#14,165
Five weeks ago, in Denmark Reports Novel H1N2 Flu Infection, for the 3rd time in just over a year we learned of novel H1N2 infection - a reassortment of A/H1N1 and A/H3N2 - detected in a northern European county (see 2019 Swedish report and 2018 Netherlands case).
Influenza reassortment can occur when a host (human, avian, porcine, etc.) is co-infected with two flu viruses. Under the right conditions they can they swap gene segments and produce a hybrid virus, but only rarely are these reassortants biologically `fit' enough to thrive.Reassortment is the primary force behind the creation of novel or pandemic flu viruses (see NIAID Video: How Influenza Pandemics Occur). Luckily, a reassortment of seasonal H1N1 and H3N2 is of far less concern than a hybrid of seasonal flu and a zoonotic flu virus.
Last February the CDC issued the following 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.
While human H1N2 infection has only rarely been reported in recent years, we've seen sporadic outbreaks in the past. These larger outbreaks were reassortments of the old H1N1 virus, not the 2009 H1N1 virus.
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.
While 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 were human-origin H1N2 viruses, not to be confused with the swine-origin H1N2v (variant) viruses that have circulated in pigs for decades and that last year was responsible for 14 of the 17 swine variant infections reported to the CDC.
Yesterday the ECDC Journal Eurosurveillance published a detailed analysis of this most recent novel H1N2 reassortant. It is a lengthy report and I've only included some excerpts, so follow the link to read it in its entirety.
Rapid communication Open Access
A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019
Ramona Trebbien1, Anders Koch2, Lene Nielsen3, Dår Kristian Kur4, Pontus Westerström5, Tyra Grove Krause2
A reassortant seasonal influenza A(H1N2) virus was identified in Denmark in a routine surveillance sample from a naturally infected patient who recovered fully. Here we describe the case and virological characterisation of the virus.
(SNIP)
The sample was from an unvaccinated woman in her 70s with asthma and chronic obstructive pulmonary disease (COPD) who was admitted to a Danish hospital on 11 April 2019 with signs of lower respiratory tract infection. The patient had travelled to Croatia, Bosnia and Herzegovina, and Montenegro between 29 March and 5 April 2019. She flew to Croatia and travelled through the three countries on an arranged tour.
After returning, she developed symptoms of lower respiratory tract infection on 7 April and was hospitalised 4 days later. Influenza A virus infection was confirmed. Her symptoms were compatible with influenza. She was discharged on 13 April and has since recovered fully.
The patient’s travel companion remained well during and after the trip. None of the other tourists on the tour developed symptoms during the trip. No information regarding their health status after the trip was available. No contacts of the patient had any symptoms of influenza after her return from her travel.
(SNIP)
Human seasonal reassortant A(H1N2) influenza viruses harbouring the HA gene from an A(H1N1)pdm09 virus and the NA gene from an A(H3N2) virus were detected in one case in Sweden in December 2018 and one case in the Netherlands during the 2017/18 influenza season [4,5].
The gene constellation of the Danish A(H1N2) reassortant virus was similar to that found in Sweden, with seven genes (HA, MP, NS, NP, PA, PB1 and PB2) of A(H1N1)pdm09 virus origin and only the NA gene originating from seasonal A(H3N2) virus. Whether this gene constellation is favourable for reassortment events is unknown and will require further investigations. The A(H1N2) virus detected in the Netherlands had another gene constellation with HA and NS from the A(H1N1)pdm09 virus and the other genes acquired from the A(H3N2) virus [5].
These recent reassortment events of seasonal influenza A viruses emphasise the importance of using detection assays that cross-combine targets for HA and NA genes of the A(H1N1)pdm09 and A(H3N2) subtypes, respectively. If detection assay algorithms do not take this into account, other means to detect reassortment events should be considered, e.g. Sanger sequencing of HA and NA genes or WGS. Besides the European cases, an A(H1N2) reassortant where the HA gene was from the former seasonal A(H1N1) virus and the other genes from seasonal A(H3N2) virus was detected in China in 1988/89. Circulation of A(H1N2) viruses genetically similar to the Chinese cases was observed globally in humans in 2000 to 2003 [6].
Dual infections with influenza A subtypes are not unusual [7,8], and pose a risk for reassortment events and the occurrence of new viruses. A special concern is the risk of reassortment events between seasonal and zoonotic viruses, which could result in viruses with pandemic potential [9]. It is important that new viruses are detected and their potential for virulence and transmission evaluated to provide proper risk assessments.
It is known that the seasonal influenza A virus subtypes (H1N1pdm09 and H3N2) have different characteristics regarding target groups, e.g. A(H3N2) viruses have a higher impact on people above 64 years of age whereas A(H1N1)pdm09 viruses have a higher illness rate in adults 18–64 years of age [10].
New reassortant viruses with a mix of genes from the seasonal viruses might change target group, virulence and transmission potential.
As the gene constellation of the reported reassortant A(H1N2) virus was from seasonal influenza A subtype H1N1pdm09 and H3N2 viruses, it is anticipated that immunity in the population exists from seasonal vaccination and natural infections with seasonal A(H1N1)pdm09 and A(H3N2) viruses.
This was further confirmed by the results from the HAI test, which indicated that the reassortant virus had similar antigenic characteristics as the vaccine virus A/Michigan/45/2015. Vaccine effectiveness (VE) studies for the 2018/19 influenza season included reports on substantial VE for A(H1N1)pdm09 viruses [11-13].
Influenza has an incubation time between 1 and 4 days [14]. With development of symptoms 2 days after her return from an 8-day trip to Croatia, Bosnia and Herzegovina, and Montenegro, it is most likely that the patient was infected either during her trip or during the travel back to Denmark.
Both influenza A virus subtypes H1N1pdm09 and H3N2 circulated during the 2018/19 influenza season in most of Europe, including Denmark and the countries the patient had visited. In seasons where both influenza A virus subtypes H1N1pdm09 and H3N2 circulate, there is a risk of co-infection with both subtypes and thereby reassortment events.
In conclusion, reassortment events of seasonal influenza A subtype H1N1pdm09 and H3N2 viruses occur. It is important that national reference laboratories are able to detect new reassortant viruses and that the potential public health impact of reassortant viruses is assessed.
(Continue . . . )
While the paucity of case detections suggests these hybrid H1N2 viruses remain rare, and probably don't transmit very well - this patient didn't show signs of recent co-infection with H1N1 and H3N2 - which suggests this patient may not have been the reassortant host.
While three seasonal reassortants detected in a year doesn't a crisis make, this is a reminder of how malleable flu viruses are, and how important it is to track their evolution in real time.
