Because you asked for it…

…Here is Part II of Barry Siegel’s reconstruction

Several years ago I posted the first part of a 1995 medical mystery written by Barry Siegel. I couldn’t make Part II fit on the same take so I invited anybody still interested to e-mail me. Four years later I’m still getting e-mails so, behold: Here is Part II online. Enjoy.

Because you asked for it...

Because you asked for it...

BATTLING TO CONTROL A KILLER BUG
By Barry Siegel

It is the medical sleuth’s constant quandary: How to respond before you know what you’re fighting? Timing is all. If everyone could breathe into the phone and provide instant lab results, Minnesota state epidemiologist Mike Osterholm likes to say, he could make incredible decisions. The trouble was, he had to act based more on the past than the present.

What to do now in Mankato?

Over one week in late January and early February, this small river town south of the Twin Cities had seven cases of deadly meningococcal disease and one death, a 15-year-old named John Janavaras. Despite a rapid response, despite giving 3,300 vaccinations to all junior and senior high students, officials had a classic outbreak on their hands.

Should they now expand the circle of who gets vaccinated? Should they start giving everyone the antibiotic rifampin? Should they close Mankato West High, where most of the stricken attend class?

Would doing so take them down a slippery slope? Or was it an aggressive but logical counterattack? Would they be caving in, pandering to community panic? Or would they be saving lives?

These were the type of questions facing Osterholm, his state Health Department colleagues and the Mankato officials who gathered late Friday afternoon, Feb. 3.

They felt sure that shutting down the school would be wrong. The bug wasn’t being transmitted through the building, but through close social contact; the students would simply congregate off campus.

About the antibiotic, they were less sure. They didn’t know if rifampin would do any good. It didn’t protect those who took it, but rather, reduced the chance of transmission. It had never been used to combat an outbreak like this. And in the strong doses needed, it couldn’t be given to people for extended periods.

For these reasons, Osterholm had resisted distributing the antibiotic earlier, hoping they’d quickly find and eliminate the source of the outbreak. They almost always did.

Not this time, though. Despite hours of interviews and detective work, they’d been unable to trace its genesis or figure out the links among the victims.

Experience indicated this outbreak would end without further action, Osterholm knew. But was that a reliable indicator?

In the end, Mankato and state health officials decided they just could not stand by idly. To buy time until the vaccines took effect in four days, they decided to give all junior and senior high students the antibiotic the next morning. What’s more, on Monday they’d give antibiotics and vaccinations to 5,000 more people: Mankato West High’s staff, the immediate family members of its students and staff, and those in close contact with its students.

Osterholm told reporters this response was “aggressive and unprecedented. . . . We’re in uncharted waters.” Not everyone applauded, however.

At a community meeting in Mankato West’s auditorium on Saturday, Feb. 4, the day after Janavaras died, 1,500 citizens-some plainly scared or irate-filled the main floor, balcony and aisles. A half-dozen parents accused officials of playing “Russian roulette” with their children’s lives. Why hadn’t they closed the school? they demanded. Why hadn’t they vaccinated everyone? Why hadn’t they given antibiotics from the start?

Osterholm’s efforts to explain “a rational scientific basis” and “slippery slope” did not mollify everyone. On the phone that weekend, several callers threatened him, held him responsible, called him arrogant and uncaring. A Minneapolis TV station charged that Osterholm was losing Mankato’s trust by giving the town “mixed messages” about risk and proper responses.

There were, in truth, only a handful of critics speaking out, but they were having an impact. By now, Osterholm, much to his regret, was devoting half his time to putting out fires. Rumors were sweeping through Mankato.

