Dengue Transmission Dynamics Research Articles

Membrane feeding of dengue patient's blood as a substitute for direct skin feeding in studying Aedes-dengue virus interaction.

BackgroundUnderstanding the interaction between Aedes vectors and dengue viruses (DENV) has significant implications in determining the transmission dynamics of dengue. The absence of an animal model and ethical concerns regarding direct feeding of mosquitoes on patients has resulted in most infection studies using blood meals spiked with laboratory-cultured DENV. Data obtained from such studies may not reflect the natural human-mosquito transmission scenario. This study explored the potential of using membrane feeding of dengue patient’s blood as a substitute for direct skin feeding.MethodsFour to six-day old female Ae. aegypti were provided the opportunity to feed via direct exposure to a patient’s forearm for 15 min or via exposure to EDTA-treated blood from the same patient through an artificial membrane for 30 min. Mosquitoes from both feeding methods were incubated inside environmental chambers. Mosquitoes were sampled at day 13 post-feeding. Midgut and salivary glands of each mosquito were dissected to determine DENV infection by RT-qPCR and viral titration, respectively.ResultsFeeding rates: Direct skin feeding assay (DSFA) consistently showed higher mosquito feeding rates (93.3–100 %) when compared with the membrane feeding assay (MFA) (48–98.2 %). Midgut infection: Pair-wise comparison between methods showed no significant difference in midgut infection rates between mosquitoes exposed via each method and a strong correlation was observed in midgut infection rates for both feeding methods (r = 0.89, P < 0.0001). Overall midgut viral titers (n = 20) obtained by both methods were comparable (P ≥ 0.06). Salivary gland infection: Pair-wise comparison between both methods revealed no significant difference in salivary gland infection rate. Strong correlation in salivary gland infection was observed between DSFA and MFA (r = 0.81, P < 0.0001). In general, mosquitoes fed directly on dengue patients and those on patients’ blood (n = 11) had comparable virus titer (P ≥ 0.09).ConclusionDENV midgut and salivary gland infection rates showed good concordance between DSFA and MFA blood meal exposure methods. Freshly-obtained venous blood in EDTA from dengue patients for MFA can be used as a substitute to DSFA, especially in circumstances where bioethics approval or patient recruitment is difficult to obtain for vector competence studies. Nevertheless, mosquito numbers will need to be increased to compensate for lower feeding rate in MFA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1469-6) contains supplementary material, which is available to authorized users.

Estimation of the potential impact of dengue vaccination on clinical outcomes in Brazil

Objective: The aim of the current analysis was to measure the public health impact of dengue vaccination in Brazil using a published transmission dynamics model. Methods: We adapted a mathematical model that represented the transmission dynamics of the four dengue fever serotypes in humans and in the mosquito. This compartmental model represents the known characteristics of dengue transmission dynamics: host-vector interactions, immunological interactions between all four dengue serotypes, age structure of the population, levels of specific transmission by age, seasonality of the disease, and growth of the human and vector population. Results: Our mathematical model showed a 22% (CI95%: 9-37) reduction of all cases of dengue fever for a smaller scenario (routine vaccination at 9 years old and catch-up campaign to 10 years of age) and 81% (CI95%: 67-89) in the largest scenario (routine vaccination at 9 years old and catch-up campaign to 40 years of age) over a 5-year period. For the 10-year impact, we estimated a 22% (CI95%: 12-39) reduction in the smaller scenario, and a 92% (CI95%: 80-95) reduction in the larger scenario. This reduction in the number of cases would lead to significant decrease in the number of hospitalizations. Up to 233,509 (CI95%: 148,534 - 331,849) and 739,378 (CI95%: 604,386 – 894,072) hospitalizations would be prevented over a 5-year and 10-year period, respectively, with the larger vaccination program. Conclusion: This analysis indicates that, within expected variations, a national dengue vaccination program in Brazil would lead to significant public health benefits by reducing dengue infections and hospitalizations.

