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From newborns to teens, an evidence-based review of pediatric flu management

It’s that time of year again. Every shift, every day, it’s fever, cough, congestion. The hospital infectious disease report confirms that you are in the middle of an influenza epidemic. Tonight has been no different.

Four Cases

In room 3 you have a fully immunized 18 month-old, with no significant past medical history. The parents brought her in tonight because she developed a fever, runny nose, sneezing and cough this afternoon after waking up from her nap. She looks great after getting an antipyretic at triage and is active and playful. Should she be tested for influenza? Should she receive Tamiflu (oseltamivir)?

In room 4 is a 5 week old with fever. He also has nasal congestion and sneezing, decreased PO intake and fussiness. Both his mother and babysitter have recently had similar symptoms and tested positive for the flu. The mother took him to his pediatrician who referred him to the ED for a fever evaluation due to his young age. A rapid flu test done in the office is positive. Does this alter your plan for work-up or treatment?

In room 6 is a 7 year-old boy whose sister was started on Tamiflu yesterday by her pediatrician for a flu-like illness. Now he has fever, cough, chills, body aches and nasal congestion. The father says this is just like his sister’s symptoms and wants this child started on Tamiflu as well. What are the pros and cons?

In room 7 there is a 17 year-old with static encephalopathy, profound developmental disability and epilepsy. She is being admitted for pneumonia. She has had a flu-like illness since last week and has gotten progressively worse. Is it too late for her to start Tamiflu? Do you need to confirm that she has influenza before you start treatment?

Discussion

Between September 29, 2013 and December 7, 2013, 90% of influenza cases have been due to influenza A. The predominant strain has been H1N1, the same pandemic strain that caused disproportionately severe illness in children and young adults in the recent past. The good news is that the vaccines that are in use include this strain. Vaccination is not fully protective however, maybe affording up to 2/3 immunity to infection with this virus. Since September 2009, more than 99% of influenza strains have been susceptible to neuraminidase inhibitors Tamiflu (oseltamivir) and Relenza (zanamivir). These drugs are active against both influenza A and B.

The other influenza A strain around is H3N2. Last year, this strain caused increased deaths over the prior year’s virus. The majority of pediatric deaths were in unvaccinated children. 44% of the children who died had no underlying risk factors while 23% had a history of reactive airway disease or asthma.

peds-table

 

Case 1: Toddler

 

Let’s start with room 3. In the middle of a flu epidemic, what looks like flu is probably flu. This child does not need blood work or urine. She does need Tamiflu. Why? Because she is at high risk of complications based on her age. The American Academy of Pediatrics issues recommendations annually for the prevention and control of influenza. The recommendation is that children who are at high risk of severe disease or complications of disease receive anti-viral therapy. Tamiflu is preferred over Relenza because it is easier to use. Relenza is inhaled, cannot be used in children with a history of wheezing or chronic lung disease and is given to children age 7 or older for treatment. Tamiflu is a liquid and can be given to children as young as 2 weeks of age. If the pharmacy is out of liquid Tamiflu, they can open a capsule and mix the contents in syrup to produce an acceptable liquid version.

Screen Shot 2014-02-18 at 4.24.05 PMThis child, at 18 months, meets high-risk criteria. Should you do a rapid flu test to confirm that it is the flu before you treat? The rapid antigen tests that are currently in use have low sensitivity, particularly for H1N1. A negative result does not mean that the child does not have the flu. In addition, treatment should not be delayed. The sooner treatment with Tamiflu is started, the better, since it carries the most benefit when started within 48 hours of symptom onset. If Tamiflu is started within 48 hours it can reduce the length of illness by one day. If started within 12 hours, it has been shown to reduce the duration of illness by as many as 3 days. It may be even better than that in very young kids. One randomized clinical trial of Tamiflu showed a reduction of 3.5 days in patients 1-3 years old. So our patient may really benefit from getting started right away.

 

So, you decide not to test this child for flu, to get her started on Tamiflu as quickly as possible and you are ready to send her on her way. Well, not so fast. You almost forgot something. Household contacts. Is there anyone high-risk that the patient is regularly exposed to that needs to be considered for chemoprophylaxis?

Chemoprophylaxis should only be given to someone exposed to the patient while she is infectious. When is she infectious? From 1 day before she developed her symptoms until 24 hours after the fever has ended. It should be started within 48 hours of exposure. It is not perfectly effective in eliminating risk, but does reduce it. The risk reduction lasts only until the drug stops. It’s not a substitute for vaccination.

You ask about high-risk contacts and the parents report that there is a 4 month-old at home who is too young for the vaccination. They don’t know the baby’s weight. You have a chart from the CDC that gives Tamiflu dosing by weight, but are unsure what to do. You check in UpToDate and find that the recommended dose when you don’t know the weight is:

  • Age 4-5 months: 17 mg daily
  • Age 6-11 months: 24 mg daily
  • The duration of treatment should be the duration of the exposure.