Despite reassurances, two-thirds of Mankato West’s students stayed away the Monday after Janavaras’ death. (Not all remained at home, though; many gathered at the shopping mall or at friends’ homes, just as Osterholm had feared.) Callers to the hospital hot line demanded the vaccine at whatever the cost. Callers to the Blue Earth County Health Department insisted that the vaccine itself was spreading the disease. Jake’s Stadium Pizza owner Vernon (Sarge) Carstensen found it necessary to call a news conference to deny a widespread rumor that his wife, Norma, was the unnamed 64-year-old woman who was among the seven who had been hospitalized.

The agitation was even greater beyond Mankato’s borders. Schools from across the state canceled sporting events. Shoppers packed the Wal-Mart in Blue Earth, 40 miles away, rather than visit Mankato’s regional mall. Visitors canceled motel reservations. A store in Wells, 34 miles to the south, refused a package delivered by a truck driver from Mankato.

A bus company wondered whether it should change its route through the area. An out-of-state candidate for a dean’s position at Mankato State University canceled his scheduled interview.

A few treated Mankato West students-”Westies”-as lepers. A K mart shopper asked a checkout clerk where she went to school, then switched to another line when the answer was Mankato West High. One student wasn’t allowed to come to work at the Civic Center for 10 days-until his vaccine became effective.

For a time, whenever the phone rang Mankato West Principal John Barnett flinched, fearing it was the hospital or Osterholm calling. Who’s going to be next? Barnett wondered.

Then, once again, the furor abated. As the days passed without a new case, hot-line calls dwindled. When only 49 called on Friday, Feb. 10, a week after Janavaras’ death, the hospital closed the hot line.

Osterholm now believed they were truly at the end of the siege.

They’d inoculated more than 5,000 at a second vaccine clinic the previous Monday. They’d discharged, over the course of the week, all the hospitalized patients: Joe Kratzke, 17; Casey Houston, 16; Sara Kleinsasser, 17; Jon Boyer, 17; a 3-year-old boy, and the 64-year-old woman. They’d finally linked the woman and the 3-year-old to Mankato West students, making their illnesses far less mysterious.

Osterholm felt certain they’d soon find the missing link among all those infected. “All these cases will tie together somehow,” he told reporters.

At a news briefing the next Monday, he more or less announced that missing link, and declared the end of the outbreak.

They had found no smoking gun, he said. They couldn’t trace the outbreak to a single person or event and didn’t expect they ever would. But they had concluded that about 100 Mankato West students had played a role in the outbreak. They’d never met as a whole, but rather, had shared activities in varying alignments of five or six at a time.

“After the first 100, the diagram didn’t get any bigger,” Osterholm said. “Just more and more lines connecting everyone in that group.” Looking back, he told the reporters, the mass immunizations were probably “overvigorous,” since the outbreak involved a small network from one school. But they hadn’t known that, so their response was “prudent.”

“I feel very confident today that we are out of the woods,” Osterholm concluded. “This outbreak followed a road map exactly as we mapped it out. This thing had no real surprise punches.”

The news that the outbreak had been traced to a small Mankato West group, the local Mankato Free Press editorialized two days later, “brings a sense of closure to a traumatic community event.”

By the end of that week, Mankato West’s attendance was back to normal and its athletic teams were back in action, no longer shunned by other schools. Osterholm was in Florida, vacationing with his children. You’re done, he was telling himself. You’re done.

He was not.

Move to New Level

After Jackie and Shayne Pitt’s two teen-age daughters had been vaccinated in the first round of inoculations, Jackie had called the hospital hot line to ask if their 7-year-old son, Ryan, should also get the shot. No, she was told, not at this time.

That made sense to Jackie. This disease was hitting teen-agers, after all. And her daughters attended Mankato East High, not Mankato West.

Just 18 months before, the Pitts had moved to Mankato from Germany, where Shayne was a company commander in the U.S. Army. Now he taught ROTC at Mankato State. The family liked Mankato’s small-town friendliness. Ryan, an exuberant second-grader at Kennedy Elementary School, had quickly learned to ice-skate and play hockey.

