["New Modalities in Cancer Imaging and Therapy" XVth edition of the workshop organized by the network "Tumor Targeting, Imaging, Radiotherapies" of the Cancéropôle Grand-Ouest, 5-8 October 2022, France]. / « New Modalities in Cancer Imaging and Therapy ¼ XVe édition de l'atelier organisé par le réseau « Vectorisation, Imagerie, Radiothérapies ¼ du Cancéropôle Grand-Ouest, 5­8 octobre 2022, Erquy, France.

The fifteenth edition of the international workshop organized by the "Tumour Targeting and Radiotherapies network" of the Cancéropôle Grand-Ouest focused on the latest advances in internal and external radiotherapy from different disciplinary angles: chemistry, biology, physics, and medicine. The workshop covered several deliberately diverse topics: the role of artificial intelligence, new tools for imaging and external radiotherapy, theranostic aspects, molecules and contrast agents, vectors for innovative combined therapies, and the use of alpha particles in therapy.

[Recurrence of dengue epidemics in Burkina Faso: Community preference for an intervention to prevent the disease]. / Épidémies récurrentes de la dengue au Burkina Faso : préférences communautaires pour une intervention de prévention de la maladie.

BACKGROUND: Community-based interventions have proven effective in several Latin American countries in controlling dengue vector Aedes aegypti and reducing the burden of the disease. However, we did not find any study reporting the assessment or implementation of such interventions in Sub-Saharan Africa. This article presents local communities' preferences for activities as part of the implementation of a community-based intervention for dengue prevention in Ouagadougou (Burkina Faso) where dengue epidemics are recurrent during the rainy season. METHODS: A mixed-method study combining qualitative and quantitative data collection was conducted. Information from 983 households and their preferences for community-based activities for dengue prevention were collected in five neighborhoods of the city using a quantitative questionnaire. Then, 15 qualitative focus groups were organized in one of the neighborhoods that was randomly selected to receive a community-based intervention for dengue prevention. These groups were made up of 216 people representing the different socio-cultural categories: community leaders, men, women, young girls and boys. RESULTS: More than 95% of household respondents to the quantitative questionnaire found community-based interventions acceptable and/or useful: to raise awareness of mosquito-borne disease transmission, to identify and remove the mosquito breeding sites and areas favorable to the development of the adult vectors. Most participants in the focus groups, preferred outreach activities such as video/debate sessions, school and home education sessions, focus groups. They also preferred the implementation of community working groups, responsible for identifying and eliminating mosquito breeding sites in the neighborhood. However, many participants had reservations about sending preventive text messages to residents. They found it feasible but not useful since most people cannot read. CONCLUSION: This study shows that it is important to get the local communities involved in the formulation of health prevention activities in sub-Saharan Africa where some interventions are often implemented using strategies from other continents.

Downscaling incidence risk mapping for a Colombian malaria endemic region.

OBJECTIVE: To map at a fine spatial scale, the risk of malaria incidence for the important endemic region is Urabá-Bajo Cauca and Alto Sinú, NW Colombia, using a new modelling framework based on GIS and remotely sensed environmental data. METHODS: The association between environmental and topographic variables obtained from remote sensors and the annual parasite incidence (API) for the years 2013-2015 was calculated using multiple regression analysis; subsequently, a model was constructed to estimate the API and to project it to the entire endemic region in order to design the risk map. The model was validated by relating the obtained API values with the presence of the three main Colombian malaria vectors, Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. RESULTS: Temperature and Normalized Difference Water Index (NDWI) showed a significant correlation with the observed API. The risk map of malaria incidence showed that the zones at higher risk in the Urabá-Bajo Cauca and Alto Sinú region were located south-east of the region, while the northern area presented the lowest malaria risk. A method was generated to estimate the API for small urban centres, instead of the used reports at the municipality level. CONCLUSIONS: These results provide evidence of the utility of risk maps to identify environmentally vulnerable areas at a fine spatial resolution in the Urabá-Bajo Cauca and Alto Sinú region. This information contributes to the implementation of vector control interventions at the microgeographic scale at areas of high malaria risk.

Use of Bacillus thuringiensis israelensis in integrated vector control of Aedes sp. in Sri Lanka: a prospective controlled effectiveness study.

OBJECTIVES: The annual incidence of dengue has been increasing over the last few years in Sri Lanka with seasonal epidemics. Biological control of the vector has not been part of the integrated vector control implemented by the public health authorities of Sri Lanka so far. This pilot study assessed the effectiveness of using Bacillus thuringiensis israelensis (Bti) spray to control the Aedes mosquito vector population density. METHODS: Prospective controlled effectiveness study in three administrative divisions of Colombo. Study areas were selected from urban, semiurban and rural administrative divisions within the district, and they were compared with two matching controls from the same division. Test areas received three cycles of Bti spraying 1 month apart. Control areas were not sprayed with Bti. Ovitrap and larval indices were calculated at baseline and 2 weeks after each spray cycle. RESULTS: There was a significant improvement in the adult vector population (ovitrap index) in the test areas after three spray cycles, but this effect had disappeared after 8 weeks (no residual effect). There was no consistent positive impact on larval indices (premise, container and Breteau indices) after each spray cycle. CONCLUSION: Bti might have a moderate impact on adult vector populations mediated via transient reductions in larval populations. However, this effect is not sustained probably due to rapid re-infestation. Bti spray, if implemented, can only play a supplementary role to other vector control methods.

Systemic insecticides used in dogs: potential candidates for phlebotomine vector control?

