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The effective reproduction number Reff is a critical epidemiological parameter that characterizes the transmissibility of a pathogen. However, this parameter is difficult to estimate in the presence of silent transmission and/or significant temporal variation in case reporting. This variation can occur due to the lack of timely or appropriate testing, public health interventions and/or changes in human behavior during an epidemic. This is exactly the situation we are confronted with during this COVID-19 pandemic. In this work, we propose to estimate Reff for the SARS-CoV-2 (the etiological agent of the COVID-19), based on a model of its propagation considering a time-varying transmission rate. This rate is modeled by a Brownian diffusion process embedded in a stochastic model. The model is then fitted by Bayesian inference (particle Markov Chain Monte Carlo method) using multiple well-documented hospital datasets from several regions in France and in Ireland. This mechanistic modeling framework enables us to reconstruct the temporal evolution of the transmission rate of the COVID-19 based only on the available data. Except for the specific model structure, it is non-specifically assumed that the transmission rate follows a basic stochastic process constrained by the observations. This approach allows us to follow both the course of the COVID-19 epidemic and the temporal evolution of its Reff(t). Besides, it allows to assess and to interpret the evolution of transmission with respect to the mitigation strategies implemented to control the epidemic waves in France and in Ireland. We can thus estimate a reduction of more than 80% for the first wave in all the studied regions but a smaller reduction for the second wave when the epidemic was less active, around 45% in France but just 20% in Ireland. For the third wave in Ireland the reduction was again significant (>70%).

Understanding the transition of epidemic to endemic dengue transmission remains a challenge in regions where serotypes co-circulate and there is extensive human mobility. French Polynesia, an isolated group of 117 islands of which 72 are inhabited, distributed among five geographically separated subdivisions, has recorded mono-serotype epidemics since 1944, with long inter-epidemic periods of circulation. Laboratory confirmed cases have been recorded since 1978, enabling exploration of dengue epidemiology under monotypic conditions in an isolated, spatially structured geographical location. A database was constructed of confirmed dengue cases, geolocated to island for a 35-year period. Statistical analyses of viral establishment, persistence and fade-out as well as synchrony among subdivisions were performed. Seven monotypic and one heterotypic dengue epidemic occurred, followed by low-level viral circulation with a recrudescent epidemic occurring on one occasion. Incidence was asynchronous among the subdivisions. Complete viral die-out occurred on several occasions with invasion of a new serotype. Competitive serotype replacement has been observed previously and seems to be characteristic of the South Pacific. Island population size had a strong impact on the establishment, persistence and fade-out of dengue cases and endemicity was estimated achievable only at a population size in excess of 175 000. Despite island remoteness and low population size, dengue cases were observed somewhere in French Polynesia almost constantly, in part due to the spatial structuration generating asynchrony among subdivisions. Long-term persistence of dengue virus in this group of island populations may be enabled by island hopping, although could equally be explained by a reservoir of sub-clinical infections on the most populated island, Tahiti.

Seoul hantavirus (SEOV) has recently raised concern by causing geographic range expansion of hemorrhagic fever with renal syndrome (HFRS). SEOV infections in humans are significantly underestimated worldwide and epidemic dynamics of SEOV-related HFRS are poorly understood because of a lack of field data and empirically validated models. Here, we use mathematical models to examine both intrinsic and extrinsic drivers of disease transmission from animal (the Norway rat) to humans in a SEOV-endemic area in China. We found that rat eradication schemes and vaccination campaigns, but below the local elimination threshold, could diminish the amplitude of the HFRS epidemic but did not modify its seasonality. Models demonstrate population dynamics of the rodent host were insensitive to climate variations in urban settings, while relative humidity had a negative effect on the seasonality in transmission. Our study contributes to a better understanding of the epidemiology of SEOV-related HFRS, demonstrates asynchronies between rodent population dynamics and transmission rate, and identifies potential drivers of the SEOV seasonality.

Despite ongoing efforts to control transmission, rabies prevention remains a challenge in many developing countries, especially in rural areas of China where re-emerging rabies is under-reported due to a lack of sustained animal surveillance. By taking advantage of detailed genomic and epidemiological data for the re-emerging rabies outbreak in Yunnan Province, China, collected between 1999 and 2015, we reconstruct the demographic and dispersal history of domestic dog rabies virus (RABV) as well as the dynamics of dog-to-dog and dog-to-human transmission. Phylogeographic analyses reveal a lower diffusion coefficient than previously estimated for dog RABV dissemination in northern Africa. Furthermore, epidemiological analyses reveal transmission rates between dogs, as well as between dogs and humans, lower than estimates for Africa. Finally, we show that reconstructed epidemic history of RABV among dogs and the dynamics of rabid dogs are consistent with the recorded human rabies cases. This work illustrates the benefits of combining phylogeographic and epidemic modelling approaches for uncovering the spatiotemporal dynamics of zoonotic diseases, with both approaches providing estimates of key epidemiological parameters.

The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-associated zoonosis caused by hantavirus. The HFRS was initially detected in northeast China in 1931, and since 1955 it has been detected in many regions of the country. Global climate dynamics influences HFRS spread in a complex nonlinear way. The quantitative assessment of the spatiotemporal variation of the "HFRS infections-global climate dynamics" association at a large geographical scale and during a long time period is still lacking.This work is the first study of a recently completed dataset of monthly HFRS cases in Eastern China during the period 2005-2016. A methodological synthesis that involves a time-frequency technique, a composite space-time model, hotspot analysis, and machine learning is implemented in the study of (a) the association between HFRS incidence spread and climate dynamics and (b) the geographic factors impacting this association over Eastern China during the period 2005-2016. The results showed that by assimilating core and city-specific knowledge bases the synthesis was able to depict quantitatively the space-time variation of periodic climate-HFRS associations at a large geographic scale and to assess numerically the strength of this association in the area and period of interest. It was found that the HFRS infections in Eastern China has a strong association with global climate dynamics, in particular, the 12, 18 and 36 mos periods were detected as the three main synchronous periods of climate dynamics and HFRS distribution. For the 36 mos period (which is the period with the strongest association), the space-time correlation pattern of the association strength indicated strong temporal but rather weak spatial dependencies. The generated space-time maps of association strength and association hotspots provided a clear picture of the geographic variation of the association strength that often-exhibited cluster characteristics (e.g., the south part of the study area displays a strong climate-HFRS association with non-point effects, whereas the middle-north part displays a weak climate-HFRS association). Another finding of this work is the upward climate-HFRS coherency trend for the past few years (2013-2015) indicating that the climate impacts on HFRS were becoming increasingly sensitive with time. Lastly, another finding of this work is that geographic factors affect the climate-HFRS association in an interrelated manner through local climate or by means of HFRS infections. In particular, location (latitude, distance to coastline and longitude), grassland and woodland are the geographic factors exerting the most noticeable effects on the climate-HFRS association (e.g., low latitude has a strong effect, whereas distance to coastline has a wave-like effect).The proposed synthetic quantitative approach revealed important aspects of the spatiotemporal variation of the climate-HFRS association in Eastern China during a long time period, and identified the geographic factors having a major impact on this association. Both findings could improve public health policy in an HFRS-torn country like China. Furthermore, the synthetic approach developed in this work can be used to map the space-time variation of different climate-disease associations in other parts of China and the World.

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons.

BACKGROUND:Increased risks for hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus have been observed since 2005, in Xi'an, China. Despite increased vigilance and preparedness, HFRS outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed HFRS cases and 88 deaths in 2010 and 2011. METHODS AND FINDINGS:Data on HFRS cases and weather were collected monthly from 2005 to 2012, along with active rodent monitoring. Wavelet analyses were performed to assess the temporal relationship between HFRS incidence, rodent density and climatic factors over the study period. Results showed that HFRS cases correlated to rodent density, rainfall, and temperature with 2, 3 and 4-month lags, respectively. Using a Bayesian time-series Poisson adjusted model, we fitted the HFRS outbreaks among humans for risk assessment in Xi'an. The best models included seasonality, autocorrelation, rodent density 2 months previously, and rainfall 2 to 3 months previously. Our models well reflected the epidemic characteristics by one step ahead prediction, out-of-sample. CONCLUSIONS:In addition to a strong seasonal pattern, HFRS incidence was correlated with rodent density and rainfall, indicating that they potentially drive the HFRS outbreaks. Future work should aim to determine the mechanism underlying the seasonal pattern and autocorrelation. However, this model can be useful in risk management to provide early warning of potential outbreaks of this disease.

BACKGROUND:China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. METHODOLOGY/PRINCIPAL FINDINGS:Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = -0.289, P

BACKGROUND: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991-2010 in Changsha, China. METHODS AND FINDINGS: Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3-4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño-Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity. CONCLUSIONS: The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease.

BackgroundIndividual variations in the use of the species niche are an important component of diversity in trophic interactions. A challenge in testing consistency of individual foraging strategy is the repeated collection of information on the same individuals.Methodology/principal findingsThe foraging strategies of sympatric fur seals (Arctocephalus gazella and A. tropicalis) were examined using the stable isotope signature of serially sampled whiskers. Most whiskers exhibited synchronous δ(13)C and δ(15)N oscillations that correspond to the seal annual movements over the long term (up to 8 years). δ(13)C and δ(15)N values were spread over large ranges, with differences between species, sexes and individuals. The main segregating mechanism operates at the spatial scale. Most seals favored foraging in subantarctic waters (where the Crozet Islands are located) where they fed on myctophids. However, A. gazella dispersed in the Antarctic Zone and A. tropicalis more in the subtropics. Gender differences in annual time budget shape the seal movements. Males that do not perform any parental care exhibited large isotopic oscillations reflecting broad annual migrations, while isotopic values of females confined to a limited foraging range during lactation exhibited smaller changes. Limited inter-individual isotopic variations occurred in female seals and in male A. tropicalis. In contrast, male A. gazella showed large inter-individual variations, with some males migrating repeatedly to high-Antarctic waters where they fed on krill, thus meaning that individual specialization occurred over years.Conclusions/significanceWhisker isotopic signature yields unique long-term information on individual behaviour that integrates the spatial, trophic and temporal dimensions of the ecological niche. The method allows depicting the entire realized niche of the species, including some of its less well-known components such as age-, sex-, individual- and migration-related changes. It highlights intrapopulation heterogeneity in foraging strategies that could have important implications for likely demographic responses to environmental variability.

BACKGROUND: Determining the factors underlying the long-range spatial spread of infectious diseases is a key issue regarding their control. Dengue is the most important arboviral disease worldwide and a major public health problem in tropical areas. However the determinants shaping its dynamics at a national scale remain poorly understood. Here we describe the spatial-temporal pattern of propagation of annual epidemics in Cambodia and discuss the role that human movements play in the observed pattern. METHODS AND FINDINGS: We used wavelet phase analysis to analyse time-series data of 105,598 hospitalized cases reported between 2002 and 2008 in the 135 (/180) most populous districts in Cambodia. We reveal spatial heterogeneity in the propagation of the annual epidemic. Each year, epidemics are highly synchronous over a large geographic area along the busiest national road of the country whereas travelling waves emanate from a few rural areas and move slowly along the Mekong River at a speed of ~11 km per week (95% confidence interval 3-18 km per week) towards the capital, Phnom Penh. CONCLUSIONS: We suggest human movements - using roads as a surrogate - play a major role in the spread of dengue fever at a national scale. These findings constitute a new starting point in the understanding of the processes driving dengue spread.

