The 2015 OXFORD COUNTY FAIR E. COLI O111:H8 Outbreak

E. coli Outbreaks in these types of settings are nothing new. On October 1, 2015 Maine Center for Disease Control and Prevention (ME CDC) staff was notified that a child was hospitalized at Maine Medical Center with Hemolytic Uremic Syndrome (HUS). The next day St. Mary’s Regional Medical Center (RMC) made a second report about the child, identified as Colton Guay, as well as a report about a second and unrelated child with HUS, Myles Herschaft. Per established protocol, Sarah Bly, Field Epidemiologist for the Western District, was assigned to investigate and interview the parents of both children. Because both children had reportedly been to the petting zoo at the Oxford County Fair, ME CDC staff notified the State Veterinarian, Michele Walsh of the common exposure to the fair by the two children.

Colton Guay

Twenty-month-old Colton Guay and his parents attended the Oxford County Fair on September 16 and again on September 19. Colton spent time at the petting zoo. He had contact with various animals and sawdust on the ground. On September 25 Colton experienced onset of diarrhea, which soon turned bloody. He was seen at the Emergency Department of St. Mary’s RMC on September 29 and admitted to Maine Medical Center on October 1. Colton developed HUS and died on October 5 from his infection. A stool specimen (Specimen ID# M00261131) collected on October 1 was culture positive for Shiga Toxin E. coli O111:nonmotile at the Maine Health and Environmental Testing Laboratories (ME HETL). This finding was confirmed by the federal Centers for Disease Control and Prevention (CDC), which further characterized Colton’s STEC infection as E. coli O111:H8 (Specimen ID#3000462626). ME HETL conducted Pulsed Field Gel Electrophoresis (PFGE) and determined that Colton was infected with strain “EXDX01.1540/EXDA26.1144.”

On October 9 Ms. Bly interviewed Colton’s parents and completed a “Hypothesis Generating Questionnaire.” Colton had no meals at restaurants and ate no beef or pork products. He did not consume unpasteurized dairy products or juices. Colton did consume green grapes purchased at Walmart located in Windham, Maine. He also ate cucumbers and pears. He had exposure to pets in the home.

Myles Herschaft

Myles Herschaft, 17 months old, attended the Oxford County Fair with his parents on September 18. He visited the petting zoo and touched animals and sawdust. Myles experienced onset of diarrhea on September 25. He was diagnosed with HUS on October 1. A stool specimen (Specimen ID# M00261130) collected on October 3 was positive for Shiga Toxin E. coli O111:nonmotile at ME HETL. This finding was confirmed by the federal CDC (Specimen ID#3000462628). ME HETL conducted Pulsed Field Gel Electrophoresis (PFGE) and determined that Myles was infected with strain “EXDX01.1540/EXDA26.1144.” Notably, this was the exact same strain that infected and killed Colton Guay.

Using the Hypothesis Generating questionnaire, Sarah Bly interviewed Myles’ parents about his potential exposures to STEC in the 7 days before illness onset. Myles consumed fresh fruits including apples, grapes, bananas, and strawberries. The grapes were purchased at Walmart located in Auburn, Maine. He also ate cucumbers, a corndog from a stand at the Oxford Fair and chicken nuggets from McDonalds.

Environmental Investigation

Public health inspectors visited the Walmart store in Auburn and the Walmart store in Windham as well as the Walmart Distribution center located in Lewiston regarding the grapes Colton and Myles consumed. Hronis, Inc., a Delano, California company was the producer. Grapes were delivered to the distribution center prepackaged and in cardboard boxes. There were no complaints of illness regionally or nationally regarding this product, effectively ruling out any link between consumption of grapes and STEC illnesses experienced by Colton Guay and Myles Herschaft.

Dr. Michele Walsh, State Veterinarian, was told by fair officials that there was no illness reported in fair staff. No animals were reported sick. On October 7, 2015[1] Dr. Walsh collected samples from three areas at the fairgrounds: poultry area in the main barn, pig/ruminant pens, and the petting zoo area. Three samples were collected from each area. Environmental sampling was conducted 18 days after the fair closed and after the area had been cleaned. Samples were sent to HETL for testing. Shiga toxin 2 was detected by polymerase chain reaction (PCR) in the outside pig area. Shiga toxin 2 was detected by PCR in one petting zoo sample. These two samples were sent to the CDC for additional testing. CDC isolated Shiga toxin E. coli O100:nonmotile in the sample collected outside pig den area. The CDC did not isolate Shiga toxin in the sample collected from the petting zoo area.

Summary

In September 2015 two children, Myles Herschaft and Colton Guay, were diagnosed with E. coli O111:nonmotile. The incubation period (i.e., the time between exposure to a bacteria and onset of symptoms) for Shiga toxin E. coli averages 2 to 5 days, (range 1 to 10 days). Colton Guay attended the Oxford Fair on September 16 and on September 19. He experienced symptom onset on September 25. Myles Herschaft attended the fair on September 18 and experienced symptom onset on September 25. The incubation period for each child was within the accepted incubation period for exposure to Shiga toxin E. coli at the Oxford County Fair.

Genetic testing showed that Myles Herschaft and Colton Guay were infected with an indistinguishable strain of E. coli O111 identified as PulseNet Pattern Identification Numbers XDX01.1540/EXDA26.1144. There were no other patients infected with this genetic strain occurring temporally in the United States. Given the rarity of strain XDX01.1540/EXDA26.1144, it stands to reason that Myles Herschaft and Colton Guay shared a common exposure to this specific strain. Public health investigators identified two potential exposures, consumption of green grapes and attending the Oxford County Fair. Investigators ruled out green grapes as a source of infection after learning the grapes were prepackaged and distributed nationally. E. coli O111 was not found when samples were collected 18 days after the fair had ended and the grounds had been cleaned. It is noteworthy, however, that a different Shiga toxin E. coli, E. coli O100:nonmotile was found in an environmental sample. There was no testing of animals that were exhibited at the Oxford County Fair.

Transmission of STEC from animal areas of fairgrounds is a well-known risk factor and multiple outbreaks have occurred in the US over the past 10 years. Exposure to petting zoo animals and the petting zoo environment at the Oxford County Fair is the only plausible exposure to explain how Colton Guay and Myles Herschaft acquired their genetically indistinguishable E. coli O111 infections.