Zoonotic visceral leishmaniasis (ZVL) is a public health problem endemic in some countries. Current control measures, in particular culling infected dogs, have not reduced ZVL incidence in humans. We evaluated the use of five systemic insecticides (spinosad, fluralaner, afoxolaner, sarolaner and moxidectin) currently used in dogs for other purposes (e.g. tick, flea control) in controlling ZVL transmission. The anti-phlebotomine capacity of these compounds confirmed in experimental studies makes their use in ZVL control programmes very promising. Limitations and benefits of using this new control tool are compared to current practices.

Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.

PURPOSE: To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization. METHODS: The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression. RESULTS: In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization. CONCLUSIONS: The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term.

Pyrethroids and DDT tolerance of Anopheles gambiae s.l. from Sengerema District, an area of intensive pesticide usage in north-western Tanzania.

OBJECTIVE: To assess the susceptibility status of malaria vectors to pyrethroids and dichlorodiphenyltrichloroethane (DDT), characterise the mechanisms underlying resistance and evaluate the role of agro-chemical use in resistance selection among malaria vectors in Sengerema agro-ecosystem zone, Tanzania. METHODS: Mosquito larvae were collected from farms and reared to obtain adults. The susceptibility status of An. gambiae s.l. was assessed using WHO bioassay tests to permethrin, deltamethrin, lambdacyhalothrin, etofenprox, cyfluthrin and DDT. Resistant specimens were screened for knock-down resistance gene (kdr), followed by sequencing both Western and Eastern African variants. A gas chromatography-mass spectrophotometer (GC-MS) was used to determine pesticide residues in soil and sediments from mosquitoes' breeding habitats. RESULTS: Anopheles gambiae s.l. was resistant to all the insecticides tested. The population of Anopheles gambiae s.l was composed of Anopheles arabiensis by 91%. The East African kdr (L1014S) allele was found in 13 of 305 specimens that survived insecticide exposure, with an allele frequency from 0.9% to 50%. DDTs residues were found in soils at a concentration up to 9.90 ng/g (dry weight). CONCLUSION: The observed high resistance levels of An. gambiae s.l., the detection of kdr mutations and pesticide residues in mosquito breeding habitats demonstrate vector resistance mediated by pesticide usage. An integrated intervention through collaboration of agricultural, livestock and vector control units is vital.

Incremental cost of implementing residual insecticide treatment with delthametrine on top of intensive routine Aedes aegypti control.

OBJECTIVE: Information on the cost of implementing residual insecticide treatment (RIT) for Aedes control is scarce. We evaluated the incremental cost on top of intensive conventional routine activities of the Aedes control programme (ACP) in the city of Santiago de Cuba, Cuba. METHODS: We conducted the cost analysis study in 2011-2012, from the perspective of the ACP. Data sources were bookkeeping records, activity registers of the Provincial ACP Centre and the accounts of an RIT implementation study in 21 clusters of on average four house blocks comprising 5180 premises. RESULTS: The annual cost of the routine ACP activities was 19.66 US$ per household. RIT applications in rounds at 4-month intervals covering, on average, 97.2% and using 8.5 g of delthametrine annually per household, cost 3.06 US$ per household per year. Delthametrine comprised 66.5% of this cost; the additional cost for deploying RIT comprised 15.6% of the total ACP routine cost and 27% of the cost related to routine adult stage Aedes control. CONCLUSIONS: The incremental cost of implementing RIT is high. It should be weighed against the incremental effect on the burden caused by the array of pathogens transmitted by Aedes. The cost could be reduced if the insecticide became cheaper, by limiting the number of yearly applications or by targeting transmission hot spots.

Biotherapies for Parkinson disease.

The clinical use of biotherapies in Parkinson disease already has 30 years' history. The transplantation of dopamine fetal cells in the striatum of advanced patients has proved to be relevant in some patients but randomized efficacy trials in the US have provided disappointing results. However, cell therapies might come back on stage with the use of stem cells in the future. Gene therapy is a more recent strategy relying on viral vectors able to transduce genes coding either for the enzymes that can increase neurotransmitters production or genes for trophic factors. Several approaches have been developed in PD and have been experimented in patients. Although, some of the studies have evidenced insufficient clinical benefit, other programs, such as those using dopamine replacement techniques are promising. We find fresh hope in this field that might be the future of PD treatment. It remains however that advanced PD might not be the ideal condition to properly benefit from biotherapies and there is a need of studies at earlier stages of the disease, a time where major change in the disease course might be expected.

Gene therapy of the central nervous system: general considerations on viral vectors for gene transfer into the brain.

The last decade has nourished strong doubts on the beneficial prospects of gene therapy for curing fatal diseases. However, this climate of reservation is currently being transcended by the publication of several successful clinical protocols, restoring confidence in the appropriateness of therapeutic gene transfer. A strong sign of this present enthusiasm for gene therapy by clinicians and industrials is the market approval of the therapeutic viral vector Glybera, the first commercial product in Europe of this class of drug. This new field of medicine is particularly attractive when considering therapies for a number of neurological disorders, most of which are desperately waiting for a satisfactory treatment. The central nervous system is indeed a very compliant organ where gene transfer can be stable and successful if provided through an appropriate strategy. The purpose of this review is to present the characteristics of the most efficient virus-derived vectors used by researchers and clinicians to genetically modify particular cell types or whole regions of the brain. In addition, we discuss major issues regarding side effects, such as genotoxicity and immune response associated to the use of these vectors.