International Journal of Infectious Diseases 104 (2021) 594–600

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

The moving epidemic method applied to influenza surveillance in

Guangdong, China
Min Kanga,b , Xiaohua Tanb , Meiyun Yeb , Yu Liaob , Tie Songb,* , Shixing Tanga,*
a
School of Public Health, Southern Medical University, Guangzhou, China
b
Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China

A R T I C L E I N F O A B S T R A C T

Article history: Objectives: The moving epidemic method (MEM) has been well used for assessing seasonal influenza
Received 24 December 2020 epidemics in temperate regions. This study used the MEM to establish epidemic threshold for influenza in
Received in revised form 20 January 2021 Guangdong, a subtropical province in China.
Accepted 22 January 2021
Methods: Influenza virology surveillance data from 2011/2012 to 2017/2018 seasons in Guangdong were
used with the MEM to calculate the epidemic thresholds and timeously detect the 2018/2019 influenza
Keywords: season epidemic. The weekly positive proportion of influenza A(H1N1)pdm09, A(H3N2), B/Victoria-
Seasonal influenza
lineage and B/Yamagata-lineage were separately adapted to calculate the subtype-specific epidemic
Moving epidemic method
Surveillance
thresholds. The performance of MEM was evaluated using a cross-validation procedure.
Results: For the 2018/2019 influenza season, the epidemic threshold of a weekly positive proportion was
15.08%. Epidemic detection for the 2018/2019 season was 1 week in advance. Influenza A(H1N1)pdm09,
B/Yamagata-lineage and B/Victoria-lineage prevailed during winter and spring and their epidemic
thresholds were 5.12%, 4.53% and 4.38%, respectively. Influenza A(H3N2) was active in the summer, with
an epidemic threshold of 11.99%.
Conclusions: Using influenza virology surveillance data stratified by types of influenza virus, the MEM was
effectively used in Guangdong, China. This study provided a practical way for subtropical regions to
establish local influenza epidemic thresholds.
© 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

Introduction Human influenza A and B types – including A(H1N1)pdm09, A

Seasonal influenza accounts for 3,000,000 to 5,000,000 severe
infections and up to 650,000 respiratory disease-associated deaths
worldwide per year (Iuliano et al., 2018; World Health Organiza-
tion, 2018). During seasonal epidemic periods, influenza signifi-
cantly increases morbidity and mortality, and causes a sudden and
significant impact on public health, healthcare systems and
socioeconomics (World Health Organization, 2018). Determining
influenza seasonal patterns and epidemic timing will enable better
resource planning and facilitate public health actions such as
timely risk communication, annual vaccination programs, anti-
virals stockpiling and health resources allocation to reduce the
impact of the disease.
* Corresponding authors at: School of Public Health, Southern Medical University,
Guangzhou, China.
E-mail addresses: kangmin@yeah.net (M. Kang), tsong@cdcp.org.cn (T. Song),
tamgshixing@smu.edu.cn (S. Tang).
(H3N2), B/Victoria-lineage and B/Yamagata-lineage – are mainly
responsible for the seasonal epidemics over the decades (World
Health Organization, 2018) and circulate with varying intensity in
different regions from year to year. Yet the seasonal pattern of each
type of influenza virus has remained extensively unexplored
(Bedford et al. 2015; Muscatello 2019; Newman et al. 2018).
Influenza seasons in temperate countries are well-documented to
occur during the winter season, which is from October to March in
the Northern Hemisphere and April to September in the Southern
Hemisphere (Muscatello 2019; Newman et al. 2018). In contrast,
multiple peaks with more than one dominant strain in a single
influenza season are often observed in tropical and subtropical
regions (Newman et al. 2018; Tamerius et al. 2011). Such variability
of influenza activity in these regions, which is affected by the
characteristics and distribution of circulating viruses, makes
epidemic timing and intensity hard to assess (Tamerius et al.
2011; Tamerius et al. 2013).
The epidemic threshold is used to signal the onset of an
influenza epidemic and provide timely triggers for public health
practices. It is defined as the level of activity that indicates the

