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Background: Identification of the source of mosquito blood meals is an important component for disease control and surveillance. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling has emerged as an effective tool for mosquito blood meal identification, using the abdomens of freshly engorged mosquitoes. In the field, mosquito abdomens are crushed on Whatman filter papers to determine the host feeding patterns by identifying the origin of their blood meals. The aim of this study was to test whether crushing engorged mosquito abdomens on Whatman filter papers was compatible with MALDI-TOF MS for mosquito blood meal identification. Both laboratory reared and field collected mosquitoes were tested. Material and methods: Sixty Anopheles gambiae Giles were experimentally engorged on the blood of six distinct vertebrate hosts (human, sheep, rabbit, dog, chicken and rat). The engorged mosquito abdomens were crushed on Whatman filter papers for MALDI-TOF MS analysis. 150 Whatman filter papers, with mosquitoes engorged on cow and goat blood, were preserved. A total of 77 engorged mosquito abdomens collected in the Comoros Islands and crushed on Whatman filter papers were tested with MALDI-TOF MS. Results: The MS profiles generated from mosquito engorged abdomens crushed on Whatman filter papers exhibited high reproducibility according to the original host blood. The blood meal host was correctly identified from mosquito abdomens crushed on Whatman filter papers by MALDI-TOF MS. The MS spectra obtained after storage were stable regardless of the room temperature and whether or not they were frozen. The MS profiles were reproducible for up to three months. For the Comoros samples, 70/77 quality MS spectra were obtained and matched with human blood spectra. This was confirmed by molecular tools. Conclusion: The results demonstrated that MALDI-TOF MS could identify mosquito blood meals from Whatman filter papers collected in the field during entomological surveys. The application of MALDI-TOF MS has proved to be rapid and successful, making it a new and efficient tool for mosquito-borne disease surveillance. [ABSTRACT FROM AUTHOR]

Proximal remote sensing is being used across a very wide range of research fields and by scientists, who are often without deep theoretical knowledge optical physics; the author of this article falls squarely in that category! This article highlights two optical phenomena, which may greatly influence the quality and robustness of proximal remote sensing: penetration and scattering. Penetration implies that acquired reflectance signals are associated with both physical and chemical properties of target objects from both the surface and internal tissues/structures. Scattering implies that reflectance signals acquired from one point or object are influenced by scattered radiometric energy from neighboring points or objects. Based on a series of laboratory experiments, penetration and scattering were discussed in the context of “robustness” (repeatability) of hyperspectral reflectance data. High robustness implies that it is possible to control imaging conditions and therefore: 1) obtain very similar radiometric signals from inert objects (objects that do not change) over time, and 2) be able to consistently distinguish objects that are otherwise highly similar in appearance (size, shape, and color) and in terms of biochemical composition. It was demonstrated that robustness of hyperspectral reflectance data (40 spectral bands from 385 to 1024 nm) were significantly influenced by penetration and scattering of radiometric energy. In addition, it was demonstrated that the influence of penetration and scattering varied across the examined spectrum. Characterization of how optical phenomena may affect the robustness of reflectance data is important when using proximal remote sensing technologies as tools used to classify engineering and biological objects. [ABSTRACT FROM AUTHOR]

Background: Until recently, the Chagas disease vector, Triatoma infestans, was widespread in Arequipa, Perú, but as a result of a decades-long campaign in which over 70,000 houses were treated with insecticides, infestation prevalence is now greatly reduced. To monitor for T. infestans resurgence, the city is currently in a surveillance phase in which a sample of houses is selected for inspection each year. Despite extensive data from the control campaign that could be used to inform surveillance, the selection of houses to inspect is often carried out haphazardly or by convenience. Therefore, we asked, how can we enhance efforts toward preventing T. infestans resurgence by creating the opportunity for vector surveillance to be informed by data? Methodology/principal findings: To this end, we developed a mobile app that provides vector infestation risk maps generated with data from the control campaign run in a predictive model. The app is intended to enhance vector surveillance activities by giving inspectors the opportunity to incorporate the infestation risk information into their surveillance activities, but it does not dictate which houses to surveil. Therefore, a critical question becomes, will inspectors use the risk information? To answer this question, we ran a pilot study in which we compared surveillance using the app to the current practice (paper maps). We hypothesized that inspectors would use the risk information provided by the app, as measured by the frequency of higher risk houses visited, and qualitative analyses of inspector movement patterns in the field. We also compared the efficiency of both mediums to identify factors that might discourage risk information use. Over the course of ten days (five with each medium), 1,081 houses were visited using the paper maps, of which 366 (34%) were inspected, while 1,038 houses were visited using the app, with 401 (39%) inspected. Five out of eight inspectors (62.5%) visited more higher risk houses when using the app (Fisher’s exact test, p < 0.001). Among all inspectors, there was an upward shift in proportional visits to higher risk houses when using the app (Mantel-Haenszel test, common odds ratio (OR) = 2.42, 95% CI 2.00–2.92), and in a second analysis using generalized linear mixed models, app use increased the odds of visiting a higher risk house 2.73-fold (95% CI 2.24–3.32), suggesting that the risk information provided by the app was used by most inspectors. Qualitative analyses of inspector movement revealed indications of risk information use in seven out of eight (87.5%) inspectors. There was no difference between the app and paper maps in the number of houses visited (paired t-test, p = 0.67) or inspected (p = 0.17), suggesting that app use did not reduce surveillance efficiency. Conclusions/significance: Without staying vigilant to remaining and re-emerging vector foci following a vector control campaign, disease transmission eventually returns and progress achieved is reversed. Our results suggest that, when provided the opportunity, most inspectors will use risk information to direct their surveillance activities, at least over the short term. The study is an initial, but key, step toward evidence-based vector surveillance. [ABSTRACT FROM AUTHOR]

Background: Phlebotomine sand flies are vectors of human leishmaniases, important neglected tropical diseases. In this study, we investigated diel patterns of oviposition behavior, effects of visual cues on oviposition-site selection, and whether these affect the attraction of gravid Phlebotomus papatasi (Scopoli), the vector of old-world cutaneous leishmaniasis, to olfactory cues from oviposition sites. Methodology/principal findings: To evaluate these questions, we conducted a series of experiments using attraction and oviposition assays within free-flight test chambers containing gravid females entrained under a 14:10 hrs light:dark photoperiod. By replacing sticky-screens or moist filter papers every three hours, we showed that oviposition site search occurs mainly in the latest part of the night whereas peak oviposition occurs during the early part of the night. Behavioral responses to olfactory oviposition cues are regulated by time-of-day and can be disrupted by transient exposure to a constant darkness photoperiod. Gravid females, but not any other stage, age, or sex, were attracted to dark, round oviposition jars, possibly resembling rodent burrow openings. This visual attraction disappeared in the absence of an illumination source. Egg deposition rate was not affected by jar color. Olfactory cues had the strongest effect when the visual cues were minimal. Conclusion and significance: Our study showed, for the first time, that visual cues in the form of oviposition-site color, lighting level, and photoperiod are important in guiding the oviposition behavior of phlebotomine sand flies. Furthermore, such visual cues could modify the flies’ sensitivity to olfactory oviposition cues. Our results suggest that chemosensory and visual cues are complementary, with visual cues used to orient gravid females towards oviposition sites, possibly at long- to medium-ranges during crepuscular periods, while olfactory cues are used to approach the burrow in darkness and assess its suitability at close-range. Implications to sand fly control are discussed. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. Methods/Principle findings: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. Conclusion: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed. Author summary: Onchocerciasis is a vector-borne tropical disease caused by the parasitc worm, Onchocerca volvulus. The vector is Simulium flies that breed in fast flowing rivers and streams. The infection can cause skin disease and loss of vision, giving risk to the common name of 'river blindness' for the condition. Ivermectin (Mectizan) mass drug administration (MDA) given at high coverage for many years can interrupt transmission such that MDA can eventually be stopped. The present paper provides highlights of onchocerciasis transmission interruption in the first known coordinated international cross border focus with ivermectin MDA program in Africa, where 99% of the global onchocerciasis burden exists. This focus known as Galabat-Metema is shared between Ethiopia and Sudan, both of which have established a nationwide policy for elimination of onchocerciasis. The paper provides the history of MDA in the border area and the results leading a coordinated end to MDA in the focus in 2017. [ABSTRACT FROM AUTHOR]

