Inter-annual variation in seasonal dengue epidemics driven by multiple interacting factors in Guangzhou, China.
ABSTRACT: Vector-borne diseases display wide inter-annual variation in seasonal epidemic size due to their complex dependence on temporally variable environmental conditions and other factors. In 2014, Guangzhou, China experienced its worst dengue epidemic on record, with incidence exceeding the historical average by two orders of magnitude. To disentangle contributions from multiple factors to inter-annual variation in epidemic size, we fitted a semi-mechanistic model to time series data from 2005-2015 and performed a series of factorial simulation experiments in which seasonal epidemics were simulated under all combinations of year-specific patterns of four time-varying factors: imported cases, mosquito density, temperature, and residual variation in local conditions not explicitly represented in the model. Our results indicate that while epidemics in most years were limited by unfavorable conditions with respect to one or more factors, the epidemic in 2014 was made possible by the combination of favorable conditions for all factors considered in our analysis.
Project description:Dengue, chikungunya, and Zika virus epidemics transmitted by Aedes aegypti mosquitoes have recently (re)emerged and spread throughout the Americas, Southeast Asia, the Pacific Islands, and elsewhere. Understanding how environmental conditions affect epidemic dynamics is critical for predicting and responding to the geographic and seasonal spread of disease. Specifically, we lack a mechanistic understanding of how seasonal variation in temperature affects epidemic magnitude and duration. Here, we develop a dynamic disease transmission model for dengue virus and Aedes aegypti mosquitoes that integrates mechanistic, empirically parameterized, and independently validated mosquito and virus trait thermal responses under seasonally varying temperatures. We examine the influence of seasonal temperature mean, variation, and temperature at the start of the epidemic on disease dynamics. We find that at both constant and seasonally varying temperatures, warmer temperatures at the start of epidemics promote more rapid epidemics due to faster burnout of the susceptible population. By contrast, intermediate temperatures (24-25°C) at epidemic onset produced the largest epidemics in both constant and seasonally varying temperature regimes. When seasonal temperature variation was low, 25-35°C annual average temperatures produced the largest epidemics, but this range shifted to cooler temperatures as seasonal temperature variation increased (analogous to previous results for diurnal temperature variation). Tropical and sub-tropical cities such as Rio de Janeiro, Fortaleza, and Salvador, Brazil; Cali, Cartagena, and Barranquilla, Colombia; Delhi, India; Guangzhou, China; and Manila, Philippines have mean annual temperatures and seasonal temperature ranges that produced the largest epidemics. However, more temperate cities like Shanghai, China had high epidemic suitability because large seasonal variation offset moderate annual average temperatures. By accounting for seasonal variation in temperature, the model provides a baseline for mechanistically understanding environmental suitability for virus transmission by Aedes aegypti. Overlaying the impact of human activities and socioeconomic factors onto this mechanistic temperature-dependent framework is critical for understanding likelihood and magnitude of outbreaks.
Project description:The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.
Project description:BACKGROUND:Many human infectious diseases are caused by pathogens that have multiple strains and show oscillation in infection incidence and alternation of dominant strains which together are referred to as epidemic cycling. Understanding the underlying mechanisms of epidemic cycling is essential for forecasting outbreaks of epidemics and therefore important for public health planning. Current theoretical effort is mainly focused on the factors that are extrinsic to the pathogens themselves ("extrinsic factors") such as environmental variation and seasonal change in human behaviours and susceptibility. Nevertheless, co-circulation of different strains of a pathogen was usually observed and thus strains interact with one another within concurrent infection and during sequential infection. The existence of these intrinsic factors is common and may be involved in the generation of epidemic cycling of multi-strain pathogens. METHODS AND FINDINGS:To explore the mechanisms that are intrinsic to the pathogens themselves ("intrinsic factors") for epidemic cycling, we consider a multi-strain SIRS model including cross-immunity and infectivity enhancement and use seasonal influenza as an example to parameterize the model. The Kullback-Leibler information distance was calculated to measure the match between the model outputs and the typical features of seasonal flu (an outbreak duration of 11 weeks and an annual attack rate of 15%). Results show that interactions among strains can generate seasonal influenza with these characteristic features, provided that: the infectivity of a single strain within concurrent infection is enhanced 2-7 times that within a single infection; cross-immunity as a result of past infection is 0.5-0.8 and lasts 2-9 years; while other parameters are within their widely accepted ranges (such as a 2-3 day infectious period and the basic reproductive number of 1.8-3.0). Moreover, the observed alternation of the dominant strain among epidemics emerges naturally from the best fit model. Alternative modelling that also includes seasonal forcing in transmissibility shows that both external mechanisms (i.e. seasonal forcing) and the intrinsic mechanisms (i.e., strain interactions) are equally able to generate the observed time-series in seasonal flu. CONCLUSIONS:The intrinsic mechanism of strain interactions alone can generate the observed patterns of seasonal flu epidemics, but according to Kullback-Leibler information distance the importance of extrinsic mechanisms cannot be excluded. The intrinsic mechanism illustrated here to explain seasonal flu may also apply to other infectious diseases caused by polymorphic pathogens.
