Disruptive technology for vector control: the Innovative Vector Control Consortium and the US Military join forces to explore transformative insecticide application technology for mosquito control programmes

Malaria vector control technology has remained largely static for decades and there is a pressing need for innovative control tools and methodology to radically improve the quality and efficiency of current vector control practices. This report summarizes a workshop jointly organized by the Innovative Vector Control Consortium (IVCC) and the Armed Forces Pest Management Board (AFPMB) focused on public health pesticide application technology. Three main topics were discussed: the limitations with current tools and techniques used for indoor residual spraying (IRS), technology innovation to improve efficacy of IRS programmes, and truly disruptive application technology beyond IRS. The group identified several opportunities to improve application technology to include: insuring all IRS programmes are using constant flow valves and erosion resistant tips; introducing compression sprayer improvements that help minimize pesticide waste and human error; and moving beyond IRS by embracing the potential for new larval source management techniques and next generation technology such as unmanned “smart” spray systems. The meeting served to lay the foundation for broader collaboration between the IVCC and AFPMB and partners in industry, the World Health Organization, the Bill and Melinda Gates Foundation and others

Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes

BACKGROUND: To be transmitted by its mosquito vector, dengue virus (DENV) must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP) is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission. RESULTS: After ingestion of DENV-2, midgut infections in Chetumal mosquitoes were characterized by a peak in virus titers between 7 and 10 days post-infection (dpi). The amount of viral antigen and viral titers in the midgut then declined, but viral RNA levels remained stable. The presence of DENV-2 antigen in the trachea was positively correlated with virus dissemination from the midgut. DENV-2 antigen was found in salivary gland tissue in more than a third of mosquitoes at 4 dpi. Unlike in the midgut, the amount of viral antigen (as well as the percent of infected salivary glands) increased with time. DENV-2 antigen also accumulated and increased in neural tissue throughout the EIP. DENV-2 antigen was detected in multiple tissues of the vector, but unlike some other arboviruses, was not detected in muscle. CONCLUSION: Our results suggest that the EIP of DENV-2 in its vector may be shorter that the previously reported and that the tracheal system may facilitate DENV-2 dissemination from the midgut. Mosquito organs (e.g. midgut, neural tissue, and salivary glands) differed in their response to DENV-2 infection

Genetic specificity and potential for local adaptation between dengue viruses and mosquito vectors

Background: Several observations support the hypothesis that vector-driven selection plays an important role in shaping dengue virus (DENV) genetic diversity. Clustering of DENV genetic diversity at a particular location may reflect underlying genetic structure of vector populations, which combined with specific vector genotype x virus genotype (G x G) interactions may promote adaptation of viral lineages to local mosquito vector genotypes. Although spatial structure of vector polymorphism at neutral genetic loci is well-documented, existence of G x G interactions between mosquito and virus genotypes has not been formally demonstrated in natural populations. Here we measure G x G interactions in a system representative of a natural situation in Thailand by challenging three isofemale families from field-derived Aedes aegypti with three contemporaneous low-passage isolates of DENV-1. Results: Among indices of vector competence examined, the proportion of mosquitoes with a midgut infection, viral RNA concentration in the body, and quantity of virus disseminated to the head/legs (but not the proportion of infected mosquitoes with a disseminated infection) strongly depended on the specific combinations of isofemale families and viral isolates, demonstrating significant G x G interactions. Conclusion: Evidence for genetic specificity of interactions in our simple experimental design indicates that vector competence of Ae. aegypti for DENV is likely governed to a large extent by G x G interactions in genetically diverse, natural populations. This result challenges the general relevance of conclusions from laboratory systems that consist of a single combination of mosquito and DENV genotypes. Combined with earlier evidence for fine-scale genetic structure of natural Ae. aegypti populations, our finding indicates that the necessary conditions for local DENV adaptation to mosquito vectors are met

SandflyMap: leveraging spatial data on sand fly vector distribution for disease risk assessments

We feature SandflyMap (www.sandflymap.org), a new map service within VectorMap (www.vectormap.org) that allows free public online access to global sand fly, tick and mosquito collection records and habitat suitability models. Given the short home range of sand flies, combining remote sensing and collection point data give a powerful insight into the environmental determinants of sand fly distribution. SandflyMap is aimed at medical entomologists, vector disease control workers, public health officials and health planners. Data are checked for geographical and taxonomic errors, and are comprised of vouchered specimen information, and both published and unpublished observation data. SandflyMap uses Microsoft Silverlight and ESRI’s ArcGIS Server 10 software platform to present disease vector data and relevant remote sensing layers in an online geographical information system format. Users can view the locations of past vector collections and the results of models that predict the geographic extent of individual species. Collection records are searchable and downloadable, and Excel collection forms with drop down lists, and Excel charts to country, are available for data contributors to map and quality control their data. SandflyMap makes accessible, and adds value to, the results of past sand fly collecting efforts. We detail the workflow for entering occurrence data from the literature to SandflyMap, using an example for sand flies from South America. We discuss the utility of SandflyMap as a focal point to increase collaboration and to explore the nexus between geography and vector-borne disease transmission

