ArticlePDF AvailableLiterature Review

Literature review of the epidemiology of influenza B disease in 15 countries in the Asia-Pacific region

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Aim: Influenza control strategies focus on the use of trivalent influenza vaccines containing two influenza A virus subtypes and one of the two circulating influenza type B lineages (Yamagata or Victoria). Mismatches between the vaccine B lineage and the circulating lineage have been regularly documented in many countries, including those in the Asia-Pacific region. We conducted a literature review with the aim of understanding the relative circulation of influenza B viruses in Asia-Pacific countries. Methods: PubMed and Western Pacific Region Index Medicus were searched for relevant articles on influenza type B published since 1990 in English language for 15 Asia-Pacific countries. Grey literature was also accessed. Results: From 4,834 articles identified, 121 full-text articles were analysed. Influenza was reported as an important cause of morbidity in the Asia-Pacific region, affecting all age groups. In all 15 countries, influenza B was identified and associated with between 0%-92% of laboratory-confirmed influenza cases in any one season/year. Influenza type B appeared to cause more illness in children aged between 1-10 years than in other age groups. Conclusion: Epidemiological data for the two circulating influenza type B lineages remain limited in several countries in the Asia-Pacific, although the co-circulation of both lineages was seen in countries where strain surveillance data were available. Mismatches between circulating B lineages and vaccine strains were observed in all countries with available data. The data suggest that a shift from trivalent to quadrivalent seasonal influenza vaccines could provide additional benefits by providing broader protection. This article is protected by copyright. All rights reserved.
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PROF. WOO JOO KIM (Orcid ID : 0000-0002-4546-3880)
DR. MELVIN JALANDO-ON SANICAS (Orcid ID : 0000-0002-2933-0666)
Article type : Expert Commentary
Literature review of the epidemiology of influenza B
disease in 15 countries in the Asia-Pacific region
Running heading: Influenza B in the Asia-Pacific
Lance Jenningsa, Qiu Sue Huangb, Ian Barrc, Ping-Ing Leed, Woo Joo Kime, Philippe
Buchyf, Melvin Sanicasf
1
, Bruce A. Mungallf, Jing Chenf
a Canterbury District Health Board, Christchurch, New Zealand.
b WHO National Influenza Centre, Institute of Environmental Science and Research,
Porirua, Wellington, New Zealand.
c WHO Collaborating Centre for Reference and Research on Influenza, Melbourne,
Australia.
d Department of Pediatrics, National Taiwan University Children's Hospital, Taipei,
Taiwan.
e Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea.
1
Present address: Sanofi Pasteur Asia & JPAC Region, Singapore
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f GSK, Singapore.
Corresponding author:
Jing Chen
GSK,
150 Beach Road, Gateway West, Singapore
+65 62 328 456, jing.j.chen@gsk.com
Authors’ email addresses:
Lance Jennings: Lance.Jennings@cdhb.health.nz
Qiu Sue Huang: Sue.Huang@esr.cri.nz
Ian Barr: Ian.Barr@influenzacentre.org
Ping-Ing Lee: pinging@ntu.edu.tw
Woo Joo Kim: wjkim@korea.ac.kr
Philippe Buchy: philippe.x.buchy@gsk.com
Melvin Sanicas: Melvin.sanicas@gmail.com
Bruce A. Mungall: bruce.a.mungall@gsk.com
Jing Chen: jing.j.chen@gsk.com
Abstract
Aim: Influenza control strategies focus on the use of trivalent influenza vaccines
containing two influenza A virus subtypes and one of the two circulating influenza type B
lineages (Yamagata or Victoria). Mismatches between the vaccine B lineage and the
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circulating lineage have been regularly documented in many countries, including those in
the Asia-Pacific region. We conducted a literature review with the aim of understanding
the relative circulation of influenza B viruses in Asia-Pacific countries.
Methods: PubMed and Western Pacific Region Index Medicus were searched for
relevant articles on influenza type B published since 1990 in English language for 15
Asia-Pacific countries. Grey literature was also accessed.
Results: From 4,834 articles identified, 121 full-text articles were analysed. Influenza
was reported as an important cause of morbidity in the Asia-Pacific region, affecting all
age groups. In all 15 countries, influenza B was identified and associated with between
0%-92% of laboratory-confirmed influenza cases in any one season/year. Influenza type
B appeared to cause more illness in children aged between 1-10 years than in other age
groups.
Conclusion: Epidemiological data for the two circulating influenza type B lineages
remain limited in several countries in the Asia-Pacific, although the co-circulation of both
lineages was seen in countries where strain surveillance data were available.
Mismatches between circulating B lineages and vaccine strains were observed in all
countries with available data. The data suggest that a shift from trivalent to quadrivalent
seasonal influenza vaccines could provide additional benefits by providing broader
protection.
Keywords: epidemiology, influenza B, Asia-Pacific, seasonality, vaccine mismatch,
literature review
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What this paper adds
By bringing together data from across the region, we show that influenza contributes to
the public health burden in Asia-Pacific countries, with a variable, but substantial
proportion due to influenza B. Influenza vaccination policies are needed in Asia-Pacific
countries, and the use of quadrivalent influenza vaccines could provide additional
benefits.
Introduction
Epidemic influenza causes global public health burden each season. The World Health
Organization (WHO) estimates that influenza severely affects between three and five
million individuals each year and causes between 250,000 and 0.5 million deaths.1 The
influenza attack rate is highest in children, while complications including hospitalisation
and death, occur most frequently in elderly individuals.1 Other specific high-risk groups
prioritised by WHO for vaccination include pregnant women, the highest priority group,
followed by individuals with a compromised immune system and individuals with co-
morbidities such as pulmonary or cardiac disease.2
Influenza type A and B viruses cause the vast majority of influenza disease in humans
and infection is preventable by vaccination. The relative proportion of influenza cases
caused by type A and type B strains varies annually, reflecting antigenic drifts in the
predominant strains and the hosts level of immunity. In the last decade, influenza A
viruses represented by three subtypes (A/H3N2, A/H1N1 and A/H1N1pdm09) have
predominated during influenza seasons. Influenza B viruses are represented by two
separate lineages (B/Victoria and B/Yamagata) that co-circulate. In the 1980s, the
B/Yamagata/16/88 lineage and its variants spread worldwide, whereas B/Victoria/2/87
lineage viruses remained geographically restricted to Asia during the 1990s for reasons
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not wholly understood. In 2002, the B/Victoria lineage strains spread to the rest of the
world.36 Influenza B has been isolated in up to 44% of laboratory samples in the United
States from 2001-02 through 2010-11 seasons (excluding the 2009-10 pandemic
period), and in up to 60% of samples in Europe during the same period, with a seasonal
average of 24% and 23% of samples, respectively.7
Seasonal influenza vaccines are modified annually to include those antigenic variants
that are likely to predominate in the following influenza season. Vaccine strain selection
is performed by the WHO using data from the Global Influenza Surveillance and
Response System, a network of over 140 institutions in 111 countries.8 The B/Yamagata
and B/Victoria influenza strains are antigenically distinct and vaccines using one lineage
induce only low levels of cross-protection to the other lineage.9,10 Trivalent seasonal
influenza vaccines only contain one influenza B lineage, and it is not always possible to
predict which B lineage will predominate during the next influenza season.11 Mismatch
between the vaccine lineage and circulating influenza B lineage has occurred regularly,
which can have a significant impact on influenza vaccine efficacy.4,1214 Since 2012, the
WHO has recommended the inclusion of strains from both B lineages in quadrivalent
seasonal influenza vaccines.15
Co-circulation of both influenza type B lineages has also been documented throughout
South East Asia and Oceania.5 The use of influenza vaccine in many Asia-Pacific
countries is limited, and the potential impact of quadrivalent influenza vaccines on illness
and hospitalisation rates in these countries is not known, but is also likely to be low.16 In
order to obtain an epidemiological view of influenza type B in the Asia-Pacific region, we
conducted a review of the available literature. We attempted to identify periods of
influenza B lineage-mismatch between vaccine and circulating strains in 15 countries
within the Asia-Pacific region to better inform health authorities of the potential benefits
of quadrivalent influenza vaccines for protection against seasonal influenza.
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Methods
Fifteen countries were selected from within the Asia-Pacific region traversing all climatic
zones (Figure 1). These included northern hemisphere countries: China (temperate to
subtropical climate), South Korea (temperate climate), Taiwan (subtropical climate),
Laos, Myanmar and Vietnam (subtropical to tropical), Cambodia, Thailand, and the
Philippines (tropical); countries in the Equatorial region: Indonesia, Malaysia, Singapore
and Papua New Guinea (tropical); and countries in the Southern hemisphere: Australia
and New Zealand (temperate).
Search strategy and selection criteria
Articles were identified from PubMed and the Western Pacific Region Index Medicus
(WPRIM) using search strings comprised of terms that identified influenza, the selected
countries of interest in the Asia-Pacific region and the epidemiology/burden of disease
(Supplementary information 1). The search covered publication dates between January
1990 until 11 April 2016, and was limited to articles published in English language. Titles
and abstracts were screened for relevance: that is, reported outcomes related to
seasonal influenza in humans and in a country of interest. Articles were excluded if they
reported pharmacokinetic or pharmacodynamic studies, case reports, case series,
clinical trials, or meta-analyses. Articles were also excluded if they reported features of
influenza pathophysiology, treatment, or diagnosis, or if they reported data in fewer than
30 patients. Publications without abstracts were only reviewed if the title fitted the review
objectives.
Full text articles were reviewed to assess their relevance and methodological quality.
Articles were excluded if the methods section were insufficiently described, if the content
did not provide relevant information to the review objectives, if the article reported
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“pneumonia and influenza” as a combined outcome (unless pneumonia was described
as a complication of influenza), outcomes from mathematical models, and if no
quantitative data could be retrieved. Grey literature including WHO websites, local
ministries of health and WHO vaccine recommendations were also assessed for
relevance. Extracted data included information on epidemiology and circulating strains.
We did not collect clinical criteria or clinical case definitions of influenza, influenza-like-
illness (ILI), febrile illness, acute respiratory infection (ARI) disease or severe acute
respiratory illness (SARI) used in individual studies. Nor did we specify the methods for
selecting cases for specimen collection or the influenza-testing method used for
laboratory-diagnosis. In our review, “laboratory-confirmed influenza” or a “positive
sample” refers to a case of influenza confirmed by the method stated in the reporting
paper.
An influenza B mismatch was defined as the circulating influenza B virus lineage strains
differing from the B lineage representative strain included in the WHO-recommended
influenza vaccine composition for that season. When <20% of the circulating influenza B
strains differed from the WHO-recommended vaccine strain, we arbitrarily considered
the degree of mismatch to be ‘low’. A difference between 20-40% was considered as
partial mismatch. We considered a significant mismatch as >40% and complete
mismatch when 95% of the circulating influenza B lineage strains did not belong to the
trivalent vaccine lineage.
The initial literature search in 2013 was conducted by Pallas Health Research and
Consultancy B.V., the Netherlands. Quality control activities included review of the first
30% of titles and abstracts and of the first 10% of full-text articles in duplicate by two
independent researchers from Pallas. Any disagreements were adjudicated by a third
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researcher. The search was updated in 2016 by BM and the articles were selected by
BM and JC.
Ethics approval was not required for this study. The majority of relevant publications
concerned surveillance or other observational epidemiological studies for which no
standard quality checklists are currently available.
Results
There were 121 English language articles included in the review (Figure 2), of which 120
articles provided information on influenza B strains as a proportion of all laboratory-
confirmed influenza from data collected between 1990 and 2015 (Table 1). Most
assessed specific, but diverse, populations of interest, such as patients hospitalized for
respiratory tract infections (RTI), patients in intensive care, and respiratory samples from
in/outpatients with a broad range of underlying respiratory syndromes. In many studies
the age range of subjects/samples was not specified. Many studies included patients
with diagnoses of low specificity for influenza such as ‘febrile illness’, ‘ILI’ and ‘acute
lower respiratory tract infection’ (ALRTI). There were 102 prospective studies (two
studies included both prospective and retrospective components). Sample sizes in
individual study groups ranged from 26 to more than 300,000.
