A team of researchers at the National Institute of Infectious Diseases in Japan has just found a new gene mutation in the Aedes aegypti mosquito that causes dengue fever, which is highly resistant to common insecticides. The increase in the number of Aedes aegypti mosquitoes that can resist insecticides in Southeast Asia, in which more than 80% of Aedes aegypti mosquitoes circulating in Vietnam and Cambodia were found to have this gene mutation. The study showed that even when the concentration of insecticide was raised 10 times higher than the concentration that can kill normal mosquitoes, about 80% of the mosquitoes collected in Hanoi still survived.
According to the research team, a new gene mutation called L982W has been identified, making mosquitoes more resistant to conventional insecticides. About 78‐99% of mosquitoes in three areas including Hanoi, Ho Chi Minh City and the capital Phnom Penh (Cambodia) have this gene mutation. Including L982W, all four current gene mutations are resistant to insecticides. The proportion of mosquitoes with 2/4 gene mutations is 91% in Phnom Penh, which shows that the resistance of mosquitoes is getting stronger.
According to the research team, it is possible that insecticide‐resistant mosquitoes have spread from Cambodia to Vietnam. Although mosquitoes carrying the L982W gene mutation have not been found in Laos, Thailand and China, this mosquito species may be spreading throughout the Indochina peninsula and other areas in Asia. In addition, Japan has also begun to worry about mosquitoes. Aedes aegypti as areas where mosquitoes can survive the winter are expanding as temperatures warm. Mr. Takeshi Kasai (World Health Organization ‐ Western Pacific Regional Director) emphasized the need to closely examine how insecticide‐resistant mosquitoes are spreading across the Indochina peninsula as well as how to reduce the use of pyrethroid insecticides, a widely used chemical.
Figure 1. Patterns of mosquito interactions and resistance to insecticides | Source: Frontier, 2021
Control and Management Strategy vector dengue fever
Prevention or reduction of dengue virus transmission depends entirely on controlling the mosquito vector or interrupting human‐vector exposure. Transmission control activities focus on the primary vector. Ae. aegypti in the adult and larvae habitats in households and neighbourhoods as well as other environments where human‐vector contact occurs (e.g. schools, hospitals and workplaces), unless there is clear evidence that Ae. albopictus or other mosquito species that are vectors of dengue fever locally.
Ae. aegypti present in many household water containers, household water containers and ornamental plants as well as rainwater containers in the living environment, including used tires, discarded food and beverage containers, clogged gutters, water trays behind refrigerators, glasses of water left on altars for a long time, water containers of dehumidifiers, water fans, etc.
Figure 2. Multidrug resistance and the kdr V410L mutation | Source: Parasites and Vectors, 2021
Usually, these mosquitoes do not fly far, but mostly stay within 100 meters of where they appear. They prefer to bite human blood, mainly during the day, both indoors and outdoors. Mosquito Ae. aegypti are controlled primarily by eliminating habitat in water bodies where they lay eggs and develop.
Habitat is eliminated by preventing mosquitoes from accessing these containers and cleaning them regularly. Development is prevented by using insecticides or biological control agents, killing adult mosquitoes with insecticides, or a combination of all methods.
Figure 3. Pyrethroid Resistance in Aedes aegypti and Aedes albopictus | Source: Science Direct, 2020
Nested or integrated vector management (Intergrated Vector Management‐IVM) is a vector control strategy developed by the World Health Organization.(TCYTTG) promotion, which includes dengue vector control, is understood as “The process of managing resources involved in implementing vector control effectively, IVM considers five key elements in the management process, which are:
· Advocacy for social policies and enforcement of laws ‐ Promote these principles in the development policies of all relevant agencies and organizations; establish or strengthen regulatory controls for public health and community empowerment;;
·Collaboration within health and with other sectors ‐Consider all options for collaboration between the public and private sectors; plan and make decisions at the lowest administrative level. Enhance communication between policy makers, vector‐borne disease control program managers and other key partners;
·Integrated approach to disease control ‐ Ensure rational use of available resources by adopting a disease control approach. Use chemical vector control measures and integrate them with other disease control measures;
· Evidence‐based decision making ‐ Tailor strategies and interventions to vector ecology, epidemiology and local resources through regular monitoring and evaluation operational research;
·Capacity building and strengthening ‐ Develop essential infrastructure, financial resources and appropriate human resources at national and local levels to manage IVM programmes;
Figure 4. Mechanisms of insecticide resistance in Aedes aegypti mosquitoes | Source: Frontier, 2020
The IVM vector control and management strategy is divided into a number of activities in various areas such as entomology, epidemiology, communication, training and services, transport, administration and finance. Some of the activities include interventions such as:
1. Environmental Management
·Improve water supply and storage systems;
· Handling of water‐containing tools and objects;
· Solid waste management ‐ non‐biodegradable items;
· Street cleaning;
·Construction management.