Climate and the Timing of Imported Cases as Determinants of the Dengue Outbreak in Guangzhou, 2014: Evidence from a Mathematical Model

As the world’s fastest spreading vector-borne disease, dengue was estimated to infect more than 390 million people in 2010, a 30-fold increase in the past half century. Although considered to be a non-endemic country, mainland China had 55,114 reported dengue cases from 2005 to 2014, of which 47,056 occurred in 2014. Furthermore, 94% of the indigenous cases in this time period were reported in Guangdong Province, 83% of which were in Guangzhou City. In order to determine the possible determinants of the unprecedented outbreak in 2014, a population-based deterministic model was developed to describe dengue transmission dynamics in Guangzhou. Regional sensitivity analysis (RSA) was adopted to calibrate the model and entomological surveillance data was used to validate the mosquito submodel. Different scenarios were created to investigate the roles of the timing of an imported case, climate, vertical transmission from mosquitoes to their offspring, and intervention. The results suggested that an early imported case was the most important factor in determining the 2014 outbreak characteristics. Precipitation and temperature can also change the transmission dynamics. Extraordinary high precipitation in May and August, 2014 appears to have increased vector abundance. Considering the relatively small number of cases in 2013, the effect of vertical transmission was less important. The earlier and more frequent intervention in 2014 also appeared to be effective. If the intervention in 2014 was the same as that in 2013, the outbreak size may have been over an order of magnitude higher than the observed number of new cases in 2014.The early date of the first imported and locally transmitted case was largely responsible for the outbreak in 2014, but it was influenced by intervention, climate and vertical transmission. Early detection and response to imported cases in the spring and early summer is crucial to avoid large outbreaks in the future.

Aedes aegypti (L.) in Latin American and Caribbean region: With growing evidence for vector adaptation to climate change?

Within Latin America and the Caribbean region the impact of climate change has been associated with the effects of rainfall and temperature on seasonal outbreaks of dengue but few studies have been conducted on the impacts of climate on the behaviour and ecology of Aedes aegypti mosquitoes.This study was conducted to examine the adaptive behaviours currently being employed by A. aegypti mosquitoes exposed to the force of climate change in LAC countries. The literature on the association between climate and dengue incidence is small and sometimes speculative. Few laboratory and field studies have identified research gaps. Laboratory and field experiments were designed and conducted to better understand the container preferences, climate-associated-adaptive behaviour, ecology and the effects of different temperatures and light regimens on the life history of A. aegypti mosquitoes. A. aegypti adaptive behaviours and changes in container preferences demonstrate how complex dengue transmission dynamics is, in different ecosystems. The use of underground drains and septic tanks represents a major behaviour change identified and compounds an already difficult task to control A. aegypti populations. A business as usual approach will exacerbate the problem and lead to more frequent outbreaks of dengue and chikungunya in LAC countries unless both area-wide and targeted vector control approaches are adopted. The current evidence and the results from proposed transdisciplinary research on dengue within different ecosystems will help guide the development of new vector control strategies and foster a better understanding of climate change impacts on vector-borne disease transmission.

Region-wide synchrony and traveling waves of dengue across eight countries in Southeast Asia

Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.

The role of residence times in two-patch dengue transmission dynamics and optimal strategies.

