The Triple Helix @ UChicago

Winter 2018

"Influenza: A Past Concern Resurfaces" by Philip Jordache

 

The current flu season has seen illness and fatality counts rise to levels unseen since the appearance of the swine flu a decade ago. The Centers for Disease Control and Prevention (CDC) has reported that roughly one out of every thirteen doctor visits across the country has centered around flu symptoms, matching the corresponding rate from the 2009 swine flu pandemic. Typically, infants and the elderly die from the flu during the cold six months of the year, the time frame most commonly considered “flu season”—the current cycle, however, has seen a surprisingly high fatality rate among young people. According to the Indiana State Department of Health, roughly 65 percent of flu symptom diagnosed cases in Indiana fell between 5 and 24 years of age, and an additional 10 percent between 25 and 49, since October of 2017. In the same time span, in Indiana the flu was identified as the cause of 14 deaths among people under 30 as well as 128 for ages 65 years or older, exhibiting that fatalities are not unique to the elderly this time around. Such alarming trends extend beyond Indiana’s borders. The CDC has reported 63 pediatric deaths for the current flu season, already a sizeable figure compared to the death tolls of recent cycles. These data strongly indicate the current flu season has been just as destructive as the 2009 swine flu pandemic.

So how can something as common as the flu be so deadly? The flu normally kills through enabling subsequent illnesses to gain potency as a result of the body’s weakening due to the virus. These secondary illnesses can take on a number of possible forms including heart attacks, pneumonia, and sepsis (potenially life-threatening complications arising from bacterial infections). While it is relatively straightforward to trace deaths back to the flu, it is difficult to properly identify and treat the virus early on and prevent possibly deadly consequences. The global community needs a reliable, inexpensive test to detect the virus that can return accurate results rapidly at the first signs of flu symptoms as well as a robust, effective vaccine to combat the virus. 

One aspect of addressing this need calls for diagnostic tests currently available and in use to be scrutinized. The most widely used tests are known collectively as “rapid influenza diagnostic tests (RIDTs).” These tests utilize antigen identification mechanisms that target microbial cell surfaces to determine whether or not microbes present in the body can provoke immune responses. There exist other specialized tests that require more sophisticated resources, but these require several hours after a sample is collected via swab salivary or mucosal sample to return results. The time and monetary costs and tendency of these tests to be available only in out-of-the-way facilities present significant concerns regarding the motivation of busy patients and their families, particularly the disadvantaged. Many, as a result, rely on RIDTs to diagnose their flu symptoms, but while they provide quick results, these tests are often inaccurate. A study published in the journal Clinical Infectious Diseases evaluated a particular RIDT, the QuickVue Influenza A+B Test, and identified low sensitivity (median, 27%; range, 19%-32%) across populations tested. Improving such inexpensive diagnostic tests, however, generally involves introduction of known benefits that are already part of more costly tests, as well as enhancement of sample collection ease for patients; the path to improvement is fairly well-tread, and this seems more a matter of time than anything else.

A more central need for improvement lies in the vaccine used to ward off influenza. The vaccine operates by introducing a weakened version of the virus to present antigens that stimulate production of antibodies to combat the virus if it ever re-enters the body. Influenza, like other viruses, adapts and changes from year to year, and this evolutionary process requires that the vaccine do the same to keep up with it. The World Health Organization (WHO) convenes annually to decide the most likely flu strains to appear in the latter half of the year in the northern hemisphere; their recommendations inform production of the year’s flu vaccines, made available by September. However, the clear insufficient efficacy of the vaccine this season highlights a clear need for further measures to be taken to make sure it actually protects those who receive it.

One promising avenue to pursue is using adjuvants, substances known to enhance immune responses to specific antigens, to augment vaccines. Adjuvants have become an area of keen interest in developing novel techniques for improving vaccines. As one example, a study published in the Immunity Review underscores the benefits of using the adjuvant MF59, an oil-in-water immersion based on the relatively easily-metabolized oil squalene, to generate more robust antibody responses to pathogens reflected in patient populations in Europe, where the adjuvant has been approved for use. Safety concerns represent the main obstacle to widespread adjuvant introduction. The aforementioned study delineates the fear of autoimmune disease enhancement that can result from infections and the potential overcoming of T-cell inhibition in the adaptive immune response as the main concerning complications. In summarizing evidence of vaccine adjuvant safety, Flinders University Professor Nikolai Petrovsky maintains that “the biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions,” and he goes on to list Alzheimer’s disease and narcolepsy as two notable such reactions. In keeping with Professor Petrovsky’s argument, however, adjuvant research is crucial in adjusting the approach to combating influenza, for more research leads to a better understanding of the benefits and potential risks, as well as how to mitigate potential risks. As shown in patient populations abroad, adjuvant use has greatly promoted the flu vaccine’s effectiveness, and they stand as one of few burgeoning vaccine research areas that promise tangible results in the near future. Funding adjuvant research will be crucial in approving more adjuvants for use in the United States and abroad, and thus reinforcing the strength of the flu vaccine to stop the carnage it leaves in its wake. Influenza will not stop adapting; it is time for us to strengthen our measures to adapt with it. 

References

[1] Bongiovanni, Domenica. "Why Are People Dying from the Flu? It's Happened Even to Those outside the At-risk Groups." Indianapolis Star. February 13, 2018. Accessed April 01, 2018. https://www.indystar.com/story/life/2018/02/10/why-people-dying-flu/326138002/.

[2] Coffman, Robert L., Alan Sher, and Robert A. Seder. "Vaccine Adjuvants: Putting Innate Immunity to Work." Immunity 33, no. 4 (October 29, 2010): 492-503. https://ac.els-cdn.com/S1074761310003626/1-s2.0-S1074761310003626-main.pdf?_tid=d653b6f9-2396-4c51-8446-093ec47acef0&acdnat=1520199104_a235b6ea987fde7a6915a7a7ff6fadd9.

[3] "How the Flu Jab Works." NHS Choices. Accessed April 01, 2018. https://www.nhs.uk/conditions/vaccinations/how-flu-vaccine-works/.

[4] "Influenza (Flu)." Centers for Disease Control and Prevention. February 23, 2018. Accessed April 01, 2018. https://www.cdc.gov/flu/about/qa/testing.htm.

[5] Petrovsky, Nikolai. "Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs." Drug Safety. November 2015. Accessed March 31, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615573/.

[6] Uyeki, Timothy M., Prasad, Ramakrishna, Vukotich, Charles, Stebbins, Samuel, Rinaldo, Charles R., Yu-hui, Morse, Stephen S., Larson, Elaine L., Aiello, Allison E., Davis, Brian, Monto, and Arnold S. "Low Sensitivity of Rapid Diagnostic Test for Influenza." OUP Academic. May 01, 2009. Accessed April 01, 2018. https://academic.oup.com/cid/article/48/9/e89/412201

 

 
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