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Enterovirus D68 in the United States: Epidemiology, Diagnosis & Treatment

Moderator: Leticia R. Davila

Presenters: Susan Gerber, MD, Mary Anne Jackson, MD, FAAP, Daniel Johnson, MD, FAAP

Date/Time: September 16, 2014 2:00 pm ET

Coordinator:
Welcome and thank you all for standing by. At this time all participants are on a listen-only mode until the question and answer session for today's conference. I would like to inform all participants that today's conference call is being recorded. If you have any objection, you may disconnect at this time. I would now like to turn today's conference over to Leticia Davila. Thank you, ma'am, you may begin.

Leticia Davila:
Thank you, (Carol). Good afternoon. I am Leticia Davila and I am representing the Clinician Outreach and Communication Activity, COCA, with the Healthcare Preparedness Activity at the Centers for Disease Control and Prevention. I'm delighted to welcome you to today's COCA call, Enterovirus D68 in the United States: Epidemiology, Diagnosis & Treatment. We are pleased to have with us today Dr. Susan Gerber, Dr. Daniel Johnson and Dr. Mary Anne Jackson here to provide information on the current enterovirus D68 situation in the U.S., laboratory testing, reporting suspected clusters, and approaches to prevention and treatment.

There is no continuing education or slides provided for this call. Additional resources for clinicians are available on our COCA Website at emergency.cdc.gov/coca under the Enterovirus call webpage.

Our first presenter today is Dr. Susan Gerber. She is the Team Lead for the Respiratory Viruses and Picornavirus Team in the Division of Viral Diseases at the CDC. She received her M.D. from Loyola University and completed a pediatric residency and pediatric infectious disease fellowship at the University of Chicago. She has over 13 years of experience in local public health with work on communicable diseases at the Cook County Department of Public Health and the Chicago Department of Public Health.

Our second presenter, Dr. Mary Anne Jackson, is the Director of the Division of Infectious Diseases and the Associate Chair of the Community and Regional Pediatric Collaboration at Children's Mercy Hospital and Clinics. She is also a professor of pediatrics at the University of Missouri-Kansas City School of Medicine. She obtained her medical degree from the University of Missouri-Kansas City School of Medicine, and completed her residency at Children's Hospital Medical Center in Cincinnati. Dr. Jackson is a fellow of the American Academy of Pediatrics and the Infectious Disease Society of America and a member of the American Pediatrics Society.

Our last presenter, Dr. Daniel Johnson, is an Associate Professor of Pediatrics at the University of Chicago Medicine. He is also Associate Chair for Pediatrics Clinical Services and works closely with hospital leadership to improve inpatient and outpatient care delivery for general pediatric patients as well as oversees the flow of patients into the non-intensive care beds at Comer Children's Hospital.

In addition to today's presenter, Dr. Cliff McDonald and Dr. Matt Arduino, from CDC's Division of Healthcare Quality Promotion, will be available to answer questions during the Q&A section of today's COCA call. At the end of the presentation, you will have the opportunity to ask the presenters questions. On the phone dialing star 1 will put you in the queue for questions. Questions will be limited to clinicians who would like information on clinical guidance related to enterovirus D68. For those who have media questions, please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. At this time, please welcome Dr. Susan Gerber.

Dr. Susan Gerber:
Thank you very much. I will start out with some background on enteroviruses or EVs. Enteroviruses, or EVs, are very common viruses. There are more than 100 types that are known. It is estimated that between 10 to 15 million infections occur in the United States each year. And enteroviruses are also common causes of respiratory illnesses, febrile rash illnesses such as hand foot and mouth disease, and neurologic illnesses such as aseptic meningitis.

Most infected people are asymptomatic or have mild symptoms. And infants and children are more likely to become ill. The typical seasonality for enteroviruses are summer and fall and that is when they mostly circulate.

Enteroviruses or enterovirus infections are not nationally notifiable. Nationally, there are two voluntary and passive laboratory surveillance systems that include information about enteroviruses at the CDC.

One is called NREVSS, which is the National Respiratory and Enteric Virus Surveillance System; and the other is called NESS, which is the National Enterovirus Surveillance System.

Talking about NREVSS first, it is a passive system that collects data on a number of viruses but not the types. The total number of tests performed and those that are positive, but not patient level data, are aggregated and reported to NREVSS. And the proportion of positive tests are tracked.

Typically, the seasonality of enteroviruses, which has been tracked by NREVSS, has been consistent yearly in the United States and tracked during the summer and the fall.

NESS, the enterovirus type system, is voluntary and passive and collects data on types of enteroviruses and also parechoviruses. In addition to these types, detections also include information about age, gender, state, specimen collection dates, specimen type and virus type.

During 2009 to 2012 approximately 15 labs, including CDC's lab, reported to NESS and detections have been reported in 43 states and Puerto Rico. And typically specimen types reported to NESS include specimen types, CSF, or cerebrospinal fluid, OP/NP swabs, oropharyngeal nasopharyngeal swabs and stool and rectal swabs. And most of the reports are specimens from young children.