https://doi.org/10.1016/j.ijid.2021.01.058
1201-9712/© 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
M. Kang, X. Tan, M. Ye et al.
beginning and end of an influenza epidemic per season (World
Health Organization, 2011, 2014). At present, there are various
methods for establishing an epidemic threshold using influenza
surveillance data, such as annual median values, the control chart
method, the regression model and the moving epidemic method
(MEM) (Kuang et al. 2012; Steiner et al. 2010; Vega et al. 2013;
World Health Organization, 2014). The MEM is a simple method
and can easily be used based on routine surveillance data (Vega
et al. 2013). The method has been well implemented in temperate
regions (Biggerstaff et al. 2018; Murray et al. 2018; Vega et al.
2015); however, few applications of MEM have been reported in
subtropical countries.
Previous studies have indicated that an influenza A(H3N2)
epidemic in South China and Southeast Asia seeds the rest of the
world, while influenza B/Yamagata-lineage in China also originates
from subtropical provinces (Li et al., 2020; Russell et al. 2008).
Guangdong is the southernmost province of mainland China,
located in the subtropical region of East Asia. Routine surveillance
in Guangdong has revealed that various influenza viruses
alternately circulate when more than one dominant strain exists
per influenza season; inconsistent patterns of influenza epidemics
have been recorded between seasons (Kang et al. 2013; Lin et al.
2013). Determining the epidemic threshold in such a region has
both regional and global implications for an influenza epidemic
response.
This study adapted the MEM to establish the epidemic
threshold for the different types of influenza virus in Guangdong,
China, and evaluated the performance and feasibility of such a
model.
Materials and methods
Influenza surveillance network in Guangdong, China
This was a retrospective study based on the Guangdong
Influenza Surveillance Network, which is part of the National
Influenza Surveillance Program and operated by the Center for
Disease Control and Prevention of Guangdong Province. The
surveillance network comprises 22 influenza reference laborato-
ries and 28 sentinel hospitals located throughout the 21
prefectures of the province. Each sentinel hospital registered
outpatient cases of influenza-like illness (ILI) (body temperature
38  C with either cough or sore throat in the absence of an
alternative diagnosis) and collected at least 20 respiratory speci-
mens per week from ILI outpatients who had a fever for no longer
than 3 days and had not yet taken antiviral drugs. Collected
specimens were sent to reference laboratories for influenza virus
testing to determine influenza virus subtypes by reverse tran-
scription polymerase chain reaction (RT-PCR) within the same
week of sampling. All ILI data and laboratory results were
electronically submitted to the web-based National Influenza
Surveillance Information System.
Data collection
For analysis purposes, week 36 through 48 each year was
defined as autumn, week 49 through week 9 of the following year
as winter, week 10 through 22 each year as spring, and week 23
through 35 as summer in Guangdong. Since historical surveillance
data show that epidemic peaks of influenza are rarely observed in
autumn in Guangdong, an influenza season was defined as starting
on week 36 and ending on week 35 of the following year. This study
covered eight influenza seasons, with 416 weeks from week 36,
2011 to week 35, 2019. Weekly visiting ILI and outpatient numbers,
weekly swab numbers and influenza virus subtype-positive
specimen numbers between 2011/2012 and 2018/2019 influenza
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International Journal of Infectious Diseases 104 (2021) 594–600
