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A simple question leads to answers in medical mystery

Humans might like to think we have nothing in common with pigs, but the facts suggest otherwise in rabies studies and others.
REUTERS/Hannibal Hanschke
Humans might like to think we have nothing in common with pigs, but the facts suggest otherwise in rabies studies and others.

In midsummer 2007, health officials at the Quality Pork Processors plant in Austin, Minn., knew something wasn't right. By then, four or five workers with symptoms of fatigue, leg weakness and numbness had been seen at the plant's clinic and referred on to the Austin Medical Center for further evaluation.

A dialogue was beginning between the two sites. Were the workers, with varying degrees of somewhat similar symptoms, really complaining of the same thing? Was this just some odd "bug" moving through the plant, or was it something job-related?


Here's the story of how a Spanish interpreter helped crack an unusual medical mystery, and how a pork-processing technology might end up resurrecting the lessons from Louis Pasteur's seminal work on the rabies vaccine more than a century ago.

Connecting the dots

For Dr. Richard Schindler, a family practitioner at the Austin Medical Center, a simple question in mid-September gave the cryptically scattered dots the beginnings of a recognizable form.

"One of our Spanish interpreters stopped me in the hallway and asked, 'What's a neuropathy?' " recalled Schindler, "and so we talked about it for a little bit, and I asked her why she was interested. She said she had interpreted for several different patients, who all had similar symptoms but were being seen by different doctors in the clinic."

Not only did they have similar symptoms, interpreter Carol Hidalgo noted, but they also were all working in the same general area at QPP.

Dr. Richard Schindler
Courtesy of Mayo Health System
Dr. Richard Schindler

Next, Schindler quickly tracked down the nurse practitioners involved with the cases Hidalgo had interpreted for, and with their help, he was able to identify several other suspect cases of nerve damage. "We started sifting through names and charts, and by noon we had six different cases for sure," Schindler said.

By week's end the number was 11.

It turns out the first case had been seen in the clinic in December 2006. Nine months might seem like a long stretch for the pattern to go unnoticed, but neuropathies like these are a rather unusual illness, and as it happened, the QPP workers were randomly assigned to different doctors or nurse practitioners.

Though clinic-based health care providers physically appear to be working shoulder to shoulder, practically speaking they can be professionally isolated. It took someone like Carol Hidalgo to see a forest in a few unusual trees. (Hidalgo declined to be interviewed for this story.)

List in hand, Schindler knew it was time to make some phone calls. He spoke with the head nurse at QPP, contacted the state epidemiologist Eric Anderson based in Rochester, and emailed several of the Mayo neurologists who had already seen a few of the six patients while doing outreach at the clinic. Again, none of the neurologists had seen more than a case or two — not enough to see a pattern.

One of Schindler's emails went to Dr. Daniel Lachance, a Mayo neurologist in charge of outreach to the Austin Medical Center who just happened to have a special interest in the area of neuropathies. "I started reviewing the cases and I realized that yes, the interpreter was correct," Lachance said.

Dr. Daniel Lachance
Courtesy of Mayo Health System
Dr. Daniel Lachance

By mid-October the Minnesota Department of Health was involved, and after a few weeks of preliminary investigation it became clear that the illness pattern didn't fit the repetitive motion injuries that are so common in the meat-packing industry.

Something else was going on.

Sounding the alarm, cautiously

Because of the way our food is produced and distributed, an outbreak involving any kind of illness at a food-processing plant draws an aggressive response from state health department officials. The department began immediately interviewing both affected and non-affected workers to identify potential exposures. They reviewed clinical data and obtained diagnostic samples.

A Dec. 3 press release from MDH made some preliminary conclusions. "All of the information we have to date indicates that the general public is not at increased risk for developing this type of illness," said Dr. Sanne Magnan, state health commissioner. "Also, there is no evidence that the food supply has been affected."

As for the cause of the outbreak, the press release said only that all of the patients had worked in an area where swine heads were processed, and that at the request of the state, QPP had implemented "additional precautionary measures" at the plant.

No doubt trying to avoid a consumer panic that would tank the pork industry, the calming tones of the Dec. 3 press release gave no indication of the rather startling findings that state epidemiologist Dr. Ruth Lynfield encountered on a tour of the QPP plant just five days earlier.

According to a New York Times article, when Dr. Lynfield toured the epidemiological epicenter of the outbreak — the "head table" — she saw workers using high-pressure compressed air to liquefy the swine brains and evacuate the skull, a procedure termed "blowing the brains." True to its description, the procedure sent swine brains splattering across a sizeable area, with some of them being aerosolized into a fine mist. Lynfield and Kelly Wadding, the plant owner, made the obvious decision: Stop the brain harvesting immediately.

MDH spokesman Doug Schultz said the unnamed "precautionary measures" alluded to in the original press release included having workers harvesting skull meat use a face shield — a clear plastic version of a welder's mask. "Prior to this, workers had either worn eye goggles or no particular protection," noted Schultz. MDH also asked that workers wear rubberized arm sleeves that extend up to armpit height. "Previously the workers were wearing gloves and a short sleeved lab coat, so there was some potential exposure between the two," he said.

