Evaluation of the sticky MosquiTRAP for detecting Aedes (Stegomyia) aegypti (L.) (Diptera: Culicidae) during the dry season in Belo Horizonte, Minas Gerais, Brazil

MosquiTRAP is a sticky trap specifically designed to capture gravid females of Aedes aegypti (L.) and allows the identification of the mosquito in the field during the inspection of the trap. This study aims to compare this sticky trap to larval and ovitrap surveys for field monitoring of A. aegypti during the dry season. The study was conducted from March to June of 2003 in 20 blocks of the district of Itapo?, Belo Horizonte, MG. The traps were monitored every week while the larval survey was conducted on a monthly basis. The larval index: Premise Index (PI) and Breteau Index (BI) had equal values throughout the experiment (1.72 in the first two months and zero in the last two). The container index (CI) during the first two months was 0.09 and 0.1%, respectively and zero in the last two. The Ovitrap Positive Index (OPI) ranged from 16.7 to 76.9%, and the MosquiTRAP Positive Index (MPI) ranged from 0 to 31.5%. The Egg Density Index (EDI) ranged from 26.6 to 82.8, while the Adult Density Index ranged from 0 to 1.6 throughout the experiment. Temperature and rainfall did not affect the Positive and Density Indices, although these environmental variables seemed to have affected the larvae indices. Although the MosquiTRAP caught a low number of Aedes mosquitoes during the study, it was more sensitive than the larval survey to detect the presence of Aedes mosquitoes.     

Risk of dengue occurrence based on the capture of gravid Aedes aegypti females using MosquiTRAP

We assessed the risk classification of dengue fever based on the capture of Aedes aegypti adults using MosquiTRAP, a type of sticky trap, in comparison with traditional larval infestation indices. A total of 27 MosquiTRAPs were installed, with one trap per block, and were inspected weekly between November 2008-February 2009. Infestation baseline data were obtained from a survey conducted prior to trap installation. The index generated by MosquiTRAP and house index (HI) classified the area "in alert situation". The set for risk of dengue occurrence proposed by the use of MosquiTRAP classify areas in the same way of the traditional HI.     

Field optimisation of MosquiTRAP sampling for monitoring Aedes aegypti Linnaeus (Diptera: Culicidae)

A sticky trap designed to capture gravid Aedes (Stegomyia) aegypti mosquitoes, MosquiTRAP, has been evaluated for monitoring this species in Brazil. However, the effects of trap densities on the capture rate of Ae. aegypti females and the sensitivity of vector detection are still unknown. After a preliminary study has identified areas of high and low female mosquito abundance, a set of experiments was conducted in four neighbourhoods of Belo Horizonte (state of Minas Gerais, Brazil) using densities of 1, 2, 4, 8, 16, 32 and 64 traps per block. Trap sensitivity (positive MosquiTRAP index) increased significantly when 1-8 MosquiTRAPs were installed per block in both high and low abundance areas. A strong fit was obtained for the total number of mosquitoes captured with increasing trap densities through a non-linear function (Box-Lucas) (r2 = 0,994), which likely exhibits saturation towards an equilibrium level. The capacity of the Mean Female Aedes Index to distinguish between areas of high and low Ae. aegypti abundance was also investigated; the achieved differentiation was shown to be dependent on the MosquiTRAP density.     

A comparison of larval,ovitrap and MosquiTRAP?surveillance for Aedes (Stegomyia) aegypti

In Brazil, the entomological surveillance of Aedes (Stegomyia) aegypti is performed by government-mandated larval surveys. In this study, the sensitivities of an adult sticky trap and traditional surveillance methodologies were compared. The study was performed over a 12-week period in a residential neighbourhood of the municipality of Pedro Leopoldo, state of Minas Gerais, Brazil. An ovitrap and a MosquiTRAP were placed at opposite ends of each neighbourhood block (60 traps in total) and inspections were performed weekly. The study revealed significant correlations of moderate strength between the larval survey, ovitrap and MosquiTRAP measurements. A positive relationship was observed between temperature, adult capture measurements and egg collections, whereas precipitation and frequency of rainy days exhibited a negative relationship.     

