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. 2025 Sep 4;19(9):e0012649. doi: 10.1371/journal.pntd.0012649

Extreme weather events and dengue in Southeast Asia: A regionally-representative analysis of 291 locations from 1998 to 2021

Sophearen Ith 1,2, Xerxes Seposo 3,4,*, Vitou Phy 5, Kraichat Tantrakarnapa 6, Geminn Louis C Apostol 4, Pandji Wibawa Dhewantara 7, Rozita Hod 8, Mohd Rohaizat Hassan 8,9, Hidayatulfathi Othman 10, Mazrura Sahani 10, Jue Tao Lim 11, Ha Hong Nhung 12, Nguyen Hai Tuan 12, Ngu Duy Nghia 12, Taichiro Takemura 13, Inthavong Nouhak 14, Paul L C Chua 1, Alex R Cook 15, Felipe J Colón-González 16,17,18, Masahiro Hashizume 1
Editor: Mohamed Gomaa Kamel19
PMCID: PMC12419652  PMID: 40906771

Abstract

Background

Climate change, leading to more frequent and intense extreme weather events (EWEs), could significantly impact dengue transmission. However, the associations between EWEs and dengue remains underexplored in the Southeast Asia (SEA) region. We investigated the association between selected EWEs (i.e., heatwaves, extremely wet, and drought conditions) and dengue in the SEA region.

Methods and findings

Monthly dengue case reports were obtained from 291 locations across eight SEA countries between 1998 and 2021. Heatwaves are defined as the monthly total number of days where temperatures exceed the 95th percentile for at least two consecutive days. Droughts and extremely wet conditions are defined by a self-calibrating Palmer Drought Severity Index (scPDSI). We implemented a generalized additive mixed model coupled with a distributed lag non-linear model to estimate the association between each EWE and dengue. Months with fewer than 12 heatwave days increased dengue risk with delayed effect after two months lag, compared with months without any heatwave. Highest dengue risk is at 7 heatwave days (RR = 1·28; 95%CI: 1·19,1·38). Compared to normal conditions (i.e. scPDSI = 0), drought conditions (i.e. scPDSI = –4) were positively associated with dengue risk (RR = 1·85; 95%CI: 1·73,1·99), while extremely wet conditions (i.e. scPDSI = 4) have reduced dengue risk (RR = 0·89; 95%CI: 0·87,0·91). Although the findings of this study are significant, its limitations arise from the inconsistency of dengue case reporting, which might complicate dengue risk estimation.

Conclusions

This study shows that the delayed effect of heatwaves and drought conditions magnifies the risk of dengue in the SEA region. The findings highlight the need for public health interventions to mitigate the potential dengue risks posed by EWEs in the context of climate change in SEA. Future research should investigate the factors influencing variations in the EWE-dengue association across the region to support the development of tailored, location-specific mitigation and prevention strategies.

Author summary

Dengue remains a major public health concern in Southeast Asia region, where the warm and humid climates create optimal conditions for dengue transmission. Extreme weather events are expected to intensify with climate change and may further influence dengue disease. In this study, we examine the association between extreme weather events—such as heatwaves, droughts, and extremely wet conditions—and dengue, using data from 291 locations across eight Southeast Asian countries from 1998 to 2021. We found that heatwaves were associated with an increased risk of dengue after a two-month lag. Drought conditions showed a significant positive association with dengue. Interestingly, while extremely wet conditions are linked to lower dengue risk, very high wetness shows a non-significant increase, requiring further investigation to better understand these patterns. These findings highlight the critical role of extreme weather events in shaping dengue transmission and provide valuable insights for targeted public health interventions. By understanding these weather-dengue relationships, policymakers can strengthen preparedness and mitigate the impacts of climate-sensitive diseases like dengue.

Introduction

Dengue is caused for flaviviruses, transmitted by the infectious bite of Aedes aegyti, and Ae. albopictus mosquitoes. Dengue poses an alarming impact on human health, and the global economy, particularly in the Southeast Asian (SEA) region [1]. The climate in the SEA region, characterized by persistent hot and humid weather throughout most of the year, offers optimal environmental conditions for mosquito development and dengue transmission [2]. According to a recent projection study, dengue incidence in SEA is expected to reach its peak in the 21st century [3]. By the end of this century, the length of dengue transmission season in the SEA region is expected to be longer with a rise in number of populations at risk of up to 696 million additional people [4].

Climate change, including extreme variations in precipitation and prolonged extreme temperatures, could modify the population density of the dengue vector [2]. Consequently, variation in the dengue transmission risk may occur following Extreme Weather Events (EWEs), including heatwaves, drought, and flood [5–7]. Briefly, heatwaves, defined as prolonged periods of extreme heat over a given threshold, could result in higher mosquito populations as heatwaves can accelerate the early development stage of mosquitoes life cycle [8]. Drought conditions have been also linked to increased dengue transmission risk via water storage in man-made containers [9]. Moreover, while cumulative precipitation might enhance mosquito abundance, heavy precipitation flushes away breeding sites, thereby decreasing mosquito populations [10].

In the context of a warming climate, EWEs are anticipated to become more frequent and intense [11]. Predictive models suggest that the dengue-endemic SEA region is becoming more susceptible to the adverse effects of climate change that included but are not limited to heat stress, heavy precipitation, widespread flooding both inland and in coastal zones, prolonged dry spells and acute deficits in water supply [11]. Heatwave intensity is projected to rise by 0·5 to 1·5 °C above a given global warming threshold, with an increase in duration of 2–10 days annually per 1°C of global temperature rise [12]. Given that Ae. aegypti is the main vector of dengue fever in Southeast Asia, rising temperatures pose a real threat of increased dengue risk [13,14]. Climate models under Representative Concentration Pathway (RCP4·5) scenario and the 14-model ensemble mean from Coupled Model Intercomparison Project Phase 5 (CMIP5) projected an increasing trend of drought in SEA in the future [15].

Despite the substantial growth in evidence regarding the impacts of EWEs on human health, their effect on mosquito-borne diseases like dengue is limited, especially in SEA, where dengue is endemic [16]. In line with WHO’s Global Vector Control Response operational framework, it is essential to investigate the impact of climate factors, particularly EWEs, on dengue using a multi-country approach in generating evidence required to efficiently prevent and manage dengue transmission and respond to subsequent outbreaks [17]. To our knowledge, this is the first study investigating the associations between multiple EWEs (i.e., heatwaves, extremely wet and drought conditions) and dengue in the SEA region, utilizing a robust statistical modelling approach.

Methods

Data collection

Dengue data.

Monthly dengue count data were obtained from the Southeast Asia Research on Climate change and Dengue (SEARCD) collaboration platform for 268 locations in seven countries including Indonesia (33 provinces during 2010–2020), Lao PDR (2 provinces during 2005–2021), Malaysia (14 states and federal territories during 2010–2017), the Philippines (79 provinces during 2010–2020), Singapore (1 city state during 2010–2017), Thailand (76 provinces during 2003–2021), and Vietnam (63 provinces during 2011–2021). Briefly, SEARCD is a platform with collaborators from the seven SEA countries that encourages research on meteorological factors and dengue. Additionally, monthly dengue count data from 23 locations in Cambodia during 1998–2010 was obtained from project Tycho 2·0 [18]. The dengue dataset used in this study was fully anonymized prior to access and analysis. All identifying information was removed to ensure the privacy and confidentiality of individuals.

Temperature and precipitation.

Monthly meteorological data, including mean temperature, mean dew point temperature, and total precipitation, were obtained from the ERA5-Land dataset generated by the European Centre for Medium-Range Weather Forecasts (ECMWF) (appendix pp. 2) [19]. ERA5-Land is a reanalysis data set providing climate information at a fine spatiotemporal resolution (0·1° × 0·1° grid) for the whole global land surface [19].

Heatwave definitions.

Heatwaves were defined using relative thresholds, which consider the long-term daily mean temperature at each location. Heatwave were defined as two or more consecutive days with a daily mean temperature surpassing the 95th percentile of its distribution in each specific location [20,21]. Hourly temperature data were averaged to compute the daily mean temperature for each location. The total number of heatwave days (HWt) was then calculated for each month and location. If a heatwave begins in the final days of one month and continues into the next, the heatwave days are included to each respective month (S2 Table).

Wet and drought conditions.

