PLOS NEGLECTED TROPICAL DISEASES

RESEARCH ARTICLE

Dengue in Myanmar: Spatiotemporal

epidemiology, association with climate and
short-term prediction
Win Zaw1, Zaw Lin2, July Ko Ko1, Chawarat Rotejanaprasert1,3, Neriza Pantanilla1,
Steeve Ebener1, Richard James Maude ID1,4,5,6*
1 Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University,
Bangkok, Thailand, 2 Vector Borne Disease Control, Department of Public Health, Ministry of Health, Nay Pyi
Taw, Myanmar, 3 Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University,
a1111111111 Bangkok, Thailand, 4 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine,
a1111111111 University of Oxford, Oxford, United Kingdom, 5 Harvard TH Chan School of Public Health, Harvard
a1111111111 University, Boston, Massachusetts, United States of America, 6 The Open University, Milton Keynes, United
a1111111111 Kingdom
a1111111111
* [email protected]

Abstract
OPEN ACCESS
Dengue is a major public health problem in Myanmar. The country aims to reduce morbidity
Citation: Zaw W, Lin Z, Ko Ko J, Rotejanaprasert C,
Pantanilla N, Ebener S, et al. (2023) Dengue in by 50% and mortality by 90% by 2025 based on 2015 data. To support efforts to reach these
Myanmar: Spatiotemporal epidemiology, goals it is important to have a detailed picture of the epidemiology of dengue, its relationship
association with climate and short-term prediction.
to meteorological factors and ideally to predict ahead of time numbers of cases to plan
PLoS Negl Trop Dis 17(6): e0011331. https://doi.
org/10.1371/journal.pntd.0011331 resource allocations and control efforts. Health facility-level data on numbers of dengue
cases from 2012 to 2017 were obtained from the Vector Borne Disease Control Unit,
Editor: Alexandra K. Heaney, University of
California Berkeley School of Public Health, Department of Public Health, Myanmar. A detailed analysis of routine dengue and dengue
UNITED STATES hemorrhagic fever (DHF) incidence was conducted to examine the spatial and temporal epi-
Received: August 17, 2022 demiology. Incidence was compared to climate data over the same period. Dengue was
found to be widespread across the country with an increase in spatial extent over time. The
Accepted: April 24, 2023
temporal pattern of dengue cases and fatalities was episodic with annual outbreaks and no
Published: June 5, 2023
clear longitudinal trend. There were 127,912 reported cases and 632 deaths from 2012 and
Copyright: © 2023 Zaw et al. This is an open 2017 with peaks in 2013, 2015 and 2017. The case fatality rate was around 0.5% through-
access article distributed under the terms of the
out. The peak season of dengue cases was from May to August in the wet season but in
Creative Commons Attribution License, which
permits unrestricted use, distribution, and 2014 peak dengue season continued until November. The strength of correlation of dengue
reproduction in any medium, provided the original incidence with different climate factors (total rainfall, maximum, mean and minimum temper-
author and source are credited. ature and absolute humidity) varied between different States and Regions. Monthly inci-
Data Availability Statement: Dengue case data dence was forecasted 1 month ahead using the Auto Regressive Integrated Moving
used in this paper were obtained from the Dengue Average (ARIMA) method at country and subnational levels. With further development and
Control Unit, Department of Public Health, Ministry
validation, this may be a simple way to quickly generate short-term predictions at subna-
of Health and Sports, Myanmar who have not
provided permission for it to be publicly shared. tional scales with sufficient certainty to use for intervention planning.
The data can be obtained by applying in writing to
the Foreign Relations Unit of the Ministry of Health
and Sports ([email protected]).

Funding: WZ and RJM were supported by a grant

from Asian Development Bank (grant number TA-

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

8656). The funders had no role in study design,

data collection and analysis, decision to publish, or Author summary
preparation of the manuscript.
The study describes country, State/Region and township level spatial and temporal epide-
Competing interests: The authors have declared
miology of dengue in Myanmar from routine surveillance data collected by the govern-
that no competing interests exist.
ment. Dengue was found to widespread across the country with an increase in spatial
extent over time, likely due to improvements in surveillance, reporting and access to
health services. Most reported cases were children with an increase in the proportion �15
years of age over time. Dengue incidence was seasonal and related to climate, with larger
annual peaks every two years, although the timing of peaks in incidence, strength and
nature of the relationship with climate differed between States and Regions. Using
ARIMA, it was possible to predict dengue incidence 1 month ahead at State/Region level
using previous incidence data. Adding monthly climate data to the model gave a marginal
improvement in model performance which did not justify the additional effort needed to
acquire and process it. With further development and validation, the method may be a
simple way to quickly generate short-term predictions at subnational scales with sufficient
certainty to use for intervention planning.

Introduction
Dengue is a tropical and sub-tropical mosquito-borne arboviral disease. The World Health
Organization (WHO) has estimated that 100–400 million people are infected with dengue
each year [1] and half of the world population are exposed to it. There has been a steady
increasing trend of dengue incidence globally since at least 1990 [2], with around 70% of the
reported burden [1] and 75% of the population exposed being in the Asia-Pacific region.
Dengue is transmitted from human to human by Aedes mosquito bites and humans are the
main host. Ae. aegypti is the most efficient vector species and the female mosquito bites
humans during the day. The infected female can transmit dengue immediately by biting
another host when its feeding is interrupted [3] or after an incubation period of 8–10 days dur-
ing which time the virus multiplies in the salivary glands. The infected mosquito host remains
active for 30–45 days [4]. Many factors affect the transmission of dengue, such as entomologi-
cal, socio-economical, environmental and demographic [5]. Most of these are difficult to mea-
sure, not available on a continuous basis and thus of limited use in real-time predictions to
inform dengue control activities. Human movement has been shown to help predict dengue
incidence as it causes virus spread across diverse geographical scales [6–9] despite limited dis-
persal ranges of Aedes mosquitoes [10, 11]. However, such data are not generally available for
routine use and modelling methods can be complex. The relationship between dengue inci-
dence and climate factors has been well established with rainfall, higher temperatures and
humidity being associated with increased mosquito numbers and dengue transmission. [12]
Climate data is collected routinely at weather stations as well as through satellite remote sens-
ing and could potentially be used to develop real-time dengue prediction models. However,
the relationship between climate and dengue incidence is not consistent across time and space
[13–16] and location-specific models are generally needed.
Myanmar is hyperendemic for dengue with all four known dengue serotypes and it is
among the top ten childhood diseases for hospitalization in the country [17]. Dengue was first
reported in Yangon in 1964 with the first major outbreak occurring in 1970 and spreading to
all other States and Regions. Yangon Region continues to have the highest incidence reported
in the country. Over time, dengue cases have spread to more townships and outbreak fre-
quency has increased [18]. Dengue cases are reported routinely by hospitals across the country

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to the Vector Borne Disease Control Programme (VBDC) but there is limited capacity for
fine-scale analysis of these data to inform planning of dengue control activities. The country
aims to reduce dengue morbidity by 50% and mortality by 90% by 2025 based on 2015 data
[18] and making better use of existing data may help move towards this goal. As found else-
where, one or more of temperature, rainfall and humidity may be associated with dengue inci-
dence, with a time lag for mosquito breeding and disease transmission to occur, thus giving
the possibility to predict dengue incidence from climate data.
This study aimed to better understand the patterns of dengue over space and time in Myan-
mar and their relationship to routinely collected climate data. This was to provide evidence to
assess the utility of these data for a weather-based early warning system for dengue.

Methods
Ethics statement
This study used anonymized, aggregated secondary data thus formal ethical approval was not
required and a waiver was provided by the Oxford Tropical Research Ethics Committee
(OxTREC) and no additional ethical approval was required by the Myanmar government.
Case data were obtained with permission from the Dengue Control Unit of the Ministry of
Health and Sports, Myanmar.

