A strain of seasonal influenza has completely vanished globally since March 2020, and due to its disappearance, health officials in Canada are changing up the annual flu vaccine.

The B/Yamagata influenza strain, once a dominant force among influenza B viruses, may have vanished entirely due to the stringent measures imposed during the COVID-19 pandemic, according to the National Advisory Committee on Immunization (NACI). No cases have been confirmed across the globe since March 2020.

Due to the strain’s disappearance, NACI announced on July 26 that expert groups have endorsed removing the B/Yamagata component from influenza vaccine formulations. As a result, Canada’s flu vaccine will shift from a quadrivalent to a trivalent formula.

“As of March 2020, following the onset of the COVID-19 pandemic and implementation of measures to reduce the transmission of SARS-CoV-2, there have been no confirmed detections of naturally circulating B/Yamagata lineage viruses worldwide, including in Canada,” NACI said in the statement.

“Based on current epidemiological data, there is global expert consensus that B/Yamagata virus strains should be removed from influenza vaccine formulations and that manufacturing should transition to trivalent vaccines exclusively,” it added.

Before the strains disappeared, there were four strains of seasonal influenza circulating: two from influenza A (H1N1 and H3N2) and two from influenza B (B/Victoria and B/Yamagata).

Since the 2014 to 2015 flu season, Canada has used quadrivalent influenza vaccines containing strains from both influenza B lineages (B/Victoria and B/Yamagata) to offer protection against circulating influenza B viruses.

Although influenza A is usually the dominant strain, both influenza A and B contribute to seasonal epidemics. Despite its lower overall prevalence, influenza B can still pose a significant burden in Canada, accounting for up to 44 per cent of reported laboratory detections in some seasons, according to NACI.

“In November, December and into January, we mostly see influenza A. And then in the latter part of the season, January, February and tailing off through March, we’ll see a little bit more influenza B,” explained infectious diseases specialist Dr. Isaac Bogoch.

“If you look at the absolute number of cases, we usually have way more influenza A compared to influenza B, but B starts to show up a little bit later on in the season.”

He said that while the diagnosis, prevention, and treatment of influenza A and B are the same, what differs is their epidemiology. This difference in epidemiology might explain why B/Yamagata disappeared while other strains persisted.

The B/Yamagata strain was first discovered in Japan in the late 1980s. It began spreading globally and became a predominant influenza strain in North America by the early 2000s.

By the 2014 to 2015 flu season, Canada had added the B/Yamagata strain to its seasonal flu vaccine, making it a quadrivalent formula to protect against more influenza types.

In Canada and globally, between 2012 and 2017, B/Yamagata viruses caused a larger proportion of influenza B infections than B/Victoria, NACI said. However, two years before the COVID-19 pandemic, the B/Yamagata lineage started becoming dominant.

Then, in March 2020, it seemingly vanished.

“During the darkest days of COVID, we stopped detecting one of the two influenza B strains and that was B/Yamagata,” Bogoch said. “Was it hiding out somewhere or was it just circulating in lower levels? Was it going to somehow emerge later on? Those are questions that were asked at that time. But, it didn’t seem to come back.”

Although it has disappeared, Bogoch emphasized that this does not mean the strain is eradicated, as eliminating any virus is extremely challenging.

But there are theories about what happened to it.

The first theory relates to the public health measures implemented at the start of the pandemic.

A 2022 study published in Nature, argued that since April 2020, many countries have seen historically low seasonal influenza virus circulation, attributable to quarantines, social distancing, school and workplace closures, mask-wearing, surface disinfection and enhanced hand hygiene.

Bogoch suggested that another factor contributing to the B/Yamagata strain’s disappearance could be the “massive drop in human mobility” during the pandemic.

“If you look at international travel, passenger volumes and human mobility patterns during that time, they were a tiny fraction of what they are normally” he explained.

“And when you look at how seasonal influenza is transmitted, it goes from the southern hemisphere and then it works up its way into the northern hemisphere during our winter months, and then back to the southern hemisphere during their winter months and ping-pongs back and forth.”

He believes that the near standstill in travel during the pandemic, along with tighter border restrictions, may have contributed to the decline of the strain.

Another reason could be “viral interference,” he said, meaning the COVID-19 strain may have helped suppress a weaker strain of influenza.

However, he stressed that these are all theories, and a combination of these factors may have contributed to the disappearance of the B/Yamagata strain.

These are just the early stages of transitioning from a quadrivalent to a trivalent seasonal influenza vaccine, so the new formula will not be available for the 2024 to 2025 flu season, according to NACI.

“For the 2024-2025 influenza season in Canada, vaccine availability is anticipated to remain unchanged. Quadrivalent formulations will continue to be supplied for public programs. No trivalent formulations will be available for standard dose or high dose inactivated influenza vaccines,” it stated.

NACI anticipates a gradual transition to trivalent influenza vaccines, acknowledging significant logistical challenges and potential regulatory complexities. More details about trivalent influenza vaccines will be included in the 2025 to 2026 Influenza Seasonal Statement.

Both quadrivalent and trivalent influenza vaccine formulations are clinically safe and effective, according to NACI.

While the updated vaccine may not be available in Canada this upcoming flu season, the U.S. has already adopted the trivalent formulation for the 2024 to 2025 season.

The Centers for Disease Control and Prevention (CDC) has announced that flu vaccines will be trivalent in the United States for the 2024-2025 season.

“Because influenza B/Yamagata lineage viruses have not been detected after March 2020, the World Health Organization (WHO) and FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the influenza B/Yamagata lineage vaccine virus component be excluded from flu vaccines as soon as possible,” the CDC website states.

Since there’s no evidence that B/Yamagata is completely eradicated, NACI said it will continue to monitor each flu season.

“Continued epidemiological and virological monitoring of influenza virus, investigation of any reports of B/Yamagata detection, and continued assessment of programmatic factors remains important, as does clear and transparent communication of updated recommendations,” it said.