2. Control of chemicals to kill larvae and adult mosquitoes
·File management;
·Research and monitor target areas;
·Control chemical type and usage cycle;
·Instructions for use and safety precautions;
·Chemical Residue Treatment;
·Chemical spraying method.
3. Assessment of insecticide susceptibility
·Purchase of standard test instruments and papers;
· Test and evaluate sensitivity to each chemical.
4. Biological control
· Fish farming;
· Using crustaceans that eat mosquito larvae.
5. Research on innovative tools for vector control
· Materials treated with insecticide;
·Egg trapping ‐ kills populations Ae. aegypti in larval or adult stage.
6. Improve knowledge and awareness
· Propaganda, training skills and knowledge on vector control;
·Organize regular courses..
7. Manufacture
·Repellent and exterminating products;
· Preventive and protective equipment.
8. Intra‐industry and cross‐industry cooperation
· Technology transfer;
· Support, funding;
·Organize seminars, community sharing;
·Links with government and non‐government organizations.
When selecting an appropriate vector control method or combination of methods, consideration should be given to whether they will affect the local ecology and behaviour of the target species, the resources available, the cultural context in which the interventions are implemented, the feasibility of timely application and the extent of coverage.
Figure 5. Problems arising from the development of insecticide resistance in mosquitoes |Source: Science Direct, 2020
In addition, the Vector Control and Management Strategy needs to be clearly and specifically allocated to each activity, each agency, including cooperation within the health sector and across sectors. Strategies aimed at this goal require a thorough understanding of the local vector ecology as well as people’s attitudes and habits towards the reservoirs ‐ the places where vectors live and breed.
Figure 6. Investigating the molecular basis of multidrug resistance | Source: Parasites and Vectors, 2022
Human body odor is important for long‐distance host‐seeking behavior of mosquitoes.
We’ve long known a lot about mosquitoes’ preferences for proximity, but how do they find us from hundreds of meters away? Using an outdoor test site the size of an ice rink in Zambia, researchers found that human body odor is crucial to mosquitoes’ long‐distance host‐seeking behavior. The team also identified specific “body odor components” in the air that could explain why some people are more attractive to mosquitoes than others. The work was published in the journal Current Biology.
Most studies on mosquito preferences have been conducted in limited laboratory settings that may not reflect the mosquito’s experience in the wild. To test how African malaria mosquitoes Anopheles gambiae searchMost studies on mosquito preferences have been conducted in limited laboratory settings that may not reflect the mosquito’s experience in the wild. To test how African malaria mosquitoes Anopheles gambiae seek out and select human hosts on a larger, more realistic spatial scale, researchers from the Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health and the Macha Research Trust collaborated to build a 1,000 m3 test site in Choma District, Zambia. This is the world’s largest system for assessing mosquito odor preferences., neuroscientist Diego Giraldo ‐ postdoctoral fellow at Johns Hopkins Bloomberg School of Public Health, one of the study’s first authors, said, “And for mosquitoes, it’s a very busy sensory environment..”