Data
Monthly health facility-based dengue incidence data aggregated at township level were col-
lected from the National Dengue Control Programme, VBDC, Ministry of Health and Sports
from 2012 to 2017. Data had already been cleaned by VBDC staff. This comprised numbers of
reported hospitalized dengue haemorrhagic fever cases (DHF), graded from I to IV; grades III
and IV being classed as dengue shock syndrome (DSS). State and Region level data were avail-
able by month and township level data were available by year. Diagnostic criteria for dengue in
Myanmar followed the 1997 World Health Organization guidelines [19]. Analysis by age
group was limited to the age bands in the surveillance database and mortality by age was only
available for 2016–2017. Dengue surveillance in Myanmar is primarily hospital-based, thus
community cases are not captured. Population data were the total population counts for each
area from the most recent census done in 2014.

Weather data
It was not possible to access monthly climate station data directly from the government. There-
fore climate station based daily minimum temperature, maximum temperature, mean temper-
ature and DEW point temperature, available from Jan 2012 to Dec 2017 for Yangon and to
May 2016 for other areas, were downloaded from the NOAA National Climatic Center, US
Government [20]. Rainfall was not available for Myanmar for this time period from NOAA.
Rasterized rainfall layers were available at 0.5 by 0.5 degree (approx. 50 by 50 km) resolution
for Jan 2012 to Dec 2017 and were downloaded from the Climatic Research Unit, (CRU) Uni-
versity of East Anglia website [21]. From the CRU, rasterized temperature was also available,
but only monthly average values. Percent humidity was calculated from DEW point tempera-
ture and mean temperature [22]. From the climate station dataset, thirty-two ground-based
weather stations in Yangon, Mandalay, Ayeyarwady, Kachin, Kayah, Rakhine, Sagaing and
Tanintharyi Regions were used for analysis and correlation with monthly dengue incidence.
Where multiple stations were present in an administrative unit, values were averaged. Due to
missing station data, Bago, Magway, Mon, Kayin and Shan States were omitted from this

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analysis. Both ground-based weather data and rasterized rainfall data were aggregated at
monthly level to match the dengue incidence data.

Statistical analysis
The data were cleaned and geo-coded at the State and Region and Township levels. Spearman
ρ correlation analysis and graphs of State/Region level morbidity and mortality were produced
using GraphPad Prism version 8.0.0 for Windows, GraphPad Software, La Jolla California
USA. Township level population risk maps and case fatality maps were produced using ArcGIS
version 10.3 (ESRI, CA). Raster data were aggregated as monthly average values for the cells
falling within the relevant administrative unit polygons.
Seasonality and trend of the log transformed dengue incidence were examined using the
multiplicative time series decomposition function in the forecast package in R Studio (1.1.383).
[23] This splits the data series into seasonality, trends and random fluctuation. The equation
can be written as follows
logYt ¼ logSt � logTt � logRt

Where Yt is dengue incidence, St is the seasonal component, Tt is the trend cycle of the dis-
ease and Rt is the remainder component.
Monthly dengue case counts and monthly weather variables from each State/Region from
2012 to 2017 were used for time series analysis using distributed lag non-linear models (DLNM).
To capture short-term non-linear associations, a univariate model with quasi-Poisson family and
log link was used to monitor dengue case counts. The DLNM was first applied to each State/
Region, tested for dengue incidence and their association with each of (mean, minimum and
maximum) temperature, total rainfall and relative humidity. The DLNM terms have two dimen-
sions, the exposure space and the lag space that allows estimation of non-linear effect of climate
variables at each lag and non-linear effect across all lags [24]. The DLNM was perform using the
dlnm package in R Studio (1.1.383). To look for the non-linear effect of climate variables, we used
“natural cubic spline” using a 3df and the lagged effect using a 3df natural cubic spline. A maxi-
mum lag of 10 months was used to ensure inclusion of a plausible range of lag periods inferred
from previous studies showing dengue transmission is highly sensitive to climate [15, 25, 26].
In the second stage, to account for confounding, different combinations of meteorological
variables were modelled together in a multivariable analysis using the same two DLNM terms.
Each climate variable was tried in turn as the exposure variable with adjustment for the other
climate variables. The best model for each State/Region was then selected based on QAIC
(Quasi-Akaike information criteria) as the quasi-likelihood is assumed for distributed lag
modeling. In this stage, due to multi-collinearity [27] issues and some states having a high pro-
portion of zero values (zero inflation), it was only possible to produce results for a some States/
Regions and using only limited subsets of variable combinations.

Dengue incidence forecasting

Autoregressive integrated moving average (ARIMA) [28] modelling was used to predict
monthly dengue incidence at country and at State/Region levels. The ARIMA model uses his-
toric incidence data to predict future trends, is relatively simple to use for programmatic pur-
poses like dengue incidence prediction [29–31] and has been shown to have more predictive
power than other models [32, 33]. ARIMA models were written in ARIMA (p, d, q) where p is
the order of the auto-regressive (AR) mode is a regression model with values of y until Pth time
as predictors also known as lag order and ε is the white noise at time t and c is a constant and
φ are parameters.

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d is the degree of differencing: the number of times raw observations are differenced until
the original data becomes stationery and q is the order of moving average (MA) of the model
on past forecast errors where ε is white noise at time t and c is the constant, θs are parameters.
The combination of all three models resulted in the ARIMA(p,d,q) model, as below:
^y 0t ¼ c þ ;1 y0t 1 þ ;2 yt0 2 þ � � � þ ;p yt0 p þ y1 �t 1 þ y 2 �t 2 þ � � � þ y q �t q þ �t

The model used the auto.arima () method [23] in the forecast package in R Studio (1.1.383)
which chooses the best ARIMA model order [23]. The function in R uses a variation of the
Hyndman-Khandakar algorithm and automatically selects the best ARIMA order. [28] This
was used as we compared a large number of models with different parameter specifications
and temporal lags. An algorithm which can be operated automatically was felt to be more
appropriate for our purpose. Studies of automatic algorithms showed this methodology to be
particularly good for short-term prediction. [28, 34] In addition, this method is implemented
in a free software package (R language) which is cost efficient and could potentially be further
utilized by the government for their dengue surveillance data analysis. The proposed algorithm
for the automatic ARIMA model is where the number of differences 0�d�2 is determined
using repeated KPSS (Kwiatkowski–Phillips–Schmidt–Shin) tests, and the values of p and q
are selected by minimizing the AIC (Akaike information criteria) after differencing the data d
times. Using this method, short-term predictions of 1 month ahead for national and sub-
national levels that included three States/Regions (Yangon, Ayeyarwady, Mandalay) with the
highest dengue incidence were analyzed using data from preceding months. This 1 month
ahead timescale was selected in consultation with the national dengue control programme
after preliminary analysis showed 2–3 month ahead predictions to be much less accurate. The
variable used for forecasting was the monthly dengue incidence per 100,000 population which
was log transformed to stabilize variance. Models were run with and without all possible com-
binations of weather variables with lags from 0 to 3 months.
The data were plotted and examined for unusual observations. The residuals of the model
were checked for white noise with an ACF (Auto Correlation Function) plot. If it did not look
like white noise, the ACF plot of the differenced data was checked. If the residuals were white
noise, the models were processed for forecasting.
The data were split into a training period from the start of the data set to 12 months before
the end and testing period of the final 12 months. Forecast accuracies were evaluated by calcu-
lating mean squared errors (MSE), which is the difference between observed data and pre-
dicted data in the testing section and predictive R2, which is the variance of time series. The
residuals graphs and ACF plot were also used to check the accuracy of the models [23]. Fore-
casts were plotted with 95% confidence Intervals (CI) and visually compared with observed
data.

