Travelers know Iquitos as the "capital of the Peruvian Amazon" but scientists know it as a hot spot for dengue, a mosquito-borne viral disease with raging outbreaks in many tropical and subtropical countries.
Amy Morrison, stationed in Iquitos full-time, has directed dengue research activities there for the past 15 years. An epidemiologist who joined the UC Davis laboratory of medical entomologist Thomas Scott (now professor emeritus) in 1996, she's a project scientist and scientific director of the Naval Medical Research Unit No. 6 (NAMRU-6) Iquitos Laboratory.
Morrison is back in the states to present a UC Davis seminar on "Targeting Aedes Aegypti Adults for Dengue Control: Infection Experiments and Vector Control in Iquitos" from 4:10 to 5 p.m., Wednesday, Jan. 10, in 122 Briggs Hall, Kleiber Hall Drive.
Hosted by the UC Davis Department of Entomology and Nematology, it's the first in a series of winter seminars coordinated by assistant professor Rachel Vannette and Ph.D student Brendon Boudinot of the Phil Ward lab.
Dengue is a threat to global health, says Morrison, who holds a doctorate in epidemiology from Yale University and a master's degree in public health from UCLA. According to the World Health Organization (WHO), the incidence of dengue has increased 30-fold over the last 50 years and almost half of the world population is now at risk. It's ranked as "the most critical mosquito-borne viral disease in the world."
"Each year, an estimated 390 million dengue infections occur around the world," according to the World Mosquito Program. "Of these, 500,000 cases develop into dengue hemorrhagic fever, a more severe form of the disease, which results in up to 25,000 deaths annually worldwide."
Of the dengue project in Iquitos, Morrison says: "Comprehensive, longitudinal field studies that monitor both disease and vector populations for dengue viruses have been carried out since 1999 in Iquitos. In addition, to five large scale-vector control intervention trials, ongoing data collection has allowed the evaluation of Ministry of Health emergency vector control using indoor ULV space sprays with pyrethroids in concert with larviciding through multiple campaigns, as well as characterize local DENV (dengue virus) transmission dynamics through two and one novel DENV serotype and strain invasions into the city."
"Our research group has also been conducting contact cluster investigations on DENV-infected and febrile control individuals since 2008," Morrison relates. "These studies demonstrated that attack rates were consistent between houses where cases were first detected and recently visited contact houses independent of distance between these locations. Furthermore, contact cluster investigations allow us to identify viremic individuals across the spectrum of disease outcomes including inapparent infections."
"Using DENV positive individuals captured through these and other febrile surveillance protocols, we exposed laboratory reared (F2) Aedes aegypti mosquitoes directly on their arms or legs, and obtained blood samples with and without EDTA for exposure of mosquitoes in an artificial membrane feeder. After a 58-participant pilot study comparing feeding methods, we initiated a direct feeding protocol exposing participants (78 feeds in 31 participants to date). Feeding, survival, midgut infection and systemic dissemination are all higher using direct feeding than indirect feeding methods. Of 22 participants without detectable fluorescent focus assay titers in their serum at the time they were exposed to mosquitoes, 14 infected mosquitoes by at least one method."
"Although virus titer was a predictor of mosquito infection, mosquitoes became infected at low or undetectable titers and with subjects experiencing mild disease. We have evaluated insecticide-treated curtains and a novel lethal ovitrap (Attractive Lethal OviTrap = ALOT) for dengue control. Only the ALOT traps showed a significant impact on dengue incidence corresponding to a modest decrease in vector densities and a shift of the mosquito population age structure in the trap area to younger mosquitoes. Recent evaluations of indoor ULV interventions with pyrethroids suggest that ULV campaigns that reduce Aedes aegypti for at least 3 weeks through multiple fumigation cycles can mitigate DENV transmission during the same season."
Bottom line: "We argue that Aedes aegypti control should focus on interrupting transmission rather than long-term suppression at operationally unachievable levels and that emergency control should be applied at area-wide scales rather than reacting to individual DENV cases."
The mosquito transmits the Zika virus, currently "the" hot medical topic.
But it also transmits dengue, yellow fever and chikungunya viruses.
“Dengue infects 400 million people worldwide each year, and 4 billion people or nearly half of the world's population are at risk for dengue,” says medical entomologist Thomas Scott, distinguished professor and now emeritus, UC Davis Department of Entomology and Nematology.
