Vector-borne disease is one of the greatest contributors to human mortality and morbidity throughout the tropics. Mosquito-transmitted diseases such as malaria, dengue, yellow fever and filariasis are the main contributors to this burden. Although insecticides have historically been used to try to control vector populations, over the past 15 years, substantial progress has been made in developing alternative vector control strategies ranging from biocontrol methods through to genetic modification of wild insect populations. Here, we review recent advances concerning these strategies and consider the potential impediments to their deployment, including the challenges of obtaining regulatory approval and community acceptance.

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Beyond insecticides: new thinking on an ancient problem

There are alarming reports of growing microbial resistance to all classes of antimicrobial agents used against different infections. Also the existing classes of anticancer drugs used against different tumours warrant the urgent search for more effective alternative agents for treatment. Broad-spectrum bioactivities of silver nanoparticles indicate their potential to solve many microbial resistance problems up to a certain extent. The antibacterial, antifungal, antiviral, antiprotozoal, acaricidal, larvicidal, lousicidal and anticancer activities of silver nanoparticles have recently attracted the attention of scientists all over the world. The aim of the present review is to discuss broad-spectrum multifunctional activities of silver nanoparticles and stress their therapeutic potential as smart nanomedicine. Much emphasis has been dedicated to the antimicrobial and anticancer potential of silver nanoparticles showing their promising characteristics for treatment, prophylaxis and control of infections, as well as for diagnosis and treatment of different cancer types.

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Broad-spectrum bioactivities of silver nanoparticles: the emerging trends and future prospects

The fight against diseases spread by mosquitoes and other insects has enormous environmental, economic and social consequences. Chemical insecticides remain the first line of defence but the control of diseases, especially malaria and dengue fever, is being increasingly undermined by insecticide resistance. Mosquitoes have a large repertoire of P450s (over 100 genes). By pinpointing the key enzymes associated with insecticide resistance we can begin to develop new tools to aid the implementation of control interventions and reduce their environmental impact on Earth. Recent technological advances are helping us to build a functional profile of the P450 determinants of insecticide metabolic resistance in mosquitoes. Alongside, the cross-responses of mosquito P450s to insecticides and pollutants are also being investigated. Such research will provide the means to produce diagnostic tools for early detection of P450s linked to resistance. It will also enable the design of new insecticides with optimized efficacy in different environments.

https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2012.0429

Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth

Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic ﬁlariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases andvectorcontrolisstillthemainformofprevention. Thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in signiﬁcant efforts to develop alternative eco-friendly methods. Biocontrol strategies aim to be sustainable and target a range of different mosquito species to reduce the current reliance on insecticide-based mosquito control. In thisreview, weoutline non-insecticide basedstrategiesthat havebeenimplemented orare currently being tested. We also highlight the use of mosquito behavioural knowledge that can be exploited for control strategies.

https://arpi.unipi.it/bitstream/11568/810174/2/Benelli_810174.pdf

Biological Control of Mosquito Vectors: Past, Present, and Future

The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium These engineered P agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98% Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)4, four copies of Plasmodium enolase–plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P falciparum in the mosquito These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria

https://www.pnas.org/content/pnas/109/31/12734.full.pdf

Fighting malaria with engineered symbiotic bacteria from vector mosquitoes

Malaria is one of the most common vector-borne diseases widespread in the tropical and subtropical regions. Despite considerable success of malaria control programs in the past, malaria still continues as a major public health problem in several countries. Vector control is an essential part for reducing malaria transmission and became less effective in recent years, due to many technical and administrative reasons, including poor or no adoption of alternative tools. Of the different strategies available for vector control, the most successful are indoor residual spraying and insecticide-treated nets (ITNs), including long-lasting ITNs and materials. Earlier DDT spray has shown spectacular success in decimating disease vectors but resulted in development of insecticide resistance, and to control the resistant mosquitoes, organophosphates, carbamates, and synthetic pyrethroids were introduced in indoor residual spraying with needed success but subsequently resulted in the development of widespread multiple insecticide resistance in vectors. Vector control in many countries still use insecticides in the absence of viable alternatives. Few developments for vector control, using ovitraps, space spray, biological control agents, etc., were encouraging when used in limited scale. Likewise, recent introduction of safer vector control agents, such as insect growth regulators, biocontrol agents, and natural plant products have yet to gain the needed scale of utility for vector control. Bacterial pesticides are promising and are effective in many countries. Environmental management has shown sufficient promise for vector control and disease management but still needs advocacy for inter-sectoral coordination and sometimes are very work-intensive. The more recent genetic manipulation and sterile insect techniques are under development and consideration for use in routine vector control and for these, standardized procedures and methods are available but need thorough understanding of biology, ethical considerations, and sufficiently trained manpower for implementation being technically intensive methods. All the methods mentioned in the review that are being implemented or proposed for implementation needs effective inter-sectoral coordination and community participation. The latest strategy is evolution-proof insecticides that include fungal biopesticides, Wolbachia, and Denso virus that essentially manipulate the life cycle of the mosquitoes were found effective but needs more research. However, for effective vector control, integrated vector management methods, involving use of combination of effective tools, is needed and is also suggested by Global Malaria Control Strategy. This review article raises issues associated with the present-day vector control strategies and state opportunities with a focus on ongoing research and recent advances to enable to sustain the gains achieved so far.

Malaria vector control: from past to future

Background: Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods: Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. Results: A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively) and An. stephensi strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m 2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies. Potentiation studies demonstrated the antagonistic effect of PBO. Conclusion: Laboratory studies with susceptible and resistant strains of An. culicifacies and An. stephensi, coupled with limited field studies with multiple insecticide-resistant An. culicifacies have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.

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Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors.

The use of frogs and tadpoles for disease vector control is still largely unexplored. Frogs are an important part of the ecosystem with a role for insect and pest control including mosquitoes. Available information suggests the existence of many direct and indirect factors affecting the growth and survival of both prey and predators. Other controphic species that have influence on this relationship also show considerable effect. Still, the associations of different prey and predator relationships in the environment to assess the feasibility of use of a species as biocontrol agent for vector control and management. However, frogs cannot be used as an independent intervention for disease vector control and more research is needed to use them effectively for mosquito control.

Biological control of mosquito populations through frogs: opportunities & constrains.

Co-inoculation of indigenous Pseudomonas oryzihabitans and Bradyrhizobium sp. modulates the growth, symbiotic efficacy, nutrient acquisition, and grain yield of soybean

Over the last few years, the microbiome has emerged as a high-priority research area to discover missing links between brain health and gut dysbiosis. Emerging evidence suggests that the commensal gut microbiome is an important regulator of the gut–brain axis and plays a critical role in brain physiology. Engaging microbiome-generated metabolites such as short-chain fatty acids, the immune system, the enteric nervous system, the endocrine system (including the HPA axis), tryptophan metabolism or the vagus nerve plays a crucial role in communication between the gut microbes and the brain. Humans are exposed to a wide range of pollutants in everyday life that impact our intestinal microbiota and manipulate the bidirectional communication between the gut and the brain, resulting in predisposition to psychiatric or neurological disorders. However, the interaction between xenobiotics, microbiota and neurotoxicity has yet to be completely investigated. Although research into the precise processes of the microbiota–gut–brain axis is growing rapidly, comprehending the implications of environmental contaminants remains challenging. In these milieus, we herein discuss how various environmental pollutants such as phthalates, heavy metals, Bisphenol A and particulate matter may alter the intricate microbiota–gut–brain axis thereby impacting our neurological and overall mental health.

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Poonam Sharma

Papers

Malaria vector control: from past to future

Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors.

Biological control of mosquito populations through frogs: opportunities & constrains.

Co-inoculation of indigenous Pseudomonas oryzihabitans and Bradyrhizobium sp. modulates the growth, symbiotic efficacy, nutrient acquisition, and grain yield of soybean

Impact of Environmental Pollutants on Gut Microbiome and Mental Health via the Gut–Brain Axis