Results
Country level
From 2012 to 2017, 127,912 dengue cases were reported. During this period, there were 632
deaths with annual case fatality rates (CFR) of 0.45%, 0.54%, 0.65%, 0.33%, 0.54% and 0.61%,
an average of 0.50%. There was no trend over time in reported cases or CFR but there were
peaks in incidence in 2013, 2015 and 2017 (‘peak years’, Fig 1). Eighty nine percent of sus-
pected cases and 86% of deaths were aged 15 years or less (5.6% <1 year, 24% 1–4 years, 42%
aged 5–9 years, 18% 10–14 years and 11%>15 years; deaths 6% <1, 24% 1–4, 38% 5–9, 14%
10–14 and 14% >15 years, Fig 2). The 5–9 year age group contributed the highest proportions
of both incidence (42% overall) and mortality (38%). 49.8% of suspected cases were male with

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Fig 1. Seasonal pattern of dengue, rainfall and temperature.

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CFRs 0.4% in males and 0.7% in females in 2016 and 2017 (the only years for which deaths
were available by gender). There was a gradual increase in the proportion 15 years or older
from 2.0% in 2012 to 12.0% in 2017 but there were no differences in age or gender breakdown
between peak and non-peak years. Historically, dengue was mostly found in urban areas in
Myanmar. In the data, the disease was equally present in both rural and urban areas (Fig A in
S1 Text) with an increase in the proportion of urban cases in 2017.

Fig 2. Proportion of dengue cases from 2012 to 2017 and deaths in 2016 and 2017 by age group.
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State and region level

Dengue was reported in all fourteen States and Regions and Nay Pyi Taw council area. There
was a strong seasonal pattern of dengue cases and deaths, both with peaks in July to September
(Figs 3 and B in S1 Text). The timing of peaks in incidence varied greatly between States and
Regions with the same seasonal pattern but peak years/outbreaks in different years in different
locations (Fig 3). Mon State had the highest average incidence rate, followed by Kayah, Kayin
and Tanintharyi (Table A in S1 Text). The highest percentages of total cases were in Yangon
with 17%, Ayeyarwaddy with 12%, Mandalay with 11% and Mon with 11%. In 2015, cases
were reported for the first time in Chin State (Table A in S1 Text). In 2015, Kayah State
recorded the highest incidence rate (384 cases per 100,000 population) during the study
period. The highest number of deaths was reported in Yangon Region (60 deaths in 2017;

Fig 3. Monthly dengue incidence and mortality for States and Regions from 2012 to 2017. Left Y axis: Incidence per 100,000 population in descending
order of overall case count. Right Y axis: Case fatality rate.
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31.3% of the annual total with CFR 0.8%). The highest CFR was in Shan North Region at 2.4%
in 2013 (Table B in S1 Text). Severity of reported dengue cases varied by State and Region
with most cases in Mandalay Region being Grade II but all other States and Regions being
mostly Grade I (Fig C in S1 Text). The proportion with DSS varied greatly across the country.
Severity data were only available from 2016 and 2017 but there was consistency in these pat-
terns in these two years.

Township level
In 2012, 195/330 townships reported dengue cases, increasing to 252, 253, 272, 304 and 292
from 2013 to 2017. (Fig 4). There was significant annual spatial variation in the distribution of
dengue cases with an overall spread into northern, eastern and western townships over time.
The townships with highest incidence varied from year to year with peaks in different years in
different townships and no clear pattern of maximum incidence across townships (Fig 5). In
2017, townships in the northern and eastern parts of the country had the highest incidence
overall (Fig 4).
The 5 townships with the highest annual average incidence rates were Mawlamyine (185/
100,000) in Mon State, Bawlake (176/100,000) in Kayah State, Hpa-An (172/100,000) in Kayin
State, Dawei in Tanintharyi Region (166/100,000) and Minbya in Rakhine State (138/100,000)
(Fig 5). The next five highest incidence rates were two townships in Mon State and one town-
ship each from Kayin, Kayah and Rakhine State with more than 100 cases per 100,000.

Case fatality rate (CFR)

CFRs varied widely between townships with a varying geographical distribution from year to
year (Fig 6). The number of townships reporting fatal cases increased from 19 in 2012 to 99 in
2017, with average 72 (26% of townships with cases) from 2012 to 2017. There was no clear
pattern in the spatial distribution of CFRs at township level, however increased incidence gen-
erally coincided with increases in numbers of deaths.

Seasonal Pattern of Dengue incidence

A seasonal pattern was observed with annual peak from June to September and highest inci-
dence in July. This followed the peak in temperature by 2 to 3 months and coincided with, or

Fig 4. Township level annual dengue incidence per 100,000 population from 2012 to 2017. Source and terms of use for shapefile: https://geonode.themimu.
info/layers/geonode%3Ammr_polbnda_adm3_250k_mimu.
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Fig 5. Top ten endemic townships with annual dengue incidence per 100,000 population from 2012 to 2017.
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preceded, the peak in rainfall by 1–2 months. The rainy season is from May to October each
year. Time series decomposition showed there was strong seasonal pattern each year with no
trend over time, a peak every 2 years and no changes in seasonality (Fig 7).

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Fig 6. Township level annual dengue case fatality rates from 2012–2017. Source and terms of use for shapefile: https://geonode.themimu.info/layers/
geonode%3Ammr_polbnda_adm3_250k_mimu.
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Serotypes
The available dengue serotype information was from selected hospitals in Yangon, Mandalay,
Nay Pyi Taw, Mon and Tanintharyi Regions. The National Health Laboratory requests speci-
mens from cases with severe complications from selected hospitals and serological analysis is
done every year in selected Regions [35]. Dengue serotype results for selected Regions were
received from the VBDC database from 1999 to June 2018. DENV-1 was the predominant
serotype in most years with DENV-2 being predominant in 2003, DENV-3 in 2004–2007 and
DENV-4 in 2017 (Fig 8 and Table D in S1 Text).

Correlation with climatic factors

Spearman ρ. Average monthly rainfall with 0, 1, 2 and 3-month lags had significant posi-
tive correlations with dengue incidence in all States and Regions except Tanintharyi Region

Fig 7. Decomposition of additive time series of dengue cases from 2012–2017. From top to bottom: reported
incidence, trend, seasonality and random component.
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Fig 8. Reported dengue serotypes from 1999 to June 2018.

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where none were significant (Figs 9 andFig E and Table E in S1 Text). The strength of corre-
lations for rainfall and humidity decreased with increasing lag. Average maximum tempera-
ture, minimum temperature and mean temperature had significant mostly positive
correlations with dengue incidence with the duration of lag with significance varying between
Regions. The strongest correlations for temperature were with minimum temperature at 1
month of lag. Dew point was mostly positively correlated, most strongly at 0–1 months. The
correlations with rainfall, temperature and dew point were strongest for Sagaing Region.
There was no significant positive correlation with any climate variable at 0, 1 or 2 months for
Tanintharyi Region.
Univariable DLNM. In Yangon Region, the RR for association of dengue incidence with
minimum temperature peaked at 23˚C (RR = 1.84, 95% CI: 1.23–2.77), mean temperature at
30˚C (RR = 1.3, 95%CI: 0.8–2.0) and maximum temperature at 37˚C (RR = 2.3, CI: 0–12.1)
(Figs 10 and D in S1 Text). The elevated risk peaked at 1-month lag for minimum and 3
months for mean and maximum temperatures (Fig 10). The risk for relative humidity percent
peaked at 73% (RR = 3.5, CI: 0–16.6), declined sharply at 76% and peaked again at 86%. The
associated peak risks were at 1-month and 8-month lags respectively. The risk for rainfall
peaked at 300mm (RR = 2.5, CI: 1.2–5.0) with peak risk at 2-month lag.
Results of risks for different lags for Ayeyarwady Region, Mandalay Region, Rakhine State,
Sagaing Region and Tanintharyi Region are shown in Figs E to I in S1 Text. The lag for peak
risk and value of relative risk varied between States and Regions across all the weather vari-
ables. For Kachin and Kayah States, the univariate model did not converge as there were many
months with zero cases.
Multi-variable DLNM. This was attempted for all seven States/Regions for which climate
data was available: Yangon, Mandalay, Ayeyarwady, Kachin, Kayah, Rakhine, Sagaing and
Tanintharyi. Final model results were produced only for Yangon Region, Rakhine State and