seasons were obtained from the web-based National Influenza
Surveillance Information System.
Two study indicators were calculated: (1) weekly proportion of
ILI cases among all visiting outpatients; (2) weekly proportion of
respiratory specimens from ILI outpatients who tested positive for
influenza (proportion positive). Except for the overall influenza-
positive proportion, the weekly positive proportions of A(H1N1)
pdm09, A(H3N2), B/Victoria-lineage and B/Yamagata-lineage were
also separately calculated. The correlation between proportion of
ILI and positive proportion was determined by Pearson correlation
coefficient.
Establishing epidemic thresholds and assessing intensity by MEM
The weekly influenza-positive proportions from the 2011/2012
to 2018/2019 seasons were applied to the MEM. Details of the MEM
process have previously been introduced (JE ; Vega et al. 2015;
Vega et al. 2013). Briefly, a specific algorithm was adapted to
determine the beginning and end of an influenza epidemic for each
season, which was then divided into three periods: pre-epidemic,
epidemic and post-epidemic. For the seasons with two distinct
epidemic waves of influenza, the data were split into two datasets
at the week after the first peak when the influenza-positive
proportion was the lowest. The MEM epidemic and non-epidemic
periods were then divided, respectively. The MEM epidemic period
with the times of beginning and peaking were identified for each
season.
For the 2018/2019 season, an epidemic threshold was calculated
as the upper limit of the 95% one-sided confidence interval of the
30 highest pre-epidemic weekly influenza-positive proportions
from 2011/2012 to 2017/2018. In addition, thresholds for medium,
high and very high intensity for the 2018/2019 season were
estimated as the upper limits of the 45%, 90% and 97.5% one-sided
confidence intervals of the geometric mean of the 30 highest
epidemic weekly influenza-positive proportions from 2011/2012
to 2017/2018, respectively. The peak value of the weekly influenza-
positive proportion per season was compared with intensity
thresholds to evaluate the epidemic peak intensity level for the
season. Due to a lack of historical surveillance data, the epidemic
and intensity thresholds for a specific season from 2011/2012 to
2017/2018 were calculated using data from all remaining seasons.
To further explore type-specific epidemic thresholds, the weekly
positive proportion of A(H1N1)pdm09, A(H3N2), B/Victoria-
lineage and B/Yamagata-lineage were used by MEM. For a target
type of influenza virus, an epidemic threshold was calculated using
weekly data in the seasons when the proportion of the target strain
exceeded 25%.
In terms of the selection of d, a key parameter in the MEM
model for defining an epidemic period, the default value of d = 2.8
was not adopted, but it was chosen with the maximum Youden’s
index (YI) as the optimal parameter within the recommended
range of 2.0–4.0%. This study only showed the results of MEM when
the optimal values of d were adopted. To calculate the epidemic
threshold for the 2018/2019 season, the value of d was determined
to be 2.0. For influenza A(H1N1)pdm09, A(H3N2), B/Victoria-
lineage and B/Yamagata-lineage dominating seasons, d of 2.0, 3.1,
2.5 and 2.1 were separately used to calculate type-specific
epidemic thresholds. Statistical analysis was performed using
the MEM package of the R Language statistical software.
Evaluation of the goodness of MEM
A cross-validation procedure was performed to evaluate the
goodness of MEM. For each season, the weeks in the epidemic/non-
epidemic periods defined by the MEM algorithm were compared
with weeks of the same season above/under the calculated MEM
M. Kang, X. Tan, M. Ye et al. International Journal of Infectious Diseases 104 (2021) 594–600