Dengue-1 Virus Clade Replacement in Thailand Associated with Enhanced Mosquito Transmission

International audienceDengue viruses (DENV) are characterized by extensive genetic diversity and can be organized in multiple, genetically distinct lineages that arise and die out on a regular basis in regions where dengue is endemic. A fundamental question for understanding DENV evolution is the relative extent to which stochastic processes (genetic drift) and natural selection acting on fitness differences among lineages contribute to lineage diversity and turnover. Here, we used a set of recently collected and archived low-passage DENV-1 isolates from Thailand to examine the role of mosquito vector-virus interactions in DENV evolution. By comparing the ability of 23 viruses isolated on different dates between 1985 and 2009 to be transmitted by a present-day Aedes aegypti population from Thailand, we found that a major clade replacement event in the mid-1990s was associated with virus isolates exhibiting increased titers in the vector's hemocoel, which is predicted to result in a higher probability of transmission. This finding is consistent with the hypothesis that selection for enhanced transmission by mosquitoes is a possible mechanism underlying major DENV clade replacement events. There was significant variation in transmission potential among isolates within each clade, indicating that in addition to vector-driven selection, other evolutionary forces act to maintain viral genetic diversity. We conclude that occasional adaptive processes involving the mosquito vector can drive major DENV lineage replacement events

Miniature Magnetic Robots For In-Pipe Locomotion

Inspection of both small and large diameter bore pipelines for pipe integrity and defect identification with a single system has previously been impractical; especially using wall-press locomotion methods with low adaptive range. A miniature magnetic wallclimbing robot has been developed as a robotic solution for the inspection of 50mm bore diameter pipelines which can scale in-pipe geometry obstacles to access larger connected pipelines. Using magnetic arrays directed through steel flux plates within the wheels, the robot uses magnetic forces to adhere to the pipe. The system is 3D printed and includes soft printed material rubber wheels. The robot prototype is wirelessly driven, controlled remotely through serial Bluetooth communication radio at 2.4 GHz rated up to 100m. The robot’s unique compact geometry and magnetic design allows it to scale concave rightangle wall cases in just a 50mm diameter bore. By entering pipe networks through these small existing access points the robot removes the need for expensive drilling procedures required to fit launch vessels

The First Prediction of a Rift Valley Fever Outbreak

El Nino/Southern Oscillation (ENSO) related anomalies were analyzed using a combination of satellite measurements of elevated sea surface temperatures, and subsequent elevated rainfall and satellite derived normalized difference vegetation index data. A Rift Valley fever risk mapping model using these climate data predicted areas where outbreaks of Rift Valley fever in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. This is the first prospective prediction of a Rift Valley fever outbreak

Timing of CGM initiation in pediatric diabetes: The CGM TIME Trial.

OBJECTIVE: To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy. METHODS: A 5-site RCT of pump-naïve subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink Pro™ software) over 6 months after CGM initiation. Secondary outcome HbA1c was measured centrally. Linear mixed-models and ordinary least squares models were fitted to estimate effect of intervention, and covariates baseline age, T1D duration, HbA1c, gender, ethnicity, hypoglycemia history, clinical site, and association between CGM adherence and HbA1c. RESULTS: The trial randomized 144/152 (95%) eligible subjects. Baseline mean age was 11.5 ± 3.3(SD) years, T1D duration 3.4 ± 3.1 years, and HbA1c 7.9 ± 0.9%. Six months after CGM initiation, adjusted mean difference in CGM adherence was 62.4 hours per 28 days greater in the Simultaneous Group compared to Delayed Group (P = .007). There was no difference in mean HbA1c at 6 months. However, for each 100 hours of CGM use per 28-day period, HbA1c was 0.39% (95% CI 0.10%-0.69%) lower. Higher CGM adherence was associated with reduced time with glucose \u3e10 mmol/L (P \u3c .001). CONCLUSION: CGM adherence was higher after 6 months when initiated at same time as pump therapy compared to starting CGM 6 months after pump therapy. Greater CGM adherence was associated with improved HbA1c

Sperm Toolbox-A selection of small molecules to study human spermatozoa

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.</p