The test area consisted of a circle of evenly spaced landing pads heated to human skin temperature (35ºC). Each night, the researchers released 200 hungry mosquitoes into the test area and tracked their activity using infrared motion cameras. They then recorded how often the mosquitoes landed on each pad (a good sign that they were ready to bite) in some detail. First, the team compared the relative importance of temperature, CO2, and human body odor for attracting mosquitoes. They found that mosquitoes were not attracted to the heated landing pads unless CO2 was added as a lure, but that body odor was a more attractive lure than CO2.
Next, the team tested the mosquitoes’ “choosiness.” To do this, they put six people in single‐person tents around the test site for six consecutive nights and used an air‐conditioning duct system to direct air from each tent, containing the scent of the people sleeping in the tent, into heated landing pads. In addition to recording the mosquitoes’ preferences, the researchers also collected nightly air samples from the tents to analyze and compare the components emitted by body odor. Mosquitoes hunt in the hours before and after midnight. They follow human scent and typically fly into homes and bite people between 10 p.m. and 2 a.m., so the researchers wanted to assess the olfactory preferences of mosquitoes during their peak activity period when they are out and about, and also assess the odors from sleeping humans during that time, said senior author and vector biologist Conor McMeniman, an assistant professor at the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins Malaria Research Institute.
They found that some people were more attractive to mosquitoes than others over the course of the night, while a volunteer with a different odor attracted very few mosquitoes. The scientists identified 40 chemicals emitted by humans at different levels. “It could be a specific mix of chemicals that mosquitoes are following,” said Stephanie Rankin‐Turner, PhD, a postdoctoral fellow at the Johns Hopkins Bloomberg School of Public Health, another first author of the study. “We don’t know exactly what skin secretions, microbial metabolites, or emissions are causing this. We hope to figure that out in the coming years.”
Although each person’s scent changed from night to night, the researchers found some consistent patterns. Those who were more attractive to mosquitoes consistently emitted more carboxylic acid, which may be produced by bacteria on their skin. Conversely, those who were least attractive to mosquitoes emitted less carboxylic acid but roughly three times more eucalyptol. It’s a compound found in many plants. The elevated levels may be related to diet, but the authors weren’t sure.
The researchers were surprised by the mosquitoes’ ability to search and choose between potential blood meals in a large area. “When you see something that contains scents that are transported from a small lab space and the mosquitoes are still finding those scents in this large space in a field in Zambia, it really shows how powerful host seekers mosquitoes are,” says Rankin‐Turner.
REFERENCES
1.Giraldo, D., et al. (2023) Human scent guides mosquito thermotaxis and host selection under naturalistic conditions. Current Biology. doi.org/10.1016/j.cub.2023.04.050.
2.Borel Djiappi‐Tchamen, Mariette Stella Nana‐Ndjangwo, Konstantinos Mavridis, Abdou Talipouo, Elysée Nchoutpouen, Idene Makoudjou, Roland Bamou, Audrey Marie Paul Mayi, Parfait Awono‐Ambene, Timoléon Tchuinkam, John Vontas, Christophe Antonio‐Nkondjio (2021). Analyses of insecticide resistance genes in Aedes aegypti and Aedes albopictus mosquito populations from Cameroon. Genes (Basel). 2021 Jun; 12(6): 828.
3.Mas Azlin M. Akhir, Mustafa F. F. Wajidi, Sébastien Lavoué, Ghows Azzam, Izhan Shahrin Jaafar, Noor Aslinda Ummi Awang Besar, Intan H. Ishak (2022). Knockdown resistance (kdr) gene of Aedes aegypti in Malaysia with the discovery of a novel regional specific point mutation A1007G. Parasites & Vectors volume 15, Article number: 122 (2022).
4.R Rebecca Love, Josh R Sikder, Rafael J Vivero, Daniel R Matute, Daniel R Schrider (2023). Strong positive selection in Aedes aegypti and the rapid evolution of insecticide resistance. Molecular Biology and Evolution, Volume 40, Issue 4, April 2023, msad072.
5.PanelM.M. Rodríguez, A. Ruiz, L. Piedra, G. Gutierrez, J. Rey, M. Cruz, J.A. Bisset (2020). Multiple insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Boyeros municipality, Cuba and associated mechanisms. Acta Tropica, Volume 212, December 2020, 105680.
