A Bayesian Hierarchical Model for Estimation of Abundance and Spatial Density of Aedes aegypti

Strategies to minimize dengue transmission commonly rely on vector control, which aims to maintain Ae. aegypti density below a theoretical threshold. Mosquito abundance is traditionally estimated from mark-release-recapture (MRR) experiments, which lack proper analysis regarding accurate vector spatial distribution and population density. Recently proposed strategies to control vector-borne diseases involve replacing the susceptible wild population by genetically modified individuals’ refractory to the infection by the pathogen. Accurate measurements of mosquito abundance in time and space are required to optimize the success of such interventions. In this paper, we present a hierarchical probabilistic model for the estimation of population abundance and spatial distribution from typical mosquito MRR experiments, with direct application to the planning of these new control strategies. We perform a Bayesian analysis using the model and data from two MRR experiments performed in a neighborhood of Rio de Janeiro, Brazil, during both low- and high-dengue transmission seasons. The hierarchical model indicates that mosquito spatial distribution is clustered during the winter (0.99 mosquitoes/premise 95% CI: 0.80–1.23) and more homogeneous during the high abundance period (5.2 mosquitoes/premise 95% CI: 4.3–5.9). The hierarchical model also performed better than the commonly used Fisher-Ford’s method, when using simulated data. The proposed model provides a formal treatment of the sources of uncertainty associated with the estimation of mosquito abundance imposed by the sampling design. Our approach is useful in strategies such as population suppression or the displacement of wild vector populations by refractory Wolbachia-infected mosquitoes, since the invasion dynamics have been shown to follow threshold conditions dictated by mosquito abundance. The presence of spatially distributed abundance hotspots is also formally addressed under this modeling framework and its knowledge deemed crucial to predict the fate of transmission control strategies based on the replacement of vector populations.     

Assessing the suitability for Aedes albopictus and dengue transmission risk in China with a delay differential equation model

Dengue is considered non-endemic to mainland China. However, travellers frequently import the virus from overseas and local mosquito species can then spread the disease in the population. As a consequence, mainland China still experiences large dengue outbreaks. Temperature plays a key role in these outbreaks: it affects the development and survival of the vector and the replication rate of the virus. To better understand its implication in the transmission risk of dengue, we developed a delay differential equation model that explicitly simulates temperature-dependent development periods and tested it with collected field data for the Asian tiger mosquito, Aedes albopictus. The model predicts mosquito occurrence locations with a high accuracy (Cohen’s κ of 0.78) and realistically replicates mosquito population dynamics. Analysing the infection dynamics during the 2014 dengue outbreak that occurred in Guangzhou showed that the outbreak could have lasted for another four weeks if mosquito control interventions had not been undertaken. Finally, we analyse the dengue transmission risk in mainland China. We find that southern China, including Guangzhou, can have more than seven months of dengue transmission per year while even Beijing, in the temperate north, can have dengue transmission during hot summer months. The results demonstrate the importance of using detailed vector and infection ecology, especially when vector-borne disease transmission risk is modelled over a broad range of climatic zones.     

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro,Brazil

Background

Rio de Janeiro, Brazil, experienced a severe dengue fever epidemic in 2008. This was the worst epidemic ever, characterized by a sharp increase in case-fatality rate, mainly among younger individuals. A combination of factors, such as climate, mosquito abundance, buildup of the susceptible population, or viral evolution, could explain the severity of this epidemic. The main objective of this study is to model the spatial patterns of dengue seroprevalence in three neighborhoods with different socioeconomic profiles in Rio de Janeiro. As blood sampling coincided with the peak of dengue transmission, we were also able to identify recent dengue infections and visually relate them to Aedes aegypti spatial distribution abundance. We analyzed individual and spatial factors associated with seroprevalence using Generalized Additive Model (GAM).

Methodology/Principal Findings

Three neighborhoods were investigated: a central urban neighborhood, and two isolated areas characterized as a slum and a suburban area. Weekly mosquito collections started in September 2006 and continued until March 2008. In each study area, 40 adult traps and 40 egg traps were installed in a random sample of premises, and two infestation indexes calculated: mean adult density and mean egg density. Sera from individuals living in the three neighborhoods were collected before the 2008 epidemic (July through November 2007) and during the epidemic (February through April 2008). Sera were tested for DENV-reactive IgM, IgG, Nested RT-PCR, and Real Time RT-PCR. From the before–after epidemics paired data, we described seroprevalence, recent dengue infections (asymptomatic or not), and seroconversion. Recent dengue infection varied from 1.3% to 14.1% among study areas. The highest IgM seropositivity occurred in the slum, where mosquito abundance was the lowest, but household conditions were the best for promoting contact between hosts and vectors. By fitting spatial GAM we found dengue seroprevalence hotspots located at the entrances of the two isolated communities, which are commercial activity areas with high human movement. No association between recent dengue infection and household''s high mosquito abundance was observed in this sample.