Introduction: Vector Borne Diseases (VBDs) have a major impact on public health and socio-economic development. Inter-sectoral collaboration was recommended as one of the key elements of Integrated Vector Management (IVM), however limited evidence measures the effect and contribution of intersectoral approaches including but not only IVM. This systematic review aims to assess the existing evidence on all forms of inter-sectoral collaboration in VBD control and prevention, identify any gaps and develop a framework from a global perspective. Methods: Articles were identified through a search of PUBMED, Science of Direct, Web of Knowledge, Google Scholar and WHO archives using key words and excluded duplications (n = 2,034). The exclusion of non-VBDs control and prevention interventions resulted in 194 eligible titles/abstract/keywords for full text assessment. Further exclusion of non-peer reviewed articles, non-declaration of ethical clearance, reviews and expert opinion articles resulted in 50 articles finally being included for analysis with the extraction of data on outcome, factor/s influencing the effectiveness, indicators of collaboration and sustainability. Results: Of the 50 articles included in the analysis, 19 articles were categorized as of moderate-strong quality. All articles compared pre- and post-intervention outcomes against disease or vector variables. Three papers included outcome variables on intersectoral collaboration and participation indicator. However, no paper undertook component analysis by different sectors or different activities. Only one paper compared cost data for community-intersectoral intervention for IRS and traditional “vertical” IRS. Six factors were identified as influencing the effectiveness of inter-sectoral collaboration. Five of six factors are the main ones, namely the approach (37/47), resources (34/47), relationships (33/47), management (29/47) and shared vision (20/47) factors. A conceptual framework has been developed based on this review. Conclusion: This review shows the importance of inter-sectoral collaboration to reduce VBDs or vector densities. However, very few studies measured how much inter-sectoral collaboration contributes to the impact. Further high-quality studies using inter-sectoral collaboration indicators are recommended to be undertaken. [ABSTRACT FROM AUTHOR]

Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don’t live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992–2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x103cfu/g for petting zoo animals, and 2.9x105cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in Canada and abroad. Within this literature, knowledge gaps were identified, and include: a lack of concentration data reported in the literature for Campylobacter spp. in animal feces, a distinction between ill and diarrheic pets in the reported studies, noted differences in shedding and concentrations for various subtypes of Campylobacter, and consistent reporting between studies. [ABSTRACT FROM AUTHOR]

The article reflects on impact of vector biology research on old and emerging neglected tropical diseases such as vector-borne diseases (VBDs). Topics include observation of trypanosomes in the human blood in 1901 by surgeon Robert Michael Forde; threat imposed by increase in insecticide resistance on the sustainability of vector control programs in several tropical regions; and research on triatomine-transmitted Chagas disease.

Background: Beyond insecticides, alternative methods to control insect pests for agriculture and vectors of diseases are needed. Management strategies involving the mass-release of living control agents have been developed, including genetic control with sterile insects and biological control with parasitoids, for which aerial release of insects is often required. Aerial release in genetic control programmes often involves the use of chilled sterile insects, which can improve dispersal, survival and competitiveness of sterile males. Currently available means of aerially releasing chilled fruit flies are however insufficiently precise to ensure homogeneous distribution at low release rates and no device is available for tsetse. Methodology/Principal Findings: Here we present the smart aerial release machine, a new design by the Mubarqui Company, based on the use of vibrating conveyors. The machine is controlled through Bluetooth by a tablet with Android Operating System including a completely automatic guidance and navigation system (MaxNav software). The tablet is also connected to an online relational database facilitating the preparation of flight schedules and automatic storage of flight reports. The new machine was compared with a conveyor release machine in Mexico using two fruit flies species (Anastrepha ludens and Ceratitis capitata) and we obtained better dispersal homogeneity (% of positive traps, p<0.001) for both species and better recapture rates for Anastrepha ludens (p<0.001), especially at low release densities (<1500 per ha). We also demonstrated that the machine can replace paper boxes for aerial release of tsetse in Senegal. Conclusions/Significance: This technology limits damages to insects and allows a large range of release rates from 10 flies/km2 for tsetse flies up to 600 000 flies/km2 for fruit flies. The potential of this machine to release other species like mosquitoes is discussed. Plans and operating of the machine are provided to allow its use worldwide. [ABSTRACT FROM AUTHOR]

Background: Indoor spraying of walls and ceilings with residual insecticide remains a primary method of malaria control. Insecticide resistance in malaria vectors is a growing problem. Novel insecticides for indoor residual spraying (IRS) which can improve the control of pyrethroid resistant malaria vectors are urgently needed. Insecticide mixtures have the potential to improve efficacy or even to manage resistance in some situations but this possibility remains underexplored experimentally. Chlorfenapyr is a novel pyrrole insecticide which has shown potential to improve the control of mosquitoes which are resistant to current WHO-approved insecticides. Method: The efficacy of IRS with chlorfenapyr applied alone or as a mixture with alpha-cypermeththrin (a pyrethroid) was evaluated in experimental huts in Cove, Southern Benin against wild free flying pyrethroid resistant Anopheles gambiae sl. Comparison was made with IRS with alpha-cypermethrin alone. Fortnightly 30-minute in situ cone bioassays were performed to assess the residual efficacy of the insecticides on the treated hut walls. Results: Survival rates of wild An gambiae from the Cove hut site in WHO resistance bioassays performed during the trial were >90% with permethrin and deltamethrin treated papers. Mortality of free-flying mosquitoes entering the experimental huts was 4% in the control hut. Mortality with alpha-cypermethrin IRS did not differ from the control (5%, P>0.656). The highest mortality was achieved with chlorfenapyr alone (63%). The alpha-cypermethrin + chlorfenapyr mixture killed fewer mosquitoes than chlorfenapyr alone (43% vs. 63%, P<0.001). While the cone bioassays showed a more rapid decline in residual mortality with chlorfenapyr IRS to <30% after only 2 weeks, fortnightly mortality rates of wild free-flying An gambiae entering the chlorfenapyr IRS huts were consistently high (50–70%) and prolonged, lasting over 4 months. Conclusion: IRS with chlorfenapyr shows potential to significantly improve the control of malaria transmission in pyrethroid resistant areas compared to pyrethroid IRS or the mixture. Thirty minute in situ cone bioassays are not predictive of the performance of chlorfenapyr IRS under field conditions. [ABSTRACT FROM AUTHOR]

