The species has now reached at least 17 California counties and its successful spread may be linked to its resistance to pyrethroids, according to newly published UC Davis research examining genetic markers of resistance at five state locations.
The work, published in the current edition of Parasites & Vectors, a BioMed Central open-access medical journal, focuses on “determining how informative well-established genetic markers of resistance to pyrethroids are in predicting the resistance phenotype of individual mosquitoes of Aedes aegypti within a population,” said Attardo, the lead author.
“Specifically, we generated mosquito colonies from invasive A. aegypti populations from four locations in the Central Valley (Dinuba, Clovis, Sanger and Kingsburg) and from collections in the Greater Los Angeles Area,” he said. “Mosquitoes from these populations have all demonstrated resistance to pyrethroid-type insecticides and we think this may be part of the reason why these mosquitoes have been so successful in spreading throughout California.”
A. aegypti transmits such viruses as dengue, Zika, chikungunya, and yellow fever. Despite California's aggressive surveillance and treatment efforts, this species presents a “significant challenge to local control agencies,” the nine-member team wrote in their research paper, “Frequency of Sodium Channel Genotypes and Association with Pyrethrum Knockdown Time in Populations of Californian Aedes aegypti.“
The paper is online and publicly accessible at https://bit.ly/3vmUxXR.
“What was interesting was that while all the mosquitoes from California show resistance to pyrethroids, there is a lot of variability from one individual to the next in terms of the level of resistance, even when they are carrying genetically identical resistance mutations,” Attardo said. “In particular, there seem to be two levels of resistance in these populations. The two levels seem to represent a resistant group and a super resistant group. However, the proportions of resistant/super-resistant differ in the sampled mosquitoes from population to population.”
Of particular interest was that mosquitoes carrying the resistance mutations at all five genetic locations were very resistant, he said. “However, there was also a large amount of unexplained variability in terms of the knockdown phenotypes demonstrated by mosquitoes of the same age and rearing conditions. We compared the knockdown times of mosquitoes positive for all five resistance mutations from different populations and found that these mutations account for only a proportion of the observed level of resistance. We believe that the unexplained variability is likely being mediated by the presence or absence of an undefined resistance mechanism.”
Although A. aegypti was first detected in California in 2013, researchers believe that its arrival involved multiple introductions. Populations in Southern California are thought to have crossed the border from Mexico, while Central Valley populations may have been introduced, in part, from the southeastern United States.
“Upon detection in 2013, the Consolidated Mosquito Abatement District implemented an integrated vector control management strategy which involved extensive public education, thorough property inspections, sanitation, insecticide treatment at larval sources and residual barrier spraying with pyrethroids,” the authors wrote. Despite their efforts, the species successfully overwintered and continued to spread, implicating that it arrived in California with genetic mutations “conferring resistance to the type I pyrethroid insecticides applied for vector control in California.”
The co-authors include former UC Davis mosquito researcher Yoosook Lee, now at the University of Florida-Florida Medical Entomology Laboratory, Vero Beach; research entomologist Anthony Cornel and staff research associate Katherine Brisco of the Mosquito Control Research Laboratory, Kearney Agriculture and Extension Center and UC Davis Department of Entomology and Nematology; and Lindsey Mack, Erin Taylor Kelly, Katherine Brisco, Kaiyuan Victoria Shen, Aamina Zahid, and Tess van Schoor, all with the UC Davis Department of Entomology and Nematology.
For more information and photos, see news story on "UC Davis Researches Examine Pyrethroid Reistance in Spread of Aedes aegypti," on the UC Davis Department of Entomology and Nematology's website.
And well it should.
Research led by UC Davis medical entomologists and published in the Sept. 15 edition of PLOS Genetics, indicates "a genetic component" to the blood-feeding behavior and host choice of Anopheles arabiensis.
The research was done in Kilombero Valley in Tanzania.
"We know that blood feeding preference among mosquitoes can be species specific,” said co-author and professor Greg Lanzaro, who leads the Vector Genetics Laboratory, UC Davis Department of Pathology, Microbiology and Immunology and is an affiliate of the UC Davis Department of Entomology and Nematology. “For example, there are mosquito species that specialize in feeding on amphibians or reptiles. We also know that many species are more catholic when choosing a meal and this can have important implications to human health—it's how some disease agents move between animals and humans.”
The publication, titled "The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis, is the work of a 13-member international team.
Medical entomologist and co-author Anthony Cornel of the UC Davis Department of Entomology and Nematology faculty--his lab is based at the Kearney Agricultural Research and Extension Center in Parlier--had this to say about the significance of the research: "From my perspective I would state that environmental anthropogenic influences by replacing natural habitats for human dwelling, need for more food and water by creating more agricultural lands and changing local water patterns, increasing domestic animal rangeland and use of insecticides can have quite dramatic influences of disease vector behavior and their genetic diversity. These changes should be monitored in the overall context of how these mosquito adaptations influence disease transmission dynamics.”
