After two and a half years of the COVID pandemic, influenza has become an after thought for many Americans. But influenza can still kill vulnerable people and even in otherwise healthy individuals, it can cause unpleasant illness, require time off of work, and cause school absences. One of the best predictors of the next U.S. influenza season is the current Australia winter influenza season that occurs during the U.S. summer.
When will the U.S. influenza season start?
The Australian Government Department of Health and Aged Care publishes an influenza epidemiology report every 2 weeks. The most recent report is from July 23, 2023.
The current influenza data is depicted in the red line in the graph above. Last year’s influenza data is in the taller orange line and the 5-year average is in the black line. In this graph, week 1 corresponds to the week of January 1, 2023. Cases of influenza began to be reported early in Australia this year and most closely matched the 2019 influenza season. Cases started to increase in number in week 8 (late February), had an initial plateau from weeks 13 – 17 (late March to late April), then rose to a peak in week 26 (last week of June).
The Centers for Disease Control publishes a weekly influenza report on the FluView website. The United States influenza season is about 6 months later than the Australian influenza season, owing to the seasonal difference between the northern and southern hemispheres. The graph below shows U.S. influenza data for the last several years with the 2022-2023 data in red. Similar to last year in Australia, influenza was seen earlier and peaked earlier in the U.S. last year.
Based on the current year data from Australia, cases of influenza would be expected to begin to rise in late August or early September in the U.S. and then peak in approximately late December or early January. This would be a much earlier influenza season than is typical in the U.S. and would resemble last year’s influenza season.
What influenza subtypes are likely?
Influenza A and influenza B are the most common varieties of influenza in humans. Each of these can be further divided into common subtypes. The most common subtypes of influenza A are H1N1 and H3N2. The most common subtypes of influenza B are the Victoria lineage and the Yamagata lineage. Each of these subtypes can be further divided into clades and each clade can be divided into subclades. Because influenza can and does mutate regularly, the dominant subclades causing human infection change from year to year. Additionally, the relative percentage of influenza cases caused by influenza A & B varies each year and the relative percentage of each influenza subtype also varies each year. The graph below shows the strains of influenza in the U.S. last year. Most cases were influenza A and most of the influenza A was H3N2 (71%, red bars); H1N1 was much less frequent (29%, orange bars). Influenza B cases were relatively uncommon and mostly seen late in the season (green bars). Notably, all of the influenza B cases were caused by the Victoria lineage (100%) and none were caused by the Yamagata lineage.
This year in Australia, influenza A (63%) was more common than influenza B (35%). The vast majority of influenza A was caused by the H3N2 subtype (82%; dark green bars) as opposed to the H1N1 subtype (18%; purple bars). For influenza B, 100% were caused by the Victoria lineage and none were caused by the Yamagata lineage.
Influenza A H3N2 clades and subclades. The two clades of H3N2 which are currently in circulation are clade 1 (limited to China) and clade 2 (the dominant clade in the U.S.). In the figure below, clade 1 is shown in purple and clade 2 is shown in green. Each clade is divided into subclades based on mutations in the influenza hemagglutinin gene. The hemagglutinin protein is located on the surface of influenza and helps the virus bind to human cells. Hemagglutinin is also the target for influenza vaccines.
Influenza A H1N1 clades and subclades. The two clades of H1N1 which are currently in circulation are 5a.1 and 5a.2. The H1N1 5a.1 influenza clade mostly made up of the subclade A/Hawaii/70/2019. This subclade is decreasing in frequency and is rarely seen in the United States.
Most H1N1 influenza in the United States is from clade 5a.2. H1N1 5a.2 subclades A/Victoria/4897/2022 and A/Wisconsin/67/2022 are dominant in the U.S. whereas H1N1 5a.2 subclade A/Sydney/5/2021is dominant in Australia.
Influenza B subtypes. Of the two influenza B lineages, only the Victoria lineage is currently circulating on Earth and the Yamagata lineage has not been detected in the U.S. or Australia in the past year. As with influenza A, mutations in the hemagglutinin gene creates clade diversity in influenza B. Currently, the 1A.3a.2 strain accounts for 99% of influenza B worldwide.
The 2023 – 2024 influenza vaccine
Every year, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets in the spring to project which influenza clades and subclades are likely to circulate during the next influenza season and then selects representative virus strains to use to manufacture the next seasonal influenza vaccines. Because the committee meets in early March, data from the Australia influenza season are not yet available when the U.S. selects influenza strains for vaccines. This year, the strains selected for the quadrivalent vaccines are similar to last year’s vaccine with the exception of the influenza A H1N1 strains; the Victoria/4897/2022 strain replaces last year’s Victoria/2570/2019 and the Wisconsin/67/2022 strain replaces last year’s Wisconsin/588/2019 strain:
The 2023-2024 trivalent influenza vaccines will be similar to the 2023 – 2024 quadrivalent cell-based and egg-based vaccines except that they will not include the Phuket/3073/2013 influenza B strain against the Yamagata lineage. Because there have been no Yamagata lineage influenza B infections in the U.S. last year or in Australia this year, it is likely that the trivalent vaccine will be equally effective as the quadrivalent vaccine this year since coverage for the influenza B Yamagata lineage is unnecessary.
When to get vaccinated. Because the Australia influenza season started early, it is likely that the U.S. influenza season will also start early. Physicians should start vaccinating patients in mid-August and aim to get all patients vaccinated by late October.
Quadrivalent versus trivalent. Because there has not been any recent influenza B Yamagata lineage virus circulating recently, the trivalent vaccine should be just as effective as the quadrivalent vaccine. Therefore, patients can get either vaccine and they can be used interchangeably.
When will hospitalizations peak? This year in Australia, hospitalizations peaked between weeks 19 and 28. This would correspond with early November through early January in the United States. This is normally a busy time for elective inpatient surgeries (such as knee and hip replacements) so hospitals should be prepared accordingly.
The holiday travel effect. Because influenza may be peaking during the U.S. Thanksgiving and Christmas holidays, there is the potential that travel for these holidays could fuel a surge in influenza cases.
Universal flu vaccines in the future?
Because the influenza hemagglutinin gene mutates so readily, the antigen targets on the hemagglutinin surface protein change. This requires new vaccines to be made to generate antibodies against these altered hemagglutinin antigens. The mRNA vaccines that were so successful against COVID offer the hope that mRNA technology could be applied to other anti-viral vaccines, including influenza. A study published November 2022 in the journal Science found that an mRNA vaccine that covered 20 strains of influenza was effective in mice and ferrets. However, recent human trials with mRNA influenza vaccines by Sanofi and Moderna were unsuccessful, mainly due to inadequate immune protection against influenza B strains. Another influenza mRNA vaccine created by Pfizer is currently undergoing phase III clinical trials.
In all likelihood, it will be several years before a universal influenza vaccine is commercially available. Until then, we will have to continue our current process of tracking the dominant circulating influenza clades and subclades in order to produce annual influenza vaccines. Based in Australia’s current influenza season, I recommend getting this year’s flu shots as soon as they are available.
August 2, 2023