The Banana Bunchy Top Virus (BBTV) is one of the most economically important vector-borne banana diseases throughout the Asia-Pacific Basin and presents a significant challenge to the agricultural sector. Current models of BBTV are largely deterministic, limited by an incomplete understanding of interactions in complex natural systems, and the appropriate identification of parameters. A stochastic network-based Susceptible-Infected-Susceptible model has been created which simulates the spread of BBTV across the subsections of a banana plantation, parameterising nodal recovery, neighbouring and distant infectivity across summer and winter. Findings from posterior results achieved through Markov Chain Monte Carlo approach to approximate Bayesian computation suggest seasonality in all parameters, which are influenced by correlated changes in inspection accuracy, temperatures and aphid activity. This paper demonstrates how the model may be used for monitoring and forecasting of various disease management strategies to support policy-level decision making. Author summary: The Banana Bunchy Top Virus (BBTV) poses one of the greatest threats to the food security of developing nations and the banana industry throughout the Asia-Pacific Basin. Decision-makers face significant challenges in mitigating BBTV spread in banana plantations due to the vector-borne spread of this disease, which is significantly influenced by a vast array of external environmental factors that are unique to each plantation. We propose a flexible network-based model that describes the spread of BBTV in a real banana plantation through a random process while accounting for individual plantation characteristics and utilise a principled methodology for estimating model parameters. Our models can be used to quantify the effects of seasonal changes and plantation configuration on BBTV spread and can be used to predict high-risk areas in this plantation. We believe that our model might be used by decision-makers to evaluate the effectiveness of current disease management strategies and explore opportunities for improvements. [ABSTRACT FROM AUTHOR]

Introduction: The widespread emergence of resistance to insecticides used to control adult Aedes mosquitoes has made traditional control strategies inadequate for the reduction of various vector populations. Therefore, complementary vector control methods, such as the Sterile Insect Technique, are needed to enhance existing efforts. The technique relies on the rearing and release of large numbers of sterile males, and the development of efficient and standardized mass-rearing procedures and tools is essential for its application against medically important mosquitoes. Methods: In the effort to reduce the cost of the rearing process, a prototype low-cost plexiglass mass-rearing cage has been developed and tested for egg production and egg hatch rate in comparison to the current Food and Agriculture Organization/International Atomic Energy Agency (FAO/IAEA) stainless-steel cage. Additionally, an adult-index was validated and used as a proxy to estimate the mosquito survival rates by counting the number of male and female mosquitoes that were resting within each of the 6 squares at a given point of time each day in the cage. Results: The study has shown that the prototype mass-rearing cage is cheap and is as efficient as the FAO/IAEA stainless-steel cage in terms of egg production, with even better overall egg hatch rate. The mean numbers of eggs per cage, after seven cycles of blood feeding and egg collection, were 969,789 ± 138,101 and 779,970 ± 123,042, corresponding to 81 ± 11 and 65 ± 10 eggs per female over her lifespan, in the prototype and the stainless-steel-mass-rearing cages, respectively. The longevity of adult male and female mosquitoes was not affected by cage type and, the adult-index could be considered as an appropriate proxy for survival. Moreover, the mass-rearing cage prototype is easy to handle and transport and improves economic and logistic efficiency. Conclusion: The low-cost mass-rearing prototype cage can be recommended to produce Ae. aegypti in the context of rear and release techniques. The proposed adult-index can be used as a quick proxy of mosquito survival rates in mass-rearing settings. [ABSTRACT FROM AUTHOR]

This paper is focused on the transmission dynamics and optimal control of Anthroponotic Cutaneous Leishmania. The threshold condition R0 for initial transmission of infection is obtained by next generation method. Biological sense of the threshold condition is investigated and discussed in detail. The sensitivity analysis of the reproduction number is presented and the most sensitive parameters are high lighted. On the basis of sensitivity analysis, some control strategies are introduced in the model. These strategies positively reduce the effect of the parameters with high sensitivity indices, on the initial transmission. Finally, an optimal control strategy is presented by taking into account the cost associated with control strategies. It is also shown that an optimal control exists for the proposed control problem. The goal of optimal control problem is to minimize, the cost associated with control strategies and the chances of infectious humans, exposed humans and vector population to become infected. Numerical simulations are carried out with the help of Runge-Kutta fourth order procedure. [ABSTRACT FROM AUTHOR]

Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalälven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalälven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind. [ABSTRACT FROM AUTHOR]

Targeted environmental and ecosystem management remain crucial in control of dengue. However, providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge. An important piece of such information is the extent of the presence of potential dengue vector breeding sites, which consist primarily of open containers such as ceramic jars, buckets, old tires, and flowerpots. In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images and to create highly detailed container density maps at unprecedented scale. We implement the approach using Google Street View images which have the advantage of broad coverage and of often being two to three years old which allows correlation analyses of container counts against historical data from manual surveys. Containers comprising eight of the most common breeding sites are detected in the images using convolutional neural network transfer learning. Over a test set of images the object recognition algorithm has an accuracy of 0.91 in terms of F-score. Container density counts are generated and displayed on a decision support dashboard. Analyses of the approach are carried out over three provinces in Thailand. The container counts obtained agree well with container counts from available manual surveys. Multi-variate linear regression relating densities of the eight container types to larval survey data shows good prediction of larval index values with an R-squared of 0.674. To delineate conditions under which the container density counts are indicative of larval counts, a number of factors affecting correlation with larval survey data are analyzed. We conclude that creation of container density maps from geotagged images is a promising approach to providing detailed risk maps at large scale. [ABSTRACT FROM AUTHOR]

In recent years, increasing associations between microRNAs (miRNAs) and human diseases have been identified. Based on accumulating biological data, many computational models for potential miRNA-disease associations inference have been developed, which saves time and expenditure on experimental studies, making great contributions to researching molecular mechanism of human diseases and developing new drugs for disease treatment. In this paper, we proposed a novel computational method named Ensemble of Decision Tree based MiRNA-Disease Association prediction (EDTMDA), which innovatively built a computational framework integrating ensemble learning and dimensionality reduction. For each miRNA-disease pair, the feature vector was extracted by calculating the statistical measures, graph theoretical measures, and matrix factorization results for the miRNA and disease, respectively. Then multiple base learnings were built to yield many decision trees (DTs) based on random selection of negative samples and miRNA/disease features. Particularly, Principal Components Analysis was applied to each base learning to reduce feature dimensionality and hence remove the noise or redundancy. Average strategy was adopted for these DTs to get final association scores between miRNAs and diseases. In model performance evaluation, EDTMDA showed AUC of 0.9309 in global leave-one-out cross validation (LOOCV) and AUC of 0.8524 in local LOOCV. Additionally, AUC of 0.9192+/-0.0009 in 5-fold cross validation proved the model’s reliability and stability. Furthermore, three types of case studies for four human diseases were implemented. As a result, 94% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 96% (Breast Neoplasms) and 88% (Carcinoma Hepatocellular) of top 50 predicted miRNAs were confirmed by experimental evidences in literature. [ABSTRACT FROM AUTHOR]