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Fig 9. Correlation coefficient of dengue incidence per 100,000 population with various weather variables at different lags for
Kachin, Kayah State, Rakhine State, Ayeyarwady Region, Mandalay Region, Sagaing Region, Tanintharyi Region and Yangon
Region.
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Fig 10. Lag response curves of overall relative risks of each meteorological variable with monthly dengue
incidence per 100,000 population in Yangon Region.
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Tanintharyi Region with results presented below and in Figs 11, and J to O in S1 Text with
correlation matrices in Tables E to G in S1 Text. In Kachin and Kayah States, zero inflation
was encountered and quasi-likelihood was used to handle the dispersion but parameters were
still not well estimated. An alternative could be to use a zero-inflation model which was unfor-
tunately unavailable in the software. In Ayeyarwady and Sagaing Regions, there was high cor-
relation among climatic variables as shown in Tables H and I in S1 Text which also caused
difficulties in parameter estimation. Thus, in those States/Regions with correlation and exces-
sive zero issues, multivariable analysis was not performed and the Spearman’s coefficient
might be more appropriate.
In Yangon Region, the best variable combination for Yangon was mean temperature, rain-
fall, and relative humidity with QAIC of 953.63. The RR for mean temperature as exposure
variable while controlling for rainfall and relative humidity was 1.92 (CI: 0.67–5.41) at 26˚C
(Fig 11). The RR for relative humidity while controlling for mean temperature and rainfall was
2.46 (CI: 0.54–11.29) at 76% (Fig J in S1 Text). The RR for rainfall while controlling for mean
temperature and relative humidity was 4.61 (CI: 0.46–35.29) at 250mm (Fig K in S1 Text).
The risk of dengue was highest at mean temperature of 26˚C with a 3-month lag (RR = 1.92,
CI: 0.69–5.41, Fig 11).
In Rakhine State, the best weather variable combination was mean temperature and rainfall
(QAIC = 204.42). The RR for mean temperature while controlling for rainfall was 12.59 (CI:

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

Fig 11. The maximum RR of dengue incidence and mean temperature adjusting for relative humidity and
rainfall in Yangon Region, A. Association with temperature at 26˚C, centered at 28˚C. B. Maximum associated risks
at lag 3 months across different temperatures.
https://doi.org/10.1371/journal.pntd.0011331.g011

0.73–216.62, Fig L in S1 Text) and RR for rainfall controlling for mean temperature is 88.53
(CI: 3.84–2040.27, Fig M in S1 Text).
The best weather variable combination for Tanintharyi Region was rainfall and relative
humidity (QAIC = 680.37). The maximum RR for rainfall and dengue incidence while control-
ling for relative humidity was 14.89 (CI: 0.80–278.61) at 700mm (Fig N in S1 Text). The risk
associated with rainfall continued to exist across all lags up to 9 months. The maximum RR for
relative humidity while controlling for rainfall was 7.80 (CI: 0.55–111.16, Fig O in S1 Text) at
76%.

Short-term Dengue incidence forecasting

The best ARIMA model was obtained by comparing and minimizing AIC values from fore-
casts generated using the auto.arima () functions [23]. Forecast accuracies were improved by
comparing MSE and R2 values in each Region.
The models with best forecast accuracies were selected after comparing MSE and R2 values.
At national level, monthly incidence alone was able to predict the overall seasonal pattern
(Figs 12 and P in S1 Text). We compared different model specifications summarized in
Table J in S1 Text. We included the seasonal component alone in models 2.4, 3.3 and 4.3 and
the results were worse than using incidence data or incidence with weather data suggesting it
didn’t contribute to short-term prediction. This may be because the seasonal information was
already absorbed in the incidence and climatic covariates in the model. In addition, the lagged
correlation also suggests short term correlation between case lags.
Forecasts for Yangon, Ayeyarwady and Mandalay Regions were all improved by including
weather variables, although the magnitude of this improvement was small (Fig 13 and Fig Q
and Table K in S1 Text). Monthly percent humidity and dew point temperature at one-
month lags and rainfall and minimum temperature at 3-month lags, were the best predictor
climate variables for monthly dengue incidence in Yangon Region. Improvements in model
performance with climate for the other Regions were more modest. In Ayeyarwady Region,
percent humidity at one-month lag, rainfall at 0-month lag and dew point temperature at

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

Fig 12. National level dengue forecasts using cases as predictor.

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1-month lag were the best predictors and in Mandalay Region, dew point temperature at
3-month lag, rainfall at 0-month lag and minimum temperature at 1-month lag were best pre-
dictor variables. Changing the duration of the lags made only a small difference to model
performance.

Discussion
From 2012 to 2017 in Myanmar there was a strong seasonal pattern of dengue incidence with
timing of peak incidence and outbreak years varying between different States and Regions.

Fig 13. Comparisons of dengue forecasts between incidence and incidence plus weather variables showing the best
performing combination of weather variables for each State/Region. Lines for observed incidence, predicted
incidence and 95% confidence interval for predicted incidence are shown.
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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

Dengue was reported in more townships over time despite significant drops in cases in non-
outbreak years in 2012, 2014 and 2016. With development of the public health surveillance sys-
tem over time in Myanmar, it seems more likely that this change is due to improvements in
surveillance and reporting and better access to health services in more remote parts of the
country than an actual spread of dengue over time [36]. There were no long-term trends in the
climate variables in our data so they were unlikely to contribute to the increasing spatial extent.
Strengthening surveillance has included support from WHO from 2014 to 2018 for better data
collection by health facilities and at township level, strengthening the Health Management
Information System, improving access to care, improving coordination and resource mobiliza-
tion, and rapid response to disease outbreaks. [36] Although incidence rates were highest in
Mon State, particularly Mawlamyine, Mudon, Paung and Kyaikmaraw townships, Yangon
Region had the highest absolute numbers of cases and deaths, likely because it is by far the larg-
est city in the country. Similar to previous observations [35], numbers of deaths reflected the
numbers of cases and the majority of the mortality was in patients diagnosed with dengue
severity grade-4 (DSS).
There was a roughly even split of cases between urban and rural areas. The urban cases
were mostly in Yangon and Mandalay Regions, which have large urban populations, with
cases and deaths in the other States and Regions being reported from rural areas. With a split
of the general population into 30% urban and 70% rural, this suggests a relative excess of cases
in urban areas, as has been reported elsewhere [37]. More recent evidence from Viet Nam sug-
gests lower population densities have higher potential for dengue outbreaks although absolute
numbers of cases in rural areas would still be lower than urban areas [38]. To meet the national
goals for dengue control [18] will require concerted efforts across much of the country engag-
ing populations in both urban and rural areas.
There were no stable spatial pattern of dengue incidence at subnational levels and it was
observed that outbreak frequency was higher compared to that reported for the previous ten
years [18]. The age distribution of cases and deaths remained the same over time among chil-
dren with the 5–9 year age group having the most morbidity and mortality. In a previous study
in Myanmar [35], the highest risk age groups for death from dengue were infants and age
group >15 years. Possible reasons for this difference are changing availability of data or report-
ing practices over time. VBDC only released age group breakdown of cases and fatalities coun-
try wide from 2016 onward. In 2015, there was an unusual increase in the occurrence of adult
dengue cases for patients admitted at Yangon General Hospital [39] and in our study, we
found that the incidence of dengue in adults increased 6-fold from 2012 to 2017. The age dis-
tribution overall had a relative lack of adults compared to other countries with similar epide-
miology [40], although this was increasing over time. This low incidence in adults may be
because of higher transmission with higher attack rates for symptomatic infection in children,
potentially compounded by under-reporting in older age groups. Another possible explanation
is reporting bias of physicians caring for adults who do not sufficiently suspect or report den-
gue; with the data suggesting a gradual improvement in this practice.
In our dataset, there was variation in the most prevalent serotype over time, although all
four were present throughout. DENV-1 was the most dominant serotype, and DENV-2,
DENV-3, DEN-4 were roughly equally distributed. There was very limited sample size with
the data being from routine surveillance and serotype data from research studies not being
included in the VBDC database thus limiting the possibility of making any inferences about
relationship to outbreaks and trends over time. Research studies looking at serotype patterns
in Myanmar [35] described larger sample sizes than in the routine surveillance database and
identified higher numbers of infections of all four serotypes from 2013 to 2015. Studies of den-
gue outbreaks in 2013 and 2015 found that there was no cross correlation among serotypes

