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By Steve Dassel, MD

October 2009: Novel H1N1

Anticipating that "swine flu" will be a hot topic this fall, I talked to Danielle Zerr, MD, MPH, about novel H1N1. Danielle is associate medical director for Patient Safety-Healthcare Associated Infections. She is an associate professor of infectious disease at Seattle Children's Hospital and the University of Washington. She earned her MD from Temple University, and both her residency and fellowship in infectious disease were completed at Seattle Children's Hospital, University of Washington School of Medicine Pediatrics Department. She has been a faculty member since 1999.

Q:Danielle, swine flu, or novel H1N1, generated a lot of headlines last spring. Is there cause for concern or is this overblown?

A:There is cause for concern. We anticipate much more activity from novel H1N1 than would otherwise be expected from seasonal flu. This isn't because we expect novel H1N1 to be more virulent, but rather because the population has no experience with it. Therefore, we expect it to spread rapidly and yield a higher numbers of cases. This means higher numbers of high-risk patients suffering complications from the flu.

Q:And who are those high-risk patients?

A:Generally speaking, the high-risk groups are the same for novel H1N1 as they are for seasonal influenza - young children, pregnant women, individuals with underlying health conditions, etc. New this year is the recognition that children with neurodevelopmental disorders appear to be at higher risk of mortality from influenza. In addition, those 65 years and older don't appear to be at significantly increased risk for complications from H1N1. Reflecting this, the Centers for Disease Control have identified the following priority groups for vaccination: pregnant women, household contacts of infants younger than 6 months (infants younger than 6 months are too young to vaccinate), individuals 6 months old to 24 years old, 25- to 64-year-olds with underlying health concerns such as chronic pulmonary or cardiac problems, diabetes, and immunocompromising conditions, and, finally, healthcare and emergency services personnel.

Q:So, we older-than-65-year-olds are excluded, huh?

A:Right - excluded as an initial high priority group, but will be included as later priority

Q:Adolescents may be at higher risk; why is that?

A:More than any other group, they are "out there" and being exposed - not only at school, but at social events like Bumbershoot, etc.

Q:Anything novel about signs and symptoms of novel H1N1?

A:Not really - overall, it's the usual "flu-like illness" with respiratory symptoms (such as sore throat and cough), fever, myalgias, etc. However, there appears to be a bit more diarrhea associated with novel H1N1 than with seasonal flu, so diarrhea shouldn't cause patients or clinicians to discount the possibility of influenza in the setting of fever and respiratory symptoms.

Q:What tools does the laboratory have for diagnosis?

A:There are a variety of office tools - the rapid tests, which, depending upon the age of the patient, the type of flu and the type of rapid test, have sensitivities ranging from 10% to 70%. There is the respiratory fluorescent antibody test, which has very good sensitivity and specificity, but requires an experienced laboratory. These tests generally have same-day results. Finally there is PCR (polymer chain reaction), which adds even more sensitivity. PCR is also the method we use for subtyping the virus.

Q:How would you construct an algorithm for the utilization of laboratory tests?

A:There is no indication for treatment except in high-risk patients or those patients ill enough to be considered for hospitalization, so that would be the indication for testing. Here at Children's, we'll go directly to fluorescent antibody testing. Office testing using the rapid options would make sense for high-risk patients who have flu-like illness but are not very sick (these patients will be treated, but not necessarily hospitalized). In the middle of flu season, when the number of patients with influenza is high, rapid office tests generally perform reasonably well in children (better than in adults). The clinician has to realize, though, that while a positive test is usually correct, a negative rapid test does not rule out influenza. At Children's, at this point in time, we're recommending that our clinicians obtain subtyping of the virus for high-risk patients because knowing the viral type can give us susceptibility information. These recommendations may change over time as we start to see a lot of patients and our epidemiology becomes clear.

Q:What is the community healthcare provider's responsibility regarding sending patients up to Children's?

A:From our experience last spring, we are very worried about being inundated by patients who have flu-like illness but aren't that sick. Seattle Children's can provide critical support for the high-risk patients, as well as patients needing IV hydration and worrisome respiratory symptoms. We ask that healthcare providers just continue to use the same judgment about utilizing Children's that they would for any other ill child. We urge community providers to ask their patients to contact them first and not just have patients head for the hospital if their child has fever and respiratory symptoms. Most patients with flu-like illness require no treatment.

Q:How should we treat those who are high risk (less than 5 years old, pregnant, chronic conditions, etc.)? Is there any advantage to starting treatment on the severely ill patient before sending to hospital?

A:Not really. Treatment should be started promptly, but that means within 48 hours of onset of symptoms. The small amount of time it would take most patients to get to the hospital won't impact the course.

Q:And just to wrap up loose ends, by treatment, we're talking about oseltamivir or Tamiflu, right?

A:Right, oseltamivir is our first-line drug, especially in pediatrics, because of the oral formulation. Another option is zanamivir or Relenza. This drug is effective against all types of influenza, but it is only available in a formulation that is inhaled. The patient must be old enough to use the inhalation delivery system (it takes some coordination and children need to be at least 5 years old). Zanamivir is a great option, though, for patients who have problems with intestinal absorption.

Q:And again, treatment should be started ideally within 48 hours of onset of symptoms, right?

A:Right. The CDC has issued new guidance this fall stating that we shouldn't wait for the laboratory tests to confirm the diagnosis if the patient is ill or at high risk.

Q:What about virus resistant to oseltamivir (Tamiflu)?

A:It is rare, and we'd like to keep it that way by restricting treatment to the high-risk or more seriously ill patient populations.

Q:Finally, let's turn to vaccines. What is the projected date for having a vaccine to novel H1N1?

A:Now it sounds like the vaccine will be released in early October and available locally by middle to late October.

Q:Why couldn't it have been included with the trivalent vaccine for seasonal flu?

A:The seasonal trivalent flu vaccine was already under production when novel H1N1 hit the scene. So there wasn't time to include it.

Q:In addition to what we now know, how much added information about efficacy and safety will be available when the vaccine comes out?

A:All indications from the several thousand people studied so far are that the vaccine is immunogenic and safe. Questions regarding rare outcomes, such as Guillain-Barré syndrome, will, in large part, be a result of ongoing surveillance, as rare outcomes require many more people than the number of people that participated in the clinical studies for the vaccine.

Q:Other than a change in antigen, is this vaccine produced in the same way?

A:Yes, the very same way.

Q:And knowledge about efficacy?

A:The clinical trials will tell us what dose and how many doses are required to get to protective antibody levels. Early results from adult studies show that about 95% of adults respond very well after a single dose of vaccine, and that adolescents appear to respond similarly. However, children younger than 9 or 10 years are probably going to need two doses.

Q:I suspect you urge all of us healthcare providers to be vaccinated.

A:I sure do, and, here at Seattle Children's, we are aiming for a 100% participation of staff - either by getting vaccinated or signing a declination.

Q:Danielle, thank you for your time.