Influenza surveillance and vaccine coverage in Asia-Pacific countries
With the exception of Myanmar, all of the countries studied use a sentinel site approach
for influenza surveillance (Table 1). All countries with a surveillance program in place
monitor ILI cases (ARI in Singapore and pneumonia in Laos instead of ILI) presenting to
general practices or hospitals. In Myanmar, epidemiological studies funded by grant
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programs in Japan were conducted in two hospitals and general practice clinics in
Yangon.
Six countries (Australia, New Zealand, South Korea, Taiwan, Thailand and the
Philippines) have/have had a publicly funded national seasonal influenza immunisation
programme and in all cases this is/was limited to at-risk groups (Table 1).
China, Indonesia, Laos, the Philippines, Singapore and Vietnam provide
recommendations for immunisation of risk groups (and Malaysia recommends
vaccination of Hajj pilgrims) outside the national schedule. No policy for influenza
vaccine use exists for Papua New Guinea, Cambodia or Myanmar.
In countries with a policy to provide free vaccine for at-risk groups, vaccine uptake
among these groups has been substantial: approximately 73% of 65+ year olds in
Australia, 67.5% in New Zealand, 80% of adults in Taiwan and 82.5% in 65+ year-olds in
South Korea were reported to have received influenza vaccine (Table 1). In China,
influenza vaccine coverage was reported as 26% in children and 7.4% in 60+ year olds,
but regional differences may exist due to subsidisation of influenza vaccines in some
regions.17,18 Approximately 300 doses of influenza vaccine were distributed per 1,000
population in Australia and New Zealand, while fewer than 10 doses per 1,000
population were distributed in Cambodia, China, Indonesia, Malaysia, and Papua New
Guinea, suggesting that influenza vaccine use is negligible in these countries.19
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Epidemiology of influenza type B in Asia-Pacific countries
Australia
Laboratory surveillance conducted by the WHO collaborating centre and National
Influenza Centres showed that during the period from 2005-15, influenza B viruses
predominated in two years: in 2005, 67% of circulating influenza viruses were type B
while 51% of the influenza B viruses mismatched the B strain contained in the seasonal
influenza vaccine; in 2015, 62% of circulating influenza viruses were type B with a partial
(36%) mismatch to the trivalent vaccine influenza B component (Table 3).2022
We identified 18 articles that described influenza B in Australia reporting studies
conducted from 1991 until 2015. Most of the articles reported data from laboratory-based
influenza surveillance or clinic/hospital-based surveillance in various states/territories.
Some of the studies were conducted in the same/overlapped seasons but in different
groups of patients.
One study in 2002-03 found that the proportion of influenza B was higher among
influenza-positive specimens from state-wise influenza surveillance program of ILI
patients at sentinel general practitioner (GP) clinics than among influenza-positive
patients hospitalised with respiratory illness (11.5% vs. 1.8%).23 Two studies conducted
in 2006 reported higher influenza detection rate among outpatients with ILI comparing to
hospitalized children with ILI, while the proportion of influenza B was higher among
laboratory-confirmed influenza in-patients comparing to outpatients.24,25
Two studies with overlapping study period in 2007 found significantly higher influenza-
positivity rate among ILI patients presenting to GP clinics than children with ARI
presenting to hospital (46.9% vs. 12.2%). The difference between the proportion of
influenza B among the two groups of patients in these two studies was much smaller
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(12.7 vs. 18.9%).26,27 Comparing to these two studies, another study encompassing the
same study period reported a much lower influenza B proportion among hospitalized
children with laboratory-confirmed influenza (2.5%).28
In 2012, GP clinic-based surveillance in Western Australia and Victoria reported similar
influenza detection rate among ILI patients.29,30 The proportion of influenza B among
influenza-positive samples obtained from ILI patients was significantly higher in Western
Australia than in Victoria (43% vs. 13.6%).
Cambodia
Since 2006, the National Influenza Centre in Cambodia carried out sentinel-site based
ILI surveillance and hospital-based ALRI surveillance. Influenza viruses were detected
from 5.8-18.7% of ILI patients between 2006 and 2011, and 1.4-3.6% of ALRI patients
from 2007-2010. Proportion of influenza B among all influenza-positive samples ranged
from 12.6% in 2009 to 64.8% in 2011. Influenza type A and B circulated year-round in
Cambodia with peak activities during the rainy season between June and November.3133
China
National surveillance of ILI has been carried out by the Chinese CDC in 95 sentinel
hospitals in Northern provinces and 99 hospitals in southern provinces since 2000. From
2005-11, 64,306 laboratory-confirmed influenza cases were recorded by the ILI
surveillance in the North. In Southern China 122,215 laboratory-confirmed influenza
cases were confirmed by the ILI surveillance during 2006-12. Around 30% of all positive
samples were influenza B.34
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Twenty-three articles reported on influenza B in China from 1995 until 2014 (Table 2).
Most of the articles reported clinic/hospital-based ILI surveillance in one city/province
and provided aggregated data over multiple seasons.
A study in Shenzhen in the southern province of Guangdong from 1995-2009 reported
an annual influenza detection rate among ILI cases ranging from 0.2% in 1998 25% in
2009. The lowest proportion of influenza B among all influenza positive samples was in
2008.35 Influenza B predominated in 4 of the 15 study years with the peak (79%)
reported in 1997. Multiple influenza B outbreaks between 2004-12 were reported in
Guangdong province, including in 2010 following the peak of A/H1N1/pdm09.36 The 2010
influenza B peak was also reported in studies conducted in northern, central, and
eastern part of China.3740
A study conducted in central China assessed SARI hospitalisations by type of influenza
and found that in 2010-11, A (H3N2) virus was associated with a higher SARI
hospitalization rate (55/100,000) than both influenza B and A (H1N1)pdm2009. In the
following year, the incidence of SARI hospitalisation was highest with influenza B
(98/100,000).39
Between the 2009-14 seasons, on average, 45% of circulating B lineages in Shanghai
differed antigenically from the vaccine strain. During the period from 2009-12, B/Victoria
lineage matching the seasonal influenza vaccines strain predominated over the
B/Yamagata lineage. The proportion of B/Yamagata lineage exceeded 97% of all
circulating influenza B viruses in late 2012 and resulted in complete vaccine B strain
mismatch. 41
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Indonesia
We identified five articles with data relevant to Indonesia (Table 2). Three of these
papers were based on ILI surveillance of multiple seasons, reporting a proportion of type
B viruses between 25.4-36% among all influenza positive samples during the overall
study period.34,42,43 Two papers provided season-specific information on the proportion of
influenza B among all ILI cases with laboratory-confirmed influenza in 2010-11 and
2011-12.44,45 One of them also provided data in SARI patients with laboratory-confirmed
influenza in 2011-12. In that study the influenza detection rate was higher among ILI
than among SARI patients (34.5% vs. 15.4%). In both patient groups 47% of laboratory-
confirmed influenza cases were influenza B.45
Laos
ILI virological surveillance started in Lao People’s Democratic Republic (PDR) in 2007.
We identified four articles assessing influenza in Laos during the period from 2007-2011.
One study based on ILI surveillance during the period 2008-10 reported influenza
positivity rate of 20.9-23% in the three years. The proportion of influenza B among all
influenza positive samples dropped from 66.7% in 2008 to 2.7% in 2009 when A/H3N2
and A/H1N1pdm09 became predominant, then increased to 33.7% in 2010.46
Two studies assessing influenza among patients hospitalised with ALRI showed that the
influenza-positivity rate (12.7%) and influenza B proportion among ALRI cases (40%)
with laboratory-confirmed influenza in 2008 were higher comparing to the findings in
2009-10 (7.9% and 21.8%, respectively). 47,48
Malaysia
Six articles were identified for Malaysia reporting studies conducted between 1982 and
2011, of which four reported aggregated data across multiple seasons.
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From 2005-2009 national ILI surveillance detected influenza in 10.2% (2008) 31.6%
(2006) of ILI cases.49 In this period, the proportion of influenza B was lowest in 2008
(18%) and highest in 2005 (51%). Peak season of influenza fell between May-August.
Complete influenza B strain mismatch with Southern hemisphere vaccine B strain was
observed in 2005 and 2009 and significant mismatch in 2007 (Table 5).
Laboratory-based surveillance of ILI patients presenting to sentinel centres showed that
the percentage of samples tested positive for influenza ranged between 3.1-13.4% in
2006-11.44,49 The percentage of B strains among the influenza-positive samples was
30.7% on average from 2005-09, and 20.2% to 62.6% annually between 2006-10.
Myanmar
Three articles reported the results of sentinel site-based surveillance study in Myanmar
between 2003 and 2007.5052 The proportion of influenza positive samples obtained from
patients with ILI ranged from 11.4% in 2006 to 24~27.0% in 2005. Few influenza B
cases were detected in 2003-04 and 2006. The proportion of influenza-positive samples
that were type B ranged from 42~46.6% in 2005 with a majority of influenza B isolates
belonging to the Victoria lineage. In 2007, 67% of influenza viruses were influenza B and
all belonged to the B/Victoria lineage.5052
New Zealand
Seven articles describing influenza in New Zealand between 1990 and 2015 were
identified. National influenza surveillance data showed that during 1997-2008, on
average 718 cases of laboratory-confirmed influenza were detected every year.53
Influenza surveillance in 2005 recorded the highest influenza B activity since 1990 with
co-circulation of influenza strains from B/Victoria and B/Yamagata lineages, which
resulted in significant B strain mismatch with the recommended vaccine composition.54
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In 2015, 44.2% of patients with ILI and 23.6% SARI patients tested positive for
influenza.55 The proportion of influenza B among all influenza-positive samples was 13%
but half of them mismatched the B strain contained in the influenza vaccines for that
season (Table 3).
Papua New Guinea
In the one study identified as providing information on influenza in Papua New Guinea,
29.3% of samples from patients with ILI received by the Papua New Guinea National
influenza Centre in 2010 had laboratory-confirmed influenza, of which 43.2% were
influenza type B.56
Philippines
Four articles provided information on influenza type B in the Philippines. Three articles
reported clinic-based surveillance of patients with ILI in different regions during an
overlapping period from 2006 to 2013. The largest study in 2006-11 collected 69,108
specimens and the influenza virus detection rate varied between 6.9% (in 2008) to
33.1% (2009).44,5759 Influenza B was the predominant type circulating in 2008 (75.7%) as
well as in 2010 (50.1%).
Surveillance in Baguio city in the North and in the Eastern Visayas region during 2010-
11 showed that regional circulation of influenza viruses and predominant types varied in
the same season. Influenza detection rate among ILI patients and the proportion of
influenza B among all influenza positive samples in Baguio city (25.6% and 61.2%,
respectively) were higher than in Eastern Visayas region (16% and 54%) in 2010 but
lower in 2011 (12.3% and 22% in Boguio city, 14.6% and 37% in Eastern Visayas
region, respectively).60,61 Surveillance in Baguio city also assessed influenza among
SARI patients. In all three study years, influenza detection rates were lower among SARI
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patients than patients with ILI, while the proportion of influenza B was higher among
SARI patients with laboratory-confirmed influenza than ILI patients with laboratory-
confirmed influenza in 2009 and 2011.60
Singapore
In Singapore the National Influenza Centre carries out influenza virus surveillance using
samples from public hospitals and sentinel clinics.62 Ten articles reporting data in
Singapore from 1990 until 2012 were identified (Table 2). Four articles report the results
of the national surveillance of samples from inpatients and outpatients presenting to
sentinel centres with ILI between 1996 and 2012. The percentage of all samples with
laboratory-confirmed influenza ranged from 2.5% in 2007 to 50.4% in 2010.34,44,62,63 The
proportion of influenza-positive samples that were influenza B was lowest in 2009 (2.7%)
and highest in 2007 (79.1%).