Conclusions/Significance

This study contributes to better understanding the dynamics of dengue in Rio de Janeiro by assessing the relationship between dengue seroprevalence, recent dengue infection, and vector density. In conclusion, the variation in spatial seroprevalence patterns inside the neighborhoods, with significantly higher risk patches close to the areas with large human movement, suggests that humans may be responsible for virus inflow to small neighborhoods in Rio de Janeiro. Surveillance guidelines should be further discussed, considering these findings, particularly the spatial patterns for both human and mosquito populations.     

The Spread of Aedes albopictus in Metropolitan France: Contribution of Environmental Drivers and Human Activities and Predictions for a Near Future

Invasion of new territories by insect vector species that can transmit pathogens is one of the most important threats for human health. The spread of the mosquito Aedes albopictus in Europe is emblematic, because of its major role in the emergence and transmission of arboviruses such as dengue or chikungunya. Here, we modeled the spread of this mosquito species in France through a statistical framework taking advantage of a long-term surveillance dataset going back to the first observation of Ae. albopictus in the Metropolitan area. After validating the model, we show that human activities are especially important for mosquito dispersion while land use is a major factor for mosquito establishment. More importantly, we show that Ae. albopictus invasion is accelerating through time in this area, resulting in a geographic range extending further and further year after year. We also show that sporadic “jump” of Ae. albopictus in a new location far from the colonized area did not succeed in starting a new invasion front so far. Finally, we discuss on a potential adaptation to cooler climate and the risk of invasion into Northern latitudes.     

Drought-induced mosquito outbreaks in wetlands

Mosquitoes are not only a nuisance, but also vector many important human and animal diseases. Here, in opposition with the dogma that increased precipitation predicts mosquito abundance, we hypothesize that mosquitoes should show population outbreaks after drought years. Specifically, we suggest that in wetlands that never dry (permanent), predators limit mosquito abundance, whereas in wetlands that dry yearly (temporary), competitors that are well adapted to predictable drying, limit mosquito abundance. However, in wetlands that dry only during drought years (semi‐permanent), mosquito predators and competitors are eliminated and must recolonize following a drought, and the abundance of wetland mosquitoes can skyrocket. We present supportive evidence for this hypothesis from surveys of natural wetlands and from a controlled mesocosm experiment. We conclude that this framework may provide a reliable way to predict and prepare for year‐to‐year variation in mosquito abundances at large spatial scales.     

Short Report: Adult Aedes abundance and risk of dengue transmission

Dengue is transmitted mainly by the adult female Aedes aegypti mosquito. However, little is known about the impact of adult Aedes abundance on the risk of dengue transmission. Here we analysed nationally representative dengue case and vector surveillance data collected from Singapore, to determine the effect of adult Aedes abundance on the risk of dengue transmission. A case was an area with active dengue transmission as indicated by the presence of dengue cluster. A control was an area where no dengue cluster was reported. Using multivariate logistic regression, we analysed 88 cases and 602 controls and estimated the odds of dengue cluster formation at various adult Aedes abundance levels, estimated by the mean number of adult female Aedes per Gravitrap per week and categorised into Low, Moderate, High and Very High abundance level. We found that the risk of dengue cluster formation was positively associated with adult Ae. aegypti abundance. We observed a three to four-fold increase in the odds of dengue clusters forming in areas with High (AOR: 3.40, 95% CI: 2.09, 5.52) and Very High (AOR: 3.99, 95% CI: 2.46, 6.46) adult Aedes aegypti abundance level compared to those with low Ae. aegypti abundance level. Our study strengthens the evidence for the use of adult Aedes indices for dengue risk assessment and early warning for dengue outbreaks. Entomological indicators of adult Ae. aegypti could be used to anticipate and prioritize areas for dengue control.     