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

with DENV-1 being predominant in 2013 [41] and all 4 serotypes being present in the 2015
[35] outbreak, both of which were consistent with our data. In the most recent year in our
serotype data, 2018, DENV-3 was the predominant serotype. More widespread collection of
serotype data from all DHF cases would be more informative.
Average mean temperature, minimum temperature and maximum temperature at different
lags were positively correlated with dengue incidence [6–9]. The survival rate of Aedes mosqui-
toes is related to increases in temperature and their ability to travel long distances travelling
with people [42–44], resulting in dengue spreading to new areas. Historical data from the Cli-
mate Change Network portal of the World Bank, show the ten-year average temperature in
Yangon to be gradually increasing, from average 22.71˚C in 1901–1910, to 23.28˚C in 2000–
2010 and 23.38˚ C in 2010–2016. Minimum temperature was consistently positively correlated
with incidence whereas the relationship for maximum temperature was weaker and sometimes
negatively correlated for some States/Regions (Yangon and Ayerawaddy). This may be a reflec-
tion of there being an ideal temperature for breeding of the mosquito vectors of 17˚C to 35˚C
[45, 46] with increases in maximum temperature beyond that range reducing the chance of
vector survival. The States/Regions with negative correlations with maximum temperature had
more days per year above this range than those with all positive correlations. In Tanintharyi
Region, the correlations were much weaker than the others, suggesting another as yet uniden-
tified factor is strongly driving transmission in this area.
There was a strong seasonal pattern of dengue incidence in Myanmar with the timing of
the season correlated with peaks in rainfall. Percent humidity and DEW point are high when
rainfall and temperature are high and these conditions enhance breeding and survival of the
vector population [47]. Other studies have also confirmed that (mean, maximum and mini-
mum) temperature was significantly associated with dengue incidence at a lag of 0 to 3 months
e.g. in Cambodia [25] and Singapore [48]. Rainfall and Humidity were positively correlated
with dengue incidence and studies suggest that global increases in temperature, rainfall and
humidity are possible factors behind the increase in dengue epidemics [42, 49, 50]. In the pres-
ent study, we found that peaks in dengue generally coincided with and sometimes preceded
peaks in rainfall. This may be because excess rainfall can wash away mosquito breeding sites
and cause a decrease in dengue transmission [51].
The models with best forecast accuracies differed by location. Predictions for the whole
country and for Yangon Region were close to observed data and had narrower confidence
intervals than those of other Regions. Time series analysis with an ARIMA model closely pre-
dicted the trend and the peak months. Incorporating weather variables improved the predic-
tive power of the ARIMA model particularly in Yangon, with more modest improvements in
Ayeyarwady and Mandalay Regions. However, sufficiently up to date climate station data is
currently difficult for the National Dengue Programme to access in time to use in a model and
there was no climate station data available in the publicly available datasets for many areas,
including other States/Regions. There is potential for remote sensing data to substitute with
further research to quantify the strength of correlation but such data is technically challenging
to process and not currently feasible for the dengue control programme to use on a short time-
scale needed for guiding interventions ahead of time. Overall, performance improvements on
adding climate data were small and the additional effort may not be warranted as the practical
impact of marginal improvements in predictive power on planning dengue control activities is
likely to be minimal. The results show ARIMA using historical incidence data is a simple and
effective method for predicting future dengue incidence and is useful for rapidly analysing sur-
veillance data as previously described [52] including in similar studies in Colombia [29], Ban-
gladesh [53], Brazil [54] and Bhutan [55]. This prediction method is better than using

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

historical seasonality alone as the timing and height of peaks in incidence varies between dif-
ferent parts of the country and changes from year to year.
The selected method for Myanmar of one month ahead prediction balances providing suffi-
cient warning for the control programme to implement interventions to reduce transmission
against the loss of prediction accuracy seen over longer timescales thus minimizing the occur-
rence of false alarms. These interventions may include mosquito habitat reduction by reducing
standing water sources for which a public health education campaign could be triggered by the
early warning from a prediction model. An alternative could be anticipatory insecticide fog-
ging of areas with high predicted incidence. With further development and testing, this
method has potential to enhance preparedness by short-term forecasting of dengue outbreaks
in Myanmar giving decision makers some advance warning and more time to plan control
measures, public health messaging and allocation of additional resources for healthcare. This
would be an improvement on the current system of reacting to changes in reported case num-
bers. Further research is needed to identify if there are other variables which could improve
the predictions whilst also being readily available to the government for use in real-time
including in other countries. Improving the certainty of predictions over longer timescales
may be particularly useful, as demonstrated using cellphone-derived mobility data in Thailand.
[9].
There are some limitations in this study. We used aggregated routine surveillance data col-
lected by the Ministry of Health from cases admitted to hospital. It was not possible to thor-
oughly assess the quality of the data as there was no comparator dataset available and no
information on completeness of reporting. Basic checks on completeness and consistency
revealed no issues. Dengue case reporting in Myanmar is health facility-based and the data
received were already aggregated at township level. This also limited the data quality checks
that could be done and constrained the spatial scale of the analysis. The township level data
was only available aggregated by year and State/Region by month which further limited the
possible analyses. During the period of the study, there have been efforts to improve the com-
municable disease surveillance system in Myanmar, including by WHO [36], but it was not
possible to quantify the impact of this on the consistency of data over time. Cases of suspected
dengue in Myanmar are not routinely tested and even where available this test result is not
recorded in the central surveillance database. Thus, most cases are diagnosed using WHO clin-
ical criteria alone. We have shown previously in a systematic review that the sensitivity of the
1997 WHO case definition is 93% with a specificity of 29%. Many of the cases reported as den-
gue may therefore have had a different diagnosis [56]. The data used in this study was DHF
cases only as that is what is collected by the government. As the case definition for DHF
requires haemorrhagic manifestations, and these are uncommon in other febrile illnesses in
Myanmar, the specificity is likely to be higher. Additionally, many people with dengue do not
attend health services and are therefore not reported, thus leading to an under-estimate of dis-
ease which is likely to be greater in areas with poorer access to health services. Thus, under-
served populations and those living in remote areas are more likely to be under-represented in
the data. It was not possible to quantify the impact of changes in surveillance on the data over
time. Assuming the under and over-reporting fractions were similar over the study period, the
methods and overall space-time incidence trend should still be valid. If surveillance substan-
tially improved, this may result in an increase in completeness of case data with better ability
to accurately predict short-term trends. We are not aware of substantial changes to these limi-
tations since 2017, although an updated analysis with data from 2018–2019 may be informative
but this data was not available to the study team. Five states (Bago, Magway, Mon, Kayin and
Shan) were omitted from the correlation and predictive analysis using climate data due to
there being no climate stations in those states. Four of these (Bago, Magway, Mon and Kayin)

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

are in the tropical climate zone with similar climates to Yangon and Ayeyarwady. The other
(Shan) is in the temperate zone with similar climate to Kachin. Thus, if climate data were avail-
able, it could be expected to have a similar modest impact on predictive ability of the models.
Further studies are needed to quantify the true burden of dengue in Myanmar and confirm
which population groups are most affected, as well as to identify modifiable risk factors to
reduce transmission. Future research might also focus on predicting where future outbreaks
are likely to occur. Climate change has also been predicted to contribute to an increase in den-
gue incidence over longer timescales [57–59] and further studies to understand this would be
important for Dengue Control Programmes to plan future interventions.
In conclusion, analysis of routine surveillance data on mostly hospitalised cases with den-
gue in Myanmar was able to show, despite limitations and biases, a clear seasonal pattern asso-
ciated with rainfall with biennial peaks in incidence and an increase in the geographic
distribution of cases over time. The timing of outbreaks varied between different parts of the
country. Using a simple model, it was possible to make accurate short-term predictions of inci-
dence which have potential to guide planning of upcoming dengue control activities.