Type was reported for 1,257 of 1,859 or 68% during this time period. And these are types of enteroviruses and parechoviruses. There was considerable variation between years regarding enterovirus and parechovirus types. Enterovirus D68 have been detected during this time along with different parecho types, Coxsackie types, echoviruses. But this surveillance system gives us a glimpse of what is circulating but is influenced by attention received and investigations performed.

Background about enterovirus D68, it is thought to occur less commonly but was first identified in 1962. It is a known cause of respiratory illness and it is known to infect children and adults. It is similar to rhinoviruses both genetically and by the illness that it causes. Clusters of EV-D68 have previously been described in the United States, Europe and Asia.

Since 2008, several small clusters of enterovirus D68 have been described. The largest described in Japan with 120 cases reported, but most clusters reported have consisted of less than 30 cases. Most of the clusters reported have not included fatalities. Two of 21 cases reported from the Philippines cluster died and one of 11 known cases from Japan was a fatality.

Now during this last time period in 2014, I will summarize some of the recent events that have occurred. It was reported to us from different sites that there was an increase in severe respiratory illnesses among children in the pediatric intensive care unit and hospitalizations as compared to the same timeframe in previous years.

Also reported to us by a few medical centers was an increase in rhinovirus and enterovirus detections from multiplex PCRS as compared to the same timeframe in previous years.

As recently described in the MMWR and as will be elaborated by colleagues, Drs. Jackson and Johnson, 19 cases were described in Kansas City in the peds ICU and 10 of 11 in the peds ICU in Chicago.

The median age for children reported in these two groups of patients was four and five years old and most of the patients described had a history of asthma or reactive airway disease, 68% in Kansas City and 73% in Chicago.

A minority of patients in this report were reported with fever, 26% febrile in Kansas City and 18% in Chicago. And children were admitted for oxygen requirements and mechanical ventilation was also reported.

More will be said from Drs. Johnson and Jackson but, right now in the United States, our current status as of today, and I would like to stress that these numbers do change as more testing is performed and as reports are received, (130) patient specimens where enterovirus D68 has been identified now at CDC today and that's also includes 13 specimens confirmed at the New York State Public Health Laboratory.

Of 117 of 219, or 53%, specimens, have been confirmed at the CDC laboratory, 12 states are affected or have at least one positive detection today. What is different in the past from reports that we have received is the increase in respiratory illness and the magnitude of EV-D68 being detected.

Respiratory viruses are circulating, other ones, in addition to enterovirus D68, so not all detections identified in the CDC laboratory have resulted in EV-D68. Other rhinoviruses, Coxsackie viruses, echoviruses are examples of other viruses that have been detected along with EV-D68.

Few states have the ability to identify EV-D68. In the CDC laboratory to determine EV-D68 requires sequencing of the VP1 region of the genome. Real-time PCR assay is being investigated currently.

Infection control precautions include standard and contact precautions as is recommended for all enteroviruses. As EV-D68 is a cause of clusters of respiratory illness similar to rhinoviruses, droplet precautions also should be considered as an interim recommendation until there is a more definitive information available on appropriate infection control.

Handwashing with soap and water is recommended for community settings and for environmental disinfection, bleach works, and a hospital grade disinfectant within EPA label claim for any of the several non-envelope to viruses is recommended.

In terms of reporting, enterovirus D68 it's not nationally notifiable. However, in most places reporting of clusters is reportable to most states. Some states may have other specific reporting requirements. It is important that clinicians should report any suspect clusters to local and state health departments if they have any suspicious clusters of respiratory illness that might be EVD68 or from another pathogen.

In terms of CDC testing, there are priorities for testing of patients that include severely ill patients, new populations of patients. Adults have been known to be infected by enterovirus D68 however, we have not detected any in this particular season but we are still testing different populations including older children and adults.

Also, group settings such as long-term care facilities, any clusters associated with any particularly group housing or group settings would also be a priority for testing. In addition, states for which we have not identified any positives would also be a priority for testing.

In conclusion, enterovirus D68 is not new. Enterovirus D68 is being identified in more specimens than expected as compared to previous years. And increased respiratory illnesses are not all enterovirus D68, although enterovirus D68 appears to be a predominant finding in some locations. And, it is likely that there is a spectrum of illness associated with enterovirus D68 infection. More investigations are being performed. I would like to turn it over right now to Dr. Jackson.

Dr. Mary Anne Jackson:
Thank you, Dr. Gerber. It's my pleasure to discuss the Children's Mercy Kansas City experience with enterovirus D68 respiratory tract infection. Our Children's Hospital is a freestanding children's hospital that straddles the state line between Missouri and Kansas. We have two hospitals with two different emergency departments and there are five urgent cares that also provide services in the six county metro area. The market share for the six county metro area is about 85.8% since 2011 so the vast majority of children in our community who are ill are hospitalized in our institution.