We used the Palmer Drought Severity Index (PDSI) to assess the effect of drought and extremely wet conditions on dengue. PDSI is a widely recognized standardized index for tracking drought and long-term variations in aridity and is computed by considering soil moisture content, the projected rate of evapotranspiration (i.e., the evaporation from soil under adequate water availability, considering mean daily temperature and numbers of days in the month) and rainfall amounts [22]. Here, we used the self-calibrating PDSI version (scPDSI) since it represents a geographically comparable index by calibrating a distinct normal condition for each location [23]. The scPDSI data were sourced at a geographical resolution of 0·5° × 0·5° grid from the Climatic Research Unit gridded Time Series (version 4·05) corresponding to the specific time in each location [24]. The scPDSI ranges from –10 (i.e., very dry conditions) to 10 (i.e., very wet conditions). Values below –4 or over 4 are categorized as drought and extremely wet conditions, respectively [23].

Population data.

Total population count for each location were obtained from the Gridded Population of the World Version 4 developed by the Socioeconomic Data and Application Center for the period 2000–2020 at five-year intervals [25]. Linear interpolation was used to estimate yearly total population values for each location over the study period.

Statistical analysis

We specified a generalized additive mixed model (GAMM) coupled with a distributed non-linear model (DLNM) to investigate the association between EWEs and dengue [26,27]. A quasi-Poisson distribution was assumed to account for potential over-dispersion in the dengue data. The logarithm of the total population for each location was included as an offset to adjust dengue case count by population. A smoothing spline with 5 degrees of freedom (df) per year was included to control for potential seasonality (S4 Table). A cross-basis function was included in each model using natural cubic spline with two equally spaced knots for heatwave and 3 df for scPDSI (i.e., the exposure dimension) and 3 df for the lag dimension based on exploratory analyses (S5 Table). We included a smoothing spline with 3 df to control for potential nonlinear effects of monthly mean temperature and total precipitation based on a previous study [28]. Long-term trends and interannual variability were accounted for incorporating an indicator term for each year in the time series. Unmeasured factors, such as public health interventions, were specified as unstructured random effects for each location. The reference value of heatwave was set at 0 heatwave days per month and scPDSI at 0. Models were fitted in R (version 4·3·1), using the packages mgcv 1·9·1 and dlnm 2·4·7 [26,27]. A flowchart summarizing the data collection and modeling steps was shown in S1 Fig.

The algebraic definition of the EWE-dengue model is given by:

Log(Yi,t)=α+Log(Pi,t)+f(EWEi,t;l)+s(Tempi,t)+s(Precii,t)+s(t)+δi,t+ νi

where Yi,t  indicates monthly dengue case at time t in location i, assumed to follow an over-dispersed quasi-Poisson distribution; α represents the intercept; Log(Pi,t) represents the logarithm of the total population per location i at the time t, included as an offset; f(EWEi,t;l) designate the cross-basis functions of either heatwave (HW) or scPDSI for maximum lag (l) of 4 months; s(Tempi,t\textrmand s(Precii,t) denotes the smooth functions of temperature and precipitation, respectively; s(t) denotes the smooth seasonals trend of time; δi,T indicates long-term trend using indicator variables for each year T in each location i; and νi expresses unstructured random effects for each location.

Sensitivity analysis

Multiple sensitivity analyses were carried out to assess the robustness of the results. We first examined the optimal exposure-response relationship in the cross-basis function by varying the df and placement of the knots, using natural cubic spline with two equally space internal knot, two knots at 25th and 75th percentile, and one knot at 50th percentile. We further applied a varying function of seasonality including smoothing spline with 3df, 4df, cyclic cubic spline, and one pair of Fourier term. Maximum lags were also varied by 3 months, 5 months, and 6 months, respectively. We repeated the analysis with adjustment relative humidity and population density in the model to account for additional confounding effects. Analyses using the data from 1998 to 2019 were also conducted to determine the potential impact of the COVID-19 pandemic on our results. Various heatwave definitions were investigated including: (i) four or more days exceeding the 95th percentile, (ii) two or more days exceeding the 97th percentile, (iii) two or more days exceeding the 99th percentile, (iv) four or more days exceeding the 97th percentile, and (v) four or more days exceeding the 99th percentile.

Results

Descriptive statistics

Table 1 shows the summary statistics of dengue cases and meteorological factors in each country. A total of 7,016,624 dengue cases was included in this study. The Philippines reported the highest mean annual dengue cases [196,719 cases (SD = 93,283)], followed by Vietnam [121,822 cases (SD = 81748)] and Indonesia [112,156 cases (SD = 42431)]. The monthly mean temperature, monthly total precipitation, mean annual heatwave days, and monthly scPDSI index at the country level ranged between 24·1°C and 26·8°C, 138mm and 254mm, 14·2 days and 17·2 days, and –0·3 and 0·3, respectively. The state of Selangor in Malaysia showed the highest monthly dengue incidence per 100,000 people followed by Khah Hoa in Vietnam (Fig 1A). The lower mean annual number of heatwave days was observed in south-eastern locations (Fig 1B). Eastern Philippines and Northern of Vietnam and Cambodia indicate wetter conditions (Fig 1C). Additional descriptive results of each climate variable and dengue incidence for each location are shown in S3 Table.

Table 1. Summary statistics of dengue cases, monthly temperature, total precipitation, heatwave days and scPDSI index in eight countries.

Period No of locations Total dengue case Annual dengue case [mean (SD)] Monthly mean temperaturea (°C) [mean (SD)] Monthly total precipitationa (mm) [mean (SD)] Annual number of heatwave daysa,b
[mean (SD)]
Monthly scPDSIa
[mean (SD)]
Cambodia 1998–2010 23 152,058 11,697 (7,611) 26·8 (0·9) 151 (37) 17·2 (2·4) 0·3 (0·8)
Indonesia 2010–2020 33 1,233,718 112,156 (42,431) 24·7 (1·2) 254 (51) 14·2 (4) 0·1 (0·6)
Lao PDR 2005–2021 2 63,391 3,729 (4,793) 25·1 (0·6) 158 (14) 17·1 (2·6) 0·1 (0·6)
Malaysia 2010–2017 14 545,479 68,185 (40,188) 25·5 (0·8) 222 (31) 15·3 (5·9) −0·3 (0·7)
Philippines 2010–2020 79 2,163,905 196,719 (93,283) 25·1 (1·4) 230 (36) 16·5 (4) 0·8 (0·9)
Singapore 2012–2019 1 91,463 11,433 (7,291) 26·9 (0·6) 207 (89) 14·6 (2·9) 0·8 (2·0)
Thailand 2003–2021 76 1,426,568 75,083 (37,736) 26·1 (1·2) 138 (32) 17 (2·3) 0 (0·4)
Vietnam 2011–2021 63 1,340,042 121,822 (81,748) 24·1 (2·3) 173 (26) 15·2 (2·9) 0 (0·8)
Total 291 7,016,624

mm: millimeter; scPDSI stands for self-calibrated Palmer drought severity index; SD is standard deviation.

a : Location specific mean climate variable (SD).

b : 95th percentile for 2 consecutive days.

Fig 1. Map of dengue case, heatwave, and scPDSI in each location of this study.

Fig 1

(A) Median monthly dengue incidence per 100,000 population in each location. (B) Mean annual number of heatwave days in each location. (C) Median monthly scPDSI index in each location. Grey areas have no data. scPDSI stands for self-calibrated Palmer drought severity index. Maps were created in R using Natural Earth data (https://www.naturalearthdata.com), accessed via the rnaturalearth R package.

Heatwave-dengue association

Fig 2A presents the pooled cumulative (lag 0–4 months) association between the total number of heatwave days per month and dengue compared to month without any heatwave day. The association between the monthly number of heatwave days and dengue was non-linear and showed a significant positive association for months with less than 12 heatwave days and a negative association between months with 12 and 27 heatwave days. The dengue risk leveled off at months with 7 heatwave days (RR = 1·28; 95%CI: 1·19,1·38) and reached the minimum dengue risk at month with 21 heatwave days (RR = 0·49; 95%CI: 0·42, 0·57). Fig 2B indicates lag-response association curves of specific monthly number of heatwave days. Month with 7 and 21 heatwave days increase dengue risk after lag 2 and 3 months, respectively. The lag-response association showed a negative association across all numbers of heatwave days per month within a lag of two months (Fig 2C). However, the dengue risk increases mostly after the lag of two months.

Fig 2. Association between the number of heatwave days per month and dengue incidence in 291 locations across the eight countries, relative to month with no heatwaves.