Ovitrap surveillance of dengue vector mosquitoes in Bandung City,West Java Province,Indonesia

Larval surveillance is the central approach for monitoring dengue vector populations in Indonesia. However, traditional larval indices are ineffective for measuring mosquito population dynamics and predicting the dengue transmission risk. We conducted a 14-month ovitrap surveillance. Eggs and immature mosquitoes were collected on a weekly basis from an urban village of Bandung, namely Sekejati. Ovitrap-related indices, namely positive house index (PHI), ovitrap index (OI), and ovitrap density index (ODI), were generated and correlated with environmental variables, housing type (terraced or high-density housing), ovitrap placement location (indoor or outdoor; household or public place), and local dengue cases. Our results demonstrated that Aedes aegypti was significantly predominant compared with Aedes albopictus at each housing type and ovitrap placement location. Ovitrap placement locations and rainfall were the major factors contributing to variations in PHI, OI, and ODI, whereas the influences of housing type and temperature were subtle. Indoor site values were significantly positively correlated to outdoor sites’ values for both OI and ODI. OI and ODI values from households were best predicted with those from public places at 1- and 0-week lags, respectively. Weekly rainfall values at 4- and 3-week lags were the best predictors of OI and ODI for households and public places, respectively. Monthly mean PHI, OI, and ODI were significantly associated with local dengue cases. In conclusion, ovitrap may be an effective tool for monitoring the population dynamics of Aedes mosquitoes, predicting dengue outbreaks, and serving as an early indicator to initiate environmental clean-up. Ovitrap surveillance is easy for surveyors if they are tasked with a certain number of ovitraps at a designated area, unlike the existing larval surveillance methodology, which entails identifying potential breeding sites largely at the surveyors’ discretion. Ovitrap surveillance may reduce the influence of individual effort in larval surveillance that likely causes inconsistency in results.     

Population density, water supply, and the risk of dengue fever in Vietnam: cohort study and spatial analysis

Background

Aedes aegypti, the major vector of dengue viruses, often breeds in water storage containers used by households without tap water supply, and occurs in high numbers even in dense urban areas. We analysed the interaction between human population density and lack of tap water as a cause of dengue fever outbreaks with the aim of identifying geographic areas at highest risk.

Methods and Findings

We conducted an individual-level cohort study in a population of 75,000 geo-referenced households in Vietnam over the course of two epidemics, on the basis of dengue hospital admissions (n = 3,013). We applied space-time scan statistics and mathematical models to confirm the findings. We identified a surprisingly narrow range of critical human population densities between around 3,000 to 7,000 people/km² prone to dengue outbreaks. In the study area, this population density was typical of villages and some peri-urban areas. Scan statistics showed that areas with a high population density or adequate water supply did not experience severe outbreaks. The risk of dengue was higher in rural than in urban areas, largely explained by lack of piped water supply, and in human population densities more often falling within the critical range. Mathematical modeling suggests that simple assumptions regarding area-level vector/host ratios may explain the occurrence of outbreaks.

Conclusions

Rural areas may contribute at least as much to the dissemination of dengue fever as cities. Improving water supply and vector control in areas with a human population density critical for dengue transmission could increase the efficiency of control efforts. Please see later in the article for the Editors'' Summary     

Dengue infection and miscarriage: a prospective case control study

Background

Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known.

Method

We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation) to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1) antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy) plus 45 controls (39 lost to follow up and six subsequent late miscarriages) were excluded from analysis.

Findings

Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection) was positive in 6/115 (5·2%) cases and 5/296 (1·7%) controls RR 3·1 (95% CI 1·0–10) P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2–14 P = 0·023).

Interpretation

Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.     

