It started with a bizarre burning sensation in her feet. Over the next two days, the searing pain crept up her legs. Any light touch made it worse, and over-the-counter pain medicine offered no relief.
On the third day, the 30-year-old, otherwise healthy woman from New England went to an emergency department. Her exam was normal. Her blood tests and kidney function were normal. The only thing that stood out was a high number of eosinophils—white blood cells that become active with certain allergic diseases, parasitic infections, or other medical conditions, such as cancer. The woman was discharged and advised to follow up with her primary care doctor.
Over the next few days, the scorching sensation kept advancing, invading her trunk and arms. She developed a headache that was also unfazed by over-the-counter pain medicine. Seven days into the illness, she went to a second emergency department. There, the findings were much the same: Normal exam, normal blood tests, normal kidney function, and high eosinophil count—this time higher. The reference range for this count was 0 to 400; her count was 1,050. She was given intravenous medicine to treat her severe headache, then once again discharged with a plan to see her primary care provider.
At home again, with little relief, a family member gave her a prescription sleep aid to help her get some rest. The next day, she awoke confused, saying she needed to pack for a vacation and couldn’t be reasoned with to return to bed. After hours in this fog, her partner brought her to an emergency department for a third time, this time the one at Massachusetts General Hospital.
Getting warmer
In a case report published in the New England Journal of Medicine, doctors explain how they figured out the source of her fiery symptoms—worms burrowing into her brain. By this point, she was alert but disoriented and restless. She couldn’t answer questions consistently or follow commands.
The doctors at Mass General, including a neurologist specializing in infectious diseases, quickly focused their attention on the fact that the woman had recently traveled. Just four days before her feet began burning, she had returned from a three-week trip that included stops in Bangkok, Thailand; Tokyo, Japan; and Hawaii. They asked what she ate. In Thailand, she ate street foods but nothing raw. In Japan, she ate sushi several times and spent most of her time in a hotel. In Hawaii, she again ate sushi as well as salads.
The doctors quickly suspected that an infection—likely a parasitic one—was behind the confusing condition. Blood smear tests showed no evidence of parasites, and a computed tomography (CT) scan of her head showed no acute intracranial abnormalities. But, the results of a spinal tap showed a clear problem: her cerebrospinal fluid showed a count of 694 white blood cells per microliter. The reference range was 0 to 5.
Scanning for data on infections that can arise in the three places she visited and align with her symptoms, they came up with a list of 10 possible infectious causes: eight parasites and two fungal pathogens. They went through them one by one, crossing things off the list that didn’t quite fit with everything they knew of her case. They ended with angiostrongyliasis, caused by the nematode (roundworm) Angiostrongylus cantonensis, also known as rat lungworm.
Sickening cycle
The parasite gets its name from its complicated life cycle, which relies on slugs and snails as well as rats. In rats, the worms reproduce, and first-stage larvae are released in the rodent’s feces. These larvae are picked up by slugs or snails, and in them, the larvae develop into third-stage larvae (L3). Rats are infected with these L3 larvae by eating an infected slug or snail. From the rat’s gastrointestinal tract, the larvae migrate to the animal’s brain, where the larvae go through L4 and L5 stages and become adults. Adult worms then move to the rat’s lungs, where they lay eggs—hence the name. The rats cough up the eggs from their lungs and then swallow them. The first-stage larvae go on to develop in the rat’s gastrointestinal tract and are then excreted, allowing the cycle to begin again.
Humans crash this process by accidentally eating the L3 larvae. This can happen if they eat undercooked snails or slugs, or undercooked creatures that eat slugs or snails, such as land crabs, freshwater prawns, or frogs. The more troubling route is eating raw vegetables or fruits that are contaminated by snails or slugs. This is possible because the L3 larvae are present in mollusk slime. For instance, if a slug or snail traverses a leaf of lettuce, leaving a slime trail in its wake, the leaf can be contaminated with the larvae. The authors of the case study note that “the infectious dose of slime is not defined.”
Once ingested by a human, the worms try resuming their normal cycle before hitting a dead end. The L3 larvae move out of the gastrointestinal tract into muscle, heading for the brain. The worms migrate through the blood or along peripheral nerves to get to the central nervous system. Movement along the peripheral nerves is what causes sensory abnormalities, like the woman’s burning feet. In the spinal cord, the migration can also cause bowel or bladder dysfunction.
The parasites’ arrival in the central nervous system is often marked by a headache. From there, a person can develop confusion, encephalopathy, seizure, cranial neuropathy, or eye problems. While the next step for the worms would be to develop into adults and migrate to the lungs, this doesn’t happen. The worms typically die as juveniles in the brain.
This nauseating roundworm is a known plague in Hawaii. In fact, it gained attention in recent years after sparking small outbreaks in the state. In 2017, there were 19 confirmed cases, but case totals in each of the years since have remained below 10.
Happy ending
Given the alignment of symptoms and the raw seafood and salads eaten in Hawaii, the doctors gave a presumptive diagnosis of central nervous system angiostrongyliasis. The diagnosis was confirmed with a genetic test for the parasite’s DNA in the patient’s cerebrospinal fluid (nucleic acid amplification testing).
There are no clear treatment strategies for angiostrongyliasis, and some can recover fully without treatment after the larvae die off. In this case, the patient and her doctors decided to use a 14-day combination of the immunosuppressive steroid prednisone and the anti-parasitic drug albendazole.
Fortunately, the woman’s symptoms cleared with the treatment, and she was discharged from the hospital after six days.