Fig 2

(A) Cumulative exposure–response associations (with 95%CI, shaded grey), (B) lag-response association curves of specific monthly number of heatwave days (with 95% CI, shaded grey), (C) Contour plot of the association between monthly number of heatwave days and dengue across each lag. The deeper the shade of red, the greater the increase in the RR of dengue, and the deeper the shade of blue, the greater the decrease in the RR of dengue. CI indicates the confidence intervals; HW stands for number of heatwave days per month; RR is the relative risk.

scPDSI-dengue association

Fig 3A shows the overall cumulative (lag 0–4 months) association between monthly scPDSI and dengue, compared to a value zero of scPDSI. The association between monthly scPDSI and dengue was non-linear and followed a reverse J-shaped curve association with minor upward tail and the minimum dengue risk observed at 2·5 scPDSI value (RR = 0·89; 95%CI: 0·87,0·91). Drought conditions (i.e. scPDSI values equal to or lower than –4) show a significant positive association with dengue incidence (RR = 1·85; 95%CI: 1·73,1·99). In contrast, the extremely wet conditions (i.e. scPDSI equal to 4) show a significant negative association with dengue risk (RR = 0·92; 95%CI: 0·87,0·96). An increase in dengue risk is observed when scPDSI is greater than 5·8, though the result is not significant.

Fig 3. Association between scPDSI and dengue incidence in 291 locations across the eight countries, relative to a scPDSI value of zero.

Fig 3

(A) Cumulative exposure–response associations (with 95%CI, shaded grey), with related PDSI distribution. Two vertical lines indicate the cut-off value for drought as a dotted line in red, and cut-off blue for extremely wet conditions as a dash-dotted line in blue. (B) lag-response association curves of specific scPDSI (with 95%CI, shaded grey). (C) Contour plot of the association between scPDSI and dengue across each lag. The deeper the shade of red, the greater the increase in the RR of dengue, and the deeper the shade of blue, the greater the decrease in the RR of dengue. CI indicates the confidence intervals; RR is the relative risk; scPDSI stands for self-calibrated Palmer drought severity index.

Fig 3B indicates association curves of specific scPDSI and dengue across all lag periods. Drought conditions (scPDSI ≤ –4) shows both immediate and delayed positive association on dengue risk within lag 0 and after two-months lag. Extremely wet conditions (scPDSI = 4) show an increased dengue risk at three-months lag, suggesting a delayed positive effect on dengue risk. Fig 3C illustrates the association between scPDSI and dengue risk across all lags. Notably, when the scPDSI exceeds 5·8, there is an increased dengue risk observed at a one month and after a three-month lag.

Sensitivity analysis

The pooled effect estimates for each EWE on dengue incidence were generally robust, amidst varying adjustments for seasonality, maximum lag, as well as inclusion of relative humidity and population density (S8, S9, S10 Figs). Changing the df for the cross-basis function did not change the direction nor the intensity of the association between scPDSI and dengue but did change it for heatwaves (S7 Fig For the heatwave model, the results show a reduction in dengue relative risk regardless of the monthly number of heatwave days when two internal knots were used at the 25th and 75th percentile or one internal knot at the 50th percentile (S7 Fig). Analyses using the data from 1998 to 2019 shows no impact of the COVID-19 pandemic on our results (S11 Fig).

Using various heatwave definitions in the sensitivity analysis did not change the direction of the association, except for heatwave with the 99th percentile for 2 and 4 consecutive days (S12 Fig). With the definition of 99th percentile for 2 and 4 consecutive days, there was a negative association between zero to 16 heatwave days per month and dengue. This was likely because of significantly fewer counts of months with heatwave days when the strictest heatwave definition was used.

Discussion

We examined the associations between several EWEs including heatwave, drought, and extremely wet conditions on dengue incidence in the SEA region. Months with fewer than 12 heatwave days showed increased dengue risks with a delayed effect observed after two months lag. This may partially be explained by the role of temperature on vector population since mosquitoes can survive even under continuous exposure to extreme heat amidst these heatwave durations [8]. In addition, heatwave events potentially facilitate vector population growth in the early development phase leading to an increased dengue transmission in the latter phase [8]. Also, the number of heatwave days may associate with a faster rate of viral replication within the vector and with a shorter extrinsic incubation period— the time required for dengue virus to become transmissible to another host after initial infection of a mosquito [2]. However, during the intense duration of heatwaves, adult mosquito survival rates and feeding activities start to decline, explaining our result of a reduction in dengue risk at month with more than 12 heatwave days [2]. In addition, while our study showed an increase in dengue risk following months with 27 heatwave days, the result is marginal due to the low number of months with an extreme frequency of heatwave days. This increase could potentially be attributed to the delayed effect of heatwaves on dengue risk. Further research is needed to investigate the impact of an extreme number of heatwave days in greater detail.

Our lag-exposure association result showed heatwaves more likely to increase dengue risk after a lag of two months. Comparing this finding with previous studies has its own limitations due to differences in heatwave definitions and statistical approaches used. However, a study in Hanoi, Vietnam, showed that heatwaves have an overall inhibitive effect at a shorter lag but were associated with increased magnitude of outbreaks at later lags [5]. In China, similar findings whereby heatwaves increase the risk of dengue outbreaks after six weeks were also observed [20]. This could be attributed to diapause behavior in mosquitoes, which is the inactive state where the dengue vectors halt their development and hatch to withstand harsh climatic conditions such as extreme heat or dry conditions [29]. The subsequent drops in temperature and increased humidity create favorable conditions for the continuation of the reproduction cycle of dengue vectors, ultimately leading to an increase in the dengue vector population [30]. The lags in mosquito outbreaks after a heatwave could result from the influence of climatic fluctuations on mosquito biology, serving as an adaptation mechanism to cope with unfavorable climate conditions [30].

Additionally, the association may be related to the change in human activities during and after heatwaves. During the heatwave, people tend to stay indoors in air conditioned environment, which limits vector-host contact [5]. However, lower temperatures after heatwaves encourage people to spend more time outside, increasing the likelihood of being bitten by mosquitoes. Another explanation might be an impairment of the host immunological response after exposure to certain sustained high temperature during heatwave [31]. Prolonged heat stress can reduce the ability of human body to mount an effective immune response, potentially making it easier for the dengue virus to be viable as an infection [31].

scPDSI index and dengue has a non-linear association with drought conditions showing an increase in dengue risk and extremely wet conditions at scPDSI value between 4 and 5.8 associated with a reduction in dengue risk. A similar association was reported in other studies in Brazil and China [7,32]. We noted that drought was positively associated with dengue risk at lags 0 and after two months. This is likely because severe dry conditions increased water storage in artificial containers, contributing to an increase in reproduction sites and the proliferation of mosquitoes [9]. Mosquito eggs can remain viable for up to 120 days during drought conditions, hatching simultaneously when favorable conditions, such as the return of water availability, are restored [33]. The observed three-month lag between extreme drought events and an increase in dengue risk may stem from gradual changes in domestic water storage practices as households adapt to water scarcity. This change might prompt individuals to adopt measures such as storing water in makeshift containers around the home during periods of water shortage. This finding indicates the importance of ongoing monitoring of drought conditions and the prompt implementation of emergency measures to reduce preventable negative effects of dry conditions on dengue risk. For instance, practical strategies to address drought-related dengue risks include discouraging open water storage, sealing rooftop water systems, and covering household containers to minimize mosquito breeding and reduce the risk of dengue.

We found that extremely wet conditions showed a reduction in dengue risk, which is in line with a study in Singapore, where a significant reduction in dengue outbreak risk followed the flushing effect of precipitation [10]. Non-standing water could flush away the mosquito eggs and shelter, consequently decreasing the dengue risk [6]. However, our results showed that severely wet conditions increase dengue risk, which could potentially be due to stagnant waters amidst severe wet conditions favoring development and reproduction of mosquitoes [6]. Moreover, severely wet conditions may also contribute to hydrological natural disasters, including floods or tropical cyclones, leading to significant deterioration of infrastructure or electricity, increasing the risk of close contact between dengue vectors and humans [6]. However, the impact of severely wet conditions needs further investigation to understand this phenomenon.

Strength and limitations

This research possesses a few strengths. First, this is the first study investigating of the EWEs-dengue association in the SEA region. This study was carried out in numerous subnational locations across most of the SEA region, representing different ranges of exposure levels and socio-demographic characteristics. By using a pooled design approach, this study provided strong evidence of the relationship between EWEs and dengue at the regional scale. Second, we used GAMM and DLNM that captures the complex non-linear and delayed relationships between climate variables and dengue incidence [26,27]. The use of GAMM enables the consideration of both spatial and temporal variations, which means the model can account for differences across locations and over time—factors that are critical when studying a vector-borne disease like dengue [26].

