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Published Date: 2010-08-05 23:50:00
Subject: PRO/AH> Influenza pandemic (H1N1) (61): seasonal strain replacement 2009
Archive Number: 20100805.2648

INFLUENZA PANDEMIC (H1N1) (61): SEASONAL STRAIN REPLACEMENT 2009
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Date: Thu 5 Aug 2010
Source: Eurosurveillance, Volume 15, Issue 31 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19631>

The impact of pandemic influenza A(H1N1) 2009 virus on seasonal
influenza viruses in the Southern Hemisphere, 2009
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Summary
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Data collected over winter 2009 by 5 World Health Organisation
National Influenza Centres in the southern hemisphere were used to
examine the circulation of pandemic and seasonal influenza A strains
during the 1st pandemic wave in the southern hemisphere. There is
compelling evidence that the pandemic influenza A(H1N1) 2009 virus
significantly displaced seasonal influenza A(H1N1) and, to a lesser
extent, A(H3N2) viruses circulating in the southern hemisphere.
Complete replacement of seasonal influenza A strains, however, was
not observed during the 1st pandemic wave.

Introduction
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Historically influenza pandemics have been associated with
replacement of the previously circulating influenza A subtype, as was
observed in 1957 when influenza A(H2N2) replaced A(H1N1), and in 1968
when influenza A(H3N2) subsequently replaced A(H2N2). As global viral
surveillance was limited during the pandemics of 1957 and 1968, the
proportion of disease attributable to seasonal influenza viruses
during the early pandemic periods and the rate of subtype replacement
are uncertain. It is postulated that cross-protective immunity
following infection with a pandemic influenza virus results in
protection against circulating seasonal influenza subtypes. This
protection results in displacement and replacement of seasonal
influenza subtypes by pandemic viruses [1-3].

Co-existence of different subtypes is possible when the introduction
of a virus does not generate a pandemic. The reintroduction of an
influenza virus in a context of considerable residual herd immunity,
as was observed with influenza A(H1N1) in 1977, can result in
co-circulation of more than one influenza subtype [1,3]. We cannot be
certain whether emerging pandemic influenza strains will replace or
co-exist with the previously circulating subtypes or strains, and if
replacement is observed, how quickly this will occur. As this outcome
has implications on the selection of viruses to be included in
influenza vaccines, improved surveillance and rapid influenza A
subtyping methods have important roles to play in monitoring the
circulation dynamics of influenza strains during modern epidemics and
pandemics.

The pandemic influenza A(H1N1) 2009 virus was 1st identified in April
2009 [4-6]. As its detection in the northern hemisphere coincided
with declining seasonal influenza activity, the impact on the
circulation of seasonal influenza viruses could not be fully assessed
[7]. In contrast, the 1st wave of the pandemic influenza virus in the
southern hemisphere coincided with the onset of the winter influenza
and respiratory virus season. Thus, data obtained from the 2009
southern hemisphere winter provide an opportunity to examine the
circulation dynamics of pandemic and seasonal viruses during the
early pandemic period.

This report presents data obtained by 5 World Health Organization
(WHO) National Influenza Centres in the southern hemisphere for the
winter of 2009. The pattern of circulating pandemic and seasonal
influenza A strains in the southern hemisphere provides important
information that can contribute to decision making regarding vaccine
strain selection, and preventative and therapeutic strategies.

Methods
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Influenza A subtyping data from all diagnostic respiratory tract
specimens submitted in winter 2009 to 5 WHO National Influenza
Centres (NICs) in Australia, New Zealand and South Africa were
collated and analysed. NICs in Melbourne, Sydney and Perth receive
samples from the Australian states of Victoria, New South Wales and
Western Australia, respectively, whereas NICs in Wellington and
Johannesburg receive the samples from across New Zealand and South
Africa, respectively.