At hockey practice on Saturday, Feb. 26, he looked a little flat to his dad, but he played OK. Not until after he went to bed that night did he start to act sick. By the middle of the night, he was vomiting every half hour.

Jackie knew about the meningitis siege but wasn’t too worried. The outbreak wasn’t in Ryan’s age group, she reasoned. His friend Jeff had the flu, and Ryan had slept over at his house the night before. Ryan must have the flu.

At 7 a.m., Ryan fell into a more peaceful sleep and seemed better. So Jackie and her daughters left for church, leaving Shayne to care for his son.

At 11:30, Ryan woke and went into the bathroom. Shayne, looking in, saw 100 or more red pinpoint dots on Ryan’s chest and the front of his legs. They resembled miniature chicken pox to Shayne, not the grape-colored bruises they’d been warned about.

Ryan had already had chicken pox, though.

Close to noon, Jackie returned from church. Come look at Ryan’s rash, her husband said. Jackie looked, and froze. Let’s get him to the hospital, she said.

As they were dressing Ryan, he started to mumble and say things that didn’t make sense. The parents hurried. By the time Shayne was carrying Ryan to the car, the boy was delirious. His babbling grew ever stranger in the five minutes it took to get to Immanuel-St. Joseph’s Hospital.

“He’s acting like he has the flu, but he’s got these dots on his body,” Shayne started to tell the admitting nurse. The nurse stopped writing. “I want the triage doctor to see him right away,” she said.

In the emergency room, they gave Ryan steroids to reduce brain swelling, took blood samples, did a spinal tap. The on-call pediatrician, John Norris, ordered massive doses of penicillin. Then, as Ryan was being wheeled to the critical care unit, Norris approached Jackie and touched her on the arm.

“Are you OK?” he asked.

Six other cases ended up OK, Jackie was thinking. So yeah, she was OK.

Norris spoke gently. “This is the form of the disease where the bacteria is in the blood, not the brain,” he said.

Jackie understood. She knew that was the form John Janavaras had.

“The first 72 hours will be critical,” Norris said. “This is a matter of life and death. Ryan could die.”

Jackie wept.

In critical care, Ryan’s blood pressure was dropping as his body, in shock from the bacteria’s toxin, bled internally. He wanted to nap, but the staff, fearing he’d stop breathing, kept talking to him. So did his mother. Ryan, garrulous as ever, responded.

He talked about a girl who hit him in the eye with a block at school. He ran through his Christmas wish list-Rollerblades, a pocketknife. He weighed possible birthday presents for his mom.

“Maybe I’ll give you earrings,” he told her. “Just like last year.”

When they announced “code blue-CCU” on the loudspeakers shortly after 8 p.m., Jackie was down the hall, Shayne in a meeting room being interviewed by state public health officer Jan Forfang. “You better get in there,” Forfang told Ryan’s father.

Ryan had stopped breathing. A nurse, desperate, crying “We’re losing him,” had started mouth-to-mouth resuscitation, despite the danger to herself. A respiratory therapist had taken over a minute later with oxygen and fluids. By the time Shayne and then Jackie burst into the room, though, Ryan was breathing again. “Mom,” he said, “it looks like you’ve been crying.”

Norris ordered fresh frozen plasma and a medication to boost blood pressure. He also urged that Ryan stay awake. If the boy “coded” a second time, Norris would have to anesthetize him and put him on a respirator.

Do you have a girlfriend? asked the respiratory therapist posted at Ryan’s bedside, struggling to keep the boy talking.

“Brittany,” Ryan answered. “You know what I’m going to do when I see Brittany? I’m going to tell her I love her very much and she can do anything she wants to me.”

Early in the morning, Ryan’s blood pressure started to stabilize. Shayne noticed the room growing calmer. Staffers who’d stayed beyond their shifts started leaving. Soon Ryan was working his nurses, calling for root beer, hot chocolate and Froot Loops.