On August 15, 2014 Dr. Irene Walsh, who is one of our pediatric emergency medicine providers sent an email to myself and Dr. Jason Newland, stating that in the last 24 hours she had personally seen five or six children disproportionately ill from their histories with respiratory distress. Most of them, she said, did not have major fever. All seemed to respond to asthma medication but only two or three had histories of asthma. And today's child, she said, was on his way to the PICU.

Over the next 48 hours, we reviewed our microbiology records. Dr. Raj Selverangan, who is the director of our microbiology laboratory, provides a weekly report to practitioners that details viruses that have been isolated, viruses that have been detected by respiratory panel and he also reports on Group A streptococcus.

We have used the BioFire respiratory panel now for several years in our institution. And this has been reserved, for the most part, only for hospitalized children particularly for children with serious or unusual respiratory tract infections.

We reviewed our records and looked at weekly entero rhinovirus detections in 2013 compared to 2014, turning our attention to weeks 32 and 33. As we looked over our data in weeks 32 and 33 in 2013, we detected rhino enteroviruses at a rate of about 5 to 7 per week.

This contrasts to 2014 where during week – 20, I'm sorry, 32 and 33 we detected 30 rhino enteroviruses each week for that prior two weeks. We were alerted at that point then that possibly our outpatient and inpatient activity maybe was being driven by an unusual rhino enterovirus. And on August 19, 2014 we notified our CDC colleagues.

Dr. Selverangan's email to them suggested that from our laboratory testing and noticing the high number of rhino enterovirus detections in the last two weeks, and from our inpatient and outpatient census, we wondered if this could be circulating new enterovirus at that point.

At the same time, Dr. Greg Connors, who is our Director of the Division of Emergency Medicine in Urgent Care and Dr. Jason Newland, who's one of my partners and our Medical Director of Patient Safety and Systems Reliability, both sent out messages on the respective listservs. Dr. Connor and his out to the Pediatric Emergency Medicine Discussion Listserv which has well over 1,000 subscribers worldwide and he sent the first message out on 8/20 asking if others had seen illness similar to what we were seeing.

On August 21, Dr. Newland sent an email to the Emerging Infection Network also saying we were seeing an unusually high census likely driven by rhino enterovirus indicated that the CDC was currently typing specimens for us.

And he described the illness that we were seeing and basically that of severe respiratory illness that for some had resulted in care in the PICU, in some that this appeared to be exacerbated asthma, in others it appeared to be an asthma like illness with many requiring continuous albuterol.

And, we wanted our members of the listserv to be aware and asked if they were seeing similar disease. From the emergency medicine listserv, we got multiple, approximately 10 that right off the bat said yes, we are seeing the same thing and we similarly had responses from colleagues on the Emerging Infection Network.

On August 20-22, we had to develop an institutional response based on the number of children we were caring for in the outpatient and inpatient setting. Our emergency department and urgent care visits were increased by 25-30%. There was an increase in the emergency department wait time. And for the first time we were seeing boarding mainly driven by prolonged treatments with continuous albuterol in that setting.

By August 22, our bed capacity was beyond 100%. And we had a census of 308; one of the very first times ever that we've seen a census that high. Our institutional response included pulling together representatives from administration, nursing hospital medicine, emergency medicine, general pediatrics, pulmonary medicine, infectious diseases, quality safety and respiratory therapy. At that point we noticed - in fact there was even a period where we were concerned about shortage of nebulizer circuits and availability of albuterol for inhalation.

On that date, I sent an email blast alert to providers in our community letting them know about our high census and the potential respiratory outbreak. The high census response in our institution required is mobilizing additional providers, both doctors and nurses, and determining how best to utilize them. Dr. Mary Ann Queen, who's our Division Director and Hospital Medicine, handled this.

We were looking at trying to maintain care for the number of patients that we were seeing on our general pediatric teams. And our innovation involved ID physicians who had experience as a hospitalist, functioning on the hospitalist service, pulmonology attendings adding extra asthma patients to their service, and then subspecialists, particularly for instance, in nephrology, gastroenterology and neurology, admitting patients to their inpatient service that would typically have gone to the general pediatric service but could have been appropriate for their subspecialty.

We were able to open additional beds. We limited some elective surgeries and added nursing staff. And the overall key to our approach was to make this a team approach by the hospital staff to safely care for these children.

On August 26, we were notified by the CDC that we had confirmed enterovirus D68. Our initial specimens that we sent to them included 22 specimens. These were all patients from patients hospitalized in our PICU. And the earliest sample was actually from August 4.