Table 1
Peak of weekly influenza-like illness (ILI) proportion and influenza-positive proportion and the distribution of influenza viruses in Guangdong, China, 2011/2012–2018/2019
seasons.

Season ILI proportion peak Positive proportion peak Percentage of positive specimens (%)

Week Value (%) Week Value (%) A(H1N1)pdm09 A(H3N2) B/Yamagata-lineage B/Victoria-lineage
2011/2012 20 5.09 9 42.86 0.04 54.89 7.47 37.6
2012/2013 24 4.91 15 22.95 81.47 15.75 2.19 0.58
2013/2014 23 5.63 9 39.17 28.03 45.76 25.31 0.9
2014/2015 24 6.6 25 44.43 1.8 60.9 36.19 1.11
2015/2016 12 6.61 14 42.93 41.45 7.3 15.77 35.48
2016/2017 28 7.00 28 40.95 16.12 80.06 1.37 2.45
2017/2018 1 6.36 3 41.92 36.89 2.34 50.38 10.39
2018/2019 2 7.3 3 45.42 51.00 19.16 0.22 29.62

epidemic threshold. Sensitivity was defined as the number of Results

weeks above the epidemic threshold divided by the total number
of epidemic weeks defined by the MEM algorithm. Specificity was
defined as the number of MEM non-epidemic weeks below the
epidemic threshold divided by the number of MEM non-epidemic
weeks. Positive predictive value (PPV) was obtained by dividing the
number of MEM epidemic weeks above the threshold by the
number of weeks above the threshold, while negative predictive
value (NPV) was calculated as the number of MEM non-epidemic
weeks below the threshold divided by the number of weeks below
the threshold. This procedure was repeated as often as the number
of seasons in the study. The YI (Sensitivity + Specitifity-1) was used
to measure the performance of the model.
For the 2018/2019 influenza season, alert week and timeliness
were also determined. Alert week was considered as the first week
of the 2018/2019 season with an observed positive proportion
above the epidemic threshold. Timeliness was the number of
weeks between the first week with a positive proportion above the
established epidemic threshold and the first week of the MEM
epidemic period. A positive value of timeliness indicated that the
alert week preceded the epidemic period or vice versa.
Seasonal influenza activity in Guangdong
From the 2011/2012 to 2018/2019 influenza seasons, the peak of
weekly ILI proportion and influenza-positive proportion per
season ranged 4.91–7.30% and 22.95–45.42%, respectively (Table 1).
Their peak timings varied between seasons. When the weekly ILI
proportion and influenza-positive proportion were plotted, the
two time series data were significantly correlated with a Pearson
correlation coefficient of 0.74 (p < 0.01). By visual inspection, the
weekly ILI proportion showed extensive fluctuations while the
influenza-positive proportion presented obvious seasonality
(Figure 1). According to virology surveillance data, there were
four epidemic peaks that occurred in winter, two in spring and two
in summer.
MEM for influenza seasons in Guangdong
For the 2018/2019 influenza season, the epidemic period
estimated by MEM started in week 49, 2018 and lasted for 33

Figure 1. Influenza epidemic periods modelled by the moving epidemic model, Guangdong, China, 2011/2012–2018/2019 seasons.
From top to bottom: the time series plots separately present weekly influenza-like illness (ILI) proportions in sentinels; weekly overall positive proportion of influenza;
weekly positive proportions of influenza A(H1N1)pdm09, A(H3N2), B/Yamagata-lineage and B/Victoria-lineage.

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Table 2
Influenza epidemic onset, length, thresholds of positive proportion and peak intensity level determined by the moving epidemic method, 2011/2012–2018/2019 seasons.

Season Epidemic start Epidemic Epidemic Medium High threshold Very high Epidemic
week length threshold threshold threshold intensity
(weeks)
2011/2012 51 26 15.74 31.09 44.29 51.78 Medium
2012/2013 8 7 15.28 34.93 43.16 47.39 Low
2013/2014 51 24 14.38 32.40 46.54 54.63 Medium