Influenza detection and subtyping was performed within each
laboratory by nucleic acid testing using polymerase chain reaction
(PCR) of type-specific targets within the matrix gene and
subtype-specific targets within the haemagglutinin gene regions of
the influenza virus genome. To assist with interpretation of the raw
data, samples that tested positive for influenza A yet were not
subtyped were removed prior to analysis. Where available, the
PCR-positive detection rates from respiratory samples received during
previous seasons (examined in similar populations using similar
surveillance methods) were compared with those from the 2009 season.

Results
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Influenza A was detected by PCR in 17 328 respiratory tract specimens
collected at the 5 NICs from May to October 2009 (week 18 to week
44). Influenza A subtyping was available for 90 percent of influenza
A positive specimens (Wellington: 73 percent; Melbourne: 95 percent,
Sydney: 89 percent, Perth: 100 percent, Johannesburg: 97 percent).
The number of typed and untyped specimens as a proportion of total
positive tests remained consistent in all centres across the study
period. Epidemic curves from the 5 NICs were constructed (Pandemic
influenza A(H1N1) 2009 activity in the southern hemisphere was 1st
detected in New Zealand in week 18 (peak activity in week 28),
followed by Melbourne, Sydney and Perth in week 21 (peak activity in
weeks 22, 25 and 29 respectively) and then South Africa in week 25
(peak activity in week 32).

Significant pandemic influenza activity was detected in all
locations: The overall proportion of influenza A-positive specimens
from May to October 2009 subtyped as pandemic influenza A(H1N1) 2009
was 78 percent in Wellington, 85 percent in Melbourne, 80 percent in
Sydney, 89 percent in Perth and 53 percent in Johannesburg. The
proportion of influenza viruses typed as pandemic influenza A(H1N1)
2009 following 1st identification of the pandemic virus was 78
percent in Wellington, 85 percent in Melbourne, 80 percent in Sydney,
90 percent in Perth and 68 percent in Johannesburg. These proportions
increased to 93 percent, 95 percent, 92 percent, 96 percent and 94
percent, respectively, if only those specimens received during the
2nd half of the pandemic from August to October 2009 (week 31 to week
44) were examined independently.

Seasonal influenza A activity coincided with pandemic influenza
activity in New Zealand, and preceded it in Australia and South
Africa. Total seasonal influenza virus activity was generally modest.
20 percent of PCR-positive specimens were subtyped as seasonal
influenza A(H1N1) in Wellington, 5 percent in Melbourne, 3 percent in
Sydney, 2 percent in Perth and less than 1 percent in Johannesburg.
The corresponding figures for influenza A(H3N2) were 2 percent in
Wellington, 10 percent in Melbourne, 17 percent in Sydney, 8 percent
in Perth and 47 percent in Johannesburg. Despite the low levels in
most catchment areas, both seasonal influenza A(H1N1) and A(H3N2)
activity were detected in all 3 countries throughout the winter 2009.

Samples from sentinel general practitioner surveillance systems
provide the best estimate of community influenza activity. The 2009
influenza season was compared with previous seasons using sentinel
data from the NICs in Wellington, Melbourne and Perth, each of which
receives samples from country-wide (Wellington) or state-wide
(Melbourne, Perth) surveillance systems operating during the winter
influenza season. In 2009, 27-35 percent of surveillance specimens
were influenza A-positive compared to 20-39 percent in 2007 and 13-27
percent in 2008. Pandemic influenza A(H1N1) 2009 virus was identified
in 71-98 percent of influenza PCR-positive samples in 2009. The
absolute number and proportion of samples positive for seasonal
influenza viruses in all 3 locations was lower in 2009 compared with
the previous 2 seasons.

Discussion and conclusions
--------------------------
The impact of the pandemic influenza A(H1N1) 2009 virus on
circulating seasonal influenza strains was demonstrated using data
obtained by 5 WHO National Influenza Centres in the southern
hemisphere in the winter of 2009. Examination of influenza strains as
a proportion of the subtyped influenza A positive specimens in 2009,
total test specimens in 2009 and 2007-2009 sentinel surveillance
specimens provides compelling evidence that the pandemic virus
significantly displaced seasonal influenza viruses. Consistently
across Australia, New Zealand and South Africa, the replacement was
rapid and progressive with seasonal strains comprising a low and
declining proportion of influenza A detections from the peak of the
pandemic wave through to the end of the season.