We have particularly wanted to make sure that we were sending them patients who were consistent with the cases that we saw, so we did develop a case definition at that time. And 21 of 22 - or 21 total patients met the case definition; 19 were positive for D68. We had two rhinoviruses and one Coxsackie. Two at that time - the child with Coxsackie infection was in the PICU with a complex febrile seizure; the other 21 with asthma type exacerbations.

We sent a second batch of specimens to the CDC that included 30 specimens. We included children at that time knowing that we were dealing with D68, wanting to make sure that anybody with unusual manifestations in our PICU that may be neurologic in nature or in unusual host, for instance, immunocompromised, that we were looking at their specimens.

And at that point of those 30, seven of them were rhinoviruses including three in our immunocompromised population; one of those patients was co-infected with PCP by the way; three were Coxsackie B and one was Coxsackie A6. There were six samples that were negative at that point which we think is sampling error since we were sharing a specimen. And so total 18 met our case definition and 14 were positive for D68.

The clinical characteristics of our initial confirmed cases were quite similar. We saw patients from both sides of our state line. Sixteen were boys; they were mainly school-aged. They all appear to have an unusually severe asthma type presentation but one third had never wheezed in the past.

We reported a proxy) of fever, as Dr. Gerber mentioned. Most of these patients were tachypneic, hypoxic, 1/3 were wheezing. They were slow to respond to albuterol and all had significant hypoxemia. Most of them required escalated therapy for respiratory failure in the PICU.

As we look at the disease extent and severity and impact on PICU transfers and admits, we reviewed data from August 4 and data up through September 10. And I'll remind you that our first alert came from Dr. Walsh on the 15th and the initial CDC specimens we sent for typing were from 4 August through 19 August.

Over this next, you know, essentially six-week period, we saw what appears to be a peak in our disease, approximately the 22nd through the 31st. And, we've slowly seen a decrease in our disease although we still have significant numbers of cases that are well above what we might see for this time of year.

Overall, we've had over 600 detections. And, of course, we don't know the extent of disease, how many of these are EV-D68 versus other viruses in our community. We know that during this timeframe there have been over 470 admissions. And to give you an idea, our average daily census for this time of year would be somewhere in the 240 to 250 range. And during our peak we were between 290 and 308.

The PICU care has been quite challenging I think. Drs. Jenna Miller and Marita Thompson were particularly interested in - they're both critical care specialists in our PICU that actually has 17 critical care trained providers.

We kept regular communication between them and myself. And looking at the types of patients that were admitted and the types of therapy that they required most of these patients required escalation of therapy beyond magnesium and two non-invasive ventilation up through mechanical ventilation.

When we look at our (care) for patients in the emergency room and urgent care we see numbers similar to what we saw with H1N1 but with higher acuity and admission rates, longer times in the emergency room for treatment. And these longer times lead at some point to a little bit of gridlock there because most of these kids were getting continuous albuterol.

We've had some return visits of patients previously admitted but I don't have clear information about that. And we have been looking to ensure that we've not seen any type of nosocomial disease up to this point.

One of the things that we did from the get go, and this goes all the way back to August 20 when we first sent our alert out to community providers, one of the very first things that we did was we used the respiratory panel for children who were admitted to the hospital who met our case definition. And in all of those cases that was an automatic initiation of infection control of isolation procedures for those patients. And we hope to some extent that's mitigated any kind of nosocomial disease.

When I look at overall total admissions for this last six week period, we definitely appear like we are on the downward curve here. But we're still seeing significant activity particularly in one of our urgent cares in our community. So that is where we stand right now at Children's Mercy Kansas City. And I'd like to turn it over to Dr. Daniel Johnson.

Dr. Daniel Johnson:
Thank you very much. This is Dr. Daniel Johnson. I'm a pediatric infectious disease specialist at the University of Chicago Medicine Comer Children's Hospital. Comer Children's Hospital sits on the Southside of Chicago and serves all of the Chicago metro area.

I'd like to thank the Chicago Department of Public Health for their help as well as one of my fellows, Dr. Emily Obringer, who collected much of the information that I will be sharing in cooperation with our sections of pediatric pulmonary emergency medicine and pediatric intensive care.

Our attention was drawn to an uptick in the number of children being admitted to our pediatric intensive care unit over a roughly two-week period between August 13 and the 26th.

On recognizing this increase, we sent specimens to the CDC for help identifying the enterovirus which of course turned out to be D68. It is the approach of the pediatric intensive care unit to obtain respiratory viral panels on patients admitted with respiratory disease to our intensive care unit. And what we found was that out of 14 specimens that were sent, 11 were positive for enterovirus D68.

The children coming into the intensive care unit during that time were remarkable for showing a history of asthma in roughly 3/4. But despite the severity of their diseases and findings of needing significant support, as was described by others, the number of patients who were febrile was relatively - in fact very low at only 18%. Patients required support anywhere from the most severe being a patient who required ECMO, two others who required intubation, BiPAP or highfrequency nasal cannula.