Novel, meso-substituted cationic porphyrin molecule for photo-mediated larval control of the dengue vector Aedes aegypti

Background

Control of the mosquito vector population is the most effective strategy currently available for the prevention of dengue fever and the containment of outbreaks. Photo-activated oxidants may represent promising tools for developing effective, safe and ecofriendly novel larvicides. The purpose of this study was to evaluate the potential of the synthetic meso-substituted porphyrin meso-tri(N-methylpyridyl), meso-mono(N-tetradecylpyridyl)porphine (C14) as a photoactivatable larvicide against the dengue vector Aedes (Stegomyia) aegypti.

Methodology

The photophysical and photochemical properties of the C14 molecule were assessed spectrophotometrically. Photomediated larvicidal efficacy, route of intake and site of action were determined on Ae. aegypti larvae by laboratory bioassays and fluorescence microscopy. Using powdered food pellet for laboratory rodents (a common larval food used in the laboratory) as a carrier for C14, loading-release dynamics, larvicidal efficacy and residual activity of the C14-carrier complex were investigated.

Main Findings

The C14 molecule was found to exert a potent photosensitizing activity on Ae. aegypti larvae. At irradiation intervals of 12 h and 1 h, at a light intensity of 4.0 mW/cm², which is 50–100 times lower than that of natural sunlight, LC₅₀ values of 0.1 µM (0.15 mg/l) and 0.5 µM (0.77 mg/l) were obtained, respectively. The molecule was active after ingestion by the larvae and caused irreversible, lethal damage to the midgut and caecal epithelia. The amphiphilic nature of C14 allowed a formulate to be produced that not only was as active against the larvae as C14 in solution, but also possessed a residual activity of at least two weeks, in laboratory conditions.

Conclusions

The meso-substituted synthetic porphyrin C14, thanks to its photo-sensitizing properties represents an attractive candidate for the development of novel photolarvicides for dengue vector control.     

Development and laboratory evaluation of chemically‐based baited ovitrap for the monitoring of Aedes aegypti

Aedes (Stegomyia) aegypti is considered to be the most important dengue vector worldwide. Studies were conducted to design and evaluate a chemically‐based baited ovitrap for monitoring Ae. aegypti under laboratory conditions. Several known chemical attractants and three types of ovitraps (ovitraps A, B, and C) were evaluated throughout the oviposition bioassays. Oviposition responses of gravid female Ae. aegypti were evaluated to n‐heneicosane, 3‐methylindole (skatole), 4‐methylphenol (p‐cresol), and phenol. Female Ae. aegypti were attracted to all the evaluated compounds. Among them, n‐heneicosane at a concentration of 10 ppm (mg/l), skatole from 50 to 1000 ppm, p‐cresol at 100 ppm, and phenol at 50 ppm showed a significant positive oviposition response. A blend of the four chemical attractants increased the oviposition response; 67% of the eggs were deposited in the treatment compared to the control. Female Ae. aegypti were signi?cantly more attracted to ovitrap A loaded with the four‐component synthetic blend compared to the standard ovitrap in the oviposition bioassays. The compound used in ovitrap A retained its attractant property for up to three days. The chemically‐based baited ovitrap may be considered as an option to be integrated during the monitoring of dengue virus vectors in México.     

Mass trapping with MosquiTRAPs does not reduce Aedes aegypti abundance

The objective of this study was to evaluate the effectiveness of Aedes aegypti mass trapping using the sticky trap MosquiTRAP (MQT) by performing a cluster randomised controlled trial in Manaus, state of Amazonas, Brazil. After an initial questionnaire and baseline monitoring of adult Ae. aegypti abundance with BG-Sentinel (BGS) traps in six clusters, three clusters were randomly assigned to the intervention arm where each participating household received three MQTs for mass trapping during 17 months. The remaining three clusters (control arm) did not receive traps. The effect of mass trapping on adult Ae. aegypti abundance was monitored fortnightly with BGS traps. During the last two months of the study, a serological survey was conducted. After the study, a second questionnaire was applied in the intervention arm. Entomological monitoring indicated that MQT mass trapping did not reduce adult Ae. aegypti abundance. The serological survey indicated that recent dengue infections were equally frequent in the intervention and the control arm. Most participants responded positively to questions concerning user satisfaction. According to the results, there is no evidence that mass trapping with MQTs can be used as a part of dengue control programs. The use of this sticky trap is only recommendable for dengue vector monitoring.     