Scott, who has studied dengue more than 25 years and is recognized as the leading expert in the ecology and epidemiology of the disease, emphasizes that “There is no vaccine nor drug that is effective against this virus." There are four serotypes: DENV-1 through DENV-4.
Now for the groundbreaking news.
Scott and his colleagues just published a study in the Public Library of Science (PLOS), Neglected Tropical Diseases, that is sure to rock the world of everyone who has ever contracted dengue.
Well, yes, you can. "Lifetime of immunity" is false.
“Our most significant result from this study is that immunity to dengue viruses does not always provide perfect protection from reinfection,” Scott said. “The public health implications include evaluation of dengue vaccines, interpretation of a person's virus exposure history and susceptibility to new infections, and design of dengue surveillance programs.”
“Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials,” the research team wrote. “Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.”
Former UC Davis researcher Steve Stoddard and senior author of the paper said it well:
“It has long been thought that infection with any one of the viruses produced lifetime immunity to that virus. This finding could help explain results of dengue vaccine trials that showed poor efficacy against one of the four serotype. It also has broad implications for vaccine development.”
The research team investigated the "validity of the fundamental assumption" by analyzing a large epidemic caused by a new strain of DENV-2 that invaded Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region.
The mosquito-borne viral disease known as “breakbone fever,” is three times more prevalent than originally thought, according to a research paper published today in Nature and co-authored by dengue expert Thomas Scott of UC Davis.
In their research paper, titled “The Global Distribution and Burden of Dengue,” Scott and the 17 other team members estimated that 350 million people are infected each year--more than triple the World Health Organization’s current estimate of 50 to 100 million.
Professor Simon Hay of the University of Oxford led the research as part of the International Research Consortium on Dengue Risk Assessment, Management and Surveillance.
“Dengue takes an enormous toll on human health worldwide, with as many as 4 billion people at risk," said Scott, a UC Davis professor of entomology and worldwide expert on the epidemiology and prevention of dengue. He chairs the mosquito-borne disease modelling group in the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, Fogarty International Center, National Institutes of Health.
“The results of our study and infrastructure that created the dengue maps fill a critical gap in the battle against dengue,” said Scott, who maintains field research programs in Iquitos, Peru, and Khamphaeng Phet, Thailand. “Prior to this, without rigorously derived dengue estimates that can be continuously updated, it was not possible to know with confidence where and when to direct interventions for greatest potential impact or to objectively assess the effectiveness of regional and global control efforts. That kind of knowledge was among the most important missing information for developing enhanced dengue prevention programs.”
The highly infectious tropical and subtropical disease is spread by the bite of an infected female Aedes aegypti, a day-biting, limited flight-range mosquito that prefers human blood to develop its eggs. Dengue is caused by four distinct, but closely related, viruses. The most severe form of disease is life-threatening dengue hemorrhagic fever or DHF.
The researchers assembled known records of dengue occurrence worldwide and used a formal modelling framework to map the global distribution of dengue risk. They then paired the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010.
“There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread,” the researchers wrote.
Dengue has now begun to appear along the southern border of the United States, including Texas. Florida has also reported cases of dengue.
Of the 96 million clinically apparent dengue infections, Asia bears 70 percent of the burden, the research paper revealed. India alone accounts for around one-third of all infections.
In an article published this week in the Proceedings of the National Academy of Sciences (PNAS), the UC Davis medical entomologists and their colleagues found that human movement—people going from house-to-house to visit their friends and relatives—is a key component to driving the virus transmission. (Read PNAS paper)
The research site is Iquitos, nestled in the heart of the Amazon rain forest of northeastern Peru. It's considered one of the world’s primary “open laboratories” to study the transmission of the virus.
The Aedes aegypti mosquito is a day-biting mosquito and we humans are its favorite host/target.
The ground-breaking research shows why it's crucial to focus on people movement, not just on the traditional mosquito control-and-prevention methods, such as applying insecticides and eliminating water-filled containers that can provide a larval habitat.
As lead author/medical entomologist Steve Stoddard said: "This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control."