Ecoregionalization is the process by which a territory is classified in similar areas according to specific environmental and climatic factors. The climate and the environment strongly influence the presence and distribution of vectors responsible for significant human and animal diseases worldwide. In this paper, we developed a map of the eco-climatic regions of Italy adopting a data-driven spatial clustering approach using recent and detailed spatial data on climatic and environmental factors. We selected seven variables, relevant for a broad set of human and animal vector-borne diseases (VBDs): standard deviation of altitude, mean daytime land surface temperature, mean amplitude and peak timing of the annual cycle of land surface temperature, mean and amplitude of the annual cycle of greenness value, and daily mean amount of rainfall. Principal Component Analysis followed by multivariate geographic clustering using the k-medoids technique were used to group the pixels with similar characteristics into different ecoregions, and at different spatial resolutions (250 m, 1 km and 2 km). We showed that the spatial structure of ecoregions is generally maintained at different spatial resolutions and we compared the resulting ecoregion maps with two datasets related to Bluetongue vectors and West Nile Disease (WND) outbreaks in Italy. The known characteristics of Culicoides imicola habitat were well captured by 2/22 specific ecoregions (at 250 m resolution). Culicoides obsoletus/scoticus occupy all sampled ecoregions, according to its known widespread distribution across the peninsula. WND outbreak locations strongly cluster in 4/22 ecoregions, dominated by human influenced landscape, with intense cultivations and complex irrigation network. This approach could be a supportive tool in case of VBDs, defining pixel-based areas that are conducive environment for VBD spread, indicating where surveillance and prevention measures could be prioritized in Italy. Also, ecoregions suitable to specific VBDs vectors could inform entomological surveillance strategies. [ABSTRACT FROM AUTHOR]

The expansion of urban ecosystems and climate change, both outcomes of massive lifestyle changes, contribute to a series of side effects such as environmental deterioration, spread of diseases, increased greenhouse gas emissions and introduction of invasive species. In the case of the Athens metropolitan area, an invasive mosquito species—the Asian tiger mosquito (Aedes albopictus)–has spread widely in the last decade. This spread is favoured within urban environments and is also affected by changing climatic trends. The Asian tiger mosquito is accompanied by risks of mosquito-borne diseases, greater nuisance levels, and increased expenses incurring for its confrontation. The main aims of this paper are (i) to estimate the various costs associated with their control of this invasive species, as well as its health and nuisance impacts, (ii) to evaluate the level of citizens’ well-being from averting these impacts and (iii) to record citizens’ and experts’ perceptions regarding alternative control measures. Evidence shows that experts tend to place a high value on mosquito control when associated with serious health risks, while citizens are more sensitive and concerned about the environmental impacts of control methods. The synthesis of results produced by the current study could act as a preliminary guide for the estimation of societal welfare from the confrontation of similar problems in the context of a complex ecosystem. [ABSTRACT FROM AUTHOR]

With the prosperity of machine learning and cloud computing, meaningful information can be mined from mass electronic medical data which help physicians make proper disease diagnosis for patients. However, using medical data and disease information of patients frequently raise privacy concerns. In this paper, based on single-layer perceptron, we propose a scheme of privacy-preserving clinical decision with cloud support (PPCD), which securely conducts disease model training and prediction for the patient. Each party learns nothing about the other’s private information. In PPCD, a lightweight secure multiplication is presented and introduced to improve the model training. Security analysis and experimental results on real data confirm the high accuracy of disease prediction achieved by the proposed PPCD without the risk of privacy disclosure. [ABSTRACT FROM AUTHOR]

Diaphorina citri is a vector of ‘Candidatus Liberibacter asiaticus,’ (CLas), associated with Huanglongbing, (HLB, or citrus greening) disease in citrus. D. citri exhibits three different color morph variants, blue, gray and yellow. Blue morphs have a greater capacity for long-distance flight as compared to non-blue morphs, but little else is known about how color morphology influences vector characteristics. In this study, we show that the color morphology of the insect is derived from pigmented cells of the fat body. Blue morphs acquire a lower level of CLas in their bodies from infected trees as compared to their gray and yellow conspecifics, referred to in this paper collectively as non-blue morphs. Accordingly, CLas titer in citrus leaves inoculated by non-blue insects was 6-fold higher than in leaves inoculated by blue insects. Blue color morphs harbored lower titers of Wolbachia and ‘Candidatus Profftella armatura,’ two of the D. citri bacterial endosymbionts. Expression of hemocyanin, a copper-binding oxygen transport protein responsible for the blue coloration of hemolymph of other arthropods and mollusks, was previously correlated with blue color morphology and is highly up-regulated in insects continuously reared on CLas infected citrus trees. Based on our results, we hypothesized that a reduction of hemocyanin expression would reduce the D. citri immune response and an increase in the titer of CLas would be observed. Surprisingly, a specific 3-fold reduction of hemocyanin-1 transcript levels using RNA silencing in blue adult D. citri morphs had an approximately 2-fold reduction on the titer of CLas. These results suggest that hemocyanin signaling from the fat body may have multiple functions in the regulation of bacterial titers in D. citri, and that hemocyanin is one of multiple psyllid genes involved in regulating CLas titer. [ABSTRACT FROM AUTHOR]

Emerging evidence has shown microRNAs (miRNAs) play an important role in human disease research. Identifying potential association among them is significant for the development of pathology, diagnose and therapy. However, only a tiny portion of all miRNA-disease pairs in the current datasets are experimentally validated. This prompts the development of high-precision computational methods to predict real interaction pairs. In this paper, we propose a new model of Logistic Model Tree for predicting miRNA-Disease Association (LMTRDA) by fusing multi-source information including miRNA sequences, miRNA functional similarity, disease semantic similarity, and known miRNA-disease associations. In particular, we introduce miRNA sequence information and extract its features using natural language processing technique for the first time in the miRNA-disease prediction model. In the cross-validation experiment, LMTRDA obtained 90.51% prediction accuracy with 92.55% sensitivity at the AUC of 90.54% on the HMDD V3.0 dataset. To further evaluate the performance of LMTRDA, we compared it with different classifier and feature descriptor models. In addition, we also validate the predictive ability of LMTRDA in human diseases including Breast Neoplasms, Breast Neoplasms and Lymphoma. As a result, 28, 27 and 26 out of the top 30 miRNAs associated with these diseases were verified by experiments in different kinds of case studies. These experimental results demonstrate that LMTRDA is a reliable model for predicting the association among miRNAs and diseases. [ABSTRACT FROM AUTHOR]

Background: The role of environmental factors in driving adaptive trajectories of living organisms is still being debated. This is even more important to understand when dealing with important neglected diseases and their vectors. Methodology/Principal Findings: In this paper, we analysed genetic divergence, computed from seven microsatellite loci, of 614 tsetse flies (Glossina palpalis gambiensis and Glossina palpalis palpalis, major vectors of animal and human trypanosomes) from 28 sites of West and Central Africa. We found that the two subspecies are so divergent that they deserve the species status. Controlling for geographic and time distances that separate these samples, which have a significant effect, we found that G. p. gambiensis from different landscapes (Niayes of Senegal, savannah and coastal environments) were significantly genetically different and thus represent different ecotypes or subspecies. We also confirm that G. p. palpalis from Ivory Coast, Cameroon and DRC are strongly divergent. Conclusions/Significance: These results provide an opportunity to examine whether new tsetse fly ecotypes might display different behaviour, dispersal patterns, host preferences and vectorial capacities. This work also urges a revision of taxonomic status of Glossina palpalis subspecies and highlights again how fast ecological divergence can be, especially in host-parasite-vector systems. Author Summary: The role of environmental factors in driving adaptive trajectories of living organisms is still being debated. This is even more important to understand when dealing with important and /or neglected diseases and their vectors. In this paper, we analysed genetic divergence, computed from several genetic markers, of 614 tsetse flies (Glossina palpalis gambiensis and Glossina palpalis palpalis, major vectors of animal and human trypanosomes) from 28 sites of West and Central Africa. We found that the two subspecies are so divergent that they deserve the species status. We found that G. p. gambiensis from different landscapes (Niayes of Senegal, savannah and coastal environments) were significantly genetically different, and thus represent different adaptive entities or even subspecies. We also confirm that G. p. palpalis from Ivory Coast, Cameroon and DRC are strongly divergent. These results provide an opportunity to examine whether these different types of tsetse fly might display different behaviour, dispersal patterns, host preferences and vectorial capacities. This work also urges a revision of taxonomic status of Glossina palpalis subspecies and highlights again how fast ecological divergence can be, especially in host-parasite-vector systems. [ABSTRACT FROM AUTHOR]