Complete seasonal influenza A strain replacement, however, was not
observed. These data are consistent with data presented by Tang et
al. when examining 2009 influenza activity in Singapore [2]. Raw data
and the shape of epidemic curves need to be interpreted with caution
given the impact of testing behaviour (particularly elevated testing
at the beginning of the pandemic) and modifications of testing
algorithms through the course of the season.

The reduction in seasonal influenza A(H1N1) activity was the most
obvious effect of the 2009 pandemic. Significant early activity of
seasonal influenza A(H1N1) was observed in New Zealand and, to a
lesser extent, Australia. Following the entry of the pandemic virus,
detection of seasonal A(H1N1) viruses quickly decreased and remained
at low levels throughout the winter. The majority of tested seasonal
influenza A(H1N1) viruses were resistant to oseltamivir (A Kelso,
unpublished data), as observed in the previous northern hemisphere
winter. Seasonal influenza A(H3N2) activity also declined as the
pandemic progressed, but the effect was less obvious and activity
continued at higher levels than those of seasonal influenza A(H1N1)
throughout the season.

A similar observation was made in North America in 2009. While the
absolute numbers of detected seasonal influenza viruses increased in
the United States (US) from April to May 2009, the proportion of
specimens positive for seasonal influenza strains continued to
decrease during this time [7]. This increase in absolute numbers yet
decrease in the proportion of positive specimens is likely to reflect
an increase in the number of influenza tests performed [7]. The
2009-2010 winter data from the US WHO and National Respiratory and
Enteric Virus Surveillance System (NREVSS) Collaborating Laboratories
demonstrated that, although more than 99 percent of reported
influenza A-positive tests were subtyped as pandemic influenza
A(H1N1) 2009, ongoing transmission of seasonal strains was detected [8].

Given the high mutation rate and continual emergence of novel genetic
lineages of influenza virus, it remains uncertain why pandemic
influenza viruses replace existing seasonal influenza A subtypes and
strains. Transient heterosubtypic immunity -- short-lived immunity
which is cross-protective against different subtypes and declines
rapidly over time -- has been shown to inhibit re-infection by any
new strain in animal models [1,9,10]. It is postulated that, during
pandemics, a substantial fraction of the global population is
infected with the new virus and is then transiently immune to
infection with the previously circulating subtypes [3]. This leaves a
critically low number of susceptible individuals, leading to the
extinction of seasonal influenza strains. It is important to note
that the effect is specific for influenza A viruses as the
replacement of circulating influenza B virus lineages is not observed.

Data from both the 2009 southern hemisphere and 2009-2010 northern
hemisphere influenza season [7,8] suggest that pandemic influenza
A(H1N1) 2009 will be the predominant influenza A strain in the 2010
influenza season in the southern hemisphere. Whether complete subtype
replacement will be observed in 2010 remains uncertain. These data
support the recommendation that seasonal influenza vaccines for the
southern hemisphere in 2010 and the northern hemisphere in 2010-2011
contain representative pandemic influenza A(H1N1) and seasonal
influenza A(H3N2) viruses (as well as an influenza B virus) [11], but
not the previously circulating seasonal influenza A(H1N1) virus.

Given the evidence of ongoing, albeit sporadic, transmission of
seasonal influenza A viruses 11 months after pandemic influenza was
1st detected, it is likely that influenza A(H3N2) and perhaps also
seasonal influenza A(H1N1) infections will be observed during the
coming season. Whether ongoing suppression of seasonal viruses will
lead to complete replacement remains to be determined.