“Interestingly, it didn’t matter how far away the visited houses were," Stoddard said. "The mosquito that transmits dengue virus prefers to stay in small areas, say in less than a 100-meter radius, but the distance between houses was often much greater than this. So it only makes sense that humans are frequently spreading the virus around as they commute between their homes and the homes of their friends and family. Altogether the data demonstrate what we expected, that human movements are really key to the transmission of this mosquito-borne virus.”
Said Scott, professor of entomology at UC Davis and director of the Mosquito Research Laboratory: “Dengue takes an enormous toll on human health worldwide, with as many as 4 billion people at risk—half of the world’s population--and 400 million new infections each year. The results from our study are focusing attention to the role human social networks in virus invasion and epidemic spread.
"At our Peru study area, we found that infection risk is based on the places a person visits and transmission dynamics are driven by overlapping movements of people who recently visited the same places, like the homes of their family and friends.”
Bottom line: The scientists found that people movement not only defined individual infection risk and local patterns of incidence, but resulted in the rapid spread of the virus and marked heterogeneity in transmission rates.
Next phase of the research? It's aimed at "understanding how variation in human behavior influences transmission and applying that knowledge in enhanced disease prevention strategies,” said Scott, the principal investigator of a National Institutes of Health (NIH)-funded grant.
With some 4 billion people worldwide at risk, and with 400,000 million new infections each year, dengue is indeed taking its toll. Every year some 500,000 people with severe dengue are hospitalized, and 2.5 percent die.
It's Halloween tomorrow (Wednesday) but what's really frightening is Aedes aegypti, a mosquito that transmits the deadly dengue. According to the World Health Organization (WHO), dengue is the world's most rapidly spreading mosquito-transmitted disease.
Some 2.5 billion people, or about 40 percent of the global population, are at risk from dengue, WHO says. The disease infects between 50 to 100 million people a year. The most severe form afflicts some 500,000 a year, killing an estimated 2.5 percent or 22,000.
Enter Sarjeet Gill, professor of cell biology and entomology at UC Riverside. He'll speak on on "Bacterial Toxins in Disease Mosquito Vector Control" at a seminar from 12:10 to 1 p.m., Wednesday, Oct. 31 in Room 1022 of the Life Sciences Building, UC Davis.
His longtime colleague and good friend, Bruce Hammock, distinguished professor of entomology at UC Davis, will host him as part of the UC Davis Department of Entomology's fall seminar series.
"Aedes aegypti is an important vector of human diseases, such as dengue fever and yellow fever," Professor Gill says. "Its control has been attempted by eliminating breeding sites, using predators and with chemical insecticides. However, such control is still difficult because of operational limitations and the development of insect resistance. Therefore, Bacillus thuringiensis has been used for decades instead of physical and chemical control methods. B. thuringiensis israelensis is highly active against Aedes aegypti."
"The high insecticidal activity and the low toxicity to other organisms," Gill says, "have resulted in the rapid use of B. thuringiensis as an alternative for the control of mosquito populations. B. thuringiensis israelensis produces a variety of toxins that act synergistically to cause toxicity to larval populations."
Gill says his seminar "will discuss our current understanding of the mode of action of these toxins and provide evidence on how resistance to these toxins has not occurred in Aedes mosquitoes in the field even though B. thuringiensis israelensis has been used for more than three decades."
Gill’s laboratory focuses on two principal research activities. "The first area attempts to elucidate the mode of action of insecticidal toxins from the Gram positive bacteria Bacillus thuringiensis and Clostridium bifermantans," he says. "This research aims to identify novel toxins, and to gain a molecular understanding of how these toxins interact with cellular targets and thereby causing toxicity. The second area focuses on understanding mosquito midgut and Malpighian tubules function, in particular ion and nutrient transport, and changes that occur following a blood meal."
Gill, who received his doctorate from UC Berkeley, joined the UC Riverside Department of Entomology faculty in 1983. He helped establish the Department of Cell Biology and Neuroscience and also served as chair. Currently he is the co-editor of the journal Insect Biochemistry and Molecular Biology.
A noted scientist and a fellow of the American Association for the Advancement of Science, Gill received his doctorate in insecticide toxicology in 1973 from UC Berkeley. See his website.
If you miss his seminar, not to worry. It's scheduled to be recorded and then posted at a later date on UCTV. (See the index of previous Department of Entomology seminars posted on UCTV.)/span>