This paper presents the development of an agent-based model (ABM) to investigate Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission. The ABM model, fitted at a fine spatial scale, was used to explore the impact of a growing host population on the spread of disease along a 75 km transect in the Luangwa Valley, Zambia. The model was used to gain a greater understanding of how increases in human and domestic animal population could impact the contact network between vector and host, the subsequent transmission patterns, and disease incidence outcomes in the region. Modelled incidence rates showed increases in rHAT transmission in both humans and cattle. The primary demographic attribution of infection switched dramatically from young children of both sexes attending school, to adult women performing activities with shorter but more frequent trips, such as water and firewood collection, with men more protected due to the presence of cattle in their routines. The interpretation of model output provides a plausible insight into both population development and disease transmission in the near future in the region and such techniques could aid well-targeted mitigation strategies in the future. [ABSTRACT FROM AUTHOR]

Due to recent advances in genetic manipulation, transgenic mosquitoes may be a viable alternative to reduce some diseases. Feasibility conditions are obtained by simulating and analyzing mathematical models that describe the behavior of wild and transgenic populations living in the same geographic area. In this paper, we present a reaction–diffusion model in which the reaction term is a nonlinear function that describes the interaction between wild and transgenic mosquitoes, considering the zygosity, and the diffusive term that represents a nonuniform spatial spreading characterized by a random diffusion parameter. The resulting nonlinear system of partial differential equations is numerically solved using the sequential operator splitting technique, combining the finite element method and Runge-Kutta method. This scheme is numerically implemented considering uncertainty in the diffusion parameters of the model. Several scenarios simulating spatial release strategies of transgenic mosquitoes are analyzed, demonstrating an intrinsic association between the transgene frequency in the total population and the strategy adopted. [ABSTRACT FROM AUTHOR]

Introduction: Molecular xenomonitoring (MX)—pathogen detection in the mosquito rather than human—is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development. Methods: Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen. Results: Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen. Conclusions: Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history. [ABSTRACT FROM AUTHOR]

Theileria parva is a protozoan parasite transmitted by the brown ear tick Rhipicephalus appendiculatus that causes East Coast fever (ECF) in cattle, resulting in substantial economic losses in the regions of southern, eastern and central Africa. The schizont form of the parasite transforms the bovine host lymphocytes into actively proliferating cancer-like cells. However, how T. parva causes bovine host cells to proliferate and maintain a cancerous phenotype following infection is still poorly understood. On the other hand, current efforts to develop improved vaccines have identified only a few candidate antigens. In the present paper, we report the first comparative transcriptomic analysis throughout the course of T. parva infection. We observed that the development of sporoblast into sporozoite and then the establishment in the host cells as schizont is accompanied by a drastic increase of upregulated genes in the schizont stage of the parasite. In contrast, the ten highest gene expression values occurred in the arthropod vector stages. A comparative analysis showed that 2845 genes were upregulated in both sporozoite and schizont stages compared to the sporoblast. In addition, 647 were upregulated only in the sporozoite whereas 310 were only upregulated in the schizont. We detected low p67 expression in the schizont stage, an unexpected finding considering that p67 has been reported as a sporozoite stage-specific gene. In contrast, we found that transcription of p67 was 20 times higher in the sporoblast than in the sporozoite. Using the expression profiles of recently identified candidate vaccine antigens as a benchmark for selection for novel potential vaccine candidates, we identified three genes with expression similar to p67 and several other genes similar to Tp1—Tp10 schizont vaccine antigens. We propose that the antigenicity or chemotherapeutic potential of this panel of new candidate antigens be further investigated. Structural comparisons of the transcripts generated here with the existing gene models for the respective loci revealed indels. Our findings can be used to improve the structural annotation of the T. parva genome, and the identification of alternatively spliced transcripts. [ABSTRACT FROM AUTHOR]

Background: Rhodnius nasutus, a vector of the etiological agent Trypanosoma cruzi, is one of the epidemiologically most relevant triatomine species of the Brazilian Caatinga, where it often colonizes rural peridomestic structures such as chicken coops and occasionally invades houses. Historical colonization and determination of its genetic diversity and population structure may provide new information towards the improvement of vector control in the region. In this paper we present thoughtful analyses considering the phylogeography and demographic history of R. nasutus in the Caatinga. Methodology/Principal findings: A total of 157 R. nasutus specimens were collected from Copernicia prunifera palm trees in eight geographic localities within the Brazilian Caatinga biome, sequenced for 595-bp fragment of the mitochondrial cytochrome b gene (cyt b) and genotyped for eight microsatellite loci. Sixteen haplotypes were detected in the cyt b sequences, two of which were shared between different localities. Molecular diversity indices exhibited low diversity and a haplotype network revealed low divergence among R. nasutus sequences, with two central haplotypes shared by five of the eight populations analyzed. The demographic model that better represented R. nasutus population dynamics was the exponential growth model. Results of the microsatellite data analyses indicated that the entire population is comprised of four highly differentiated groups, with no obvious contemporary geographic barriers that could explain the population substructure detected. A complex pattern of migration was observed, in which a western Caatinga population seems to be the source of emigrants to the eastern populations. Conclusions/Significance: R. nasutus that inhabit C. prunifera palms do not comprise a species complex. The species went through a population expansion at 12–10 ka, during the Holocene, which coincides with end of the largest dry season in South America. It colonized the Caatinga in a process that occurred from west to east in the region. R. nasutus is presently facing an important ecological impact caused by the continuous deforestation of C. prunifera palms in northeast Brazil. We hypothesize that this ecological disturbance might contribute to an increase in the events of invasion and colonization of human habitations. [ABSTRACT FROM AUTHOR]

Introduction: This paper discusses the presence of Aedes aegypti pupae in different types of containers considering: volume, pH of the container, among other variables. Methods: A nonlinear method for selection was applied, based on Mutual Information, by placing in order of importance the most appropriate variables for identifying containers with and without Aedes aegypti pupae. Such variables were used for input into a Neural Network in layers for classification. Results: Among the experiments carried out, the best result obtained used the first eight variables selected by order of importance. The percentage of hits for containers which had no Aedes aegypti pupae was 73.3%, and 80.9% for those which did have Aedes aegypti pupae in the containers. This Neural Network method, a model with the capacity to emulate non-linear data, got better results in comparison with the discriminant power of the Logistic Regression model. Thus, the outcomes of using the Neural Networks method achieved better separability in classifying the containers with pupae and those with no pupae. Conclusion: This type of analysis will aid in the efforts to design an efficient program to control Aedes aegypti that can concentrate principally on containers which present the greatest productivity. [ABSTRACT FROM AUTHOR]