The reemergence and geographical dispersal of vector-borne diseases challenge global health experts around the world and in particular, dengue poses increasing difficulties in the Americas, due in part to explosive urban and semi-urban growth, increases of within and between region mobility, the absence of a vaccine, and the limited resources available for public health services. In this work, a simple deterministic two-patch model is introduced to assess the impact of dengue transmission dynamics in heterogeneous environments. The two-patch system models the movement (e.g. urban versus rural areas residence times) of individuals between and within patches/environments using residence-time matrices with entries that budget within and between host patch relative residence times, under the assumption that only the human budgets their residence time across regions. Three scenarios are considered: (i) resident hosts in Patch i visit patch j, where i≠j but not the other way around, a scenario referred to as unidirectional motion; (ii) symmetric bi-directional motion; and (iii) asymmetric bi-directional motion. Optimal control theory is used to identify and evaluate patch-specific control measures aimed at reducing dengue prevalence in humans and vectors at a minimal cost. Optimal policies are computed under different residence-matrix configurations mentioned above as well as transmissibility scenarios characterized by the magnitude of the basic reproduction number. Optimal patch-specific polices can ameliorate the impact of epidemic outbreaks substantially when the basic reproduction number is moderate. The final patch-specific epidemic size variation increases as the residence time matrix moves away from the symmetric case (asymmetry). As expected, the patch where individuals spend most of their time or in the patch where transmissibility is higher tend to support larger patch-specific final epidemic sizes. Hence, focusing on intervention that target areas where individuals spend "most" time or where transmissibility is higher turn out to be optimal. Therefore, reducing traffic is likely to take a host-vector system into the world of manageable outbreaks.

Modelling the transmission dynamics of dengue in the presence of Wolbachia

Use of the bacterium Wolbachia is an innovative new strategy designed to break the cycle of dengue transmission. There are two main mechanisms by which Wolbachia could achieve this: by reducing the level of dengue virus in the mosquito and/or by shortening the host mosquito’s lifespan. However, although Wolbachia shortens the lifespan, it also gives a breeding advantage which results in complex population dynamics. This study focuses on the development of a mathematical model to quantify the effect on human dengue cases of introducing Wolbachia into the mosquito population. The model consists of a compartment-based system of first-order differential equations; seasonal forcing in the mosquito population is introduced through the adult mosquito death rate. The analysis focuses on a single dengue outbreak typical of a region with a strong seasonally-varying mosquito population. We found that a significant reduction in human dengue cases can be obtained provided that Wolbachia-carrying mosquitoes persist when competing with mosquitoes without Wolbachia. Furthermore, using the Wolbachia strain WMel reduces the mosquito lifespan by at most 10% and allows them to persist in competition with non-Wolbachia-carrying mosquitoes. Mosquitoes carrying the WMelPop strain, however, are not likely to persist as it reduces the mosquito lifespan by up to 50%. When all other effects of Wolbachia on the mosquito physiology are ignored, cytoplasmic incompatibility alone results in a reduction in the number of human dengue cases. A sensitivity analysis of the parameters in the model shows that the transmission probability, the biting rate and the average adult mosquito death rate are the most important parameters for the outcome of the cumulative proportion of human individuals infected with dengue.

On a reaction–diffusion system modeling the dengue transmission with nonlocal infections and crowding effects

In this paper, we intend to understand the influences of the spatial heterogeneity, crowding effect and non-local infection caused by the movements of the latent mosquitoes on the dynamics of dengue transmission. For this purpose, we modify the homogeneous system provided in Esteva and Vargas (1998) to obtain a nonlocal and time-delayed reaction–diffusion system with the Neumann condition on the boundary. Then the basic reproduction number R0 is defined for the model system, and it can be obtained explicitly when all model parameters are constants. Finally, we show that the global threshold dynamics of the model system can be determined by R0.

Risk factors associated with an outbreak of dengue fever/dengue haemorrhagic fever in Hanoi, Vietnam.

Dengue fever/dengue haemorrhagic fever (DF/DHF) appears to be emerging in Hanoi in recent years. A case-control study was performed to investigate risk factors for the development of DF/DHF in Hanoi. A total of 73 patients with DF/DHF and 73 control patients were included in the study. The risk factor analysis indicated that living in rented housing, living near uncovered sewers, and living in a house discharging sewage directly into to ponds were all significantly associated with DF/DHF. People living in rented houses were 2·2 times more at risk of DF/DHF than those living in their own homes [adjusted odds ratio (aOR) 2·2, 95% confidence interval (CI) 1·1-4·6]. People living in an unhygienic house, or in a house discharging sewage directly to the ponds were 3·4 times and 4·3 times, respectively, more likely to be associated with DF/DHF (aOR 3·4, 95% CI 1-11·7; aOR 4·3, 95% CI 1·1-16·9). These results contribute to the understanding of the dynamics of dengue transmission in Hanoi, which is needed to implement dengue prevention and control programmes effectively and efficiently.

