Episode 23 - Influenza Diagnosis and Management in the Emergency Department

  Jeff: Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta. This month, we’re talking about a topic that is ripe for review this time of year. We’re talking Influenza… Diagnosis and Management. Nachi: Very appropriate as the cold is settling in here in NYC and we’re already starting to see more cases of influenza. Remember that as you listen through the episode, the means we’re about to cover one of the CME questions for those of you listening at home with the print issue handy. Jeff: This month’s issue was authored by Dr. Al Giwa of the Icahn School of Medicine at Mount Sinai, Dr. Chinwe Ogedegbe of the Seton Hall School of Medicine, and Dr. Charles Murphy of Metrowest Medical Center. Nachi: And this issue was peer reviewed by Dr. Michael Abraham of the University of Maryland School of Medicine and by Dr. Dan Egan, Vice Chair of Education of the Department of Emergency Medicine at Columbia University. Jeff: The information contained in this article comes from articles found on pubmed, the cochrane database, center for disease control, and the world health organization. I’d say that’s a pretty reputable group of sources. Additionally, guidelines were reviewed from the american college of emergency physicians, infectious disease society of america, and the american academy of pediatrics. Nachi: Some brief history here to get us started -- did you know that in 1918/1919, during the influenza pandemic, about one third of the world’s population was infected with influenza? Jeff: That’s wild. How do they even know that? Nachi: Not sure, but also worth noting -- an estimated 50 million people died during that pandemic. Jeff: Clearly a deadly disease. Sadly, that wasn’t the last major outbreak… fifty years later the 1968 hong kong influenza pandemic, H3N2, took between 1 and 4 million lives. Nachi: And just last year we saw the 2017-2018 influenza epidemic with record-breaking ED visits. This was the deadliest season since 1976 with at least 80,000 deaths. Jeff: The reason for this is multifactorial. The combination of particularly mutagenic strains causing low vaccine effectiveness, along with decreased production of IV fluids and antiviral medication because of the hurricane, all played a role in last winter’s disastrous epidemic. Nachi: Overall we’re looking at a rise in influenza related deaths with over 30,000 deaths annually in the US attributed to influenza in recent years. The ED plays a key role in outbreaks, since containment relies on early and rapid identification and treatment. Jeff: In addition to the mortality you just cited, influenza also causes a tremendous strain on society. The CDC estimates that epidemics cost 10 billion dollars per year. They also estimate that an epidemic is responsible for 3 million hospitalized days and 31 million outpatient visits each year. Nachi: It is thought that up to 20% of the US population has been infected with influenza in the winter months, disproportionately hitting the young and elderly. Deaths from influenza have been increasing over the last 20 years, likely in part due to a growing elderly population. Jeff: And naturally, the deaths that we see from influenza also disproportionately affect the elderly, with up to 90% occurring in those 65 or older. Nachi: Though most of our listeners probably know the difference between an influenza epidemic and pandemic, let’s review it anyway. When the number of cases of influenza is higher than what would be expected in a region, an epidemic is declared. When the occurrence of disease is on a worldwide spectrum, the term pandemic is used. Jeff: I think that’s enough epidemiology for now. Let’s get started with the basics of the influenza virus. Influenza is spread primarily through direct person-to-person contact via expelled respiratory secretions. It is most active in the winter months, but can be seen year-round. Nachi: The influenza virus is a spherical RNA-based virus of the orthomyxoviridae family. The RNA core is associated with a nucleoprotein antigen. Variations of this antigen have led to the the 3 primary subgroups -- influenza A, B, and C, with influenza A being the most common. Jeff: Influenza B is less frequent, but is more frequently associated with epidemics. And Influenza C is the form least likely to infect humans -- it is also milder than both influenza A or B. Nachi: But back to Influenza A - it can be further classified based on its transmembrane or surface proteins, hemagglutinin and neuraminidase - or H and N for short. There are actually 16 different H subtypes and 9 different N subtypes, but only H1, H2, H3, and N1 and N2 have caused epidemic disease. Jeff: Two terms worth learning here are antigen drift and anitgen shift. Antigen drift refers to small point mutations to the viral genes that code for H and N. Antigen shift is a much more radical change, with reassortment of viral genes. When cells are infected by 2 or more strains, a new strain can emerge after genetic reassortment. Nachi: With antigen shift, some immunity may be maintained within a population infected by a similar subtype previously. With antigen drift, there is loss of immunity from prior infection. Jeff: The appearance of new strains of influenza typically involves an animal host, like pigs, horses, or birds. This is why you might be hear a strain called “swine flu”, “equine flu”, or “avian flu”. Close proximity with these animals facilitates co-infection and genetic reassortment. Nachi: I think that’s enough basic biology for now, let’s move on to pathophysiology. When inhaled, the influenza virus initially infects the epithelium of the upper respiratory tract and alveolar cells of the lower respiratory tract. Viral replication occurs within 4 to 6 hours. Incubation is 18 to 72 hours. Viral shedding is usually complete roughly 7 days after infection, but can be longer in children and immunocompromised patients. Jeff: As part of the infectious process and response, there can be significant changes to the respiratory tract with inflammation and epithelial cell necrosis. This can lead to viral pneumonia, and occasionally secondary bacterial pneumonia. Nachi: The secondary bacterial pathogens that are most common include Staph aureus, Strep pneumoniae, and H influenzae. Jeff: Despite anything you may read on the internet, vaccines work and luckily influenza happens to be a pathogen which we can vaccinate against. As such, there are 3 methods approved by the FDA for producing influenza vaccines -- egg-based, cell-based, or recombinant influenza vaccine. Once the season’s most likely strains have been determined, the virus is introduced into the medium and allowed to replicate. The antigen is then purified and used to make an injection or nasal spray. Nachi: It isn’t easy to create vaccines for all strains. H3N2, for example, is particularly virulent, volatile, and mutagenic, which leads to poor prophylaxis against this particular subgroup. Jeff: In fact, a meta-analysis on vaccine effectiveness from 2004-2015 found that the pooled effectiveness against influenza B was 54%, against the H1N1 pandemic in 2009 was 61%, and against the H3N2 virus was 33%. Not surprisingly, H3N2 dominant seasons are currently associated with the highest rates of influenza cases, hospitalizations, and death. Nachi: Those are overall some low percentages. So should we still be getting vaccinated? The answer is certainly a resounding YES.. Despite poor protection from certain strains, vaccine effectiveness is still around 50% and prevents severe morbidity and mortality in those patients. Jeff: That’s right. The 2017-2018 vaccine was only 40% effective, but this still translates to 40% less severe cases and a subsequent decrease in hospitalizations and death. Nachi: But before we get into actual hospitalization, treatment, and preventing death, let’s talk about the differential. We’re not just focusing on influenza here, but any influenza like illness, since they can be hard to distinguish. The CDC defines “influenza-like illness” as a temperature &gt; 100 F, plus cough or sore throat, in the absence of a known cause other than influenza. <p cl...