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Visions of a honeymoon in Hawaii call to mind scenic sunsets, warm waves, and palm trees swaying in the breeze. But when Eliza Lape and Ben Manilla headed to Maui in January to get hitched, their two weeks in paradise transformed into an experience unforgettable for all the wrong reasons.

The first hints of trouble began just before heading back home to San Francisco. Lape, a 57-year-old communications consultant, developed a dull headache that slowly grew more intense, then began having difficulty sleeping.

“She had been waking up in the middle of the night feeling as though she wanted to crawl out of her skin,” said Dr. Brian Schwartz, the physician who cared for the pair when they returned home and an infectious disease specialist at the University of California, San Francisco.


Lape was plagued by other strange sensations, too. Stabbing chest and leg pains came and went, and her right earlobe was exquisitely tender to the touch, although it wasn’t red or warm.

A little over a week later, Manilla, a 64-year-old journalism professor at the University of California, Berkeley, began feeling exhausted. His sleep, too, became restless. Then his hands and arms started shaking uncontrollably, and his right hand began to feel weak.


That’s when Schwartz received a message from a colleague about the couple’s case. He wasn’t quite sure what to make of their symptoms, but he had a few ideas. Two days later, the three were talking in Schwartz’s office in San Francisco.

‘I remembered how unusual that was’

The similarities between the couple’s symptoms — and the fact that they developed them in close succession — was what struck Schwartz first. These factors pointed to either an infection or exposure to an environmental toxin as the cause of their affliction. Neither smoked, used drugs, or drank much alcohol. And they hadn’t traveled recently, aside from the trip to Hawaii.

In the office, Lape and Manilla’s vital signs were normal; neither had a fever, a fast heartbeat, or low blood pressure. Schwartz judged that the two were not gravely ill. Still, Manilla’s weakness raised the possibility of a stroke. When Schwartz asked him to try to hold a pen, the instrument fell from his grasp. Then the doctor tested Manilla’s coordination and found he struggled with that, too.

Schwartz made a mental note to send Manilla to the emergency room after their appointment for brain imaging to look for a stroke, although he thought this was unlikely. A stroke wouldn’t explain the couple’s other symptoms. What disease might account for everything going on?

Schwartz fleetingly considered ciguatera, fish-borne food poisoning from toxin-producing algae. Victims have headaches, muscle aches, pins-and-needles sensations, and vomiting. Ciguatera can also toy with temperature perception; hot soup may feel cold, and ice feels burning hot. But Lape and Manilla hadn’t eaten any of the types of fish known to cause ciguatera, such as barracuda and hogfish, making this unlikely.

A handful of infections could be at play as well. Leptospirosis, for example, can cause muscle aches, headache, vomiting, belly pain, and a high fever; contaminated horse, cattle, or dog urine spreads the infection. But these symptoms didn’t quite fit Lape and Manilla’s, and the pair hadn’t been in contact with animals.

They could also have meningitis, Schwartz supposed. Viruses and bacteria are most commonly at its root, but parasites and fungi can be too. Headache is a hallmark, as are neck stiffness and eye pain when looking at bright lights. Notably, the couple wasn’t having the latter symptoms, nor had they developed the fevers, confusion, and vomiting that can accompany common types of meningitis.

Yet another possibility was eosinophilic meningitis, a rare variety usually caused by parasites. In that condition, blood and brain tests reveal plentiful white blood cells called eosinophils, a marker of allergies or a parasitic infection. Symptoms and preliminary testing may not differentiate between the various parasites that cause eosinophilic meningitis — and specialized testing can take weeks — so for a speedy diagnosis, it’s crucial to take stock of where each can be found and whether a patient may have been exposed.

“A slam-dunk [diagnosis based on basic testing] would be very hard,” Bobbi Pritt, director of the Mayo Clinic’s clinical parasitology laboratory, who was not involved in the case, told STAT. “It has to be a clinical suspicion based on travel to an endemic area.”

Gnathostomiasis, for example, is a parasitic worm from undercooked fish or frogs that can cause meningitis — but it’s native to Southeast Asia. Another possibility was brain-invading roundworms — toxocara and baylisascaris — picked up from eating contaminated soil, which the pair hadn’t done.