Drs. John Dunn and Kirk Smith are uniquely qualified to assess the facts of this case. Co-authors of the “Compendium of Measures to Prevent Disease Associated with Animals in Public Settings, 2013” published by the National Association of State Public Health Veterinarians and the CDC, Dr. Dunn and Dr. Smith reviewed ME CDC outbreak investigation documents. Independently they reached the same conclusion that Colton Guay and Myles Herschaft became ill with STEC O111 as a result of attending the Oxford County Fair.

Dr. Smith opines that the source of the E. coli O111 infections experienced by Myles Herschaft and Colton Guay was more likely than not the Oxford County Fair (“Fair”). Dr. Smith also opines that the Fair did not implement at least several critical prevention measures recommended in long-standing, widely available, national recommendations to prevent illness in visitors to public animal contact venues. He asserts that had these critical recommendations been implemented at the Fair, more likely than not the boys’ infections would have been avoided.

Dr. Dunn concurs stating that with regard to the outbreak of STEC O111 and subsequent HUS affecting Colton Guay and Myles Herschaft, “…with a reasonable degree of epidemiological certainty it is more likely than not that transmission occurred at the Oxford County Fair petting zoo.”  He notes that information about measures taken to prevent disease transmission to fairgoers was limited but writes that “applicable recommendations from the Compendium [Compendium of Measures to Prevent Disease Associated with Animals in Public Settings, 2013] were not implemented or implementation was not clearly evident in the materials” he reviewed. He states that in his opinion “to a reasonable degree of epidemiologic certainty, had the recommendations from the Compendium been implemented, it is more likely than not that the risk of STEC O111 infection for Colton Guay and Myles Herschaft would have been minimized and potentially prevented.”

COLTON JAMES-BRIAN GUAY’S E. COLI O111:H8-INDUCED HUS ILLNESS

Jon and Beth Guay are a married couple who reside in Poland, Maine. They are the proud parents of an adorable little boy by the name of Colton James-Brian Guay, who died on October 5, 2015 at just 20 months of age. Colton was the innocent victim of a deadly enteric pathogen, Enterohemorrhagic Escherichia Coli (EHEC), Serotype O111:H8, which he was exposed to during what was supposed to be an enjoyable and educational outing to the local county fair.

Colton James-Brian Guay

Despite his and Beth’s incomprehensible loss, Colton’s dad Jon has taken the time to describe his precious son as only a loving parent can. Jon remembers his little boy as the light of their lives:

Our son Colton James-Brian Guay was a very bright, funny, loving child whose death came much too soon. He loved music, reading, his two dogs, rocking to sleep in his father’s arms, cleaning the house with his mother, and anything to do with police cars and equipment. Colton would often forgo playing with toys in exchange for anything mechanical or electrical. Colton would spend hours trying to figure out the mechanics any particular device in order to learn how they worked. At only 20 months old he knew how to perform basic functions with a touch screen cellphone, he knew how to operate and likewise add attachments to the vacuum cleaner, knew how to reset the entire Direct TV system! and could plug electrical items into sockets and make them run. He also had an infectious smile and laugh that would lighten the worst of any moods. Colton was beginning to speak in sentences and the final words he learned prior to his death were “thank you.” Colton learned how to share the first moment he picked up a toy and was by and large the light of our lives.

A busy young man

Beth and I were always very protective of Colton, but realized that he could not grow up in a bubble. We always fed him proper and nutritious food and kept him clean and sanitized at all times. Colton’s trips to the Oxford Fair were his only exposure to the outside world in the ten days leading up to his illness. I had worked a massive amount of overtime and the days I took Colton to the fair were the only days I had time to spend with him. It was this period of constant working that Colton only ate pasta, toast, and cereal and did not have any uncooked meat, raw vegetables, or any other foods out of the ordinary.

On Thursday, September 17, 2015, at approximately 8:00 AM, Jon took Colton to the Oxford County Fair located at 68 Pottle Road in the town of Oxford, Maine. Beth had worked the previous night and Jon decided to take Colton out of the house in order to give her some time to sleep and also to spend some quality time with his son. When they arrived at the fair, Jon placed Colton in his stroller and began walking around the fairgrounds. Most of the venues, vendors, and rides were closed as it was early in the morning.

Jon had decided to take Colton to the Oxford Fair Petting Zoo as he thought his son might like to see the various farm animals for the first time in his life. Upon entering the petting barn, there were sheep, chickens, rabbits, pigs, and goats available to see and touch. Jon recalls:

I took Colton out of his stroller and allowed him to walk around the petting area. I was in direct contact with Colton at all times and did not notice if he pet any of the animals or not. Colton was very intrigued by them as one would assume a child would be, but Colton was slow and the animals walked much faster than he did. I do recall that Colton touched a few hay bales, support beams, and one or more wooden steps on a platform that were in the petting area. After approximately 10 minutes we left the petting barn where Colton was placed back in his stroller and I placed hand sanitizer on his hands and wiped them as best I could. The hand sanitizer used was the one that I had brought myself. There was one hand sanitizer that I saw in the barn, but it was empty. In addition, the only sign I observed was a white poster board that forbid children from chasing the animals. The same sign advertised cups of food to feed the animals for the price of $1.00.

As Colton and his dad left the petting barn, he remained in his stroller as Jon walked him through many of the open animal barns. Jon’s recollection is that Colton did not have any physical contact with any further farm animals. After approximately one and a half hours, they left the fair and returned back home to Poland. Colton did not eat anything at the fair, since most of the food vendors were not open anyway.

A couple of days later, Jon, Beth and Colton returned to the Oxford Fair. It was about 7:30 PM on Saturday, September 19^th when they arrived for the purpose of watching a demolition derby that the fairgrounds had advertised in their schedule of events. Jon recalls:

Upon arrival Beth and I decided to bring Colton back to the petting barn as the demolition derby had not yet started. Once in the petting barn, Colton was taken out of his stroller and allowed to walk inside the petting area. I supervised him the same as I did the time before. The same animals were in the petting barn as I had recognized from our last trip the previous Thursday with the addition of what appeared to be a new born baby calf. It is my recollection that Colton touched a baby goat while in the petting barn as well as hay bales, wooden steps, beams, and a metal gate. I do recall that there was feces of an unknown animal on one of the wooden platforms. Colton and I stayed in the petting barn for approximately 15 minutes when the decision was made to leave. Upon leaving the petting zoo Beth placed hand sanitizer that she had brought on Colton’s hands and then washed them with baby wipes. As was the case before, the hand sanitizer in the petting zoo was empty.

