The Patterns And Drivers Of Dengue Coupled Disease System Under Global Change

BackgroundDengue is a globally widespread arthropod-borne viral disease that relies on the interplay of biotic and abiotic factors,encompassing the interactions among the environment,pathogens,vectors,and hosts.As a consequence of human activities leading to a series of global changes with profound impacts on the Earth system,the planet has entered a new geological epoch known as the "Anthropocene." The manifestations of global changes include climate change,land use changes,increased landscape connectivity,and the introduction of invasive species,among others.These changes are closely associated with the transmission of environmentally sensitive diseases such as dengue,altering the inherent connections within the interacting systems and objectively facilitating its global spread.In recent years,dengue outbreaks and epidemics in China have exhibited the source-sink characteristics of the metacoupling,driven by the imported cases.The dengue virus carried by imported cases can be considered as the "source," while the geospatial distribution of the mosquito vector Aedes albopictus represents the "sink" for dengue transmission.Currently,in certain regions of China,the biotic-abiotic landscape ecological conditions are already in place(potential ecological niches).Once the dengue virus is repeatedly introduced into these areas,the trophic interactions among the dengue virus,Aedes albopictus,and humans,as well as their interactions with the external environment,will rapidly establish in the invaded areas.This will lead to the swift outbreak and diffusion of dengue,which will then spread to its appropriate ecological niches,forming a complete biological invasion process.Based on the ecological-epidemiological framework,integrating perspectives from invasion ecology and landscape ecology,and considering the interactions within the coupled human-nature system,this study proposes a conceptual framework for coupled disease systems applied in infectious diseases.Taking dengue as a representative example of vector-borne diseases,it elucidates the architecture of disease coupled systems based on macro-systems in the context of eco-epidemiological processes.The study aims to explore the telecoupling of dengue(the source-sink system relationship in China)and intracoupling(the pattern and driving factors of the ecological niche of dengue in China)within the framework of macro-systems and theoretical epidemiology.Objectives1.To characterize the patterns,source-sink relationship,and driving forces of dengue invasions in China,deconstruct the telecoupling relationship between the global dengue disease coupled system and the dengue disease coupling system in China.2.To construct a human-environment coupled system for dengue fever disease in China,and based on this coupled system,to estimate the future risk pattern and relative benefits of mitigation measures under global change drivers.Methods1.Data collection(1)Dataset for mapping invasion patterns and driving forcesWe collected reported dengue cases in mainland China from 2006 to 2020,distinguishing between local and imported cases,as well as environmental data.The gridded environmental driving factors dataset covered information in five dimensions:climate,phenology,vegetation cover,socioeconomic development,and human activity.Climate,phenology,and vegetation data(except for NDVI)were obtained from CHELSA.Population and human modification index data were obtained from the United States National Aeronautics and Space Administration(NASA).GDP and human footprint data were obtained from Scientific Data,while NDVI data were obtained from the Chinese National Earth System Science Data Center.(2)Dataset for dengue coupled disease systemWe collected relevant distribution information of Aedes albopictus and Aedes aegypti from published literature and related databases.Distribution information of dengue virus was obtained from Scientific Data,and data on dengue in mainland China were partly obtained from the National Infectious Disease Mandatory Reporting Information System(2005-2019),and data from Taiwan province were obtained from the Center for Disease Control and Prevention in Taiwan Province(1998-2019).Climate and elevation data were obtained from WorldClim(including current and future scenarios,covering elevation,bioclimatic factors,monthly maximum temperature,monthly minimum temperature,and precipitation).Land use data were obtained from Land Use Harmonization 2.Population data were obtained from NASA,and GDP data were obtained from the Zenodo database(including current and future scenarios).In addition,data on China’s animal geographic zones,spatial distribution of land ecosystem types in China,species richness of primates,and human footprint were collected and used as the base map for the study.2.Statistical analysis(1)Analysis of invasion pattern and driving forces of telecouplingWe identified the local and imported cases(2006-2020)and assembled the datasets on environmental conditions.The vector auto-regression model was applied to detect the crossrelations of source-sink patterns.We selected the major environmental drivers via the Boruta algorithm to assess the driving forces in dengue outbreak dynamics by applying generalized additive models.We reconstructed the internal connections among imported cases,local cases,and external environmental drivers using the structural equation modeling.(2)The simulation and construction of dengue coupled systemAn ecological niche model of Aedes albopictus,Aedes aegypti,and dengue virus was established using a Maxent model,characterizing the natural niche of dengue and predicting future nature niches.A social niche of dengue was developed by an boosted regression tree model and projected into future scenarios.The changes of exposure areas in the latitude gradient of each component of the natural niche of dengue were analyzed,and the pulse trend relationship was depicted using a generalized additive model.The changes dengue risks in the latitude bands of the social niche of dengue were analyzed,and the impact value was calculated using a spatial case-control design concept to quantify the benefits of mitigating global change.A two-stage study was conducted:the pattern driving force and exposure-response relationship of the main factors on the latitude band were analyzed using the framework of the generalized additive model,and the effects of each latitude band were combined using a meta-analysis to obtain the average effect at the national level.The coupling relationship between the structural systems was structured using a structural equation model to complete the decoupling of the dengue disease coupling system.Results1.Invasion patterns and driving forces of dengue source-sink system(Metacoupling)From 2006 to 2020,81,652 