However, some limitations need to be acknowledged. First, a significant limitation is the use of a single set of modeling parameters across all the locations, which may heavily impact location/country-specific estimations. Specifically, the chosen modeling may not fit the data well in certain locations, even if it results in the best overall fit. However, the robustness of the results to various modeling choices and selections was assessed by exploring different model specifications for exposure and lag. Additionally, dengue case reporting can vary due to regional and temporal differences in diagnosis approaches, leading to over- or under-reporting of dengue cases (S1 Table). These variations may complicate accurate assessments of dengue risk, potentially skewing understanding of the climate true impact on dengue. Moreover, utilizing monthly data to study dengue risks may not capture short-term climate effects and dengue incubation periods. Relying on monthly total heatwave days might overlook the nuances of individual heatwave episode impacts on dengue transmission. The potential influence of serotype information on the climate-dengue association is acknowledged. Due to data availability limitations, the analysis could not be stratified by dengue serotypes, highlighting the need for future research in this aspect. Due to the ecological design of our study, there is a potential for ecological fallacy, where the findings at the regional level may not accurately reflect the outcomes for individual countries or specific locations. Although factors such as urbanization and dengue control measures may influence or modify the impact of EWEs on dengue risk, we did not include these variables in our models as the study focused on the overall relationship between EWEs and dengue. Future research should explore how these factors modify the relationship between EWEs and dengue risk to provide a more comprehensive understanding of their interactions.

Conclusions

Given the anticipated rise in the number and intensity of EWEs, this research offers insights into estimating the dengue risk associated with heatwave, drought, and extremely wet conditions introduced by the global climate in a real-world setting. Our study showed that delayed heatwaves and drought effects contribute to increased dengue risk. The findings highlight the need for public health interventions to mitigate the potential dengue risks posed by EWEs in the context of climate change in SEA.

Supporting information

S1 Appendix. Climate data collection.

(DOCX)

pntd.0012649.s001.docx (16.8KB, docx)
S1 Table. Summary information of dengue data for each country.

(DOCX)

pntd.0012649.s002.docx (21.7KB, docx)
S2 Table. Example calculation of monthly number of heatwave days (HWt).

(DOCX)

pntd.0012649.s003.docx (16.5KB, docx)
S3 Table. Location-specific summary table of mean and standard deviation of each variable of each country.

(DOCX)

pntd.0012649.s004.docx (104.1KB, docx)
S4 Table. Generalized cross-validation score of base dengue model with varying seasonality functions.

(DOCX)

pntd.0012649.s005.docx (16.1KB, docx)
S5 Table. Generalized cross-validation score of varying cross basis specification in main model.

(DOCX)

pntd.0012649.s006.docx (14.8KB, docx)
S6 Table. Pooled relative risks of heatwave-dengue association, relative to month with no heatwaves.

(DOCX)

pntd.0012649.s007.docx (14.6KB, docx)
S7 Table. The relative risks at each lag up to 4 months of heatwave-dengue association, relative to month with no heatwaves.

(DOCX)

pntd.0012649.s008.docx (15.1KB, docx)
S8 Table. Pooled relative risks of scPDSI-dengue association, relative to a scPDSI value of zero.

(DOCX)

pntd.0012649.s009.docx (14.9KB, docx)
S9 Table. The relative risks at each lag up to 4 months of scPDSI-dengue association, relative to a scPDSI value of zero.

(DOCX)

pntd.0012649.s010.docx (15.1KB, docx)
S1 Fig. Flowchart summarizing the data collection and modeling steps.

(DOCX)

pntd.0012649.s011.docx (24.7KB, docx)
S2 Fig. Map of the study area including 291 locations in eight Southeast Asia countries.

(DOCX)

pntd.0012649.s012.docx (5.4MB, docx)
S3 Fig. Time-series plot of total yearly dengue cases in eight Southeast Asia countries.

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pntd.0012649.s013.docx (58.7KB, docx)
S4 Fig. Pearson’s correlation coefficients among dengue and climate variables.

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pntd.0012649.s014.docx (52.7KB, docx)
S5 Fig. Time series plot of monthly dengue and climate variables for the selective locations with the highest number of total dengue case for each country.

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pntd.0012649.s015.docx (307.4KB, docx)
S6 Fig. Heatwave-dengue association at different time lags (0–4 months).

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pntd.0012649.s016.docx (64.2KB, docx)
S7 Fig. scPDSI-dengue association at different time lags (0–4 months).

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pntd.0012649.s017.docx (67.2KB, docx)
S8 Fig. Sensitivity analysis result of varying cross-basis function for each heatwave-dengue, and scPDSI-dengue associations.

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pntd.0012649.s018.docx (57.6KB, docx)
S9 Fig. Sensitivity analysis result of using different seasonality functions for heatwave-dengue, and scPDSI-dengue associations.

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pntd.0012649.s019.docx (72.7KB, docx)
S10 Fig. Sensitivity analysis result of different maximum lag for heatwave-dengue, and scPDSI-dengue associations.

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pntd.0012649.s020.docx (67.1KB, docx)
S11 Fig. Sensitivity analysis result of adjusting for relative humidity and population density for heatwave-dengue, and scPDSI-dengue associations.

(DOCX)

pntd.0012649.s021.docx (56.6KB, docx)
S12 Fig. Sensitivity analysis result of conducting analysis with data from 1998–2019 (excluding covid year).

(DOCX)

pntd.0012649.s022.docx (50.7KB, docx)
S13 Fig. Sensitivity analysis result of different heatwave definitions.

(DOCX)

pntd.0012649.s023.docx (60.2KB, docx)
S14 Fig. Sensitivity analysis result of excluding Cambodia and Laos data.

(DOCX)

pntd.0012649.s024.docx (38.7KB, docx)

Acknowledgments

We would like to extend our sincere gratitude to Dr. Futoshi Hasebe and all collaborators for their valuable contributions to this study, who was supported by the Japan Agency for Medical Research and Development (AMED) (JP20wm0125006).

Data Availability

Dengue data of Cambodia can be freely downloaded from Project Tycho (https://doi.org/10.25337/T7/ptycho.v2.0/KH.38362002). Climate data can be downloaded from Copernicus (https://doi.org/10.24381/cds.68d2bb30). The self-calibrating PDSI can be sourced from the Climate Research Unit (https://crudata.uea.ac.uk/cru/data/hrg/). Population data can be downloaded from the Socioeconomic Data and Application Center (https://doi.org/10.7927/H4PN93PB). We are unable to share the dengue case data used in this study because, except for the data from Cambodia, all other dengue case data were obtained through a collaborative platform under the Southeast Asia Research on Climate Change and Dengue (SEARCD) initiative. This data was accessed under a formal data-sharing agreement, which restricts public dissemination. The dataset was acquired with explicit permission from SEARCD members representing each participating country, and any further sharing is subject to the agreement’s terms and conditions. The data sets and the analysis scripts may be accessed upon formal request by contacting the Department of Hygiene, Graduate School of Medicine, Hokkaido University, via email at eisei@med.hokudai.ac.jp.

Funding Statement

This work was funded by the Japan Society for the Promotion of Science Early-Career Scientist Grant (22K17374) awarded to XS, Start-up Grant awarded to SI (24K23711) and the Japan Science and Technology Agency (JST) as part of SICORP (JPMJSC20E4) awarded to MH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