A campaign for malaria control, using Long Lasting Insecticide Nets (LLINs) was launched in South Sudan in 2009. The success of such a campaign often depends upon adequate available resources and reliable surveillance data which help officials understand existing infections. An optimal allocation of resources for malaria control at a sub-national scale is therefore paramount to the success of efforts to reduce malaria prevalence. In this paper, we extend an existing SIR mathematical model to capture the effect of LLINs on malaria transmission. Available data on malaria is utilized to determine realistic parameter values of this model using a Bayesian approach via Markov Chain Monte Carlo (MCMC) methods. Then, we explore the parasite prevalence on a continued rollout of LLINs in three different settings in order to create a sub-national projection of malaria. Further, we calculate the model’s basic reproductive number and study its sensitivity to LLINs’ coverage and its efficacy. From the numerical simulation results, we notice a basic reproduction number, , confirming a substantial increase of incidence cases if no form of intervention takes place in the community. This work indicates that an effective use of LLINs may reduce and hence malaria transmission. We hope that this study will provide a basis for recommending a scaling-up of the entry point of LLINs’ distribution that targets households in areas at risk of malaria. [ABSTRACT FROM AUTHOR]

Cannibalism is a commonly observed phenomenon in arthropod species having relevant consequences for population dynamics and individual fitness. It is a context-dependent behaviour and an understanding of the factors affecting cannibalism rate is crucial to highlight its ecological relevance. In mosquitoes, cannibalism between larval stages has been widely documented, and the role of density, food availability and length of contact between individuals also ascertained. However, although mosquitoes can develop in temporary water habitats with very heterogeneous topologies, the role of the site shape where cannibals and victims co-occur has been instead overlooked. In this paper, we investigated this issue by using a simulation approach and laboratory cannibalism experiments between old (third- and fourth-instars) and young (first-instar) larvae of the tiger mosquito Aedes albopictus. Three virtual spaces with different shapes were simulated and the number of larval encounters was estimated in each one to assess whether the spatial shape affected the number of encounters between cannibal and victims. Then, experimental trials in containers with similar shapes to those used in the simulations were performed, and the cannibalism rate was estimated at 24 and 48h. Our results showed that the spatial shape plays a role on cannibalism interactions, affecting the number of encounters between individuals. Indeed, in the experimental trials performed, we observed the highest cannibalism rate in the container with the highest number of encounters predicted by the simulations. Interestingly, we found also that spatial shape can affect cannibalism not only by affecting the number of encounters, but also the number of encounters “favorable” for cannibalistic events. Temporary waters are inhabited by several species other than mosquitoes. Our results, showing an influence of the spatial shape on cannibalism in Ae. albopictus larvae, add a new critical factor to those affecting ecological interactions in these habitats. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, public health managers employed pyrethroids against Ae. aegypti adults from 1989 to 2000, when a robust insecticide resistance monitoring system detected resistance to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also the preferred compounds engaged in household applications due to their rapid knockdown effect, lower toxicity to mammals and less irritating smell. Methodology/Principal findings: We evaluated pyrethroid resistance in Ae. aegypti populations over the course of a decade, from 2004 to 2015, after interruption of pyrethroid public applications in SP. Qualitative bioassays with papers impregnated with a deltamethrin diagnostic dose (DD) performed with insects from seven SP municipalities and evaluated yearly from 2006 to 2014, detected resistance in most of the cases. Quantitative bioassays were also carried out with four populations in 2011, suggesting a positive correlation between resistance level and survivorship in the DD bioassays. Biochemical tests conducted with seven insect populations in 2006 and 2015, detected increasing metabolic alterations of all major classes of detoxifying enzymes, mostly of mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV, the pyrethroid target-site) with a TaqMan real time PCR based technique was performed from 2004 to 2014 in all seven localities. The two kdr mutations, Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always present with a severe decrease of the susceptible allele over time. Conclusions/Significance: These results are discussed in the context of public and domestic insecticide use, the necessity of implementation of a strong integrated vector control strategy and the conceptual misunderstanding between 'vector control' and 'chemical control of vectors'. [ABSTRACT FROM AUTHOR]

Background: This paper presents the development of an agent-based model (ABM) to incorporate climatic drivers which affect tsetse fly (G. m. morsitans) population dynamics, and ultimately disease transmission. The model was used to gain a greater understanding of how tsetse populations fluctuate seasonally, and investigate any response observed in Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission, with a view to gaining a greater understanding of disease dynamics. Such an understanding is essential for the development of appropriate, well-targeted mitigation strategies in the future. Methods: The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The model incorporates climatic factors that affect pupal mortality, pupal development, birth rate, and death rate. In combination with fine scale demographic data such as ethnicity, age and gender for the human population in the region, as well as an animal census and a sample of daily routines, we create a detailed, plausible simulation model to explore tsetse population and disease transmission dynamics. Results: The seasonally-driven model suggests that the number of infections reported annually in the simulation is likely to be a reasonable representation of reality, taking into account the high levels of under-detection observed. Similar infection rates were observed in human (0.355 per 1000 person-years (SE = 0.013)), and cattle (0.281 per 1000 cattle-years (SE = 0.025)) populations, likely due to the sparsity of cattle close to the tsetse interface. The model suggests that immigrant tribes and school children are at greatest risk of infection, a result that derives from the bottom-up nature of the ABM and conditioning on multiple constraints. This result could not be inferred using alternative population-level modelling approaches. Conclusions: In producing a model which models the tsetse population at a very fine resolution, we were able to analyse and evaluate specific elements of the output, such as pupal development and the progression of the teneral population, allowing the development of our understanding of the tsetse population as a whole. This is an important step in the production of a more accurate transmission model for rHAT which can, in turn, help us to gain a greater understanding of the transmission system as a whole. [ABSTRACT FROM AUTHOR]

There is a growing necessity to integrate morphological and genetic studies. This paper proposes a new technique that allows DNA extraction of arthropods while still keeping intact the entire morphology of the specimens. The technique uses Proteinase K to dissolve protein tissues and preserve the chitinous exoskeleton of specimens. The method is fast, cheap, non-toxic, and allows for good morphological preparations of specimens retaining much of their tridimensional structure. The methodology works fine with specimens preserved in different kinds of media, such as for dry (pinned) specimens, and specimens preserved in Ethanol. In addition, it allows the extraction of DNA from fresh specimens, as well as from specimens preserved for a long time. The technique works well for morphological studies alone, but allows the generation of an associated genomic library at an individual-scale. Among the advantages of the new technique is the possibility of extracting DNA from the entire specimen (necessary for the study of diseases transmitted by arthropod vectors), while still keeping the morphology intact for correct taxonomic identification. In addition, in comparison with methods that extract DNA from small tissue samples (e.g., from legs or wings), the method allows for the extraction of a larger amount of DNA and is better suited for small specimens. [ABSTRACT FROM AUTHOR]

Understanding the factors that govern the dynamics and distribution of animal and plant parasites and pathogens has taken on a new urgency in the face of global climate change. Many disease-causing organisms are strongly influenced by environmental factors such as temperature, rainfall and humidity, which are in turn influenced by climate change. If a disease can be controlled effectively, the consequence of climate (and climate change) could largely be mitigated, but where control is difficult or impossible, the consequences could be substantial. [Extracted from the article]

