- Author: Kathy Keatley Garvey
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 lead author Geoffrey Attardo, medical entomologist-geneticist in the UC Davis Department of Entomology and Nematology.
“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.”
In launching the project, the researchers designed an assay “to test for the presence of mutations in the gene coding for the pyrethroid target protein, the voltage gated sodium channel (the para gene),” Attardo explained. “Detection of these mutations is used to monitor the level or resistance in populations. However, the actual link between the effect the genotype has on the phenotype of individual mosquitoes has not been looked at in detail. “
The scientists identified mutations from genetic sequences of Californian mosquitoes provided by co-author Yoosook Lee, a former UC Davis mosquito researcher now at the University of Florida-Florida Medical Entomology Laboratory, Vero Beach.
The authors also include 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.
First, they tested the individual resistance phenotype of mosquitoes by placing them into bottles coated with the pyrethroid insecticide permethrin, and observed them to determine how long it takes for them to respond to the insecticide. Said Attardo: “This is a modified version of the assay used by the Center for Disease Control and Prevention to evaluate phenotypic resistance in groups of mosquitoes.”
Then they isolated the DNA from and performed a high-throughput genetic analysis on each individual to determine the composition of the five mutations in each individual. Next they looked at the resulting data to see how well knockdown time correlates with individual genotypes of mosquitoes.
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 project drew financial support from the Pacific Southwest Regional Center of Excellence for Vector-Borne Diseases, funded by the U.S. Centers for Disease Control and Prevention.
- Author: Kathy Keatley Garvey
The research, published in the Sept. 15 edition of PLOS Genetics, involved the study of Anopheles arabiensis, in Kilombero Valley in Tanzania. The mosquito is the primary vector of malaria in east Africa.
"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 is the work of a 13-member international team. Bradley Main, a researcher in the Vector Genetics Lab, is the lead author.
“Whether there is a genetic basis to feeding preferences in mosquitoes has long been debated,” said lead author Bradley Main, a researcher in the Vector Genetics Lab. “Using a population genomics approach, we have established an association between human feeding and a specific chromosomal rearrangement in the major east African malaria vector. This work paves the way for identifying specific genes that affect this critically important trait.”
Other co-authors, in addition to Lanzaro, are Anthony Cornel of the UC Davis Department of Entomology and Nematology faculty; 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.
In their summary, they wrote: “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.”
The publication, "The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis," is online at http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006303
- Author: Kathy Keatley Garvey
Spotlighted are parasitologist and entomologist Shirley Luckhart, professor in the UC Davis School of Medicine's Department of Medical Microbiology and immunology and the Department of Entomology and Nematology; medical entomologist Gregory Lanzaro, professor, Department of Pathology, Microbiology and Immunology (PMI), UC Davis School of Veterinary Medicine, and an associate of the UC Davis Department of Entomology and Nematology; chemical ecologist Walter Leal, professor in the UC Davis Department of Molecular and Cellular Biology and former chair of the UC Davis Department of Entomology; virologist Lark Coffey of PMI; and UC Davis post-doctoral researcher Young-Moo Choo of the Leal's lab who discovered a receptor by dissecting mosquitoes' mouthparts and genetically testing them.
The KQED piece, drawing widespread interest, is the work of Gabriela Quirós, coordinator producer of Deep Look, KQED Science.
Luckhart said that the mosquitoes detect body heat and substances called volatile fatty acids. “The volatile fatty acids given off by our skin are quite different," Luckhart told Quirós. "They reflect differences between men and women, even what we've eaten. Those cues are different from person to person. There's probably not one or two. It's the blend that's more or less attractive.”
“Mosquitoes don't find the blood vessel randomly," Leal said, pointing out that the receptors respond to chemicals in the blood.
The receptor that the Leal lab discovered is called 4EP, and may lead to drug companies developing new mosquito repellents. “First they'd need to find a repellent against the receptors," Choo told Quirós. "Then they'd treat people's skin with it. When the mosquito tried to penetrate the skin, it would taste or smell something repulsive and fly away.”
Lanzaro said that the latest malaria statistics--more than 300 million people contracted malaria in 2015, and some 635,000 died--are "probably an underestimate."
- Author: Kathy Keatley Garvey
“It's ‘super' with respect to its ability to survive exposure to the insecticides on treated bed nets,” said medical entomologist Gregory Lanzaro of the University of California, Davis, who led the research team.