  • 1.Shepard DS, Undurraga EA, Halasa YA. Economic and disease burden of dengue in Southeast Asia. PLoS Negl Trop Dis. 2013;7(2):e2055. doi: 10.1371/journal.pntd.0002055 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Morin CW, Comrie AC, Ernst K. Climate and dengue transmission: evidence and implications. Environ Health Perspect. 2013;121(11–12):1264–72. doi: 10.1289/ehp.1306556 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Colón-González FJ, Gibb R, Khan K, Watts A, Lowe R, Brady OJ. Projecting the future incidence and burden of dengue in Southeast Asia. Nat Commun. 2023;14(1):5439. doi: 10.1038/s41467-023-41017-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Colón-González FJ, Sewe MO, Tompkins AM, Sjödin H, Casallas A, Rocklöv J, et al. Projecting the risk of mosquito-borne diseases in a warmer and more populated world: a multi-model, multi-scenario intercomparison modelling study. Lancet Planet Health. 2021;5(7):e404–14. doi: 10.1016/S2542-5196(21)00132-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Cheng J, Bambrick H, Yakob L, Devine G, Frentiu FD, Toan DTT, et al. Heatwaves and dengue outbreaks in Hanoi, Vietnam: New evidence on early warning. PLoS Negl Trop Dis. 2020;14(1):e0007997. doi: 10.1371/journal.pntd.0007997 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Coalson JE, Anderson EJ, Santos EM, Madera Garcia V, Romine JK, Dominguez B, et al. The Complex Epidemiological Relationship between Flooding Events and Human Outbreaks of Mosquito-Borne Diseases: A Scoping Review. Environ Health Perspect. 2021;129(9):96002. doi: 10.1289/EHP8887 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Lowe R, Lee SA, O’Reilly KM, Brady OJ, Bastos L, Carrasco-Escobar G, et al. Combined effects of hydrometeorological hazards and urbanisation on dengue risk in Brazil: a spatiotemporal modelling study. Lancet Planet Health. 2021;5(4):e209–19. doi: 10.1016/S2542-5196(20)30292-8 [DOI] [PubMed] [Google Scholar]
  • 8.Jia P, Liang L, Tan X, Chen J, Chen X. Potential effects of heat waves on the population dynamics of the dengue mosquito Aedes albopictus. PLoS Negl Trop Dis. 2019;13(7):e0007528. doi: 10.1371/journal.pntd.0007528 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Islam S, Haque CE, Hossain S, Rochon K. Role of container type, behavioural, and ecological factors in Aedes pupal production in Dhaka, Bangladesh: An application of zero-inflated negative binomial model. Acta Trop. 2019;193:50–9. doi: 10.1016/j.actatropica.2019.02.019 [DOI] [PubMed] [Google Scholar]
  • 10.Benedum CM, Seidahmed OME, Eltahir EAB, Markuzon N. Statistical modeling of the effect of rainfall flushing on dengue transmission in Singapore. PLoS Negl Trop Dis. 2018;12(12):e0006935. doi: 10.1371/journal.pntd.0006935 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Intergovernmental Panel on Climate Change. In: Pörtner HO, Roberts DC, Tignor MBM, et al. Editors. Climate change 2022: impacts, adaptation, and vulnerability. Working Group II contribution to the sixth assessment report of the Intergovernmental Panel on Climate Change. Cambridge (UK), New York (USA):Cambridge University Press; 2022. [Google Scholar]
  • 12.Perkins-Kirkpatrick SE, Gibson PB. Changes in regional heatwave characteristics as a function of increasing global temperature. Sci Rep. 2017;7(1):12256. doi: 10.1038/s41598-017-12520-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Bonnin L, Tran A, Herbreteau V, Marcombe S, Boyer S, Mangeas M, et al. Predicting the Effects of Climate Change on Dengue Vector Densities in Southeast Asia through Process-Based Modeling. Environ Health Perspect. 2022;130(12):127002. doi: 10.1289/EHP11068 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Brady OJ, Golding N, Pigott DM, Kraemer MUG, Messina JP, Reiner RC Jr, et al. Global temperature constraints on Aedes aegypti and Ae. albopictus persistence and competence for dengue virus transmission. Parasit Vectors. 2014;7:338. doi: 10.1186/1756-3305-7-338 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Dai A. Increasing drought under global warming in observations and models. Nat Clim Chang. 2012;3:52–8. [Google Scholar]
  • 16.Damtew YT, Tong M, Varghese BM, Anikeeva O, Hansen A, Dear K, et al. Effects of high temperatures and heatwaves on dengue fever: a systematic review and meta-analysis. EBioMedicine. 2023;91:104582. doi: 10.1016/j.ebiom.2023.104582 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.World Health Organization. Global vector control response 2017-2030. Geneva: WHO; 2017. Available from: https://iris.who.int/bitstream/handle/10665/259205/9789241512978-eng.pdf?sequence=1 [Google Scholar]
  • 18.Van Panhuis W, Cross A, Burke D, Choisy M. Counts of dengue reported in Cambodia: 1980-2011. Project Tycho. 2018. [cited 2022 Aug 11]. Available from: doi: 10.25337/T7/ptycho.v2.0/KH.38362002 [DOI] [Google Scholar]
  • 19.Muñoz Sabater J. ERA5-Land monthly averaged data from 1950 to present. Copernicus Climate Change Service (C3S) Climate Data Store (CDS). [cited 2022 Aug 11]. Available from: 10.24381/cds.68d2bb30 [DOI]
  • 20.Cheng J, Bambrick H, Frentiu FD, Devine G, Yakob L, Xu Z, et al. Extreme weather events and dengue outbreaks in Guangzhou, China: a time-series quasi-binomial distributed lag non-linear model. Int J Biometeorol. 2021;65(7):1033–42. doi: 10.1007/s00484-021-02085-1 [DOI] [PubMed] [Google Scholar]
  • 21.Guo Y, Gasparrini A, Armstrong BG, Tawatsupa B, Tobias A, Lavigne E, et al. Heat Wave and Mortality: A Multicountry, Multicommunity Study. Environ Health Perspect. 2017;125(8):087006. doi: 10.1289/EHP1026 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Palmer WC. Meteorological drought. US Department of Commerce, Weather Bureau. 1965. [Google Scholar]
  • 23.Wells N, Goddard S, Hayes MJ. A self-calibrating Palmer Drought Severity Index. J Clim. 2004;17:2335–51. [Google Scholar]
  • 24.Harris I, Osborn TJ, Jones P, Lister D. Version 4 of the CRU TS monthly high-resolution gridded multivariate climate dataset. Sci Data. 2020;7(1):109. doi: 10.1038/s41597-020-0453-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Center for International Earth Science Information Network-CIESIN-Columbia University. Gridded Population of the World, Version 4 (GPWv4): Population Count Adjusted to Match 2015 Revision of UN WPP Country Totals, Revision 11. Palisades, New York: NASA Socioeconomic Data and Applications Center (SEDAC); 2018. [cited 2021 Jul 25]. Available from: doi: 10.7927/H4PN93PB [DOI] [Google Scholar]
  • 26.Wood SN. Generalized additive models: an introduction with R. 2nd ed. Boca Raton: Chapman and Hall/CRC. 2017. [Google Scholar]
  • 27.Gasparrini A, Armstrong B, Kenward MG. Distributed lag non-linear models. Stat Med. 2010;29(21):2224–34. doi: 10.1002/sim.3940 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Ramadona AL, Lazuardi L, Hii YL, Holmner Å, Kusnanto H, Rocklöv J. Prediction of Dengue Outbreaks Based on Disease Surveillance and Meteorological Data. PLoS One. 2016;11(3):e0152688. doi: 10.1371/journal.pone.0152688 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Diniz DFA, de Albuquerque CMR, Oliva LO, de Melo-Santos MAV, Ayres CFJ. Diapause and quiescence: dormancy mechanisms that contribute to the geographical expansion of mosquitoes and their evolutionary success. Parasit Vectors. 2017;10(1):310. doi: 10.1186/s13071-017-2235-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Chaves LF, Scott TW, Morrison AC, Takada T. Hot temperatures can force delayed mosquito outbreaks via sequential changes in Aedes aegypti demographic parameters in autocorrelated environments. Acta Trop. 2014;129:15–24. doi: 10.1016/j.actatropica.2013.02.025 [DOI] [PubMed] [Google Scholar]
  • 31.Presbitero A, Melnikov VR, Krzhizhanovskaya VV, Sloot PMA. A unifying model to estimate the effect of heat stress in the human innate immunity during physical activities. Sci Rep. 2021;11(1):16688. doi: 10.1038/s41598-021-96191-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Li C, Liu Z, Li W, Lin Y, Hou L, Niu S, et al. Projecting future risk of dengue related to hydrometeorological conditions in mainland China under climate change scenarios: a modelling study. Lancet Planet Health. 2023;7(5):e397–406. doi: 10.1016/S2542-5196(23)00051-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Trpis M. Dry season survival of Aedes aegypti eggs in various breeding sites in the Dar es Salaam area, Tanzania. Bull World Health Organ. 1972;47(3):433–7. [PMC free article] [PubMed] [Google Scholar]
PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0012649.r001

Decision Letter 0

Nigel Beebe, Mohamed Gomaa Kamel

7 Jan 2025

PNTD-D-24-01566

Extreme weather events and dengue in Southeast Asia: a regionally-representative analysis of 291 locations from 1998 to 2021

PLOS Neglected Tropical Diseases

Dear Dr. Seposo,

Thank you for submitting your manuscript to PLOS Neglected Tropical Diseases. After careful consideration, we feel that it has merit but does not fully meet PLOS Neglected Tropical Diseases's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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PLOS Neglected Tropical Diseases

Nigel Beebe

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

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Reviewers' Comments:

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: The objectives and tested hypothesis are clearly articulated.The study design and sample size (>7 MM Dengue cases) apppropriate and robust. The population description and appropriateness has the usual limitations eg reporting bias of only severe vs severe +non severe dengue cases acknowledged by the authors.

There are no ethical nor regulatory issues.