2014/2015 11 12 15.76 31.31 44.87 52.61 High
2015/2016 5 11 15.95 31.07 44.14 51.55 High
2016/2017 19 14 14.34 31.41 45.15 53.00 Medium
2017/2018 50 15 15.81 31.37 45.02 52.81 Medium
2018/2019 49 33 15.08 31.90 45.11 52.57 High

Figure 2. Weekly influenza-positive proportions, and moving epidemic model (MEM) epidemic and intensity thresholds for 2018/2019 season, Guangdong, China.

weeks. The epidemic threshold was 15.08% (Table 2). By the
threshold value, the alert week of the 2018/2019 season was week
48, 2018, which was the 13th week of the season. The timeliness of
epidemic detection was 1 week. There was no detection lag for the
2018/2019 season. The peak intensity was estimated at a high level
in this season (Figure 2).
The MEM estimated that the epidemic period for each season
from 2011/2012 to 2018/2019 started between week 49 and week
19 of the following year. The epidemic threshold of the weekly
influenza-positive proportion for each season was between 14.38%
and 15.95%. The MEM epidemic length for influenza seasons in
Guangdong ranged 7–33 weeks. The peak intensity level was low
in 2012/2013, high in 2014/2015, 2015/2016 and 2018/2019, and
medium in all the other seasons (Table 2).
A total of 181,373 ILI outpatients were sampled and tested for
the influenza virus. Of them, 24,821 (13.69%) samples were
positive. Multiple types of influenza virus co-circulated and the
predominant strains frequently changed over seasons (Figure 1,
Tables 1 and 3). Influenza A(H1N1)pdm09 epidemics were
recorded in five of eight seasons, with the highest values of
weekly positive proportions. Its epidemic period lasted between
winter and spring. Influenza A(H3N2) accounted for 36.25% of the
positive samples and caused summer epidemics with an epidemic
threshold of 11.99%, which was higher than the other influenza
viruses. B/Victoria-lineage and B/Yamagata-lineage mostly domi-
nated in the winter of the three seasons.
Model goodness of MEM
For the 2018/2019 season, the sensitivity, specificity, PPV and
NPV of the epidemic threshold were 1.00, 0.86, 0.91 and 1.00,
respectively. By the cross-validation process, the statistics of
goodness varied between seasons (Table 4). Sensitivity and YI were
lowest in the 2012/2013 season. The MEM model provided a
sensitivity of 0.98 and specificity of 0.96 for the 2017/2018 season,
with the highest YI of 0.94 among seasons.
The statistics of goodness were high in MEM models for type-
specific epidemic thresholds. All YI of epidemic threshold for
Influenza A(H1N1)pdm09, A(H3N2), B/Yamagata-lineage and B/
Victoria-lineage season exceeded 0.80. The sensitivity and NPV
were 1 for the epidemic threshold of the B/Victoria-lineage. The
highest specificity and PPV were observed in MEM for A(H3N2),
with values of 0.98 and 0.90.
Discussion
Using the virology surveillance data from eight influenza
seasons and the MEM model, this study established the epidemic
and intensity thresholds for seasonal influenza in Guangdong,
China. The epidemic threshold signaled the epidemic onset of the
2018/2019 season one week in advance, with high sensitivity and
specificity. A similar value of epidemic threshold was reported in
Scotland. However, the epidemic duration estimated by MEM in
Guangdong, a subtropical province, was longer than that in
temperate regions (Murray et al. 2018; Rakocevic et al. 2019; Vega
et al. 2015; Vega et al. 2013). These findings indicated the feasibility
of using the MEM in Guangdong and provided regional implica-
tions for other areas in the subtropics. It is believed that this is one
of the first documented applications of MEM for determining type-
specific epidemic thresholds for influenza in the subtropics.
Assessing the effectiveness of a given model for calculating
epidemic thresholds requires evaluation criteria. The MEM uses an