Several studies reported influenza detection rates and proportions of influenza B viruses
in various seasons among specific groups. Among students and staff at the National
University of Singapore presenting with ILI, 21.1% had laboratory-confirmed influenza in
2007 and 32.8% in 2007-09. Though the study conducted in 2007-09 detected a higher
influenza-positivity rate, the proportion of influenza B was lower comparing to the study
in 2007 (6.7% vs.16.1%) as influenza A/H1N1pdm09 became the predominant type in
the second half of the 2007-09 study.64,65
Three studies evaluated influenza in military personnel with febrile respiratory illness in
2006-07, 2009-10, and 2009-12.6668 Influenza detection rate was 36.1% and 28.7% in
the two earlier seasons, both with the proportion of influenza B at 33%. Season-specific
influenza positivity and the proportion of influenza B after 2010 were not reported.
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South Korea
Eleven articles reported the distribution of influenza A and B viruses in South Korea
between 1990 and 2013 (Table 2). Six studies were conducted in hospital emergency or
outpatient departments, one included hospitalised children, one included adults in the
intensive care unit (ICU), and three studies reported laboratory surveillance. Between
2007 and 2015, the Korean Influenza Surveillance System reported three influenza
seasons with around 50% or higher proportion of influenza B; all three seasons had B
lineage mismatch of >20% (Table 3). The highest percentage of influenza B positive
samples was reported in a retrospective laboratory-based study in which 43.4% of
children and 55.8% of adults with laboratory-confirmed influenza had type B.69 The study
period encompassed the 2007-08 influenza season, in which 64.1% of circulating
influenza viruses were type B strains with a complete vaccine mismatch (Table 3).
Taiwan
Thirteen studies conducted between 1995 and 2012 were identified for Taiwan (Table 2).
Five articles reported data in children and no studies specifically reported on influenza B
in adults. All studies conducted before 2009 detected influenza B from the study
population but information on B lineages was not reported. The proportion of influenza-
positive samples that were type B varied across seasons, age groups, and diagnoses.
One study conducted in 2009-11 with low level of B strain mismatch found that in both
seasons the proportion of influenza B among all laboratory-confirmed influenza cases
was lower among patients hospitalized with pulmonary complications of influenza (2.9-
6.3%) comparing to patients with acute respiratory tract infection (ARTI, 13.7-17.7%).70
In the following season (2011-12) when influenza B was predominant and the circulating
B strain significantly mismatched the vaccine strain, one study reported a significantly
higher proportion of influenza B in both ILI patients with laboratory-confirmed influenza
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(72.5%) and patients of suspected influenza with complications (60.7%), suggesting that
the high proportion of influenza B together with the significant B strain mismatch (86%)
resulted in heavy morbidity in that season.71
National Influenza Surveillance by the Taiwan CDC showed that since 2009, in all but
one season, the proportion of influenza B viruses was >20% among all influenza viruses
detected, including in 2009 during the A/H1N1/pdm09 pandemic. Significant influenza B
mismatches were observed in three seasons, especially in 2011-12 when 76% of the
circulating influenza viruses were type B (Table 3).
Thailand
Influenza sentinel surveillance throughout Thailand during 2005-10 found that 15-25% of
samples from ILI patients tested positive for influenza. The highest proportion of
influenza B among all laboratory-confirmed influenza patients was 40% in 2007, while
the lowest was 13% in 2009.72
Thirteen relevant articles were identified for Thailand that reported for seasons between
1998 and 2014. One large laboratory-based surveillance study detected influenza
viruses in 18.4-25.5% of samples collected from patients with ILI between 2007-11.44,73
The percentages of influenza positive samples that were influenza B ranged from 12.9%
in 2009 to 42.9% in 2008.73
Seven articles included hospitalised patients with RTIs, pneumonia or SARI from 2003-
11. The percentage of clinical specimens with laboratory-confirmed influenza varied from
4.1% among patients hospitalized with pneumonia in 2006 to 21.1% among hospitalized
SARI patients in 2010. Among hospitalized patients, the highest proportion (45%) of
laboratory-confirmed influenza cases that were influenza B was seen in 2008, when
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circulation of influenza B predominated but with significant mismatch with the influenza B
strain included in the Southern hemisphere vaccine.74
Vietnam
National influenza surveillance using sentinel sites across Vietnam reported influenza
detection rates among ILI patients between 18% and 26% during 2006-10. In this period,
the lowest proportion of influenza B among all laboratory-confirmed influenza cases was
in 2007 and 2009 at 23%. The proportion of influenza B was highest (51.6%) in 2010
following the A/H1N1pdm09 pandemic.44,5759
There were seven published articles reporting relevant data from Vietnam. Five articles
reported influenza or ILI surveillance during various periods from 2001-13. Two studies
assessed influenza among patients hospitalised with respiratory infections. Influenza
was detected in 13.9% of patients aged 15 years or older during Sep 2009-Aug 2010,
and 28.9% of all influenza viruses detected belonged to the B type.75
Distribution of influenza B by age group
There were 22 articles that provided information on influenza B in different age groups
(Table 4). The grouping of ages differed between studies which hinders easy
comparisons.
In studies reporting age-stratified data, the proportions of influenza caused by influenza
type B were higher amongst children aged between 1 and 10 years than in older age
groups.23,30,46,50,51,56,58,59,7685 In 17 studies using comparable age strata, between 10.9%-
90% of all influenza B cases were detected in children aged <10 years (Table 4).
Considering 18 studies with a cut-off at <20 year of age, in all but one study, more than
50% (and up to 100%) of all influenza type B cases occurred in age strata that included
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children and adolescents until 20 years of age. With some exceptions, in most studies
(19/21), few influenza B cases (13.1%) were reported in adults aged 65+ years. Within
the limitations of data, the age-distribution of influenza B followed similar trends in each
country.
One study from Victoria, Australia, estimated the rate of notified laboratory-confirmed
influenza cases (reported in 2012 to the Victorian Department of Health) to be
154/100,000 persons in those aged 04 years, 137/100,000 in those aged 65 years,
and 6190/100,000 for other age groups.30 The proportion of notified cases that were
influenza B was highest in those aged 5-15 years (30.3%) and 15-29 years (20.5%),
followed by those aged 30-49 years (14.2%), 50-64 years (10.7%), <5 years (8.7%) and
65 years (8.6%).
Circulating influenza B strains
The available data indicate that both Yamagata and Victoria influenza type B lineages
have circulated in Asia-Pacific countries during the last decade. The ratio of Yamagata
to Victoria strains varied from year to year, and sometimes differed between countries in
the northern and southern hemispheres within the same season (Table 3). Furthermore,
the predominant lineage was not always the same in countries within the same region.
For example, in 2012, an influenza type B Victoria strain predominated in Australia,
whereas a Yamagata strain predominated in New Zealand (Table 3). In 2007, a
Yamagata strain predominated in Malaysia, whereas a Victoria strain predominated in
Indonesia (Table 5).
In northern hemisphere and tropical countries, mismatches with the northern hemisphere
vaccine occurred in 2004-05 in Thailand, 200506 in Malaysia, Indonesia, Myanmar and
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Thailand, 2006-07 in Thailand, 200708 in South Korea and Indonesia, 2008-09 in
China, 201112 in Taiwan, 2012-13 in Thailand, 2012-13 and 201314 in South Korea
and China, 2013-14 and 2014-15 in Taiwan.
In southern hemisphere and tropical countries, mismatches with the southern
hemisphere trivalent influenza vaccine occurred in 2005 in Australia, New Zealand,
Malaysia, Indonesia, Thailand and Myanmar, 2006 in Thailand, 2007 in Australia, New
Zealand and Malaysia, 2008 in Australia and New Zealand, 2009 in Australia, Malaysia,
Laos, Thailand and Cambodia, 2012 in New Zealand and Thailand, and 2015 in
Australia and New Zealand.
In countries that provided seasonal numerical estimates of lineage distribution, the
majority of mismatched seasons in each country were significant or complete
mismatches (Table 3 and 5). In mismatched years without precise estimates of the
distribution of type B lineages, the available descriptions suggest that all of the
mismatches were likely to be significant or complete.
Discussion
The evidence we reviewed from the published literature indicates that influenza is an
important cause of morbidity in the Asia-Pacific region and affects all age groups.
Influenza type B was identified in all 15 of the countries studied, and the proportion of
influenza B isolated in clinical specimens from different settings varied markedly from
season to season, ranging between 0% and as high as 92%. This variability is consistent
with the unpredictable seasonal influenza burden that results from co-circulation of
several types/lineages, the degree of antigenic drift, combined with the hosts’ immune
status, which together ensure the continuing ability of the virus to cause illness.9
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Significant or complete mismatches between the circulating and trivalent vaccine type B
strain were observed on numerous occasions in countries with available data. Our study
was not designed to quantify the possible public health implications in seasons where
vaccine mismatch existed. Influenza vaccine efficacy is reduced when there is a
mismatch between vaccine and circulating strains,14,86 suggesting that a mismatch
season is likely to be associated with a higher clinical disease burden.
Influenza B causes similar morbidity as influenza A.87 In mismatch seasons,
hospitalization due to influenza type B can exceed that due to influenza A in all age-
groups.71 The available data suggest that consistent with observations in other
regions,7,9 in the Asia-Pacific region influenza B occurs more frequently in children aged
between 1-10 years than in other age groups, and causes more severe disease in this
age-group than influenza A.88
Evidence suggests differences in the age distribution of patients infected with the
B/Yamagata or B/Victoria lineages, with the latter appearing to be more frequently
identified in younger age groups.8993 Although the lineage seems to have generally no
impact on the clinical outcome of the infection, recent data from Hong Kong suggested
that B/Victoria viruses may be associated with more influenza B hospitalization in
children compared with B/Yamagata viruses.94 Both the B/Yamagata and B/Victoria
lineages have been included in recommendations by WHO since September 2012 for
the southern hemisphere vaccines for 2013 and thereafter for both hemispheres, but
extensive use of quadrivalent vaccines lagged until 2015 or later and then it was mostly
used in developed countries such as USA, Japan, Australia and some European
countries. As younger children have a globally higher probability of being infected with
the influenza B viruses, this group is most likely to benefit more from a quadrivalent
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vaccine containing both B lineages due to the frequent mismatch and co-circulation of
both influenza B lineages.
The articles included in this review varied with respect to their design, population
characteristics (for example age range, mild versus severe cases), the illness definition
selected for study (specific versus non-specific diagnoses), the laboratory methods used
to detect influenza, and the methods of case surveillance (population-based, laboratory-
based, hospital or emergency department-based, sentinel general practice). Therefore,
the results of individual studies cannot be easily compared, and are unlikely to be
broadly representative. In some articles data were not stratified per year, and only an
average proportion of influenza type B over the study period could be obtained. In many
studies, proportions of influenza B among any laboratory-confirmed influenza cases
were only available within a specified population. Most information was retrieved for
China, Australia, South Korea and Taiwan, but four articles or fewer were identified for
Laos, Myanmar, the Philippines and Papua New Guinea.
This review has identified important knowledge gaps within the region. In several
countries, the epidemiology of influenza and influenza type B is not well described, little
is known about the age groups most affected by influenza type B and the relative
contribution of the two type B lineages to the disease burden. Epidemiological data for
the two circulating influenza B lineages in the Asia-Pacific region are extremely limited.
Co-circulation of Yamagata and Victoria lineages occurred in most countries where
strain surveillance data were available, with considerable fluctuation from year to year. A
variable, but substantial influenza B burden, as well as variable mismatch between
circulating lineages and vaccine lineages was observed in all countries with available
data regardless of geographical location, suggesting that a shift from trivalent to
quadrivalent seasonal influenza vaccines that include both influenza B lineages would
be beneficial in many seasons. Establishing or enhancing existing influenza surveillance
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networks in individual countries across the Asia-Pacific region is needed to contribute to
an improved understanding of the burden of influenza. Education of the medical
profession and public, vaccine implementation strategies including the development of
specific national recommendations in countries where they are lacking, and improved
access to influenza vaccines, are needed to improve influenza vaccine uptake and
reduce the influenza disease burden in Asia-Pacific countries.