Other co-authors are researchers Yoosook Lee, Heather Ferguson, Travis Collier, Catelyn Nieman, Allison Weakley, all of the Vector Genetics Lab; Katharina Kreppel, Nicodem Govella and Anicet Kihonda of the Ifakara Health Institute, Ifakara, United Republic of Tanzania; and computer scientists Eleazar Eskin and Eun Yong Kang of UCLA.
“Malaria transmission is driven by the propensity for mosquito vectors to bite people, while its control depends on the tendency of mosquitoes to bite and rest in places where they will come into contact with insecticides. In many parts of Africa, where coverage with Long Lasting Insecticide Treated Nets is high, Anopheles arabiensis is the only remaining malaria vector. We sought to assess the potential for An. arabiensis to adapt its behavior to avoid control measures by investigating the genetic basis for its host choice and resting behavior. Blood-fed An. arabiensis were collected resting indoors and outdoors in the Kilombero Valley, Tanzania. We sequenced a total of 48 genomes representing 4 phenotypes (human or cow fed, resting in or outdoors) and tested for genetic associations with each phenotype. Genomic analysis followed up by application of a novel molecular karyotyping assay which revealed a relationship between An. arabiensis that fed on cattle and the standard arrangement of the 3Ra inversion. This is strong support that An. arabiensis blood-feeding behavior has a substantial genetic component. Controlled host choice assays are needed to confirm a direct link between allelic variation within the 3Ra inversion and host preference.”
You can read the paper online in PLOS Genetics.
It shouldn't be, nor is it, at the University of California, Davis.
Medical entomologists and other scientists at UC Davis are planning a Malaria Awareness Day from 10 a.m. to 1:30 p.m. on Monday, April 25 in the Memorial Union.
The event will take place in MU II (second floor) and is free and open to the public.
Statistics from the Center for Disease Control and Prevention (CDC) tell the alarming story.
"It is a leading cause of death and disease in many developing countries, where young children and pregnant women are the groups most affected," the CDC points out, citing these figures from the World Health Organization's World Malaria Report 2013 and the Global Malaria Action Plan:
- 3.4 billion people (half the world's population) live in areas at risk of malaria transmission in 106 countries and territories
- In 2012, malaria caused an estimated 207 million clinical episodes, and 627,000 deaths. An estimated 91% of deaths in 2010 were in the African Region.
The most vulnerable groups, CDC says, are young children, who have not yet developed partial immunity to malaria; pregnant woman, whose immunity is decreased by pregnancy, especially during the first and second pregnancies; and travelers or migrants coming from areas with little or no malaria transmission, who lack immunity.
Africa, according to CDC, is the most affected due to a combination of factors:
- A very efficient mosquito (Anopheles gambiae complex) is responsible for high transmission.
- The predominant parasite species is Plasmodium falciparum, which is the species that is most likely to cause severe malaria and death.
- Local weather conditions often allow transmission to occur year round.
- Scarce resources and socio-economic instability have hindered efficient malaria control activities.
The schedule for the UC Davis Malaria Awareness Day:
10 to 10:30 am.: Coffee/social/posters
10:30 to 10:50: "General Malaria Biology" by medical entomologist Gregory Lanzaro, professor, Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine.
10:50 to 11:20: Conducting Field Research in Rural Africa" by medical entomologist Anthony Cornel, associate professor, UC Davis Department of Entomology and Nematology and based at the UC Kearney Agriculture and Research Center, Parlier
11:10 to 11:30: "Marlaria Parasites in the Mosquito" by molecular biologist Shirley Luckhart, professor, UC Davis Department of Medical Microbiology and Immunology and an adjunct professor in the Department of Entomology and Nematology
11:30 to 11:50: "Mosquito-Borne Viral Diseases" by medical entomologist Chris Barker, assistant adjunct professor and assistant research scientist, UC Davis Department of Pathology, Microbiology and Immunology
11:50 to 12:10: "Disease Transmission by Non-Mosquito Vectors" by epidemiologist/veterinarian and disease ecologist Janet Foley, professor, UC Davis Department of Medicine and Epidemiology
12:10 to 1:30: A free lunch will be provided, but reservations must be made by April 21 to email@example.com.
The species has spread to at least seven counties in California since June 2013, says UC Davis medical entomologist Anthony Cornel of the UC Kearney Agricultural Research and Extension Center, Parlier, and the UC Davis Department of Entomology.
“It's an issue of great concern, especially as current control methods do not appear to be working well," says Cornel, who collaborates on research projects in Clovis, Fresno County, with the Consolidated Mosquito Abatement District. The district, based in Fresno, covers 1,058 square miles, including part of Kings County.
“We can't predict how far this mosquito will go in California,” he says, but it has spread “south of Fresno to San Diego. The furtherest site north is Madera in the Central Valley, but it's also been found in the more coastal area of Menlo Park in San Mateo.”
As far north as Sacramento?
