Enterovirus 68: Talking Points

Yesterday, I discussed the recent emergence of EV68 in the US and its association with respiratory illness in children. Naturally, there has been a lot of media interest and parental concern. In addition, CDC released a new MMWR earlier today that describes the two best characterized EV68 outbreaks in Kansas City and Chicago. Of note, the CDC report necessarily describes only the sickest patients with EV68, those admitted to the hospital and tested. Like most viral illnesses, we expect the vast majority of infected children to either not develop symptoms or develop less severe symptoms that might require a visit to a clinic but not require hospitalization. Personally, I have replied to dozens of emails, attended internal meetings and completed several interviews with the media, so I thought I'd share a few general discussion points that have come up more than once today.

For Parents:

1) What is EV68? Enterovirus 68 (EV68) is not a new virus, but over the past few years it has caused outbreaks of respiratory distress in the fall. These outbreaks are similar to what we see later in the year with influenza and RSV. What's different is that this is happening earlier in the fall and with a rarer virus.

2) Who does this virus infect? In the current outbreak, most patients are children under 16 with a prior history of asthma or wheezing. Symptoms include rapid onset of cough, wheezing and difficulty breathing. EV68 rarely causes fever. Most children with suspected EV68 infection respond quickly to supportive care that includes breathing treatments, such as inhalers prescribed by a health care provider.

3) What should I look out for? If your child or family member (or friend) develops rapid onset cough, wheezing or difficulty breathing, please contact their health care provider. While most patients do not require hospitalization, children can develop symptoms rapidly, so a quick call or visit to a health care clinic might be necessary.

4) Is there an antibiotic I can take or a vaccine? No, there are no currently available antiviral medications that treat EV68. There is also no vaccine. However, that does not mean that your child can't be treated. Children with severe respiratory distress can receive several forms of breathing treatments that reduce their symptoms and get them on the road to recovery.

For Hospital Epidemiologists and other Health Care Workers:

1) EV68 is only rarely associated with high fevers. Thus, presence of fever is not an effective question for screening visitors for illness. Thus, facilities currently experiencing an outbreak of EV68 or an uptick in viral respiratory illnesses, should consider restricting access to visitors under the age of 15 or 16 (the oldest confirmed cases in the CDC report). Of course, exceptions should be made in certain situations.

2) HCW who are ill or suspect they might have a viral respiratory illness should follow their hospital policies concerning work attendance. As we've mentioned before, presenteeism (coming to work sick) is a big problem, so avoid it if at all possible.

Disclaimer: This post is not intended to provide specific healthcare advice to an individual patient or healthcare facility. Please contact a doctor or other healthcare provider if you have specific questions about your or your child's health. Also, I will not respond to specific comments asking questions about the care of individual patients. Finally, don't trust any healthcare advice you receive over the internet. Oh, and all of this information will be obsolete and expire by tomorrow.

E is for...Enterovirus 68

Never a dull moment. Just as facilities have begun wrapping up their Ebola preparation plans, there's gathering evidence that several US states may be facing large clusters of acute respiratory illness associated with human enterovirus 68 (EV68).

Last week the Missouri Department of Health released an Alert describing increased cases in St. Louis and an outbreak of over 300 acute respiratory illnesses in a Kansas City pediatric hospital with 15% requiring ICU care. 19 of 22 specimens sent to the CDC from the Kansas City outbreak were positive for EV68. Many St. Louis cases were positive for enterovirus but specific typing is pending. Denver is seeing severe respiratory illness in very young children and children with asthma. Children's Hospital Colorado has treated 900 children and admitted 86 since August 18th, but so far the specific viral pathogen has not been confirmed. CDC reports similar cases have appeared in at least 10 states -- Missouri, Kansas, Illinois, Kentucky, Iowa, Colorado, Ohio, Oklahoma, North Carolina, and Georgia.

There are a few publications over the last 5 years describing EV68 associated outbreaks including an MMWR covering 2008-2010 clusters and individual reports from the EV68 emergence in the Netherlands, and an Indian Health Services (IHS) outbreak in children (both were already covered in MMWR). The Netherlands has seen the majority of cases in September to November (Figure above) with the highest prevalence in patients ages 50-59, while the IHS outbreak occurred in August-September in children with a median age of 4.8 years.

Clinical Findings: Signs and symptoms include cough, tachypnea, hypoxemia, and wheezing, particularly new-onset. In the Arizona IHS outbreak, at least half of the children had infiltrates on CXR and short hospital stays (median 1.5 days). The clinical presentations of the 18 IHS patients are listed in the table below.

Diagnosis: There are commercially available, FDA-approved, multi-pathogen detection systems including Luminex xTAG RVP, Idaho Technologies FilmArray Respiratory Panel. However, these non-specifically identify pathogens as "entero-rhinovirus" or "human rhinovirus/enterovirus." Most facilities can't currently perform enterovirus typing. Identification of EV68 requires partial sequencing of the structural protein genes, VP4-VP2 or VP1.