Few countries in the Asia-Pacific region have policies, recommendations or funding
methods in place supporting influenza immunisation, and those that do limit publicly
funded re-imbursement to at-risk groups. Our review provides evidence of a substantial
influenza burden in the Asia-Pacific. The data suggest that countries in the Asia-Pacific
stand to benefit from development of immunisation policy targeting influenza prevention.
Additionally, quadrivalent influenza vaccines that reduce the likelihood of vaccine
mismatch among influenza type B strains are likely to provide improved protection
against influenza type B infection.
Supplementary information captions
Supplementary information 1: Search terms
Acknowledgments
The authors thank Marleen Buijssen and Eveline M. Bunge (Pallas Health research and
consultancy, on behalf of GSK) for technical support in conducting the literature search.
The authors thank Business & Decision Life Sciences platform for editorial assistance
and manuscript coordination on behalf of GSK. Jesse Quigley Jones (GSK) and
Jonathan Ghesquière (Business & Decision Life Sciences) coordinated manuscript
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development and editorial support. The authors also thank Jo Wolter (independent, on
behalf of GSK) for providing medical writing support.
Conflict of Interest
LJ is immediate-past Chairperson of the Asia Pacific Advisory Committee for Influenza
Ltd. (APACI), a Charitable Trust registered in Hong Kong. He reports unrestricted
research funding from F. Hoffman - La Roche and honoraria & travel assistance for
participating in scientific meetings from F. Hoffman - La Roche, the GSK group of
companies, Baxter and Sanofi Pasteur, outside of the submitted work. QSH, P-IL and
WJK report no conflict of interest. IB reports personal shares holding from an influenza
vaccine manufacturer (not GSK). PB, BAM and JC are employees of the GSK group of
companies and report holding hold shares in the GSK group of companies as part of
their employee remuneration. MS was an employee of the GSK group of companies at
the time of the study.
Contributorship
LJ, QSH and WJK participated in the design of the review. LJ also participated in
assembling and analysis of data and provided Asia-Pacific regional knowledge for the
interpretation of the published material collected. QSH, IB, P-IL, WJK participated in
assembling and interpreting the data. MS, P-IL and WJK participated in the analysis and
interpretation of data. PB and BAM participated in collecting, assembling, analysis and
interpretation of data. BAM also participated in the design of the review. JC participated
in the design of the review, collecting the data, the supervision of the analysis, and the
interpretation of data. All authors were involved in the development of this manuscript,
had full access to the data and gave final approval before submission.
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Sources of support
GlaxoSmithKline Biologicals SA was the funding source and was involved in design and
conduct of the study; management, analysis, and interpretation of the data; preparation,
review and approval of the manuscript and decision to submit the manuscript for
publication. Pallas was involved in the design of the study and conducted the literature
review GlaxoSmithKline Biologicals SA funded all costs associated with the development
and the publishing of the present manuscript. The corresponding author had full access
to the data and was responsible for submission of the publication. The Melbourne WHO
Collaborating Centre for Reference and Research on Influenza is supported by the
Australian Government Department of Health.
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Figure Legends
Figure 1: Countries included in the review according to climate
Northern hemisphere: temperate = dark blue, subtropical = light blue, subtropical to
tropical = yellow, tropical = orange. Southern hemisphere: tropical = red, temperate =
green.
Figure 2: Article selection procedure
WPRIM: Western Pacific Region Index Medicus. Other includes studies with sample size
<30, same data (or better quality data) provided in other articles, article in Korean
language.
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Table 1: Influenza surveillance systems and estimates of influenza vaccine coverage in fifteen Asia-Pacific countries
Country
Influenza surveillance systems
Doses
distributed
per 1,000
population*
Influenza vaccine
coverage
Recommendation
Recommending
body
Australia 19,95,96
State and Territory-based Influenza surveillance:
General Practice Sentinel Surveillance, Influenza
Complications Alert network, Emergency
Department, Hospital Mortality and Laboratory
surveillance
299.73 (2013)
39% of adults 18yrs,
73% of 65+ (2014)
All individuals from
6 months
Australian
Technical
Advisory Group
on Immunisation
Cambodia32,33,97
National Influenza Center: ILI sentinel surveillance
and hospitalbased ALRI surveillance since 2006
2.21 (2013)
12% among ILI patients
(May 2010-Dec 2012)
None
Ministry of Health
China1719,98100
National Influenza Center: ILI sentinel and hospital-
based surveillance since 2000
7.81 (2013)
9.0% (2011) overall,
7.4% in 60+yrs
9.4% chronic disease
9.5% healthcare workers
26% in children
16 doses/1000 in
Shanghai (Zhao 2015)
Highest (108 doses/1000
population) in Beijing
where vaccination is free
or subsidised for some
age groups
Healthcare workers,
elderly 60+,
pregnant women,
children from 6 yrs
National Health
and Family
Planning
Commission
Indonesia45,101
ILI sentinel surveillance, enhanced surveillance for
seasonal and avian influenza in East Jakarta
1.81 (2011)
No reports identified
Prior to Hajj
Indonesian
Technical
Advisory Group
on Immunization,
Indonesian
Pediatrician
Association, Adult
Immunisation
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Task Force,
Medicine
Specialist
Association of
Indonesia
Laos19,98
Laboratory based surveillance from 2007, hospital-
based surveillance (3-8 sites) of pneumonia from
2008. Department of Health
15.21 (2013)
No reports identified
Healthcare workers,
elderly 50+,
pregnant women,
chronic disease,
children
Ministry of Health
Malaysia19,98,102
Sentinel surveillance for ILI (OPD) and SARI
(hospital) Coordinated by the
Surveillance Sector, Disease Control Division,
Ministry of Health
7.48 (2013)
7.2% of HCW in 2011
Healthcare workers,
chronic disease,
elderly with 1
chronic disease,
Hajj pilgrims
Ministry of Health
Myanmar101
None
None recorded
(2001)
No reports identified
-
-
New Zealand19,103,104
National Influenza surveillance: General Practice
Sentinel Surveillance of ILI, Laboratory-based
surveillance
312.5 (2013)
67.5% of 65+ (2014),
66% of healthcare
workers (2015)
All individuals from
6 months
Ministry of Health
Philippines19,98,105
Sentinel surveillance for ILI (outpatient) and SARI
(outpatient and hospital-based), laboratory-based
surveillance, Department of Health
35.28 (2013)
No reports identified
Healthcare workers,
chronic disease,
elderly 60+,
pregnant women,
children (6m -
18yrs)
Department of
Health. Input and
advice from
Philippine Society
for Microbiology
and Infectious
Diseases,
Pediatric
Infectious
Disease Society
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of the Philippines,
Philippine
Foundation for
Vaccination
PNG19,98
PNG National Influenza Centre, ILI surveillance in
2 hospitals
0 (2013)
No reports identified
None
Ministry of Health
Singapore19,62,98,106,107,
Outpatient (polyclinic and ED) attendance and
admissions for ARI, influenza virus surveillance by
National Influenza Centre
78.48 (2013)
30.6% among diabetics
(2007)
Healthcare workers,
chronic disease,
elderly 65+,
pregnant women,
children (6m - 5yrs),
Children 6-18m on
long-term aspirin,
residents of nursing
homes
Ministry of Health
South Korea19,108112
Korean Influenza Surveillance System (KISS) (ILI
surveillance at 630 sentinel clinics and 396
laboratories), Hospital-based Influenza Morbidity
and Mortality (HIMM) and inpatient surveillance
(ED surveillance)
335.7 (2013)
34.3% in the general
population, 61.3% high
risk groups (2005),
82.4% of 65+ year olds
(2016)
Elderly 65+,
pregnant women,
chronic diseases,
children 6m-5yrs,
residents of nursing
homes and long-
term care facilities,
healthcare workers,
children 6m-18yrs
on long-term aspirin,
adults 50-64yrs,
household contacts
and caregivers
those at risk
Centers for
Disease Control
and Prevention
Taiwan113,114
Taiwan National Influenza Surveillance System
(NISS): laboratory surveillance,
sentinel ED and OPD ILI surveillance, case-based
surveillance of influenza with complications and
deaths
40% <3 yrs of age
80% in adults (2012)
All individuals from
6 months
Centers for
Disease Control
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Thailand 72,101,115117
Sentinel surveillance for ILI (outpatient) and SARI
(hospital-based), Thai National Institute of Health
103.3 (2011)
30% of 6m-2yrs (2011-
2012), 9% of 50s
hospitalised with ARI
Healthcare workers,
65+ underlying
disease, children
6m-2yrs, pregnant
women, obese
Ministry of Public
Health
Vietnam59,98,101
National Influenza Surveillance System (NISS)
since 2006. Sentinel surveillance for ILI
(outpatient)
None recorded
No reports identified
Healthcare workers,
chronic disease,
elderly 65+, children
from 6m
Ministry of Health
CAP: Community-acquired pneumonia; ED: Emergency department; HCAP: Healthcare-associated pneumonia; ICU: Intensive care unit; ILI: Influenza-like illness;
LRTI: Lower respiratory tract infections; NA: Not applicable; OPD: outpatient department; PNG: Papua New Guinea; P&I: pneumonia and influenza; RTI: respiratory
tract infection; SARI: Severe acute respiratory illness
*pertains to trivalent influenza vaccines
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Table 2: Articles reporting the proportion of influenza B among all laboratory-confirmed influenza
Author
Design
Study years
Patient population
Number tested
for influenza
Number (n)
(proportion, %) of
N with laboratory-
confirmed
influenza
Number (n)
(proportion, %) of
type B among all
laboratory-
confirmed
influenza
Australia
Roche 2002118
Passive-laboratory-based
surveillance
1991-2000
Laboratory reports (nationwide network)
340,730
16,805 (4.9, 4.6-
87.2 annually)
3,614 (21.5, 12.8-
95.4 annually)
Teichtahl 1997119
Case-control study
Aug 1993-July 1994
Hospitalised adults with asthma exacerbation
79
20 (25.2)
2 (10.0)
Moore 2009120
Retrospective descriptive
May 1997-Dec 2005
Specimens from children <18yrs (1 hospital)
32,741
specimens
1,951 (6.0)
304 (15.6)
Kelly 2000121
Prospective laboratory-supported
surveillance
1998-1999
Patients with ILI (17-26 general practitioners)
152
65 (42.8)
3 (4.6)
Caini 201534
Prospective national surveillance of
patients with ILI
2001-2012
Laboratory-confirmed influenza
179,137
179,137(100)
28,700 (16.0)
Druce 200523
Prospective hospital-based
surveillance
May-Sept
2002 & 2003
Hospitalised patients with respiratory illness
3,095
Only data by age
55 (1.8)
Specimens collected from state-wide influenza
surveillance programme
1,159
-
133 (11.5)
Fielding 200725
Prospective surveillance
May-Oct 2006
Patients with ILI (74 general practitioners)
384
126 (32.8)
15 (11.9)
Iskander 200924
Prospective hospital-based
surveillance
June-Oct 2006
Hospitalised children <5yrs with ILI (1 hospital)
273
31 (11.4)
9 (29.0)
Lambert 200826
Prospective hospital-based
surveillance
July 2006-Aug 2007
Children with ARI presenting to hospital (1
hospital)
303 specimens
(295 patients)
37 (12.2)
7 (18.9)
Lester-Smith
200928
Retrospective descriptive
Jan-Dec 2007
Hospitalised children with influenza (1 hospital)
122
122 (100)
3 (2.5)
Miller 200827
Prospective surveillance
Apr-Sept 2007
Patients with ILI (21 sentinel general practices)
403
189 (46.9)
24 (12.7)
Notified laboratory-confirmed influenza
1,343
1,343 (100)
186 (13.8)
Grant 2011122
Prospective and retrospective
surveillance
2010
Patients with ILI (32 general practices)
478
170 (35.6)
4 (2.4)
Notifications of laboratory-confirmed influenza to
Health Department
1,914
1,914 (100)
88 (4.6)
Macesic 2013123
Prospective hospital-based
surveillance
April-Nov 2010 &
2011
Community-acquired influenza (8-15 hospitals)
572
572 (100)
58 (10.1)
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Nosocomial influenza
26
26 (100)
2 (7.7)
Levy 201429
Prospective surveillance
2010-2012
Patients with ILI (31-57 general practices)
448 (2010)
351 (2011)
1361 (2012)
146 (32.6)
84 (29.9) (2011)
603 (44.3) (2012)
56 (38.4) (2010)
18 (20.7) (2011)
259 (43) (2012)
Fielding 201330
Prospective surveillance
2012
Patients with ILI (41 general practices)
709
280 (39.5)
38 (13.6)
Notified laboratory-confirmed influenza
5,058
5,058 (100)
745 (14.7)
Influenza complications network
389
389 (100)
50 (12.8)
Sullivan 2014124
Prospective surveillance
2012
Patients with ILI (110 General practices nationally)
1,414
593 (41.9)
106 (17.9)
Jennings 2015125
Prospective surveillance
15 Jun-12 Jul 2015
Laboratory-confirmed influenza (13 laboratories in
New South Wales)
1,234
1,234 (100)
821 (66.5)
1 Apr-18 Jul
Laboratory-confirmed influenza presenting to
Emergency Departments (4 hospitals)
88
88 (100)
41 (46.6)
WHO 55
Prospective national surveillance
Jan-Sept 2015
Laboratory-confirmed influenza
Not given
-
(61%)
Laboratory-confirmed influenza from general
practices
2,565
(30.9%)
(64%)
Hospitalised laboratory-confirmed influenza
-
-
(52%)
Cambodia
Buecher 201031
Prospective hospital-based
surveillance
Feb-May 2005-2007
Patients with ILI during dry season (5 hospitals)
234
4 (1.7)
2 (50)
Mardy 200932
Prospective hospital- and clinic-
based surveillance
2006-2008
Patients with ILI (5 outpatient departments) and
ALRTI (2 hospitals) (2007-08)
3,148 (ILI)
1,868 (ALRI)
338 (10.7) (5.8-15.3
annually)
64 (3.4) (1.4-3.6
annually)
ILI & ALRTI
148 (43.8) (34-57.7
annually)
Kasper 2012126
Prospective hospital-based
surveillance
Dec 2006-Dec 2009
Acutely ill patients with fever (9 hospitals in South-
central Cambodia)
9,968
1,983 (19.9)
631 (31.8)
Saha 201444
Prospective clinic-based surveillance
2006-2011
Patients with ILI at sentinel centres
10,105
1,574 (15.6) (7.6-
18.8 annually)
(22.9-65.6)
(annually)
Horm 201433
Prospective hospital-based
surveillance
2009-2011
Patients with ILI (11 sites nationally) and
ALRTI (2 hospitals)
7,376 (ILI)
2,248 (ALRI)
1,262 (16.9) (14.5-
18.7 annually)
59 (2.6 (1.5-3
annually)
ILI & ALRTI
515 (30.6) (12.6-
64.8 annually)
Timmermans
201697
Prospective surveillance
May 2010-Dec 2012
Patients with ILI (4 sites in Western Cambodia)
586
168 (29.7)
76 (45.2)
China
Cheng 201335
Prospective hospital- and clinic-
1995-2009
Patients with URTI until 2003 (8 sites), ILI after
25,377
2,678 (10.6) (0.2-25
757 (28.3) (2-79
Accepted Article
This article is protected by copyright. All rights reserved.