Local and Global Effects of Climate on Dengue Transmission in Puerto Rico

The four dengue viruses, the agents of dengue fever and dengue hemorrhagic fever in humans, are transmitted predominantly by the mosquito Aedes aegypti. The abundance and the transmission potential of Ae. aegypti are influenced by temperature and precipitation. While there is strong biological evidence for these effects, empirical studies of the relationship between climate and dengue incidence in human populations are potentially confounded by seasonal covariation and spatial heterogeneity. Using 20 years of data and a statistical approach to control for seasonality, we show a positive and statistically significant association between monthly changes in temperature and precipitation and monthly changes in dengue transmission in Puerto Rico. We also found that the strength of this association varies spatially, that this variation is associated with differences in local climate, and that this relationship is consistent with laboratory studies of the impacts of these factors on vector survival and viral replication. These results suggest the importance of temperature and precipitation in the transmission of dengue viruses and suggest a reason for their spatial heterogeneity. Thus, while dengue transmission may have a general system, its manifestation on a local scale may differ from global expectations.     

Pandemic-associated mobility restrictions could cause increases in dengue virus transmission

BackgroundThe COVID-19 pandemic has induced unprecedented reductions in human mobility and social contacts throughout the world. Because dengue virus (DENV) transmission is strongly driven by human mobility, behavioral changes associated with the pandemic have been hypothesized to impact dengue incidence. By discouraging human contact, COVID-19 control measures have also disrupted dengue vector control interventions, the most effective of which require entry into homes. We sought to investigate how and why dengue incidence could differ under a lockdown scenario with a proportion of the population sheltered at home.Methodology & principal findingsWe used an agent-based model with a realistic treatment of human mobility and vector control. We found that a lockdown in which 70% of the population sheltered at home and which occurred in a season when a new serotype invaded could lead to a small average increase in cumulative DENV infections of up to 10%, depending on the time of year lockdown occurred. Lockdown had a more pronounced effect on the spatial distribution of DENV infections, with higher incidence under lockdown in regions with higher mosquito abundance. Transmission was also more focused in homes following lockdown. The proportion of people infected in their own home rose from 54% under normal conditions to 66% under lockdown, and the household secondary attack rate rose from 0.109 to 0.128, a 17% increase. When we considered that lockdown measures could disrupt regular, city-wide vector control campaigns, the increase in incidence was more pronounced than with lockdown alone, especially if lockdown occurred at the optimal time for vector control.Conclusions & significanceOur results indicate that an unintended outcome of lockdown measures may be to adversely alter the epidemiology of dengue. This observation has important implications for an improved understanding of dengue epidemiology and effective application of dengue vector control. When coordinating public health responses during a syndemic, it is important to monitor multiple infections and understand that an intervention against one disease may exacerbate another.     

Impact of Land-use Change on Dengue and Malaria in Northern Thailand

Land-use change, a major constituent of global environmental change, potentially has significant consequences for human health in relation to mosquito-borne diseases. Land-use change can influence mosquito habitat, and therefore the distribution and abundance of vectors, and land use mediates human–mosquito interactions, including biting rate. Based on a conceptual model linking the landscape, people, and mosquitoes, this interdisciplinary study focused on the impacts of changes in land use on dengue and malaria vectors and dengue transmission in northern Thailand. Extensive data on mosquito presence and abundance, land-use change, and infection risk determinants were collected over 3 years. The results of the different components of the study were then integrated through a set of equations linking land use to disease via mosquito abundance. The impacts of a number of plausible scenarios for future land-use changes in the region, and of concomitant behavioral change were assessed. Results indicated that land-use changes have a detectable impact on mosquito populations and on infection. This impact varies according to the local environment but can be counteracted by adoption of preventive measures.     

Mosquito Surveillance Revealed Lagged Effects of Mosquito Abundance on Mosquito-Borne Disease Transmission: A Retrospective Study in Zhejiang,China

Mosquito-borne diseases (MBDs) are still threats to public health in Zhejiang. In this study, the associations between the time-lagged mosquito capture data and MBDs incidence over five years were used to examine the potential effects of mosquito abundance on patterns of MBDs epidemiology in Zhejiang during 2008–2012. Light traps were used to collect adult mosquitoes at 11 cities. Correlation tests with and without time lag were performed to investigate the correlations between MBDs incidence rates and mosquito abundance by month. Selected MBDs consisted of Japanese encephalitis (JE), dengue fever (DF) and malaria. A Poisson regression analysis was performed by using a generalized estimating equations (GEE) approach, and the most parsimonious model was selected based on the quasi-likelihood based information criterion (QICu). We identified five mosquito species and the constituent ratio of Culex pipiens pallens, Culex tritaeniorhynchus, Aedes albopictus, Anopheles sinensis and Armigeres subalbatus was 66.73%, 21.47%, 6.72%, 2.83% and 2.25%, respectively. The correlation analysis without and with time lag showed that Culex mosquito abundance at a lag of 0 or 1 month was positively correlated with JE incidence during 2008–2012, Ae. albopictus abundance at a lag of 1 month was positively correlated with DF incidence in 2009, and An. sinensis abundance at a lag of 0–2 months was positively correlated with malaria incidence during 2008–2010. The Poisson regression analysis showed each 0.1 rise of monthly mosquito abundance corresponded to a positive increase of MBD cases for the period of 2008–2012. The rise of mosquito abundance with a lag of 0–2 months increased the risk of human MBDs infection in Zhejiang. Our study provides evidence that mosquito monitoring could be a useful early warning tool for the occurrence and transmission of MBDs.     

