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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary 2 Vector-Borne Disease Detection and Control OVERVIEW Several workshop presentations focused on specific vector-borne diseases, permitting participants to explore them not only as diverse and unique public health challenges in their own right, but also more generally as examples that might inform the detection and control of other vector-borne disease agents. Workshop speakers described opportunities, successes, and obstacles in managing dengue, West Nile virus (WNV), Rift Valley fever (RVF), malaria, bluetongue, hantavirus pulmonary syndrome, and Sudden Oak Death (SOD). Epidemiologists investigating infectious disease outbreaks seek to determine the route of transmission; in the case of vector-borne diseases, their efforts necessarily focus on the presence, abundance, and ecology of the vector, which in turn are frequently influenced by environmental conditions and human behavior. To illustrate these connections, Ned Hayes, of the Centers for Disease Control and Prevention (CDC), described his experiences investigating three different vector-borne diseases in diverse settings: pneumonic plague in Ecuador, 1998; dengue at the Mexico-Texas border, 1999; and tularemia in Martha’s Vineyard, Massachusetts, 2000. The investigation of each outbreak proceeded according to the following principles, as defined by Hayes: Determine that an outbreak exists. Categorize the outbreak by time, person, and place. Establish surveillance using an appropriate case definition. Collect and test diagnostic samples.
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary Formulate hypotheses to explain risk of disease. Test hypotheses with one or more epidemiologic studies. Implement preventive interventions. Communicate results of the investigation through written reports or published papers. Through the application of these principles, investigators attempt to determine the presence, abundance, and ecology of the vector; to identify reservoirs of infection; to evaluate modes of transmission and the ways in which they are influenced by the environment; and to implement disease control and prevention measures. The plague outbreak in Ecuador occurred in a remote high mountain community with medieval housing conditions, in some ways reminiscent of Europe at the time of the Black Death. Based on their analyses, the researchers concluded that the first people infected had acquired plague from fleas that had previously bitten infected guinea pigs (which are raised locally for meat), and that the pathogen was subsequently transmitted directly among humans, abetted by primitive living conditions and poor access to health care. Hayes said that local climatic conditions, influenced by El Niño, had apparently influenced rodent population dynamics so as to favor the epizootic of plague that preceded the human outbreak. A post-outbreak comparison of dengue incidence in the contiguous cities of Nuevo Laredo, Mexico, and Laredo, Texas, further illustrated the profound influence of environment on vector-borne disease (Reiter et al., 2003). There, Hayes and coworkers found that although the dengue vector, the mosquito Aedes aegypti, was abundant in the U.S. city, disease incidence was higher in its poorer Mexican neighbor, where far fewer houses were equipped with intact window screens and air conditioners. An investigation of a pneumonic tularemia outbreak on Martha’s Vineyard, Massachusetts, which affected 10 adults, found that mowing lawns or cutting brush was the predominant risk factor for illness. The researchers findings point to small mammals, which presumably contaminated the foliage with the pathogen; the bacteria was then aerosolized and inhaled by workers during mowing. The single fatal case in this outbreak was a man who had limited access to health care. However, the ecological determinants that might explain why this outbreak—the second ever reported in the United States—occurred at that particular time remain unclear. Turning from outbreak investigation to disease prevention, the authors of the chapter’s first paper, workshop speaker Thomas Scott and Amy Morrison, of the University of California, Davis, present considerable evidence in favor of the use of locally adaptable tools and strategies for dengue prevention, a detailed set of goals for defining and measuring risk factors for human dengue infection, and four “conceptual shifts” in vector control strategy that, they argue, “will substantially improve dengue prevention.” Central to the authors’ recommendations are the observations that (1) dengue transmission risk is strongly associated with
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary adult (but not immature) vector population densities, and (2) that the vast majority of human dengue infections occur in the home. Advantages to insect control strategies focused within homes can transcend Ae. aegypti and dengue—and even vector-borne disease—by decreasing population densities and lifespans of various disease-transmitting insects, as well as those of pests such as bed bugs, cockroaches, and filth flies. Thus, Scott and Morrison conclude, “what was originally conceived as an Ae. aegypti control program can be leveraged into a cost and operationally effective public health program that reduces a variety of diseases and pest problems.” The second essay in this chapter, from Lars Eisen and workshop presenter Barry Beaty of Colorado State University, discusses initiatives by a private-public partnership, the Innovative Vector Control Consortium (IVCC; see also Summary and Assessment section, “Disease Prevention Strategies”), to reduce the impact of dengue. The consortium is funding the construction of a computer-based decision support system to inform the design and implementation of effective local and regional vector control programs, as well as the development and dissemination of proactive indoor vector control measures. A second paper by Beaty and Eisen in Chapter 3 reviews public health and scientific responses to a broad range of vector-borne disease issues raised in the Institute of Medicine report Microbial Threats to Health (2003). A subsequent paper, by