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03/27/2018

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If You’ve Seen One Flu Season..

By Dr. David E. Hogan DO MPH FACEP
Director TeamHealth National Academic Consortium
Director of Education TeamHealth West Group

There’s an old adage “if you’ve seen one flu season, you’ve seen one flu season.” After years of working in the Emergency Department, most of us will attest to the truth of that saying. The data confirm what we already know – this is one of the most severe seasonal influenza epidemics in years. Clinicians have a lot of questions. What is the nature of the Influenza virus? Why do we see it every year, and why are some years more severe than others? What are the issues with the influenza vaccine and antiviral drugs? The Influenza virus is the most adaptable, and likely most dangerous virus on the planet. Clinicians and Public Health professionals are currently engaged in a struggle to keep pace with this entity – a struggle we can ill afford to lose.

The Influenza virus consists of a capsule with surface antigens surrounding its RNA core genes. There are two surface antigens, hemagglutinin and neuraminidase. The hemagglutinin binds to the surface of the respiratory cells allowing entry of the virus. Hemagglutinin is the site where blocking antibodies act to prevent binding and infection. This is the location of action for naturally acquired immunity and vaccines. Once the virus enters the cell and replicates, it needs to be released to infect other cells. The neuraminidase antigen allows this. Neuraminidase antigen production is blocked by neuraminidase inhibitor drugs (NAI). Without neuraminidase proteins, the virus cannot escape the cell and spread.

Influenza viral strains are named using an international system. Influenza A is the most severe and is sub-typed based on the Hemagglutinin (H) and Neuraminidase (N) proteins on its surface. Influenza B is typically named after the location it is first detected. Influenza B is usually less severe and much less adaptable than A. Influenza C is not commonly seen. There are currently 4 types of influenza virus circulating in Humans – Influenza A(H3N2), Influenza A(H1N1), Influenza B Yamagata and Victoria.

It is important to maintain a proper perspective. Influenza has been circulating in the human population for 500 years. It is thought to have initially made the jump to our species from birds. Each year new strains of the virus evolve that are resistant to our immune response and vaccines. If that isn’t bad enough, about every 40 years a more lethal strain emerges and circulates globally in a pandemic killing multiple millions and sickening billions.

Annual burden of influenza
The United States sees up to 56,000 deaths, 700,000 admissions and, 35.6 million symptomatic influenza cases each year – with direct and indirect medical costs in excess of $90 billion. These statistics alone make influenza one of the most impactful infectious diseases faced by clinicians. The 2017-2018 Influenza season is on track to be towards the upper level of those numbers. This season, Influenza A(H3N2) accounts for over 78% of all influenza cases. Typically-seasons that are A(H3N2) are worse causing higher numbers of hospitalizations and deaths. This season, many Emergency Departments and Hospitals are overcapacity. Some areas have declared a Public Health Emergency to meet increased care demands. In addition, shortages of antiviral drugs have been noted in some areas.
The problem with A(H3N2) Influenza

The A(H3N2) strain is a modification of avian influenza that first jumped into humans in 1968 and has now fully adapted to us. This virus evolves more rapidly than any other influenza virus known (a high level of plasticity). This provides new virus populations with different H and N surface antigens from the parent. These differences confer the new virus with resistance to host immunity and vaccines. This plasticity is why the influenza virus is so adept at evading human immunity. In reality each person is infected with hundreds of influenza virons which should be thought of as a “swarm of viruses” not a single viral species. When viewed in this perspective one begins to get a sense of the tenacious nature of the influenza virus and the difficulties presented in combatting it with vaccines and drugs.
The 2017-2018 Influenza Season

In January 2018 every state in the United States reported widespread influenza activity. This is the first time this has happened since starting flu surveillance programs. The season began early with a very rapid rise tracking along a similar path to previous A(H3N2) seasons with a similar severity of illness. It’s important to note that deaths occurring secondary to influenza are not all from A(H3N2) but rather a mixture of A(H3N2), A(H1N1) and influenza B. This season is indeed severe, but is not predicted to exceed the severity of A(H3N2) seasons of the past.
Influenza Vaccine

The Influenza Vaccine is our primary defense against this killer virus. Given the challenges in creating a vaccine for a new viral swarm each season, I am amazed my Public Health colleagues ever pull it off – but they do. On a twice-yearly basis the CDC meets with agencies around the globe to discuss the circulating influenza viruses. The objective is to select viruses for the upcoming influenza vaccine. The group must choose one each from influenza A(H3N2), A(H1N1), and B Yamagata and Victoria, about six months before the time of vaccination. This makes getting an effective vaccine a huge challenge. The virus candidates are then sent to the vaccine manufacturers.

The CDC monitors Vaccine Effectiveness (VE). In the past VE for all Influenza types is 41% – with A(H3N2) about 30%. This season VE is about 40% overall and 33% A(H3N2). What does this mean in real life? Last season, the vaccine prevented 85,000 hospitalizations, 2.6 million outpatient visits, and 5.3 million people from becoming ill. We also know getting the vaccine decreases mortality by 50% in patients who still caught influenza and required admission. Everyone six months old or greater should receive a yearly influenza vaccination.
Antiviral drugs

Antiviral drugs represent the second line of defense after vaccination against influenza. All current antivirals used for Influenza are neuraminidase inhibitors (NAI). There are three FDA approved NAIs; oral Oseltamivir (age ≥14 days), inhaled Zanamivir (age ≥ 7 years), and intravenous Peramivir (age ≥ 2 years). This year there is no evidence of significant drug resistance in the strains circulating. Given the plasticity of the Virus, the risk for developing drug resistance is high – so – is there evidence for benefit with NAIs? NAIs shorten the duration of the illness by 24 hours if started within 48 hours of symptoms. There are no controlled trials on severe outcomes prevention using NAIs. A meta-analysis of outpatient pediatric data demonstrated decreases of post-influenza otitis media by 34%. In adults and children post-influenza lower respiratory tract infections are reduced 44%. Adult hospitalizations are reduced by 63 to 75%, and the need for ventilators in children is reduced by 34 to 77%.

Based on the data, antiviral treatment is recommended as early as possible for patients with suspected or confirmed influenza who are hospitalized, have severe complicated illness, or at high risk for influenza complications. In addition, antiviral treatment can be considered for previously healthy symptomatic outpatients not at high risk with confirmed or suspected influenza based on the judgment of the clinician – if treatment is started within 48 hours of symptoms.

This has been a severe influenza season mainly due to the Influenza A(H3N2) predominance with characteristics similar to previous A(H3N2) years. The vaccine has had about an average level of effectiveness and is strongly recommended for anyone ≥ 6 months. The NAIs are effective and should be used following the CDC recommendations. Clinicians should continue to employ droplet and contact precautions when evaluating possible or confirmed influenza patients, until the virus swarm is no longer in active circulation.