Project description:BACKGROUND:Proper early warning thresholds for defining seasonal influenza epidemics are crucial for timely engagement of intervention strategies, but are currently not well established in China. We propose a novel moving logistic regression method (MLRM) to determine epidemic thresholds and validate them with the Chinese influenza surveillance data. METHODS:For each province, historical epidemic waves are formed as weekly percentages of laboratory-confirmed patients among all clinically diagnosed influenza cases. For each epidemic curve that is approximately symmetric, a series of logistic curves are fitted to increasing temporal range of the epidemic, and the threshold is determined based on the best-fitting logistic curve. RESULTS:Using surveillance data of seasonal influenza collected during 2010-2014 in 30 provinces of China, we screened 153 epidemic waves and identified 100 as approximately symmetric; and 85 of the 100 waves were satisfactorily fitted. Compared to two published approaches, the MLRM identified lower thresholds of seasonal influenza epidemics, leading to about three weeks earlier detection of onset and about four weeks later detection of closure of the epidemics. The potential misclassification proportion of influenza epidemic waves was 6% for the MLRM, comparable to that for the two published approaches. CONCLUSIONS:The MLRM offers an alternative to existing methods for defining early warning thresholds for the surveillance of seasonal influenza, and can be readily generalized to other countries and other infectious agents. The thresholds we identified can be used for early detection of future influenza epidemics in China.
Project description:The recent emergence and established presence of Aedes aegypti in the Autonomous Region of Madeira, Portugal, was responsible for the first autochthonous outbreak of dengue in Europe. The island has not reported any dengue cases since the outbreak in 2012. However, there is a high risk that an introduction of the virus would result in another autochthonous outbreak given the presence of the vector and permissive environmental conditions. Understanding the dynamics of a potential epidemic is critical for targeted local control strategies. Here, we adopt a deterministic model for the transmission of dengue in Aedes aegypti mosquitoes. The model integrates empirical and mechanistic parameters for virus transmission, under seasonally varying temperatures for Funchal, Madeira Island. We examine the epidemic dynamics as triggered by the arrival date of an infectious individual; the influence of seasonal temperature mean and variation on the epidemic dynamics; and performed a sensitivity analysis on the following quantities of interest: the epidemic peak size, time to peak, and the final epidemic size. Our results demonstrate the potential for summer and autumn season transmission of dengue, with the arrival date significantly affecting the distribution of the timing and peak size of the epidemic. Late-summer arrivals were more likely to produce large epidemics within a short peak time. Epidemics within this favorable period had an average of 11% of the susceptible population infected at the peak, at an average peak time of 95 days. We also demonstrated that seasonal temperature variation dramatically affects the epidemic dynamics, with warmer starting temperatures producing large epidemics with a short peak time and vice versa. Overall, our quantities of interest were most sensitive to variance in the date of arrival, seasonal temperature, transmission rates, mortality rate, and the mosquito population; the magnitude of sensitivity differs across quantities. Our model could serve as a useful guide in the development of effective local control and mitigation strategies for dengue fever in Madeira Island.
Project description:There is limited information on influenza and respiratory syncytial virus (RSV) seasonal patterns in tropical areas, although there is renewed interest in understanding the seasonal drivers of respiratory viruses.We review geographic variations in seasonality of laboratory-confirmed influenza and RSV epidemics in 137 global locations based on literature review and electronic sources. We assessed peak timing and epidemic duration and explored their association with geography and study settings. We fitted time series model to weekly national data available from the WHO influenza surveillance system (FluNet) to further characterize seasonal parameters.Influenza and RSV activity consistently peaked during winter months in temperate locales, while there was greater diversity in the tropics. Several temperate locations experienced semi-annual influenza activity with peaks occurring in winter and summer. Semi-annual activity was relatively common in tropical areas of Southeast Asia for both viruses. Biennial cycles of RSV activity were identified in Northern Europe. Both viruses exhibited weak latitudinal gradients in the timing of epidemics by hemisphere, with peak timing occurring later in the calendar year with increasing latitude (P<0.03). Time series model applied to influenza data from 85 countries confirmed the presence of latitudinal gradients in timing, duration, seasonal amplitude, and between-year variability of epidemics. Overall, 80% of tropical locations experienced distinct RSV seasons lasting 6 months or less, while the percentage was 50% for influenza.Our review combining literature and electronic data sources suggests that a large fraction of tropical locations experience focused seasons of respiratory virus activity in individual years. Information on seasonal patterns remains limited in large undersampled regions, included Africa and Central America. Future studies should attempt to link the observed latitudinal gradients in seasonality of viral epidemics with climatic and population factors, and explore regional differences in disease transmission dynamics and attack rates.