[Byline: C C Blyth1,2, A Kelso3, K A McPhie1, V M Ratnamohan1, M
Catton4, J D Druce4, D W Smith5, S H Williams5, Q S Huang6, L Lopez6,
B D Schoub7, M Venter7, D E Dwyer1
At: 1 - Centre for Infectious Diseases and Microbiology
Laboratory Services, Institute of Clinical Pathology and Medical
Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia
2 - School of Paediatrics and Child Health, University of Western
Australia, Princess Margaret Hospital, Subiaco, Western Australia, Australia
3 - World Health Organisation Collaborating Centre for Reference and
Research on Influenza, Victorian Infectious Diseases Reference
Laboratory (VIDRL), North Melbourne, Victoria, Australia
4 - Victorian Infectious Diseases Reference Laboratory, North
Melbourne, Victoria, Australia
5 - Pathwest Laboratory Medicine, Queen Elizabeth II Medical Centre,
Nedlands, Western Australia, Australia
6 - World Health Organisation National Influenza Centre, Institute of
Environmental Science and Research, Wellington, New Zealand
7 - National Institute for Communicable Diseases, Sandringham,
Johannesburg, South Africa.]

References
----------------
(1) Ferguson NM, Galvani AP, Bush RM. Ecological and immunological
determinants of influenza evolution. Nature. 2003;422(6930):428-33.
(2) Tang JW, Lee CK, Lee HK, Loh TP, Chiu L, Tambyah PA, et al.
Tracking the emergence of pandemic Influenza A/H1N1/2009 and its
interaction with seasonal influenza viruses in Singapore. Ann Acad
Med Singapore. 2010;39(4):291-4.
(3) Ferguson NM, Bush RM. Influenza evolution and immune selection.
International Congress Series. 2004;1263:12-6.
(4) Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team,
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of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J
Med. 2009;360(25):2605-15.
(5) Centers for Disease Control and Prevention. Outbreak of
swine-origin influenza A H1N1) virus infection - Mexico, March-April
2009. MMWR Morb Mortal Wkly Rep. 2009;58(17):467-70
(6) World Health Organisation (WHO). Swine influenza - update 4.
Disease Outbreak News. Geneva: WHO; 28 Apr 2009. Available from:
<http://www.who.int/csr/don/2009_04_28/en/index.html>
(7) Centers for Disease Control and Prevention (CDC). FluView.
2008-2009 influenza season week 39 ending 3 Oct 2009 [Accessed 26 Feb
2009]; Atlanta: CDC; 2009. Available from:
<http://www.cdc.gov/flu/weekly/weeklyarchives2008-2009/weekly39.htm>
(8) Centers for Disease Control and Prevention (CDC). FluView.
2009-2010 influenza season week 6 ending 13 Feb 2010. [Accessed 26
Feb 2009]. Atlanta: CDC; 2009. Available from:
<http://www.cdc.gov/flu/weekly/weeklyarchives2009-2010/weekly06.htm>
(9) Grebe KM, Yewdell JW, Bennink JR. Heterosubtypic immunity to
influenza A virus: where do we stand? Microbes Infect. 2008;10(9): 1024-9.
(10) Schulman JL, Kilbourne ED. Induction of partial specific
heterotypic immunity in mice by a single infection with influenza A
virus. J Bacteriol. 1965;89:170-4.
(11) World Health Organisation (WHO). Recommendations for influenza
vaccines. [Accessed 22 Feb 2010]. Geneva: WHO Available from:
<http://www.who.int/csr/disease/influenza/vaccinerecommendations/en/index.html>.

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Communicated by:
ProMED-mail
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[The graphical presentation of the data contained in this report has
been omitted and interested readers should refer to the original
article for easier comprehension.

Over the whole southern hemisphere region the reduction in seasonal
influenza A(H1N1) activity was the most obvious effect of the 2009
pandemic. Seasonal influenza A(H3N2) activity also declined as the
pandemic progressed, but the effect was less obvious and activity
continued at higher levels than those of seasonal influenza A(H1N1)
throughout the season. It remains uncertain why pandemic influenza
viruses replace existing seasonal influenza A subtypes and strains.
Data from both the 2009 southern hemisphere and 2009-2010 northern
hemisphere influenza season suggest that pandemic influenza A(H1N1)
2009 will be the predominant influenza A strain in the 2010 influenza
season in the southern hemisphere. Whether complete subtype
replacement will be observed in 2010 as yet remains uncertain. - Mod.CP]

See Also