Thursday, February 28, 2019

Eurosurveillance: Novel influenza A(H1N2) Seasonal Reassortant - Sweden, January 2019


Three weeks ago, and for the second time in a year, we saw a reassortant H1N2 virus report reported out of Europe (CDC: Sweden Reports An Influenza A(H1N2) Reassortant Infection) that contained genes from both seasonal H1N1 and H3N2.

While only rarely reported over the past 15 years, in 1988-1989 in China (see Human influenza A (H1N2) viruses isolated from China), and again between 2000 and 2003 in the Northern Hemisphere, we saw the brief appearance of a human H1N2 virus - a reassortment between the old (pre-2009) seasonal H1N1 and H3N2.
A minor player in most regions, H1N2 was the predominant Influenza A(H1) virus reported during the UK's 2001–02 influenza season (cite).
These two recent European cases, however, are the only ones recorded with the 2009 H1N1 virus.  Earlier this month the CDC issued a risk assessment:
Risk Assessment:

This A(H1N2) reassortant virus is thought to pose a health risk similar to other seasonal influenza viruses. The virus has not been detected beyond this one person and current seasonal influenza vaccines would likely offer protection against this virus. Additionally, this virus does not have markers associated with resistance to the neuraminidase inhibitor class of antiviral drugs and, thus, should be susceptible to treatment with the currently recommended drugs oseltamivir, zanamivir and peramivir.

It should be noted that these are human-origin H1N2 viruses, not swine-origin variant H1N2 viruses that have circulated in pigs for decades and that we've seen occasionally jump to humans over the past decade.

Today the journal Eurosurveillance has published a Rapid Communications describing both the virus, and the patient who has recovered after a severe illness. 

Rapid communication Open Access
Novel influenza A(H1N2) seasonal reassortant identified in a patient sample, Sweden, January 2019 

Åsa Wiman1,2, Theresa Enkirch1,2, AnnaSara Carnahan3, Blenda Böttiger4, Tove Samuelsson Hagey1, Per Hagstam5, Rosmarie Fält5, Mia Brytting1

As part of Swedish national influenza surveillance, a seasonal reassortant influenza A(H1N2) virus with a novel genetic constellation was identified. This is the second detected seasonal A(H1N2) reassortant in a human in Europe within 1 year. Here, we describe the detection of the virus, its genetic characteristics and follow-up investigations.


Case description
In the last week of December (week 52 2018), a 68-year-old female patient with a history of chronic obstructive pulmonary disease consulted her primary care physician following 5 days of fever up to 40°C. On clinical suspicion of pneumonia, she was referred to a local hospital in Skåne County where she was hospitalised.
A nasopharyngeal swab taken on the day of admission was positive for influenza A virus and the patient was treated with oseltamivir (75 mg, two times daily) for 5 days. She recovered quickly and was discharged 5 days after admission. The patient had not been vaccinated against influenza during the 2018/19 season.

Diagnosis of influenza A virus infection at the local hospital was performed by real-time PCR using Simplexa Flu A/B and RSV direct kit, (DiaSorin Molecular LLC, California, United States (US)). The sample was forwarded to the Clinical Microbiology Laboratory in Lund for subtyping (as are all influenza A virus-positive samples in Skåne County) with in-house real-time PCRs targeting H3 and N1pdm09 [1].
As this sample was negative in these assays, it was forwarded to the PHAS where influenza A(H1)pdm09 virus was detected by in-house real-time PCR. The presence of A(H1)pdm09 virus was also subsequently confirmed by Filmarray Respiratory Panel BioFire (Diagnostics LLC, Utah, US) at the Clinical Microbiology Laboratory in Lund.
Genetic characterisation
The virus, initially subtyped as A(H1)pdm09 by real-time PCR, was revealed as A(H1N2) on 22 January 2019, after WGS on an Ion Torrent platform (Thermo Fisher Scientific, Waltham, Massachusetts, US). Seven segments (HA, matrix (M) non-structural (NS), polymerase components PB1, PB2 and PA and nucleoprotein (NP)) of this virus are derived from seasonal A(H1N1)pdm09 virus, while the neuraminidase (NA) segment is derived from seasonal A(H3N2) virus. The gene sequence of this strain, A/Ystad/1/2018, is available from the Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu database (EPI_ISL_336041) [2,3].


While co-infections with seasonal A(H1N1) and A(H3N2) influenza strains are not unusual [4-7], only a few studies have described reassortant viruses as a consequence of such co-infections [8-10]. This suggests that reassortment is a rare occurrence and that reassorted A(H1N2)-viruses do not easily spread between humans [11], with the exception of A(H1N2) reassortant viruses circulating in 1988/89 in China [12,13] and worldwide between 2001 and 2003 [14].
Interestingly, a human natural infection with an A(H1N2) reassortant virus harbouring gene segments from seasonal influenza A(H1N1)pdm09 virus (HA and NS) and A(H3N2) virus (PB2, PB1, PA, NP, NA and M) was described as recently as March 2018, by Meijer et al. [15]. In accordance with the hypothesis of limited spread, no further cases were observed, as is the case also (as at 24 February 2019) for the Swedish A(H1N2) reassortant.

Real-time PCR assays targeting at least two genes can detect or give an indication of a reassortment, depending on the combination of targets used and segments reassorted, respectively. Targeting both the HA and NA genes is of interest because a change of the HA and NA constellation might have a possible impact on immune protection. However, WGS provides a powerful tool to both detect and characterise reassortants of all eight gene segments. Here, WGS showed that A/Ystad/1/2018 harbours seven gene segments from seasonal A(H1N1)pdm09 virus and one segment (NA) from A(H3N2) virus.

To our knowledge, this is the first human seasonal A(H1N2) reassortant with this gene segment constellation detected in humans. Since the HA is closely related genetically to that of the A(H1N1)pdm09 viruses circulating in Sweden so far during the 2018/19 season, we expect no difference in vaccine effectiveness (VE) against this reassortant virus compared with seasonal A(H1N1)pdm09 viruses. This season, substantial interim VE has been shown against circulating A(H1N1)pdm09 viruses in studies from Canada, Hong Kong and Europe [16-18]. Antigenic characterisation of this reassortant virus will be conducted at WHO CC.

In conclusion, our results support the observation that the currently co-circulating viruses of A(H1N1)pdm09 and seasonal A(H3N2) viruses have the potential to reassort and form new strains that can spread globally causing epidemics. Reassortment between seasonal and zoonotic influenza might lead to novel pandemic strains and therefore molecular surveillance of circulating influenza strains is of high importance.
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