Case 2: Febrile newborn

On to the next case. This is a full term infant, now 5 weeks old. He has no significant medical history and has been well until his symptoms started last night. He is febrile in the ED, but does not appear toxic. As stated before, he has two direct contacts that are influenza positive and his own test was positive at the pediatrician’s office. What is his risk of serious occult bacterial infection? Of pneumonia? Does he need a full sepsis work-up?

Screen Shot 2014-02-18 at 4.23.54 PMNot necessarily. There have been several studies of the risk of bacterial infection in young infants with fever and viral illnesses, including influenza. These have all shown a small increased risk of UTIs but not bacteremia or meningitis. The rate of pneumonia has also been small in infants aged 60 days or less presenting with new onset of fever and a positive test for influenza. If the physical exam is benign, it is reasonable to check a urine and start Tamiflu, at a dose of 3 mg/kg/dose given twice daily for 5 days. Further work-up is up to the provider. Most of us would do a full sepsis work-up and admit an infant in the first 28 days of life. This child is slightly older. You chose to obtain a urine specimen, give him Tylenol and observe him in the ED. His temperature comes down, he feeds well, and his exam remains benign. His urine is negative. You send him home just with Tamiflu and close follow-up with his pediatrician.

 

Case 3: Healthy 7-year-old

Now to the room with the seven year-old who has new onset of flu-like symptoms in the past 24 hours and an influenza-positive sick contact. This kid is healthy. He has no risk factors for a severe or complicated course. The father wants him treated. What should be considered here?

Do you test him? Remember, you cannot rule out flu if the test is negative. If you’re going to treat him you should do it as soon as possible and not wait for the test. If that’s the case, why test anyone? The answer is to establish the cause of fever in a patient where you might consider other testing if the fever persists.

Fine, you decide not to test him. Why would you treat him? Tamiflu gets you a shorter duration of illness, although in this case, it would only be about one day. The burden of disease in childhood influenza includes time missed from school and time missed from work for the parents. Children are vectors for disease spread. In addition, Tamiflu is associated with decreased prescriptions of antibiotics. Tamiflu may decrease the likelihood of pneumonia, hospitalization or severe disease. In the US, between 2004 and 2012 there were 830 pediatric deaths from influenza. The median age was 7 years. The medical history was known in 794 of these cases. Of those, 43% had no high-risk conditions. So, this healthy, low risk 7 year-old has a risk of death that is small, but not zero.

Reasons not to treat him? Most healthy kids do fine with the flu. Tamiflu costs money. If you treat every low risk child with Tamiflu, there may not be enough drug around to treat those who really need it. Tamiflu can cause side effects, mostly mild, but the drug has been associated with serious skin reactions including Stevens-Johnson syndrome as well as neuro-psychiatric symptoms, seen mainly in Japan where it is widely utilized. Finally, there is the risk of inducing drug resistant strains with widespread use. 

You have a chat with the father. He is not particularly moved by the public health arguments but he agrees that the child looks well and is likely to recover uneventfully. He can’t fill the prescription until tomorrow anyway, at which point the benefit would be much reduced. He decides to pass on the Tamiflu. You send him home with notes for school and work.

Case 4: Disabled Teen

Lastly, we have the teenager with significant neurologic disability, pneumonia and a severe course, who is requiring admission. Treatment guidelines indicate that hospitalized children with presumed influenza should be treated with Tamiflu regardless of the time of onset of symptoms. Several studies have shown that neuraminidase inhibitors (usually Tamiflu) have reduced severity of illness and mortality in hospitalized pediatric patients with the flu. While you decide to send a flu swab to the lab, you start Tamiflu immediately without waiting for lab confirmation, and send her upstairs.

A lot of patients, a lot of flu, a lot to think about.

 

Amy Levine, MD, is an associate professor of pediatric emergency medicine at UNC Chapel Hill.

 

References

 

1. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children,2013-2014. Pediatr 2013;132:e1089-e1104.

 

2. Munoz FM. Seasonal influenza in children: prevention and treatment with antiviral drugs. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2014.

 

3. Thorner AR. Treatment and prevention of pandemic H1N1 influenza. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2014.

 

4. Wong KK, Jain S, Blanton L, et al. Influenza-associated pediatric deaths in the United States, 2004-2012. Pediatr 2013;132:796-804.

 

5. Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk of serious bacterial infections in young febrile infants. Pediatr 2009;124:30-39.

 

6. Piedra PA, Schulman KL, Blumentals WA. Effects of oseltamivir on influenza-related complications in children with chronic medical conditions. Pediatr 2009;124:170-178.

 

 

 

Comments   

# RE: Pediatric Flu: A Nuanced ApproachLong Time E.D. Doc 2014-02-26 17:41
Pediatric flu review, brought to you by Genentech,a division of Roche, the makers of Tamiflu.

Conclusion: everyone should get Tamiflu along with the people who have had contact with people with flu...The next Roche sponsored article will "recommend" taking it if you see someone in either a grocery store or department store who looks like they might have the flu.)

I believe Dr. Bukata has a nice article on the Tamiflu studies within the past few weeks on EPMonthly.
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