EXECUTIVE SUMMARY

Frontline providers confronted an unusual influenza season, with flu activity spiking as early as December. B virus strains, which usually lead to worse outcomes in children, was predominant in the early part of the season. By mid-February, flu activity remained widespread throughout the United States.

Typically, A strains are predominant in the early part of flu season, with B virus cases increasing later on. The reverse is true this year.

The predominant strain during the first half of the season has been B Victoria, a strain that is particularly hard on children.

As the season has progressed, cases of A(H1N1)pdm09, a strain that tends to produce worse outcomes for adults, have surged.

As of Feb. 15, the CDC reported hospitalizations for flu were estimated at 47.4 per 100,000 people, a similar rate observed in recent flu seasons, but a bit higher among children and young adults than what has been typical.

Deaths attributed to flu or pneumonia stood at 6.8% as of Feb. 15, slightly below the epidemic threshold of 7.3%. However, the total number of pediatric deaths for the 2019-2020 season totaled 105.


While the world is focused on COVID-19, frontline providers across the United States have their hands full with what is shaping up to be an unusual influenza season.

The CDC reports that not only was there an early start to the season, with flu activity jumping sharply in December, but the predominant strains of flu circulating in the early part of this season were from B lineage viruses, in particular the B Victoria strain.

“Typically, when we think of B activity in the U.S., we think of the later wave of flu activity that happens,” noted Alicia Budd, MPH, an epidemiologist in the influenza division of the National Center for Immunization and Respiratory Diseases at the CDC. Budd provided an assessment of the 2019-2020 influenza season during a Clinician Outreach and Communication Activity (COCA) call on Jan. 28.

However, as the season has progressed, Budd reported epidemiologists have observed an increase in A strains, especially A(H1N1)pdm09. This is a reverse of how flu seasons typically unfold. Generally, a season starts with A strain activity, followed by an uptick in B activity as the season progresses.

While the B Victoria strain tends to lead to worse outcomes in children, the A(H1N1)pdm09 strain is worse for adults, Budd explained. This trend is holding true thus far this season. “We are actually seeing a different predominant virus in the different age groups,” Budd said. “In our kids, the B Victoria viruses are predominant. In the adult age groups, it is the A(H1N1)pdm09 that are predominant.”

By mid-February, the CDC reported the numbers of B Victoria and A(H1N1)pdm09 viruses were about equal for the season overall, as cases of A(H1N1)pdm09 have continued to surge in recent weeks. Furthermore, widespread influenza activity remained prevalent in most regions of the country.

Hospitalizations for flu were estimated at 47.4 per 100,000 people, a rate similar to recent flu seasons, but a bit higher among children and young adults than what has been typical. Of all deaths that occurred in the United States, 6.8% of those were attributed to flu or pneumonia, slightly below the epidemic threshold of 7.3%. However, in the week ending Feb. 15, the CDC reported there were 13 pediatric deaths attributed to influenza, bringing the total number of pediatric deaths for the 2019-2020 season to 105.1

(Editor’s Note: For information about these mortality rates, which are based on National Center for Health Statistics surveillance data, please visit: http://bit.ly/38aEqjD.)

Overall, the CDC reported there have been at least 29 million flu illnesses, 280,000 hospitalizations, and 16,000 deaths related to the flu this season. As of mid-February, epidemiologists observed evidence of influenza activity had only slightly decreased from previous weeks.1

In a bit of good news, the first estimates on flu vaccine effectiveness, unveiled in late February, show the current formula is reducing doctor visits for flu by about 45% overall and 55% in children. Further, data show the vaccine is effective against both predominant circulating virus strains.

Clinicians can expect to see many typical manifestations of uncomplicated flu virus when patients present, explained Angela Campbell, MD, MPH, a medical officer in the CDC’s influenza division who also spoke during the Jan. 28 COCA call. “This can range from asymptomatic infection to a more typical upper respiratory tract illness, typically consisting of an abrupt onset of fever and cough with other symptoms that may include chills, muscle aches, fatigue, headache, sore throat, and runny nose,” she explained. “A runny nose and nasal congestion symptoms also occur with more common cold viruses as well, but they may occur in young children with the flu. GI symptoms such as abdominal pain, vomiting, and diarrhea tend to be more common in children.”

However, Campbell stressed young infants may not exhibit any respiratory symptoms at all, and may present with fever alone, often accompanied by irritability. She also noted elderly patients and those who are immune-suppressed may present with atypical symptoms and may not even report with any fever.

Clinicians also should be aware of the complications that can go along with flu. For instance, Campbell noted otitis media can develop in up to 40% of children younger than age 3 years who have the flu. It also can exacerbate chronic underlying conditions such as asthma. “Other common causes of hospitalization with flu include dehydration and pneumonia, and pneumonia can be primary viral pneumonia or secondary bacterial pneumonia,” Campbell explained.

