EXCERPT: 'Kill Shot' probes shadow industry, deadly disease

EDITOR’S NOTE — This is an exclusive excerpt adapted from “Kill Shot: The Untold Story of the Worst Contaminated Drug Crisis in U.S. History,” by Associated Press investigative reporter Jason Dearen. The book chronicles the rare fungal meningitis outbreak in 2012 that killed more than 100 people, and infected some 750 others.

When the first patients began dying, doctors were confused; none of the usual tests identified the cause. An epidemiological investigation would help expose a little-known part of the pharmaceutical industry: a compounding pharmacy where pharmacists mix customized drugs outside the purview of the Food and Drug Administration’s safety system.

In 3 1/2 years of research and writing, Dearen drew on thousands of public documents, interviewed some 150 sources and reported from eight states and Washington, D.C. “Kill Shot” is being published Tuesday by Avery Books, a Penguin Random House imprint.

In this excerpt, Dr. Rachel Smith, a disease investigator with the Centers for Disease Control and Prevention in Atlanta, is looking into a mysterious cluster of deaths in Tennessee Smith and her colleague, Dr. Benjamin Park, raced to discover if the problem was spreading, or confined just to Tennessee. They began by tracing the supply chain for every medical product used on the sick patients.

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DAY 10: SEPT. 27, 2012: CENTERS FOR DISEASE CONTROL AND PREVENTION, ATLANTA

Dr. Rachel Smith sat at her desk in a beige cubicle surrounded by a few dozen colleagues at the CDC. While the other scientists worked quietly, Smith had a telephone headset tangled in her hair and was dialing numbers as fast as she could. She had the unenviable but critical task of cold-calling 76 clinics and hospitals around the U.S. that had received thousands of vials of possibly contaminated steroids that had been injected into people’s spines. She started with those that had received the largest shipments.

The previous evening, the CDC had sent out its first nationwide alert about the concerning meningitis-stroke cases over the Epidemic Information Exchange, or Epi-X:

“On 9/18/2012, the Tennessee Department of Health was notified of a patient with culture-confirmed Aspergillus fumigatus meningitis following epidural steroid injection at a TN ambulatory surgical center. Patients have generally received antibacterial antibiotics without improvement. All patients received injections of preservative-free methylprednisolone, preservative-free normal saline, lidocaine, and skin prep with povidone-iodine. To understand the scope of this cluster and identify possible etiologies (sources), we are seeking information on patients with clinical meningitis or possible neurological infection following epidural injections since July 1.”

The decision to alert the nation had come 10 days after the first known case. Patient zero was a previously healthy man in his 50s who was close to death after a diagnosis of fungal meningitis and a devastating stroke. Two days before Smith’s flurry of calls, she and her boss, Dr. Benjamin Park, had spoken with a pharmacist named Barry Cadden. He was the owner of a compounding pharmacy located in suburban Boston called the New England Compounding Center, or NECC.

His steroids were among a list of injectable drugs used on the ill patients, but he’d assured them that his drugs had been made under strict sterility standards. Park and Smith had to take his word for it; no one had inspected the pharmacy’s sterile “clean rooms” in years. They didn’t know NECC had signed fake prescriptions for patients named Donald Trump, Tom Brady and even Edgar Allan Poe.

After the call with Cadden, NECC’s email appeared in Park’s inbox. Park double-clicked to open the attachment. He scrolled: some 17,675 vials from three different batches had been distributed to twenty-three different states.

Park held back a rising tide of panic. There were no confirmed cases outside of Tennessee yet. But if even a handful of the other vials were contaminated, this was a manmade public health threat of a complexity he had never seen.

After CDC’s Epi-X alerted the nation, patients in Tennessee who had received steroid injections began demanding to be tested. A sudden spike in spinal taps created a crush for lab technicians to perform the cultures, and it became clear that the state would need help.

That only about 12% of the samples extracted from people so far had yielded enough clean fluid to be tested was complicating matters. Each painful spinal tap produced less than a quarter of a teaspoon of fluid, and the amount and quality depended on who was doing the procedure.

Emergency room doctors who rarely performed spinal taps were suddenly on the hook to do an increasing number of them, and quickly. This had an effect on testing. An experienced neurologist could get a clean spinal tap with one skin prick, but less experienced doctors often rooted around trying to find the right spot, filling the sample with blood and not enough spinal fluid. Most of the samples coming into the labs in Nashville were not usable.

The Tennessee Department of Health asked the CDC for help, and they quickly agreed. Doctors began shipping vials of spinal fluid to Atlanta overnight packed in dry ice. If the case count continued to grow, as seemed likely, the CDC’s labs would be invaluable.

For a new epidemiologist like Smith, the project was terrifying, but also electrifying. She fidgeted while listening to a conference call with the latest from Nashville. The Tennessee update was important, so Smith ignored the click of an incoming call. Moments later, the click again.

So far, most clinic directors she’d contacted had been more annoyed at the CDC for asking them to contact patients than they were alarmed at the prospect of an outbreak.

An email marked urgent appeared in her inbox. A doctor from North Carolina had called the emergency hotline with a case matching the description in the Epi-X alert.

Smith hung up and dialed the High Point clinic in North Carolina. A group of clinic staff repeated the information from the email. They were concerned that a case there was related to the growing cluster hundreds of miles west in Tennessee. As Smith listened to the nurse, she sent an email to Park: “Potential case in North Carolina. Getting info now.” She was trying to reach the doctor who treated the patient, but he was with someone at the moment, she added. Park shot back: “If you have to, page them.”