Jon and Beth placed Colton back in his stroller and they walked through the various animal barns and exhibits. Looking back, they remember that Colton did not have any further physical contact with animals nor did he come out of his stroller again. After a short while, they made their way over to the demolition derby, which was packed with people. Because there were no seats available and visibility was obstructed, they ended up leaving the fairgrounds at approximately 9:00 PM and returned home.

Jon and Beth recall that Colton was not acting like his usual self a few days later, when on Wednesday, September 23^rd he was fussier than he had ever been before. Colton also had a runny nose, was lethargic, and had a decreased appetite. Over the next few days, his symptoms progressed to stomach cramps, diarrhea, and then watery diarrhea that would require several diaper changes an hour. At this point, Beth contacted Colton’s primary care doctor at Pediatric Associates, who advised them to just monitor the baby as medication or antibiotics were not recommended for a child of his age. Jon recalls, “This was the first time in Colton’s life that he became sick.”

Jon and Beth followed the doctor’s directions to watch Colton and keep him fed and well hydrated, which was not easy given Colton’s diarrhea. They became alarmed on Sunday, September 27^th, when Colton began showing signs of blood in his diarrhea. Beth contacted the on-call doctor for Pediatric Associates, who assumed that the blood they were seeing was a result of irritation to the bowels from all of the diarrhea he had endured. Jon remembers getting more advice on the phone:

We were advised to administer fluids, which was difficult as Colton showed little to no interest in eating or drinking. We are also advised to place a protective cream such as Desitin on his bottom to assist in healing the irritation (which we were already doing). The bloody diarrhea persisted over the course of the day on Monday 9/28/15. It was also on Monday that Colton vomited twice, could not hold any food down, and ultimately refused to eat.

By Tuesday, September 29^th, Jon and Beth were becoming increasingly alarmed—they had had enough “advice,” as Colton was not getting better. That morning, Beth contacted Pediatric Associates and demanded that Colton be seen, as his condition was not improving and it was clear he was becoming severely dehydrated. The only available time slot for an appointment was slated for 6:00 PM. They had no choice but to wait, while Colton became worse throughout the day and started vomiting. He continued to have bloody, foul smelling diarrhea.

In the midst of their worries over Colton, the couple had to get Beth to a medical appointment at 3 PM that afternoon, which had been set up earlier. Beth was scheduled to have an obstetrical ultrasound at St. Mary’s Hospital. The two of them tried to remain optimistic during this much-anticipated event, as they were overjoyed to be pregnant with a new baby on the way. It was during this appointment that they learned they were expecting a “girl” in mid-February 2016. However, Jon and Beth’s celebration over the exciting news was short-lived when they arrived for Colton’s appointment only to find he was so sick he had to be hospitalized.

On September 29, 2015 at 6:30 PM, Caitlin Wiscount, MD evaluated Colton at her office. Despite finding only a low-grade fever of 99ºF, Dr. Wiscount could see right away that the toddler was seriously dehydrated with what she thought was simple viral gastroenteritis. However, when Beth described how little urine Colton was passing—and that he was not producing any tears when he cried—the doctor became highly concerned. An exam confirmed dry mucous membranes and a very sick little boy. Dr. Wiscount called over to St. Mary’s Regional Medical Center, ordered lab tests, and arranged for Colton to bypass the emergency department to be admitted directly to the hospital.

Dr. Wiscount dictated an admission history and physical examination at 6:54 PM, documenting “moderate dehydration” and “viral gastroenteritis” as Colton’s admitting diagnoses; however, it is not clear whether she dictated the note from her office or whether she met the Guay’s at the hospital. Her “PLAN” was to admit Colton to St. Mary’s under Pediatric Associates, “will place an IV and will give 2 normal saline boluses of 20 ml per kg,” “will start maintenance IV fluids,” “will obtain a basic metabolic panel,” “will allow a clear liquid diet including Pedialyte,” and “will supply Tylenol or ibuprofen as needed for fevers.” The last part of Dr. Wiscount’s admission history and physical did not reflect the high level of concern felt by Jon and Beth, where she commented: “The parents are aware that this admission is likely for 24-48 hours or until Colton is able to maintain his fluid status.”

Despite Dr. Wiscount’s care plan, Jon recalls that nothing really happened quickly that evening:

We were placed in a room where several blood draws and stool samples were taken. We waited nearly three hours for Colton’s first intravenous drip. Dr. George Glass of Pediatric Associates arrived at around 9:00 p.m. where he evaluated Colton and determined that they would wait until the following morning to determine if the intravenous fluid would help his dehydration. As the next morning came, 10/1/15, Colton’s condition continued to worsen. He was in extreme pain and the intravenous fluid had little to no effect on him.

At approximately 12:00 p.m. on 10/1/15, we were met by Dr. Linda Glass of Pediatric Associates who arrived to check on Colton’s condition. Beth expressed her frustration with the lack of answers from St. Mary’s as to what was going on with our son. Beth insisted that something be done as she felt Colton was slipping away.

A hospital lab printout for blood collected on September 29^th at 7:27 PM, showed results for blood chemistries with a marginally elevated BUN of 19 (RR 6-17) and normal serum creatinine of 0.27 (RR 0.2-0.8); however, Colton’s CO2 was abnormal at 17 (RR 21-32). Another blood draw at 2:34 PM on September 30^th showed that Colton’s test results were profoundly abnormal – white blood cell count (WBC) was 23.6 (RR 6.2-14.5), his hemoglobin and hematocrit were in normal range, but his platelet count was very low at 64 (RR 140-440). Colton’s stool was also positive for blood.

Jon recalls what the doctor told him about Colton’s blood work:

Dr. Glass looked into the matter and later told us that Colton’s blood work should results that “were all over the place.” Dr. Glass was also upset as the intravenous fluid given to Colton was far below the recommended amount. We also found out through Dr. Glass that St Mary’s had apparently botched one of more of the stool sample cultures and thus had no determination of what may be wrong with Colton.

