Details of the Outbreak in Rhode Island

From The Providence Journal

By Felice J. Freyer and Cynthia NeedhamJournal Staff Writers
When 7-year-old Dylan Gleavey fell ill in late November, with what seemed like a bad cold, his parents took him to a walk-in health center. He was diagnosed with a sinus infection. It seemed like a routine childhood illness.
Dylan’s family never dreamed that within three weeks their boy would be dead.
Nor did they imagine that his death would be linked to several other illnesses in his Warwick school that continue to puzzle health officials and alarm the community, leading to the closing of schools in three districts last week.
Health officials have no evidence of a continuing infection spreading in the state. But the sicknesses in the last few months hold many mysteries that have yet to be unraveled. Here’s an account of what has happened so far.
Dylan got sicker. On Thursday, Nov. 30, while watching cartoons in bed, he started vomiting and quickly lapsed into semiconsciousness, unable to move his head. His parents took him to Hasbro Children’s Hospital, and he was admitted in the early hours of Dec. 1. Doctors told his parents that he probably had viral meningitis, an infection of the fluid around the spinal cord and brain. The state sees about 300 to 400 cases of viral meningitis every year, and children who get it usually recover.
But by Dec. 6, Dylan’s diagnosis had changed. He had suffered several more seizures and was lapsing in and out of consciousness. When he was awake, he seemed confused, sometimes yelling out curses, sometimes not talking at all, his mother said. Doctors thought he had encephalitis, a rare and dangerous inflammation of the brain. Informed by the hospital, the Health Department contacted the U.S. Centers for Disease Control and Prevention, asking for laboratory support and consultation. The standard testing for encephalitis was undertaken.
Meanwhile, in the first week of December, a girl who attended the same second-grade class as Dylan also started to feel sick. Like Dylan, Hannah Leahy missed a few days of school and was diagnosed with a sinus infection. And like Dylan, she didn’t get better.
Around Dec. 13, both Dylan and Hannah took a turn for the worse.
Dylan, who was already in the hospital, was admitted to the intensive care unit, according to his parents, Denise and Charles Spoerer. Doctors told them their son’s brain was swollen and drilled a hole in his head, to relieve the pressure.
Hannah, who was at home in Warwick, had awakened in the night screaming in pain. “As a mom, I just knew something wasn’t right,” her mother, Heidi Leahy, recalled in a recent interview. Hannah’s parents rushed her to the hospital, and she was admitted. Doctors said she appeared to have meningitis. It might have been bacterial, but because she had taken so many antibiotics, they could not detect bacteria in her blood.
Over the course of that week, Heidi Leahy said she often saw Dylan’s parents in the hallways of Hasbro, on breaks from their constant bedside watches. The parents shared hugs and, at times, doubts. Each said it was hard to imagine that the classmates’ illnesses were not somehow related, but that’s what doctors kept telling them.
According to Hasbro officials, the hospital on Dec. 13 notified the Health Department that two children from the same school had been admitted with neurological illnesses. Their symptoms, however, were very different. The boy had encephalitis; the girl had what looked like meningitis.
Back in Warwick, the rumor mill had kicked into high gear, as news of the classmates’ illnesses spread.
At Greenwood Elementary School, where both children were students, school nurse Carole Sivo had already contacted the Health Department when Dylan was first diagnosed with encephalitis, to ask whether the school should send a letter notifying parents. “They had said no, we didn’t need to send a notice home about encephalitis,” principal Rosemary Hunter recalled.
But when Hannah was admitted to Hasbro, Hunter said she called the Health Department herself. That phone call touched off what became a string of almost daily conversations that have continued ever since with Dr. Uptala Bandy, the state’s epidemiologist.
Schools Supt. Robert J. Shapiro said it was the Health Department that decided that parents needed to be informed and suggested a letter be sent out. “They really gave us instructions along the way, even to the point of assisting and drafting that letter,” the superintendent said.