Supporting information
S1 RECORD Checklist. The RECORD statement–checklist of items, extended from the
STROBE statement, that should be reported in observational studies using routinely col-
lected health data.
(PDF)
S1 Text. Fig A in S1 Text. Proportion of dengue cases in urban and rural areas. Fig B in S1
Text. State/Region level monthly dengue cases and number of deaths. Fig C in S1 Text. Den-
gue severity grades by States and Regions in 2016 and 2017. Source and terms of use for shape-
file: https://geonode.themimu.info/layers/geonode%3Ammr_polbnda_adm1_250k_mimu.
Fig D in S1 Text. Overall association of univariate analysis with minimum temperature, mean
temperature, maximum temperature, rainfall and relative humidity percent with dengue inci-
dence in Yangon Region. Fig E in S1 Text. Lag response curves of overall relative risks of each
meteorological variable with monthly dengue incidence per 100,000 population for Ayerar-
wady Region. Fig F in S1 Text. Lag response curves of overall relative risks of each meteoro-
logical variable with monthly dengue incidence per 100,000 population for Mandalay Region.
Fig G in S1 Text. Lag response curves of overall relative risks of each meteorological variable
with monthly dengue incidence per 100,000 population for Rakhine State. Fig H in S1 Text.
Lag response curves of overall relative risks of each meteorological variable with monthly den-
gue incidence per 100,000 population for Sagaing Region. Fig I in S1 Text. Lag response
curves of overall relative risks of each meteorological variable with monthly dengue incidence
per 100,000 population for Thanintharyi Region. Fig J in S1 Text. Results of multivariable
analysis of maximum RR of dengue incidence and climate for relative humidity percent adjust-
ing for mean temperature and rainfall and in Yangon Region. A. Lag response curve, associa-
tion with relative humidity at 76%, centered at 82.5%. B. Maximum associated risks at lag 6
months across different humidity levels. Fig K in S1 Text. Results of multivariable analysis of
maximum RR of dengue incidence and climate for rainfall adjusting for mean temperature
and relative humidity in Yangon Region. A. Lag response curve, association with rainfall at
250mm, centered at 500mm. B. Maximum associated risks at lag 8 months across different
rainfall levels. Fig L in S1 Text. Results of multivariable analysis of maximum RR of dengue
incidence and climate for mean temperature adjusting for rainfall in Rakhine State. A. Lag
response curve, association with mean temperature at 29˚C, centered at 27˚C. B. Maximum
associated risks at lag 8 months across different mean temperatures. Fig M in S1 Text. Results

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

of multivariable analysis of maximum RR of dengue incidence and climate for rainfall adjust-
ing for mean temperature in Rakhine State. A. Lag response curve, association with rainfall at
350mm, centered at 1250mm. B. Maximum associated risks at lag 10 months across different
rainfall levels. Fig N in S1 Text. Results of multivariable analysis of maximum RR of dengue
incidence and climate for rainfall adjusting for relative humidity in Tanintharyi Region. A. Lag
response curve, association with rainfall at 700mm, centered at 400mm. B. Maximum associ-
ated risks at lag 8 months across different rainfall levels. Fig O in S1 Text. Results of multivari-
able analysis of maximum RR of dengue incidence and climate for relative humidity adjusting
for rainfall in Tanintharyi Region. A. Lag response curve, association with relative humidity at
76%, centered at 80%. B. Maximum associated risks at lag 9 months across different humidity
levels. Fig P in S1 Text. Residuals of incidence prediction results using ARIMA model without
(left) and with (right) weather variables for the whole country. A. Residuals of the model by
month, B. Autocorrelation plot (ACF), C. Histograms of the residuals. Fig Q in S1 Text. Resid-
uals of incidence prediction results using ARIMA model without (left) and with (right)
weather variables for Yangon, Mandalay, Ayeyarwady. A. Residuals of the model by month, B.
Autocorrelation plot (ACF), C. Histograms of the residuals. Table A in S1 Text. Annual den-
gue incidence per 100,000 population by State and Region. Table B in S1 Text. Annual dengue
case fatality rates by State and Region. Table C in S1 Text. Reported dengue serotypes from
1999 to June 2018. Table D in S1 Text. Correlation of dengue incidence per 100,000 popula-
tion with different weather variables in Kachin, Kayah, Ayeyarwady, Mandalay, Sagaing,
Tanintharyi and Yangon Regions. Table E in S1 Text. Correlation matrix of climate variables
for Yangon Region. Table F in S1 Text. Correlation matrix of climate variables for Rakhine
State. Table G in S1 Text. Correlation matrix of climate variables for Thanintharyi Region
Table H in S1 Text. Correlation matrix of climate variables for Ayeyarwady Region. Table I
in S1 Text. Correlation matrix of climate variables for Sagaing Region. Table J in S1 Text.
Comparisons of different regions’ ARIMA model order with and without covariates for the
whole country, and for Yangon, Mandalay and Ayeyarwady Regions. Table K in S1 Text. Pre-
diction comparisons of observed and predicted data with the best model and seasonality alone
(first seasonal autoregressive and difference order) for the whole country and Mandalay
Region, Mon State, Yangon Region and Ayeyarwady Region.
(DOCX)

Acknowledgments
The authors would like to thank healthcare workers and staff of the Myanmar Ministry of
Health and Sports who collected and managed the data analysed in this manuscript. MORU/
Mahidol Oxford Tropical Medicine Research Unit was funded in part by the Wellcome Trust
[Grant numbers 220211 and 106698/Z/14/Z]. For the purpose of open access, the author has
applied a CC BY public copyright licence to any Author Accepted Manuscript version arising
from this submission.

Author Contributions
Conceptualization: Win Zaw, Zaw Lin, Neriza Pantanilla, Steeve Ebener, Richard James
Maude.
Data curation: Win Zaw, Zaw Lin, July Ko Ko, Neriza Pantanilla, Steeve Ebener.
Formal analysis: Win Zaw, Chawarat Rotejanaprasert, Richard James Maude.
Funding acquisition: Richard James Maude.

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PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

Investigation: Zaw Lin, Chawarat Rotejanaprasert, Richard James Maude.

Methodology: Zaw Lin, Chawarat Rotejanaprasert, Neriza Pantanilla, Steeve Ebener, Richard
James Maude.
Project administration: July Ko Ko, Neriza Pantanilla, Richard James Maude.
Resources: Zaw Lin, Richard James Maude.
Software: Chawarat Rotejanaprasert, Richard James Maude.
Supervision: Chawarat Rotejanaprasert, Richard James Maude.
Validation: Zaw Lin, July Ko Ko, Richard James Maude.
Visualization: Win Zaw.
Writing – original draft: Win Zaw, Richard James Maude.
Writing – review & editing: Zaw Lin, July Ko Ko, Chawarat Rotejanaprasert, Neriza
Pantanilla, Steeve Ebener, Richard James Maude.

