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Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA—GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA—GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models’ predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA—GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA—GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals’ movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

Surveillance is an essential work on infectious diseases prevention and control. When the pandemic occurred, the inadequacy of traditional surveillance was exposed, but it also provided a valuable opportunity to explore new surveillance methods. This study aimed to estimate the transmission dynamics and epidemic curve of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BF.7 in Beijing under the emergent situation using Baidu index and influenza-like illness (ILI) surveillance. A novel hybrid model (multiattention bidirectional gated recurrent unit (MABG)–susceptible–exposed–infected–removed (SEIR)) was developed, which leveraged a deep learning algorithm (MABG) to scrutinize the past records of ILI occurrences and the Baidu index of diverse symptoms such as fever, pyrexia, cough, sore throat, anti-fever medicine, and runny nose. By considering the current Baidu index and the correlation between ILI cases and coronavirus disease 2019 (COVID-19) cases, a transmission dynamics model (SEIR) was formulated to estimate the transmission dynamics and epidemic curve of SARS-CoV-2. During the COVID-19 pandemic, when conventional surveillance measures have been suspended temporarily, cases of ILI can serve as a useful indicator for estimating the epidemiological trends of COVID-19. In the specific case of Beijing, it has been ascertained that cumulative infection attack rate surpass 80.25% (95% confidence interval (95% CI): 77.51%–82.99%) since December 17, 2022, with the apex of the outbreak projected to transpire on December 12. The culmination of existing patients is expected to occur three days subsequent to this peak. Effective reproduction number (Rt) represents the average number of secondary infections generated from a single infected individual at a specific point in time during an epidemic, remained below 1 since December 17, 2022. The traditional disease surveillance systems should be complemented with information from modern surveillance data such as online data sources with advanced technical support. Modern surveillance channels should be used primarily in emerging infectious and disease outbreaks. Syndrome surveillance on COVID-19 should be established to following on the epidemic, clinical severity, and medical resource demand.

Abstract Background The US confronted a “triple-demic” of influenza, respiratory syncytial virus (RSV), and COVID-19 in the winter of 2022, leading to increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze these epidemics and their spatial-temporal co-occurrence, identifying hotspots and informing public health strategies. Methods We employed retrospective and prospective space-time scan statistics to assess the situations of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and from October 2022 to February 2023, respectively. This enabled monitoring of spatiotemporal variations for each epidemic individually and collectively. Results Compared to winter 2021, COVID-19 cases decreased while influenza and RSV infections significantly increased in winter 2022. We found a high-risk cluster of influenza and COVID-19 (not all three) in winter 2021. In late November 2022, a large high-risk cluster of triple-demic emerged in the central US. The number of states at high risk for multiple epidemics increased from 15 in October 2022 to 21 in January 2023. Conclusions Our study offers a novel spatiotemporal approach that combines both univariate and multivariate surveillance, as well as retrospective and prospective analyses. This approach offers a more comprehensive and timely understanding of how the co-occurrence of COVID-19, influenza, and RSV impacts various regions within the United States. Our findings assist in tailor-made strategies to mitigate the effects of these respiratory infections.

Abstract Background The Hubei Province in China reported its last indigenous malaria case in September 2012, but imported malaria cases, particularly those related to Plasmodium vivax and Plasmodium falciparum, threaten Hubei’s malaria-free status. This study investigated the epidemiological changes in P. vivax and P. falciparum malaria in this province to provide scientific evidence for preventing malaria resurgence. Methods The prevalence, demographic characteristics, seasonal features, and geographical distribution of malaria were assessed using surveillance data and were compared across three stages: control stage (2005–2009) and elimination stages I (2010–2014) and II (2015–2019). Results In 2005–2019, 8483 malaria cases were reported, including 5599 indigenous P. vivax cases, 275 imported P. vivax cases, 866 imported P. falciparum cases, and 1743 other cases. Imported P. falciparum cases accounted for 0.07% of all cases reported in 2005, but increased to 78.81% in 2019. Most imported P. vivax and P. falciparum malaria occurred among males, aged 21–60 years, during elimination stages I and II. The number of regions affected by imported P. falciparum and P. vivax increased markedly in Hubei from the control stage to elimination stage II. Overall, 1125 imported P. vivax and P. falciparum cases were detected from 47 other nations. Eight imported cases were detected from other provinces in China. From the control stage to elimination stage II, the number of cases of malaria imported from African countries increased, and that of cases imported from Southeast Asian countries decreased. Conclusions Although Hubei has achieved malaria elimination, it faces challenges in maintaining this status. Hence, imported malaria surveillance need to be strengthened to reduce the risk of malaria re-introduction.