Estimating the basic reproduction number for single-strain dengue fever epidemics

BackgroundDengue, an infectious tropical disease, has recently emerged as one of the most important mosquito-borne viral diseases in the world. We perform a retrospective analysis of the 2011 dengue fever epidemic in Pakistan in order to assess the transmissibility of the disease. We obtain estimates of the basic reproduction number R0 from epidemic data using different methodologies applied to different epidemic models in order to evaluate the robustness of our estimate.ResultsWe first estimate model parameters by fitting a deterministic ODE vector-host model for the transmission dynamics of single-strain dengue to the epidemic data, using both a basic ordinary least squares (OLS) as well as a generalized least squares (GLS) scheme. Moreover, we perform the same analysis for a direct-transmission ODE model, thereby allowing us to compare our results across different models. In addition, we formulate a direct-transmission stochastic model for the transmission dynamics of dengue and obtain parameter estimates for the stochastic model using Markov chain Monte Carlo (MCMC) methods. In each of the cases we have considered, the estimate for the basic reproduction number R0 is initially greater than unity leading to an epidemic outbreak. However, control measures implemented several weeks after the initial outbreak successfully reduce R0 to less than unity, thus resulting in disease elimination. Furthermore, it is observed that there is strong agreement in our estimates for the pre-control value of R0, both across different methodologies as well across different models. However, there are also significant differences between our estimates for the post-control value of the basic reproduction number across the two different models.ConclusionIn conclusion, we have obtained robust estimates for the value of the basic reproduction number R0 associated with the 2011 dengue fever epidemic before the implementation of public health control measures. Furthermore, we have shown that there is close agreement between our estimates for the post-control value of R0 across the different methodologies. Nevertheless, there are also significant differences between the estimates for the post-control value of R0 across the two different models.

Impact of combined vector-control and vaccination strategies on transmission dynamics of dengue fever: a model-based analysis

Dengue fever is a vector-borne disease prevalent in tropical and subtropical regions. It is an important public health problem with a considerable and often under-valued disease burden in terms of frequency, cost and quality-of-life. Recent literature reviews have documented the development of mathematical models of dengue fever both to identify important characteristics for future model development as well as to assess the impact of dengue control interventions. Such reviews highlight the importance of short-term cross-protection; antibody-dependent enhancement; and seasonality (in terms of both favourable and unfavourable conditions for mosquitoes). The compartmental model extends work by Bartley (2002) and combines the following factors: seasonality, age-structure, consecutive infection by all four serotypes, cross-protection and immune enhancement, as well as combined vector-host transmission. The model is used to represent dengue transmission dynamics using parameters appropriate for Thailand and to assess the potential impact of combined vector-control and vaccination strategies including routine and catch-up vaccination strategies on disease dynamics. When seasonality and temporary cross-protection between serotypes are included, the model is able to approximate the observed incidence of dengue fever in Thailand. We find vaccination to be the most effective single intervention, albeit with imperfect efficacy (30.2 %) and limited duration of protection. However, in combination, control interventions and vaccination exhibit a marked impact on dengue fever transmission. This study shows that an imperfect vaccine can be a useful weapon in reducing disease spread within the community, although it will be most effective when promoted as one of several strategies for combating dengue fever transmission.

Reduced Risk of Disease During Postsecondary Dengue Virus Infections

Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1-4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics.

