As you’re bombarded this winter with sick flu patients and sensational flu headlines, it helps to go back to basics
As you’re bombarded this winter with sick flu patients and sensational flu headlines, it helps to go back to basics
Recall from med school that Influenza A and B viruses – the kinds responsible for seasonal epidemics – consist of an envelope containing the glycoproteins hemagglutinin (H) and neuraminidase (N). Infection results when the hemagglutinin binds to respiratory epithelial cells, and the virus replicates. Neuraminidase causes viral dissemination. Viral strains are classified with detailed nomenclature based upon glycoprotein variation (H1N1, H5N1, etc…) and other identifiers.
Genetic reassortment causes major changes in the H and N glycoproteins, resulting in antigenic shift. Influenza A antigenic shift evolves rapidly and Influenza B evolves at a much slower rate, but there is still enough antigenic variability in both A and B that we get no lasting immunity from infection. Consequently, we depend upon genetic surveillance to determine the optimal combinations for each year’s influenza vaccine. This surveillance must be performed well in advance of flu season, as it takes months to grow enough virus in eggs for vaccines.
Hence, there is potential to guess the wrong strains that will predominate, come winter.
For 2014-2015, the US trivalent influenza vaccine consists of A/California/7/2009/H1N1, A/Texas/50/2012/H3N2, and B/Massachusetts/2/2012. The quadrivalent vaccine contains additionally B/Brisbane/60/2008 [1]. I personally had to search around for the quadrivalent vaccine and finally got it from my local health department. Every attending or resident I asked had no idea what type of vaccine they had received.
The Texas H3N2 strain that went into this year’s vaccine, however, is not the strain we’re seeing so far in the community. This summer a Switzerland H3N2 strain started making the rounds. Unfortunately it was too late to incorporate the Switzerland strain in the vaccine – the eggs were already growing. In the future, developing vaccine from cell culture, instead of eggs, may reduce the lag time and help match the vaccine contents with what’s circulating, boosting effectiveness. (This is the first year where a small fraction of trivalent vaccines given to people were actually grown from cell culture – dog kidney cells, if you must know.) Another consequence of this approach is that the “egg allergy” excuse won’t work anymore, if you’re trying to get out of your annual shot.
For the record, both avian and swine flu are Influenza A viruses, and occur naturally in wild aquatic birds, domestic poultry, and pigs. These do not normally infect humans except through close direct contact. Some of these strains – like H5N1 – are quite virulent and have resulted in high mortality in Asia, Europe, and Africa. There is real concern that, through this huge animal reservoir, H5N1 will mutate into a form where humans could spread the disease amongst each other, and millions could die. At this time, focus is on H5N1 disease prevention by culling animals and other infection control measures.
Disease Transmission
Seasonal influenza spreads through large respiratory droplets (>5μm, carried about 3-6 feet by coughing, sneezing – surgical masks can be protective); possible aerosolized airborne transmission4 (data unclear); and contaminated surfaces [2]. Aerosols are suspensions of small particles that can remain airborne for long periods. Surgical masks do not prevent aerosolized transmission, but the N95 respirator can.
Influenza A and B survive for 24 to 48 hours on hard nonporous surfaces such as stainless steel and plastic, but less than 12 hours on cloth, paper, and tissues. The virus can be transferred from steel surfaces to hands for 24 hours and from tissues to hands for 15 minutes [3]. This information is important to consider so we can properly protect ED personnel during respiratory outbreaks. We need to go beyond the bedside to consider disease transmission potential by telephones, keyboards, and during case presentations by students and residents.
Disease transmission occurs from day -1 to days 7-10 of illness. Children are major vectors of transmission and apparently can transmit disease for the longest time period during illness.
Vaccination
In general, CDC suggests there can be up to a 70% risk reduction of hospitalization in adults from vaccination, but I think there are too many variables to make this a hard number. It takes two weeks after the flu shot to get antibody levels. There are apparent benefits from cross-protection, and vaccine benefits vary even with a good antigenic match [1]. For these reasons, do not assume that vaccination excludes a flu diagnosis.
Flu Testing
What flu tests does your hospital use? There are a variety of rapid test methods appropriate for the ED. These test for influenza A and B. Hospital laboratories typically report sensitivities and specificities for the tests, but the data are comparisons to viral culture and have nothing to do with sensitivity and specificity for diagnosis in the individual patient. Because of Bayes Theorem, test performance depends upon, among other factors like test sensitivity and specificity, the pretest probability of the disease in question. So, when flu prevalence is low, the PPV of the test is low; and when flu prevalence is high, the PPV of the test is high [5]. So, we should use our clinical skills for diagnosing flu, and individualize the need for testing. Especially given the charge for testing, which in my hospital is said to be $250.
Flu Treatment
CDC guidelines recommend using clinical judgement for treatment with antiviral medications. Prioritize treatment to those with severe illness needing hospitalization; those older than 65; pregnant women; children under two years old; immunosuppressed. If medication is given, oseltamivir (Tamiflu) or zanamivir (Relenza) are recommended for Influenza A and B. Oseltamivir is recommended for pregnant women. For more details on treatment, see Amy Levine’s article on treatment for children, and Rick Bukata’s piece on Tamiflu. Post-exposure antiviral treatment could be considered for health care personnel who have had close contact with infected individuals, although PPE should be the first line of defense to avoid exposure [6].
Judith Tintinalli, MD, MS is the Editor-in-Chief of Emergency Physicians Monthly
REFERENCES
1. http://www.cdc.gov/flu/protext/keyfacts.htm and http://www.cdc.gov/flu/professionals
2. Brankston G, Gitterman L, Nirji Z et al ‘Transmission of Influenza A in human beings’ The Lancet Infectious Diseases, 7:4, april 2007, 257-265.
3. Bean B, Moore BM, Sterner B, et al ‘Survival of Influenza Viruses on Environmental Surfaces’ J InfectDis 146:1, 47-51
4. Tellier R ‘Review of aerosol transmission of influenza A virus Emerg Infect Dis 2006 12:11, 1657-1662
5. www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm
6. http://www.cdc.gov/h1n1flu/antiviral.htm
7. http://emergency.cdc.gov/HAN/han00374.asp
8. http://time.com/3548419/flu-shot-flucelvax/
9. http://www.cdc.gov/flu/protect/keyfacts.htm