IntroductionGiven the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions, potentially due to the neglect of prior water availability in mosquito breeding sites as an effect modifier.MethodsIn this study, we addressed this research gap by considering the impact of prior water availability for the first time. We measured prior water availability as the cumulative precipitation over the preceding 8 weeks and utilized a distributed lag non-linear model stratified by the level of prior water availability to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China.ResultsOur findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24–55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 [95% credible interval (CI): 1.02–1.83] occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7–121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43–0.79), occurring at a lag of 45 days.DiscussionThese findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk.

Abstract Targeted public health interventions for an emerging epidemic are essential for preventing pandemics. During 2020-2022, China invested significant efforts in strict zero-COVID measures to contain outbreaks of varying scales caused by different SARS-CoV-2 variants. Based on a multi-year empirical dataset containing 131 outbreaks observed in China from April 2020 to May 2022 and simulated scenarios, we ranked the relative intervention effectiveness by their reduction in instantaneous reproduction number. We found that, overall, social distancing measures (38% reduction, 95% prediction interval 31-45%), face masks (30%, 17-42%) and close contact tracing (28%, 24-31%) were most effective. Contact tracing was crucial in containing outbreaks during the initial phases, while social distancing measures became increasingly prominent as the spread persisted. In addition, infections with higher transmissibility and a shorter latent period posed more challenges for these measures. Our findings provide quantitative evidence on the effects of public-health measures for zeroing out emerging contagions in different contexts.

BackgroundInfluenza outbreaks pose a significant threat to global public health. Traditional surveillance systems and simple algorithms often struggle to predict influenza outbreaks in an accurate and timely manner. Big data and modern technology have offered new modalities for disease surveillance and prediction. Influenza-like illness can serve as a valuable surveillance tool for emerging respiratory infectious diseases like influenza and COVID-19, especially when reported case data may not fully reflect the actual epidemic curve. ObjectiveThis study aimed to develop a predictive model for influenza outbreaks by combining Baidu search query data with traditional virological surveillance data. The goal was to improve early detection and preparedness for influenza outbreaks in both northern and southern China, providing evidence for supplementing modern intelligence epidemic surveillance methods. MethodsWe collected virological data from the National Influenza Surveillance Network and Baidu search query data from January 2011 to July 2018, totaling 3,691,865 and 1,563,361 respective samples. Relevant search terms related to influenza were identified and analyzed for their correlation with influenza-positive rates using Pearson correlation analysis. A distributed lag nonlinear model was used to assess the lag correlation of the search terms with influenza activity. Subsequently, a predictive model based on the gated recurrent unit and multiple attention mechanisms was developed to forecast the influenza-positive trend. ResultsThis study revealed a high correlation between specific Baidu search terms and influenza-positive rates in both northern and southern China, except for 1 term. The search terms were categorized into 4 groups: essential facts on influenza, influenza symptoms, influenza treatment and medicine, and influenza prevention, all of which showed correlation with the influenza-positive rate. The influenza prevention and influenza symptom groups had a lag correlation of 1.4-3.2 and 5.0-8.0 days, respectively. The Baidu search terms could help predict the influenza-positive rate 14-22 days in advance in southern China but interfered with influenza surveillance in northern China. ConclusionsComplementing traditional disease surveillance systems with information from web-based data sources can aid in detecting warning signs of influenza outbreaks earlier. However, supplementation of modern surveillance with search engine information should be approached cautiously. This approach provides valuable insights for digital epidemiology and has the potential for broader application in respiratory infectious disease surveillance. Further research should explore the optimization and customization of search terms for different regions and languages to improve the accuracy of influenza prediction models.

Seasonal influenza activity typically peaks in the winter months but plummeted globally during the current coronavirus disease 2019 (COVID-19) pandemic. Unraveling lessons from influenza’s unprecedented low profile is critical in informing preparedness for incoming influenza seasons. Here, we explored a country-specific inference model to estimate the effects of mask-wearing, mobility changes (international and domestic), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interference in China, England, and the United States. We found that a one-week increase in mask-wearing intervention had a percent reduction of 11.3%–35.2% in influenza activity in these areas. The one-week mobility mitigation had smaller effects for the international (1.7%–6.5%) and the domestic community (1.6%–2.8%). In 2020–2021, the mask-wearing intervention alone could decline percent positivity by 13.3–19.8. The mobility change alone could reduce percent positivity by 5.2–14.0, of which 79.8%–98.2% were attributed to the deflected international travel. Only in 2019–2020, SARS-CoV-2 interference had statistically significant effects. There was a reduction in percent positivity of 7.6 (2.4–14.4) and 10.2 (7.2–13.6) in northern China and England, respectively. Our results have implications for understanding how influenza evolves under non-pharmaceutical interventions and other respiratory diseases and will inform health policy and the design of tailored public health measures.