Spatial and temporal clustering of dengue virus transmission in Thai villages

Background

Transmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted.

Methods and Findings

Cluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1–19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children.

Conclusions

Our data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention strategies. Cluster methodology could serve as a useful research tool for investigation of other temporally and spatially clustered infectious diseases.     

Scanning electron microscopy of the four larval instars of the Dengue fever vector Aedes aegypti (Diptera: Culicidae)

Aedes aegypti is the main insect vector of Dengue fever and dengue hemorrhagic fever/dengue shock syndrome and represents the only vulnerable element in the control of this disease. Therefore, the identification and quantification of this mosquito is an important task; however, the majority of taxonomic keys are based on the 4th larval instar. For that reason, this study describes the four larval instars ofA. aegypti using scanning electron microscopy. Morphological changes during larval development were observed at the pecten, comb scales and the ventral brush of the abdominal segment X; however, the 3rd and 4th instars showed similar structures with only a slight variation. The structures described in this study will be helpful in the identification of the four instars of A. aegypti, a fundamental task for comprehending the natural history of dengue mainly in new territories affected.     

Determining the spatial autocorrelation of dengue vector populations: influences of mosquito sampling method,covariables, and vector control

We investigated spatial autocorrelation of female Aedes aegypti L. mosquito abundance from BG‐Sentinel trap and sticky ovitrap collections in Cairns, north Queensland, Australia. BG‐Sentinel trap collections in 2010 show a significant spatial autocorrelation across the study site and over a smaller spatial extent, while sticky ovitrap collections only indicate a non‐significant, weak spatial autocorrelation. The BG‐Sentinel trap collections were suitable for spatial interpolation using ordinary kriging and cokriging techniques. The uses of Premise Condition Index and potential breeding container data have helped improve our prediction of vector abundance. Semiovariograms and prediction maps indicate that the spatial autocorrelation of mosquito abundance determined by BG‐Sentinel traps extends farther compared to sticky ovitrap collections. Based on our data, fewer BG‐Sentinel traps are required to represent vector abundance at a series of houses compared to sticky ovitraps. A lack of spatial structure was observed following vector control treatment in the area. This finding has implications for the design and costs of dengue vector surveillance programs.     

Surveillance of Aedes aegypti: Comparison of House Index with Four Alternative Traps

Introduction

The mosquito Aedes aegypti, vector of dengue, chikungunya and yellow fever viruses, is an important target of vector control programs in tropical countries. Most mosquito surveillance programs are still based on the traditional household larval surveys, despite the availability of new trapping devices. We report the results of a multicentric entomological survey using four types of traps, besides the larval survey, to compare the entomological indices generated by these different surveillance tools in terms of their sensitivity to detect mosquito density variation.

Methods

The study was conducted in five mid-sized cities, representing variations of tropical climate regimens. Surveillance schemes using traps for adults (BG-Sentinel, Adultrap and MosquiTRAP) or eggs (ovitraps) were applied monthly to three 1 km² areas per city. Simultaneously, larval surveys were performed. Trap positivity and density indices in each area were calculated and regressed against meteorological variables to characterize the seasonal pattern of mosquito infestation in all cities, as measured by each of the four traps.

Results

The House Index was consistently low in most cities, with median always 0. Traps rarely produced null indices, pointing to their greater sensitivity in detecting the presence of Ae. aegypti in comparison to the larval survey. Trap positivity indices tend to plateau at high mosquito densities. Despite this, both indices, positivity and density, agreed on the seasonality of mosquito abundance in all cities. Mosquito seasonality associated preferentially with temperature than with precipitation even in areas where temperature variation is small.