References
1. WHO. Dengue and severe dengue Geneva: World Health Organization; 2020 [Available from: https://
www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue.
2. WHO. Dengue data application. Geneva: World Health Organization; 2018 [cited 2018. Available from:
https://ntdhq.shinyapps.io/dengue5/.
3. Sujariyakul A, Prateepko S, Chongsuvivatwong V, Thammapalo S. Transmission of Dengue Haemor-
rhagic Fever: At Home or School? Dengue Bulletin. 2005; 29:32–40.
4. Gubler DJ, Ooi EE, Vasudevan J, Farrar J. Dengue and dengue haemorrhagic Fever, 2nd Edition:
CAB International; 2014. 606 p.
5. Guzman MG, Harris E. Dengue. Lancet. 2015; 385(9966):453–65. https://doi.org/10.1016/S0140-6736
(14)60572-9 PMID: 25230594
6. Findlater A, Moineddin R, Kain D, Yang J, Wang X, Lai S, et al. The use of air travel data for predicting
dengue importation to China: A modelling study. Travel Med Infect Dis. 2019; 31:101446. https://doi.
org/10.1016/j.tmaid.2019.07.002 PMID: 31284067
7. Tian H, Sun Z, Faria NR, Yang J, Cazelles B, Huang S, et al. Increasing airline travel may facilitate co-
circulation of multiple dengue virus serotypes in Asia. PLoS Negl Trop Dis. 2017; 11(8):e0005694.
https://doi.org/10.1371/journal.pntd.0005694 PMID: 28771468
8. Verma S, Kanga A, Singh D, Verma GK, Mokta K, Ganju SA, et al. Emergence of travel: Associated
dengue fever in a non-endemic, hilly state. Adv Biomed Res. 2014; 3:239. https://doi.org/10.4103/2277-
9175.145744 PMID: 25538925
9. Kiang MV, Santillana M, Chen JT, Onnela JP, Krieger N, Engo-Monsen K, et al. Incorporating human
mobility data improves forecasts of Dengue fever in Thailand. Sci Rep. 2021; 11(1):923. https://doi.org/
10.1038/s41598-020-79438-0 PMID: 33441598
10. David MR, Lourenco-de-Oliveira R, Freitas RM. Container productivity, daily survival rates and dis-
persal of Aedes aegypti mosquitoes in a high income dengue epidemic neighbourhood of Rio de
Janeiro: presumed influence of differential urban structure on mosquito biology. Mem Inst Oswaldo
Cruz. 2009; 104(6):927–32. https://doi.org/10.1590/s0074-02762009000600019 PMID: 19876569
11. Maciel-De-Freitas R, Codeco CT, Lourenco-De-Oliveira R. Body size-associated survival and dispersal
rates of Aedes aegypti in Rio de Janeiro. Med Vet Entomol. 2007; 21(3):284–92. https://doi.org/10.
1111/j.1365-2915.2007.00694.x PMID: 17897370
12. Bhatia S, Bansal D, Patil S, Pandya S, Ilyas QM, Imran S. A Retrospective Study of Climate Change
Affecting Dengue: Evidences, Challenges and Future Directions. Front Public Health. 2022; 10:884645.
https://doi.org/10.3389/fpubh.2022.884645 PMID: 35712272
13. Shepard DS, Undurraga EA, Betancourt-Cravioto M, Guzman MG, Halstead SB, Harris E, et al.
Approaches to refining estimates of global burden and economics of dengue. PLoS Negl Trop Dis.
2014; 8(11):e3306. https://doi.org/10.1371/journal.pntd.0003306 PMID: 25412506

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011331 June 5, 2023 21 / 24

PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

14. Zhang Y, Wang T, Liu K, Xia Y, Lu Y, Jing Q, et al. Developing a Time Series Predictive Model for Den-
gue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data. PLoS Negl
Trop Dis. 2016; 10(2):e0004473. https://doi.org/10.1371/journal.pntd.0004473 PMID: 26894570
15. Campbell KM, Haldeman K, Lehnig C, Munayco CV, Halsey ES, Laguna-Torres VA, et al. Weather
Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosqui-
toes. PLoS Negl Trop Dis. 2015; 9(7):e0003957. https://doi.org/10.1371/journal.pntd.0003957 PMID:
26222979
16. Ehelepola ND, Ariyaratne K, Buddhadasa WM, Ratnayake S, Wickramasinghe M. A study of the corre-
lation between dengue and weather in Kandy City, Sri Lanka (2003–2012) and lessons learned. Infect
Dis Poverty. 2015; 4:42. https://doi.org/10.1186/s40249-015-0075-8 PMID: 26403283
17. Myat TW, Myat H, Kyaw YM, Aye KM, Win MM, Mar W, et al. Identification of Dengue Virus Serotypes
in Children with Dengue Infection Admitted to Yangon Children’s Hospital in 2014. Myanmar Health Sci-
ences Research Journal. 2016; 28(1):60–4.
18. Myanmar V. National Strategic Plan for Dengue Prevention and Control 2016–2020. Myanmar; 2016.
19. WHO. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control 2nd edition. Geneva:
World Health Organization; 1997.
20. Menne MJ, Durre I, Vose RS, Gleason BE, Houston TG. An Overview of the Global Historical Climatol-
ogy Network-Daily Database. Atmos Oceanic Technol. 2012; 29:897–910.
21. Camarillo-Naranjo JM, Álvarez-Francoso JI, Limones-Rodrı́guez N, Pita-López MF, Aguilar-Alba M.
The Global Climate Monitor System: From Climate Data-Handling to Knowledge Dissemination. Inter-
national Journal of Digital Earth. 2019; 12(4):394–414.
22. Alduchov OA, Eskridge RE. Improved Magnus Form Approximation of Saturation Vapor Pressure. Jour-
nal of Applied Meteorology. 1996; 35(4):601–9.
23. Hyndman RJ G. A. Forecasting: principles and practice, 2nd edition [Online Ebook]. Melbourne:
OTexts; 2018. Available from: https://otexts.com/fpp2/.
24. Gasparrini A. Modeling exposure–lag–response associations with distributed lag non-linear models.
Statistics in Medicine. 2014; 33(5):881–99. https://doi.org/10.1002/sim.5963 PMID: 24027094
25. Choi Y, Tang CS, McIver L, Hashizume M, Chan V, Abeyasinghe RR, et al. Effects of weather factors
on dengue fever incidence and implications for interventions in Cambodia. BMC Public Health. 2016; 16
(1):241. https://doi.org/10.1186/s12889-016-2923-2 PMID: 26955944
26. Van Kleef E, Bambrick H, Hales S. The geographic distribution of dengue fever and the potential influ-
ence of global climate change. TropIKAnet. 2010.
27. Luo C, Qian J, Liu Y, Lv Q, Ma Y, Yin F. Long-term air pollution levels modify the relationships between
short-term exposure to meteorological factors, air pollution and the incidence of hand, foot and mouth
disease in children: a DLNM-based multicity time series study in Sichuan Province, China. BMC Public
Health. 2022; 22(1):1484. https://doi.org/10.1186/s12889-022-13890-7 PMID: 35927638
28. Hyndman RJ, Khandakar Y. Automatic Time Series Forecasting: The forecast Package for R. Journal
of Statistical Software. 2008; 27(3):1–22.
29. Lopez-Montenegro LE, Pulecio-Montoya AM, Marcillo-Hernandez GA. Dengue Cases in Colombia:
Mathematical Forecasts for 2018–2022. MEDICC Rev. 2019; 21(2–3):38–45. https://doi.org/10.37757/
MR2019.V21.N2-3.8 PMID: 31373583
30. Siriyasatien P, Phumee A, Ongruk P, Jampachaisri K, Kesorn K. Analysis of significant factors for den-
gue fever incidence prediction. BMC Bioinformatics. 2016; 17:166. https://doi.org/10.1186/s12859-016-
1034-5 PMID: 27083696
31. Wongkoon S, Jaroensutasinee M, Jaroensutasinee K. Development of temporal modeling for prediction
of dengue infection in northeastern Thailand. Asian Pac J Trop Med. 2012; 5(3):249–52. https://doi.org/
10.1016/S1995-7645(12)60034-0 PMID: 22305794
32. Nobre FF, Monteiro AB, Telles PR, Williamson GD. Dynamic linear model and SARIMA: a comparison
of their forecasting performance in epidemiology. Stat Med. 2001; 20(20):3051–69. https://doi.org/10.
1002/sim.963 PMID: 11590632
33. Yurekli K, Kurunc A, Ozturk F. Application of linear stochastic models to monthly flow data of Kelkit
Stream. Ecological Modelling. 2005; 183(1):67–75.
34. Hyndman RJ, Koehler AB, Snyder RD, Grose S. A state space framework for automatic forecasting
using exponential smoothing methods. Int J forecasting. 2002; 18(3):439–54.
35. Oo PM, Wai KT, Harries AD, Shewade HD, Oo T, Thi A, et al. The burden of dengue, source reduction
measures, and serotype patterns in Myanmar, 2011 to 2015-R2. Trop Med Health. 2017; 45:35. https://
doi.org/10.1186/s41182-017-0074-5 PMID: 29118655