Abstract Background The impact of coronavirus diseases 2019 (COVID-19) related non-pharmaceutical interventions (NPIs) on influenza activity in the presence of other known seasonal driving factors is unclear, especially at the municipal scale. This study aimed to assess the impact of NPIs on outpatient influenza-like illness (ILI) consultations in Beijing and the Hong Kong Special Administrative Region (SAR) of China. Methods We descriptively analyzed the temporal characteristics of the weekly ILI counts, nine NPI indicators, mean temperature, relative humidity, and absolute humidity from 2011 to 2021. Generalized additive models (GAM) using data in 2011–2019 were established to predict the weekly ILI counts under a counterfactual scenario of no COVID-19 interventions in Beijing and the Hong Kong SAR in 2020–2021, respectively. GAM models were further built to evaluate the potential impact of each individual or combined NPIs on weekly ILI counts in the presence of other seasonal driving factors in the above settings in 2020–2021. Results The weekly ILI counts in Beijing and the Hong Kong SAR fluctuated across years and months in 2011–2019, with an obvious winter-spring seasonality in Beijing. During the 2020–2021 season, the observed weekly ILI counts in both Beijing and the Hong Kong SAR were much lower than those of the past 9 flu seasons, with a 47.5% [95% confidence interval (CI): 42.3%, 52.2%) and 60.0% (95% CI: 58.6%, 61.1%) reduction, respectively. The observed numbers for these two cities also accounted for only 40.2% (95% CI: 35.4%, 45.3%) and 58.0% (95% CI: 54.1%, 61.5%) of the GAM model estimates in the absence of COVID-19 NPIs, respectively. Our study revealed that, “Cancelling public events” and “Restrictions on internal travel” measures played an important role in the reduction of ILI in Beijing, while the “restrictions on international travel” was statistically most associated with ILI reductions in the Hong Kong SAR. Conclusions Our study suggests that COVID-19 NPIs had been reducing outpatient ILI consultations in the presence of other seasonal driving factors in Beijing and the Hong Kong SAR from 2020 to 2021. In cities with varying local circumstances, some NPIs with appropriate stringency may be tailored to reduce the burden of ILI caused by severe influenza strains or other respiratory infections in future. Graphical Abstract

A novel coronavirus emerged in late 2019, named as the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). This study was originally conducted in January 2020 to estimate the potential risk and geographic range of COVID-19 spread at the early stage of the transmission. A series of connectivity and risk analyses based on domestic and international travel networks were conducted using historical aggregated mobile phone data and air passenger itinerary data. We found that the cordon sanitaire of the primary city was likely to have occurred during the latter stages of peak population numbers leaving the city, with travellers departing into neighbouring cities and other megacities in China. We estimated that there were 59,912 international air passengers, of which 834 (95% uncertainty interval: 478–1,349) had COVID-19 infection, with a strong correlation seen between the predicted risks of importation and the number of imported cases found. Given the limited understanding of emerging infectious diseases in the very early stages of outbreaks, our approaches and findings in assessing travel patterns and risk of transmission can help guide public health preparedness and intervention design for new COVID-19 waves caused by variants of concern and future pandemics to effectively limit transmission beyond its initial extent.

Non-pharmaceutical interventions (NPIs) and COVID-19 vaccination have been implemented concurrently, making their relative effects difficult to measure. Here, the authors show that effects of NPIs reduced as vaccine coverage increased, but that NPIs could still be important in the context of more transmissible variants.

Understanding disease treatment-seeking behaviors is a fundamental issue for national and regional healthcare management. However, treatment-seeking behaviors are complex and affected by various factors, including disease incidence, healthcare resources, and population accessibility to hospitals. Geospatial analysis is a practical approach to investigating treatment-seeking behaviors. Still, methods and cases are limited due to the lack of long-term data, interdisciplinary knowledge, and data analytic techniques. We develop a new paradigm for investigating spatial patterns and factors affecting bone disease treatment-seeking behaviors. We leverage consecutive long-term records of over 50,000 nationwide bone disease patients outside Beijing who had surgeries in a prestigious hospital in Beijing, China. Five categories of patient individual-level geographical and environmental variables are derived from multi-source remote sensing and geospatial data to explain treatment-seeking behaviors. First, we develop a scaling approach to assess the relationships between bone patients and population migration. Next, we develop a treatment-seeking index to measure treatment-seeking behaviors and develop spatial models to identify their regional disparities, i.e., hotspots and coldspots. Finally, we develop spatial heterogeneity models to explore the complex factors affecting treatment-seeking behaviors. Results show that the developed paradigm is effective in examining national variations of the patterns of disease treatment-seeking behaviors. We find that (i) population migration is an effective predictor of the treatment-seeking behaviors of bone patients, (ii) significant hotspots and coldspots are identified for informing regional disparities, and (iii), multiple types of factors affecting the treatment-seeking behaviors through a geospatially overlapped approach. This study pioneers the development of geospatial models and implementation of patient individual-level data derived from satellite remote sensing for large-scale disease treatment-seeking behaviors assessment. The proposed paradigm provides solid evidence for previous and future policies and actions to address the regional inequality of disease treatments.