We then followed and investigated additional patients and have now identified 46 patients that were admitted in the past month who were positive for rhino entero by RVP. This includes the 11 that I've already mentioned.

Their median ages, as with our first group, five years. And their length of stay is also similar in that patients are staying in the intensive care unit for two days and their median length of stay total is approximately three days.

We've seen a slight increase in the number of febrile patients, up to 28%, and have continued to see a history of asthma, wheezing in 3/4 of those patients. Of the patients who were admitted to the intensive care unit 44% have required high-frequency nasal cannula, or high flow nasal cannula, excuse me, 28% BiPAP, and 11% have required intubation.

The 46 patients all, but 11 now have been - have uncertainty about what the enterovirus is and those specimens have been sent to the CDC for further confirmation. But it is our assumption that those patients, likely based on case definition, have EV-D68.

We continue to see a rising number of children who are rhino entero positive being admitted to our PICU with the week ending 9/13 showing our highest number yet. So it appears as if we have yet to hit the peak of this occurrence.

Our emergency department has seen a 33% increase from expected with the flow of patients, and the highest census days have been September 9 and 10 where 1/3 of the patients had respiratory symptoms and we saw 20% of patients admitted.

We had such a crush of patients that on September 9 we had to take the extraordinary step of closing our emergency room and putting it on bypass, so closing it to ambulance admissions.

Our general pediatric service over the past three weeks has had 80% of its admissions due to respiratory illness. And our census has, in the past week from 9/6 to 9/12, was equivalent to what we would normally have seen in two weeks during the period of August.

The natural history of this is that patients see an acute onset of 1-2 days prior to admission complaining of symptoms of cough, shortness of breath and wheezing. As noted fever is rare. And the majority, but not all, have a history of wheezing.

Diagnosis has been made using a film array respiratory panel by BioFire Diagnostics. And as already mentioned, our PICU screens all patients with respiratory problems where as our emergency room and inpatient area it is at the discretion of the attending and their judgment.

As far as acute management, the patients receive a trial bronchodilators, either a nebulized solution or a metered dose inhaler. And, if there is a history of asthma, then they're generally treated with a short course of steroid, either prednisone or prednisolone. We're not using antibiotics unless there's a clinical impression of superimposed bacterial infection.

Patients are managed in the hospital when needed and are being discharged on albuterol and if a history of (atopy) or previous wheezing, they're started on low dose inhaled cortical steroids with pulmonary follow up.

Our approach to isolation has been standard along with contact plus and droplet. We have not chosen to restrict patient visiting and that's because we've had no nosocomial transmission. We have looked for similar activity on the adult side and have found that we have 20 samples that have tested rhino entero positive over the three weeks and four of those patients have required treatment in the intensive care unit.

So in summary, we have seen a significant and atypical increase in the number of respiratory related admissions to Comer Children's Hospital with an unusual peak of entero rhino positivity. We have been able to prove in 11 the presence of enterovirus D68 and others are pending at this time. We continue to see a rise in the number of respiratory patients requiring attention and continue to see a rise in the number of patients testing positive for enterovirus D68. Thank you.

Leticia Davila:
Thank you, Dr. Gerber, Jackson and Johnson, for providing our COCA audience with such a wealth of information. As a reminder, Dr. Cliff McDonald and Dr. Matt Arduino from CDC are available during the question and answer portion of today's COCA call.

Questions are limited to clinicians who would like information on clinical guidance related to enterovirus D68. For those who have media questions please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov.

Due to the overwhelming response to today's call, we understand that some may have experienced technical difficulties at the beginning of the call. We do apologize for the inconvenience. The recording and the transcript for the call will be available on our COCA Website within the next few days. We will now open up the lines for the question and answer session. Operator.

Coordinator:
Okay. At this time if you have a question or comment, you may press star 1 on your touch tone phone and please state your name clearly when prompted. And we'll give it one moment please. Our first question...

(Arnita):
...for specimen collection.

Coordinator:
...(Arnita), your line is open.

(Arnita):
Yes, hi. I wanted to know what are the specifics for specimen collection? Are we doing, you know, what are the specifics for that?

Dr. Susan Gerber:
This is Dr. Gerber. Our lab is coordinating with state and local health departments.

(Arnita):
Okay.

Dr. Susan Gerber:
So some of the details about where people are can be worked out with them. But we are accepting respiratory specimens. We have accepted nasopharyngeal swabs. We could accept other respiratory specimens for testing.

(Arnita):
Okay so there's not really specifics just basically the swabs. Do we have PCRs for this?

Dr. Susan Gerber:
This is Dr. Gerber again. In general, many labs do have available multiplex assays for respiratory viruses that include detection of rhinoviruses and enteroviruses. It is difficult and many times not possible to identify a rhinovirus versus an enterovirus...

(Arnita):
Right.

Dr. Susan Gerber:
...from these findings from these multiplex assays.

(Arnita):
Okay.