Treatment: There is no specific treatment for EV68. Care is usually supportive and only a minority of patients require brief hospitalization. Currently, there are no vaccines available.

Infection Prevention: The CDC currently (2007) recommends Standard Precautions for enteroviral infections but recommends "Contact Precautions for diapered or incontinent children for duration of illness and to control institutional outbreaks." However, most of the data that informed these recommendations were not derived from respiratory EV68 outbreaks. Recommendations from Hong Kong are very similar. 

I contacted a hospital epidemiologist in one of the states experiencing an outbreak, who has graciously shared their current protocol. Currently, they use symptoms to drive precautions so their respiratory patients are placed on droplet plus contact isolation for the duration of their hospitalization. In addition, they started their usual winter respiratory visitation restrictions last week so that children under 13 yo cannot visit and increased their focus on year-round routine screening of all visitors/family members for illness. Finally, they noted that this was the earliest they've ever started respiratory visitation restrictions.

Are you pro procalcitonin?

Clinicians over prescribe antibiotics. I spent several years exploring the risk-averse nature of physicians (specifically ID physicians) when it comes to avoiding treatment failure in diabetic foot ulcer, community-acquired pneumonia (CAP), and CVC bacteremia. Using binary choice contingent-valuation analysis our group determined that ID docs were very risk averse. For example, three of 34 ID physicians found a failure rate of 1% in CAP to be unacceptably high. So how do we acknowledge the risk-averse nature of clinicians, while at the same time safely improving antimicrobial stewardship through reducing over-prescription or shortening duration of therapy?

One possible and much heralded solution was going to be improved diagnostic microbiological tests, such as PNA FISH, which can rapidly detect clinically important (ie you need to alter therapy) pathogens, such as MRSA. These require waiting for positive blood cultures and haven't yet fully caught on, for whatever reason.  Importantly, these micro tests can't tell you if the patient is infected vs. colonized or what clinical syndrome they might have, such as pneumonia. Even a chest xray can't tell you if your patient has pneumonia.  That's why I was cautiously hopeful as I read a meta-analysis by Philipp Schuetz et al. of procalcitonin in directing antibiotic initiation and duration in acute respiratory infection, published online May 9th in CID.

Procalcitonin has gotten a lot of attention recently since it's been found that levels are high in severe bacterial infections but lower in viral or non-specific illnesses. Thus, algorithms that include procalcitonin cut-offs might help target initiation and withdrawal of antibiotic therapy without impacting clinical outcomes. To verify this claim, the authors reviewed 14 clinical trials with a total of 4221 patients to determine mortality, treatment failure and total antibiotic exposure in patients treated under procalcitonin-guided algorithms versus standard therapy. Mortality was similar in both groups (OR 0.94, 95% CI [0.71-1.23]) and treatment failure was slightly lower with procalcitonin (OR 0.82 [0.71-0.97]. Both of these were despite relatively poor-adherence in some of the studies. Importantly, total antibiotic exposure was decreased when using procalcitonin containing algorithms with a statistically significant reduction of 3.47 days. However, sample size was low when limited to ICU patients, so further studies are needed there.

These results do suggest that procalcitonin-containing antibiotic treatment algorithms may have an important role in respiratory tract infection therapy, particularly from a public-health, antibiotic resistance standpoint.  It remains to be seen if algorithms with limited clinical benefit for the individual patient but large potential benefits in terms of stewardship and public health will ever be widely adopted. Physicians are still risk averse, after all. Fingers crossed.

Source: Schuetz P. et al Clin Infect Dis 2012 (online May 9, 2012)

Image source: July 2009, Clinical Laboratory News

Don't Let the Patient RIDE THE BUS!!!

If you have a child under 10, you've probably enjoyed Mo Willems classic, Don't Let the Pigeon Drive the Bus!  I've never thought of it as a public health advice book for the Blue's Clues set, but perhaps I should have.

Researchers from Nottingham University wondered if exposure to public transport (bus or tram) within the most recent 5 days was a risk factor for acute respiratory tract infection.  They report in BMC-ID a small case (n=72) - control (n=66) study that riding public transport was associated with a 6-fold increase in presenting to a primary care physician with an acute respiratory infection (adjusted OR=5.94 95% CI 1.33-26.5).  Another interesting result was that it appeared that more frequent riding was associated with a lower risk of respiratory infection: (1-3 uses/week: adjusted OR=0.54, 95% CI: 0.15-1.95; >3 uses/week: adjusted OR=0.37, 95% CI: 0.13-1.06).

Some important caveats: (1) The unadjusted OR for public transportation was only 1.10, 95% CI: 0.55-2.21.  (2) To get to the adjusted OR, they controlled for age, gender, comorbidity, deprivation, child cohabitants, flu vaccination and habitual public transport use.  So, while the findings are intriguing,  negative confounders are extremely rare, so I think this study needs to be repeated.

Now off to read my favorite Mo Willems book: Don't Let the Hospital Epidemiologist Stay Up Late!

Troko J. et al BMC ID, published 1/14/2011