Chemical ecologist and mosquito researcher Walter Leal, distinguished professor in the UC Davis Department of Molecular and Cellular Biology, and his lab collaborated with scientists in Recife to ask “Does Zika Virus Infection Affect Mosquito Response to Repellents?”
The work, funded by the National Institutes of Health, was published Feb. 16 in Scientific Reports of the journal Nature. The researchers used mosquitoes originating from colonies reared by UC Davis medical entomologist Anthony Cornel and from colonies in Recife.
“We used assays mimicking the human arm to test the mosquitoes infected with the Zika virus,” Leal said, “and we asked whether the Zika infection affects mosquito response to repellents.” They tested DEET and Picaridin, considered the top two mosquito repellents. “We discovered that DEET works better than Picaridin against the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti, whether infected or not.”
The researchers also found that old mosquitoes that already had a blood meal “were less sensitive to repellents,” said Leal, adding “It was not clear whether this was due to the virus, but mostly likely because of age. ”
“Lower doses--normally used in commercial products--work well for young mosquitoes,” Leal said, “but the old ones are the dangerous ones because they may have had a blood meal infected with virus and there was enough time for the virus to replicate in the mosquito body.”
“The bottom line: to prevent bites of infected mosquitoes, higher doses of repellent are needed. The data suggest that 30 percent DEET should be used. Lower doses may repel nuisance young mosquitoes, but not the dangerous, infected, old females.”
Leal, a native of Brazil, collaborates with Rosangela Barbosa and Constancia Ayres of the Oswaldo Cruz Foundation (FIOCRUZ-PE), Recife, Brazil. The work with infected mosquitoes was conducted at FIOCRUZ-PE.
Leal, Barbosa and Ayres co-authored the paper with Fangfang Zeng and Kaiming Tan, both of the Leal lab; and Rosângela M. R. Barbosa, Gabriel B. Faierstein, Marcelo H. S. Paiva, Duschinka R. D. Guedes, and Mônica M. Crespo, all of Brazil.
The World Health Organization (WHO) recommends that people traveling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt preventive measures, including the use of insect repellents, to reduce or eliminate mosquito bites. Prior to the Feb. 16 published research, it was not known whether the most widely repellents are effective against ZIKV-infected mosquitoes, “in part because of the ethical concerns related to exposing a human subject's arm to infected mosquitoes in the standard arm-in-cage assay,” the researchers pointed out.
They used a previously developed, human subject-free behavioral assay, which mimics a human subject to evaluate the top two recommended insect repellents.
Scientists isolated the Zika virus (ZIKV) nearly seven decades ago from a sentinel rhesus monkey while they were trying to unravel the cycle of sylvan yellow fever virus in Uganda..
According to the Centers for Disease Control and Prevention:
- Zika is spread mostly by the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus). These mosquitoes bite during the day and night. The virus can also be sexually transmitted.
- Zika can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause certain birth defects.
- There is no vaccine or medicine for Zika.
- Local mosquito-borne Zika virus transmission has been reported in the continental United States.
That's what UC Davis chemical ecologist Walter Leal, co-chair of the International Congress of Entomology (ICE 2016) recently held in Orlando, Fla., wrote in his newly published opinion piece, titled "Zika Mosquito Vectors: the Jury Is Still Out" in F1000 Research.
Leal, a mosquito researcher and distinguished professor in the UC Davis Department of Molecular and Cellular Biology, co-chaired ICE 2016 with Alvin Simmons, research entomologist with the United States Department of Agriculture's Agricultural Research Service (USDA/ARS), U.S. Vegetable Laboratory in Charleston, S.C.
The conference, themed "Entomology Without Borders," drew 6,682 delegates from 102 countries. The last time ICE met in the United States was four decades ago. The venue then: Washington, D.C.
One of the symposia at the Orlando meeting was the Zika Symposium, "which covered multiple aspects of the Zika epidemic, including epidemiology, sexual transmission, genetic tools for reducing transmission, and particularly vector competence," Leal wrote. "While there was a consensus among participants that the yellow fever mosquito, Aedes aegypti, is a vector of the Zika virus, there is growing evidence indicating that the range of mosquito vectors might be wider than anticipated. In particular, three independent groups from Canada, China, and Brazil presented and discussed laboratory and field data strongly suggesting that the southern house mosquito, Culex quinquefasciatus, also known as the common mosquito, is highly likely to be a vector in certain environments."
Leal based his opinion piece mainly on the current literature and the Zika Symposium at ICE 2016, which was organized by Constância Ayres, Oswaldo Cruz Foundation (FIOCRUZ-PE), Recife, Brazil (he collaborates with Ayres) and Adriana Costero, National Institutes of Health, Bethesda, Md. The speakers included worldwide experts from the United States, Brazil, China and Canada.