“I heard a nurse say, `We’re losing him,’ ” Ryan recalled. “I thought I might die, and my mom and dad would be crying.” At 5 a.m., Jackie and Shayne settled onto cots and went to sleep.

By now accustomed to the recurring peril, the Mankato community at first responded calmly to the news of Ryan’s illness. A town meeting in the Mankato West auditorium on Tuesday night, Feb. 28, two days after Ryan entered the hospital, drew a quiet crowd of 200.

To Osterholm, though, Ryan’s case was easily the most unsettling and ominous of all they’d seen in Mankato. Until now, he’d felt sure they were traveling a familiar if dreadful road. Suddenly, the terrain looked strange.

Based on everything he knew, Osterholm had always assumed this bug would stay confined to linked individuals at a single institution-Mankato West High School. In the epidemiological literature, that’s how it always worked. Ryan, though, had no apparent links to the other cases; he came from a different age group, a different social setting.

It looked as if this bug had now moved to a broader, more random population. An institutional outbreak had evolved into a community outbreak, which meant it might continue for many months. That had never happened before.

At meetings with Mankato officials, Osterholm found himself for once fueling rather than quelling concern. Well, you told us there’d be sporadic cases, some said. Osterholm had to be honest.

“I meant connected to Mankato West High,” he said. “This has jumped the fire line. It’s like it jumped to another forest.”

The group quickly fixed on a plan. If genetic fingerprinting showed that Ryan’s bug matched the strain in the other cases, they’d vaccinate all kids from preschool through sixth grade, about 4,500 total. While waiting for lab results, they’d get ready, make arrangements, reopen the hot line.

Late Wednesday, March 1, the state lab confirmed that Ryan’s bug matched the others. Then, early the next morning, even more disturbing news arrived.

An 18-year-old Mankato State University freshman, Christopher Wilson, had been hospitalized in the Twin Cities with classic signs of meningitis. Wilson had no apparent link to Mankato West. He was from a Twin Cities suburb, he lived at MSU, he had no job in Mankato.

What in the world, Osterholm wondered, was going on?

He felt flat-out bewildered. He thought he knew this bug. He thought he could predict its behavior. It was like watching an old familiar relative act in an utterly bizarre way.

The bacteria’s movement, he told reporters, “has never been previously demonstrated in the United States. . . . The outbreak has moved to a new level. . . . This type of shift has never been documented in any previous outbreak of meningococcal disease.”

The public health team’s determination to act only on a rational, scientific basis was eroding.

More than 1,000 calls a day once again flooded the hot line. Those from outsiders now included a few demands that they “close down” Mankato. Some used the word “quarantine.” MSU students’ parents questioned whether to let them come home. Truckers from Illinois refused to deliver ad inserts to the Mankato paper.

To those making decisions, the threat of mass hysteria seemed utterly real, and more than a little scary. The 18-year-old MSU student had been given penicillin before a blood sample was drawn, so they’d never really know if he had the outbreak bug. But they had to respond aggressively, they quickly decided-even if it was as much to quell community panic as to fight the bug.

They wouldn’t just vaccinate the kids. Over four days, they’d vaccinate everyone 29 and younger in the Mankato area-22,000 more in all. With that, they’d have inoculated half of the region.

Whether also to give everyone rifampin did draw some debate.

It wasn’t just that rifampin had uncertain efficacy. It also had complications. It wasn’t safe for pregnant women. It shouldn’t be taken with alcohol. It negated birth-control pills. It sometimes caused side effects-diarrhea, headache, fatigue, vomiting, fever.

Still, they’d already given it to so many others in town. People would ask, why them, not us? People would demand it. People thought it protected them. It cost only 50 cents a dose.

They’d give rifampin to everyone, the Mankato and state health officials decided. They’d give it even if it was almost a placebo. They’d give it even though Osterholm’s carefully constructed consensus was starting to weaken.

