EXECUTIVE SUMMARY

This year’s flu season is not overwhelming EDs like last year’s record-breaking season. However, the circulating viruses remain dangerous, particularly to groups most at risk. By mid-February, the CDC reported there had been 41 flu-related pediatric deaths, with flu activity still on the rise across the country. To help frontline providers, the CDC is offering new tools to help them keep track of flu activity and severity. Further, there is a new antiviral medication that has been approved by the FDA.

  • By the week ending Feb. 16, the CDC reported widespread flu activity in 48 states and Puerto Rico, with the proportion of people seeing healthcare providers for influenza-like illnesses increasing from 4.8% in the previous week to 5.1%.
  • This year, epidemiologists are seeing primarily an H1 virus-predominant season, although in the Southeast, epidemiologists are seeing more H3 viruses circulating.
  • Early data suggest the circulating viruses are well-matched to the vaccines prepared for this year’s flu season. Also, vaccination rates are up a few percentage points over last year.
  • The CDC recommends antiviral treatment for any patient with suspected or confirmed flu who is hospitalized; has severe, complicated, or progressive illness; or is at high risk for influenza complications. Also, children younger than 2 years of age are considered at highest risk for complications.

Although not nearly as challenging as 2017-2018, this year’s flu season is nonetheless proving dangerous for those at highest risk. The CDC noted that by mid-February, 41 flu-related pediatric deaths had been reported so far this season, including seven deaths that occurred in the week ending Feb. 16.

Also by mid-February, influenza-like illness was at a high point for the year and still on the rise, according to epidemiologists. They reported widespread flu activity in 48 states and Puerto Rico, with the proportion of people seeing healthcare providers for influenza-like illnesses increasing from 4.8% in the previous week to 5.1%. For comparison purposes, the CDC noted that over the past five years, the peak proportion of people seeking treatment from a healthcare provider for influenza-like illness has ranged between 3.6% in the 2015-2016 flu season to a high of 7.5% during the 2017-2018 season.

After last year’s brutal season, when EDs were repeatedly challenged by soaring volumes and a particularly nasty flu strain, frontline providers are naturally on guard about what this season portends. It turns out there are some new tools at their disposal this year as well as one new antiviral option for treating patients.

Epidemiologists from the CDC shared the latest information about this year’s circulating viruses in a Clinician Outreach and Communications Activity presentation on Feb. 5, highlighting what disease investigators know about this flu season thus far as well as the panoply of recommended treatment choices.

H1 Influenza Dominates

When describing the trajectory of this year’s flu season, Alicia Budd, MPH, an epidemiologist in the influenza division at the National Center for Immunization and Respiratory Diseases at the CDC, noted that flu activity, based on specimens testing positive for the circulating viruses, was low across the country in October and November 2018, but then began to pick up in December.

There was a brief decrease in the number of specimens testing positive just after the holidays when most children were out of school. However, Budd said public health authorities have seen steady increases in specimens testing positive ever since.

While public health labs primarily test specimens for surveillance purposes, they also inform public health authorities on the types of flu viruses that are circulating, and in what proportion, Budd explained. For example, there are two influenza A subtypes: H1 and H3. Also, there are two influenza B lineages: either Victoria or Yamagata.

“This year, we are seeing primarily an H1-predominant season. That is the most commonly reported virus nationwide, and that is true in nine of the 10 surveillance regions,” Budd said. “However, the southeast part of the country ... is actually seeing more H3 viruses than H1 viruses, although they are seeing significant H1 activity as well.”

Budd noted that public health authorities have found very little influenza B activity this season, with labs showing only about 1% of the specimens testing positive for influenza B viruses. Most of these are Yamagata lineage viruses.

Public health labs send a subset of their positive flu specimens to the CDC for genetic and antigenic testing so that epidemiologists can monitor the circulating viruses for any changes as the season progresses. Epidemiologists also use these samples to assess how susceptible the strains are to vaccines that have been prepared to protect people from the flu. Budd reported that the information culled from these examinations has yielded good news so far.

“Nearly all of the H1, H3, and B Yamagata lineage viruses collected in the U.S. this season that have been antigenically characterized are similar to their respective cell-grown, vaccine-referenced viruses,” Budd said. “There is a little bit more diversity when you look at the B Victoria viruses. Even so, more than 71% of those viruses that have been tested are antigenically similar to the vaccine-[referenced] viruses.”

Vaccines Well-Matched

These data suggest that the flu vaccines prepared for this season are well-matched to circulating virus strains that have been tested by the CDC to this point. Further, Budd noted that tests of susceptibility to antiviral medications also have produced positive results so far.

“All the viruses tested — around 700 viruses — have shown susceptibility to zanamivir. More than 99% of [viruses] showed susceptibility to oseltamivir and also peramivir,” Budd said. However, she added that only a small number of H1 viruses have demonstrated reduced or highly reduced susceptibility to antiviral medications.