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Table 3
Epidemics by influenza virus types in Guangdong, 2011/2012–2018/2019 seasons.

Influenza virus Positive samples Maximum peaka (%) Moving epidemic model estimation

n Percentage (%) n of seasons Start week Epidemic length (weeks) Epidemic threshold (%)
A(H1N1)pdm09 9054 31.64 39.83 5 5 18 5.12
A(H3N2) 10374 36.25 39.02 4 21 8 11.99
B/Yamagata-lineage 4914 17.17 32.46 3 50 12 4.53
B/Victoria-lineage 4278 14.95 27.45 3 8 16 4.38
a
Maximum peak: maximum value of weekly positive proportion (%)

Table 4 thresholds were calculated and their epidemic onset and epidemic
Moving epidemic model goodness of fit, Guangdong, 2011/2012–2018/2019 length were identified. The data showed that epidemic thresholds
seasons. are different between types of influenza virus. It is suggested that a
Season Sensitivity Specificity PPVa NPVa YIa type-specific threshold for ongoing predominant strains is more
sensitive for early detection of seasonal epidemics.
2011/2012 0.98 0.68 0.49 0.99 0.66
2012/2013 0.52 1.00 1.00 0.86 0.52 Stratification by virus types to determine thresholds helps to
2013/2014 0.95 0.91 0.90 0.95 0.86 better understand epidemic characteristics of influenza in the
2014/2015 0.75 0.92 0.71 0.93 0.67 subtropics. This study proved its usefulness. Previous studies have
2015/2016 0.85 0.99 0.98 0.95 0.84
demonstrated that influenza A commonly causes summer
2016/2017 0.87 0.93 0.71 0.97 0.80
2017/2018 0.98 0.96 0.90 0.99 0.94 epidemics in southern China, while influenza B dominates in
2018/2019 1.00 0.86 0.91 1.00 0.86 the winter (Yang et al. 2018; Yu et al. 2013). The current findings
A(H1N1)pdm09 0.98 0.85 0.74 0.98 0.82 revealed that seasonality of influenza by types of viruses in
A(H3N2) 0.92 0.98 0.90 0.98 0.90 Guangdong was more complex. Differing substantially from
B/Yamagata-lineage 0.95 0.94 0.81 0.99 0.89
influenza A(H1N1)pdm09 and B lineages, A(H3N2) normally
B/Victoria-lineage 1.00 0.89 0.76 1.00 0.89
caused summer peaks with a shorter MEM epidemic length and
a
PPV: positive predictive value; NPV: negative predictive value; YI: Youden’s higher epidemic threshold. Influenza A(H1N1)pdm09 and both B
index. lineages had temporally overlapping epidemics during winter and
spring in Guangdong. Influenza B was less active and had a lower
epidemic threshold than influenza A.
algorithm to define epidemic and non-epidemic periods based on It was noted that the influenza B/Victoria-lineage after A(H1N1)
routine surveillance data. The sensitivity, specificity, PPV and NPV pdm09 prevailed in summer 2019, resulting in the longest
can then be calculated and compared to evaluate the performance epidemic in the study period. These results revealed that influenza
of the model. The MEM results of this study showed that epidemic B can also dominate in the summer in Guangdong. In the same
thresholds for overall influenza-positive populations in Guang- season, the United States of America also experienced the longest
dong were slightly different between seasons, but their sensitivity epidemic of influenza in a decade. Yet its dominant subtypes were
and specificity greatly varied. Variation of epidemic seasonality A(H1N1)pdm09 and A(H3N2) (Xu et al. 2019). These unexpected
and intensity hampered the effectiveness of MEM in subtropical epidemics emphasized the significance of global collaboration for
regions. As the seasonal pattern of influenza in subtropical regions influenza surveillance. The MEM can be an option for a general
is complex, the MEM was modified to improve its application in approach for interpreting routine surveillance data and comparing
Guangdong. influenza epidemic patterns among different regions.
First, this study used virology data rather than ILI data in the Long-term establishment of an epidemic threshold is helpful in
MEM model. In temperate regions, such as Europe and the United determining the ideal timing for annual influenza vaccinations
States of America, ILI data have routinely been used by MEM (WHO 2014). This study highlighted the complex epidemic
(Biggerstaff et al. 2018; Rakocevic et al. 2019; Vega et al. 2015; patterns of influenza in Guangdong, which is critical for an
Vega et al. 2013). However, in subtropical and tropical regions, ILI evidence-based decision-making process for local vaccination
data have shown fewer seasonal patterns and been unsuitable for policies. Diverse epidemic features of influenza in Guangdong have
MEM application (AbdElGawad et al. 2019; Ly et al. 2017). The ILI challenged the current national influenza immunization policy,
proportion is a syndromic indicator that could be attributed to a which is deemed to be more suitable for temperate regions. The
number of pathogens (Azziz Baumgartner et al. 2012). It is also global influenza vaccine manufacturing cycle aligns with the
easily affected by factors such as health-seeking patterns and the influenza activity in temperate regions with the Northern
effect of holidays and weekends. Influenza surveillance in Hemisphere and Southern Hemisphere single-peak seasons (Saha
Guangdong showed that the virology data were well correlated et al. 2014). All licensed influenza vaccines in mainland China use
with ILI data and generally exhibited more distinct seasonal the Northern Hemisphere formulation based on the WHO strain
waves. Since the reference laboratories followed a standard recommendations issued in February and distributed by November
procedure provided by the Guangdong CDC, it is believed that the of the same year. Influenza vaccination is recommended before
virology surveillance data are an accurate and timely reflection of winter. However, China spans a large geographical region with
influenza activity in the population. Using virology data to distinct influenza seasonality. Thus, it may require distinct
establish epidemic thresholds by MEM has been justified by influenza vaccination strategies based on local seasonality (Hirve
studies in other regions (AbdElGawad et al. 2019; Murray et al. et al. 2016). The current data support the consideration that
2018). alternative vaccination timing for summer epidemics and South-
Furthermore, by separately applying weekly positive propor- ern Hemisphere vaccine formulation for influenza be introduced to
tions of A(H1N1)pdm09, A(H3N2), B/Victoria-lineage and B/ optimize the influenza immunization strategy in the south of
Yamagata-lineage to the MEM model, type-specific epidemic China.