BackgroundDengue is a major global public health problem with increasing incidence and geographic spread. The epidemiology is complex with long inter-epidemic intervals and endemic with seasonal fluctuations. This study was initiated to investigate dengue transmission dynamics in Binh Thuan province, southern Vietnam.MethodologyWavelet analyses were performed on time series of monthly notified dengue cases from January 1994 to June 2009 (i) to detect and quantify dengue periodicity, (ii) to describe synchrony patterns in both time and space, (iii) to investigate the spatio-temporal waves and (iv) to associate the relationship between dengue incidence and El Niño-Southern Oscillation (ENSO) indices in Binh Thuan province, southern Vietnam.Principal findingsWe demonstrate a continuous annual mode of oscillation and a multi-annual cycle of around 2-3-years was solely observed from 1996-2001. Synchrony in time and between districts was detected for both the annual and 2-3-year cycle. Phase differences used to describe the spatio-temporal patterns suggested that the seasonal wave of infection was either synchronous among all districts or moving away from Phan Thiet district. The 2-3-year periodic wave was moving towards, rather than away from Phan Thiet district. A strong non-stationary association between ENSO indices and climate variables with dengue incidence in the 2-3-year periodic band was found.ConclusionsA multi-annual mode of oscillation was observed and these 2-3-year waves of infection probably started outside Binh Thuan province. Associations with climatic variables were observed with dengue incidence. Here, we have provided insight in dengue population transmission dynamics over the past 14.5 years. Further studies on an extensive time series dataset are needed to test the hypothesis that epidemics emanate from larger cities in southern Vietnam.

The recurrence of influenza A epidemics has originally been explained by a "continuous antigenic drift" scenario. Recently, it has been shown that if genetic drift is gradual, the evolution of influenza A main antigen, the haemagglutinin, is punctuated. As a consequence, it has been suggested that influenza A dynamics at the population level should be approximated by a serial model. Here, simple models are used to test whether a serial model requires gradual antigenic drift within groups of strains with the same antigenic properties (antigenic clusters). We compare the effect of status based and history based frameworks and the influence of reduced susceptibility and infectivity assumptions on the transient dynamics of antigenic clusters. Our results reveal that the replacement of a resident antigenic cluster by a mutant cluster, as observed in data, is reproduced only by the status based model integrating the reduced infectivity assumption. This combination of assumptions is useful to overcome the otherwise extremely high model dimensionality of models incorporating many strains, but relies on a biological hypothesis not obviously satisfied. Our findings finally suggest the dynamical importance of gradual antigenic drift even in the presence of punctuated immune escape. A more regular renewal of susceptible pool than the one implemented in a serial model should be part of a minimal theory for influenza at the population level.

BackgroundSeveral factors, including environmental and climatic factors, influence the transmission of vector-borne diseases. Nevertheless, the identification and relative importance of climatic factors for vector-borne diseases remain controversial. Dengue is the world's most important viral vector-borne disease, and the controversy about climatic effects also applies in this case. Here we address the role of climate variability in shaping the interannual pattern of dengue epidemics.Methods and findingsWe have analysed monthly data for Thailand from 1983 to 1997 using wavelet approaches that can describe nonstationary phenomena and that also allow the quantification of nonstationary associations between time series. We report a strong association between monthly dengue incidence in Thailand and the dynamics of El Niño for the 2-3-y periodic mode. This association is nonstationary, seen only from 1986 to 1992, and appears to have a major influence on the synchrony of dengue epidemics in Thailand.ConclusionThe underlying mechanism for the synchronisation of dengue epidemics may resemble that of a pacemaker, in which intrinsic disease dynamics interact with climate variations driven by El Niño to propagate travelling waves of infection. When association with El Niño is strong in the 2-3-y periodic mode, one observes high synchrony of dengue epidemics over Thailand. When this association is absent, the seasonal dynamics become dominant and the synchrony initiated in Bangkok collapses.