based surveillance (Shenzhen)
2003 (22-31 sites)
annually)
annually)
Tang 2008127
Prospective hospital-based
descriptive (Gangzhou)
Jan-2001-Dec 2006
Hospitalised children <14 yrs with ALRI
34,885
760 (2.2)
72 (9.5)
Lin 201336
Prospective hospital and laboratory-
based surveillance (Guangdong)
Jan 2004-Dec 2012
Patients with ILI (14 hospitals)
107,115
17,454 (16.3)
4,978 (28.5)
ILI outbreak surveillance
919 outbreaks
828 outbreaks
(90.1)
Multiple B
outbreaks in 2005,
2007, 2010, 2012
Caini 201534
Prospective national ILI surveillance
2006-2012
Laboratory-confirmed influenza (South)
122,215
122,215 (100)
35,910 (29.4)
2005-2011
(North)
64,306
64,306 (100)
19,956 (31.0)
Yang 2012128
Prospective outpatient surveillance
(Beijing)
May 2006-Jan 2010
Patients 14 yrs with ARI (1 hospital)
7,776
1,854 (23.8)
405 (21.8)
Ji 2010129
Retrospective hospital based
descriptive (Suzhou)
Jan 2007-Dec 2008
Hospitalised children <5 yrs respiratory infection (1
hospital)
7,789
120 (1.5)
25 (20.8)
Yang 200937
Prospective outpatient and ED
surveillance (Beijing)
Sept 2007-Apr 2008
Patients with ILI (14 hospitals)
2,057
611 (29.7)
450 (73.6)
Guo 2012130
Prospective outpatient surveillance
(Zhuhai City)
2008
Patients with ILI (28 hospitals)
1,485
135 (9.1)
(23.7)
2009
2,144
604 (28.2)
(9.1)
Peng 2012131
Prospective hospital-based
surveillance (Wuhan)
Jul 2008-Jun 2010
Children 14 yrs with ILI (1 hospital)
1,472
455 (30.9)
100 (22.0)
Ge 201238
Prospective outpatient surveillance
(Shanghai)
Jun 2009-May 2011
Children with ILI (1 hospital)
2,356
608 (25.8)
142 (23.4)
Lu 2013132
Prospective descriptive (Jinan)
Aug 2009-Sept 2010
Patients 14 yrs with ARI (1 hospital)
596
124 (20.8)
75 (60.5)
Wei 201340
Prospective hospital-based
surveillance
Apr 2009-Mar 2011
Patients with ILI
6143
1,645 (26.8)
348 (21.2)
Zhu 2013133
Laboratory-based descriptive (Hubei
& Zhejiang)
2009-2010
Patients with respiratory infection (inpatients and
outpatients)
341
54 (15.8)
18 (33.3)
Zhao 201541
Prospective outpatient surveillance
(Shanghai)
2009-2014
Patients with ILI
71,354
19,974 (28.0)
6,688 (33.5)
Li 2013134
Prospective outpatient surveillance
(Zhuhai City)
Jan-Dec 2010
Patients with ILI (1 hospital)
924
187 (20.2)
96 (51.3)
Yu 201339
Prospective hospital-based
surveillance (Jingzhou City)
2010-2012
Hospitalised patients with SARI (4 hospitals)
16,208
2,057 (12.7)
998 (48.5)
Huo 2012135
Prospective outpatient surveillance
(Nanjing)
Nov 2010- Oct 2011
Patients with ILI (2 hospitals, 1 laboratory)
486
178 (36.3)
37 (20.8)
Accepted Article
This article is protected by copyright. All rights reserved.
Chen 2014136
Prospective hospital-based
surveillance (Changsha)
2010-2012
Patients with ILI (2 hospitals)
2,955
278 (9.4)
83 (29.9)
Wang 2014137
Retrospective modelling study
(Gangzhou)
Jan 2010-Dec 2012
Patients with ILI
8,258
1,081 (13.1)
360 (33.3)
Yu 2012138
Prospective hospital-based
descriptive (Beijing)
May 2010-Apr 2011
Patients 14 yrs in ED with ARI (1 hospital)
416
70 (16.8)
3 (4.3)
Fu 2015139
Prospective clinic-based surveillance
(Shanghai)
Jan 2011-Dec 2013
Patients with ILI (2 hospitals)
1,970
392 (19.9)
162 (41.3)
Ju 2014140
Prospective hospital descriptive
(Huizhou)
Jul 2011-Jul 2013
Hospitalised patients with ILI (1 hospital)
1,046
209 (20.0)
74 (35.4)
Wang 2016141
Prospective hospital-based
surveillance (Suzhou))
Apr 2011-Mar 2014
Children <5 yrs with ILI presenting to outpatient or
ED
3,662
619 (16.9)
349 (56.4)
Indonesia
Beckett 200442
Laboratory-based surveillance
Aug 1999-Jan 2003
Children >4 and adults with ILI at 6 sentinel centres
1,372
130 (9.5)
33 (25.4)
Kosasih 201343
Prospective health centre and
hospital-based
surveillance
Jan 2003-Dec 2007
Inpatients and outpatients with ILI at 5 (2003) to 48
(2006-07) sentinel centres
21,030
4,236 (20.1)
1,487 (35.1)
Caini 201534
Prospective national surveillance of
patients with ILI
2003-2007
Laboratory-confirmed influenza
3,653
3,653 (100)
1,314 (36.0)
Saha 201444
Prospective clinic-based surveillance
2010-2011
Patients with ILI at sentinel centres
15,150
specimens
2,511 (16.6)
(49.9 in 2010, 24.8
in 2011)
Storms 201545
Enhanced prospective surveillance in
East Jakarta
Oct 2011-Sept 2012
Patients with ILI at 4 outpatient clinics
3,278
1,131 (34.5)
536 (47.4)
Patients with SARI at 6 hospitals
1,787
276 (15.4)
132 (47.8)
Laos
Vongphrachanh
201047
Prospective hospital-based
surveillance
Jan 2007-Dec 2008
Patients with ILI presenting to hospital OPD/ED (3
hospitals)
526
155 (29.5)
92 (59.3)
Aug-Dec 2008
Hospitalised ALRTI
79
10 (12.7)
4 (40.0)
Khamphaphongph
ane 201346
Laboratory-based surveillance
Jan 2008- Dec 2010
Patients with ILI presenting to hospital OPD/ED (7
hospitals)
2,338 specimens
523 (22.4) (20.9-23
annually)
142 (27.7) (2.7-66.7
annually)
Saha 201444
Prospective clinic-based surveillance
2006-2011
Patients with ILI at sentinel centres
5,949
1,302 (21.9) (12.8-
29.8 annually)
(2.2-56.5 annually)
Sentilhes 201348
Prospective hospital-based
surveillance
Aug 2009-Oct 2010
Patients hospitalised with ALRTI
292 specimens
23 (7.9)
5 (21.8)
Malaysia
Chan 1999142
Retrospective descriptive
Jan 1982-Dec 1997
Children <24 months with LTRI
5,697
77 (1.4)
18 (23.4)
Accepted Article
This article is protected by copyright. All rights reserved.