“You may have heard that two students at Greenwood Elementary School have been admitted to the hospital,” the letter begins. “… These are isolated and unrelated cases.” The letter was signed by a school official and included fact sheets on encephalitis and meningitis.
That weekend the school was cleaned and parents were invited to a meeting on Dec. 18. No one alerted the media, but parents who attended the meeting later said that Bandy also told them that the two illnesses were probably not related. “Dr. Bandy explained that if it had been a mass outbreak, you’d have seen cases every three to four days,” said Bethany Furtado, a School Committee member and former chairwoman of the Greenwood Parent Teacher Organization.
Those at the meeting, including Hunter, recalled a high level of anxiety. Dylan’s father said he went to the meeting to voice the concerns that had bothered him for days: How could the two cases not be connected? Two kids from the same classroom with neurological illnesses?
On Thursday, Dec. 21, Dylan Gleavey died in the ICU at Hasbro.
The 7-year-old who loved riding his scooter and pretending to be a superhero spent his last few days heavily sedated, in and out of a coma, his parents said.
Test results ruled out two possible causes of encephalitis — rabies and Eastern equine encephalitis. No one knew what caused the encephalitis that killed Dylan Gleavey. About 80 percent of the time, the cause of encephalitis cannot be determined.
But health officials were growing concerned. They learned that Hannah Leahy was taking a long time to recover, and it looked like she, too, might have encephalitis. They also learned of another encephalitis case in a middle schooler from West Warwick that occurred earlier the same month.
Faced with the death of a 7-year-old and two other cases of encephalitis, a rare condition, within a narrow geographic area, Dr. David R. Gifford, the state director of health, decided to get some help. On Dec. 22, he filed a formal request with the CDC asking the federal agency to deploy an epidemiological team.
Meanwhile, Hannah started to get better. She returned home on Dec. 23, the Saturday before Christmas.
The day after Christmas, while schoolchildren were on vacation, the Greenwood School sent home a second letter, announcing the loss of a “sweet, kind and loveable little boy who won the hearts of all who knew him.” The letter did not mention Hannah Leahy. The same day, two doctors from the CDC’s Epidemic Intelligence Service arrived in Rhode Island. They asked school officials for access to attendance rolls. They identified every child at the Greenwood School who had been absent for more than two days, and contacted the children’s parents and then their pediatricians. They turned up several cases of pneumonia, including a number that had been confirmed by chest x-ray. And they did tests to identify the cause.
On Friday, Dec. 29, two test results returned from the CDC. One showed that another child at the Greenwood School, who’d had pneumonia, had been infected with mycoplasma pneumoniae, a common bacteria. By itself, this was not significant; mycoplasma causes a number of pneumonia cases every year.
But the second test result gave pause: Hannah Leahy had also been infected with mycoplasma. She never had pneumonia, but she probably had encephalitis. Only very rarely does mycoplasma lead to encephalitis.
It was time to act. The state’s incident command system was activated. This is an emergency management structure with prearranged roles, terminology and lines of authority. A command center was established at the Emergency Management Agency in Cranston.
Gifford asked the CDC to send more investigators, and three more were dispatched. A typical CDC investigation involves one or two people. Rhode Island would soon have five.
The concern was not simply with the discovery of mycoplasma pneumoniae. They are commonplace bacteria that health officials don’t track and doctors don’t often worry about. Many people get infected with them, usually suffering symptoms like a common cold and then getting better without treatment. Sometimes mycoplasma can lead to “walking pneumonia,” a mild inflammation of the lungs that is common in school-age children and young adults.