The statistical modeling methods used are the essential tools and needs to be validated by reviewer(s) / experts in these matters ie statisticians /modelers..as I am not enough versed in these two critical areas.

Reviewer #2: The objectives of the study clearly articulated.

The study design appropriate to address the stated objectives.

The population is clearly described and appropriate for the hypothesis being tested.

Correct statistical analysis used to support conclusions.

There are no concerns about ethical or regulatory requirements.

Reviewer #3: The aim of the study was to verify the association between extreme weather events and dengue transmission in Southeast Asia.

The association between dengue incidence with three extreme weather variables (heatwaves, droughts and extereme wet conditions) was analyzed in an ecologic design, using different time lags.

The "population" of the study was composed of 291 administrative and geographic divisions of seven countries located in the region.

The study used publicly available data from disease surveillance systems and weather variables.

A GAMM model was used to fit the data.

Reviewer #4: (No Response)

Reviewer #5: This reviewer gives a mixed assessment on the methods. Several strengths deserve commendation: (1) The authors have assembled a rich data set on dengue cases spanning multiple countries, many decades, and monthly level data. (2) They have applied a sophisticated statistical methodology; (3) The approach appears to be well executed. In addition, their thorough review of the literature deserves praise.

On the other hand, the methods seem to have some limitations. The greatest concern is the absence of considering the "multiple" comparisons problem. Classical significance tests fit well to a single, pre-specified test. The methods in this paper did not indicate which, if any, parts of the specification had been chosen before the authors started their analysis, and how their revised their approach based on their interim results. As is well known, the more tests that are performed, the greater the chance that some "significant" result can be found by chance. In this study, apparent opportunities for multiple comparison could arise in many ways, such as: (1) The choice of the statistical model. The authors chose smoothed splines. They could have chosen averages, a specific form, a model incorporating the month of the year as an independent variable, or some other structure. (2) The specific parameters within the chosen model. For example, the spline used 5 degrees of freedom. The sensitivity analyses considered a small limited range but not a full defense against multiple comparisons; (3) The definition of the heat index. The authors give citations 18 and 19, but do not say whether they explicitly followed those prior definitions. (4) The drought index. While the use of an established index is a virtue, they authors did not give a prior endorsement as to why an index developed for agriculture would apply to dengue risk.

Additional concerns relate to the exclusion of potentially relevant variables. The authors explicitly acknowledged the exclusion of dengue control measures, which might have been very relevant However, they also excluded time and items associate with it, such as increasing national per capita income, degree of urbanization (as dengue is a primarily urban disease, and variations among sites. The authors' hypothesis around drought responses would seem especially affected by these omitted variables. Higher income and more urban environments might be more likely to use air conditioning or have household members spending time in such settings working, studying, or shopping. Likewise, storing water in unsealed containers would apply most to locations mostly in lower income countries.

If the authors were able to incorporate some of these variables in their models their paper would be strengthened. If they cannot, they may wish to acknowledge that limitation and mention some of the topics as promising areas for further research.

Reviewer #6: -Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

Answer Yes

-Is the study design appropriate to address the stated objectives?

Answer Not sure

-Is the population clearly described and appropriate for the hypothesis being tested?

Answer Yes

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

Answer Yes

-Were correct statistical analysis used to support conclusions?

Answer Not sure

-Are there concerns about ethical or regulatory requirements being met?

Answer Not sure

**********

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Yes

Yes

The figures lack simplicity for a non expert reader. Maybe some clarifications could be made

Reviewer #2: The analysis presented match the analysis plan.

The results are clearly and completely presented.

Figures are of sufficient quality for clarity?

Reviewer #3: Yes, the analysis matches the analysis plan. In my view the tables and images are clear.

Reviewer #4: (No Response)

Reviewer #5: Generally satisfactory. However, it was not clear why the variability in dengue reporting was a factor. Passive dengue reporting is known to capture only a portion of dengue cases. Generally the proportion increases with the quality of the country's health system (see papers by Shepard DS, Undurraga E and colleagues). But if that fraction were consistent over time, it would be captured in the location-specific constant.

Reviewer #6: -Does the analysis presented match the analysis plan?

Answer The analysis presented partially aligns with the analysis plan.

-Are the results clearly and completely presented?

Answer No

The analysis presented partially aligns with the analysis plan.

Answer No

**********

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: yes to all.

I think the summary conclusion "Our finding offer stakeholders sizeable amount of time to organize and implement public health interventions in minimizing the prospective dengue risks" need to be rewritten in a more rigorous way underscoring the quantitative study outcomes.

Reviewer #2: The conclusions are supported by the data presented.

The limitations of analysis are clearly described.

The authors discuss how these data can be helpful to advance our understanding of the topic under study.

Public health relevance is addressed.

Reviewer #3: The limitations related to the ecologic design should be acknowledged.

Reviewer #4: (No Response)

Reviewer #5: Despite the noted strengths, this reviewer is concerned about the effect of the limitations in the methods on the conclusions. Trying to slow long term global warming may be a long term approach. Based on the study's complex relationships, it would be helpful to summarize the next impact of global warming on dengue cases.

I would encourage the authors to clarify their purpose of their study by inserting the word "cases" after "dengue" and the adjective "exploratory) before the words "regionally- representative..." in the title of their manuscript.

Reviewer #6: -Are the conclusions supported by the data presented?

Answer Partly

-Are the limitations of analysis clearly described?

Answer Partly

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

Answer Partly

-Is public health relevance addressed?

Answer No

**********

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Confirm the contributions of the impressive co-authors list ie from 18 institutions vs acknowledgments..

Reviewer #2: Minor revision

Reviewer #3: (No Response)

Reviewer #4: (No Response)

Reviewer #5: line 59. Change "Flaviviruses" to lower case.

line 80. After "2 to 10 days" insert the time period (e.g. annually).

line 84. After "limited," insert a comma.

line 139. Inset "a" before "previous study"

line 172. Insert "The" before "State of Selangor

line 178. Column for precipitation. Add units to label (e.g. mm)

line 212 Add "the" before result and change "result" to "results."

line 226 Change "event" to "events"

line 278 Change "We" to lower case "we"

line 319 Change" Researcher" to "Researchers"

Reviewer #6: Minor Revision

**********

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: Study is novel, supported by a large data set, statistical/modeling methods need to be validated by experts in these areas, Confirm the contributions of the impressive co-authors list ie from 18 institutions vs acknowledgments for publication ethics.

Discussion is well balanced and the conclusions are impactful.

Reviewer #2: This study was very well presented. The study’s idea was also clear and was practical for epidemiological and community health purpose. I can see that the authors did many attempts in statistical analyses to check every possibilities those might affect the results of the study. The results were also explained well in the discussion section.

To improve this article, there are some issues authors need to elaborate. Those are:

1. Table 1: data for each country covered different time period, e.g. Cambodia 1998-2010 while Indonesia 2010-2020. As we all know, ideally data must be collected in similar time period. Different timing in data collection may potentially lead to ’temporal bias’. Is there any analysis/ strategy authors provided to overcome this period differences?

2. Different mosquito species have different characteristic. From a literature (http://www.parasitesandvectors.com/content/7/1/338), we could learn that temperature does not limit the persistence of Ae. albopictus. In this study, authors analysed the dengue incidence in association with selected EWEs. Providing data about the dominant mosquito species in each region will be a valuable addition to the explanation/ discussion.

3. Is it possible that each country gave different result when analysed separately? As each country might have different weather variability and different vector control strategy (e.g. some countries apply ‘closing, draining, and burying water-filled container’. This behaviour might reduce dengue incidence even in drought/ heatwave).

Reviewer #3: Extreme weather events have become more frequent. They have occurred on a worldwide scale. Analysis of its association with the occurrence of vector-borne diseases should be encouraged. However, local factors may have significant importance in this relationship.

Reviewer #4: This manuscript investigates the associations between extreme weather events (EWEs)—heatwaves, droughts, and extremely wet conditions—and dengue incidence across Southeast Asia. Using extensive data spanning over two decades from multiple locations, the study employs advanced statistical methodologies, including a generalized additive mixed model (GAMM) combined with a distributed lag non-linear model (DLNM). It addresses a timely and critical public health issue in the context of climate change, demonstrating methodological rigor, integrating diverse datasets, and offering actionable insights for policymakers. Additionally, the study carefully considers and excludes potential confounding influences, such as COVID-19. However, the manuscript would benefit from addressing the following issues:

1. The dengue data collection periods vary across countries, with some data not covering the full span from 1998 to 2021. For instance, only two provinces in Lao PDR are included. This raises questions about potential biases or limitations in the results. The manuscript should clarify the rationale behind these inconsistencies and assess their impact on the study's findings.