Khor 201281
Retrospective hospital-based
descriptive
1982-2008
Samples from hospitalised children 5yrs (1
hospital)
10,269
297 (2.9)
64 (21.9)
Sam 2015143
Laboratory-based surveillance
1995-2008
Laboratory-confirmed influenza 1 month to 49 yrs
338
338 (100)
88 (26.0)
Sam 2010144
Retrospective descriptive
2002-2007
Hospitalised children <15 yrs with laboratory-
confirmed influenza
132
132 (100)
35 (26.5)
Saat 201049
Prospective laboratory-based
surveillance
Jan 2005-Dec 2009
Patients with ILI (nationwide)
7,117 specimens
993 (14.0) (10.2-
31.6 annually)
305 (30.7) (18-51
annually)
Saha 201444
Prospective clinic-based surveillance
2006-2011
Patients with ILI at sentinel centres
10,323
894 (8.7) (3.1-13.4
annually)
(20.2-62.6, 2006-
2010)
Myanmar
Hasegawa 200650
Prospective hospital-and clinic-based
surveillance
Sept 2003-Dec 2004
Patients with ILI (1 hospital, 2 general
practitioners)
616
139 (22.6)
6 (4.3)
Hasegawa 200651
Prospective hospital-and clinic-based
surveillance
2005
Patients with ILI (1 hospital, 2 general
practitioners)
992
268 (27.0)
125 (46.6)
Dapat 200952
Prospective hospital-and clinic-based
surveillance
2005-2007
Patients with ILI (1 hospital, 1 clinic)
2,618
522 (19.9) (24 in
2005, 11.4 in 2006,
19 in 2007)
267 (51.1) (42 in
2005, 0 in 2006, 67
in 2007)
New Zealand
Huang 200853
Prospective national surveillance
1997-2006
All influenza diagnoses sentinel general practice,
laboratory, hospital, and mortality surveillance
-
Average 718
annually
(0-92 annually)
Laing 2001145
Prospective hospital-based
surveillance
Jul 1999-Jul 2000
Hospitalised adults >18 with CAP
474
39 (8.2)
8 (20.5)
Caini 201534
Prospective national surveillance of
patients with ILI
2000-2012
Laboratory-confirmed influenza
17,629
17,629 (100)
2,965 (16.8)
Jennings 2004146
Prospective hospital-based
descriptive
Jul-Nov 2001
Children with ARI (1 hospital)
75
10 (13.3)
7 (70.0)
Huang 200754
Prospective national surveillance
2005
Laboratory-confirmed influenza sentinel general
practice, laboratory and hospital-based
surveillance
845
845 (100)
734 (86.9)
Turner 2014147
Prospective hospital-and clinic-based
surveillance
Apr-Sept 2013
Patients with ILI (18 sentinel general practices) and
SARI (4 hospitals)
1,298 (ILI)
886 (SARI)
182 (21)
391 (30)
ILI&SARI
221 (39)
WHO 55
Sentinel ILI & SARI and laboratory
surveillance
Jan-Sept 2015
Laboratory-confirmed influenza
Not given
5,235 (100)
680 (13%)
Patients with ILI
SARI patients
1,389
1,206
614 (44.2%)
285 (23.6)
308 (50%)
Not mentioned
Philippines
Accepted Article
This article is protected by copyright. All rights reserved.
Saha 201444
Prospective clinic-based surveillance
2006-2011
Patients with ILI at sentinel centres
69,108
12,607 (18.2) (6.9-
33.1 annually)
(Range 2.3-75.7)
Suzuki 2012148
Prospective descriptive
May 2008-May 2009
Hospitalised children 8 day-13yrs with severe CAP
(1 centre)
819
29 (3.5)
11 (37.9)
Tallo 201460
Prospective clinic-based surveillance
Jan 2009-Dec 2011
Patients with ILI and SARI at sentinel centres
5915 (ILI)
2659 (SARI)
1282 (21.7)
(12.3-25.6
annually)
226 (8.5) (6-11.2
annually)
397 (31.0) (6-61.2
annually)
72 (31.9) (11.4-49.4
annually)
Otomaru 201561
Prospective clinic-based surveillance
Jan 2010-Mar 2013
Patients with ILI at sentinel centres
2,031
225 (11.1) (3.2-16.0
annually)
104 (46.2) (23.8-
81.3 annually)
PNG
Kono 201456
Prospective surveillance
2010
Patients with ILI (2 hospitals)
300
88 (29.3)
38 (43.2)
Singapore
Chew 199882
Retrospective descriptive
Sept 1990-Sept 1994
Patients tested for respiratory pathogens (2
hospitals)
12,354
specimens
426 (3.4)
92 (21.6)
Chow 200662
Retrospective surveillance
Jan 1996-
Dec 2003
Samples from outpatients or inpatients with ILI
(National Influenza Centre)
57,060
specimens
3,829 (6.7)
333 (13.9)
Yang 201163
Retrospective surveillance
2004-2006
Samples from outpatients or inpatients with ILI
(Ministry of Health)
29,329
specimens
1,291 (5.5)
305 (23.6) (16.3-
33.0 annually)
Seah 201068
Prospective descriptive
Mar 2006-Apr
2007
Military personnel with febrile respiratory illness (1
camp)
1,354 specimens
489 (36.1)
159 (32.5)
Virk 201465
Prospective surveillance
May-Oct 2007
Students and staff with ILI (National University of
Singapore)
266
56 (21.1)
9 (16.1)
Tan 201564
Prospective surveillance
2007-2009
Students and staff with ILI (National University of
Singapore)
500
164 (32.8)
11 (6.7)
Saha 201444
Prospective clinic-based surveillance
2007-2011
Patients with ILI at sentinel centres
55,449
12,801 (23.1)
(2.7-79.1 2007-
2011)
Caini 201534
Prospective national surveillance of
patients with ILI
2007-2012
Laboratory-confirmed influenza
12,001
12,001 (100)
2,311 (19.3)
Yap 201267
Prospective descriptive
May 2009-June 2010
Military personnel with febrile respiratory illness (4
camps)
2,858
821 (28.7)
269 (32.8)
Tan 201466
Prospective surveillance
May 2009-Oct 2012
Military personnel with febrile respiratory illness (5
camps)
7,733
972 (12.6)
449 (46.2)
South Korea
Yun 199578
Prospective hospital-based
Nov 1990-Apr 1994
Children with ALRI + children visiting the OPD or
804 specimens
42 (5.2)
11 (26.2)
Accepted Article
This article is protected by copyright. All rights reserved.
descriptive
with nosocomial ALRI
(712 patients)
Lee 2007149
Prospective clinical & laboratory-
based surveillance
Sept 2000-Oct 2001
Patients with ILI
2,972
144 (4.8)
0 (0)
Kim 200877
Retrospective descriptive
Mar 2004-Dec 2005
Hospitalised children <15 yrs with LRTI with NPA
400
76 (19)
32 (42.1)
Seo 201469
Retrospective laboratory-based
descriptive
Jan 2005-Dec 2008
Children <19 years with ARI
21,641
specimens
1116 (5.2)
484 (43.4)
Adults with ARI
2,165 specimens
217 (10.0)
121 (55.8)
Choi 2012150
Prospective descriptive
Mar 2010-Feb 2011
Adults 18 yr in ICU with severe CAP or HCAP
198
12 (6.1)
1 (8.3)
Noh 2013151
Prospective hospital-based
surveillance
Sept 2011-Jun 2012
Adults 18 yrs who visited an ED with ILI
1,983
846 (42.7)
169 (20.0)
Song 201376
Prospective ED-based surveillance
Oct 2011-Sept 2012
Laboratory-confirmed influenza
7,213
7,213 (100)
3,217 (44.6)
Wie 2013152
Prospective ED-based surveillance
Oct 2011-May 2012
Adults with ILI
2,129
850 (39.9)
194 (22.8)
Seo 2014153
Prospective ED-based surveillance
Oct-2011-June 2012
Patients with ILI at ED
4,490 tested
Not given
Max 58% of weekly
samples
Choi 2015154
Retrospective case control
Sept 2011-May 2012
Patients visiting hospital with ILI
7,390 tested
1,130 (15.3)
452 (40)
Ahn 2015155
Retrospective laboratory-based
descriptive
Jan 2012-Apr 2013
Adults >16 tested for respiratory viruses
291 specimens
(282 patients)
47 (16.1)
4 (8.5)
Taiwan
Lin 200480
Prospective hospital-based
descriptive
Aug 1995-July 1997
Paediatric outpatients with URTI
910
112 (12.3)
58 (51.8)
Tsai 200179
Prospective hospital and clinic-based
Surveillance
Jan 1997-Dec 1999
Children <12yrs with RTI (inpatients and
outpatients)
6,986
565 (8.1)
181 (32.0)
Huang 2009156
Retrospective descriptive
Jan 1997-May 2007
Laboratory-confirmed influenza
2,651
2,651 (100)
1,168 (44.1)
Hu 2004157
Retrospective descriptive
Jan 2000-Dec 2001
Children with laboratory-confirmed influenza
197
197 (100)
124 (62.9)
Shih 2005158
Prospective laboratory surveillance
Oct 2000-Mar 2004
Patients with suspected RTI (inpatients and
outpatients)
32,775
3,244 (9.9)
1,2.75 (39.3)
Chi 2008159
Retrospective hospital-based
descriptive
Jan 2001-Dec 2006
Children with LRTI (inpatients and outpatients)
20,405
specimens
745 (3.7)
118 (15.8)
Jian 2008160
Prospective laboratory surveillance
2003-2006
Patients with suspected RTI (inpatients and
outpatients)
34,312
4,007 (11.7)
1,336 (33.3)
Lin 2013161
Prospective laboratory and sentinel
physician-based surveillance
2003-2007
Patients with URTI or LRTI symptoms
12,190
1,150 (9.4)
651 (56.6)
Jian 2008162
Prospective laboratory surveillance
2004-2005
Laboratory-confirmed influenza
1,183
1,183 (100)
971 (82.1)
2006-2007
1,534
1,534 (100)
1,219 (79.5)
Wang 2009163
Retrospective and prospective
descriptive
Nov 2006-Feb 2007
Children <18 yrs with ILI (inpatients, ED,
outpatients)
198 specimens
(196 children)
101 (51.0)
87 (86.1)
Chen 201270
Prospective hospital-based
Jan 2009-March
Children <24 months hospitalised with bronchiolitis
113
5 (4.4)
0 (0)
Accepted Article
This article is protected by copyright. All rights reserved.
descriptive
2011
Chuang 2012113
Prospective national surveillance
2009-2010
Samples from patients with ARTI
14,788
specimens
3,970 (26.9)
545 (13.7)
2010-2011
Samples from patients with ARTI
11,813
specimens
2,767 (23.4)
489 (17.7)
2009-2010
Patients with influenza hospitalised with
1,297
1,297 (100)
82 (6.3)
2010-2011
pulmonary complications
1,751
1,751 (100)
50 (2.9)
Lo 201371
Prospective national surveillance
Jun 2011-Jun 2012
Outpatients with ILI
14,943
3,285 (22.0)
2, 382 (72.5)
Suspected influenza with complications
2,675
1,704 (63.7)
1,034 (60.7)
Thailand
Suzuki 1997164
Prospective surveillance
Each August
1991-1994
Patients with suspected influenza (2 hospitals)
186 specimens
32 (17.2)
11 (34.4)
Sirivichayakul
2000165
Prospective descriptive
June 1998-May 1999
Nursing students with ILI (University)
106
35 (33.0)
2 (5.7)
Thawatsupha
2000166
Prospective hospital-based
surveillance
Jan-Dec
2001
Outpatients with ARI (6 hospitals)
711 specimens
338 (54.6)
102 (30.2)
Olsen 201084
Prospective hospital-based
surveillance
Sept 2003-Dec 2005
Hospitalised patients with acute LRTI
(all hospitals in 2 provinces)
3,910
586 (15.0)
150 (25.6)
Suntarattiwong
2007167
Prospective descriptive hospital-
based study
July 2004-July 2005
Hospitalised children 0-5yrs with LRTI (1 hospital)
456
39 (8.6)
5 (12.8)
Chittaganpitch
201172
Prospective surveillance
2004-2010
Patients with ILI at 11 sentinel centres,
19,121
3,896 (20.4) (15-25
annually*)
1,284 (33.0 range
13-43*)
Sep-Dec 2010
Inpatients with SARI at 3 hospitals
336
71 (21.1)
20 (28.2)
Simmerman 200974
Prospective hospital-based
surveillance
Jan 2005-Dec 2008
Hospitalised patients with pneumonia (all hospitals
in 2 provinces)
13,119
1,391 (10.6)
(4.1-16.0 annually)
444 (31.9) (range
13.6-44.9 per year)
Hara 2011168
Hospital based descriptive
2006-2008
Hospitalised patients with CAP (hospital and HIV
centre)
119
7 (5.9)
1 (14.3)
Saha 201444
Prospective clinic-based surveillance
2007-2011
Patients with ILI at sentinel centres
17,421
3,802 (21.8) (18.4-
25.5 annually)
(12.9-42.9)
Baggett 201283
Prospective active, population-based
surveillance
Jan 2009-Dec 2010
Hospitalised patients with acute LRTI (all hospitals
in 2 provinces)
7,207
902 (12.5)
120 (13.3)
Prachayangprecha
2013169
Prospective hospital-based
surveillance
Jun 2009-Jul 2012
Patients with ILI attending hospitals in Bangkok
6,050
2,969 (49.0)
3% of tested
samples
Dawood 2014115
Prospective hospital-based
surveillance
July-Dec 2010, 2011
Hospitalised patients with ARI
(all hospitals in 2 provinces)
1,545
279 (18.1)
32 (11.5)
Tewawong 201573
Laboratory-based surveillance
Jan 2010-Feb 2014
Samples from patients with ILI (3 provinces)
14,418
specimens
3,050 (21.2)
471 (15.4)
Accepted Article
This article is protected by copyright. All rights reserved.