Among others, Jerry Crest, head of Immanuel-St. Joseph’s, didn’t think such a massive response was necessary medically. “Some of us frankly felt we shouldn’t, that we didn’t need to,” he would later recall. “But we had to be consistent, we had to bring this to an end. There would have been such a reaction if we didn’t. Parents of every college kid would be down here with guns. This was definitely an emotional reaction, based on mental health concerns.”

Jane Schwickert, the hospital’s infection control nurse practitioner, saw it a little differently. “It’s not that we’re going against science,” she said. “It’s that there isn’t a whole lot of science there.”

Osterholm saw it yet another way. True, they had no choice, the community required a response. “But the science was there,” he insisted.

Late on Thursday, March 2, Jerry Crest appeared at the desk of Mary Bauer, in the hospital’s material management department. “Mary,” he began, “if I were to ask you for 20,000 syringes by tomorrow, can you do it?”

Laboring through the night, county and state health workers hand-counted antibiotic pills into 25,000 bottles. When the pediatrician who’d signed the order for the young children’s medicine decided he was uncomfortable signing for adults, they had to find another doctor, then relabel every bottle with his name. When the new labels wouldn’t stick, they had to start using Scotch tape.

The next morning, the Red Cross brought coffee, food and water to the vaccination clinic at the Army Reserve Center in Mankato. The National Guard put up tents and directed traffic. The owner of A to Z Rental donated portable heaters. Grocery stores and restaurants donated food. Sixteen counties sent public health officials, 150 volunteers, scores of nurses. More than 3,000 citizens called the hot line, some asking for times and directions, others pleading.

Why not me, what about me? they implored. I’m two months past my 30th birthday. I work with kids.

By noon, 6,000 had converged in chill winter air at the Army Reserve Center, enduring traffic jams, shuttle buses and two-hour waits in a 400-yard-long line. On Saturday, with light snow falling and crying children huddling in parents’ arms, officials increased the number of buses, expanded the vaccination stations from 14 to 25, added portable toilets, lights, tents. For 30 hours the marathon continued-781 shots per hour, 13 a minute, one every 2.2 seconds.

At 5 p.m. Monday, cheers and applause erupted as health workers administered the last of 23,452 vaccines. In all, public health officials had provided the vaccine and antibiotics to more than 30,000 since the outbreak began, at a cost of $1.03 million to the state and an equal amount to Immanuel-St. Joseph’s and county health departments.

Still, not everyone was satisfied. Why not give vaccinations to the entire community? some demanded in phone calls and at a public meeting Monday on the MSU campus. Why not vaccinate people older than 29?

“I don’t think you have to be Jonas Salk to figure this out,” one MSU faculty member declared. “We’re all at risk.”

No, Osterholm flatly responded. He would not slip further down that slope; he would not divert resources from true health problems. Driving to the Twin Cities is riskier for adults than is meningitis.

Some nonetheless pressed: What about those willing to pay the entire cost themselves?

No, Osterholm said. They were done. They would conduct no more clinics.

Evolving Outlaw Bug

Late in the day on March 16, Osterholm returned to Mankato to give a wrap-up summary of the outbreak, and what he called his “swan’s song” to a community he’d come to admire greatly.

The town was more or less back to normal by then. There’d been no more cases reported, and the panic had abated. Joe Kratzke was playing basketball for Mankato West High, Ryan Pitt hockey for Kennedy Elementary. An early hint of spring had warmed the air, dispatching most sore throats and symptoms of flu.

Many talked about how proud and appreciative they were of their community for working together under such duress. Students wrote essays. Those who’d battled the bug planned a “post-meningital outbreak debriefing,” with volleyball, boccie ball and music, at the Army Reserve Center, site of the last marathon vaccination session.

Lingering still, though, was a sense of vulnerability, a sense of a once-safe world now marked by constant, invisible, unavoidable peril. What a revelation this has been, people remarked, over and over. We didn’t realize that this could happen.