Breaking the symmetry: Immune enhancement increases persistence of dengue viruses in the presence of asymmetric transmission rates

The dengue viruses exist as four antigenically distinct serotypes. These four serotypes co-circulate and interact with each other through multiple immune-mediated mechanisms. Though the majority of previous efforts to understand the transmission dynamics of dengue have assumed identical characteristics for these four serotypes, empirical data suggests that they differ from one another in important ways. Here, we examine dynamics and persistence in models that do not assume symmetry between the dengue viruses. We find that for serotype transmission rates that are only slightly asymmetric, increased transmissibility of secondary infections through immune enhancement increases the persistence of all dengue viruses in opposition to findings in symmetric models. We identify an optimal magnitude of immune enhancement that maximizes the probability of persistence of all four serotypes. In contrast to other pathogen systems where heterogeneity between serotypes in transmissibility facilitates competitive exclusion (Bremmermann and Thieme, 1989), here we find that in the presence of Antibody Dependent Enhancement (ADE) heterogeneity can increase the persistence of multiple serotypes of dengue.

Dynamic Epidemiological Models for Dengue Transmission: A Systematic Review of Structural Approaches

Dengue is a vector-borne disease recognized as the major arbovirose with four immunologically distant dengue serotypes coexisting in many endemic areas. Several mathematical models have been developed to understand the transmission dynamics of dengue, including the role of cross-reactive antibodies for the four different dengue serotypes. We aimed to review deterministic models of dengue transmission, in order to summarize the evolution of insights for, and provided by, such models, and to identify important characteristics for future model development. We identified relevant publications using PubMed and ISI Web of Knowledge, focusing on mathematical deterministic models of dengue transmission. Model assumptions were systematically extracted from each reviewed model structure, and were linked with their underlying epidemiological concepts. After defining common terms in vector-borne disease modelling, we generally categorised fourty-two published models of interest into single serotype and multiserotype models. The multi-serotype models assumed either vector-host or direct host-to-host transmission (ignoring the vector component). For each approach, we discussed the underlying structural and parameter assumptions, threshold behaviour and the projected impact of interventions. In view of the expected availability of dengue vaccines, modelling approaches will increasingly focus on the effectiveness and cost-effectiveness of vaccination options. For this purpose, the level of representation of the vector and host populations seems pivotal. Since vector-host transmission models would be required for projections of combined vaccination and vector control interventions, we advocate their use as most relevant to advice health policy in the future. The limited understanding of the factors which influence dengue transmission as well as limited data availability remain important concerns when applying dengue models to real-world decision problems.

Climate Change, Population Immunity, and Hyperendemicity in the Transmission Threshold of Dengue

BackgroundIt has been suggested that the probability of dengue epidemics could increase because of climate change. The probability of epidemics is most commonly evaluated by the basic reproductive number (R0), and in mosquito-borne diseases, mosquito density (the number of female mosquitoes per person [MPP]) is the critical determinant of the R0 value. In dengue-endemic areas, 4 different serotypes of dengue virus coexist–a state known as hyperendemicity–and a certain proportion of the population is immune to one or more of these serotypes. Nevertheless, these factors are not included in the calculation of R0. We aimed to investigate the effects of temperature change, population immunity, and hyperendemicity on the threshold MPP that triggers an epidemic.Methods and FindingsWe designed a mathematical model of dengue transmission dynamics. An epidemic was defined as a 10% increase in seroprevalence in a year, and the MPP that triggered an epidemic was defined as the threshold MPP. Simulations were conducted in Singapore based on the recorded temperatures from 1980 to 2009 The threshold MPP was estimated with the effect of (1) temperature only; (2) temperature and fluctuation of population immunity; and (3) temperature, fluctuation of immunity, and hyperendemicity. When only the effect of temperature was considered, the threshold MPP was estimated to be 0.53 in the 1980s and 0.46 in the 2000s, a decrease of 13.2%. When the fluctuation of population immunity and hyperendemicity were considered in the model, the threshold MPP decreased by 38.7%, from 0.93 to 0.57, from the 1980s to the 2000s.ConclusionsThe threshold MPP was underestimated if population immunity was not considered and overestimated if hyperendemicity was not included in the simulations. In addition to temperature, these factors are particularly important when quantifying the threshold MPP for the purpose of setting goals for vector control in dengue-endemic areas.