This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. Since 2011, progress has been made in a number of areas. The extent of submicroscopic and asymptomatic infections is better understood, as are the biological parameters governing transmission of sexual stage parasites. Limitations of existing transmission measures have been documented, and proof-of-concept has been established for new innovative serological and molecular methods to better characterise transmission. Finally, there now exists a concerted effort towards the use of ensemble datasets across the spectrum of metrics, from passive and active sources, to develop more accurate risk maps of transmission. These can be used to better target interventions and effectively monitor progress toward elimination. The success of interventions depends not only on the level of endemicity but also on how rapidly or recently an area has undergone changes in transmission. Improved understanding of the biology of mosquito-human and human-mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission. [ABSTRACT FROM AUTHOR]

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination. [ABSTRACT FROM AUTHOR]

This paper summarises key advances and priorities since the 2011 presentation of the Malaria Eradication Research Agenda (malERA), with a focus on the combinations of intervention tools and strategies for elimination and their evaluation using modelling approaches. With an increasing number of countries embarking on malaria elimination programmes, national and local decisions to select combinations of tools and deployment strategies directed at malaria elimination must address rapidly changing transmission patterns across diverse geographic areas. However, not all of these approaches can be systematically evaluated in the field. Thus, there is potential for modelling to investigate appropriate 'packages' of combined interventions that include various forms of vector control, case management, surveillance, and population-based approaches for different settings, particularly at lower transmission levels. Modelling can help prioritise which intervention packages should be tested in field studies, suggest which intervention package should be used at a particular level or stratum of transmission intensity, estimate the risk of resurgence when scaling down specific interventions after local transmission is interrupted, and evaluate the risk and impact of parasite drug resistance and vector insecticide resistance. However, modelling intervention package deployment against a heterogeneous transmission background is a challenge. Further validation of malaria models should be pursued through an iterative process, whereby field data collected with the deployment of intervention packages is used to refine models and make them progressively more relevant for assessing and predicting elimination outcomes. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored. [ABSTRACT FROM AUTHOR]

In this paper, we present and analyze an SEIR Zika epidemic model. Firstly, we investigate the model with constant controls. The steady states of the model is found to be locally and globally asymptotically stable. Thereafter, we incorporate time dependent controls into the model in order to investigate the optimal effects of bednets, treatments of infective and spray of insecticides on the disease spread. Furthermore, we used Pontryagin’s Maximum Principle to determine the necessary conditions for effective control of the disease. Also, the numerical results were presented. [ABSTRACT FROM AUTHOR]

Background: Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment. Methodology/Principal findings: First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors–data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences), but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections. Conclusions/Significance: Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is a major public health problem in Libya. In this paper, we describe the eco-epidemiological parameters of CL during the armed conflict period from January 2011 till December 2012. Current spatiotemporal distributions of CL cases were explored and projected to the future using a correlative modelling approach. In addition the present results were compared with our previous data obtained for the time period 1995–2008. Methodology/Principal findings: We investigated 312 CL patients who presented to the Dermatology Department at the Tripoli Central Hospital and came from 81 endemic areas distributed in 10 districts. The patients presented with typical localized lesions which appeared commonly on the face, arms and legs. Molecular identification of parasites by a PCR-RFLP approach targeting the ITS1 region of the rDNA was successful for 81 patients with two causative species identified: L. major and L. tropica comprised 59 (72.8%) and 22 (27.2%) cases, respectively. Around 77.3% of L. tropica CL and 57.7% of L. major CL caused single lesions. Five CL patients among our data set were seropositive for HIV. L. tropica was found mainly in three districts, Murqub (27.3%), Jabal al Gharbi (27.3%) and Misrata (13.7%) while L. major was found in two districts, in Jabal al Gharbi (61%) and Jafara (20.3%). Seasonal occurrence of CL cases showed that most cases (74.2%) admitted to the hospital between November and March, L. major cases from November till January (69.4%), and L. tropica cases mainly in January and February (41%). Two risk factors were identified for the two species; the presence of previously infected household members, and the presence of rodents and sandflies in patient’s neighborhoods. Spatiotemporal projections using correlative distribution models based on current case data and climatic conditions showed that coastal regions have a higher level of risk due to more favourable conditions for the transmitting vectors. Conclusion: Future projection of CL until 2060 showed a trend of increasing incidence of CL in the north-western part of Libya, a spread along the coastal region and a possible emergence of new endemics in the north-eastern districts of Libya. These results should be considered for control programs to prevent the emergence of new endemic areas taking also into consideration changes in socio-economical factors such as migration, conflicts, urbanization, land use and access to health care. [ABSTRACT FROM AUTHOR]

Epidemic or pathogen emergence is the phenomenon by which a poorly transmissible pathogen finds its evolutionary pathway to become a mutant that can cause an epidemic. Many mathematical models of pathogen emergence rely on branching processes. Here, we discuss pathogen emergence using Markov chains, for a more tractable analysis, generalizing previous work by Kendall and Bartlett about disease invasion. We discuss the probability of emergence failure for early epidemics, when the number of infected individuals is small and the number of the susceptible individuals is virtually unlimited. Our formalism addresses both directly transmitted and vector-borne diseases, in the cases where the original pathogen is 1) one step-mutation away from the epidemic strain, and 2) undergoing a long chain of neutral mutations that do not change the epidemiology. We obtain analytic results for the probabilities of emergence failure and two features transcending the transmission mechanism. First, the reproduction number of the original pathogen is determinant for the probability of pathogen emergence, more important than the mutation rate or the transmissibility of the emerged pathogen. Second, the probability of mutation within infected individuals must be sufficiently high for the pathogen undergoing neutral mutations to start an epidemic, the mutation threshold depending again on the basic reproduction number of the original pathogen. Finally, we discuss the parameterization of models of pathogen emergence, using SARS-CoV1 as an example of zoonotic emergence and HIV as an example for the emergence of drug resistance. We also discuss assumptions of our models and implications for epidemiology. [ABSTRACT FROM AUTHOR]

The equine South African pointy vector mosquito, Aedes caballus, poses a significant threat to human health due to its capacity for transmitting arboviruses. Despite favorable climate for its existence in southeast Iran, previous records of this species in the area have indicated very low abundance. This comprehensive field and laboratory study aimed to assess its current adult population status in this region, utilizing a combination of ecological, morphological and molecular techniques. Four distinct types of traps were strategically placed in three fixed and two variable mosquito sampling sites in the southern strip of Sistan and Baluchistan Province. Subsequently, DNA was extracted from trapped mosquitoes and subjected to PCR amplification using the molecular markers COI, ITS2, and ANT. In total, 1734 adult Ae. caballus specimens were collected from rural areas, with the majority being captured by CO2-baited bednet traps. A notable increase in the abundance of this species was observed following rainfall in February. The genetic analysis revealed multiple haplotypes based on COI and ITS2 sequences, with COI gene divergence at 0.89%, and ITS2 sequence divergence at 1.6%. This suggests that previous challenges in morphological identification may have led to misidentifications, with many adults previously classified as Ae. vexans potentially being Ae. caballus. The findings of this study hold significant implications for public health authorities, providing valuable insights for integrated and targeted vector control and disease management efforts. [ABSTRACT FROM AUTHOR]