Heterogeneous Feeding Patterns of the Dengue Vector,Aedes aegypti,on Individual Human Hosts in Rural Thailand

Background

Mosquito biting frequency and how bites are distributed among different people can have significant epidemiologic effects. An improved understanding of mosquito vector-human interactions would refine knowledge of the entomological processes supporting pathogen transmission and could reveal targets for minimizing risk and breaking pathogen transmission cycles.

Methodology and principal findings

We used human DNA blood meal profiling of the dengue virus (DENV) vector, Aedes aegypti, to quantify its contact with human hosts and to infer epidemiologic implications of its blood feeding behavior. We determined the number of different people bitten, biting frequency by host age, size, mosquito age, and the number of times each person was bitten. Of 3,677 engorged mosquitoes collected and 1,186 complete DNA profiles, only 420 meals matched people from the study area, indicating that Ae. aegypti feed on people moving transiently through communities to conduct daily business. 10–13% of engorged mosquitoes fed on more than one person. No biting rate differences were detected between high- and low-dengue transmission seasons. We estimate that 43–46% of engorged mosquitoes bit more than one person within each gonotrophic cycle. Most multiple meals were from residents of the mosquito collection house or neighbors. People ≤25 years old were bitten less often than older people. Some hosts were fed on frequently, with three hosts bitten nine times. Interaction networks for mosquitoes and humans revealed biologically significant blood feeding hotspots, including community marketplaces.

Conclusion and significance

High multiple-feeding rates and feeding on community visitors are likely important features in the efficient transmission and rapid spread of DENV. These results help explain why reducing vector populations alone is difficult for dengue prevention and support the argument for additional studies of mosquito feeding behavior, which when integrated with a greater understanding of human behavior will refine estimates of risk and strategies for dengue control.     

Modelling the Use of Wolbachia to Control Dengue Fever Transmission

Experiments and field trials have shown that the intracellular bacterium Wolbachia may be introduced into populations of the mosquito Aedes aegypti, the primary vector for dengue fever. In the absence of Wolbachia, a mosquito acquiring the dengue virus from an infected human enters an exposed (infected but not infectious) period before becoming infectious itself. A Wolbachia-infected mosquito that acquires dengue (i) may have a reduced lifespan, so that it is less likely to survive the exposed period and become infectious, and (ii) may have a reduced ability to transmit dengue, even if it has survived the exposed period. Wolbachia introduction has therefore been suggested as a potential dengue control measure. We set up a mathematical model for the system to investigate this suggestion and to evaluate the desirable properties of the Wolbachia strain to be introduced. We show that Wolbachia has excellent potential for dengue control in areas where R ₀ is not too large. However, if R ₀ is large, Wolbachia strains that reduce but do not eliminate dengue transmission have little effect on endemic steady states or epidemic sizes. Unless control measures to reduce R ₀ by reducing mosquito populations are also put in place, it may be worth the extra effort in such cases to introduce Wolbachia strains that eliminate dengue transmission completely.     

Exploring the utility of social-ecological and entomological risk factors for dengue infection as surveillance indicators in the dengue hyper-endemic city of Machala,Ecuador

The management of mosquito-borne diseases is a challenge in southern coastal Ecuador, where dengue is hyper-endemic and co-circulates with other arboviral diseases. Prior work in the region has explored social-ecological factors, dengue case data, and entomological indices. In this study, we bring together entomological and epidemiological data to describe links between social-ecological factors associated with risk of dengue transmission at the household level in Machala, Ecuador. Households surveys were conducted from 2014–2017 to assess the presence of adult Aedes aegypti (collected via aspiration) and to enumerate housing conditions, demographics, and mosquito prevention behaviors. Household-level dengue infection status was determined by laboratory diagnostics in 2014–2015. Bivariate analyses and multivariate logistic regression models were used to identify social-ecological variables associated with household presence of female Ae. aegypti and household dengue infection status, respectively. Aedes aegypti presence was associated with interruptions in water service and weekly trash collection, and household air conditioning was protective against mosquito presence. Presence of female Ae. aegypti was not associated with household dengue infections. We identified shaded patios and head of household employment status as risk factors for household-level dengue infection, while window screening in good condition was identified as protective against dengue infection. These findings add to our understanding of the systems of mosquito-borne disease transmission in Machala, and in the larger region of southern Ecuador, aiding in the development of improved vector surveillance efforts, and targeted interventions.     

