprise. It differs from a vaccine, which aims at prevention, in that immunotherapy works much more quickly and in a different way.
"You need six, seven months to produce immunity," Mendoza said. "We don't have the time to do that."
Lauren's family approved the treatment, which has proven to be 75 percent effective in horses and 55 percent effective in dogs. Mendoza planned for four doses, the first of which was administered Aug. 12, Arnold said.
But after the third dose, Lauren fell seriously ill and was taken to intensive care and placed on a ventilator. Treatment stopped.
"We did not give her the last dose because it could have killed her," Arnold said. "It's very hard to say why she reacted in such a strange way. There's obviously something about her immune system that allowed her to get infected with this."
Arnold said it likely was a result of Lauren's immune system going into "overdrive" to aggressively combat the infection after the treatment.
But both doctors are cautiously optimistic that, given time, Lauren will make a full recovery.
Lauren understands the extent of her illness, her mother said, and remains upbeat and positive even though she has lost weight and is often tired.
The swelling is decreasing, Mendoza said, which he thinks might be a sign that the pathogen is no longer in her system and that, instead, she developed a secondary infection.
"She's out of danger because Pythium insidiosum will kill people in two, three or four months, and she's lasted longer than that," he said, adding that it likely will take two more months before she is better. "She actually opened her eye and she couldn't do it before, and that's something that's good to hear."
But the work won't stop. Mendoza hopes to use Lauren's case as a learning opportunity when the next one arises.
For Mendoza, whose self-described research specialty is "unusual microbes," Lauren's case provided an opportunity to learn more about what made her so sick, when people who have received the treatment in Thailand did not have that reaction.
"We learned a lot of things with this case," Mendoza said. "We don't know why she reacted like that.
"The good news is that she's still alive and she's fighting and she's doing good."