Dr. Glass then called the Barbara Bush Children’s Hospital at Maine Medical Center in Portland, ME and spoke to a nephrologist. That conversation resulted in the urgency for Colton to be sent to Maine Medical Center as soon as possible. Within the next two hours Colton was prepared for transport and sent to Maine Medical Center in Portland by ambulance.

On October 1, 2015, Dr. Glass wrote Colton’s “Transfer Summary,” which told the story of what had occurred since his arrival at St. Mary’s. She indicated that Colton’s renal function labs had worsened that morning, with a BUN that was now elevated to 53 and a creatinine of 2.70. His white count was even higher at 30 and his platelets had fallen even lower to 26. His CO2 had fallen further to 12. Dr. Glass commented in her chart note: “Based on the findings of acute renal injury as well as thrombocytopenia and leukocytosis, Maine Medical Center has been consulted regarding transfer to a nephrology service for further workup at this particular time.” The admitting nephrologist was identified as Dr. Oliver Fremont, who advised Dr. Glass to adjust Colton’s IV fluids to include sodium bicarbonate to correct the metabolic acidosis evident in his CO2 level, and to transfer the child to their hospital as rapidly as possible with a nurse escort. Dr. Glass assigned Colton the discharge diagnoses as “…A 20-month-old with bloody gastroenteritis with onset of acute renal injury and thrombocytopenia as well as leukocytosis.”

United Ambulance Service was dispatched around 11 AM to transport Colton to Barbara Bush Children’s Hospital at Maine Medical Center (MMC) in Portland, Maine. Paramedic Robert Sharkey documented that the transfer was requested for treatment of possible disseminated intravascular coagulation (DIC). “Patient has had a cold for 8 days and diarrhea for the last 3. Patient has multiple abnormal lab values. RN riding along for patient care.” The ambulance left St. Mary’s at 11:03 AM and arrived at Maine Medical Center at 12:40 PM.

Pediatric critical care resident Sarah Sedney, MD received Colton at the hospital, where a history and physical exam was underway around 2 PM. Dr. Sedney took a history from Jon and Beth about Colton’s illness onset and asked about possible exposures to substances or sick people. Beth told the doctor about taking Colton to the Oxford Fair where he had pet some animals—however, she knew she had washed his hands afterwards. She thought it possible he could have put his thumb in his mouth before she could do so.

Beth and Jon recounted that Colton’s illness had begun with congestive symptoms, which progressed to loose, watery stools that soon turned bloody—the latter had occurred about four days before their arrival at the hospital. At that time, they noticed Colton acting fussy, not wanting to eat or drink, and having decreased urine output. While his congestive symptoms resolved, his stools continued to be loose and watery with blood, prompting his parents to bring him to Pediatric Associates, “… who then admitted him to St. Mary’s on Tuesday 9/29.” Beth told the doctor that while at St. Mary’s, Colton vomited yellow fluid and since then he had been dry heaving without anything coming up. “At St. Mary’s, he received fluids, Tylenol, and ibuprofen (one dose at 0200 AM on Wednesday, 9/30).” To the parents’ knowledge, no imaging or stool culture was performed.

Dr. Sedney noted that Colton’s labs during his 40+ hours at St. Mary’s evidently demonstrated a sharp increase in his serum creatinine, which prompted the urgent transfer to MMC on October 1^st for more comprehensive care with a pediatric nephrologist. She documented in the chart that the labs from St. Mary’s showed that Colton’s serum creatinine had jumped from 0.27 to 2.70 and his BUN had spiked from 19 to 53. His WBC count was 37.0, and his liver transaminases were markedly elevated with an AST 217 and ALT 146. His bicarbonate was also low, falling from 17 down to 12.

On exam, Colton appeared tired and pale and uncomfortable, crying sporadically and otherwise lying in the hospital bed without energy. Dr. Sedney had some difficulty trying to examine Colton’s abdomen—auscultating hypoactive active bowel sounds in his left lower quadrant, and Colton becoming disrupted and unhappy with any attempts at palpation of his right lower abdomen.

Dr. Sedney wasted no time in coming to a diagnosis for Colton—she opined that he had hemolytic uremic syndrome (HUS)—as evidenced by bloody loose stools for about four days and the dramatic increase in his serum creatinine. She ordered stat lab tests to include another CBC, metabolic panel, and stool culture. She ordered IV fluids with bicarbonate added to his base fluid of D5 ½ normal saline. She warned Jon and Beth that Colton was likely going to need dialysis as he probably had renal damage, immediately contacting surgery to prepare for the placement of a peripherally inserted central catheter (PICC line) on October 2^nd if he did not show significant improvement and continued to be anuric (producing no urine). Dr. Sedney told Jon and Beth that antibiotics were not indicated in HUS, as they could cause worsening of Colton’s condition and increase the release of toxins. Colton was admitted to the Pediatric Intensive Care Unit.

Jon recalls hearing how sick Colton was:

Upon arrival at Maine Medical Center’s Barbara Bush Hospital located at 22 Bramhall in Portland, ME we told by a nephrologist that Colton had HUS Hemolytic Uremic Syndrome. We were advised of the complications of the e coli that was invading his body and that the treatment for the disease was supportive in nature as there was no cure. The doctors at Barbara Bush told us that part of the treatment included dialysis and that Colton was to have a procedure the following morning to install the tubes in order to make that happen.

At some point in the day on October 1^st, the Nordx Scarborough Campus Laboratory reported a critical value from Colton’s stool collection that Shiga toxin STX1 and STX2 had been detected by PCR testing. This was reported to the State Health Department and the isolate sent for confirmation and typing. (The laboratory also later reported growth of “E. coli O111: NON-MOTILE isolated” – the CDC later confirmed positive Escherichia coli, Serotype O111:H8.)

Pediatric nephrology attending Oliver Fremont, MD came in to see Colton at 4:35 PM and found it notable that the little boy had been a generally healthy 20-month old toddler in his usual state of good health until about ten days earlier, at which time he developed a fever and cold symptoms. Dr. Fremont reviewed Colton’s lab test results showing that Colton’s metabolic panel at the time he was admitted to St. Mary’s on September 29^th was unremarkable with a serum creatinine of 0.27, although his CO2 was “a little low” at 7 meq/L. Colton’s platelets were significantly low at 64K, however, and his hemoglobin was 11.8. Dr. Fremont observed that, while Colton had been started on IV fluids, he continued to have copious bloody diarrhea, making it impossible to tell how much urine he was actually producing.