The mosquito Aedes spp. holds important relevance for human and animal health, as it serves as a vector for transmitting multiple diseases, including dengue and Zika virus. The microbiome's impact on its host's health and fitness is well known. However, most studies on mosquito microbiomes have been conducted in laboratory settings. We explored the mixed microbial communities within Aedes spp., utilizing the 16S rRNA gene for diversity analysis and shotgun metagenomics for functional genomics. Our samples, which included Ae. aegypti and Ae. albopictus, spanned various developmental stages—eggs, larvae, and adults—gathered from five semiurban areas in Mexico. Our findings revealed a substantial diversity of 8,346 operational taxonomic units (OTUs), representing 967 bacterial genera and 126,366 annotated proteins. The host developmental stage was identified as the primary factor associated with variations in the microbiome composition. Subsequently, we searched for genes and species involved in mosquito biocontrol. Wolbachia accounted for 9.6% of the 16S gene sequences. We observed a high diversity (203 OTUs) of Wolbachia strains commonly associated with mosquitoes, such as wAlb, with a noticeable increase in abundance during the adult stages. Notably, we detected the presence of the cifA and cifB genes, which are associated with Wolbachia's cytoplasmic incompatibility, a biocontrol mechanism. Additionally, we identified 221 OTUs related to Bacillus, including strains linked to B. thuringiensis. Furthermore, we discovered multiple genes encoding insecticidal toxins, such as Cry, Mcf, Vip, and Vpp. Overall, our study contributes to the understanding of mosquito microbiome biodiversity and metabolic capabilities, which are essential for developing effective biocontrol strategies against this disease vector. [ABSTRACT FROM AUTHOR]

There are cases in which CKD progression is difficult to evaluate, because the changes in estimated glomerular filtration rate (eGFR) and proteinuria sometimes show opposite directions as CKD progresses. Indices and models that enable the easy and accurate risk prediction of end-stage-kidney disease (ESKD) are indispensable to CKD therapy. In this study, we investigated whether a CKD stage coordinate transformed into a vector field (CKD potential model) accurately predicts ESKD risk. Meta-analysis of large-scale cohort studies of CKD patients in PubMed was conducted to develop the model. The distance from CKD stage G2 A1 to a patient's data on eGFR and proteinuria was defined as r. We developed the CKD potential model on the basis of the data from the meta-analysis of three previous cohort studies: ESKD risk = exp(r). Then, the model was validated using data from a cohort study of CKD patients in Japan followed up for three years (n = 1,564). Moreover, the directional derivative of the model was developed as an index of CKD progression velocity. For ESKD prediction in three years, areas under the receiver operating characteristic curves (AUCs) were adjusted for baseline characteristics. Cox proportional hazards models with spline terms showed the exponential association between r and ESKD risk (p<0.0001). The CKD potential model more accurately predicted ESKD with an adjusted AUC of 0.81 (95% CI 0.76, 0.87) than eGFR (p<0.0001). Moreover, the directional derivative of the model showed a larger adjusted AUC for the prediction of ESKD than the percent eGFR change and eGFR slope (p<0.0001). Then, a chart of the transformed CKD stage was developed for implementation in clinical settings. This study indicated that the transformed CKD stage as a vector field enables the easy and accurate estimation of ESKD risk and CKD progression and suggested that vector analysis is a useful tool for clinical studies of CKD and its related diseases. [ABSTRACT FROM AUTHOR]

Hematophagous mosquitoes require vertebrate blood for their reproductive cycles, making them effective vectors for transmitting dangerous human diseases. Thus, high-intensity metabolism is needed to support reproductive events of female mosquitoes. However, the regulatory mechanism linking metabolism and reproduction in mosquitoes remains largely unclear. In this study, we found that the expression of estrogen-related receptor (ERR), a nuclear receptor, is activated by the direct binding of 20-hydroxyecdysone (20E) and ecdysone receptor (EcR) to the ecdysone response element (EcRE) in the ERR promoter region during the gonadotropic cycle of Aedes aegypti (named AaERR). RNA interference (RNAi) of AaERR in female mosquitoes led to delayed development of ovaries. mRNA abundance of genes encoding key enzymes involved in carbohydrate metabolism (CM)—glucose-6-phosphate isomerase (GPI) and pyruvate kinase (PYK)—was significantly decreased in AaERR knockdown mosquitoes, while the levels of metabolites, such as glycogen, glucose, and trehalose, were elevated. The expression of fatty acid synthase (FAS) was notably downregulated, and lipid accumulation was reduced in response to AaERR depletion. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSA) determined that AaERR directly activated the expression of metabolic genes, such as GPI, PYK, and FAS, by binding to the corresponding AaERR-responsive motif in the promoter region of these genes. Our results have revealed an important role of AaERR in the regulation of metabolism during mosquito reproduction and offer a novel target for mosquito control. Author summary: Following a blood meal in female mosquitoes, carbohydrate and lipid metabolism become activated, aligned with the high demands of reproductive requirements. Concurrently, the estrogen-related receptor (AaERR) mRNA level in Aedes aegypti rises dramatically. We found that AaERR is regulated by 20-hydroxyecdysone (20E), which is the main regulatory hormone during the post blood meal (PBM) reproductive phase. The 20E receptor, ecdysone receptor (EcR), directly binds to the AaERR gene promoter region, activating transcription of this gene. 20E promotes glycolysis and glycogen catabolism, accelerating carbohydrate utilization. AaERR stimulates fatty acid synthesis and leads to lipid accumulation. We confirmed the direct regulatory relationship between AaERR and metabolism-related enzymes. Further investigation revealed that AaERR depletion inhibited the expression of vitellogenin (Vg) in female mosquitoes and disrupted the development of the ovaries, affirming the critical role of AaERR in 20E-dependent metabolism. These findings highlight the essential part AaERR plays in maintaining metabolic homeostasis and promoting normal reproductive development in female mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Zoonotic visceral leishmaniasis is endemic in the Mediterranean Basin, where the dog is the main reservoir host. The disease's causative agent, Leishmania infantum, is transmitted by blood-feeding female sandflies. This paper reports an integrative study of canine leishmaniasis in a region of France spanning the southwest Massif Central and the northeast Pyrenees, where the vectors are the sandflies Phlebotomus ariasi and P. perniciosus Methods: Sandflies were sampled in 2005 using sticky traps placed uniformly over an area of approximately 100 by 150 km. High- and low-resolution satellite data for the area were combined to construct a model of the sandfly data, which was then used to predict sandfly abundance throughout the area on a pixel by pixel basis (resolution of c. 1 km). Using literature- and expert-derived estimates of other variables and parameters, a spatially explicit R0 map for leishmaniasis was constructed within a Geographical Information System. R0 is a measure of the risk of establishment of a disease in an area, and it also correlates with the amount of control needed to stop transmission. Conclusions: To our knowledge, this is the first analysis that combines a vector abundance prediction model, based on remotely-sensed variables measured at different levels of spatial resolution, with a fully mechanistic process-based temperature-dependent R0 model. The resulting maps should be considered as proofs-of-principle rather than as ready-touse risk maps, since validation is currently not possible. The described approach, based on integrating several modeling methods, provides a useful new set of tools for the study of the risk of outbreaks of vector-borne diseases [ABSTRACT FROM AUTHOR]