Ironically, the Zika virus wasn't a household word or in most entomologists' vocabulary when Leal and Simmons began planning the ICE 2016 meeting several years ago.
Now scores of researchers are tackling the Zika virus (ZIKV), first isolated first from a febrile monkey and later from the mosquito Aedes africanus. "ZIKV was isolated from humans for the first time in 1954 during an outbreak of jaundice suspected of being yellow fever," Leal recounted.
"During the discussion at the end of the symposium, the forum was opened for questions and comments," Leal wrote. Scott Ritchie of James Cook University, Australia, asked “Is anyone looking for the virus in birds?”
"This question captures the sentiment that both questions were thought provoking, and we still do not have all or many answers when it comes to ZIKV. Hopefully, we will be better prepared when convening in Finland for ICE 2020. Wouldn't it be wonderful to report in Helsinki that mosquito vector populations have been reduced or eliminated, the Zika and other epidemics were contained, vaccines have been made available, and entomologists are ready to further improve the human condition by tackling other problems than the Zika epidemic?"
In a groundbreaking discovery, a scientific team of Brazilians and Brazilian-born chemical ecologist Walter Leal of the University of California, Davis, has announced that the Zika virus has been detected in wild-caught Culex quinquefasciatus mosquitoes in Recife, the epicenter of the Zika epidemic.
Scientists from the Fiocruz Institute, Pernambuco, confirmed the discovery July 21. The detection could have widespread repercussions, as the Culex mosquitoes are more common and widespread than the yellow fever mosquito, Aedes aegypti, known as the primary carrier of the Zika virus.
Leal, who collaborates with Fiocruz Institute researcher Constancia Ayres in a National Institutes of Health-sponsored project on the investigation of Zika in the C. quinquefasciatus, said that the Brazilian lab earlier discovered that Culex had the capability of transmitting the virus. Although the scientists were able to infect the lab mosquitoes with the virus, they had not found the virus in wild-caught mosquitoes—until now.
“This could have major repercussions here in the United States and in other parts of the world,” said Leal, a distinguished professor in the UC Davis Department of Molecular and Cellular Biology who is co-chairing the International Congress of Entomology meeting Sept. 25-30 in Orlando, Fla. The conference is expected to draw some 7000 entomologists throughout the world.
Leal said more work needs to be done to see if Culex mosquitoes are playing a role in the current epidemic. In an interview July 21 with health reporter Jennifer Yang of the Toronto Star, Canada's largest daily, he commented: “It looks like there were more vectors than we thought, and this is one of them. We don't have to panic, but we have to know. And now that we know, we have to take care of the Culex.”
A. aegypti is already established in California; it has spread to at least seven counties since its discovery in Clovis, Fresno County, in June 2013, according to medical entomologist Anthony Cornel of the UC Davis Department of Entomology and Nematology and the UC Kearney Agricultural Research and Extension Center, Parlier.
The Zika virus, which can result in birth defects in pregnancy, can be transmitted through exposure to infected blood or sexual contact. The Centers for Disease Control estimates that between 400,000 and 1.3 million cases have been discovered across South, Central, and North America, where the disease was previously unknown.
Leal and a group of 18 students just hosted a Zika Public Awareness Symposium on May 26 at Giedt Hall, UC Davis campus. The podcast can be accessed at https://video.ucdavis.edu/media/Zika+Virus+Public+Awareness+Symposium/0_n3aupf5c
It's good to see UC Davis mosquito researchers featured in the KQED's science program, "Deep Look."
KQED journalists recently traveled to the UC Davis campus to visit several mosquito labs. The end result: The KQED news article on “How Mosquitoes Use Six Needles to Suck Your Blood,” which includes an embedded video. The National Public Radio's health blog, “Shots,” includes a shorter version. You can also see the Deep Look video on YouTube (embedded below).
- 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
- 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.
“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.”
But back to the video. The narrator reveals the sophisticated tools that the mosquito uses to draw your blood.
- A protective sheath retracts: inside are six needles, and two of them have sharp, tiny teeth
- The mosquito uses the sharp, toothed needles to saw through your skin
- Other needles hold the tissues apart while she works
- Receptors on the tip of one of her needles guide her to your blood vessel.
- She uses the same needle like a straw to sip your blood
- She uses another needle to spit chemicals into you so your blood will flow easily. That's what gives you the itchy, scratch-me-now welts.
Of course, it's the viruses or parasites that the mosquito transmits that can sicken and kill us. Depending on the species, they give us such diseases as malaria, dengue, yellow fever, West Nile virus, Zika virus and elephantiasis.
As KQED says "This is the deadliest animal in the world. Mosquitoes kill hundreds of thousands of people each year...the most vulnerable people: children and pregnant women."
KQED performed an excellent public service in reporting and sharing this scientific information, gleaned from the UC Davis labs. The first day the video was posted, it drew nearly 400,000 views.