Dr. Fremont reviewed Colton’s lab results from that morning before he was transported, showing a serum creatinine of 2.7 mg/dL, platelets acutely low at 26K, and a hemoglobin of 10.7. He agreed with Dr. Sedney’s assessment that Colton was suffering from anuric acute kidney injury, thrombocytopenia, and evolving anemia in the setting of bloody diarrhea. He commented: “This is consistent with hemolytic uremic syndrome (HUS).” Dr. Fremont did not believe Colton had any appreciable urine production, and Beth told him she thought Colton also appeared to be slightly swollen.

Dr. Fremont told Beth and Jon that if Colton’s current creatinine upward trend continued, they needed to consider placing a hemodialysis catheter as early as the next morning. Dr. Fremont took great care to thoroughly explain the implications of shiga-toxin-mediated HUS with Beth and Jon, reassuring them that the outcome was usually excellent; however, there were no therapies that had been proven to affect the course of the illness. Antibiotics in particular could make things worse. Dr. Fremont also explained that Colton’s electrolyte balance favored acidosis at the moment, but they would replace his diarrheal losses with supplemental bicarbonate in his IV. Dr. Fremont put no restrictions on what Colton could eat, but he was hardly eating anyway because he was so sick.

While Colton was getting sicker and sicker, Jon encountered another parent whose child was going through something similar, and becoming suddenly aware of where his son had picked up his illness:

On 10/1/15, I met Victor Herschaft whose son, Myles, was admitted to Maine Medical Center six hours after Colton. Victor told me that he too brought Myles to St. Mary’s hospital for the same concerns and symptoms Colton had been experiencing. The St. Mary’s staff was quick to recognize the similarities between the two boys and quickly transported Myles to Maine Medical Center. During my time with Victor we spoke to one another about where our children could have picked up the e coli that was causing them severe health complications. Neither I nor my family knew Victor or his family. Our children had never met either. The only common denominator was that both of our children had visited the petting zoo at the Oxford Fair a day apart. We ruled out food as Colton never ate anything at the fair. We also ruled out exposure from a different source as Colton did not go anywhere else in the ten days leading up to his illness.

Throughout the night on October 1^st, Colton had trouble sleeping, would not eat or drink, vomited frequently, and continued to have bloody diarrhea. The following morning of October 2^nd, Molly Douglas, MD and Jeffrey Halter, MD came in for the pediatric surgery service to assess Colton for placement of a hemodialysis access line. A transfusion was ordered before the PICC line could be done because of its inherent risk for bleeding during the procedure. Colton was becoming even more critical, with his serum creatinine rising from 2.97 to 3.59 overnight. At 9:34 AM, Dr. Halter took Colton to the operating room and placed a tunneled right internal jugular hemodialysis catheter under ultrasound guidance and fluoroscopy. After the procedure, Colton was transferred back to the Pediatric Special Care Unit.

That afternoon, Dr. Sedney came in for pediatric critical care, noting that Colton had pulled out his peripheral IV and it had to be replaced during his hemodialysis catheter procedure so he could receive a blood transfusion. Hemodialysis was scheduled to begin later that night instead of the next day because of Colton’s worsening condition. Pediatric resident Jackson Ryan, MD and PICU attending Eric Lee Gunnoe, MD came in to see Colton to follow-up on the placement of his dialysis catheter. On exam, they found him slightly tachycardic, which they thought was probably from anemia and dehydration—they ordered continuous telemetry and wrote orders for the administration of hydralazine (a vasodilator drug) as needed for high blood pressure.

At 3:39 PM, Megan Brown, RN was supervising Colton’s initial hemodialysis treatment, which took about 45 minutes. Colton appeared to tolerate the procedure without any acute events, but the nurse was concerned that the baby had no interest in eating or drinking anything. She informed the doctors and suggested they consider placement of a nasogastric tube if he continued that through the next day. Pediatric surgery resident Molly Jackson, MD came in during dialysis and noted the line was functioning well, signing off for the surgery service at that time.

During the night on October 3, 2015, Colton took a turn for the worse. At about 3 AM, Beth was changing Colton’s diaper and Jon noticed that his eyes were not focusing and seemed to be crossing instead of tracking. Meaghan Wildes, RN repositioned Colton, during which he exhibited tremors and stiffened his entire body. The nurse also noticed that Colton’s left foot/ankle was somewhat stiff and extended and would not flex. She alerted the doctors immediately.

At 4 AM, Dr. Gunnoe came in to see Colton and ordered the administration of Ativan, a benzodiazepine. The medication seemed to improve Colton’s gaze, and he began looking at people in the room again. Pediatric intensivist Elizabeth Dougherty, MD arrived at 4:28 AM and reviewed Colton’s current mental status changes. Colton was still tachycardic, and the doctor also noticed him crossing his eyes frequently. Dr. Dougherty did a neurologic assessment was concerned that Colton’s eye-crossing could be postictal.[2] She ordered a noncontrast CT scan of Colton’s head to rule out an acute bleed. Dr. Dougherty noticed that Colton’s most recent hemoglobin had dropped even lower to 6.5—she did not order an immediate transfusion, deferring it to be implemented during dialysis to reduce the stress on Colton.

Steven Braff, MD performed a noncontrast CT of Colton’s head at 4:40 AM, but he felt that the resolution on this exam was insufficient to adequately assess him. However, he did note bilateral low density in the basal ganglia. He recommended an MRI for further revaluation.

Critical care attending Dr. Gunnoe came back in at 5 AM and assessed Colton, who remained afebrile and required no oxygen supplementation. He reviewed the CT and Colton’s current metabolic labs, noting azotemia[3], metabolic acidosis, increased anion gap[4], and a hematocrit of 19%. He did an exam, noting no posturing. Dr. Gunnoe continued Colton’s diagnosis of HUS, now with central nervous system (CNS) involvement, “probably due to local brain ischemia due to the microangiopathic process. This is not due to electrolyte abnormalities or hypoglycemia.” He consulted with neurology, who asked him to hold off on giving Colton Keppra (levetiracetam, an antiepileptic drug) until after an electroencephalogram (EEG) could be done.