A review of other pork processors in the country found only two others that were "blowing brains": one in Nebraska, the other in Indiana. Both have stopped the practice. The Indiana plant is being investigated by the U.S. Centers for Disease Control for several cases of neuropathy. No other similar cases have been identified.

Putting a name to the symptoms
So, we know the illness started with the head table and a high-pressure hose. But what was actually causing the neuropathy?

Back at Mayo Clinic, Lachance's team was ready to give the patients' constellation of symptoms a name: progressive inflammatory neuropathy.

Magnetic Resonance Imaging of the patients' spinal cords and electrical testing of the affected nerves showed that the protective casing of the nerves was being destroyed. Many of the nerves in the human body are wrapped in a fatty sheath called myelin. This myelin casing insulates the long tentacle of each neuron, similar to the way household copper wire is insulated by a plastic sheath. The protective covering allows the nerve to conduct impulses much more quickly (five- to 50-fold faster) and much more efficiently (100 times less energy needed).

When this myelin sheath is damaged ("demyelinated"), nerve conduction slows down and begins to malfunction, firing irregularly — a toaster on the blink, if you will. Sometimes the nerve itself, the copper wire, can be injured as well. Either way, sensation is altered and often becomes painful, and the muscles weaken under a barrage of irregular nervous impulses.

If that answers Carol Hidalgo's original question, "So what's a neuropathy?" there was still the question of what was triggering the nerve destruction.

"We are finding evidence of antibody formation and immune system activation towards nervous tissue," Lachance said. In other words, the patients' own immune systems seemed to be attacking their nerves. "But we're also waiting on final information about whether there could be a common infective etiology," he cautioned. In that scenario, antibodies against some infectious agent — a bacteria or virus — might be cross-reacting with the workers' nerves.

The link to the rabies virus
When Dr. Stephen Marker, a pediatric infectious disease specialist with Park Nicollet, first heard about the outbreak, he thought he knew exactly what was going on. Early in his training, Marker spent three years working in the U.S. Army Medical Research Institute of Infectious Diseases' virology lab, and he was certain that the answer could be found, historically speaking, in the rabies virus.

"Pasteur knew about this 110 years ago," said Marker. "The earliest version of his rabies vaccine was made up of dried spinal cord from rabbits who had been infected with the rabies virus. The dried spinal cord was injected into humans, and though most people did OK with it, a number of people had an allergic response to the rabbit nerve tissue and came down with what was eventually termed 'acute disseminated encephalomyelitis (ADEM).' " That's longhand for a widespread demyelinating process.

To Marker, the parallels were clear. "It was obvious what they were doing: using high pressure hoses to spread rabbit, or in this case, pig brains all around the room. Anyone involved in this knew it seemed like a really bad idea. I'm sure the investigators understood it that way right away, but in the press they were taking a more measured, cautious approach."

Whether or not this will be the final answer to the QPP outbreak, Marker is right about the rabies vaccine. Because the rabies virus replicates best within nerve tissue, for years rabies vaccines were routinely cultured in animal nerve tissue. Recipients of the vaccine then took a small risk of developing antibodies to the myelin surrounding the animal nerves, with the chance that some of those antibodies would cross-react with their own myelin. (Humans might like to think that we have nothing in common with pigs or rabbits, but the facts suggest otherwise).

Eventually, scientists figured out a way to culture a rabies virus in a human cell line so that any tissue contamination in the vaccine is strictly human, making today's rabies vaccine very safe.

The market for swine brains
After liquefaction, the swine brains from QPP were pooled into containers and shipped to Asia or South America, where such things are stir-fried or scrambled. Eating nerve tissue doesn't seem to carry a risk for acute disseminated encephalomyelitis, presumably because the heat of cooking and the digestive process destroys the proteins that stimulate the immune response. That doesn't happen when a protein is inhaled into the lungs, or absorbed through the skin, as it was at the pork plants.

That's also different from Mad Cow disease, where the infective agent called a "prion" is found in high concentrations in nerve tissue and can be heat-resistant. That's why, after the Mad Canuck Cow scare of 2003, the U.S. Food and Drug Administration mandated changes in the meat-processing industry as an extra precaution to keep nerve tissue out of meat supplies.

In acute disseminated encephalomyelitis (the immune reaction to the old rabies vaccine), some patients have inflammation not just in the peripheral nerves, but also in the brain. Thankfully, this has not been the case in the QPP workers, whose problems involve just the peripheral nerves as they exit the spinal cord. According to Lachance, those workers ill enough to require treatment seem to be responding.

"We've treated a few of the more seriously affected workers with immune suppressants like steroids, and we've seen some good responses," Lachance said. "But it's too early to know whether the disease could have a chronic relapsing course; that is, will the syndrome recur once treatment is stopped?"

Nerves are not the most resilient of tissues; they heal slowly, and the road to recovery could be long or even incomplete.

"None of the workers has completely normalized, but I have a few who presented with mild illness who are getting close to being back to doing their normal activities," he said.

Dr. Craig Bowron is a Twin Cities internist and writer who reports on medical topics for MinnPost. He can be reached at cbowron [at] minnpost [dot] com.

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