When the clinic staff hung up, Smith ran to Park’s office. She arrived flush-faced and out of breath.

“North Carolina,” she panted. “It’s so bad.”

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A DAY EARLIER, SEPT. 26, 2012: HIGH POINT, NORTH CAROLINA

Elwina Shaw lay in an emergency room. This was the third time in a month that she had come to the hospital with an unusual migraine. Once again, after hours of waiting, the neurologist on duty recommended Tylenol and prepared to send her home.

But this time, her daughter Dawn a nurse at a country hospital cancer ward, was not having it. Dawn recognized the symptoms of meningitis, a disease that afflicted the cancer patients she saw on a regular basis. It had also killed her aunt, Jamie Rie.

The daughter of sharecroppers, Elwina had suffered from back pain since 2007, after her home had burned to ashes. She and her husband, Rex, had lived decades in that farmhouse, and it was full of the memorabilia of a well-lived life. The Shaws had been stationed all around the world with Rex’s Air Force postings, and Elwina collected rare and interesting pieces of furniture. Before the fire she had been offered $40,000 for a 16th-century desk from a monastery in Spain. It was destroyed in the fire along with everything else.

Elwina and Rex rebuilt, doing a lot of the work themselves. Even though she was in her 70s, Elwina took on the landscaping, bending over her plants and hauling heavy bricks around the yard so it would look just right. Over time, she developed pain from an ulcerated disk. Medicare required that Elwina go through three steroid injections, a method both cheaper and less invasive than surgery, which is notoriously ineffective. Rex was due for a kidney transplant, and Elwina wanted to get her back fixed as soon as possible so she could take care of him after his surgery. The headaches started after her third and final injection.

In the ER, Dawn, who had worked at the hospital and knew people on staff, insisted that the attending anesthesiologist perform a spinal tap. “We’re not leaving here with her,” she said. High Point is small, and the doctor on rotation knew Elwina from the rural pain clinic where she had received her injections. The doctor asked Dawn if she understood what she was asking for; a spinal tap is a painful procedure. Dawn reminded him that she worked with cancer patients. She’d seen spinal taps and much worse. Do it, she said.

The staff turned Elwina onto her side. The doctor pierced her back with the needle, slowly. When the spinal fluid began to drip out, Dawn recoiled: it was milky white. Healthy cerebrospinal fluid is clear. Dawn didn’t need to wait for the lab results to recognize the signs of meningitis.

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DAY 11, SEPT. 28, 2012

A voicemail was waiting for the staff of the High Point Surgery Center, the clinic where Elwina Shaw received her steroid injections. It was Rachel Smith from the CDC. She asked them to call her immediately if they saw any possible meningitis cases and stroke in patients who had received injections of steroids from the New England Compounding Center.

The next morning, Dr. Smith spoke with Elwina’s hospital and epidemiologists at North Carolina’s Department of Health and Human Services. Her anesthesiologist told them about Elwina’s cloudy spinal fluid and explained symptoms consistent with fungal meningitis. Then he said that she’d had a stroke overnight.

Smith and Park perked up. Elwina’s stroke was similar to that of the first case that had alerted CDC to the growing outbreak, a man in Tennessee. The anesthesiologist happened to be a partner at the clinic where Elwina had received her injections and confirmed that she’d been given the steroid. The doctor did not think Elwina had long to live. And it wasn’t just the steroids that were suspect. The clinic had used the same iodine solution as an antiseptic and the same anesthetic as the Tennessee cases.

For a fungus to gain purchase in the nervous system of a human host, it needed a lot of help. Healthy people inhale fungi regularly with few problems; human skin and cilia are among our bodies’ first-line defenses.

If contaminated steroids had been administered orally, the most common drug delivery method until the mid-1920s, any fungus would have perished in stomach acid. But the move toward delivering drugs by injection opened a new pathway into the human body.

The invention of disposable plastic syringes in 1955 increased the speed and ubiquity of the method. No more cleaning and reloading needles, as in the old days. In 1926, the U.S. Pharmacopeia, the pharmacy industry’s safety standards setter and creator of the country’s official drug “cookbook,” listed two injectable medications for the first time. By 2013, the USP listed 566 different types of approved drug injections. For an opportunistic pathogenic fungi, this innovation was its Trojan horse.

The CDC had requested brain tissue and cerebrospinal samples for any new cases so they could see if it was a fungus matching the one in the index patient’s body. That patient, Thomas Rybinksi, would be moved into hospice care and die within days. If Elwina’s family consented to an autopsy, samples from her body could be flown to Atlanta quickly.

The request for an autopsy reached Elwina Shaw before she died. Her other daughter, Anna Allred, worked as a hospital chaplain, and had been against the idea. She saw it as intrusive and disrespectful.

Elwina sat up in her hospital bed and told everyone except Anna to leave. “You and I have to talk, and then we have to pray,” she said.

Anna had participated in many deathbed conversations, but this was her mother. Anna had an aversion to autopsies after a particularly difficult visit to a morgue during her chaplain training.

“You have to accept that this needs to be done,” Elwina told her gently. If her body could provide clues that might save other lives, they should not stand in the way.

Anna delivered Elwina’s wishes to her family. They signed the papers. Shortly afterward, she stopped communicating entirely. Three weeks later, Elwina Shaw was dead.

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“Kill Shot” goes on sale Tuesday.