Vietnam
Prospective laboratory-based
surveillance
Nguyen 200757
2001-2003
Outpatients with ILI (12 centres)
4,708
119 (2.5)
59 (49.6) (range 0-
77)
Do 2011170
Prospective hospital-based
descriptive
Nov 2004-Jan 2008
Hospitalised children <15 yrs with ARI (1 centre)
309
51 (16.5)
24 (47.1)
Nguyen 200958
Prospective hospital and clinic-based
surveillance
Jan 2006-Dec 2007
Outpatients with ILI (15 clinics)
11,082
2,112 (19.1)
585 (27.7)
Nguyen 201359
Prospective surveillance
Jan 2006- Dec 2010
Outpatients with ILI (7-15 centres)
29,804
6,616 (21.9) (18-26
annually)
2,163 (33.2) (23.3-
51.6 annually)
Saha 201444
Prospective clinic-based surveillance
2006-2011
Patients with ILI at sentinel centres
29,499
5,241 (17.8)
(Range 0-41.3.8)
Caini 201534
Prospective national surveillance of
patients with ILI
2006-2013
Laboratory-confirmed influenza
8,647
8,647 (100)
3011 (34.8)
Takahasi 201375
Prospective descriptive
Sept 2009-Aug 2010
Hospitalised patients 15 yrs with LRTI (1 centre)
323
45 (13.9)
13 (28.9)
WHO Western Pacific region
14 countries171
Regional ILI and laboratory
surveillance
2006
Data from national influenza centres (patients with
ILI)
65,103
7,425 (11.4)
3,032 (40.8)
2007
92,939
11,143 (12.0)
3,846 (34.5)
2008
94,274
11,025 (11.7)
3,599 (32.6)
2009
366,164
115,554 (31.6)
4,886 (4.2)
2010
307,584
51,573 (16.8)
25,565 (49.6)
A(L)RTI: acute (lower) respiratory tract infection; CAP: Community-acquired pneumonia; ED: Emergency department; GP: general practice; HCAP: Healthcare-
associated pneumonia; HIV: human immunodeficiency virus; ICU: Intensive care unit; ILI: Influenza-like illness; LRTI: Lower respiratory tract infections; NPA:
nasopharyngeal aspirate; OPD: outpatient department; PNG: Papua New Guinea; P&I: pneumonia and influenza; RTI: respiratory tract infection; SARI: Severe acute
respiratory illness
*Percentage from 2004 data not taken as only 11 subjects included in the 2004 surveillance.
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Table 3: Circulating and vaccine influenza type B lineages in northern and southern hemisphere temperate/subtropical
countries
Year
Vaccine
lineage
%
type
B
Circulating lineage
(%)
Degree of
mismatch
%
type
B
Circulating lineage (%)
Degree of
mismatch
%
type
B
Circulating
lineage
(%)
Degree of
mismatch
Victoria
Yamagata
Victoria
Yamagata
Victoria
Yamagata
Northern hemisphere
countries
South Korea (surveillance172)
Taiwan (surveillance 173)
China (clinical samples41, surveillance90)
2007-08
Victoria
64.1
0
100
Complete
-
-
-
-
73.6
-
Dominant
-
2008-09
Yamagata
1.2
Reported
Reported
-
-
-
-
-
-
74
26
Significant
2009-10
Victoria
26.4
100
0
-
32
91
9
-
-
-
-
-
2010-11
Victoria
0.9
Reported
Reported
-
21
83
17
-
-
-
-
-
2011-12
Victoria
48.5
73
27
Partial
76
14
86
Significant
-
-
-
-
2012-13
Yamagata
5.6
65
35
Significant
2
13
87
-
-
97
3
Complete
2013-14
Yamagata
53
86
14
Significant
25
81
19
Significant
-
-
97
-
2014-15
Yamagata
37
-
-
-
26
55
45
Significant
-
-
98
-
Southern hemisphere
countries
Australia (surveillance2022)
New Zealand (surveillance55,174)
2005
Yamagata
23
51
49
Significant
87
82
18
Significant
2006
Victoria
35
94
6
-
1
60
40
Significant
2007
Victoria
7
21
79
Significant
23
1
99
Complete
2008
Yamagata
67
51
49
Significant
58
77
23
Significant
2009
Yamagata
1
62
38
Significant
0
0
0
-
2010
Victoria
7
91
9
-
1
100
0
-
2011
Victoria
38
98
2
-
50
98
2
-
2012
Victoria
33
89
11
-
14
16
84
Significant
2013
Yamagata
37
7
93
-
40
1
99
-
2014
Yamagata
4
10
90
-
11
4
96
-
2015
Yamagata
62
36
64
Partial
51
48
52
Significant
Shading indicates mismatch years. Partial mismatch: between 20% - <40% of circulating influenza type B strain was not the vaccine strain; significant mismatch 40%;
complete mismatch 95%; -: no data, or not a mismatch year. Degree of mismatch not categorised for countries/seasons without numerical lineage distribution
estimates.
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Table 4: Age distribution of confirmed influenza B cases (as a percentage of all influenza B)
Country
Data source
N. of influenza
Age distribution (years)
B cases
<5
5-9
10-19
20-49
50-64
65
Australia
Surveillance (Notified influenza cases) 30
745
6.4
45 (5-14)
46 (15-49)
10
13
GP surveillance 30
38
5
24 (5-14)
63 (15-49)
5
3
Surveillance (Complications alert network) 30
50
10
8 (5-14)
44 (15-49)
8
30
Clinical samples 23
55
0
10.9
0
34.5
34.5
20.0
Surveillance 23
133
4.5
10.5
35.3
24.8
23.3
6.0
China
Clinical patients 136
83
14.5
34.9 (5-14)
25.3 (15-24)
22.9 (25-59)
2.4 ( 60)
Clinical patients 139
162
5.6
34.0 (5-14)
14.2 (15-24)
43.2 (25-59)
3.1 ( 60)
Clinical patients 134
96
29.2
68.8 (5-14)
0 (15-24)
2.1 (25-59)
0 ( 60)
Clinical patients 140
74
21.6
43.2 (5-14)
18.9 (15-24)
16.2 (25-59)
0 ( 60)
Clinical patients 128
404
-
- (5-14)
29.5 (15-24)
65.5 (25-59)
5.0 ( 60)
Clinical patients 132
75
-
- (5-14)
50.7 (15-24)
49.3 (25-59)
0 ( 60)
Clinical patients 41
6,688
9.7
23.5 (6-17)
61.4 (18-64)
5.5
Indonesia
Surveillance 43
1,487
15.0
33.8 (5-12)
8.5 (13-17)
38.0 (18-49)
3.6
1.1
Laos
Surveillance 46
142
25.4
34.8 (5-17)
39.8 (18-64)
0
Surveillance 47
92
13.0
41.3 (5-17)
44.6 (18-49)
1.1
0
Malaysia
Clinical patients 143
338
73.8
16.4
8.2
1.6
-
-
Myanmar
Clinical patients 51
125
43.2
32.6
13.8
2.2 (20-59)
0 ( 60)
Clinical patients 50
6
33
50
16.7
0
0
0
PNG
Surveillance 56
38
76
24 (>5)
Singapore
Clinical samples 82
92
45.3
10.5
8.2
36.0 ( 20)
South Korea
Surveillance 76
3,217
48.7
18.4
5.0
7.7
6.5
13.1
Thailand
Surveillance 83
120
25.8
43.8 (5-17)
12.5 (18-49)
15.6
12.5
Surveillance 84
150
26
34.7 (5-17)
18.7 (18-49)
20.7 ( 50)
Vietnam
Surveillance 58
585
22
41.5 (5-14)
17.4 (25-64)
1.7
Surveillance 59
2,163
68 (0-15)
11.8 (16-24)
18.0 (25-64)
1.8
N: number; PNG: Papua New Guinea; GP: general practice; ILI: Influenza-like illness; LRTI: Lower respiratory tract infection. Shading indicates values covering the
combined shaded age groups
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Table 5: Circulating and vaccine influenza type B lineages in tropical countries
Year
Vaccine
lineage 15
% type
Circulating lineage
(%)
% type
Circulating
lineage (%)
% type
Circulating
lineage (%)
B
Victoria
Yamagata
B
Victoria
B
Victoria
Malaysia (clinical samples49)
Indonesia (surveillance43)
Laos (surveillance46**)
2005
Yamagata
51
99
1
-
Predominant
-
-
2005-06
Yamagata
2006
Victoria
43
94
6
-
Predominant
-
-
2006-07
Victoria
2007
Victoria
30
27
73
-
Predominant
-
-
2007-08
Victoria
2008
Yamagata
18
0
100
-
-
66.7
-
2008-09
Yamagata
2009
Yamagata
22
97
3
-
-
2.7
100
2009-10
Victoria
2010
Victoria
-
-
-
-
-
33.7
98.4
Year
Thailand (surveillance72 clinical
samples73*)
Cambodia (surveillance32,33)
Myanmar (clinical
samples52)
2004
Yamagata
16
32
68
-
-
-
-
2004-05
Victoria
2005
Yamagata
32
41
59
-
-
42
85
2005-06
Yamagata
2006
Victoria
29
55
45
0
-
0
-
2006-07
Victoria
2007
Victoria
34
62
38
57.7
All
67
100
2007-08
Victoria
2008
Yamagata
40
40
60
34
None
-
-
2008-09
Yamagata
2009
Yamagata
12
100
0
12.6
All
-
-
2009-10
Victoria
2010
Victoria
35
100
0
23.1
All
-
-
2010-11
Victoria
2011
Victoria
-
90
10
64.8
All
-
-
2011-12
Victoria
2012
Victoria
-
50
50
-
-
-
-
2012-13
Yamagata
2013
Yamagata
-
0
100
-
-
-
-
2013-14
Yamagata
2014
Yamagata
-
0
100
-
-
-
-
* 2011-2014 limited to 35 isolates over the 5-year period
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Figure 1
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Figure 2
4,173 unique articles
retrieved from PubMed
Screening
Included
Eligibility
Identification
779 unique articles retrieved
from WPRIM
4834 articles screened after
duplicates removed (n=118)
4486 articles excluded
after title/abstract review
355 full-text articles
assessed for eligibility.
234 full-text articles excluded:
No relevant information (84)
Non-pertinent publication type (45)
Methods insufficiently described (14)
Full article not available (69)
Population not of interest (6)
Other (16)
121 articles included
in this review
extraction
3 additional
references
identified
4,173 unique articles
retrieved from PubMed
Screening
Included
Eligibility
Identification
779 unique articles retrieved
from WPRIM
4834 articles screened after
duplicates removed (n=118)
4487 articles excluded
after title/abstract review
353 full-text articles
assessed for eligibility.
232 full-text articles excluded:
No relevant information (82)
Non-pertinent publication type (45)
Methods insufficiently described (14)
Full article not available (69)
Population not of interest (6)
Other (16)
121 articles included
in this review
extraction
2 additional
references
identified
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been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1111/irv.12522
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Supplementary resource (1)

... The influenza positivity rate in this study is within the range of influenza detection rates previously described (rates of up to 5-14%) among adults hospitalized with severe acute respiratory symptoms in countries in East and Southeast Asia [6,7]. While influenza is typically present year-round in tropical and subtropical regions, available data have shown peaks of influenza activity occurring earlier and/or later in the year, depending on the country [8,[19][20][21][22]. Accordingly, reports of the presence or absence of seasonal peaks in Malaysia have been inconsistent [8,19,21]. ...