Conclusions

All investigated traps performed better than the House Index in measuring the seasonal variation in mosquito abundance and should be considered as complements or alternatives to larval surveys. Choice between traps should further consider differences of cost and ease-of-use.     

Use of saliva for early dengue diagnosis

Background

The necessity of a venous blood collection in all dengue diagnostic assays and the high cost of tests that are available for testing during the viraemic period hinder early detection of dengue cases and thus could delay cluster management. This study reports the utility of saliva in an assay that detects dengue virus (DENV)–specific immunoglobulin A (Ig A) early in the phase of a dengue infection.

Methods and Findings

Using an antigen capture anti-DENV IgA (ACA) ELISA technique, we tested saliva samples collected from dengue-confirmed patients. The sensitivity within 3 days from fever onset was over 36% in primary dengue infections. The performance is markedly better in secondary infections, with 100% sensitivity reported in saliva samples from day 1 after fever onset. Serum and salivary IgA levels showed good correlation (Pearson''s r = 0.69, p<0.001). Specificity was found to be 97%.

Conclusion

Our findings suggest that this technique would be very useful in dengue endemic regions, where the majority of dengue cases are secondary. The ACA-ELISA is easy to perform, cost effective, and especially useful in laboratories without sophisticated equipment. Our findings established the usefulness and reliability of saliva for early dengue diagnosis.     

An Explosive Epidemic of DENV-3 in Cairns,Australia

From November 2008-May 2009 Cairns Queensland Australia was struck by an explosive epidemic of DENV-3 that exceeded the capacity of highly skilled dengue control team to control it. We describe the environmental, virological and entomological factors associated with this outbreak to better understand the circumstances leading to its occurrence. Patient interviews, serological results and viral sequencing strongly suggest that the imported index case was infected in Kalimantan, Indonesia. A delay in notification of 27 days from importation of the index case until Queensland Health was notified of dengue transmission allowed the virus to amplify and spread unchecked through November 2008. Unseasonably warm weather, with daily mean temperatures exceeding 30°C, occurred in late November and would have shortened the extrinsic incubation period of the virus and enhanced transmission. Analysis of case movements early in the outbreak indicated that the total incubation period was as low as 9–11 days. This was supported by laboratory vector competence studies that found transmission by Aedes aegypti occurred within 5 days post exposure at 28°C. Effective vector competence rates calculated from these transmission studies indicate that early transmission contributed to the explosive dengue transmission observed in this outbreak. Collections from BG sentinel traps and double sticky ovitraps showed that large populations of the vector Ae. aegypti occurred in the transmission areas from November – December 2008. Finally, the seasonal movement of people around the Christmas holiday season enhanced the spread of DENV-3. These results suggest that a strain of DENV-3 with an unusually rapid transmission cycle was able to outpace vector control efforts, especially those reliant upon delayed action control such as lethal ovitraps.     

Quantifying the spatial dimension of dengue virus epidemic spread within a tropical urban environment

Background

Dengue infection spread in naive populations occurs in an explosive and widespread fashion primarily due to the absence of population herd immunity, the population dynamics and dispersal of Ae. aegypti, and the movement of individuals within the urban space. Knowledge on the relative contribution of such factors to the spatial dimension of dengue virus spread has been limited. In the present study we analyzed the spatio-temporal pattern of a large dengue virus-2 (DENV-2) outbreak that affected the Australian city of Cairns (north Queensland) in 2003, quantified the relationship between dengue transmission and distance to the epidemic''s index case (IC), evaluated the effects of indoor residual spraying (IRS) on the odds of dengue infection, and generated recommendations for city-wide dengue surveillance and control.