But this situation was different. Only in one-tenth of 1 percent of the cases does mycoplasma lead to meningitis or encephalitis. And here there were two cases of encephalitis arising in one classroom, one of them clearly linked to mycoplasma. (Mycoplasma was never found in any specimens from Dylan Gleavey, but the bug is difficult to detect, and health officials presume that Dylan, too, was infected with it.)
At the same time, several cases of pneumonia had occurred in the same school — and one of them had already been linked to mycoplasma. (By the end of the New Year’s Day weekend, health officials would confirm that mycoplasma had caused a total of five pneumonia cases at the Greenwood School in November and December, in addition to the two encephalitis cases.)
So what to do about the Greenwood School? Health officials weighed their options. When mycoplasma outbreaks have occurred in places like long-term-care facilities or military training schools, the CDC has recommended that antibiotics be distributed to everyone who lives or works there, even if they don’t have symptoms. This has sometimes, but not always, stopped the outbreak.
But an elementary school is not like a military base. Children and staff don’t live at the school — they come and go, intermingling with the community. Never before had antibiotics been distributed to an entire school as a preventive measure. But Gifford and his CDC advisers decided it was worth a try.
On Dec. 30, the Health Department held a news conference announcing that the Greenwood School would be closed till Jan. 8, and antibiotics would be offered to every family who had a child there, to stop a possible outbreak of mycoplasma. On Dec. 31, Jan. 1 and Jan. 2, health officials met with every family with children in the school, about 275 families. Nearly all agreed to take the antibiotics, and 1,182 doses were distributed at a cost of $57,000.
On Tuesday, health officials concluded that the West Warwick encephalitis case they’d heard about, involving a child from John F. Deering Middle School, had also been linked to mycoplasma. Little information was released about that case, not even the child’s age or sex. Health officials would only say that the child went to Hasbro Children’s Hospital early last month, was diagnosed with a mild case of encephalitis, and later went home to recover.
Meanwhile, the investigation was broadening. CDC doctors asked hospitals for information on any neurological illnesses, and checked attendance records at schools in neighboring towns. They found that two schools in Coventry had unusually high absenteeism rates. They interviewed families and pediatricians and sent throat swabs and blood samples to the CDC lab in Atlanta for analysis. They were trying to determine why a normally insignificant infection had led to three encephalitis cases in a narrow geographic area. Had the bug mutated into something more dangerous?
They also wanted to know if any unusual infection was continuing to spread. In the first days of the new year, it appeared not. But the data had not been completed or analyzed, so no one could be sure. The incubation period for mycoplasma — that is, the time from when a person becomes infected until the person shows symptoms — is typically two to three weeks, four at the most. If no new cases occurred, then it would seem that whatever happened at the Greenwood School had come and gone.
Then, on Wednesday evening, health director Gifford got word that a child from Coventry had been admitted to Hasbro Children’s Hospital with a probable case of meningitis. Actually, it looked like viral meningitis — but so had the cases from the Greenwood School. And Coventry was one of the towns were CDC doctors were investigating higher-than-normal absenteeism.
It would take a few days to find out whether the Coventry child had been infected with mycoplasma.
After several hours of pre-dawn consultations among state, health and school officials, it was decided that, in “an abundance of caution,” all schools in Warwick, West Warwick, and Coventry would close for Thursday and Friday, affecting more than 20,000 youngsters.
Yesterday, test results showed that — as expected, as hoped — the Coventry child had not been infected with mycoplasma.
What happened in December remains under study. Meanwhile, schools in Coventry, West Warwick and Warwick will reopen tomorrow.