Abstract Pandemics such as COVID-19 and their induced lockdowns/travel restrictions have a significant impact on people’s lives, especially for lower-income groups who lack savings and rely heavily on mobility to fulfill their daily needs. Taking the COVID-19 pandemic as an example, this study analysed the risk of returning to poverty for low-income households in Hubei Province in China as a result of the COVID-19 lockdown. Employing a dataset including information on 78,931 government-identified poor households, three scenarios were analysed in an attempt to identify who is at high risk of returning to poverty, where they are located, and how the various risk factors influence their potential return to poverty. The results showed that the percentage of households at high risk of returning to poverty (falling below the poverty line) increased from 5.6% to 22% due to a 3-month lockdown. This vulnerable group tended to have a single source of income, shorter working hours, and more family members. Towns at high risk (more than 2% of households returning to poverty) doubled (from 27.3% to 46.9%) and were mainly located near railway stations; an average decrease of 10–50 km in the distance to the nearest railway station increased the risk from 1.8% to 9%. These findings, which were supported by the representativeness of the sample and a variety of robustness tests, provide new information for policymakers tasked with protecting vulnerable groups at high risk of returning to poverty and alleviating the significant socio-economic consequences of future pandemics.

Measurement(s) public holiday • school holiday • airline passenger volume Technology Type(s) digital curation Factor Type(s) geographic location • temporal interval Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.17833922

Mobile phone data have been increasingly used over the past decade or more as a pretty reliable indicator of human mobility to measure population movements and the associated changes in terms of population presence and density at multiple spatial and temporal scales. However, given the fact mobile phone data are not available everywhere and are generally difficult to access and share, mostly because of commercial restrictions and privacy concerns, more readily available data with global coverage, such as night-time light (NTL) imagery, have been alternatively used as a proxy for population density changes due to population movements. This study further explores the potential to use NTL brightness as a short-term mobility metric by analysing the relationship between NTL and smartphone-based Google Aggregated Mobility Research Dataset (GAMRD) data across twelve African countries over two periods: 2018–2019 and 2020. The data were stratified by a measure of the degree of urbanisation, whereby the administrative units of each country were assigned to one of eight classes ranging from low-density rural to high-density urban. Results from the correlation analysis, between the NTL Sum of Lights (SoL) radiance values and three different GAMRD-based flow metrics calculated at the administrative unit level, showed significant differences in NTL-GAMRD correlation values across the eight rural/urban classes. The highest correlations were typically found in predominantly rural areas, suggesting that the use of NTL data as a mobility metric may be less reliable in predominantly urban settings. This is likely due to the brightness saturation and higher brightness stability within the latter, showing less of an effect than in rural or peri-urban areas of changes in brightness due to people leaving or arriving. Human mobility in 2020 (during COVID-19-related restrictions) was observed to be significantly different than in 2018–2019, resulting in a reduced NTL-GAMRD correlation strength, especially in urban settings, most probably because of the monthly NTL SoL radiance values remaining relatively similar in 2018–2019 and 2020 and the human mobility, especially in urban settings, significantly decreasing in 2020 with respect to the previous considered period. The use of NTL data on its own to assess monthly mobility and the associated fluctuations in population density was therefore shown to be promising in rural and peri-urban areas but problematic in urban settings.

Data-driven approaches predict infectious disease dynamics by considering various factors that influence severity and transmission rates. However, these factors may not fully capture the dynamic nature of disease transmission, limiting prediction accuracy and consistency. Our proposed data-driven approach integrates spatiotemporal human mobility patterns from detailed point-of-interest clustering and population flow data. These patterns inform the creation of mobility-informed risk indices, which serve as auxiliary factors in data-driven models for detecting outbreaks and predicting prevalence trends. We evaluated our approach using real-world COVID-19 outbreaks in Beijing and Guangzhou, China. Incorporating the risk indices, our models successfully identified 87% (95% Confidence Interval: 83–90%) of affected subdistricts in Beijing and Guangzhou. These findings highlight the effectiveness of our approach in identifying high-risk areas for targeted disease containment. Our approach was also tested with COVID-19 prevalence data in the United States, which showed that including the risk indices reduced the mean absolute error and improved the R-squared value for predicting weekly case increases at the county level. It demonstrates applicability for spatiotemporal forecasting of widespread diseases, contributing to routine transmission surveillance. By leveraging comprehensive mobility data, we provide valuable insights to optimize control strategies for emerging infectious diseases and facilitate proactive measures against long-standing diseases.