Project description:BACKGROUND:To optimize seasonal influenza vaccination programs in regions with potentially complicated seasonal patterns, the epidemiological characteristics of seasonal influenza activity in a subtropical city of China were explored. MATERIALS AND METHODS:Influenza virus data of patients with influenza-like illness (ILI) during 2013-2019 were collected from two sentinel hospitals in a subtropical region of China, Yichang city. The influenza virus positive rate among sampled ILI cases served as a proxy to estimate influenza seasonal characteristics, including periodicity, duration, peaks, and predominant subtypes/lineages. Epidemiological features of different years, seasons and age groups were analyzed, and vaccine mismatches were identified. RESULTS:In total, 8693 ILI cases were included; 1439 (16.6%) were laboratory-confirmed influenza cases. The influenza A positive rate (10.6%) was higher than the influenza B positive rate (5.9%). There were three influenza circulation patterns in Yichang: (1) annual periodicity (in 2013-2014, 2015-2016 and 2018-2019), (2) semiannual periodicity (in 2014-2015), and (3) year-round periodicity (in 2016-2017 and 2017-2018). Summer epidemics existed in two of the six years and were dominated by influenza A/H3N2. Winter and spring epidemics occurred in five of the six years, and A/H1N1, A/H3N2, B/Victoria, and B/Yamagata were codominant. During the study period, the predominant lineages, B/Victoria in 2015-16 and B/Yamagata in 2017-2018, were both mismatched with the influenza B component of the trivalent vaccine. Children 5-14 years old (26.4%) and individuals over 60 years old (16.9%) had the highest influenza positive rates. CONCLUSIONS:The seasonal epidemic period and the predominant subtype/lineage of influenza viruses in Yichang city are complex. Influenza vaccination timing and strategies need to be optimized according to the local features of influenza virus activity.
Project description:Seasonal influenza epidemics cause consistent, considerable, widespread loss annually in terms of economic burden, morbidity, and mortality. With access to accurate and reliable forecasts of a current or upcoming influenza epidemic's behavior, policy makers can design and implement more effective countermeasures. This past year, the Centers for Disease Control and Prevention hosted the "Predict the Influenza Season Challenge", with the task of predicting key epidemiological measures for the 2013-2014 U.S. influenza season with the help of digital surveillance data. We developed a framework for in-season forecasts of epidemics using a semiparametric Empirical Bayes framework, and applied it to predict the weekly percentage of outpatient doctors visits for influenza-like illness, and the season onset, duration, peak time, and peak height, with and without using Google Flu Trends data. Previous work on epidemic modeling has focused on developing mechanistic models of disease behavior and applying time series tools to explain historical data. However, tailoring these models to certain types of surveillance data can be challenging, and overly complex models with many parameters can compromise forecasting ability. Our approach instead produces possibilities for the epidemic curve of the season of interest using modified versions of data from previous seasons, allowing for reasonable variations in the timing, pace, and intensity of the seasonal epidemics, as well as noise in observations. Since the framework does not make strict domain-specific assumptions, it can easily be applied to some other diseases with seasonal epidemics. This method produces a complete posterior distribution over epidemic curves, rather than, for example, solely point predictions of forecasting targets. We report prospective influenza-like-illness forecasts made for the 2013-2014 U.S. influenza season, and compare the framework's cross-validated prediction error on historical data to that of a variety of simpler baseline predictors.
Project description:We analyze the impact of birth seasonality (seasonal oscillations in the birth rate) on the dynamics of acute, immunizing childhood infectious diseases. Previous research has explored the effect of human birth seasonality on infectious disease dynamics using parameters appropriate for the developed world. We build on this work by including in our analysis an extended range of baseline birth rates and amplitudes, which correspond to developing world settings. Additionally, our analysis accounts for seasonal forcing both in births and contact rates. We focus in particular on the dynamics of measles. In the absence of seasonal transmission rates or stochastic forcing, for typical measles epidemiological parameters, birth seasonality induces either annual or biennial epidemics. Changes in the magnitude of the birth fluctuations (birth amplitude) can induce significant changes in the size of the epidemic peaks, but have little impact on timing of disease epidemics within the year. In contrast, changes to the birth seasonality phase (location of the peak in birth amplitude within the year) significantly influence the timing of the epidemics. In the presence of seasonality in contact rates, at relatively low birth rates (20 per 1000), birth amplitude has little impact on the dynamics but does have an impact on the magnitude and timing of the epidemics. However, as the mean birth rate increases, both birth amplitude and phase play an important role in driving the dynamics of the epidemic. There are stronger effects at higher birth rates.
Project description:The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005-2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%-151%] in the north versus 37% [95% CI 27%-47%] in the south, p<0.0001). Epidemics peaked in January-February in Northern China (latitude ?33°N) and April-June in southernmost regions (latitude <27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January-February and June-August (periodicity ratio >0.6 in provinces located within 27.4°N-31.3°N, slope of latitudinal gradient with latitude -0.016 [95% CI -0.025 to -0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4-6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region. More broadly, our findings are consistent with the role of climatic factors on influenza transmission dynamics. Please see later in the article for the Editors' Summary.