Nephrologist Carrie Gordon, MD arrived to evaluate Colton after being filled in by the overnight nurse on the phone, the ICU team, and the day ICU nurse and Beth that morning. She learned that Colton had a rough night, developing more abnormal CNS symptoms. He was tremulous and seemed to posture on one side of his body (the leg) and his eyes were crossing. After a dose of Ativan, he seemed to improve. Dr. Gordon came in during Colton’s EEG and hemodialysis was soon to begin. Colton’s hemoglobin had dropped to 6.5 (RR 10.3-12.7) and a transfusion was planned during dialysis. Colton’s other lab results that morning included a WBC of 35.6 (RR 6.2.14.5), platelets 78 (RR 140-440), BUN 76, creatinine 3.48, AST 98 (RR 0-81), ALT 149 (RR 0-40), and LDH >2500 (RR 180-430). Dr. Gordon noted that Colton’s Shiga toxin positive stool had been sent to the State Health Department for confirmation and typing. She commented that Colton’s increased platelet count was secondary to the transfusion of platelets he received the day before.

Dr. Gordon spoke with Beth and answered her questions—she noted Beth is a med tech and had a good friend who was an RN and a sister in Florida who was an RN, and both were planning to come help support the family.

During Colton’s dialysis, things appeared to be going well; however, about 30-40 minutes following dialysis, at about 10:40 AM he started having seizure activity. Thomas Reynolds, DO had just come in for a neurology consultation and observed that Colton appeared to be “somnolent”; however, he immediately began having a convulsive seizure. The doctor was unable to stop the seizure with Ativan or Cerebyx (fosphenytoin, a relative of Dilantin), and Colton was also dosed with Keppra while a pediatric emergency code was called.

Pediatric intensivist Kristine Pleacher, MD arrived to perform an endotracheal intubation under sedation with etomidate and paralytic rocuronium. The intubation proved somewhat difficult and required three attempts to pass the endotracheal tube, which finally succeeded under direct laryngoscopy. Colton’s seizure broke upon administration of the etomidate. Despite the seizure activity and intubation, Colton was able to complete 90 minutes of dialysis, and he received a transfusion of pRBC’s during treatment.

After Colton was stabilized, Dr. Reynolds reviewed the EEG of the seizure episode, observing that it had lasted close to sixty minutes overall. He also observed that the EEG post seizure showed generalized high amplitude and disorganized slowing “as would be expected.” Dr. Reynolds opined that Colton’s seizure, as well as the preceding events during the night that required Ativan, were reflective of microangiopathic changes from HUS; however, he also felt that Colton was at risk for a more significant ischemic stroke as well. He advised that Colton continue to be dosed with Keppra at 10 mg/kg/dose every 24 hours with dialysis. If his seizures continued despite this, he recommended maintenance Cerebyx (fosphenytoin) with dosing determined by nephrology and pharmacy. If Colton had another generalized convulsive event, Dr. Reynolds ordered a 1.2 mg Versed infusion at 0.05 mg/kg/hour. Dr. Reynolds thought that Colton should have a brain MRI prior to extubation whenever he was stable enough to be transported to the scanner, but it should be done without any contrast medium. He ordered continuous EEG monitoring through at least the next 24 hours, possibly longer pending Colton’s clinical course and potential need for Versed infusion.

Dr. Pleacher, MD reviewed the events that transpired during the night and that morning. She reviewed Colton’s abnormal lab results from that morning and assessed his physical condition. His long list of diagnoses now included thrombocytopenia, anemia, acute kidney injury consistent with HUS, as well as “status epilepticus[5]” requiring Ativan, Keppra, Cerebyx, and intubation. Dr. Pleacher wrote in her chart note: “Patient’s elevated WBC, severe GI involvement resulting in rectal prolapse and now with neurologic involvement is concerning for a complicated disease process.” Colton was currently both tachycardic and hypertensive, and Dr. Pleacher wrote orders for antihypertensives (Hydralazine) to use if needed. She kept Colton on IV fluids with added bicarbonate for his metabolic acidosis. Because he kept needing blood transfusions for anemia and thrombocytopenia, she suggested the use of Darbepoetin (a bone marrow stimulant) once a week if needed. Dr. Pleacher deferred to nephrology and neurology for Colton’s dialysis and antiseizure medication orders.

Colton’s dad Jon describes the agony of watching his son endure a progression of symptoms he was powerless to stop:

Colton was transferred to the Pediatric Special Care Unit where he remained throughout his time at Maine Medical Center. As each day passed, Colton developed severe seizures, which we were told caused damage to his brain. The seizures affected the body maintenance portion of his brain as well as the part of the brain that gives each of us our unique identity and consciousness of mind. In addition, the seizures would not stop on their own and as a result Colton had to be placed on a respirator as the medication to force the seizures to stop had the side effect of also stopping his breath. The seizures, medications, and machines keeping our son alive left him unable to communicate with us. It pained us beyond belief to see what our son was going through.

We felt utterly helpless as Colton suffered set back after set back. Each day seemed to be worse than the day before. What started as a condition that might have kept in the hospital for a few weeks was now transforming into a disease that was taking the life out of him.

Dr. Gordon had planned to start feeding Colton through a nasogastric tube that day, but given his seizures she withheld those orders. A repeat metabolic panel and magnesium level was ordered. She started Colton on Darbepoetin as well as Zemplar (paricalcitol, a vitamin commonly used during dialysis).

On Sunday, October 4, 2015 at 7:30 AM, Colton became bradycardic during a diaper change, which required the nursing staff to suction and deliver bag and mask respirations before he recovered from the episode. An hour later, Colton’s heart rate dropped back down into the 90’s from the 120’s while stooling. Shortly after that, the nurse observed that Colton was experiencing brief apneic episodes in between several regular breaths. The nurse immediately notified Dr. Gordon, who ordered blood gases drawn.

Intensivist Sandra Bagwell, MD came in to see Colton that morning after his bradycardic episodes, noting he had developed an irregular breathing pattern that progressed into agonal[6] breathing and different sized pupils that dilated with each agonal breath. Colton was taken urgently for a CT scan and MRI imaging that showed changes through portions of the medulla, pons, thalamus, and white matter that were concerning for stroke. He also developed coffee ground emesis in his orogastric output. Dr. Bagwell looked at Colton’s EEG and observed a diffuse slowing pattern consistent with a comatose state. The critical care team conferred with each other as well as with Beth and Jon.