Travel restrictions and physical distancing have been implemented across the world to mitigate the coronavirus disease 2019 (COVID-19) pandemic, but studies are needed to understand their effectiveness across regions and time. Based on the population mobility metrics derived from mobile phone geolocation data across 135 countries or territories during the first wave of the pandemic in 2020, we built a metapopulation epidemiological model to measure the effect of travel and contact restrictions on containing COVID-19 outbreaks across regions. We found that if these interventions had not been deployed, the cumulative number of cases could have shown a 97-fold (interquartile range 79–116) increase, as of May 31, 2020. However, their effectiveness depended upon the timing, duration, and intensity of the interventions, with variations in case severity seen across populations, regions, and seasons. Additionally, before effective vaccines are widely available and herd immunity is achieved, our results emphasize that a certain degree of physical distancing at the relaxation of the intervention stage will likely be needed to avoid rapid resurgences and subsequent lockdowns.

Abstract Understanding seasonal human mobility at subnational scales has important implications across sciences, from urban planning efforts to disease modelling and control. Assessing how, when, and where populations move over the course of the year, however, requires spatially and temporally resolved datasets spanning large periods of time, which can be rare, contain sensitive information, or may be proprietary. Here, we aim to explore how a set of broadly available covariates can describe typical seasonal subnational mobility in Kenya pre-COVID-19, therefore enabling better modelling of seasonal mobility across low- and middle-income country (LMIC) settings in non-pandemic settings. To do this, we used the Google Aggregated Mobility Research Dataset, containing anonymized mobility flows aggregated over users who have turned on the Location History setting, which is off by default. We combined this with socioeconomic and geospatial covariates from 2018 to 2019 to quantify seasonal changes in domestic and international mobility patterns across years. We undertook a spatiotemporal analysis within a Bayesian framework to identify relevant geospatial and socioeconomic covariates explaining human movement patterns, while accounting for spatial and temporal autocorrelations. Typical pre-pandemic mobility patterns in Kenya mostly consisted of shorter, within-county trips, followed by longer domestic travel between counties and international travel, which is important in establishing how mobility patterns changed post-pandemic. Mobility peaked in August and December, closely corresponding to school holiday seasons, which was found to be an important predictor in our model. We further found that socioeconomic variables including urbanicity, poverty, and female education strongly explained mobility patterns, in addition to geospatial covariates such as accessibility to major population centres and temperature. These findings derived from novel data sources elucidate broad spatiotemporal patterns of how populations move within and beyond Kenya, and can be easily generalized to other LMIC settings before the COVID-19 pandemic. Understanding such pre-pandemic mobility patterns provides a crucial baseline to interpret both how these patterns have changed as a result of the pandemic, as well as whether human mobility patterns have been permanently altered once the pandemic subsides. Our findings outline key correlates of mobility using broadly available covariates, alleviating the data bottlenecks of highly sensitive and proprietary mobile phone datasets, which many researchers do not have access to. These results further provide novel insight on monitoring mobility proxies in the context of disease surveillance and control efforts through LMIC settings.

Non-pharmaceutical interventions (NPIs) implemented to interrupt COVID-19 transmission may also impact the spread of other infectious diseases. Here, the authors estimate that influenza activity in China and the United States reduced by up to 80% when NPIs were in place in the 2019–2020 season.

Abstract Background Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection. Methods We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses. Results Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0–0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4–1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7–3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0–0.5%) (p

Here the authors analyze disease burden and clinical severity of COVID-19 during the first wave in Wuhan, China in comparison to past influenza virus pandemics and COVID-19 in the US and Canada. These estimates of symptomatic cases, medical consultations, hospitalizations and deaths should guide preparedness for this disease.

Scrub typhus, a miteborne rickettsiosis, has emerged in many areas globally. We analyzed the incidence and spatial–temporal distribution of scrub typhus in China during 1952–1989 and 2006–2016 using national disease surveillance data. A total of 133,623 cases and 174 deaths were recorded. The average annual incidence was 0.13 cases/100,000 population during 1952–1989; incidence increased sharply from 0.09/100,000 population in 2006 to 1.60/100,000 population in 2016. The disease, historically endemic to southern China, has expanded to all the provinces across both rural and urban areas. We identified 3 distinct seasonal patterns nationwide; infections peaked in summer in the southwest, summer-autumn in the southeast, and autumn in the middle-east. Persons >40 years of age and in nonfarming occupations had a higher risk for death. The changing epidemiology of scrub typhus in China warrants an enhanced disease control and prevention program.

The intensity of influenza epidemics varies significantly from year to year among regions with similar climatic conditions and populations. However, the underlying mechanisms of the temporal and spatial variations remain unclear. We investigated the impact of urbanization and public transportation size on influenza activity. We used 6-year weekly provincial-level surveillance data of influenza-like disease incidence (ILI) and viral activity in northern China. We derived the transmission potential of influenza for each epidemic season using the susceptible–exposed–infectious–removed–susceptible (SEIRS) model and estimated the transmissibility in the peak period via the instantaneous reproduction number (Rt). Public transport was found to explain approximately 28% of the variance in the seasonal transmission potential. Urbanization and public transportation size explained approximately 10% and 21% of the variance in maximum Rt in the peak period, respectively. For the mean Rt during the peak period, urbanization and public transportation accounted for 9% and 16% of the variance in Rt, respectively. Our results indicated that the differences in the intensity of influenza epidemics among the northern provinces of China were partially driven by urbanization and public transport size. These findings are beneficial for predicting influenza intensity and developing preparedness strategies for the early stages of epidemics.