Dr. Susan Gerber:
So here at the CDC we have methods to identify specific rhinoviruses and enteroviruses. And for EV-D68, we have been using sequencing of the VP1 section of the genome. But, we are working on a - our lab is working on a real-time PCR assay.

(Arnita):
Oh perfect. Okay. Thank you so much.

Coordinator:
(Laura McAver), your line is open.

(Laura McAver):
Yes, can you use alcohol hand rub on a patient with suspected or confirmed enterovirus D68?

Dr. Cliff McDonald:
This is Cliff McDonald from the Division of Healthcare Quality Promotion. And as you know our current guide, recommendations, are standard precautions which of course involve the use of gloves anytime you're going to touch any body substances.

Contact precautions and special circumstances and droplet precautions - droplet precautions routinely - in these patients and that probably means you're going to start employing droplet precautions for a while as you're seeing this activity in your ambulatory interactions.

The use of gloves or contact precautions is recommended for diapered children, certainly, it also is mentioned in our guidance for outbreaks and healthcare associated outbreaks. It wouldn't be unreasonable to just routinely institute contact precautions.

As you know, the non-envelope viruses are not as sensitive to alcohol as say the envelope viruses or other vegetative bacteria. Nonetheless, certain alcohol concentrations and types of alcohol certainly do have activity. And we often, as you know, in healthcare walk a fine line between compliance and feasibility and laboratory-based efficacy.

So our recommendations at present are not to change hand hygiene recommendations. If you're concerned about the efficacy of alcohol for some reason because of, you know, local expertise or concern thereof we don't know, at least in our division, we don't necessarily share that concern for the same degree. But use of gloves would be the best bet.

We don't generally recommend switching to handwashing except maybe in the case of spores and CDIF and you're familiar with that issue. So we would say rather use gloves, focus on the use of gloves, continue to use alcohol-based hand sanitizer as your primary method of hand hygiene.

(Laura McAver):
Okay, thank you very much.

Coordinator:
(Vera Fishkey), your line is open.

(Vera Fishkey):
Yes, my question is regarding any healthcare worker recommendations. We've had a nurse today say she was - said she was diagnosed with enterovirus and I'm just wondering if there are any specific recommendations for healthcare workers. Thank you.

Dr. Cliff McDonald:
We have not made any in this particular outbreak. Generally respiratory viral infections - it depends upon the population. If you're working a bone marrow transplant unit then there are times in our guidance that we recommend exclusion from duties otherwise, you know, covering the cough and good hand hygiene. Certainly if someone has a fever they should not report to work.

In a case like this you could institute some standard policies for certainly emphasizing the issue of don't report to work if febrile. We don't - I don't think we really know what the roles that we've heard already from Dr. Gerber, we don't really know the full transmission among adult population, that could be any number of enteroviruses and be kind of curious even how, you know, could someone test for - presumably that was in the ambulatory setting and why for a simple upper respiratory infection was someone subjected to a full respiratory panel.

You know, it maybe it was that she had some underlying lung disease or something of that nature. But the bottom line is, we don't have any specific recommendations for this virus in this particular outbreak. That could change, you know, I don't think we know yet fully the role of adult reservoirs. Sue, you could certainly comment further.

Dr. Susan Gerber:
Thanks, Cliff. Actually, we know from some of the outbreaks that have previously been reported that adults can be infected with EV-D68. However, in this particular outbreak thus far we are not aware of any confirmed cases among adults. That said, it would not be surprising to identify this virus in adults. We are still investigating and still doing quite a bit of testing in our laboratory.

Dr. Mary Anne Jackson:
This is...

Dr. Cliff McDonald:
One thing I just want to add is, you know, one thing to think about is especially if these are pediatric hospitals which we've heard about here on the call today but also other pediatric ambulatory settings and pediatric parts of community hospitals and EDs, be thinking about maybe employing some of the practices you employ during the winter, viral season, at this time.

Certainly waiting room policies, separation of sick patients, reemphasizing that, and perhaps even also, you know, routine use of droplet precautions for all respiratory illness in this population.

Dr. Mary Anne Jackson:
This is Dr. Jackson from Kansas City. We did institute our sibling visitation policy that we utilize in the winter months at the early part of this outbreak. We had attention about the use of infection control precautions for the many outpatients that were being seen. We estimate the burden of extra outpatients were upwards of 1,300 children per week that were being seen in our emergency room and our urgent care settings.

And I think that those are important and may have been helpful in our institution at least at this point in preventing nosocomial disease.

(Vera Fishkey):
Thank you.

Coordinator:
Dr. (Colleen Evican), your line is open.

(Colleen Evican):
One of the previous speakers asked my question. Thank you.

Coordinator:
Kansas Department of Health, your line is open.