By mid-February, flu-related hospitalizations amounted to 27.4 per 100,000 people, with the highest rates occurring among adults 65 years of age and older, according to the Influenza Hospitalization Surveillance Network. Among this older age group, there were 75.6 hospitalizations per 100,000 people. Children younger than 5 years of age were hospitalized at a rate of 40.2 per 100,000. Adults 50-64 years of age were hospitalized at a rate of 37.7 per 100,000.

The data seem to correlate with the two most recent H1-predominant seasons. For example, in 2015-2016, the end-of-season flu hospitalization rate amounted to 31 per 100,000 people. In the 2013-2014 season, the end-of-season hospitalization rate was 35 per 100,000 people, Budd noted.

“We do expect the hospitalization rates [this year] to continue to increase as the season progresses, but we certainly don’t expect to see hospitalization rates anywhere near the record-breaking rates we saw in the H3-predominant season we had last year,” Budd offered.

In the 2017-2018 season, hospitalization rates were the highest ever recorded since surveillance was expanded to include all age groups in 2005, according to the CDC. The hospitalization rate ranged from 58 per 100,000 people in adults 18-49 years of age to 260 per 100,000 people in adults 65 years of age and older. In children younger than 5 years of age, the hospitalization rate was 139 per 100,000 people.

“It was the first time that we had a season where all three age groups were at a level of high severity,” Budd noted.

Tools Track Activity, Severity

As in past years, the CDC posts an update on the influenza data it has gathered each week throughout the flu season. This “FluView” report (Read more about this report online at: https://bit.ly/2veekNl) includes mostly national-level activity, but there is some discussion of regional and state-level activity, too.

Further, there is an online tool that is called “FluView Interactive” (Read more about this report online at: https://bit.ly/2loFOKK), which enables clinicians to study surveillance data in greater depth. For instance, clinicians can examine data from different regions as well as from past seasons, Budd explained. The FluView and FluView Interactive data are updated every Friday morning. Also, there is a new report the CDC is debuting this year that provides updates on the severity classification for the current flu season as well as preliminary burden estimates. (Read more online at: https://bit.ly/2T6EMVN).

“The severity assessment is based on a couple of the surveillance system components, and it is how we are objectively classifying the severity of this season,” Budd noted. “Basically, we are taking the data ... and comparing where we are right now to different threshold indicators of severity based on data we have from past seasons.”

In the past, the CDC only produced such a report at the end of the season when the surveillance data were final. This year, updated reports are released weekly as the season unfolds, Budd said.

“What this [report does] is use mathematical models to translate some of our surveillance data into estimated numbers of illnesses, hospitalizations, and deaths,” she explained. “We do this because we know the surveillance system cannot provide those actual counts. It does a great job of tracking activity, but not providing those numbers of cases. And we know that information can be helpful.”

Certain Groups at Higher Risk

Most clinicians are aware that influenza can be associated with a range of symptoms that include upper respiratory tract illness, an abrupt onset of fever, coughing, chills, sore throat, fatigue, muscle aches, and headache. However, Angela Campbell, MD, MPH, medical director of the influenza division in the National Center for Immunization and Respiratory Diseases, noted that flu may present differently in certain age groups. For example, gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea are more common in children with the flu. Infants may present with fever but no respiratory symptoms at all. “On the other end of the age spectrum, elderly people as well as people who are immunosuppressed may have atypical symptoms and may not have fever,” Campbell added.

Campbell noted that while most adults hospitalized with the flu present with some type of underlying medical condition such as diabetes or cardiovascular disease, that is not necessarily the case for children.

“More than half of children hospitalized with flu actually have no previously known underlying medical conditions,” she said.

One common complication of flu is otitis media, which can develop in up to 40% of children younger than 3 year of age. Another mild to moderate complication of flu is sinusitis.

“Influenza can also exacerbate chronic underlying conditions such as asthma or heart disease,” Campbell explained. “Other common causes of hospitalization with flu actually include the dehydration that goes along with it or pneumonia. This can be either viral pneumonia or secondary bacterial pneumonia.” The flu can cause other types of respiratory symptoms such as croup, bronchiolitis, or extra-pulmonary complications, including renal failure, myocarditis, myositis, rhabdomyolysis, encephalitis, and even sepsis, Campbell observed. “Sepsis, in fact, has been found to be listed as a complication in up to 30% of pediatric death reports,” she said.

Campbell added that the most common bacteria found in co-infections with the flu are Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes (or group A strep).

Test and Treat

Generally, Campbell said that influenza testing should be performed when the results are likely to influence clinical management. This may be by decreasing lab testing for other etiologies, decreasing the unnecessary use of antibiotics, facilitating the implementation of infection prevention and control measures, increasing the use of appropriate antiviral drugs, or potentially decreasing length of stay in the hospital.