Here is a timeline of the 2003 SARS outbreak. Notice it begins with an unusual outbreak of pneumonia.

1918 Flu Provides Clue

1918 killer flu tested on monkeys
By SETH BORENSTEIN, AP Science Writer Wed Jan 17, 11:06 PM ET
WASHINGTON - Scientists who tested monkeys with the resurrected 1918 killer flu virus now have a better idea of how the deadliest epidemic in history attacked and killed so many people — by over-amping the victims' own immune systems.
Those findings in a first-of-its-kind experiment also help explain why so many of the roughly 50 million who died in the Spanish flu pandemic were young and healthy. Based on what was seen in monkeys, the human victims' strong immune systems likely were overstimulated, causing their lungs to rapidly fill with fluid.
"Essentially people are drowned by themselves," said University of Wisconsin virology professor Yoshihiro Kawaoka, lead author of a study being published Thursday in the journal Nature.
Scientists believe the results open a window into what could happen if the current bird flu in Asia morphs into a highly lethal strain that spreads easily among people.
The 1918 virus was reconstructed with reverse genetics, relying on tissue from victims of the early-day flu pandemic. The virus is kept only in two labs where scientists are studying it: the U.S. Centers for Disease Control and Prevention in Atlanta and the Public Health Agency of Canada's lab in Winnipeg where the monkey experiment was done.
When seven macaques were given the virus at the high-level biosafety lab there, scientists were struck by how suddenly and overwhelmingly the flu struck. The virus spread faster than a normal flu bug and triggered a "storm" response in the animal's immune systems.
Their bodies' defenses went haywire, not knowing when to stop, researchers said. The lungs became inflamed and filled with blood and other fluids.
The scientists believe the virus had the same effect on humans in 1918.
The macaque experiment was supposed to last 21 days, but after eight days the monkeys were so sick — feverish, in pain, and struggling to breathe — that ethical guidelines forced the researchers to euthanize them.
"There was some surprise that it was that nasty," University of Washington virologist and study co-author Michael Katze said. "It was the robustness of the immune system that helped victimize them."
The virus is very good at replicating itself, said Peter Palese, chairman of the microbiology department at Mount Sinai School of Medicine in New York. Its effect on the immune system "triggers what one refers to as a cytokine storm," he said. Cytokines transmit messages among cells in the immune system. Palese wasn't part of the study but has worked on the resurrected virus before.
No other flu virus is deadly to monkeys, and the speed in its spread and the overwhelming immune system response is similar to those in the H5N1 bird flu, Kawaoka said.
If bird flu spreads person-to-person, scientists believe understanding the 1918 virus may give them clues about how to protect people from the new one.
The new work "gives us another tool," said Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, who was not part of the research. Fauci praised the study and said what it found in the effects on the body are stunning: "There aren't a lot of things that can induce that robust of an inflammatory response that quickly."
The 1918 flu research suggests that those fighting the bird flu in the future could try using drugs that reduce inflammation and control the body's immune response, Katze said.
In the Winnipeg research, the first controlled introduction of the 1918 flu to primates, the monkeys were given extra high doses of the flu virus by nose, mouth, eye, and direct injection into the trachea to ensure infection.
The virus had been tested before on mice, but macaques provide better models of how viruses work on humans, the scientists said.
The fate of the monkeys was sealed within hours of their infections, Katze theorized.
In normal flu, the immune system response wanes, but in the 1918 flu "the innate response stayed up and didn't go down," Katze said.
Adolfo Garcia-Sastre, a Mount Sinai microbiology professor who conducted some of the earlier mouse work, cautioned that it may be a mistake to focus so heavily on immune system response. The 1918 flu "induces an overwhelming and probably damaging immune response system" but it is largely because the virus grows so much, he said.
In mice, when the overactive immune response was eliminated, mice died because of high viral levels.
"It's like a vicious circle, you get more viruses, you get more immune response and this results in damage," Garcia-Sastre said.
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On the Net:
http://www.nature.com

Rhode Island School Closed Due to Outbreak

By JUSTIN M. NORTON, Associated Press Writer

COVENTRY, R.I. - Rhode Island officials canceled school Thursday for more than 20,000 students while health experts search for any connection between a suspected case of meningitis and a second-grader's encephalitis death two weeks ago.
"Given the parents' concerns and our concerns, we felt that out of abundance of caution we would keep schools closed for the next two days," Dr. David Gifford, director of the state's Public Health Department, said early Thursday.
"Calling it an outbreak at the time is premature," he said.
The meningitis case was reported late Wednesday in a student at Hopkins Hill School in Coventry. Meningitis is an inflammation of membranes protecting the brain and spinal cord that requires hospitalization in severe cases.
Encephalitis also involves brain inflammation caused by a virus. It was blamed for the death of one Warwick student last month and two other children's illnesses.
There has been an unusually high incidence of pneumonia in those communities, Gifford said. Several Warwick students in recent months developed infections of mycoplasma pneumonia, or "walking pneumonia," which is common and can, in rare cases like that of the Warwick second-grader, progress to encephalitis or meningitis.
Health investigators will spend the next few days talking to school nurses and looking for possible additional cases in hospitals.
More epidemiologists from the U.S. Centers for Disease Control and Prevention are also headed to the state to assist the half-dozen scientists already in Rhode Island, officials said Thursday.
Health and school officials will then meet over the weekend to determine when the public schools will reopen.
Classes were called off Thursday and Friday for 11,500 public school students in Warwick, 6,000 in Coventry, and 4,000 in West Warwick. Schools in other parts of the state will remain open, Gifford said.