local dengue cases and 12,701 imported dengue cases in Chinese mainland were reported.The hotspots of dengue introductions and outbreaks were in southeast and southwest China,originating from South and Southeast Asia.Oversea-imported dengue cases,as the Granger-cause,were the initial driver of the dengue dynamic;the suitable local bio-socioecological environment is the fundamental factor for dengue epidemics.The Bio8(OR=2.11,95%CI:1.67-2.68),Bio9(OR=291.62,95%CI:125.63-676.89),Bio15(OR=4.15,95%CI:3.30-5.24),normalized difference vegetation index in March(OR=1.27,95%CI:1.06-1.51)and July(OR=1.04,95%CI:1.00-1.07),and the imported cases are the major drivers of dengue local transmissions(OR=4.79,95%CI:4.34-5.28).The intermediary effect of an index on population and economic development to local cases via the path of imported cases was detected in the dengue dynamic system.2.Coupling and decoupling the dengue disease coupling system in ChinaCurrently,the northern boundary of the suitable area for Aedes albopictus is around 42°N,while that of Aedes aegypti is expected to move northward to around 26°N,and most of the ecological niche of DENV is located south of 24°N.The suitable areas for Aedes albopictus,Aedes aegypti,and DENV in China were 2,885,713.704(95%CI:2,703,365.413,055,073.83),211,678.77(95%CI:175,747.90249,351.90),and 611,423.14(95%CI:354,612.43～1,145,933.78)km2,respectively.In terms of latitude gradient,the potential critical points of exposed area of natural and social ecological niches were different:for the natural ecological niche,the maximum suitable area was near 23.5°N,which may be due to the transition zone with potential ecological system transition;for the dengue social ecological niche,it was around 30°N,possibly influenced by population mobility and vector efficiency.In terms of future changes in the natural ecological niche,under the extreme SSP5-8.5 scenario,the maximum increase in area of all components of the natural ecological niche can be detected during the period from 2081 to 2100.Aedes albopictus will extend northward along the Heihe-Tengchong line,and the maximum weighted change rate of the exposed area will occur around 45.8°N,which is the same latitude as the largest city in northeastern China,Harbin.In addition,the distribution range of Aedes aegypti will expand to the central China region,with an increase of about 62%in the exposed area at 23.3°N.The suitable area for DENV will be dispersed to the north and south borders of China,with a sharp increase of around 89%at 25.5°N.For threshold effects,the lowest temperature in November was positively correlated with dengue risk,demonstrating the characteristics of the natural-social relationship.Similar to the results found in the previous section,November was in a transition state from an endemic area to a non-endemic area in Sichuan and Jiangxi provinces.Most of the latitudes in these provinces are between 27-30°N,which explains why this latitude has a more significant impact and can be mutually corroborated.Regarding the structural relationships,the atmospheric system exhibited a significant impact on the natural niche of dengue CDS with a standardized path coefficient(SPC)of 0.795,while the socioeconomic system showed the least impact(SPC:0.072).With respect to the direct effects on the social niche,the natural niche had the greatest impact(SPC:0.375),followed closely by the land system(SPC:0.343).The total effect of the atmospheric system on the social niche was 0.524(SPC),whereas the hydrological system exhibited a total effect of 0.23 1(SPC),the land system had a total effect of 0.408(SPC),and the socioeconomic system had a total effect of 0.171(SPC).Conclusions1.Imported cases are the intersection connecting China’s dengue disease coupled system and the global dengue disease coupled system,and their "source-sink nexus" is the relationship of introduction-colonization-spreading-reintroduction,with a lag effect of up to 3 months.Southeast Asia and South Asia are important "sources" of imported dengue cases in China.The"sink" is mainly concentrated in the southeast of the Heihe-Tengchong line,which leads to the establishment of China’s dengue disease coupled system.The main distribution area is the vast area south of 30°N and southeast of the Heihe-Tengchong line.The seasonal transmission of dengue in this area shows a clear phenological regression phenomenon,driven by landscape factors.In the dengue source-sink system(telecoupling),socio-economic drivers promote the generation of domestic cases by affecting the imported cases.2.We predicted that the future geographic ranges of the natural and social dengue niche would shift to higher latitudes tracking with environmental changes,driving the increasing numbers of exposed areas and vulnerable populations under the threat of dengue.Our results suggested that different ecological responses at latitude-gradient on dengue in China would be exploited under global change.We further showed that the nationwide dengue risk transition will be restrained in the mid-term and begin to benefit in the long term if we limit the temperature warming to 2℃.We decoupled the major driving forces and the structure of the dengue coupled disease system,which could provide empirical evidence for nature-based solutions and land-use planning.3.More efforts should be paid in higher latitudes to control the introduction and establishment of vectors and dengue virus,whereas areas in lower latitudes should focus on preventing invasions,localizations,and concomitant bridgehead effects on dengue epidemiological processes.Our results highlight that not only ambitious targets on mitigations to coordinate with environmental change,but adaptations such as the viral surveillance for hosts should be strengthened to minimize the risks of dengue under the rapid anthropogenic environmental change.4.The research has established a theoretical framework known as the "source-sink system"to delve into the invasion and transmission of non-endemic diseases.This framework not only provides a foundation for understanding the surface processes and states of disease episystems but also explores their regional responses within the context of global changes,all within the intricate context of human-environment interaction.This research not only offering insights into the formation of disease outbreaks but also by providing a conceptual and methodological backbone for comprehending the dynamic interplay between human activities and landscape factors.Furthermore,the theoretical framework serves as a springboard for developing coupled systems for diverse diseases,culminating in the ultimate integration into Earth system models.This holistic approach contributes to our broader understanding of disease dynamics,enabling us to better anticipate and manage public health challenges in an ever-evolving world.