One diagnosis in particular, though, stood out in Schwartz’s mind: Angiostrongylus cantonensis, the most common cause of eosinophilic meningitis. The worm lives in the blood vessels of a rat’s lungs, giving it the nickname rat lungworm. Slugs and snails can pick up the larvae from rat droppings, passing the infection on to humans who eat the tiny animals or consume vegetables contaminated with their slime.

The couple’s headache, shooting pains, and weakness reminded Schwartz of a case of rat lungworm disease he’d seen three or four years ago in a patient who had traveled recently to Thailand.

“The person had a headache and a lot of [abnormal sensations] and pain in different parts of the body, and I remembered how unusual that was,” Schwartz said.

Schwartz verified that rat lungworm could be found in Hawaii, and that Lape and Manilla had eaten vegetables from their garden in Hana, the village where they stayed on Maui. He now had a hunch that rat lungworm might be to blame, and the thought of clinching a rare diagnosis and providing the pair with an answer was exciting.

“I had this hypothesis, and lot of these pieces were fitting,” Schwartz said.

But he couldn’t know for sure until the two underwent further testing.

Tests and an answer

From Schwartz’s office, Manilla headed straight to the emergency department, where imaging thankfully showed he hadn’t had a stroke. Although a spinal tap to examine the fluid bathing the brain and spinal cord would have provided vital information, it was precluded by a risk of bleeding, since Manilla was taking a blood thinner for an irregular heartbeat.

He did, however, have high blood levels of eosinophils. That finding, along with the pair’s symptoms, was enough to make rat lungworm disease overwhelmingly likely in Schwartz’s mind. He opted to start the pair on medicine to help their symptoms.

Doctors don’t usually use worm-killing medicines to treat rat lungworm disease because the dying organisms cause an intense reaction, potentially worsening symptoms. Instead, treatment focuses on minimizing symptoms and tamping down on brain inflammation with steroid medicines. Schwartz started the two on a daily steroid pill, and within 24 hours, Lape’s headache had almost vanished.

A few days later, a sample of the fluid bathing Lape’s brain and spinal cord contained the telltale eosinophils, and Schwartz sent samples from both patients to the Centers for Disease Control and Prevention in Atlanta. Testing there confirmed rat lungworm disease.

The aftermath

A few months later, authorities revealed that Lape and Manilla were two of nine cases of rat lungworm disease contracted in Hawaii in early 2017 — a cluster of cases that stands out in an area that usually sees a handful of cases per year, Hawaii Department of Health spokeswoman Janice Okubo said in an email. The disease is exceedingly rare in the continental United States; the only known case was in 1993 in a Louisiana boy who ate a raw snail on a dare.

Schwartz’s diagnosis no doubt gave Lape and Manilla the best shot at a speedy recovery, although the larvae eventually die on their own inside the human body.

“I had built an illness script after seeing the case before, which highlighted how different the disease is from other classic causes of meningitis,” Schwartz said. For example, in rat lungworm disease, there’s often no fever or vomiting, two common symptoms of viral or bacterial meningitis.

Another defining characteristic of rat lungworm disease is the way sufferers have unusual body-wide sensations, such as shooting pains, likely because the larvae can push against or even burrow into the brain itself.

“I’ve seen cases where it’s boring through the brain, so you can get some localized damage,” said Pritt, the Mayo pathologist, adding that invasion into the brain usually is no deeper than a millimeter or so.

Even in milder cases, it’s not uncommon for symptoms to linger for two or three months. Although Lape is back to normal, Manilla has had some major bumps in the road, including dangerously low blood sodium levels and an intestinal clot requiring surgery. Still, he’s on the mend.

“We love Hawaii and can’t wait to go back,” Lape and Manilla wrote in a joint media statement. “We’ll do it a bit differently next time knowing what we know now about rat lungworm disease. … Had we known, we would have more thoroughly cleaned our fruits and vegetables.”

If you have dealt with a diagnostic puzzle, either as a caregiver or a patient, please email Allison at [email protected]