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M. Kang, X. Tan, M. Ye et al.
This study had several limitations. Splitting the dataset is
recommended in the MEM for seasons with consecutive multiple
epidemic waves of influenza. However, the data process needs
enough interval time between epidemic peaks in a single season.
Overlapping influenza epidemics were observed in 2011/2012,
2013/2014 and 2018/2019 seasons in Guangdong. The interval of
epidemic peaks in each of these seasons were too small to split
epidemic periods. This issue might affect the determination of
epidemic thresholds. More measures need to be explored to
improve the application of the MEM for subtropical regions.
Second, data from three to five seasons were available to determine
the type-specific thresholds and other MEM statistics. Although
fewer than five seasons can be used by MEM (Closas et al. 2012),
data from more seasons would increase the robustness of the
model. Third, this study did not evaluate and compare the severity
of influenza seasons. The MEM can only be applied to explore
thresholds and assess the intensity of influenza epidemics. More
methods and research are needed to comprehensively analyze the
intensity and severity of influenza seasons.
Conclusion
In conclusion, this study in Guangdong proved the utility of the
MEM for detecting seasonal influenza in subtropical regions.
Laboratory data stratified by types of influenza virus expanded the
implementation of MEM. It provided a practical way for subtropi-
cal regions to better utilize surveillance data to determine local
epidemic thresholds and estimate peak intensity for influenza.
Further exploration of the MEM in subtropical regions might help
to better understand diverse epidemic patterns of influenza and
also contribute to global influenza surveillance and response.
Conflict of interest
The authors have declared that no competing interests exist.
Contributions
Min Kang, Tie Song and Shixing Tang contributed to the
conception and design, interpreted data and drafted the article.
Xiaohua Tan, Meiyun Ye and Yu Liao contributed to the collection,
analysis and interpretation of data. Min Kang, Min Kang and Yu
Liao performed statistical analysis and interpreted the results.
Shixing Tang critically revised the importance of intellectual
content.
Funding
This study was supported by Guangdong Provincial Research
and Development Projects in Key Areas (Grant
No.2019B111103001). This study was also supported by National
Natural Science Foundation of China (Grant No.82041030).
Role of the sponsors
The sponsors had no role in the study design and conduction;
collection, management, analysis and interpretation of data;
preparation, review or approval of the manuscript; and decision
to submit the manuscript for publication.
Ethical approval
This study was reviewed and approved by the Ethics Committee
of the Guangdong CDC. No written consent was required from
patients as the study was based on aggregated and de-identified
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International Journal of Infectious Diseases 104 (2021) 594–600
data. No information about the identity of any patients was
retained.
Statement
No data has been previously published.
Acknowledgements
We gratefully acknowledge the assistance of all sentinels from
Guangdong Influenza Surveillance Network.
References
AbdelGawad B, Vega T, El Houssinie M, Mohsen A, Fahim M, Abu ElSood H, et al.
Evaluating tools to define influenza baseline and threshold values using
surveillance data, Egypt, season 2016/17. J Infect Public Health 2019;.
Azziz Baumgartner E, Dao CN, Nasreen S, Bhuiyan MU, Mah EMS, Al Mamun A, et al.
Seasonality, timing, and climate drivers of influenza activity worldwide. J Infect
Dis 2012;206:838–46.
Bedford T, Riley S, Barr IG, Broor S, Chadha M, Cox NJ, et al. Global circulation
patterns of seasonal influenza viruses vary with antigenic drift. Nature
2015;523:217–20.
Biggerstaff M, Kniss K, Jernigan DB, Brammer L, Bresee J, Garg S, et al. Systematic
assessment of multiple routine and near real-time indicators to classify the
severity of influenza seasons and pandemics in the United States, 2003-2004
through 2015-2016. Am J Epidemiol 2018;187:1040–50.
Closas P, Coma E, Mendez L. Sequential detection of influenza epidemics by the
Kolmogorov-Smirnov test. BMC Med Inform Decis Mak 2012;12:112.
Hirve S, Newman LP, Paget J, Azziz-Baumgartner E, Fitzner J, Bhat N, et al. Influenza
seasonality in the Tropics and Subtropics – when to vaccinate?. PLoS One
2016;11:e0153003.