Man:
Thank you. So in last Tuesday's call it had been suggested that alcohol-based hand sanitizers were not effective against non-envelope viruses. The Association for Public Health labs has gone on board as saying that. You mentioned that glove use is preferred with contact and droplet precautions. What method of hand hygiene are you recommending after glove removal? Are you recommending hand washing or alcohol-based hand sanitizer? Because there seems to be a lot of confusion.

Dr. Cliff McDonald:
Well, you know, absolutely the non envelope viruses including enterovirus are less susceptible to alcohol than other viruses. Are they completely non-susceptible? No, they're relatively nonsusceptible.

Is hand washing in practice completely effective? No, it's not. We know that in practice as hand washing is employed in many healthcare settings it is not always effective because of compliance issues and feasibility and completeness.

This especially gets true in the winter months where there's increased skin irritation and atopic dermatitis and things of that nature. So our recommendation is specifically to not change the overall hand hygiene policy in your facility but focus again, if you're concerned, if you have increased activity like this just go to contact precautions which would be glove use, continue to use alcohol-based hand sanitizer on removal of gloves realizing of course that the gloves are an important hand hygiene measure.

And we actually have more experience with them, you know, interrupting transmission with a variety of agents for which alcohol is less effective than we do trying to revert to soap and water.

So again, both are true, yes, there is activity of alcohol in many of these viruses and documented, you can read about that in the WHO most recent hand hygiene guideline. Is it as effective as alcohol is for other agents? No. Is it - still have activity? Yes. Is the equation of activity in compliance still in favor of keeping alcohol-based hand sanitizer as the default hand hygiene in your facility? Yes. And add gloves if the concern is there because of increased activity.

Coordinator:
Next question, Dr. (McBride), your line is open.

Leticia Davila:
Operator, before we go to the next question - excuse me - how many questions do we have in the queue?

Coordinator:
Twelve.

Leticia Davila:
Thank you.

Coordinator:
You're welcome.

Leticia Davila:
Next question - or this question please.

Dr. (McBride):
Yeah, one of the speakers mentioned a case definition for the condition - the disease. Is there a case definition for the disease in general? I notice - I noticed they mentioned a lot about lack of a fever.

Dr. Susan Gerber:
Hi, this is Dr. Gerber.

((Crosstalk))

Dr. Susan Gerber:
Hi, this is Dr. Gerber. Thanks for that question about case definition. And I think afterward Dr. Jackson has more - some experience with the case definition that was helpful in her hospital. But in general, right now as we're doing - as we're investigating with local and state public health partners we have talked amongst ourselves about a broad case definition that would be any respiratory syndrome that might include cough, wheezing, shortness of breath.

Fever would not be included in the case definition. And we are actually investigating cases to understand the spectrum of disease caused by this virus in the setting and gain more understanding.

However, there may be further utility in other settings. And I will refer to Dr. Jackson and her experience.

Dr. Mary Anne Jackson:
Thanks, Sue. We utilized the case definition starting on August 21. And this is very broad but it is what we wanted to identify was a trigger for using the respiratory panel and, number two, for instituting our infection control precautions.

And so our case definition was any child admitted with: cough and difficulty breathing, with or without fever, with or without wheeze, who required supplemental oxygen and/or continuous albuterol.

We were trying to really target the more seriously ill patient and we were kind of - and we were trying to highlight the fact that not every patient - Dr. Johnson also mentioned had fever and not every patient wheezed even in the children who'd previously had a history of asthma.

So we made this very broad to begin with. It's proved to be pretty accurate though in targeting our patients. And as we looked at the number of patients, for instance, who met our criteria and then looked at our PICU admission, we've had over 100; in fact I think we're at 101 patients admitted to our PICU who met the case definition as of September 10. And of those I think we have confirmed D68 in 47 of them so far.

But I do agree with Dr. Gerber that, you know, a broader definition is probably reasonable as we tackle this further and make sure that other providers are alert to recognizing this clinical illness.

Coordinator:
Are you ready for the next question?

Leticia Davila:
Yes please.

Coordinator:
(Jar Nader), your line is open.

(Jan Nader):
Thank you, my previous question was previously answered so thank you.

Coordinator:
All right thank you.

Leticia Davila:
We'll take two more questions.

Coordinator:
Dr. (Lisa Ferrero), your line is open.

(Lisa Ferrero):
Hi. I'm hoping that you can comment on any surveillance methods that are being done in the community kind of the way we do for a flu. Can you comment on anything you know about the attack rate so that I have something that I could say to families about the likelihood of other people, particularly children, being affected by this illness?

And also, if you can comment about how effective clinically albuterol seems to be at least until we get our probable affected patients to a referral center. I think that might be useful information for us.

Dr. Susan Gerber:
Hi, this is Dr. Gerber. I think two questions. I am going to try to address the transmission question in communities. We know that enteroviruses are transmitted or spread person to person. And we are still in this particular marked season of increased respiratory illness at least in some locations and a predominant finding of EV-D68.