At the request of Dr. Bagwell, Michael Epstein, MD came in for a pediatric cardiology consultation regarding Colton’s current apnea and bradycardia in the setting of hemolytic uremic syndrome requiring dialysis. Dr. Epstein observed that, since approximately 8:30 that morning, Colton had endured numerous episodes of bradycardia with abrupt decreases in heart rate to the 80’s, associated with apnea. More recently, as Dr. Bagwell identified, Colton had developed an abnormal breathing pattern with frequent sighing vs. agonal breaths. Hemodynamically Colton had been stable without hypotension of poor perfusion. His heart rate was now elevated in the 160’s. Dr. Bagwell reviewed Colton’s bedside telemetry readout, which showed sinus rhythm/tachycardia with frequent episodes of heart rate slowing and occasional dysrhythmias. Dr. Bagwell performed a limited echocardiogram, and commented that he suspected Colton’s episodic heart rate slowing was centrally-mediated and associated with the same process resulting in the abnormal breathing pattern. He noted regional wall motion abnormalities “likely secondary to micro-infarcts within the left ventricle, as part of the vasculitis process seen in HUS.” Dr. Epstein recommended a repeat head CT as soon as possible to evaluate Colton for cerebral edema and impending herniation, as well as a full echocardiogram study the next day.

Brian Livingston, MD performed another head CT at 2:15 PM on October 4^th. He unfortunately identified progression of the expansile abnormality that was noted on prior CT. He commented: “This is almost certainly related to a metabolic insult and is not clear from this examination whether or not there is an associated infarct or if this is secondary edema.” He saw no obvious hemorrhage or impact upon the brainstem at that time, and no venous thrombosis.

After conferring with Colton’s critical care team, Dr. Livingston performed an MRI of Colton’s head and found it correlated with the CT findings, identifying abnormal diffusion changes that “certainly suggest infarcts but should be interpreted with caution in this context.” Dr. Livingston was most concerned about the extent of periventricular white matter involvement, which was not typical of posterior reversible encephalopathy syndrome (PRES). He commented in the chart note: “I suspect this is related to a cytotoxic event at the level of the endothelium with no evidence for convincing embolic disease.”

Dr. Livingston also performed a head MRA during the imaging procedures, using axial 3-D time–of-flight MRA sequences with 3-dimensional maximum intensity projection reformats. He identified this as a normal head MRA with no evidence for vasospasm or obvious vasculopathy/vasculitis.

In the late afternoon of October 4, 2015, neurologist Dr. Reynolds returned to see Colton to review the imaging results. He observed that Colton’s clinical status was worsening at that point, with more significant respiratory changes and irregular breathing patterns, as well as changes in his heart rate and pupillary exam—Dr. Reynolds thought this was consistent with worsening cerebral edema. After extensive discussion of Colton’s case with neuroradiology, neurosurgery, nephrology, and the PICU team, “as well as review of a case series from 2004 describing a series of 6 patients with very similar MRI findings ultimately having good clinical outcome,” Dr. Reynolds and the critical care team elected to continue Colton’s current level of care with dialysis, as well as continuous EEG monitoring and treatment of his seizures. They did not want to pursue any neurosurgical management of Colton’s intracranial pressure because of his thrombocytopenia, and they did not want to attempt to induce a pharmacological coma with pentobarbitol for now; however, Dr. Reynolds did not rule out reconsidering that decision pending Colton’s clinical course.

Dr. Reynolds held an extensive discussion with family about “the lack of clarity surrounding long-term prognosis and the chance for both good and severe outcomes neurologically.”

Late in the evening of October 4^th, the critical care staff called cardiologist Dr. Epstein to report an episode of bradycardia (sinus) beginning around 7:30 PM, but without a ST elevation on telemetry monitoring. However, Colton developed a ST elevation just prior to the onset of a burst of ventricular tachycardia that suddenly flatlined. A pediatric emergency code was called, and the critical care team started CPR immediately, giving Colton a single dose of epinephrine. Dr. Epstein commented in his chart note: “Suspect neurally mediated bradycardia with subsequent ST segment elevation secondary to cardiac hypoperfusion. In this setting, developed a nonsustained run of PMVT[7] (polymorphic ventricular tachycardia). If this recurred, Dr. Epstein ordered a bolus of Amiodarone (an antiarrhythmic medication) to be given over 30 minutes for arrhythmia prophylaxis.

After the code, Colton returned to sinus rhythm with good peripheral pulses. The critical care team placed a double lumen femoral line and started a norepinephrine drip, as well as a second left radial arterial line for better blood pressure monitoring. After a discussion with neurologist Dr. Reynolds, a Keppra and Cerebyx drip was started. Dr. Reynolds also ordered Versed to be given as needed for clinical seizures, which order he changed to a continuous drip that needed to be started when Colton demonstrated continued subclinical and clinical seizures.

In the early hours of Monday, October 5, 2015, Colton’s condition worsened dramatically. At around 6:30 AM, his EEG became very slowed just prior to starting his Versed drip. Colton had continued with spontaneous movement and coughing since that point; however, a pupil check by the nurse at 6:15 PM showed changes in his left pupil. Colton’s left pupil had been briskly reactive overnight and was now 4 mm and nonreactive. His right pupil, which was previously sluggishly reactive was now nonreactive and 5 mm. The nurse immediately called critical care attending Mark McGill, MD to Colton’s bedside, who ordered a stat CT.

At 7:19 AM, Umesh Sarma, MD performed Colton’s head CT for the indication of “blown pupils bilaterally, concern for raised intracranial pressure.” Dr. Sarma identified progressive diffuse intracerebral edema, “which can be seen in the setting of hypoxic ischemic injury or anoxic brain injury.” He notified the critical care team immediately.

At 8:16 AM, pediatric intensivist Dr. Pleacher was at Colton’s bedside to read his EEG. She observed that it was currently characterized by marked voltage suppression bilaterally, and there was no evidence of cerebral activity. She commented in the chart: “This is a markedly abnormal EEG characterized by electrocerebral silence.” She called Dr. Reynolds to Colton’s bedside.

Neurologist Thomas Reynolds, DO arrived to review the continuous video EEG monitor recording. He wrote his impression in Colton’s chart:

“This was a markedly abnormal record because of the generalized and disorganized slowing intermixed with rhythmic delta. This is likely representative of metabolic encephalopathy secondary to the patient’s HUS with neurological manifestations but is also reflective of the medications he has been receiving.