Developing new methods for modelling infectious diseases outbreaks is important for monitoring transmission and developing policy. In this paper we propose using semi-mechanistic Hawkes Processes for modelling malaria transmission in near-elimination settings. Hawkes Processes are well founded mathematical methods that enable us to combine the benefits of both statistical and mechanistic models to recreate and forecast disease transmission beyond just malaria outbreak scenarios. These methods have been successfully used in numerous applications such as social media and earthquake modelling, but are not yet widespread in epidemiology. By using domain-specific knowledge, we can both recreate transmission curves for malaria in China and Eswatini and disentangle the proportion of cases which are imported from those that are community based.

In 2014 Guangzhou, China experienced its worse dengue epidemic on record. To determine the reasons for this the authors model historical data under combinations of four time-varying factors and find that past epidemics were limited by one or more unfavourable conditions, but the 2014 epidemic faced none of these restraints.

Abstract Background Historically, malaria had been a widespread disease in China. A national plan was launched in China in 2010, aiming to eliminate malaria by 2020. In 2017, no indigenous cases of malaria were detected in China for the first time. To provide evidence for precise surveillance and response to achieve elimination goal, a comprehensive study is needed to determine the changing epidemiology of malaria and the challenges towards elimination. Methods Using malaria surveillance data from 2011 to 2016, an integrated series of analyses was conducted to elucidate the changing epidemiological features of autochthonous and imported malaria, and the spatiotemporal patterns of malaria importation from endemic countries. Results From 2011 to 2016, a total of 21,062 malaria cases with 138 deaths were reported, including 91% were imported and 9% were autochthonous. The geographic distribution of local transmission have shrunk dramatically, but there were still more than 10 counties reporting autochthonous cases in 2013–2016, particularly in counties bordering with countries in South-East Asia. The importation from 68 origins countries had an increasing annual trend from Africa but decreasing importation from Southeast Asia. Four distinct communities have been identified in the importation networks with the destinations in China varied by origin and species. Conclusions China is on the verge of malaria elimination, but the residual transmission in border regions and the threats of importation from Africa and Southeast Asia are the key challenges to achieve and maintain malaria elimination. Efforts from China are also needed to help malaria control in origin countries and reduce the risk of introduced transmission.

BackgroundThe emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies.Methodology/principal findingsScrub typhus cases in Qingdao city during 2006-2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006-2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection.Conclusions/significanceMany locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes.

In order to monitor progress towards malaria elimination, it is crucial to be able to measure changes in spatio-temporal transmission. However, common metrics of malaria transmission such as parasite prevalence are under powered in elimination contexts. China has achieved major reductions in malaria incidence and is on track to eliminate, having reporting zero locally-acquired malaria cases in 2017 and 2018. Understanding the spatio-temporal pattern underlying this decline, especially the relationship between locally-acquired and imported cases, can inform efforts to maintain elimination and prevent re-emergence. This is particularly pertinent in Yunnan province, where the potential for local transmission is highest. Using a geo-located individual-level dataset of cases recorded in Yunnan province between 2011 and 2016, we introduce a novel Bayesian framework to model a latent diffusion process and estimate the joint likelihood of transmission between cases and the number of cases with unobserved sources of infection. This is used to estimate the case reproduction number, Rc. We use these estimates within spatio-temporal geostatistical models to map how transmission varied over time and space, estimate the timeline to elimination and the risk of resurgence. We estimate the mean Rc between 2011 and 2016 to be 0.171 (95% CI = 0.165, 0.178) for P. vivax cases and 0.089 (95% CI = 0.076, 0.103) for P. falciparum cases. From 2014 onwards, no cases were estimated to have a Rc value above one. An unobserved source of infection was estimated to be moderately likely (p>0.5) for 19/ 611 cases and high (p>0.8) for 2 cases, suggesting very high levels of case ascertainment. Our estimates suggest that, maintaining current intervention efforts, Yunnan is unlikely to experience sustained local transmission up to 2020. However, even with a mean of 0.005 projected up to 2020, locally-acquired cases are possible due to high levels of importation.

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016–2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.