2. While the methodological details are well-presented, the inclusion of a flowchart summarizing the data collection and modeling steps would enhance transparency and aid reader comprehension.

3. Prolonged heatwaves often lead to drought conditions. The manuscript should explore whether there is any overlap or interaction between these two EWEs and how this might influence dengue risk.

4. The descriptions of **Figure 2B**, **Figure 3B**, and **Figure 3C** (Page 9, lines 188-190, 202-206; Page 11, lines 245-255) appear unclear or inaccurate. The manuscript would benefit from specifying and clearly labeling the coordinate axes to improve interpretability.

5. On Page 10-11, lines 230-232, the manuscript explains the decline in dengue risk during months with more than 12 heatwave days due to reduced mosquito survival and feeding activity. However, the subsequent increase in dengue risk during months with over 27 heatwave days is not adequately addressed. The authors should provide a plausible explanation for this observation.

6. The statement on Page 11, line 253, that "extremely wet conditions show a reduction in dengue risk" is misleading. An increase in dengue risk is observed when the scPDSI exceeds 5.8, even if the result is not statistically significant. This should be rephrased for accuracy.

7. On Page 12, lines 257-258, the manuscript notes that mosquito eggs can survive up to 120 days in drought conditions. However, Figure 3B shows a rising relative risk (RR) of dengue after a lag of more than three months, with greater increases over time. The authors should reconcile these findings and provide a detailed explanation.

This manuscript has the potential to significantly advance our understanding of the complex interactions between climate change and dengue risk. Addressing the outlined issues will enhance its clarity, robustness, and practical implications.

Reviewer #5: Besides areas for further research, the authors' conclusions should indicate implications for mitigating climate risks, such as avoiding the storage of water or ensuring that rooftop systems are airtight and household containers are covered to avoid breeding mosquitoes.

Reviewer #6: This study is interesting, featuring a large and diverse population spanning 291 locations across eight Southeast Asian countries. It incorporates sensitivity analysis, considers confounding factors, and takes into account the impact of COVID-19. However, there are some points of concern and recommendations for improvement as follows:

1. Rationale for Selecting the Models: This study utilized functions to control environmental factors, considering various related factors such as seasonality, environmental influences, and random variables. However, the rationale for selecting this model raises the question of how confident we can be that the chosen model (GAMM) is the optimal one. To determine the optimal analytical methodology for examining the association between EWEs and dengue for this dataset, how can this confidence be justified?

2. Smoothing Spline with 3 df: Your study employs a smoothing spline with 3 degrees of freedom based on a previous study conducted in Yogyakarta Province, Indonesia, which used Generalized Linear Regression Models (DOI:10.1371/journal.pone.0152688). Additionally, alternative methods, such as cross-basis functions, were also applied. How confident are you that these methods are the most appropriate for the dataset used in this study?

3. Definition of Heatwave: How confident can you be that the definition of heatwave used in this study aligns with the conditions in the areas studied and effectively represents its actual impact across all locations?

4. Managing Overfitting: How did you address the impact of overfitting when conducting multiple sensitivity analyses?

5. Statistical Reporting: The statistical reporting should include measures of size and/or distribution. For example, in lines 168-169, only the mean annual dengue case count is shown. These details should be more comprehensive.

6. Assessment Results: The results from the assessment between the independent and dependent variables should comprehensively present the magnitude and distribution while clearly indicating statistical significance levels.

7. Reporting Dengue Cases: Why was only RR used to report dengue case numbers?

8. Consistency of Terminology: Ensure consistent use of terms. For example, in line 184, the term "dengue relative" is used, in line 194, "only dengue," and in line 203, "dengue risk." Consistency in terminology would enhance clarity.

9. Abstract and Conclusions: The abstract and conclusions should be clearer and more robust. Recommendations for future research should build on this study, and practical implications for dengue prevention and control should be more explicitly addressed.

10. Appendix Formatting: Table headers should be included on every page of the appendix.

11. I do not see any mention of the ethical considerations in the manuscript. I am not certain whether any identifiable personal data was collected (even if it was not utilized or reported in this study). Since this study involves data collected from multiple countries, if no identifiable personal data or other ethically sensitive information was collected, it should be explicitly stated in the manuscript.

**********

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Reviewer #1: Yes:  Jean Lang MD PhD FASTMH

Reviewer #2: Yes:  Leonard Nainggolan

Reviewer #3: Yes:  Expedito Luna

Reviewer #4: No

Reviewer #5: Yes:  Donald S. Shepard, PhD

Reviewer #6: No

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Reproducibility:

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PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0012649.r003

Decision Letter 1

Nigel Beebe, Mohamed Gomaa Kamel

8 Aug 2025

Dear Dr. Seposo,

We are pleased to inform you that your manuscript 'Extreme weather events and dengue in Southeast Asia: a regionally-representative analysis of 291 locations from 1998 to 2021' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Nigel Beebe, PhD

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

***********************************************************

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #2: I do not have any further comments on the methods. Methods has been covered very well by Reviewer #5.

Reviewer #3: The authors have properly addressed the issues raised by the reviewers.

Reviewer #4: (No Response)

Reviewer #6: -Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

ANS Yes

-Is the study design appropriate to address the stated objectives?

ANS Partially, While the study’s regional scope and focus on climate-related determinants of dengue incidence are well-aligned with the stated objectives, there are critical gaps in the research design that limit its ability to fully address those objectives.

-Is the population clearly described and appropriate for the hypothesis being tested?

ANS Yes

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

ANS YES

-Were correct statistical analysis used to support conclusions?

ANS Partially.The selection of the Generalized Additive Mixed Model (GAMM) appears appropriate given the study’s intent to capture potentially non-linear associations between environmental variables (e.g., heatwave, drought) and dengue incidence. However, several important statistical considerations remain unaddressed.

-Are there concerns about ethical or regulatory requirements being met?

ANS No

**********

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #2: Results have been clearly presented. It has addressed my previous comments about the different time period of data collection.

Reviewer #3: The authors have properly addressed the issues raised by the reviewers.

Reviewer #4: (No Response)

Reviewer #6: -Does the analysis presented match the analysis plan?

ANS Yes

-Are the results clearly and completely presented?

ANS Partially

-Are the figures (Tables, Images) of sufficient quality for clarity?

ANS Partially

**********

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #2: Conclusion supported the data presented.

Reviewer #3: The authors have properly addressed the issues raised by the reviewers.

Reviewer #4: (No Response)

Reviewer #6: -Are the conclusions supported by the data presented?

ANS Yes

-Are the limitations of analysis clearly described?

ANS Partially

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

ANS Yes

-Is public health relevance addressed?

ANS Yes

**********

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #2: Authors has addressed my other comments regarding the role of different mosquito species and the possibility of analysing each individual location.

In the 1st sentence of introduction (line 75 of manuscript): “Dengue is caused for flaviviruses, transmitted by the infectious bite of Aedes aegyti, and Ae. albopictus mosquitoes.”

I suggest that it is better if the phrase “caused for” change to “caused by” or “caused from”.

Reviewer #3: The authors have properly addressed the issues raised by the reviewers.

Reviewer #4: (No Response)

Reviewer #6: Minor Revision

**********

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #2: The authors have addressed all the comments from the reviewer (either into revision to the article or into explanation to the reviewer).

Reviewer #3: The authors have properly addressed the issues raised by the reviewers.

Reviewer #4: (No Response)

Reviewer #6: This study presents valuable contributions to the field, particularly in its aim to examine dengue epidemiology across the Southeast Asian (SEA) region. By covering data from seven countries and 268 locations (including 23 in Cambodia), the study provides a potentially impactful dataset that could inform the design of region-specific public health interventions for dengue prevention and control, as well as serve as a reference for future research.

However, several critical issues must be addressed to enhance the validity and reliability of the findings. These concerns are mainly related to two major components of the research process: the data collection process and the statistical methodology.

1. Data Collection Process

The study identifies heatwaves and humidity/drought conditions as key independent variables, while dengue incidence is the primary outcome. While several aspects are discussed in the manuscript, the following key points require further clarification or improvement:

1.1 Variable Definitions and Regional Heterogeneity

Given the regional scope, the study must ensure consistency and clarity in the definition and operationalization of key variables, particularly across diverse national contexts. For example:

- The operational definitions of “heatwave” and “drought” should be contextually adapted to local climatic and public health standards.

- The study should clarify whether these thresholds have been validated or shown to have empirical effects on dengue transmission.

