Saturday, June 15, 2013

Lancet: Coinfection With H7N9 & H3N2



# 7400


While it hardly seems fair, it is possible for a human to be infected by more than one respiratory virus at the same time. This can not only confuse and complicate a patient’s diagnosis and treatment, it can – in rare instances – result in the creation of a new, hybrid virus.


Earlier this year, a positive influenza A test in a UK patient recently returned from the Arabian peninsula resulted in a week’s delay in diagnosing his more serious underlying MERS-CoV infection (see Eurosurveillance: H2H Transmission of NCoV In UK Family Cluster).


Interestingly, two family members he passed the virus on to both were found to be coninfected with Type 2 parainfluenza virus. A reminder that a positive flu test doesn’t always rule out the possibility of a more serious underlying illness.


Of greater concern, however, is when a host (be it human, swine, avian, or other mammal) is infected with two influenza strains at the same time.


Yesterday, The Lancet published a report on a dual influenza infection last March in a 15 year-old boy living in China; the emerging H7N9 virus and seasonal H3N2.



Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China

Yefei Zhu PhD a, Xian Qi PhD a, Lunbiao Cui a, Minghao Zhou PhD a, Prof Hua Wang MD a

The Lancet, Volume 381, Issue 9883, Page 2134, 15 June 2013  doi:10.1016/S0140-6736(13)61135-6


Alas, the bulk of this article is behind a pay wall, but CIDRAP NEWS  summarized the report last night here, where we learn that – while two influenza viruses were isolated from the same patient - no reassorted virus was detected.


Influenza viruses evolve via two well established routes; Antigenic drift & Antigenic Shift (reassortment).


Antigenic drift causes small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and often come about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).


Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus.  This is known as reassortment. While far less common than drift, shift can produce abrupt, dramatic, and sometimes pandemic inducing changes to the virus (see NIAID Video: How Influenza Pandemics Occur).


While successful reassortment is a rare event (else we’d be hip deep in reassortant viruses all the time), as any virologist will tell you . . . Shift happens.


This is basically how the 2009 H1N1 pandemic virus evolved, although it took multiple gene swaps over a decade or longer before it finally emerged from swine into the human population.


And the recently emerged H7N9 virus in China came about through multiple reassortments in birds.


So reassortments do happen, but only rarely do they result in a biologically fit virus capable of causing a pandemic.


Most hybrid viruses are evolutionary dead-ends, are unable to compete, and die out within the host.


While swine and birds are considered to be the most likely `mixing vessels’ for flu (because they are often crowded together and are susceptible to a wide variety of strains), humans can reassort flu viruses as well.




In 2011 we saw an influenza co-infection in Canada that led to the creation of a unique hybrid reassorted virus (see Webinar: pH1N1 – H3N2 A Novel Influenza Reassortment).


In this case, the patient was a 16-month old boy from the Greater Toronto Area who was admitted briefly to a local hospital for respiratory and gastrointestinal symptoms in January of 2011.


The child was sent home, and recovered without incident, and no other family members or contacts reported flu-like symptoms.


It wasn’t until later, when viral cultures showed a hybrid (reassorted) H1N1-H3N2 virus, did scientists realize that something unusual had occurred. Details of this event were presented in an online webinar on June 16th of 2011. From the abstract:


pH1N1 – H3N2: A Novel Influenza Virus Reassortment


Dr. Jonathan Gubbay- Medical Microbiologist, OAHPP


Dr. Jonathan Gubbay, medical microbiologist at the Toronto Public Health Laboratory, will present on a new influenza virus that has been discovered by the Ontario Agency for Health Protection and Promotion (OAHPP). It is the first Canadian confirmed finding of a patient with a coinfection of seasonal H3N2 and pH1N1 followed by reassortment.

(Continue . . .)



While rarely detected, influenza A coinfections are probably more common than we realize.  Luckily, most do not result in the production of a hybrid strain.


In 2010, in EID Journal: Co-Infection By Influenza Strains, I wrote about a study in New Zealand during the opening months of the 2009 pandemic that discovered at least 11 co-infections (out of 1,044 samples tested) with the older seasonal H1N1 virus and the newly emergent pandemic H1N1 virus.


Pandemic (H1N1) 2009 and Seasonal Influenza A (H1N1) Co-infection, New Zealand, 2009

Matthew Peacey , Richard J. Hall, Stephanie Sonnberg, Mariette Ducatez, Shevaun Paine, Mackenzie Nicol, Jacqui C. Ralston, Don Bandaranayake, Virginia Hope, Richard J. Webby, and Sue Huang

The authors state that the rate of co-infection could actually be higher, since samples were not checked for any other flu strains such as H3N2 and influenza B.


In 2011, the following study which appeared in the American Journal of Tropical Medicine & Hygiene


Dual Infection of Novel Influenza Viruses A/H1N1 and A/H3N2 in a Cluster of Cambodian Patients

Christopher A. Myers, Matthew R. Kasper, Chadwick Y. Yasuda, Chin Savuth, David J. Spiro, Rebecca Halpin, Dennis J. Faix, Robert Coon, Shannon D. Putnam, Thomas F. Wierzba and Patrick J. Blair


The details are behind a pay wall, but as the authors point out in their abstract:


This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses to coinfect and possibly, reassort where they cocirculate.


And going back even further, Maryn McKenna wrote – in an article for CIDRAP News – of an Indonesian teen who was found to have been co-infected with an avian (H5N1) and a human (H3N2) influenza strain.


Avian, human flu coinfection reported in Indonesian teen

Maryn McKenna * Contributing Writer

Mar 17, 2008 – ATLANTA (CIDRAP News) – An Indonesian teenager has been brought forward as a case of simultaneous infection with seasonal and avian strains of influenza—a possibility that health planners have long warned could give rise to a pandemic flu strain.

(Continue . . . )


Again, no hybrid flu virus was produced. 


But the more influenza viruses that are co-circulating (in humans, birds, or pigs), the more possible genetic combinations that can be produced. 


And right now, in addition to our seasonal H1N1 and H3N2 strains, we’ve also got H5N1, H7N9, H9N2 (and other minor avian strains), along with swine variant (H1N1v, H1N2v, H3N2v) viruses all out there, all looking for an evolutionary advantage.


Which means that with billions of susceptible hosts, and a growing number of influenza A genetic contributors, the greater the odds are that one of these viral assignations will produce another viable hybrid strain.


Which is why we watch flu outbreaks around the world with such interest, looking for signs that anything unusual has occurred.