“I don't want to exclude the possibility that it may spread as far north as Sacramento,” said Cornel, who collects, rears and researches mosquitoes from all over the world, including the United States, Mali, Cameroon, Comoros, Tanzania, South Africa and Brazil. “We need to see if it overwinters as eggs or adults or both.”
Infected Aedes aegypti can transmit dengue, yellow fever, Zika and chikungunya viruses. The Zika virus was first identified in Uganda in 1947 in rhesus monkeys, according to the World Health Organization. It was subsequently identified in humans in 1952 in Uganda and the United Republic of Tanzania. Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific.
Although the mosquito species is in California, it's important to point out that there are no reported cases of locally transmitted Zika virus in the state or in contiguous United States, according to the Centers for Disease Control and Prevention. The cases have all involved travelers returning home from countries plagued with disease outbreaks.
Cornel and his colleagues published a 27-slide document, “Surveillance and Control of Aedes aegypti Mosquito in Clovis, Calif.,” on Feb. 8 in F1000 Research, http://f1000research.com/slides/5-149. They called attention to the widespread invasion and establishment of the species in California. The research, illustrated with maps, is the work of Cornel and Yoosook Lee of UC Davis; Stephen Dobson of the University of Kentucky; Corey Bansfield of MosqMate Inc. and Jodi Holeman, Mark Amireno, Charles Smith and Stephen Mulligan III of the Consolidated Mosquito Control District.
The California team collaborates with University of Kentucky scientists to develop novel control strategies. One trial involves coating male mosquitoes with insect growth regulators, which are passed on to the females. Males are also infested with a biopesticide or “a good bacteria-like organism,” Wolbachia. “The male transfers it to the female, which affects the ovaries and negatively affects immature development,” Cornel explains. “It's not new, but it's not been employed in large trials.”
The researchers target mosquito breeding sites, primarily yard drains. “Despite the drought and the elimination of visible bodies of water, such as bird baths, pet bowls and flower pots, there's a major issue: yard drains,” Cornel says. “Yard drains installed in new home developments empty into the gutter or street and are cryptic breeding sites for mosquitoes.” He speculates that these mosquitoes are breeding underground.
“These drains are not easily accessible and we can't see the mosquitoes,” Cornel points out. “We need to blow out the water and plug these yard drains to eliminate these breeding sites.” He suggests that cities everywhere address this public safety issue and “redesign the yard drains.”
It's crucial for the public to become involved, Cornel emphasizes. “We have to focus on public education. We have to get the message across to eliminate mosquito breeding sites. We can't go to every house. We must rely on the public to eliminate the breeding sites.”
It's possible—but he hopes not—that what is now a “mosquito nuisance” will result in a disease outbreak.
It was just a matter of time before the so-called "super mosquito" surfaced, resulting in the failure of insecticide-treated nets to provide meaningful control from malaria in some localities in Africa.
"It's a ‘super' with respect to its ability to survive exposure to the insecticides on treated bed nets,” said medical entomologist Gregory Lanzaro, director of the Vector Genetics Laboratory at the School of Veterinary Medicine, University of California, Davis, who led the research team.
He and his colleagues recently discovered that interbreeding of two malaria mosquito species in the West African country of Mali, has resulted in “a super mosquito” hybrid that's resistant to insecticide-treated bed nets.
Anopheles gambiae, a major malaria vector, is interbreeding with isolated pockets of another malaria mosquito, A coluzzii.
The research, published in “The Proceedings of the National Academy of Sciences, “provides convincing evidence indicating that a man-made change in the environment--the introduction of insecticides--has altered the evolutionary relationship between two species, in this case a breakdown in the reproductive isolation that separates them,” said Lanzaro, a professor in the Department of Pathology, Microbiology and Immunology in the School of Veterinary Medicine.
Lanzaro and his "blood brother" medical entomologist Anthony Cornel of the Department of Entomology and Nematology have been researching mosquitoes in Mali since 1991.
Lanzaro called the need to develop new and effective malaria vector control strategies "urgent.”
Said Lanzaro: "A number of new strategies are in development, including new insecticides, biological agents--including mosquito killing bacteria and fungi--and genetic manipulation of mosquitoes aimed at either killing them or altering their ability to transmit the malaria parasite. These efforts need to be stepped up.”
The paper is titled “Adaptive Introgression in an African Malaria Mosquito Coincident with the Increase Usage of Insecticide-Treated Bed Nets.” First author is Laura Norris, then a postdoctoral scholar in the UC Davis Department of Entomology and Nematology who was supported by a National Institutes of Health T32 training grant awarded to Lanzaro. Norris has since accepted a position with the President's Malaria Initiative in Washington, D.C.
In addition to Lanzaro and Cornel, the co-authors include Yoosook Lee and Travis Collier of the Vector Genetics Lab and the Department of Pathology, Microbiology and Immunology; and Abdrahamane Fofana of the Malaria Research and Training Center at the University of Bamako, Mali. Three grants from the National Institutes of Health funded the research.