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011331 June 5, 2023 22 / 24

PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

36. Myanmar. WHOCOf. WHO Country Cooperation Strategy: 2014–2018, Myanmar. Yangon: World
Health Organization. Country Office for Myanmar; 2014 2014. Report No.: 9789290224495.
37. Gubler DJ. Cities spawn epidemic dengue viruses. Nature medicine. 2004; 10(2):129–30. https://doi.
org/10.1038/nm0204-129 PMID: 14760418
38. Schmidt W-P, Suzuki M, Dinh Thiem V, White RG, Tsuzuki A, Yoshida L-M, et al. Population Density,
Water Supply, and the Risk of Dengue Fever in Vietnam: Cohort Study and Spatial Analysis. PLOS
Medicine. 2011; 8(8):e1001082. https://doi.org/10.1371/journal.pmed.1001082 PMID: 21918642
39. Myat TW, Thu HM, Win HM, Than KS, Tun ZT, Aye KM, et al. Clinical Profile and Circulating Dengue
Virus Serotype among Adults Admitted to Yangon General Hospital during the 2015 Dengue Outbreak.
OSIR. 2017; 10(2):8–13.
40. Phanitchat T, Zhao B, Haque U, Pientong C, Ekalaksananan T, Aromseree S, et al. Spatial and tempo-
ral patterns of dengue incidence in northeastern Thailand 2006–2016. BMC Infectious Diseases. 2019;
19(1):743. https://doi.org/10.1186/s12879-019-4379-3 PMID: 31443630
41. Ngwe Tun MM, Thant KZ, Inoue S, Kurosawa Y, Lwin YY, Lin S, et al. Serological characterization of
dengue virus infections observed among dengue hemorrhagic fever/dengue shock syndrome cases in
upper Myanmar. J Med Virol. 2013; 85(7):1258–66. https://doi.org/10.1002/jmv.23577 PMID:
23595687
42. Murray NEA, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects.
Clin Epidemiol. 2013; 5:299–309. https://doi.org/10.2147/CLEP.S34440 PMID: 23990732
43. Wilder-Smith A, Gubler DJ. Geographic expansion of dengue: the impact of international travel. Med
Clin North Am. 2008; 92(6):1377–90, x. https://doi.org/10.1016/j.mcna.2008.07.002 PMID: 19061757
44. Reiter P. Climate change and mosquito-borne disease. Environmental Health Perspectives. 2001; 109
(suppl 1):141–61. https://doi.org/10.1289/ehp.01109s1141 PMID: 11250812
45. Shapiro LLM, Whitehead SA, Thomas MB. Quantifying the effects of temperature on mosquito and par-
asite traits that determine the transmission potential of human malaria. PLOS Biology. 2017; 15(10):
e2003489. https://doi.org/10.1371/journal.pbio.2003489 PMID: 29036170
46. Mordecai EA, Caldwell JM, Grossman MK, Lippi CA, Johnson LR, Neira M, et al. Thermal biology of
mosquito-borne disease. Ecol Lett. 2019; 22(10):1690–708. https://doi.org/10.1111/ele.13335 PMID:
31286630
47. Focks DA, Haile DG, Daniels E, Mount GA. Dynamic Life Table Model for Aedes aegypti (Diptera: Culi-
cidae): Analysis of the Literature and Model Development. Journal of Medical Entomology. 1993; 30
(6):1003–17. https://doi.org/10.1093/jmedent/30.6.1003 PMID: 8271242
48. Hii YL. Climate and Dengue Fever: early warning based on temperature and rainfall. Sweden: Umeå
University; 2013.
49. Russell RC, Currie BJ, Lindsay MD, Mackenzie JS, Ritchie SA, Whelan PI. Dengue and climate change
in Australia: predictions for the future should incorporate knowledge from the past. Medical Journal of
Australia. 2009; 190(5):265–8. https://doi.org/10.5694/j.1326-5377.2009.tb02393.x PMID: 19296793
50. Van Kleef E, Bambrick H, Hales S. The geographic distribution of dengue fever and the potential influ-
ence of global climate change. TropIKAnet. 2010:1–22.
51. Benedum CM, Seidahmed OME, Eltahir EAB, Markuzon N. Statistical modeling of the effect of rainfall
flushing on dengue transmission in Singapore. PLoS neglected tropical diseases. 2018; 12(12):
e0006935–e. https://doi.org/10.1371/journal.pntd.0006935 PMID: 30521523
52. Allard R. Use of time-series analysis in infectious disease surveillance. Bull World Health Organ. 1998;
76(4):327–33. PMID: 9803583
53. Zahirul Islam M, Rutherford S, Phung D, Uzzaman MN, Baum S, Huda MM, et al. Correlates of Climate
Variability and Dengue Fever in Two Metropolitan Cities in Bangladesh. Cureus. 2018; 10(10):e3398.
https://doi.org/10.7759/cureus.3398 PMID: 30533332
54. Cortes F, Turchi Martelli CM, Arraes de Alencar Ximenes R, Montarroyos UR, Siqueira Junior JB, Gon-
calves Cruz O, et al. Time series analysis of dengue surveillance data in two Brazilian cities. Acta Trop.
2018; 182:190–7. https://doi.org/10.1016/j.actatropica.2018.03.006 PMID: 29545150
55. Wangdi K, Singhasivanon P, Silawan T, Lawpoolsri S, White NJ, Kaewkungwal J. Development of tem-
poral modelling for forecasting and prediction of malaria infections using time-series and ARIMAX anal-
yses: a case study in endemic districts of Bhutan. Malar J. 2010; 9:251. https://doi.org/10.1186/1475-
2875-9-251 PMID: 20813066
56. Raafat N, Loganathan S, Mukaka M, Blacksell SD, Maude RJ. Diagnostic accuracy of the WHO clinical
definitions for dengue and implications for surveillance: A systematic review and meta-analysis. PLOS
Neglected Tropical Diseases. 2021; 15(4):e0009359. https://doi.org/10.1371/journal.pntd.0009359
PMID: 33901191

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011331 June 5, 2023 23 / 24

PLOS NEGLECTED TROPICAL DISEASES Epidemiology of dengue in Myanmar

57. Bannister-Tyrrell M, Williams C, Ritchie SA, Rau G, Lindesay J, Mercer G, et al. Weather-driven varia-
tion in dengue activity in Australia examined using a process-based modeling approach. Am J Trop
Med Hyg. 2013; 88(1):65–72. https://doi.org/10.4269/ajtmh.2012.11-0451 PMID: 23166197
58. Anyamba A, Small JL, Britch SC, Tucker CJ, Pak EW, Reynolds CA, et al. Recent weather extremes
and impacts on agricultural production and vector-borne disease outbreak patterns. PLoS One. 2014; 9
(3):e92538. https://doi.org/10.1371/journal.pone.0092538 PMID: 24658301
59. Li C, Wang X, Wu X, Liu J, Ji D, Du J. Modeling and projection of dengue fever cases in Guangzhou
based on variation of weather factors. Sci Total Environ. 2017;605–606:867–73. https://doi.org/10.
1016/j.scitotenv.2017.06.181 PMID: 28683431

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011331 June 5, 2023 24 / 24