Controlling Dengue with Vaccines in Thailand

BackgroundDengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes.Methodology/Principal FindingsWe developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period.Conclusions/SignificanceVaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.

Modelización del efecto de la variabilidad climática local sobre la transmisión de dengue en Medellín (Colombia) mediante análisis de series temporales

Dengue fever is a major impact on public health vector-borne disease, and its transmission is influenced by entomological, sociocultural and economic factors. Additionally, climate variability plays an important role in the transmission dynamics. A large scientific consensus has indicated that the strong association between climatic variables and disease could be used to develop models to explain the incidence of the disease. To develop a model that provides a better understanding of dengue transmission dynamics in Medellin and predicts increases in the incidence of the disease. The incidence of dengue fever was used as dependent variable, and weekly climatic factors (maximum, mean and minimum temperature, relative humidity and precipitation) as independent variables. Expert Modeler was used to develop a model to better explain the behavior of the disease. Climatic variables with significant association to the dependent variable were selected through ARIMA models. The model explains 34% of observed variability. Precipitation was the climatic variable showing statistically significant association with the incidence of dengue fever, but with a 20 weeks delay. In Medellin, the transmission of dengue fever was influenced by climate variability, especially precipitation. The strong association dengue fever/precipitation allowed the construction of a model to help understand dengue transmission dynamics. This information will be useful to develop appropriate and timely strategies for dengue control.

The Interactive Roles of Aedes aegypti Super-Production and Human Density in Dengue Transmission

Background A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling.Methodology/Principal FindingsUsing data from seven censuses of A. aegypti pupae (2007–2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban ‘patches’ (1–3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R0) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R0, and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities.Significance/ConclusionsThese results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person's home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy.

Space‐time analysis of hospitalised dengue patients in rural Thailand reveals important temporal intervals in the pattern of dengue virus transmission

To determine the temporal intervals at which spatial clustering of dengue hospitalisations occurs. Space-time analysis of 262 people hospitalised and serologically confirmed with dengue virus infections in Kamphaeng Phet, Thailand was performed. The cases were observed between 1 January 2009 and 6 May 2011. Spatial coordinates of each patient's home were captured using the Global Positioning System. A novel method based on the Knox test was used to determine the temporal intervals between cases at which spatial clustering occurred. These intervals are indicative of the length of time between successive illnesses in the chain of dengue virus transmission. The strongest spatial clustering occurred at the 15-17-day interval. There was also significant spatial clustering over short intervals (2-5 days). The highest excess risk was observed within 200 m of a previous hospitalised case and significantly elevated risk persisted within this distance for 32-34 days. Fifteen to seventeen days are the most likely serial interval between successive dengue illnesses. This novel method relies only on passively detected, hospitalised case data with household locations and provides a useful tool for understanding region-specific and outbreak-specific dengue virus transmission dynamics.

Potential impacts of climate change on the ecology of dengue and its mosquito vector the Asian tiger mosquito (Aedes albopictus)

Shifts in temperature and precipitation patterns caused by global climate change may have profound impacts on the ecology of certain infectious diseases. We examine the potential impacts of climate change on the transmission and maintenance dynamics of dengue, a resurging mosquito-vectored infectious disease. In particular, we project changes in dengue season length for three cities: Atlanta, GA; Chicago, IL and Lubbock, TX. These cities are located on the edges of the range of the Asian tiger mosquito within the United States of America and were chosen as test cases. We use a disease model that explicitly incorporates mosquito population dynamics and high-resolution climate projections. Based on projected changes under the Special Report on Emissions Scenarios (SRES) A1fi (higher) and B1 (lower) emission scenarios as simulated by four global climate models, we found that the projected warming shortened mosquito lifespan, which in turn decreased the potential dengue season. These results illustrate the difficulty in predicting how climate change may alter complex systems.