We worry about what mosquitoes do to us. If mosquitoes could talk--if they could communicate with us--they ought to be worried about what we're going to do to them.
(Access the American Mosquito Control Association website to learn the biology of mosquitoes.)
The unique symposium, the work of chemical ecologist Walter Leal, professor in the UC Davis Department of Molecular and Cellular Biology and his 18 biochemistry students, drew an attentive crowd and scores of questions about the mosquito-borne virus, which is primarily transmitted by the yellow fever mosquito, Aedes aegypti.
In pregnant women, the Zika virus can cause fetal microcephaly and other severe brain anomalies, as well as a number of other medical issues. In adults, it can be sexually transmitted and can cause Guillain–Barré syndrome, a disorder of the immune system that damages the peripheral nervous system.
“I am certain that every person in attendance, either online or in Giedt Hall, whether specialist or not, knows more about Zika now then when the symposium started,” Leal said. “Mission accomplished! Those who did not attend and/or think that my statement is exaggerated or not accurate should go watch the recorded version of the symposium at https://video.ucdavis.edu/media/Zika+Virus+Public+Awareness+Symposium/0_n3aupf5c.”
“The highlight of the symposium, however, was the level of participation of the students," said Leal, a fellow of the Entomological Society of America and co-chair of the International Congress of Entomology meeting, set Sept. 25-30 in Orlando, Fla. "Clearly, new teaching approaches lead to students' engagement. This was an experiment that worked.”
A native of Brazil, Leal is a noted mosquito researcher (his lab discovered the secret mode of DEET) who collaborates with colleagues in Brazil. He recently participated in the international Zika scientific conference there.
What prompted the symposium? Leal and the 18 students decided that a scientific symposium would generate increased public awareness about the growing threat. They brought in speakers from the Brazilian frontlines (through Skype) and a Colorado State University researcher who contracted the Zika virus in Senegal and transmitted it to his wife. He was the first to discover that the virus is transmitted sexually.
The 18 students excelled, drawing praise from attendees and participants alike. In an email to Leal, James Carey, distinguished professor of entomology, UC Davis Department of Entomology and Nematology, wrote: "All were poised, confident, well prepared and articulate. You should be given a lot of credit for this creative outcome of your teaching efforts."
Symposium speakers included:
"The Zika Epidemic – An Overview"
Professor Walter S. Leal
UC Davis Department of Molecular and Cellular Biology
"Congenital Zika Syndrome"
Dr. Regina Coeli Ramos, University of Pernambuco, Brazil (remote)
"Zika Virus and Me"
Professor Brian Foy (remote)
Department of Microbiology, Immunology, and Pathology, Colorado State University
Zika Virus: Looking into Mosquitoes' Vectorial Capacity
Professor Constância F. J. Ayres
Department of Entomology, Fundação Oswaldo Cruz-Pernambuco, Brazil (remote)
"Don't Let Mosquitoes Bug You with Zika – Repel Them"
Professor Walter S. Leal
UC Davis Department of Molecular and Cellular Biology
"DEET vs. Zika – I Would Go with the Former"
Dr. Emanual Maverakis
Department of Dermatology, UC Davis School of Medicine
"Keeping Mosquito at Bay, Not in Your Backyard"
Dr. Paula Macedo
Laboratory Director, Sacramento-Yolo Mosquito & Vector Control District
"Friends Don't Let Friends Get Zika"
Dr. Stuart H. Cohen
Chief of the Division of Infectious Diseases and director of Hospital Epidemiology and Infection Control, UC Davis Medical School.
Some key points from the symposium
- Most people who contract Zika do not exhibit any symptoms whatsoever
- Zika virus is sexually transmitted; if you contract Zika, you can transmit it to your sexual partner.
- The mosquito, Aedes aegypti, is already in California, including the Clovis area and Palo Alto area
- Nearly 600 cases of Zika have already been reported in the United States, mostly in New York, Florida and California. Each case involved a U.S. traveler from a Zika virus "hot spot"
- Zika can persist up to 62 days in human semen
- Laboratory tests show that the common mosquito, Culex, can vector the virus and field tests are underway. Culex transmits West Nile Virus, Japanese encephalitis, and equine encephalitis.
- The two mosquitoes have varying feeding and breeding patterns: Culex feeds at night; and Aedes aegypti in the day, while Culex lays its eggs in polluted water, and Aedes aegypti in clean/clear water
- Culex quinquefasciatus, the southern house mosquito, is a potential vector; it has similar vector competence, and is much more abundant
The Zika virus was first isolated in 1947, in a rhesus monkey in a forest near Entebbe, Uganda. Brazil reported a human outbreak in early 2015. The virus is now spreading to other parts of South, Central and North America. The World Health Organization says the virus is likely to spread throughout most of the Americas by the end of the year. It is advising that people returning from known Zika outbreak areas to follow safe sex practices or abstain from sex for at least eight weeks.