Influenza or Influenza-like Illness: Does It Matter?

Pam Harrison

Disclosures

February 16, 2018

It's been a very bad year for the flu. For the week ending February 3, 2018, the Centers for Disease Control and Prevention estimates that almost 8% of people saw their healthcare providers for an influenza-like illness (ILI), the highest rate of ILI since the 2009 pandemic.[1] Many more can be expected to be felled by the flu until the bug burns itself out around April. Bit not all ILI is caused by the influenza virus. Depending on the population, 60%-80% of ILI is caused by influenza, and the rest by other acute respiratory viruses masquerading as the flu. Does the distinction matter? Medscape turned to influenza expert Andrew T. Pavia, MD, professor of pediatrics at the University of Utah, to clarify the subtleties between influenza and its imitators.

Andrew T. Pavia, MD

Medscape: What is meant by the term "influenza-like illness"?

Dr Pavia: ILI is a way of tracking the burden of influenza. The term began to be used back in the days when relatively little influenza testing was done. ILI defined a patient with a documented fever and either a sore throat or a cough. These symptoms increase the likelihood that a respiratory illness is due to influenza and not some other virus, although this depends a lot on the time of year and how much influenza is circulating. So ILI is a surrogate—a way of looking for influenza mixed in with other things.

Medscape: So the likelihood of a patient having an ILI instead of influenza depends on the season?

Dr Pavia: Yes; the proportion of patients who come in with ILI depends on the time of year and what's circulating. Right now, there is so much influenza around that if you meet the definition of ILI, you probably have the flu. However, a fair amount of ILI may be caused by other viruses, like adenovirus or the respiratory syncytial virus (RSV) that we see in the middle of the summer when nobody is testing positive for influenza. There are no national data but there are sites, including our own, where a subset of patients who meet the definition of ILI are tested for influenza and other viruses. What we are seeing this year is that a small proportion of patients who look like they have ILI have what we call the "human metapneumovirus."

The other virus that does a pretty good job of masquerading as influenza is RSV. However, RSV mostly causes ILI in patients over the age of 65 and in children under the age of 2. In general, you can tell the difference between RSV-ILI and influenza in young children because they have a lot of wheezing and not as much fever. In infants, we call it bronchiolitis, which is a wheezing illness without much fever. So RSV-ILI doesn't give you a high fever, sore throat, and cough as reliably, but it certainly can in some patients.

Medscape: Which symptoms reliably predict influenza?

Dr Pavia: This has been studied by, among others, Monto and colleagues,[2] who carried out a retrospective pooled analysis of baseline signs and symptoms in patients who were mostly unvaccinated against the flu but who presented with ILI and were tested for influenza. Their symptoms included headache, myalgia, cough, and sore throat. Among nearly 3800 people in the study, almost two thirds tested positive for influenza, and in this group, patients with influenza were more likely to have cough compared with those without confirmed influenza. About two thirds of patients with confirmed influenza presented with fever, compared with only about 40% of those who were negative for influenza. Together, cough and a body temperature of 37.8°C or higher predicted influenza 79% of the time, and the higher the patient's temperature, the more likely they were to have influenza. So, when influenza is circulating in a community, patients who have both cough and fever within 48 hours of symptom onset are very likely to have influenza, and clinicians may consider the use of an antiviral where appropriate in such situations.

Medscape: Does it matter if a patient's non-influenza ILI is attributed to influenza, or vice versa?

Dr Pavia: It's more complicated than that. If someone presents with symptoms that you think are the flu and flu is highly likely, you don't need to test blood or urine, and you probably don't need to do a Strep swab of the patient's throat. However, several studies[3,4] have shown that when the diagnosis of influenza is confirmed by a rapid diagnostic test in a pediatric emergency room setting, physicians were more likely to take the right approach—no more tests, fewer x-rays, less antibiotic prescribing, and more use of antivirals. Unfortunately, when clinicians aren't certain, they tend to do more just to make sure. But if you are in a setting where you can't test to confirm influenza, then you just have to make a clinical decision about whether this really is the flu, even though the diagnosis may not be completely accurate.

Medscape: Does the management of an ILI caused by a non-influenza virus differ from that of influenza?

Dr Pavia: Yes, because right now, we don't have any antivirals for ILI caused by other viruses. The drugs we have to treat non-influenza ILI are probably at least 2 to 3 years away from making it to the clinic, if they make it at all. However, if patients come in with what you believe is influenza and they are in a high-risk group—heart disease, lung disease, diabetes, or an immune disorder—or they are very young or very old, you should treat them with oseltamivir (Tamiflu®). For otherwise healthy people, we don't strongly recommend treatment with any antiviral drug, although oseltamivir does help people feel better about a day faster than they otherwise would.

Medscape: Are other acute respiratory viral infections as serious as influenza?

Dr Pavia: Influenza can be mild, causing only a 2- to 3-day illness, although the symptoms can last 1-2 weeks. On the other hand, we are going to have tens of thousands of deaths this year from the flu and we've got hundreds of thousands of people in hospitals with influenza, and that generally doesn't happen to the same degree with the other viruses. So, influenza is typically more severe than ILI caused by other viruses.

Medscape: Why is this particular influenza season so bad?

Dr Pavia: Everything about the flu is complicated, and the reasons why this is such a severe year are probably multifactorial. First, the H3N2 virus we have seen a lot of this year can cause more severe illness. Second, although H3N2 influenza is starting to slow down a little, another flu virus, influenza B, is starting to increase quite rapidly—a double whammy. The fact that we don't have a great flu vaccine this year is certainly a contributor as well. The good news is that all indications are that the current vaccine works very well against influenza B, so although this season's vaccine is only about 20% effective against H3N2, the same vaccine appears to be effective against influenza B.

Medscape: Can someone be infected a second time with influenza or ILI during the same season?

Dr Pavia: Yes. You can definitely become infected with the H3N2 influenza strain and then become infected with the influenza B strain during the same season. You can get another ILI in the same season as well. At least seven to eight viruses are known to cause ILI, and you could be infected with all of them in a single year if you are really unlucky. People who have a lot of exposure to young children—for example, a kindergarten teacher—can be sick all winter!

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