We are still investigating what this means for the community. And right now all I can say is we don't have hard numbers but it would be likely that we would detect less severe cases. As I said, at CDC, we're prioritizing testing of more severe cases at this time. However, we are hoping to gain a better understanding of community and less severe illness due to EV-D68. In terms of your albuterol question I'm going to refer to that to Dr. Johnson to comment.

Dr. Daniel Johnson:
Thanks, Dr. Gerber. This is Dr. Johnson. And we are recommending that all patients who come in with symptoms that include wheezing, significant cough, who require some type of respiratory support be it oxygen, or of course something more extensive, be given a trial of bronchodilation using albuterol either by nebulization or handheld inhaler.

We have found that most patients who have a history of asthma have shown a good response to the albuterol. We've found that patients who don't have a history of asthma or (A to B) don't necessarily respond to albuterol. We are recommending though that everyone be given a clinical trial in order to see how they respond to the drug and that's what I certainly would recommend to anyone else.

(Lisa Ferrero):
Thank you.

Coordinator:
Our final question comes from (Barbara Caruso). Your line is open.

(Barbara Caruso):
Thank you very much. Maybe this has been answered in one way or the other but you have consistently referred to children with a history of asthma as far as being more susceptible to this virus. Has there been any suggestion there will be a crossover into more of the general population as looking for the future as far as what we're going to be able to do for them?

Dr. Susan Gerber:
Hi, this is Dr. Gerber. Thanks for that question. Right now we're still investigating with our medical community partners and public health partners the role of a history of asthma or wheezing reactive airway disease as - relating to more severe disease. So that investigation is still ongoing but we are aware that at least in the limited groups of patients that we reported in our MMWR, the majority did have a history of asthma or wheezing.

However, what that means is in terms of a risk factor is still under investigation. However, to emphasize there were other children who did not have a history of asthma or wheezing who did become severely ill. And as we continue our investigations we hope to learn more about those - that particular group of patients as well.

((Crosstalk))

Dr. Mary Anne Jackson:
Dr. Gerber, this is Dr. Jackson. I'd also like to say that based on - well we don't know the true extent of the burden of this disease that it is pretty clear it does run a spectrum from mild disease that is just basically URI to these severe cases that Dr. Johnson and I described.

In our pediatric community with the five urgent cares and two emergency medicine departments, there have been in excess of 100 children a day being seen. Now not every child is being admitted to the hospital of course over this entire six-week period, there's been, you know, substantial numbers of admissions and substantial admissions to the PICU but a large, large number of children out in the community.

And then the second thing is that as we're kind of getting further out into, you know, toward the end of September into October and based on looking at the typing of our viruses, there are a number of other different viruses in our community too.

And so even for children with mild URI, not every child with a cold has EV-D68 and but certainly those children who are being admitted with these unusually severe clinical symptoms to the PICU it still looks like the predominant virus in our institution.

Dr. Daniel Johnson:
This is Dr. Johnson. I would echo the comments of Dr. Jackson and mention that we certainly are seeing the tip of the iceberg most likely because we're seeing a large number of children coming into the emergency room but thankfully most of those are able to go home.

So it was the most severe cases that drew our attention to this but one can imagine that there are many cases out there that are not being - that are not coming to medical attention. We know in our general pediatric clinic that we are seeing more patients who are coming in with emergent problems but again most of those patients are going home.

We're also seeing that there are patients being admitted with disease that has nothing to do with the respiratory track who, for one reason or another, have undergone testing and are being found to be entero/rhino positive suggesting that they may have had symptoms from the rhino/entero by history prior to whatever is bringing them to medical attention now and further suggesting that we're seeing more disease out in the community than is being recognized.

(Barbara Caruso):
Okay, thank you very much. That was a very comprehensive answer. Thank you.

Leticia Davila:
Thank you. On behalf of COCA I would like to thank everyone for joining us today with a special thank you to Dr. Gerber, Dr. Jackson and Dr. Johnson. We invite you to communicate to our presenters after the call. If you have additional questions for today's presenters please email us at coca@cdc.gov. Put enterovirus COCA call in the subject line of your email and we will ensure that your question is forwarded to them for a response. Again that email address is coca@cdc.gov.

The recording of the call and transcript will be posted to the COCA Website at emergency.cdc.gov/coca within the next few days. There are no continuing education credits for this call. Resources for clinicians related to enterovirus D68 are available on the COCA call Webpage. Go to emergency.cdc.gov/coca click COCA Calls and then follow the links for the enterovirus call.

To receive information on upcoming COCA calls subscribe to COCA by sending an email to coca@cdc.gov and write Subscribe in the subject line. Please join us for our next COCA call this Thursday, September 18, Management and Prevention of Pediatric Influenza in Healthcare Settings.

Thank you again for participating in today's COCA call. Have a great day.

Coordinator:
This does conclude the conference for today. All participants may disconnect at this time. Thank you.

END

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