Campbell added flu can cause other respiratory syndromes and extrapulmonary complications such as renal failure, myocarditis, pericarditis, myositis, and extreme rhabdomyolysis. “Flu is also known to cause encephalopathy and encephalitis, particularly in children, as well as sepsis and multiorgan failure,” she shared. “In fact, in a relatively recent review of death reports of children who died with flu, sepsis was actually found to be listed as a complication in up to 30% of those reports.”

Bacterial co-infections can cause severe disease when present with flu, Campbell said. She noted the most common bacteria involved in these cases include Streptococcus pneumoniae, Staphylococcus aureus, and group A streptococcus.

When should clinicians order tests for the flu? Campbell noted such testing is in order when the results are likely to influence clinical management. For example, if the results may decrease unnecessary lab testing for other etiologies or the unnecessary use of antibiotics, testing is advised. Further, if the results might facilitate implementation of infection prevention and control measures, increase the appropriate use of influenza antiviral medicines, and potentially shorten length of stay, flu testing is indicated.

“Another reason for testing is if it will influence a public health response. It can be very useful for outbreak identification and intervention,” Campbell said. “One of the most common situations where this is the case is in long-term care facilities or nursing home outbreaks.”

The Infectious Diseases Society of America (IDSA) produced an algorithm that can be used to help clinicians determine whether to order flu testing. This graph, along with additional guidance, is included online at: http://bit.ly/2HZZz5m.

“If a patient with suspected flu is being admitted to the hospital, testing is actually recommended both by IDSA and by CDC, along with empiric antiviral treatment while results are pending,” Campbell said. “If [the patient] is not being admitted, but if results will influence clinical management, the same recommendation applies.” In cases where flu testing results will not influence whether empiric treatment can be initiated based on a clinical diagnosis, then there probably is no need for it, Campbell added. However, she also noted empiric treatment is recommended in cases in which the patient is at high risk or presents with a progressive disease.

When considering antiviral treatment for flu, the focus of CDC’s treatment guidance is on the prevention of severe outcomes, Campbell noted. Consequently, this guidance is particularly aimed at patients with severe disease and those at the highest risk for severe disease. “Clinical trials and observation data show that early antiviral treatment can shorten the duration of fever and flu systems,” she said.

In particular, Campbell observed early treatment reduces the risk of otitis media in children and lower respiratory tract complications that require antibiotics and hospital admission in adults. Further, she noted both observational studies and meta-analyses have shown early antiviral treatment reduces the risk of hospitalization in high-risk children and adults.

Regarding oseltamivir, one antiviral medication, studies have revealed early treatment reduces the likelihood of death in hospitalized adult patients, and the drug has been shown to shorten the duration of hospitalization in both adults and children, Campbell said.

Considering the demonstrated benefits, the CDC recommends antiviral treatment as early as possible for any patient with suspected or confirmed influenza and severe, complicated, or progressive illness, or who is at high risk for influenza complications. This includes children younger than age 2 years, adults age 65 years and older, pregnant and postpartum women, American Indians and Alaska natives, children on long-term aspirin therapy, people with underlying medical conditions, and residents of nursing homes and chronic care facilities. “Clinical benefit is absolutely greatest when antiviral treatment is initiated as close to illness onset as possible. Treatment really shouldn’t be delayed while testing results are pending,” Campbell stressed.

However, she noted antiviral treatment initiated after 48 hours can still be beneficial in some patients. “There have been observational studies in hospitalized patients that suggest treatment might be beneficial even when initiated four or five days after symptom onset. Similarly, there have been observational data in pregnant women that have shown treatment to provide benefit when started three to four days after symptom onset,” Campbell reported. “But by and large, the earlier [treatment commences], the better. Even within the first 12 hours is better than within 24 or 48 hours.” Beyond the high-risk groups, antiviral treatment also can be considered for any previously healthy patients with suspected or confirmed flu. This determination can be made on the basis of clinical judgment if treatment can begin within 48 hours of illness onset, Campbell said.

Currently, there are currently four antiviral medications that are FDA-approved, including oseltamivir, zanamivir, peramivir, and baloxavir. However, which drug can be used depends, in part, on age. “Oseltamivir can be given to anyone of any age, zanamivir is for treatment of children age 7 and up, peramivir age 2 and up, and baloxavir age 12 years and up,” Campbell explained.

Considering zanamivir can cause bronchospasm, it should not be used in patients with underlying airway disease. Further, baloxavir is not recommended for pregnant or breast-feeding mothers because there are not enough data to support efficacy or safety in these groups. For hospitalized patients, treatment with oseltamivir is recommended as there are enough data to support the use of the other antiviral drugs in patients with severe influenza. For patients who cannot tolerate oseltamivir, intravenous peramivir should be considered, Campbell said.

Regarding corticosteroid drugs, Campbell noted they are not recommended as an adjunctive therapy for suspected or confirmed flu, for flu-associated pneumonia, for respiratory failure, or acute respiratory stress syndrome unless they are indicated for some other reason.

REFERENCE

  1. Centers for Disease Control and Prevention. Weekly U.S. influenza surveillance report. Available at: http://bit.ly/398N2bO. Accessed Feb. 26, 2020.