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, director of the Vector Genetics Laboratory and professor in the Department of Pathology, Microbiology and Immunology in the School of Veterinary Medicine.
“What we provide in this new paper is an example of one unusual mechanism that has promoted the rapid evolution of insecticide resistance in one of the major malaria mosquito species.”
The insecticide resistance came as no surprise. “Growing resistance has been observed for some time,” Lanzaro said. “Recently it has reached a level at some localities in Africa where it is resulting in the failure of the nets to provide meaningful control, and it is my opinion that this will increase.”
Lanzaro, who has researched mosquitoes for 36 years, and in Mali since 1991, credits insecticide-treated nets with “saving many thousands, probably tens of thousands of lives in Mali.” The World Health Organization's World Malaria Report indicates that deaths from malaria worldwide have decreased by 47 percent since 2000. Much of that is attributed to the insecticide-treated bed nets.
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, co-authors include medical entomologist Anthony Cornel, Department of Entomology and Nematology and Vector Genetics Lab; 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.
Lanzaro has researched mosquitoes in Mali for 24 years with “blood brother” Anthony Cornel, associate professor in the UC Davis Department of Entomology and Nematology who is headquartered at the UC Kearney Agriculture and Research Center, Parlier. Both are graduate student advisors in the department, training medical entomologists of tomorrow.
Related Links:
Vector Genetics Lab
Anthony Cornel: Mosquito Man
Time Magazine
- Author: Kathy Keatley Garvey
Sanford, lead author of "Plasmodium falciparum Infection Rates for Some Anopheles spp. from Guinea-Bissau, West Africa,” completed the research at UC Davis while she was funded by a National Institutes of Health T-32 training grant.
Sanford worked closely with medical entomologists Anthony Cornel of the UC Davis Department of Entomology and Nematology; and Gregory Lanzaro and Yoosook Lee of the Vector Genetics Laboratory, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine. Cornel is based at the Kearney Agricultural Research and Extension Center, Parlier, and also works in the Vector Genetics Lab.
"Malaria is among the leading causes of childhood mortality in Guinea-Bissau, comprising 18% of mortality of children less than five years of age as of 2010 (WHO, 2010). However, the human malaria incidence rate in Guinea Bissau varies considerably from year to year with a general decrease in recent years to about 3 children (Ursing et al., 2014). Plasmodium falciparum predominates, causing 98% cases, followed by a few cases of Plasmodium malariae and Plasmodium ovale. Mixed infections of P. malariae, and to a lesser extent P. ovale, have been recorded but appear to be rare and highly variable in both Guinea-Bissau (Snounou et al., 1993) and neighboring Senegal (Fontenille et al., 1997a; Fontenille et al., 1997b).
"Limited research has been conducted on the vectors and malaria parasite infection rates in Guinea-Bissau populations of Anopheles species in general and there is no data on comparative infection rates between A. gambiae and A. coluzzii and members of the A. gambiae complex. Variability is also high among the Anopheles spp. implicated as vectors in this region of West Africa in terms of both their temporal population dynamics as well as species composition among study sites (Carnevale et al., 2010; Fontenille et al., 1997a; Jaenson et al., 1994; Snounou et al., 1993).
"Here we present much needed data on P. falciparum infection of Anopheles spp. specimens collected from inside and around associated human habitations at eight sites in Guinea-Bissau."
Other co-authors, in addition to Cornel, Lanzaro and Lee are Catelyn Nieman, Allison Weakley and Sarah Han, all of the UC Davis Vector Genetics Lab; and Joao Dinis and Amabelia Rodrigues, National Institute of Public Health, Bissau, Guinea-Bissau.,
Sanford now works as a forensic entomologist at the Harris County Institute of Forensic Sciences, Texas Medical Center, Houston. While at UC Davis, she helped organize the World Malaria World Day observances.
Sanford received her bachelor of science degree in biology, with a minor in entomology, from UC Riverside in 2000; her master's degree in entomology from UC Riverside in 2003 and her doctorate in entomology from Texas A&M University in 2010. Her dissertation: “Observations on the Associative Learning Capabilities of Adult Culex quinquefasciatus Say and Other Mosquitoes.”
Active in the Entomological Society of America (ESA), Sanford won the John Henry Comstock Award, Southwestern Branch of ESA, in 2009. She received the 2010 Outstanding Achievement in Doctoral Research Award from Texas A&M in 2010, and a U.S. Fulbright Fellowship to Thailand in 2007.