... While influenza is typically present year-round in tropical and subtropical regions, available data have shown peaks of influenza activity occurring earlier and/or later in the year, depending on the country [8,[19][20][21][22]. Accordingly, reports of the presence or absence of seasonal peaks in Malaysia have been inconsistent [8,19,21]. Observations based on laboratory surveillance between 2011 and 2016 demonstrated variable periods of higher transmission coinciding with winter seasons of northern (November-February) and/or southern (July-September) hemisphere regions [23]. ...
Article
Full-text available
Background Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings. Methods We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018–August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis. Results Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January–February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329–0.970)], p = 0.038) and of dyspnea (0.544 (0.341–0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death). Conclusions Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population. Study registration, NMRR ID: NMRR-17-889-35,174.
... In the 1980s, the B/Yamagata/16/88 lineage and its variants spread worldwide. Whereas, B/Victoria/2/87 lineage viruses remained geographically restricted to Asia during the 1990s, for reasons not entirely understood, to spread to the rest of the world in 2002 (Shaw et al., 2002;Jennings et al., 2018;Caini et al., 2019). ...
... In addition, the incidence of influenza B infections can differ drastically from one influenza season to another (Ambrose and Levin, 2012). For those reasons, influenza B is an important cause of morbidity and mortality during inter-pandemic periods, and its prevention entails a global public health challenge (Jennings et al., 2018;Caini et al., 2019). ...
Article
Full-text available
Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.
... In recent years, more research data on the in uenza burden in the tropics and countries in the Asia Paci c have improved our understanding. [3][4][5][6] In the tropics, the pattern of in uenza cases has also been di erent. 3,5 In essence, in uenza activity in the tropics occurs throughout the year. ...
... [3][4][5][6] In the tropics, the pattern of in uenza cases has also been di erent. 3,5 In essence, in uenza activity in the tropics occurs throughout the year. For the countries near the equator, multiple minor peaks. ...
... The incidence rate and mortality rate of infection were high, especially with children and adolescents [3][4][5]. In the long-term evolution, IBV could be divided into two main lineages according to the nucleotide sequence difference of HA fragment, namely B-victoria branch represented by B/ Victoria/2/87strain and B-yamagata branch represented by B/ Yamagata/ 16/88 strain [6,7]. The neuraminidase inhibitor was main clinical treated. ...
... As these effects were mostly driven by the Asian subpopulation in Taiwan, this finding may be influenced by detection bias due to differences in practices of admitting patients and diagnosing pneumonia between US and Taiwanese hospitals. However, previous studies have documented geographic variation in the burden of influenza B,33,[41][42][43] especially across Asia with Taiwan frequently reporting influenza B circulation.33,42,44 While these effects should be interpreted with caution, this finding underscores the importance of recruiting diverse populations in future clinical research on influenza B to elucidate the role of race/ethnicity and geographic origin in disease severity.There are several limitations associated with this study. ...
Article
Full-text available
Background Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. Methods Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014–2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). Results Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14–7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25–4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98–3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80–3.78, p = 0.166]). Conclusion Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B.
Article
Since 2000, two lineages of influenza B viruses, Victoria and Yamagata, have been circulating at similar frequencies worldwide. Little is known about the circulation of those viruses in Egypt. This study aims to describe the epidemiology of influenza B virus infections in Egypt, 2017–2019. This was performed through a household prospective cohort study on influenza infections among 2400 individuals from five villages. When a study participant had influenza like symptoms, a nasal swab and an oropharyngeal swab were obtained and tested by RT-PCR for influenza B infections. A serum sample was obtained from all participants annually to detect neutralizing antibodies using microneutralization assay. 9.1% of subjects were positive for influenza B viruses during season 2017–2018 mostly among preschoolers and 7.6% were positive during the season 2018–2019 with higher risk in females, potentially due to mothers being infected after contact with their children. The overall seroprevalence among the participants was 53.2% and 52.2% against the Victoria and Yamagata lineages respectively, the majority of seropositive participants were students. Multivariate analysis showed that age and having chronic diseases were the strongest predictors of infection. Our results show that both influenza B lineages circulated between 2017 and 2020 in Egypt almost in equal proportion. Encouraging the uptake of seasonal influenza vaccines is recommended.
Article
Influenza is a major public health concern causing millions of hospitalizations every year. The current vaccines need annual updating based on prediction of likely strains in the upcoming season. However, mismatches between vaccines and the actual circulating viruses can occur, reducing vaccine effectiveness significantly because of the remarkably high rate of mutation in the viral glycoprotein, hemagglutinin (HA). Clearly, it would be of great interest to determine the potential role of universally conserved epitopes in inducing protective immunity. Here, an antibody against the 14-aa fusion peptide sequence at the N-terminus of the HA2 subunit (Uni-1) was investigated for its ability to elicit antibody-dependent cellular cytotoxicity (ADCC) in vitro and cross-protection against lethal infection in animals. Uni-1, known to neutralize influenza type A (IAV) in vitro, was found to induce strong ADCC against diverse influenza viruses, including human and avian IAVs and both lineages of type B (IBV). The ADCC effects against human IAVs by Uni-1 was comparable to ADCC induced by well-characterized antibodies, F10 and FI6V3. Importantly, mice treated with Uni-1 were protected against lethal challenge of IAV and IBV. These results revealed the versatile effector functions of this universal antibody against markedly diverse strains of both IAV and IBV.
Article
In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide an overview of viral proteins as cross-protective vaccine targets, along with other updated broadly protective vaccine strategies. The importance of developing such vaccines lies not only in influenza B prevention, but also in the very attractive prospect of eradicating the influenza B virus in the human population.
Article
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through recognition of cognate sequences and interference of transcriptional, translational, or epigenetic processes. Hundreds of miRNA genes have been found in diverse viruses, and many of these are phylogenetically conserved. Respiratory viruses are the most frequent causative agents of disease in humans, with a significant impact on morbidity and mortality worldwide. Recently, the role of miRNAs in respiratory viral gene regulation, as well as host gene regulation during disease progression, has become a field of interest. This review highlighted the importance of various miRNAs and their potential role in fighting with respiratory viruses as therapeutic molecules with a focus on COVID-19.
Article
Background Several countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE. Methods We estimated the 2015–2016, 2017–2018, 2019–2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years. Results Since 2011–2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015–2016 and 2017–2018 seasons, the 2019–2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI –22.5 to 43.1) and −25.8 (95% CI −85.3 to 14.6) for the 2019–2020, 2017–2018 and 2015–2016 seasons, respectively. The 2019–2020 VE point estimated were the highest for the 0.5–4, 5–17 and 18–44 years age groups and for more 15-year age intervals as compared to the other seasons. Conclusions Our results support the rapid transition from the TIV to the QIV.
Article
Full-text available
Background: The extent to which influenza A and B infection differs remains uncertain. Methods: Using active surveillance data from the Canadian Immunization Monitoring Program Active at 12 pediatric hospitals, we compared clinical characteristics and outcomes of children ≤16 years admitted with laboratory-confirmed influenza B or seasonal influenza A. We also examined factors associated with ICU admission in children hospitalized with influenza B. Results: Over 8 nonpandemic influenza seasons (2004-2013), we identified 1510 influenza B and 2645 influenza A cases; median ages were 3.9 and 2.0 years, respectively (P < .0001). Compared with influenza A patients, influenza B patients were more likely to have a vaccine-indicated condition (odds ratio [OR] = 1.30; 95% confidence interval [CI] = 1.14-1.47). Symptoms more often associated with influenza B were headache, abdominal pain, and myalgia (P < .0001 for all symptoms after adjustment for age and health status). The proportion of deaths attributable to influenza was significantly greater for influenza B (1.1%) than influenza A (0.4%); adjusted for age and health status, OR was 2.65 (95% CI = 1.18-5.94). A similar adjusted OR was obtained for all-cause mortality (OR = 2.95; 95% CI = 1.34-6.49). Among healthy children with influenza B, age ≥10 years (relative to <6 months) was associated with the greatest odds of ICU admission (OR = 5.79; 95% CI = 1.91-17.57). Conclusions: Mortality associated with pediatric influenza B infection was greater than that of influenza A. Among healthy children hosptialized with influenza B, those 10 years and older had a significant risk of ICU admission.
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Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (
Article
Full-text available
Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 sea-son in Australia saw an unusual predominance of influ-enza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria infecting a younger population than B/Yamagata, that could not be explained by potential prior exposure. © 2016, European Centre for Disease Prevention and Control (ECDC). All rights reserved.
Article
Laboratory-supported influenza surveillance is important as part of pandemic preparedness, for identifying and isolating candidate vaccine strains, for supporting trials of anti-influenza drugs and for refining the influenza surveillance case definition in practice. This study describes the implementation of laboratory-supported influenza surveillance in Victorian sentinel general practices and provides an estimate of the proportion of patients with an influenza-like illness proven to have influenza. During 1998 and 1999, 25 sentinel general practices contributed clinical surveillance data and 16 metropolitan practices participated in laboratory surveillance. Serological, virus-antigen detection, virus culture and multiplex polymerase chain reaction procedures were used to establish the diagnosis of influenza. Two laboratories at major teaching hospitals in Melbourne provided additional data on influenza virus identification. General practice sentinel surveillance and laboratory identification of influenza provided similar data on the pattern of influenza in the community between May and September. The clinical suspicion of influenza was confirmed in 49 to 54 per cent of cases seen in general practice.
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Background: Influenza B virus has been perceived to cause less disease burden and milder disease when compared to influenza A, but recent studies suggest influenza B does have a significant impact. We aimed to estimate the burden of influenza B virus infections on hospitalizations in Hong Kong, in the context of virus lineage changes over time. Methods: The pediatric age-specific rates of influenza B hospitalization in Hong Kong for 2004-2014 were estimated based on admissions to two hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza B virus was detected by immunofluorescence and culture on nasopharyngeal aspirates. Lineage typing was performed by RT-PCR. Results: A total of 5085 children were recruited on one designated day each week, year-round during the 11 years, and 221 (4.3%) tested positive for influenza B. Hospitalization rates were highest in children aged 2-<5 years with year to year variation. Victoria-lineage viruses appeared to be associated with a greater fraction of influenza B hospitalizations in children than of influenza B infections in the general community. Influenza B did not cause significant hospitalization in infants <1 year of age. Conclusions: We report one of the first population-based age-specific and lineage-specific studies of pediatric hospitalization for influenza B. We found that changes in lineage were associated with higher hospitalization rates and we documented that Victoria lineage viruses were associated with greater pediatric hospitalization burden compared with Yamagata lineage viruses.
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Background: Limited information is available on the non-influenza etiology and epidemiology of influenza-like illness (ILI) in China. Methods: From April 2011 to March 2014, we collected oropharyngeal swabs from children less than 5 years of age with symptoms of ILI who presented to the outpatient departments of Suzhou University Affiliated Children's Hospital (SCH). We used reverse transcription polymerase chain reaction (rt-PCR) or PCR to detect 11 respiratory viruses. Results: Among 3662 enrolled ILI patients, 1292 (35.3%) tested positive for at least one virus. Influenza virus (16.9%) was detected most frequently (influenza A 7.4%, influenza B 9.5%), followed by respiratory syncytial virus (RSV) (5.6%), parainfluenza virus (PIV) types 1-4 (4.8%), human bocavirus (HBoV) (3.8%), human metapneumovirus (HMPV) (3.5%) and adenovirus (ADV) (3.0%). Co-infections were identified in 108 (2.9%) patients. Influenza virus predominantly circulated in January-March and June-July. The 2013-2014 winter peaks of RSV and influenza overlapped. Compared with other virus positive cases, influenza positive cases were more likely to present with febrile seizure, and RSV positive cases were more likely to present with cough and wheezing, and were most frequently diagnosed with pneumonia. Conclusion: These data provide a better understanding of the viral etiology of ILI among children less than 5 years of age in Suzhou, China. Influenza is not only the most frequently identified pathogen but it's also the only vaccine preventable illness among the 11 pathogens tested. Such findings suggest the potential value of exploring value of influenza vaccination among this influenza vaccination target group. This article is protected by copyright. All rights reserved.