Determinants of Heterogeneous Blood Feeding Patterns by Aedes aegypti in Iquitos,Peru

Background

Heterogeneous mosquito biting results in different individuals in a population receiving an uneven number of bites. This is a feature of many vector-borne disease systems that, if understood, could guide preventative control efforts toward individuals who are expected to contribute most to pathogen transmission. We aimed to characterize factors determining biting patterns of Aedes aegypti, the principal mosquito vector of dengue virus.

Methodology/Principal Findings

Engorged female Ae. aegypti and human cheek swabs were collected from 19 houses in Iquitos, Peru. We recorded the body size, age, and sex of 275 consenting residents. Movement in and out of the house over a week (time in house) and mosquito abundance were recorded on eight separate occasions in each household over twelve months. We identified the individuals bitten by 96 engorged mosquitoes over this period by amplifying specific human microsatellite markers in mosquito blood meals and human cheek swabs. Using a multinomial model assuming a saturating relationship (power), we found that, relative to other residents of a home, an individual''s likelihood of being bitten in the home was directly proportional to time spent in their home and body surface area (p<0.05). A linear function fit the relationship equally well (ΔAIC<1).

Conclusions/Significance

Our results indicate that larger people and those who spend more time at home are more likely to receive Ae. aegypti bites in their homes than other household residents. These findings are consistent with the idea that measurable characteristics of individuals can inform predictions of the extent to which different people will be bitten. This has implications for an improved understanding of heterogeneity in different people''s contributions to pathogen transmission, and enhanced interventions that include the people and places that contribute most to pathogen amplification and spread.     

Meteorologically Driven Simulations of Dengue Epidemics in San Juan,PR

Meteorological factors influence dengue virus ecology by modulating vector mosquito population dynamics, viral replication, and transmission. Dynamic modeling techniques can be used to examine how interactions among meteorological variables, vectors and the dengue virus influence transmission. We developed a dengue fever simulation model by coupling a dynamic simulation model for Aedes aegypti, the primary mosquito vector for dengue, with a basic epidemiological Susceptible-Exposed-Infectious-Recovered (SEIR) model. Employing a Monte Carlo approach, we simulated dengue transmission during the period of 2010–2013 in San Juan, PR, where dengue fever is endemic. The results of 9600 simulations using varied model parameters were evaluated by statistical comparison (r²) with surveillance data of dengue cases reported to the Centers for Disease Control and Prevention. To identify the most influential parameters associated with dengue virus transmission for each period the top 1% of best-fit model simulations were retained and compared. Using the top simulations, dengue cases were simulated well for 2010 (r² = 0.90, p = 0.03), 2011 (r² = 0.83, p = 0.05), and 2012 (r² = 0.94, p = 0.01); however, simulations were weaker for 2013 (r² = 0.25, p = 0.25) and the entire four-year period (r² = 0.44, p = 0.002). Analysis of parameter values from retained simulations revealed that rain dependent container habitats were more prevalent in best-fitting simulations during the wetter 2010 and 2011 years, while human managed (i.e. manually filled) container habitats were more prevalent in best-fitting simulations during the drier 2012 and 2013 years. The simulations further indicate that rainfall strongly modulates the timing of dengue (e.g., epidemics occurred earlier during rainy years) while temperature modulates the annual number of dengue fever cases. Our results suggest that meteorological factors have a time-variable influence on dengue transmission relative to other important environmental and human factors.     

Developing arbovirus resistance in mosquitoes

Diseases caused by arthropod-borne viruses are increasingly significant public health problems, and novel methods are needed to control pathogen transmission. The hypothesis underlying the research described here is that genetic manipulation of Aedes aegypti mosquitoes can profoundly and permanently reduce their competence to transmit dengue viruses to human hosts. Recent key findings now allow us to test the genetic control hypothesis. We have identified viral genome-derived RNA segments that can be expressed in mosquito midguts and salivary glands to ablate homologous virus replication and transmission. We have demonstrated that both transient and heritable expression of virus-derived effector RNAs in cultured mosquito cells can silence virus replication, and have characterized the mechanism of RNA-mediated resistance. We are now developing virus-resistant mosquito lines by transformation with transposable elements that express effector RNAs from mosquito-active promoters.