“Testing should also be performed if the results would influence a public health response, such as for outbreak identification and invention,” she said, noting that this could pertain to a long-term care facility, for example. “If a patient with suspected flu is being admitted to the hospital, testing is recommended along with empiric antiviral treatment while results are pending. If the patient is not being admitted, but if results will influence clinical management, the same recommendation applies.”

For cases in which testing results are not likely to influence clinical management, testing is not necessary, Campbell added.

“For example, if flu can be clinically diagnosed, empiric treatment can simply be initiated,” she said. “Empiric treatment is recommended if the patient is in a high-risk group or has progressive disease.”

Regarding what tests should be used to diagnose influenza, Campbell said that for outpatients, rapid molecular assays are highly sensitive and offer better detection than rapid influenza diagnostic tests that rely on antigen detection.

“For hospitalized patients, molecular assays, including RT-PCR or other multiplex molecular assays, should be used to improve detection of influenza. For immune-compromised patients specifically, multiplex molecular panels are recommended,” she said.

Experts agree that the best way to prevent flu is with annual vaccinations. There is some evidence that the harsh 2017-2018 season may have prompted an uptick in vaccination rates this year, Campbell said. For instance, she noted that by November 2018, flu vaccination coverage among children aged 6 months to 17 years was 45.6%, reflecting a 6.8% increase over November 2017, according to the National Internet Flu Survey (NIFS). Similarly, NIFS data show vaccination coverage for adults in November 2018 stood at 44.9%, reflecting an increase of 6.4% over November 2017.

While vaccination is the primary method for preventing flu, antiviral medications are an important adjunct to vaccination in that they can help to prevent severe outcomes, Campbell said. Further, she noted that of particular importance is the treatment of patients with severe disease and those at the highest risk of developing severe influenza complications.

“Clinical trials and observational data show that early antiviral treatment shortens the duration of fever and flu symptoms,” Campbell said. “Meta-analyses of randomized, controlled trials have demonstrated that early treatment reduces the risk of otitis media in children and lower respiratory tract complications requiring antibiotics and hospital admission in adults.”

Further, Campbell noted that data from observational studies suggest early antiviral treatment reduces the risk of hospital admissions among high-risk outpatient children and adults. Also, early treatment of hospitalized children and adult patients with oseltamivir, one of the available antiviral medications, shortened hospitalization. Data also show that early treatment of hospitalized adults with oseltamivir reduced the likelihood of death.

In brief, Campbell noted that antiviral treatment is recommended for any patient with suspected or confirmed flu who is hospitalized; has severe, complicated, or progressive illness; or is at high risk for influenza complications. Campbell reiterated that children younger than 2 years of age are considered at highest risk for complications.

“We also note that antiviral treatment can certainly be considered for any previously healthy symptomatic patient not at high risk with suspected or confirmed flu on the basis of clinical judgment if treatment can be initiated within 48 hours of onset,” she said. Currently, there are four FDA-approved antiviral medications, including one new medication (baloxavir), which the FDA approved in October 2018. Although the CDC does not recommend any particular antiviral medication over another, there are some differences among the options. For example, oseltamivir, which is taken orally, is FDA-recommended for anyone 2 weeks of age or older, although Campbell noted that the CDC supports its use from birth even in preterm infants. Oseltamivir also is recommended for chemoprophylaxis, to prevent flu, and is the preferred antiviral medication for pregnant women as well as hospitalized patients. Adverse events associated with oseltamivir include nausea, vomiting, and headache, although Campbell noted that these issues can be ameliorated if the medication is taken with food.

Zanamivir is an inhaled medication recommended for patients 7 years of age and older. This drug also is recommended for chemoprophylaxis. One adverse reaction (bronchospasm) is associated with this drug, so it is not recommended for patients with underlying airway diseases, Campbell noted.

Peramivir is administered intravenously in a single dose. This drug is recommended for patients 2 years of age and older. It is associated with one adverse reaction (diarrhea).

Baloxavir is taken orally in a single dose. The dose measurement is based on weight and age. The drug is recommended for patients 12-64 years of age. Currently, there are no adverse reactions associated with the drug.

Complications and Severe Illness

Clinicians should be aware that certain groups are at higher risk for complications and severe illness from the flu. These groups include:

  • children younger than 5 years of age, particularly those younger than 2 years of age;
  • adults 65 years of age and older;
  • people with immunosuppression or chronic medical conditions;
  • pregnant and postpartum women;
  • children taking long-term aspirin therapy;
  • American Indians;
  • Alaska natives;
  • individuals who are extremely obese;
  • residents of nursing homes and other long-term care facilities.