Wednesday, August 21, 2019

ERJ: When “B” becomes “A” : The Emerging Threat of Influenza B Virus

Credit NIAID


Only a decade ago, Influenza B was still viewed as a `less serious '  health threat than influenza A; mainly affecting children, often coming at the tail end of the flu season, and usually producing relatively mild illness in adults.

An example of that view can be found in this 2009 study from Viral Immunology, called Influenza B virus causes milder pathogenesis and weaker inflammatory responses in ferrets than influenza A virus, which 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.
Since then, however, we've seen several studies that challenge that notion; showing the severity of Influenza B infections can often be comparable to Influenza A.

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

Lisa Schnirring |

Feb 1, 2012 (CIDRAP News) – An autopsy study involving influenza B infections revealed how histologically similar the disease is to fatal influenza A and how quickly it can kill, challenging the notion that it is milder than influenza A.

The investigators, from the US Centers for Disease Control and Prevention (CDC), also found a high level of cardiac injury with fatal influenza B infections, especially in younger patients. 
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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 (see Comparing Clinical Characteristics Between Hospitalized Adults With Laboratory-Confirmed Influenza A and B Virus Infection).

The CDC, which partnered in this study, published the following summary:
New CDC Study Compares Severity of Illness Caused by Flu A and B Viruses

Influenza B virus infections can be just as severe as influenza A virus infections

As late-season influenza B viruses currently predominate in the United States, a new study published by CDC and partners highlights the comparative severity of illness associated with influenza A versus influenza B virus infections. The results of the study showed that among hospitalized adults, flu B viruses caused equally severe disease outcomes and clinical characteristics as flu A viruses.
This contradicts a common misconception that flu B viruses are associated with milder disease than flu A viruses.
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In January of 2018 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.
And last summer, in Denmark's Flu 2017-18 Season: Attack of The Killer B's, we saw a press release from the Statens Serum Institute (SSI) describes the previous winter's influenza B dominated flu season in Denmark.

Flu season 2017/18 was very unusual
13. juni 2018
Credit Statens Serum Institute (SSI)

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
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Denmark wasn't alone in seeing a high prevalence of Influenza B that year, as did other European nations, China and much of Asia (see China: NHFPC Statement On Current Flu Epidemic).

Today we've two items; an article and a study, published this week in the European Respiratory Journal that further challenge the notion that influenza B is somehow weaker than influenza B.

When “B” becomes “A”: the emerging threat of influenza B virus
Lokesh Sharma 1 , Andre Rebaza 2 and Charles S. Dela Cruz 1


Influenza B virus can be as virulent as influenza A

Cite this article as: Sharma L, Rebaza A, Dela Cruz CS. When “B” becomes “A”: the emerging threat of influenza B virus. Eur Respir J 2019; 54: 1901325 [].

This single-page version can be shared freely online.

Influenza virus (flu) caused the worst disease mediated devastation in recorded human history in 1918, when global death was estimated to be between 50 and 100 million people [1]. Flu continues to kill more people every year with no apparent decrease in its pathogenicity despite advancement in our understanding of the disease and with the availability of vaccines and antiviral agents. Last year, the death toll of influenza was estimated to be 80 000 in the USA alone, making it the most lethal infectious disease [2]. 
One apparent change that occurred in the influenza virus is the emergence of influenza B strain as a significant contributor to the annual disease over the years. The origin of influenza B is unclear but was first isolated around 1940 and later separated into two clear lineages by 1983, the Yamagata-like and Victoria-like strains [3]. The scientific and healthcare community has been underplaying this important event and influenza B has been labelled as the “B” team compared to influenza A. Influenza B is believed to be a milder virus compared to some strains of influenza A, such as H3N2, but more potent than the influenza A strains like H1N1 [4].
In fact, multiple studies have suggested increased potency of influenza B virus in causing severe disease and mortality. Influenza B is the most prominent circulating strain of influenza every four to five years. Furthermore, influenza B infections carried higher risks of hospitalisations compared to influenza A infections in HIV patients [5].
Similarly, influenza B has been described to have significantly higher mortality rates compared to influenza A strains. For example, during the flu season in 2010–2011, influenza B was responsible for 38% of deaths in the paediatric population. National Respiratory and Enteric Virus Surveillance System collaborating laboratories indicated that only 26% of circulating strains of flu were influenza B viruses during this period [6].
Similarly, a Canadian study from 2004 to 2013 found significantly higher mortality rates due to influenza B compared to influenza A in children younger than 16 years of age [7]. These data strongly refute the claims that influenza B is the milder version of the flu. In this issue of the European Respiratory Journal, the study by B UI et al. [8] sheds light on influenza B interactions within the human respiratory tract and lung to demonstrate its pathogenicity and its potential to spread and cause severe lung infections.
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You can read the entire article at this link.

For a much deeper dive into the science, in the same August 15th edition of the European Respiratory Journal you'll find a related study entitled:
Tropism of influenza B viruses in human respiratory tract explants and airway organoids
Christine H.T. Bui, Renee W.Y. Chan, Mandy M.T. Ng, M-C. Cheung, Ka-chun Ng, Megan P.K. Chan, Louisa L.Y. Chan, Joanne H.M. Fong, J.M. Nicholls, J.S. Malik Peiris, Michael C.W. Chan
European Respiratory Journal 2019 54: 1900008; DOI: 10.1183/13993003.00008-2019
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Since influenza B viruses have only been found in humans and seals, they tend to evolve slowly, and are not viewed as posing the same kind of pandemic threat as influenza A. 
Nevertheless, they can spark large epidemics that produce significant morbidity and mortality in both adults and children.
While far from perfect - given the moderate effectiveness of the quadrivalent seasonal flu against both influenza B lineages - it makes sense to grab whatever protection you can get.  Which is why I'll be rolling up my sleeve again this year when the vaccine becomes available.