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, et al.
Estimates of global seasonal influenza-associated respiratory mortality: a
modelling study. Lancet 2018;391:1285–300.
Kang M, Zhong H, He J, Rutherford S, Yang F. Using Google Trends for influenza
surveillance in South China. PLoS One 2013;8:e55205.
Kuang J, Yang WZ, Zhou DL, Li ZJ, Lan YJ. Epidemic features affecting the
performance of outbreak detection algorithms. BMC Public Health 2012;12:418.
Li X, Chan KKY, Xu B, Lu M, Xu B. Spatial, temporal and genetic dynamics
characteristics of influenza B viruses in China, 1973–2018. Virologica Sinica
2020;35(01):18–24.
Lin J, Kang M, Zhong H, Zhang X, Yang F, Ni H, et al. Influenza seasonality and
predominant subtypes of influenza virus in Guangdong, China, 2004-2012. J
Thorac Dis 2013;5(Suppl 2):S109–117.
Ly S, Arashiro T, Ieng V, Tsuyuoka R, Parry A, Horwood P, et al. Establishing seasonal
and alert influenza thresholds in Cambodia using the WHO method:
implications for effective utilization of influenza surveillance in the tropics
and subtropics. Western Pac Surveill Response J 2017;8:22–32.
Murray JLK, Marques DFP, Cameron RL, Potts A, Bishop J, von Wissmann B, et al.
Moving epidemic method (MEM) applied to virology data as a novel real time
tool to predict peak in seasonal influenza healthcare utilisation. The Scottish
experience of the 2017/18 season to date. Euro Surveill 2018;23:.
Muscatello DJ. Redefining influenza seasonality at a global scale and aligning it to
the influenza vaccine manufacturing cycle: a descriptive time series analysis. J
Infect 2019;78:140–9.
Newman LP, Bhat N, Fleming JA, Neuzil KM. Global influenza seasonality to inform
country-level vaccine programs: an analysis of WHO FluNet influenza
surveillance data between 2011 and 2016. PLoS One 2018;13:e0193263.
Rakocevic B, Grgurevic A, Trajkovic G, Mugosa B, Sipetic Grujicic S, Medenica S, et al.
Influenza surveillance: determining the epidemic threshold for influenza by
using the Moving Epidemic Method (MEM), Montenegro, 2010/11 to 2017/18
influenza seasons. Euro Surveill 2019;24:.
Russell CA, Jones TC, Barr IG, Cox NJ, Garten RJ, Gregory V, et al. The global
circulation of seasonal influenza A (H3N2) viruses. Science 2008;320:340–6.
Saha S, Chadha M, Al Mamun A, Rahman M, Sturm-Ramirez K, Chittaganpitch M,
et al. Influenza seasonality and vaccination timing in tropical and subtropical
areas of southern and south-eastern Asia. Bull World Health Organ
2014;92:318–30.
Steiner SH, Grant K, Coory M, Kelly HA. Detecting the start of an influenza outbreak
using exponentially weighted moving average charts. BMC Med Inform Decis
Mak 2010;10:37.
Tamerius J, Nelson MI, Zhou SZ, Viboud C, Miller MA, Alonso WJ. Global influenza
seasonality: reconciling patterns across temperate and tropical regions. Environ
Health Perspect 2011;119:439–45.
Tamerius JD, Shaman J, Alonso WJ, Bloom-Feshbach K, Uejio CK, Comrie A, et al.
Environmental predictors of seasonal influenza epidemics across temperate
and tropical climates. PLoS Pathog 2013;9:e1003194.
Vega T, Lozano JE, Meerhoff T, Snacken R, Beaute J, Jorgensen P, et al. Influenza
surveillance in Europe: comparing intensity levels calculated using the moving
epidemic method. Influenza Other Respir Viruses 2015;9:234–46.
M. Kang, X. Tan, M. Ye et al.
Vega T, Lozano JE, Meerhoff T, Snacken R, Mott J, Ortiz de Lejarazu R, et al. Influenza
surveillance in Europe: establishing epidemic thresholds by the moving
epidemic method. Influenza Other Respir Viruses 2013;7:546–58.
World Health Organization. Influenza (Seasonal) Factsheet. World Health Organi-
zation; 2018.
World Health Organization. WHO Global epidemiological surveillance standards for
influenza. World Health Organization; 2014.
World Health Organization. WHO global technical consultation: global standards
and tools for influenza surveillance. World Health Organization; 2011.
600
International Journal of Infectious Diseases 104 (2021) 594–600
Xu X, Blanton L, Elal AIA, Alabi N, Barnes J, Biggerstaff M, et al. Update: Influenza
Activity in the United States During the 2018-19 Season and Composition of the
2019-20 Influenza Vaccine. MMWR 2019;68:544–51.
Yang J, Lau YC, Wu P, Feng L, Wang X, Chen T, et al. Variation in Influenza B Virus
Epidemiology by Lineage, China. Emerg Infect Dis 2018;24:1536–40.
Yu H, Alonso WJ, Feng L, Tan Y, Shu Y, Yang W, et al. Characterization of regional
influenza seasonality patterns in China and implications for vaccination
strategies: spatio-temporal modeling of surveillance data. PLoS Med 2013;10:
e1001552.