He also displayed multiple prolonged episodes of status epilepticus primarily involving the right hemisphere. His ultimate development of severe suppression of brain activity is likely reflective of both worsening injury to the brain from the microangiopathic processes of HUS as well as the administration of large doses of benzodiazepines.

In summary, this record is reflective of severe disturbances in brain function with marked worsening of findings as compared to the previous 24-hour epoch. Clinical correlation is required.”

Michael Ferguson, MD arrived to perform Colton’s “Brain Death Exam” and discharge summary, pronouncing Colton’s official time of death as 12:35 PM. He listed Colton’s final diagnoses:

• Hemolytic uremic syndrome
• Cardiac dysfunction
• Hypotension
• Status epilepticus, generalized convulsive
• Respiratory failure, acute
• Acute renal failure on dialysis
• AKI (acute kidney injury)

Colton’s obituary was published in the local paper soon after his death:

A life cut short

Visitation was at the Fortin Group Funeral Home on Friday, October 9, 2015. Colton’s surviving family members were named, and Beth and Jon thanked Colton’s pediatric special care team at the Barbara Bush Children’s Hospital of Maine, “who tried everything in their power to save this little boy.”

Jon recalls his precious son’s final hours, and the indescribable agony he and Beth were forced to endure while observing a process they could only watch helplessly:

On Monday 10/5/15 in the early morning hours Colton had his final seizure, which swelled his brain to the point where it compressed on his spine leaving him brain dead.

It is said that the death of child is the most painful thing a person can endure. Beth and I can attest to the truthfulness of that statement. The pain of his loss to our family has left us devastated and beyond despair. Colton had such an impact on us as our first child and was loved by family, friends, and strangers alike. Everyone holds their children in high regard, but we found that Colton’s spirit attracted complete strangers to him. Colton was very interactive with people and as a result everywhere he went others gravitated towards him. During the week that Colton was hospitalized Beth and I were in agony as we could do nothing to ease his pain. As a result, she and I did not eat, hardly slept, and went on medication for anxiety.

As a police officer I battle with the frustration of not being able to see this coming or prevent it. Police, Fire, and EMS officials have the ability to know a little bit about a lot of things based on our experiences and exposures to many different circumstances and tragedies. In all of my years of experience I had no idea that HUS existed or that it could be transmitted by farm animals. None of my fellow officers knew about it either. I have experienced anger in that no one warned us about this terrible disease. A $.99 cent poster board and magic marker warning of possible risk to exposure to e coli would have been all that was needed to make us aware. Knowing that information would prevented us in taking Colton to a fair in the first place. As parents we thought a petting zoo would be a fun and safe family activity for our son to partake in. Never in a million years could we have guessed that he would pick up a bacteria that would ultimately end his life.

Colton

Furthermore, I am frustrated at the investigation into my son’s death by the Maine Center for Disease Control and any other agency responsible in determining the cause. I received my first of only two phone calls from the CDC one hour after my son’s death for a total of five minutes. From that conversation samples of the petting barn were taken without ever having talked to me about my observations, willingness to assist them in a walk through, or any other means to paint an accurate picture of what was going on and where we went. As a police officer it would be the equivalent of me investigating a fatal motor vehicle crash by solely going off the 911 call. In other words, it can’t be done with any degree of accuracy. Any update I have received from this investigation has only been obtained through the media as no one from the CDC or Oxford Fair has contacted me to date.

In experiencing the death of my child I find a new resolve in ensuring that parents are aware of H.U.S. and likewise take precautions to protect their own children. In learning about H.U.S it is my opinion that educational materials such as signage should be erected in every location farm animals are in contact with the general public. I firmly believe that hand washing stations should be included in these areas and that a designated person be charged with monitoring petting zoos to ensure that any and all safety precautions are adhered too.

___________________

[1]           The Oxford County Fair was open to the public from September 16^th through 19^th 2015.

[2]           Occurring after a sudden attack or stroke, as an epileptic seizure or apoplexy.  Venes, Donald (2013-02-07). Taber’s Cyclopedic Medical Dictionary (Taber’s Cyclopedic Medical Dictionary (Thumb Index Version)) (Page 1877). F.A. Davis Company. Kindle Edition.

[3]           Presence of increased amounts of nitrogenous waste products,  esp. urea, in the blood. Venes, supra note 63, at 245.

[4]           Anion gap refers to the difference between the measured cations sodium (Na) and potassium (K) and the measured anions chloride (Cl) and bicarbonate (HCO3). In accordance with the principle of electroneutrality, in any body fluid the number of net positive charges contributed by cations must equal the number of net negative charges contributed by anions. The unmeasured anions include lactate, sulfates, phosphates, proteins, ketones, and other organic acids. In general an anion gap of 10 to 14 mmol/L is normal. An increased value is present in metabolic acidosis. Venes, supra note 63, at 993.

[5]           Status epilepticus refers to continuous seizure activity without a pause for 30 min, i.e., without an intervening period of normal brain function. Status can include two back-to-back seizures without a lucid interval or any seizure lasting more than 5 to 10 min. Venes, supra note 63, at 2203.

[6]           Agonal respiration, gasping respiration or agonal breathing is an abnormal pattern of breathing and brainstem reflex characterized by gasping, labored breathing, accompanied by strange vocalizations and myoclonus. Possible causes include cerebral ischemia, extreme hypoxia or even anoxia. Agonal breathing is an extremely serious medical sign requiring immediate medical attention, as the condition generally progresses to complete apnea and heralds death. The duration of agonal respiration can be as brief as two breaths or last up to several hours. Perkin, R., & Resnik, D. (2002). The agony of agonal respiration: is the last gasp necessary? Journal of Medical Ethics, 28(3), 164–169. http://doi.org/10.1136/jme.28.3.164

[7]           Also known at “torsade de pointes,” polymorphic ventricular tachycardia refers to a rapid, unstable form of ventricular tachycardia in which the QRS complexes appear to twist, or shift, electrical orientation around the isoelectric line of the electrocardiogram. It often occurs as a life-threatening effect of a  medication (such as quinidine, amiodarone, or a tricyclic antidepressant) that prolongs the Q-T interval but may also complicate congenital long QT syndromes. Intravenous magnesium sulfate may be used to treat this arrhythmia. Venes, supra note 63, at 2340.