Brucellosis, a zoonotic disease, was made statutorily notifiable in China in 1955. We analyzed the incidence and spatial–temporal distribution of human brucellosis during 1955–2014 in China using notifiable surveillance data: aggregated data for 1955–2003 and individual case data for 2004–2014. A total of 513,034 brucellosis cases were recorded, of which 99.3% were reported in northern China during 1955–2014, and 69.1% (258, 462/374, 141) occurred during February–July in 1990–2014. Incidence remained high during 1955–1978 (interquartile range 0.42–1.0 cases/100,000 residents), then decreased dramatically in 1979–1994. However, brucellosis has reemerged since 1995 (interquartile range 0.11–0.23 in 1995–2003 and 1.48–2.89 in 2004–2014); the historical high occurred in 2014, and the affected area expanded from northern pastureland provinces to the adjacent grassland and agricultural areas, then to southern coastal and southwestern areas. Control strategies in China should be adjusted to account for these changes by adopting a One Health approach.

We compared the epidemiology of hepatitis A and hepatitis E cases in China from 1990–2014 to better inform policy and prevention efforts. The incidence of hepatitis A cases declined dramatically, while hepatitis E incidence increased. During 2004–2014, hepatitis E mortality rates surpassed those of hepatitis A.

We conducted sentinel-based surveillance for norovirus in the Pudong area of Shanghai, China, during 2012–2013, by analyzing 5,324 community surveys, 408,024 medical records, and 771 laboratory-confirmed norovirus infections among 3,877 diarrhea cases. Our analysis indicated an outpatient incidence of 1.5/100 person-years and a community incidence of 8.9/100 person-years for norovirus-associated diarrhea.

Using national surveillance data for 120,111 human anthrax cases recorded during 1955−2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005−2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax.

BackgroundFrom 2013 to 2017, more than one thousand avian influenza A (H7N9) confirmed cases with hundreds of deaths were reported in mainland China. To identify priorities for epidemic prevention and control, a risk assessing framework for subnational variations is needed to define the epidemic potential of A (H7N9).MethodsWe established a consolidated two-stage framework that outlined the potential epidemic of H7N9 in humans: The Stage 1, index-case potential, used a Boosted Regression Trees model to assess population at risk due to spillover from poultry; the Stage 2, epidemic potential, synthesized the variables upon a framework of the Index for Risk Management to measure epidemic potential based on the probability of hazards and exposure, the vulnerability and coping capacity.ResultsProvinces in southern and eastern China, especially Jiangsu, Zhejiang, Guangzhou, have high index-case potential of human infected with A (H7N9), while northern coastal provinces and municipalities with low morbidity, i.e. Tianjin and Liaoning, have an increasing risk of A (H7N9) infection. Provinces in central China are likely to have high potential of epidemic due to the high vulnerability and the lack of coping capacity.ConclusionsThis study provides a unified risk assessment of A (H7N9) to detect the two-stage heterogeneity of epidemic potential among different provinces in mainland China, allowing proactively evaluate health preparedness at subnational levels to improve surveillance, diagnostic capabilities, and health promotion.

[This corrects the article DOI: 10.1371/journal.pone.0205500.].

Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005-15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.

BACKGROUND:Human brucellosis has become a major public health problem in China. However, the available clinical data on brucellosis cases are limited. METHODS:We retrospectively reviewed medical charts of 2041 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. These patients were admitted to the Sixth People's Hospital of the Xinjiang Uygur Autonomous region between 1st January and 31st December 2014. Data on these patients were collected from hospital medical records. RESULTS:Many patients presented with fatigue (67%), fever (64%), arthralgia (63%) and sweating (54%). High erythrocyte sedimentation rate (ESR) (69%), high C-reactive protein (CRP) (39%), high alanine aminotransferase (ALT) (33%) and high aspartate aminotransferase (AST) (20%) were the most common laboratory findings, especially in acute patients. There was evidence of focal involvement in 90% of patients. A total of 61.5% of brucellosis patients recovered. Multivariate logistic regression analyses suggested that the risk factors key to unfavorable prognosis were: age≥45 years (OR = 1.75, 95% CI 1.36-2.24), back pain (OR = 1.50, 95% CI 1.16-1.94) and joint tenderness (OR = 1.73, 95% CI 1.13-2.65). The increasing duration of the illness increased the risk of poor prognosis. CONCLUSION:Patients with brucellosis showed different characteristics in different clinical stages. In China, the chronicity rate of human brucellosis is high. The risk of poor prognosis is increased in patients aged 45 years or older, patients who have had brucellosis for a substantial period of time, and patients with back pain or joint tenderness. The clinical management of brucellosis should be improved to include sensitive diagnostic methods for subacute and chronic brucellosis.

During May-August 2013, a malaria outbreak comprising 874 persons in Shanglin County, China, was detected among 4,052 persons returning from overseas. Ghana was the predominant destination country, and 92.3% of malarial infections occurred in gold miners. Preventive measures should be enhanced for persons in high-risk occupations traveling to malaria-endemic countries.

