Flu can be seasonal or pandemic.
Pandemic flu is exceptional in causing severe complications (morbidity) and death (mortality) as is well known from the 1918 pandemic.
Seasonal flu indeed isn’t fatal for most people who catch it. However, the WHO points out that annually seasonal flu is (below from 1).
“estimated to result in about 3 to 5 million cases of severe illness, and about 290 000 to 650 000 respiratory deaths”
This toll from seasonal flu is easily overlooked because it leaves the young and healthy relatively unscathed. Instead it causes considerable morbidity and mortality in select subsets of the population – the very young, the elderly and pregnant women, especially those with a history of health problems (below from 1).
It takes analyzing excess mortality rates to render seasonal flu’s toll most clearly visible. EMR is an estimate of the death toll by a specific disease or condition in excess of, i.e., over and above, the usual predicted death rate for a given population. A 2018 analysis found (below from 2; modified as bullet points for easier perusal),
“The estimated mean annual influenza-associated respiratory EMR ranged from
- 0·1 to 6·4 per 100 000 individuals for people younger than 65 years,
- 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and
- 17·9 to 223·5 per 100 000 for people older than 75 years.
We estimated that 291 243–645 832 seasonal influenza-associated respiratory deaths (4·0–8·8 per 100 000 individuals) occur annually.
The highest mortality rates were estimated in
- sub-Saharan Africa (2·8–16·5 per 100 000 individuals),
- southeast Asia (3·5–9·2 per 100 000 individuals),
- and among people aged 75 years or older (51·3–99·4 per 100 000 individuals).
For 92 countries, we estimated that among children younger than 5 years, 9243–105 690 influenza-associated respiratory deaths occur annually.”
In other words, disproportionate deaths from seasonal flu and related complications are in those aged 65 and over. Since flu is a vaccine preventable disease, excess mortality is avoidable mortality and such estimates suggest sub-Saharan Africa and southeast Asia have the greatest need for flu vaccine coverage.
Since seasonal flu vaccines do reduce morbidity and mortality among those with highest risk, given such a segmented population risk, different countries differ in their recommendations but overall, most mandate or highly recommend coverage for those over 65 years of age, those with weakened immune systems, pregnant women and health care workers, idea being to reduce flu-specific morbidity and mortality and related costs to society (below from 3, 4).
Seasonal flu vaccines do present a dilemma because they vary quite a bit in their effectiveness (5, 6).
- Each year different flu strains circulate in temperate zones, spreading from the tropics where flu circulates year-round. Absent universal flu vaccines, seasonal flu vaccines need to be reformulated each year to try to achieve an optimal antigenic match between flu strains predicted to be circulating during flu season and those in the vaccine.
- A group of national flu centers and global WHO collaborating centers continuously monitors flu strains circulating among humans and recommends specific flu strains to be included in the seasonal flu vaccine for a given year. This turns out to be a hit-or-miss process because of a ~6 month lag between recommendation and deployment.
- Hit years are those when circulating strains well match those recommended. On the flip side, some years the circulating strains end up being substantially different from those recommended earlier, i.e., antigen mismatch.
- Better the match between recommended and actual circulating strains, better the vaccine efficacy (5, 6).
- Unfortunately, the most commonly used conventional trivalent inactivated flu vaccines are made using an old and outmoded egg-based method. Hence the 6 month lag between recommendation and deployment.
- No way to know ahead of time whether the coming seasonal flu vaccine will be a hit or a miss creates the dilemma. In turn, uncertainty as to whether the vaccine is even effective among the healthy (7) makes those with relatively low risk reluctant to get vaccinated even as evidence remains weak that vaccinating healthy people protects their more susceptible contacts (8).
- IIV (inactivated influenza vaccine where the entire virus is inactivated) and LAIV (live-attenuated influenza vaccine) reduce mismatch risk, especially for influenza B, but don’t eliminate it. Effectiveness issues also dog LAIV (9).
- Faster and more nimble methods of vaccine production able to switch strains and still be deployed in time would be able to keep pace with changes in circulating strains.Even better would be a universal flu vaccine that wouldn’t need reformulating each year; such a vaccine doesn’t exist yet.
Bibliography
1. https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal
2. Iuliano, A. Danielle, et al. “Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.” The Lancet 391.10127 (2018): 1285-1300. https://www.researchgate.net/profile/Wan-Ting_Huang/publication/321798481_Estimates_of_global_seasonal_influenza-associated_respiratory_mortality_A_modelling_study/links/5a3486060f7e9b10d842b94b/Estimates-of-global-seasonal-influenza-associated-respiratory-mortality-A-modelling-study.pdf
3. Grohskopf, Lisa A., et al. “Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 influenza season.” MMWR Recommendations and Reports 67.3 (2018): 1. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 Influenza Season
4. Zhou, Fan, et al. “Improving influenza vaccines: challenges to effective implementation.” Current opinion in immunology 53 (2018): 88-95.
5. Osterholm, Michael T., et al. “Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis.” The Lancet infectious diseases 12.1 (2012): 36-44. https://www.reliefmedicalgroup.com/images/articles/Flu_meta_10.11.pdf
6. Morimoto, Nobuhisa, and Kenta Takeishi. “Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis.” Vaccine 36.7 (2018): 949-957.
7. Demicheli, Vittorio, et al. “Vaccines for preventing influenza in healthy adults.” Cochrane database of systematic reviews 2 (2018). https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001269.pub6/epdf/full
8. Thomas, Roger E., Tom Jefferson, and Toby J. Lasserson. “Influenza vaccination for healthcare workers who care for people aged 60 or older living in long‐term care institutions.” Cochrane Database of Systematic Reviews 6 (2016). https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005187.pub5/epdf/full
9. Chung, Jessie R., et al. “Live Attenuated and Inactivated Influenza Vaccine Effectiveness.” Pediatrics 143.2 (2019): e20182094. Live Attenuated and Inactivated Influenza Vaccine Effectiveness