Nothing Osterholm had to say could restore the town’s lost sense of security. Instead, talking to about 40 medical and county officials gathered in Immanuel-St. Joseph’s education room, he could offer only added mystery.

He didn’t know why or how the outbreak had occurred, he allowed. He didn’t know why some got sick while others didn’t. He didn’t know why one succumbed while others survived. Despite extensive follow-up, they’d never been able to link Ryan Pitt and the MSU student to the Mankato West cases. It was unlikely they ever would.

What they had learned, Osterholm revealed, was even more unsettling than what they had not.

During the last marathon vaccination round, they’d taken throat swabs from 3,000 elementary school children, seeking insights into the bug. Because this bacteria normally resides passively in the nasal passages of up to 4% of the population, in Mankato they’d expected to find it colonizing in hundreds of people, in order to get a few actual meningitis cases.

But out of 3,000 swabs, Osterholm reported, they had not found a single person carrying the outbreak bug.

The doctors listening in the education room exchanged glances.

That, they all knew, meant the bug was not running wild in the community. Rather, those few people the bug colonized, it made sick. This was, in other words, one extraordinarily virulent bug. This bug had an incredible ability to create severe disease.

Mankato had been hit not by a new bug, but an evolving bug-a representative of what the Journal of the American Medical Assn. editors and scientists were calling a “new clonal group in North America.” It looked similar to a strain responsible for a doubling of meningitis cases in Oregon since 1991. Osterholm’s old familiar relative was changing its personality.

Such evolution happens all the time, Osterholm knew, for a variety of reasons. Such is the world Darwin described. The more forcefully we attack the microbes, the more we accelerate the emergence of varied and resistant strains. We live in the bugs’ world, they don’t live in ours.

Yet something was strange in Mankato. It is not in a bug’s best interest to kill off all its hosts, for it needs hosts. This one was doing just that, though. This one was an outlaw bacteria.

Bizarre, fascinating, scary-but it made sense. A new, more virulent outlaw bug would explain the dramatic increase in outbreaks in recent years. It would also explain why the Mankato outbreak had jumped its fire lines.

Of course, it would also mean that they most likely had not needed to spend more than $2 million and vaccinate 30,000 people, since the bug wasn’t running rampant. They’d aimed far more broadly than the situation required.

If he had to do it over again, though, Osterholm told those gathered in the education room, he would do the same thing. Acting before information was available, what else could he do? “We had no choice,” Osterholm said. “We didn’t want to wait, then two weeks later find out this is what we should have done.”

Left unsaid was another reason for the aggressive response. They acted as they did also because it was something they could do. The alternative-not to act-was simply unthinkable, both to health officials and the public.

Whether in fact they’d had any impact on the Mankato outbreak remains an unanswerable question.

It is “appropriate” to provide vaccines, a recent Journal of the American Medical Assn. editorial observed, but “unlikely to have substantial impact.” Prevention will be an “elusive goal,” the journal concluded, until an effective vaccine for routine use with infants is developed.

By starting early, Osterholm had hoped to alter this usual course of events. Had he?

Osterholm’s best guess, based on previous outbreaks, is they prevented cases and deaths in Mankato. But it is hard, he allows, to say just what they did.

What about coming back to Mankato? asked one of the doctors at the meeting. What about swabbing more throats, doing follow-up studies, learning more?

No, Osterholm said, there was no time or resources for that. In fact, there was no time for further questions.

He was already late for another meeting, 80 miles to the east in Rochester. Another outbreak was under way there, this time of Group A strep-six cases, four deaths. Another town needed calming, another bug needed a response.

“We’ve forgotten the lessons of evolution,” Osterholm said, juggling a beeper and cellular phone as he rushed through the hospital lobby toward his car. “The notion that we can dominate the world-Darwin never said that. It is misleading that we’ve had substantial gains against microbes in recent times. The truth is, it’s not even halftime.”