Objective To evaluate the performance of China’s infectious disease automated alert and response system in the detection of outbreaks of hand, foot and mouth (HFM) disease. Methods We estimated size, duration and delay in reporting HFM disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and between 1 May 2010 and 30 April 2012, before and after automatic alert and response included HFM disease. Sensitivity, specificity and timeliness of detection of aberrations in the incidence of HFM disease outbreaks were estimated by comparing automated detections to observations of public health staff. Findings The alert and response system recorded 106 005 aberrations in the incidence of HFM disease between 1 May 2010 and 30 April 2012 – a mean of 5.6 aberrations per 100 days in each county that reported HFM disease. The response system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay between the reporting of the first case of an outbreak and detection of that outbreak by the response system was 2.1 days. Between the first and second study periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8 cases and the mean interval between the onset and initial reporting of such an outbreak to the public health emergency reporting system decreased from 10.0 to 9.1 days. Conclusion The automated alert and response system shows good sensitivity in the detection of HFM disease outbreaks and appears to be relatively rapid. Continued use of this system should allow more effective prevention and limitation of such outbreaks in China.

Acute diarrhea leads to a substantial disease burden among the elderly worldwide. However, in the context of increasingly aging trend in China, the prevalence of etiological agents among elderly diarrheal patients was undetermined. This study aimed to explore the major enteropathogens of acute diarrhea among outpatients older than 65 years in China, and also the epidemiological features of the pathogens. Demographic and clinical data for acute diarrhea among outpatients older than 65 years were collected from 213 participating hospitals from 2009 to 2014. Stool specimens were collected and tested for 13 enteric viruses and bacteria. The proportion of outpatients positive for targeted pathogens was analyzed by residential areas and seasonal patterns. Among the 7,725 patients enrolled, 1,617 (20.9%)were positive for any one of the 13 study pathogens. The predominant pathogen was norovirus (9.0%), followed by diarrheagenic Escherichia coli (DEC) (5.5%), rotavirus (3.9%), non-typhoidal Salmonella (NTS) (2.9%), and Shigella spp. (2.5%). The prevalence of Shigella spp. among rural patients (6.9%) was higher than that among urban patients (1.6%) (p < 0.001), with opposite trend for DEC (3.6% versus 5.9%, p = 0.007). An obvious seasonal pattern was observed for major pathogens, with peak for norovirus in autumn, rotavirus in winter and DEC, NTS, and Shigella spp. in summer. A wide variety of enteropathogens were detected among the elderly with acute diarrhea in China, with norovirus and DEC being the most commonly isolated pathogens. A strong seasonal pattern was observed for major pathogens of acute diarrhea among the elderly.

Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged

Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

An outbreak detection and response system, using time series moving percentile method based on historical data, in China has been used for identifying dengue fever outbreaks since 2008. For dengue fever outbreaks reported from 2009 to 2012, this system achieved a sensitivity of 100%, a specificity of 99.8% and a median time to detection of 3 days, which indicated that the system was a useful decision tool for dengue fever control and risk-management programs in China.

BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged

We evaluated a novel strategy to improve the performance of outbreak detection algorithms, namely setting the alerting threshold separately in each region according to the disease incidence in that region. By using data on hand, foot and mouth disease in Shandong province, China, we evaluated the impact of disease incidence on the performance of outbreak detection algorithms (EARS-C1, C2 and C3). Compared to applying the same algorithm and threshold to the whole region, setting the optimal threshold in each region according to the level of disease incidence (i.e., high, middle, and low) enhanced sensitivity (C1: from 94.4% to 99.1%, C2: from 93.5% to 95.4%, C3: from 91.7% to 95.4%) and reduced the number of alert signals (the percentage of reduction is C1∶4.3%, C2∶11.9%, C3∶10.3%). Our findings illustrate a general method for improving the accuracy of detection algorithms that is potentially applicable broadly to other diseases and regions.

BackgroundOver the past two decades, major epidemics of hand, foot, and mouth disease (HFMD) have occurred throughout most of the West-Pacific Region countries, causing thousands of deaths among children. However, few studies have examined potential determinants of the incidence of HFMD.MethodsReported HFMD cases from 2912 counties in China were obtained for May 2008. The monthly HFMD cumulative incidence was calculated for children aged 9 years and younger. Child population density (CPD) and six climate factors (average-temperature [AT], average-minimum-temperature [AT(min)], average-maximum-temperature [AT(max)], average-temperature-difference [AT(diff)], average-relative-humidity [ARH], and monthly precipitation [MP]) were selected as potential explanatory variables for the study. Geographically weighted regression (GWR) models were used to explore the associations between the selected factors and HFMD incidence at county level.ResultsThere were 176,111 HFMD cases reported in the studied counties. The adjusted monthly cumulative incidence by county ranged from 0.26 cases per 100,000 children to 2549.00 per 100,000 children. For local univariate GWR models, the percentage of counties with statistical significance (pConclusionChild population density and climate factors are potential determinants of the HFMD incidence in most areas in China. The strength and direction of association between these factors and the incidence of HFDM is spatially heterogeneous at the local geographic level, and child population density has a greater influence on the incidence of HFMD than the climate factors.