Methods and Findings

We retrospectively analyzed data from 383 DENV-2 confirmed cases and 1,163 IRS applications performed during the 25-week epidemic period. Spatial (local k-function, angular wavelets) and space-time (Knox test) analyses quantified the intensity and directionality of clustering of dengue cases, whereas a semi-parametric Bayesian space-time regression assessed the impact of IRS and spatial autocorrelation in the odds of weekly dengue infection. About 63% of the cases clustered up to 800 m around the IC''s house. Most cases were distributed in the NW-SE axis as a consequence of the spatial arrangement of blocks within the city and, possibly, the prevailing winds. Space-time analysis showed that DENV-2 infection spread rapidly, generating 18 clusters (comprising 65% of all cases), and that these clusters varied in extent as a function of their distance to the IC''s residence. IRS applications had a significant protective effect in the further occurrence of dengue cases, but only when they reached coverage of 60% or more of the neighboring premises of a house.

Conclusion

By applying sound statistical analysis to a very detailed dataset from one of the largest outbreaks that affected the city of Cairns in recent times, we not only described the spread of dengue virus with high detail but also quantified the spatio-temporal dimension of dengue virus transmission within this complex urban environment. In areas susceptible to non-periodic dengue epidemics, effective disease prevention and control would depend on the prompt response to introduced cases. We foresee that some of the results and recommendations derived from our study may also be applicable to other areas currently affected or potentially subject to dengue epidemics.     

Climate-based models for understanding and forecasting dengue epidemics

Background

Dengue dynamics are driven by complex interactions between human-hosts, mosquito-vectors and viruses that are influenced by environmental and climatic factors. The objectives of this study were to analyze and model the relationships between climate, Aedes aegypti vectors and dengue outbreaks in Noumea (New Caledonia), and to provide an early warning system.

Methodology/Principal Findings

Epidemiological and meteorological data were analyzed from 1971 to 2010 in Noumea. Entomological surveillance indices were available from March 2000 to December 2009. During epidemic years, the distribution of dengue cases was highly seasonal. The epidemic peak (March–April) lagged the warmest temperature by 1–2 months and was in phase with maximum precipitations, relative humidity and entomological indices. Significant inter-annual correlations were observed between the risk of outbreak and summertime temperature, precipitations or relative humidity but not ENSO. Climate-based multivariate non-linear models were developed to estimate the yearly risk of dengue outbreak in Noumea. The best explicative meteorological variables were the number of days with maximal temperature exceeding 32°C during January–February–March and the number of days with maximal relative humidity exceeding 95% during January. The best predictive variables were the maximal temperature in December and maximal relative humidity during October–November–December of the previous year. For a probability of dengue outbreak above 65% in leave-one-out cross validation, the explicative model predicted 94% of the epidemic years and 79% of the non epidemic years, and the predictive model 79% and 65%, respectively.

Conclusions/Significance

The epidemic dynamics of dengue in Noumea were essentially driven by climate during the last forty years. Specific conditions based on maximal temperature and relative humidity thresholds were determinant in outbreaks occurrence. Their persistence was also crucial. An operational model that will enable health authorities to anticipate the outbreak risk was successfully developed. Similar models may be developed to improve dengue management in other countries.     

Both viremia and cytokine levels associate with the lack of severe disease in secondary dengue 1 infection among adult Chinese patients

Secondary dengue infections are frequently associated with increased risk for dengue hemorrhagic fever and dengue shock syndrome. Surprisingly, we observed no dengue hemorrhagic fever cases among 353 hospitalized dengue-infected patients including 212 with primary, and 141 with secondary dengue 1 infection in China. To explore virological and immunological mechanisms which may account for this unexpected clinical observation, we assessed dengue viremia, type I interferon and inflammatory cytokine levels in these patients. While the levels of viremia and inflammatory cytokines are indistinguishable between primary and secondary infections, IFNα levels are significantly higher in primary than that in secondary infection. However, IFNα levels are positively correlated with dengue viremia levels (p<0.0001), but negatively correlated with the platelet counts (p<0.0001) and serum ALT levels (p = 0.0003). These results provide direct in vivo evidence that clinical dengue disease severity is affected by both viral and human immune factors.     

Socio-economic and Climate Factors Associated with Dengue Fever Spatial Heterogeneity: A Worked Example in New Caledonia

Background/Objectives

Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon.

Methods

We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections.

Results

The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people''s way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double.

Conclusion

In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries.