Giovanni Benelli

Research in mosquito control: current challenges for a brighter future

Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating pathogens and parasites. In this scenario, vector control is crucial. Mosquito larvae are usually targeted using organophosphates, insect growth regulators, and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment and induce resistance in a number of vectors. Newer and safer tools have been recently implemented to enhance control of mosquitoes. Here, I focus on some crucial challenges about eco-friendly control of mosquito vectors, mainly the improvement of behavior-based control strategies (sterile insect technique (“SIT”) and “boosted SIT”) and plant-borne mosquitocidals, including green-synthesized nanoparticles. A number of hot areas that need further research and cooperation among parasitologists, entomologists, and behavioral ecologists are highlighted.

Plant-borne ovicides in the fight against mosquito vectors of medical and veterinary importance: a systematic review

Mosquitoes (Diptera: Culicidae) are a huge threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. Culicidae control is of crucial importance. Mosquito eggs, larvae, and pupae are usually targeted using organophosphates, insect growth regulators, and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment, and induce resistance in a number of species. Eco-friendly tools have been recently implemented against mosquito vectors, including botanical insecticides. The majority of researches focused on larvicides (745 SCOPUS results, July 2015) and adult repellents (434 SCOPUS results), while limited efforts were conducted to identify effective ovicides of botanical origin (59 SCOPUS results). Here, I review current knowledge on the effectiveness of plant-borne ovicides against major mosquito vectors of medical and veterinary importance. The majority of researches focused on the toxicity of crude extracts, their fractions, or essential oils against three important mosquito vectors, Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus. As a general trend, C. quinquefasciatus eggs were the most resistant to botanical ovicides. Five studies proposed selected compounds from plant extracts and essential oils as ovicides effective at few parts per million. However, no efforts were conducted to shed light on possible mechanisms underlying the toxicity of plant-borne ovicides. In the final section, a number of hot issues needing further research and cooperation among parasitologists, entomologists, and researchers working in natural product chemistry are outlined.

Green synthesized nanoparticles in the fight against mosquito-borne diseases and cancer-a brief review.

Nanobiomedicine and parasitology are facing a number of key challenges, which mostly deal with the paucity of effective preventive and curative tools against mosquito-borne diseases and cancer. In this scenario, the employ of botanical and invertebrate extracts as reducing, stabilizing and capping agents for the synthesis of nanoparticles is advantageous over chemical and physical methods, since it is one-pot, cheap, and does not require high pressure, energy, temperature, or the use of highly toxic chemicals. Considering the overlooked connection between mosquito vector activity and the spread of cancer in USA, this review focused on the current knowledge available about green synthesized nanoparticles with efficacy against mosquito-borne diseases and cancer. Green fabricated metal nanoparticles showed antiplasmodial activity that often encompasses the efficacy of currently marked drugs for malaria treatment. They have been also reported as growth inhibitors against dengue virus (serotype DEN-2), with moderate cytotoxicity on mammalian cells. However, this feature is strongly dependent to the botanical agents employed during nanosynthesis. In addition, green nanoparticles have been successfully used to reduce mosquito young instar populations in the field. The final section focuses on some issues for future research, with special reference to the chemical standardization of the botanical extracts used for nanosynthesis and the potential effects on green fabricated nanoparticles on non-target organisms.

Cymbopogon citratus-synthesized gold nanoparticles boost the predation efficiency of copepod Mesocyclops aspericornis against malaria and dengue mosquitoes

Plant-borne compounds can be employed to synthesize mosquitocidal nanoparticles that are effective at low doses. However, how they affect the activity of mosquito predators in the aquatic environment is unknown. In this study, we synthesized gold nanoparticles (AuN) using the leaf extract of Cymbopogon citratus, which acted as a reducing and capping agent. AuN were characterized by a variety of biophysical methods and sorted for size in order to confirm structural integrity. C. citratus extract and biosynthesized AuN were tested against larvae and pupae of the malaria vector Anopheles stephensi and the dengue vector Aedes aegypti. LC₅₀ of C. citratus extract ranged from 219.32 ppm to 471.36 ppm. LC₅₀ of AuN ranged from 18.80 ppm to 41.52 ppm. In laboratory, the predatory efficiency of the cyclopoid crustacean Mesocyclops aspericornis against A. stephensi larvae was 26.8% (larva I) and 17% (larva II), while against A. aegypti was 56% (I) and 35.1% (II). Predation against late-instar larvae was minimal. In AuN-contaminated environment,predation efficiency against A. stephensi was 45.6% (I) and 26.7% (II), while against A. aegypti was 77.3% (I) and 51.6% (II). Overall, low doses of AuN may help to boost the control of Anopheles and Aedes larval populations in copepod-based control programs.

Essential Oils as Ecofriendly Biopesticides? Challenges and Constraints

Recently, a growing number of plant essential oils (EOs) have been tested against a wide range of arthropod pests with promising results. EOs showed high effectiveness, multiple mechanisms of action, low toxicity on non-target vertebrates and potential for the use of byproducts as reducing and stabilizing agents for the synthesis of nanopesticides. However, the number of commercial biopesticides based on EOs remains low. We analyze the main strengths and weaknesses arising from the use of EO-based biopesticides. Key challenges for future research include: (i) development of efficient stabilization processes (e.g., microencapsulation); (ii) simplification of the complex and costly biopesticide authorization requirements; and (iii) optimization of plant growing conditions and extraction processes leading to EOs of homogeneous chemical composition.

Mosquito vectors and the spread of cancer: an overlooked connection?

Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, vectoring important pathogens and parasites, including malaria, dengue, filariasis, and Zika virus. Besides mosquito-borne diseases, cancers figure among the leading causes of mortality worldwide. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Notably, there are few contrasting evidences of the relationship between cancer and mosquito-borne diseases, with special reference to malaria. However, analogies at the cellular level for the two diseases were reported. Recently, a significant association of malaria incidence with all cancer mortality in 50 USA states was highlighted and may be explained by the ability of Plasmodium to induce suppression of the immune system. However, it was hypothesized that Anopheles vectors may transmit obscure viruses linked with cancer development. The possible activation of cancer pathways by mosquito feeding events is not rare. For instance, the hamster reticulum cell sarcoma can be transmitted through the bites of Aedes aegypti by a transfer of tumor cells. Furthermore, mosquito bites may influence human metabolic pathways following different mechanisms, leading to other viral infections and/or oncogenesis. Hypersensitivity to mosquito bites is routed by a unique pathogenic mechanism linking Epstein–Barr virus infection, allergy, and oncogenesis. During dengue virus infection, high viral titers, macrophage infiltration, and tumor necrosis factor alpha production in the local tissues are the three key important events that lead to hemorrhage. Overall, basic epidemiological knowledge on the relationships occurring between mosquito vector activity and the spread of cancer is urgently needed, as well as detailed information about the ability of Culicidae to transfer viruses or tumor cells among hosts over time. Current evidences on nanodrugs with multipotency against mosquito-borne diseases and cancers are reviewed, with peculiar attention to their mechanisms of action.

Old ingredients for a new recipe? Neem cake, a low-cost botanical by-product in the fight against mosquito-borne diseases

Mosquitoes (Diptera: Culicidae) represent an important threat to millions of people worldwide, since they act as vectors for important pathogens, such as malaria, yellow fever, dengue and West Nile. Control programmes mainly rely on chemical treatments against larvae, indoor residual spraying and insecticide-treated bed nets. In recent years, huge efforts have been carried out to propose new eco-friendly alternatives, with a special focus on the evaluation of plant-borne mosquitocidal compounds. Major examples are neem-based products (Azadirachta indica A. Juss, Meliaceae) that have been proven as really effective against a huge range of pests of medical and veterinary importance, including mosquitoes. Recent research highlighted that neem cake, a cheap by-product from neem oil extraction, is an important source of mosquitocidal metabolites. In this review, we examined (i) the latest achievements about neem cake metabolomics with special reference to nor-terpenoid and related content; (ii) the neem cake ovicidal, larvicidal and pupicidal toxicity against Aedes, Anopheles and Culex mosquito vectors; (iii) its non-target effects against vertebrates; and (iv) its oviposition deterrence effects on mosquito females. Overall, neem cake can be proposed as an eco-friendly and low-cost source of chemicals to build newer and safer control tools against mosquito vectors.

Ethnobotanical knowledge on botanical repellents employed in the African region against mosquito vectors - A review.

Mosquitoes (Diptera: Culicidae) represent a huge threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and important arboviruses, such as dengue, West Nile and Zika virus. No vaccines or other specific treatments are available against the arboviruses transmitted by mosquitoes, and avoidance of mosquito bites remains the best strategy. African regions are usually hit most whose inhabitants are poor, and the use of repellent plants is the only efficient protection against vectors they have. Ethnobotanical knowledge of such plants and their use is usually passed on orally from one generation to another. However, it is also important to preserve this information in a written form, as well. Ethnobotanical research projects carried out in the regions of todays Ethiopia, South Africa, Nigeria, Kenya, and Tanzania indicate that the native inhabitants of the African study regions traditionally use 64 plant species, belonging to 30 families. Aromatic plants (i.e., Citrus spp., Eucalyptus spp., Lantana camara, Ocimum spp. and Lippia javanica) the most commonly used in all the study regions. Native people know three major methods of using repellent plants: (i) production of repellent smoke from burning plants, (ii) hanging plants inside the house or sprinkling leaves on the floor, (iii) the use of plant oils, juices from crushed fresh parts of the plants, or various prepared extracts applied on uncovered body parts. Overall, this review covers studies conducted only in a limited part of the African continent, highlighting the importance to undertake further research efforts to preserve the unique knowledge and traditions of the native tribes.

Commentary: Making Green Pesticides Greener? The Potential of Plant Products for Nanosynthesis and Pest Control

The resurgence of interest on natural substances and their progressive affirmation in the market open doors for novel marketed products, with intrinsic original approaches. Evident examples are in the food supplements sector as well as in mix of synthetic drugs and natural substances, as novel drugs. A decisive key role will be played by technology and the capacity of throw novel opportunities out of the normal landscape. As in other fields, most of the future technology developments rely on nanotechnology. In this Commentary, after the discussion focused on the novel roles of natural products, we report the recent results in the application of nanotechnology in one of the most relevant challenge for mankind, consisting in the resurgence of important vector-borne diseases and emergence of new epidemic alerts. In particular, the green synthesis of nanopesticides is cheap and environmental friendly, since it does not require the employment of highly toxic chemicals or elevate energy inputs. In the conclusions, a brief agenda summarizing the challenges for nano-based pest control is outlined.

Current vector control challenges in the fight against malaria

The effective and eco-friendly control of Anopheles vectors plays a key role in any malaria management program. Integrated Vector Management (IVM) suggests making use of the full range of vector control tools available. The strategies for IVM require novel technologies to control outdoor transmission of malaria. Despite the wide number of promising control tools tested against mosquitoes, current strategies for malaria vector control used in most African countries are not sufficient to achieve successful malaria control. The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS. Larvicidal treatments can be useful, but are not recommended for rural areas. The research needed to improve the quality and delivery of mosquito vector control should focus on (i) optimization of processes and methods for vector control delivery; (ii) monitoring of vector populations and biting activity with reliable techniques; (iii) the development of effective and eco-friendly tools to reduce the burden or locally eliminate malaria and other mosquito-borne diseases; (iv) the careful evaluation of field suitability and efficacy of new mosquito control tools to prove their epidemiological impact; (v) the continuous monitoring of environmental changes which potentially affect malaria vector populations; (vi) the cooperation among different disciplines, with main emphasis on parasitology, tropical medicine, ecology, entomology, and ecotoxicology. A better understanding of behavioral ecology of malaria vectors is required. Key ecological obstacles that limit the effectiveness of vector control include the variation in mosquito behavior, development of insecticide resistance, presence of behavioral avoidance, high vector biodiversity, competitive and food web interactions, lack of insights on mosquito dispersal and mating behavior, and the impact of environmental changes on mosquito ecological traits. Overall, the trans-disciplinary cooperation among parasitologists and entomologists is crucial to ensure proper evaluation of the epidemiological impact triggered by novel mosquito vector control strategies.