Thursday, June 14, 2018

Denmark's Flu 2017-18 Season: Attack of The Killer B's

Credit Statens Serum Institute (SSI)


Until a few years ago, the conventional wisdom regarding influenza B was that it generally produced `less serious' illness than does influenza A - affects mainly children - and produces relatively mild illness in adults.

A 2009 study from Viral Immunology, called Influenza B virus causes milder pathogenesis and weaker inflammatory responses in ferrets than influenza A virus  opens with the following statement:
It is unknown why the influenza B virus causes less severe clinical signs than the influenza A virus in humans. Here we show that influenza B virus induces a lower levels of inflammatory cytokines in the lungs of infected ferrets, and causes less pathological damage to their lung tissues than does influenza A virus.
A growing number of studies, however, challenge these notions, and slowly we are seeing a change in perception of the severity of influenza B infection.

In 2012 Lisa Schnirring of CIDRAP News wrote a story on a JID study (Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection) entitled Study finds influenza B may be more severe than thought.

Two years later another important study was published, this time in the Clinical Infectious Diseases Journal, that once again challenged the old ideas about influenza B.
Comparing Clinical Characteristics Between Hospitalized Adults With Laboratory-Confirmed Influenza A and B Virus Infection
Su Su Sandra S. Chaves Alejandro Perez Tiffany D'Mello Pam D. Kirley Kimberly Yousey-Hindes Monica M. Farley Meghan Harris Ruta Sharangpani Ruth Lynfield ...

Clinical Infectious Diseases, Volume 59, Issue 2, 15 July 2014, Pages 252–255, Published: 18 April 2014

We challenge the notion that influenza B is milder than influenza A by finding similar clinical characteristics between hospitalized adult influenza-cases. Among patients treated with oseltamivir, length of stay and mortality did not differ by type of virus infection.
And just last January we looked at a study in the NEJM (see Acute Myocardial Infarction After Laboratory-Confirmed Influenza Infection), where it was Influenza B (rather than A) that produced the highest coronary risk, at least among their limited sample size (n=364).
A finding that harkens back to the 2012 JID study mentioned above.
Last winter the United States saw the worst flu season in recent memory (see MMWR: Reviewing Our High Severity 2017-2018 Flu Season)- due primarily to severe influenza A/H3N2 season - while other parts of the world (including Asia, and parts of Europe) were hit hard by influenza B.  
We are starting to see some analysis of these severe influenza B epidemics published, and they now appear on par with past severe influenza A epidemics.
Complicating matters, particularly in Europe and Asia, the trivalent vaccine is still widely used, which incorporates only one lineage (Victoria or Yamagata) of the influenza B virus each year - meaning a mismatch can severely curtail vaccine effectiveness. 
Last year, the trivalent flu vaccine contained the Victoria virus while most places saw the Yamagata strain.  For those of us in the United States, the quadrivalent vaccine (2 A's & both B's) is now the norm, which reduces the chances of a mismatch.
The following press release from the Statens Serum Institute (SSI) describes this past winter's flu season in Denmark.
Flu season 2017/18 was very unusual
13. juni 2018

There was a very long season marked by many flu cases in which influenza B dominated.

Statens Serum Institut sends this week overall figure out the flu season 2017/18.
There were many ways of dealing with a very unusual season. It was elongated and characterized by a very high flu activity. This proved by a very high number of people who were confirmed as influenza, a high number of admissions and a significant excess mortality among the adult and elderly population.

The predominant virus was influenza B type Yamagata. However, there were also some cases of influenza A, especially in the latter part of the season.

"It is unusual that it is the influenza B, which is the dominant influenza virus. Influenza B most often as a tail at the end of the season for influenza A and does not typically lead to hospitalizations and deaths among elderly" - Chief Tyra Grove Krause, Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut

Lower power of the vaccine

Season 2017/18 was also marked by the seasonal flu vaccine had a lower power than would have been expected. It had that, among other things, because there was a discrepancy between the influenza B virus in the vaccine and B influenza viruses circulating in the population. Despite it prevented vaccinations Nevertheless, overall, 22% of infections with influenza A in the elderly over 65 and 30% of infections with influenza B.

The vast majority (95%) of the patients who were hospitalized with influenza, belonged to one of the groups at risk for influenza. This means that they either had a chronic illness or were older than 65 years. This shows the importance of the prevention of influenza in these groups through vaccination. Influenza vaccination is offered each year for free to these groups from October to December. Despite this, the majority of in-patients not vaccinated against influenza (63%).

"Although the flu vaccine this season had less power than expected, vaccination is still the best weapon we have against the flu. Even at low power is prevented sickness, hospitalizations and deaths in the population. Influenza also often have a milder course, if one were to get sick, even if you are vaccinated, "says Tyra Grove Krause.

Next season's trivalent influenza vaccine, the contents of the vaccine virus recommended by WHO, are not to contain influenza B / Yamagata. This is because it is not assumed that this virus comes into circulation in the same way again next season because of the massive spread of infection in this season.

The full week 23-24 influenza surveillance report provides more details, and a remarkable chart (below) comparing the number of influenza hospitalizations this past winter compared to recent influenza A dominated years.

A few excerpts from the report include:
  • Among the patient samples National Influenza Center of the WHO on SSI surveyed during the season, 68% were positive for influenza B / Yamagata, 17% of influenza A (H3N2) and 14% for influenza A (H1N1) pdm09.
  • The total estimated excess mortality related to influenza for the entire 2017/18 season was at 1,644 deaths, the highest observed since 2010/11. The excess mortality was most pronounced among adults aged 15-64 years and elderly aged 65 and above.
  • Flu season 2017/18 was a tough season in which many in Denmark was hit by flu and particularly of influenza B. This led to more hospitalizations and more deaths than are registered in previous influenza seasons. In the rest of Europe was reported a similar picture with many hospitalizations and increased mortality in many countries. Influenza B is - unlike influenza A (H3N2) - not normally associated with serious illness leading to hospitalization and mortality among the elderly, with influenza B virus typically affects school children and young adults. In the last part of the season, there were also many cases of influenza A.
Since influenza B viruses have only been found in humans and seals, they tend to evolve slowly, and are not viewed as serious pandemic threats. Nevertheless, they can spark large epidemics that produce significant morbidity and mortality. 

While old ideas about the severity of influenza B still persist, the evidence increasingly shows that influenza B viruses deserve the same level of respect as their A-list cousins.