Saturday, February 10, 2018

Double-Whammied By Influenza

#13,137


With H3N2 still raging - and influenza B on the ascendant -  during yesterday's CDC Flu briefing a question was asked about dual, or co-infection, with both influenza A and Influenza B viruses (see transcript excerpt below).

BRENDA GOODMAN: Hi Dr. Schuchat. I just have a question about the B strain starting to peak and whether you have seen such a close overlap before between the A and the B strains. We have heard from some of our readers’ questions about could I get the flu twice in once season if I get difference strains and anecdotally we have heard reports that some people have been diagnosed with A and B strain at the same time. Are you hearing about that? Is that contributing to some of the severity?

ANNE SCHUCHAT: The B strains often, or it’s not uncommon for B strains to increase later in the season. The idea that a person can get infected with A and during the same season get infected with B definitely happens. It’s one of the reasons we say even if you have already had the flu this season it makes sense to get vaccinated because it could protect you against the other strain. In a season that’s so intense like this we may hear of more of those cases such as your readers are reporting where a person got on and then the other. It is possible to get the two at the same time. I have a virologist sitting across the table shaking her head vigorously so we know it is not a lab error. That can happen. Next question operator.

Co-infection with two types of Influenza A viruses (in birds, humans, swine, and other hosts) is something we discuss quite often, as it is the setup required for influenza reassortment (aka `antigenic shift') to occur.

 

Most products of antigenic shift are evolutionary failures, but occasionally a new, biologically `fit'  hybrid virus will be spawned.  Some may even have pandemic potential (see NIAID Video: How Influenza Pandemics Occur).
While rare, as any virologist will tell you, Shift happens.
Which is why we pay particular attention whenever outbreaks of seasonal influenza and avian (or swine) influenza's coincide.  A few past blogs on Influenza A co-infection include:

There are other dual infection possibilities that - while they do not carry reassortment concerns  -  can still impact a patient's degree of illness and/or recovery, including
  • Influenza A and bacterial co-infection
  • Influenza A or B with a non-influenza virus (i.e. Adenovirus, Rhinovirus, RSV, etc.)
  • a combination of Influenza A and B (or C)
Of these, influenza (or other respiratory virus) with secondary bacterial infection is most worrisome. A few examples:
  • In 2008, we saw a study in The Journal of Infectious Diseases by Morens, Taubenberger, and Fauci that looks at the role of bacterial pneumonia in the high death toll of 1918 (see Viral-Bacterial Copathogenesis).
  • In 2011, during the post-mortem on the 2009 H1N1 pandemic, we saw a number of studies linking extensive lung damage to dual H1N1 and bacterial infection (see mBio: Lethal Synergism of H1N1 Pandemic Influenza & Bacterial Pneumonia).
  • And in 2012, in TLR7: Bacteria’s Little Helper, we looked at an unwanted side effect of the innate immune system when fending off a viral infection; evidence that Toll-like Receptor 7 (TLR7) can actually promote secondary bacterial growth.
Even during this heavy flu season, only about half of the samples sent to the CDC have tested positive for any type of influenza, meaning that there is a lot of non-influenza respiratory illness out there as well.
Not surprisingly, a lot of people end up co-infected with a variety of influenza and non-influenza viruses.  Luckily, influenza A and B are not known to reassort (cite) - nor do influenza and non-influenza viruses - taking at least one bad outcome off the table. 
While there isn't a lot of research into these dual viral infections, they don't appear to produce significantly worse outcomes than influenza by itself. 
 Of course, YMMV (Your Misery May Vary).
A couple of recent studies on point: From a 2016 article in European Journal of Clinical Microbiology:
Influenza A and B co-infection: a case–control study and review of the literature
March 2016 DOI: 10.1007/s10096-016-2620-1
Felipe Pérez García  V. Vásquez Viviana de Egea E. Bouza

Abstract


Influenza virus infection remains a major cause of morbidity and mortality during winter seasons. Bacterial and virus co-infection is a commonly described situation in these patients. However, data on co-infection by influenza A and B viruses are lacking. 


In this study, we present the cases of co-infection by influenza A and B viruses during the winter season of 2014–2015 in our institution. We analyzed 2759 samples from 2111 patients and found that 625 samples corresponding to 609 patients were positive for influenza A or B virus.
A total of 371 patients had influenza A, 228 had influenza B, and 10 (1.6 %) had influenza A and B virus detection in the same sample. The median age of co-infected patients was 78.6 years, and only one of the co-infected patients died because of the infection.

Comparison with a control group of mono-infected patients revealed that co-infection was significantly associated with nosocomial acquisition [odds ratio (OR) = 4.5, 95 % confidence interval (CI) = 1.05–19.25, p = 0.042]. 

However, co-infection was not associated with worse outcome, previous underlying condition, or vaccination status. Multivariate analysis revealed that co-infection was not an independent risk factor for death and that no single risk factor could predict co-infection.

Another study, this time from 2017, from the Journal of Clinical Virology.

Influenza A(H1N1)pdm 2009 and influenza B virus co-infection in hospitalized and non-hospitalized patients during the 2015-2016 epidemic season in Israel
January 2017 DOI: 10.1016/j.jcv.2017.01.002

Rakefet Pando, Yaron Drori , Nehemya Friedman, Michal Mandelboim





Highlights

  • Characterization of unusually high number of patients co-infected with influenza A (H1N1)pdm 2009 and influenza B viruses during the 2015–2016 influenza season in Israel.
  • During the past 15 years we have not witnessed such prevalence of double infections and the reports on such events are scares.
  • The unusually high number of patients dually infected with these two viruses encourages continuously monitoring this observation and raising the importance of evaluating the influenza virus strains present in the vaccine cocktail.
  • In this report the clinical presentation of the immunocompetent patients dually infected with influenza A (H1N1)pdm 2009 and influenza B viruses did not differ from patient infected with either of the two viruses.
  • Unlike other recent reports the majority of the influenza double infection occurred in the population and they will not nosocomial/health care associated infections.

Abstract

Background

Influenza A and B viruses co-infections are rare events and mainly occurred in immunocompromised patients.
Objectives

In this study we report an unusually high occurrence of influenza A (H1N1)pdm 2009 and influenza B virus co-infections during the epidemic year 2015–2016.

Study design


Nasopharyngeal swabs were collected from 1919 patients visiting 26 outpatient clinics distributed throughout Israel and presenting with influenza-like illness. In addition, hospitalized patient tested for influenza viruses were also included in the study. Patients samples collected between October 2015 and April 2016 were tested for the presence of influenza viruses by real-time PCR.

Results

Of the 1919 patient samples tested, 11 (0.6%) were co-infected with both influenza A(H1N1)pdm 2009 and influenza B/Victoria viruses. Similar observation was noted in four hospitalized patients during the same period. Patients at ages 1–72 years, and their clinical symptoms were similar to that of patients infected with either influenza A or B viruses. Of all patients, only one hospitalized patient was immunocompromised.

In conclusion
Co-infection of influenza A(H1N1)pdm 2009 and influenza B viruses is an increasingly recognized phenomenon. This co-infection can occur not only in immunocompromised individuals, but also in immunocompetent patients. Although co-infection appears to be a rare event, it may still play a role in the epidemiology, pathogenicity and evolution of influenza viruses.
We are obviously still learning about the impact of viral co-infections, but as the cost of doing molecular respiratory diagnostic testing decreases - and their use becomes more common - we should begin to fill in those knowledge gaps.

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