In addition, data sources should be validated repositories, and the authors must account for potential biases, such as inconsistent reporting mechanisms (e.g., passive surveillance systems) and national differences in data availability. Furthermore, potential confounding factors—notably urban versus rural setting, population density, and socioeconomic factors—must be considered, as they are known to influence dengue dynamics.

1.2 Data Quality Control and Ethics Internal validation procedures such as double data entry or cross-referencing across multiple datasets would strengthen data reliability. Furthermore, the manuscript lacks any mention of Institutional Review Board (IRB) approval or ethical clearance procedures. IRB review is essential not only for data anonymization but also for ensuring transparency, data acquisition appropriateness, and ethical integrity, especially when dealing with health surveillance data.

2. Statistical Methods Assuming that the data collection process is refined as above, attention must also be given to the statistical modeling and interpretation:

2.1 Model Selection and Comparison The use of a Generalized Additive Mixed Model (GAMM) is appropriate for capturing non-linear relationships. However, model selection should be justified through comparison with alternative models (e.g., GLMM, GEE) using statistical criteria such as AIC, BIC, or cross-validation errors. This would demonstrate that the chosen model is not just reasonable but optimal.

2.2 Control of Type I Error in Multiple Testing Given the number of variables and comparisons performed, it is important to control for multiple comparisons using appropriate techniques, such as Bonferroni correction or Benjamini-Hochberg FDR control, to avoid inflated false-positive rates.

2.3 Confounding Variables Variables such as urbanization, access to healthcare, and socioeconomic status are known to mediate both exposure (heat/humidity) and outcome (dengue). Failing to account for these may lead to spurious associations. Their inclusion as covariates or the use of hierarchical or multilevel modeling would improve the robustness and generalizability of the findings.

2.4 Diagnostics and Model Assumptions The manuscript lacks discussion of model diagnostics (e.g., residual checks, overdispersion, autocorrelation), which are crucial for validating the assumptions of the GAMM framework.

3. Implications of Data Validity

If the data collection process is flawed—e.g., lacking standardization or containing systematic errors—then the indicators such as heatwaves or drought may be inaccurately correlated with dengue incidence. This misalignment may lead to erroneous conclusions, compromising the effectiveness of future public health interventions. Misguided policy decisions based on unreliable evidence can result in the misallocation of resources, public health costs, and reduced trust in surveillance-driven research. Moreover, it undermines the foundation for future investigations, potentially skewing the trajectory of research and policy development in vector-borne disease control.

**********

PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: Yes:  Leonard Nainggolan, MD, PhD

Reviewer #3: Yes:  Expedito Luna

Reviewer #4: Yes:  Ran Wang

Reviewer #6: No

PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0012649.r004

Acceptance letter

Nigel Beebe, Mohamed Gomaa Kamel

Dear Dr. Seposo,

We are delighted to inform you that your manuscript, " 

Extreme weather events and dengue in Southeast Asia: a regionally-representative analysis of 291 locations from 1998 to 2021," has been formally accepted for publication in PLOS Neglected Tropical Diseases.

We have now passed your article onto the PLOS Production Department who will complete the rest of the publication process. All authors will receive a confirmation email upon publication.

The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Editorial, Viewpoint, Symposium, Review, etc...) are generated on a different schedule and may not be made available as quickly.

Soon after your final files are uploaded, the early version of your manuscript will be published online unless you opted out of this process. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers.

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Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix. Climate data collection.

    (DOCX)

    pntd.0012649.s001.docx (16.8KB, docx)
    S1 Table. Summary information of dengue data for each country.

    (DOCX)

    pntd.0012649.s002.docx (21.7KB, docx)
    S2 Table. Example calculation of monthly number of heatwave days (HWt).

    (DOCX)

    pntd.0012649.s003.docx (16.5KB, docx)
    S3 Table. Location-specific summary table of mean and standard deviation of each variable of each country.

    (DOCX)

    pntd.0012649.s004.docx (104.1KB, docx)
    S4 Table. Generalized cross-validation score of base dengue model with varying seasonality functions.

    (DOCX)

    pntd.0012649.s005.docx (16.1KB, docx)
    S5 Table. Generalized cross-validation score of varying cross basis specification in main model.

    (DOCX)

    pntd.0012649.s006.docx (14.8KB, docx)
    S6 Table. Pooled relative risks of heatwave-dengue association, relative to month with no heatwaves.

    (DOCX)

    pntd.0012649.s007.docx (14.6KB, docx)
    S7 Table. The relative risks at each lag up to 4 months of heatwave-dengue association, relative to month with no heatwaves.

    (DOCX)

    pntd.0012649.s008.docx (15.1KB, docx)
    S8 Table. Pooled relative risks of scPDSI-dengue association, relative to a scPDSI value of zero.

    (DOCX)

    pntd.0012649.s009.docx (14.9KB, docx)
    S9 Table. The relative risks at each lag up to 4 months of scPDSI-dengue association, relative to a scPDSI value of zero.

    (DOCX)

    pntd.0012649.s010.docx (15.1KB, docx)
    S1 Fig. Flowchart summarizing the data collection and modeling steps.

    (DOCX)

    pntd.0012649.s011.docx (24.7KB, docx)
    S2 Fig. Map of the study area including 291 locations in eight Southeast Asia countries.

    (DOCX)

    pntd.0012649.s012.docx (5.4MB, docx)
    S3 Fig. Time-series plot of total yearly dengue cases in eight Southeast Asia countries.

    (DOCX)

    pntd.0012649.s013.docx (58.7KB, docx)
    S4 Fig. Pearson’s correlation coefficients among dengue and climate variables.

    (DOCX)

    pntd.0012649.s014.docx (52.7KB, docx)
    S5 Fig. Time series plot of monthly dengue and climate variables for the selective locations with the highest number of total dengue case for each country.

    (DOCX)

    pntd.0012649.s015.docx (307.4KB, docx)
    S6 Fig. Heatwave-dengue association at different time lags (0–4 months).

    (DOCX)

    pntd.0012649.s016.docx (64.2KB, docx)
    S7 Fig. scPDSI-dengue association at different time lags (0–4 months).

    (DOCX)

    pntd.0012649.s017.docx (67.2KB, docx)
    S8 Fig. Sensitivity analysis result of varying cross-basis function for each heatwave-dengue, and scPDSI-dengue associations.

    (DOCX)

    pntd.0012649.s018.docx (57.6KB, docx)
    S9 Fig. Sensitivity analysis result of using different seasonality functions for heatwave-dengue, and scPDSI-dengue associations.

    (DOCX)

    pntd.0012649.s019.docx (72.7KB, docx)
    S10 Fig. Sensitivity analysis result of different maximum lag for heatwave-dengue, and scPDSI-dengue associations.

    (DOCX)

    pntd.0012649.s020.docx (67.1KB, docx)
    S11 Fig. Sensitivity analysis result of adjusting for relative humidity and population density for heatwave-dengue, and scPDSI-dengue associations.

    (DOCX)

    pntd.0012649.s021.docx (56.6KB, docx)
    S12 Fig. Sensitivity analysis result of conducting analysis with data from 1998–2019 (excluding covid year).

    (DOCX)

    pntd.0012649.s022.docx (50.7KB, docx)
    S13 Fig. Sensitivity analysis result of different heatwave definitions.

    (DOCX)

    pntd.0012649.s023.docx (60.2KB, docx)
    S14 Fig. Sensitivity analysis result of excluding Cambodia and Laos data.

    (DOCX)

    pntd.0012649.s024.docx (38.7KB, docx)
    Attachment

    Submitted filename: Response to reviewers.docx

    pntd.0012649.s026.docx (46.4KB, docx)

    Data Availability Statement

    Dengue data of Cambodia can be freely downloaded from Project Tycho (https://doi.org/10.25337/T7/ptycho.v2.0/KH.38362002). Climate data can be downloaded from Copernicus (https://doi.org/10.24381/cds.68d2bb30). The self-calibrating PDSI can be sourced from the Climate Research Unit (https://crudata.uea.ac.uk/cru/data/hrg/). Population data can be downloaded from the Socioeconomic Data and Application Center (https://doi.org/10.7927/H4PN93PB). We are unable to share the dengue case data used in this study because, except for the data from Cambodia, all other dengue case data were obtained through a collaborative platform under the Southeast Asia Research on Climate Change and Dengue (SEARCD) initiative. This data was accessed under a formal data-sharing agreement, which restricts public dissemination. The dataset was acquired with explicit permission from SEARCD members representing each participating country, and any further sharing is subject to the agreement’s terms and conditions. The data sets and the analysis scripts may be accessed upon formal request by contacting the Department of Hygiene, Graduate School of Medicine, Hokkaido University, via email at eisei@med.hokudai.ac.jp.


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