presenter Lyle Petersen of the CDC, describes the history and impact of WNV in the United States and identifies challenges to the surveillance and prevention of this emerging vector-borne disease in his contribution to this chapter. As part of its response to the 1999 WNV outbreak in New York City, the CDC established ArboNET, the first national human-animal disease surveillance system. Administered by the CDC, ArboNET is a real-time electronic reporting system that captures data on WNV in humans, dead birds, mosquitoes, horses, and live captive sentinels of disease (chickens). “A combination of human and veterinary surveillance will be essential to monitor the ongoing ecological impact of WNV and to guide disease prevention efforts,” Petersen concludes. The experience with WNV demonstrates that the epidemiological pattern in areas of importation of an exotic arbovirus may bear little resemblance to that which occurred in its previously endemic area. As discussed in the Summary and Assessment (see “Weather, Climate, and Prediction”) and in Chapter 1, a climate-based model predicted a recent outbreak of RVF in Kenya, significantly improving response time and outcome. In his contribution to this chapter, workshop presenter C. J. Peters, of the University of Texas Medical Branch, Galveston, discusses the epidemiology and ecology of RVF—essential factors in its status as an emerging arboviral disease agent—and describes work in progress toward the development of veterinary and human vaccines to achieve better control of this deadly and costly disease. Peters warns of the potential of the RVF virus to expand its geographic range to the United
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary States and urges greater appreciation for the threat it poses to people and livestock throughout the world. A combination of vector control and treatment with an effective drug are currently used to control malaria, the most burdensome of vector-borne diseases with regard to morbidity and mortality. In the chapter’s fifth essay, presenter Michael Coleman of the Medical Research Council of South Africa and co-author Janet Hemingway of the Liverpool School of Tropical Medicine, United Kingdom, describe the use of routine entomological surveillance to increase the effectiveness of malarial vector control. Such surveillance permits earlier detection of, and response to, increases in pathogen transmission, which may indicate the development of insecticide resistance. The authors review vector surveillance techniques and describe their successful application to guide local vector control efforts. They also discuss potential uses of these techniques in modeling disease transmission and by decision support systems that inform national or regional vector control efforts. Bluetongue, a viral disease transmitted primarily among ruminant animals (sheep and cattle) by biting midges of the genus Culicoides, results in economic losses worldwide of approximately $3 billion per year due to morbidity and mortality of animals, trade embargoes, and vaccination costs (FAO, 2007; Osburn, 2007). In his contribution to this chapter, presenter Bennie Osburn of the University of California, Davis, describes the history, distribution, and impact of the disease, which is present on six continents. Bluetongue has become established in Europe only within the past 5 years, coincident with abnormally high summer temperatures, and thus may provide insights into the behavior of other vector-borne diseases potentially expanding their geographic range with increasing temperatures associated with global climate change. Osburn notes that bluetongue has so far been adequately controlled in eastern and southern Europe; however, this has been achieved primarily through the use of modified live virus vaccines, which pose the threat of reassortment, via vector transmission, with wild-type viruses. The chapter’s final paper, by presenter Charles Calisher of Colorado State University and co-authors, describes a comprehensive, longitudinal study of the transmission of Sin Nombre hantavirus (SNV), the pathogen that causes the rodent-borne viral disease hantavirus pulmonary syndrome (HPS) among deer mice (Peromyscus maniculatus) in Colorado. The first human epidemic of HPS, reported in the spring of 1993, and a subsequent outbreak in 1998, occurred in the Four Corners region of the continental United States, where the borders of Utah, Colorado, New Mexico, and Arizona meet. Research by Calisher and coworkers on the transmission and maintenance of SNV reveals important environmental influences on these processes and thereby provides a model that may be extrapolated to other vector-borne zoonotic agents. Such longitudinal studies, they conclude, “may be the only current means available to identify predictors of risk for rodent acquisition of this virus and for subsequent transmission to humans.” In
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary addition, they note, “although particular zoonotic diseases have particular etiologic agents, the controlling conditions for each may have enough similarities to provide us with predictors of risk for acquisition and, therefore, with bases for prevention and control measures.” As a rodent-borne viral disease, HPS has invited consideration of nonarthropod vectors of infectious disease. The role of “vector” might be further expanded to include humans in the case of SOD, an infectious plant disease that has been spread across wild lands by hikers, mountain bikers, and equestrians. Speaker David Rizzo, of the University of California, Davis, has worked to understand and mitigate the effects of SOD in California since shortly after its emergence there in the mid-1990s (see Summary and Assessment section, “Lessons Learned: Case Studies of Vector-Borne Diseases”). The disease was first recognized after it caused widespread dieback of several tree species in West Coast forests; it also causes nonfatal leaf disease in many other plants, including rhododendrons and California bay laurel, and has been detected in the United Kingdom and Europe (Rizzo and Garboletto, 2003). The infectious agent of SOD is the fungus-like water mold Phytopthora ramorum, which thrives in the cool, wet climate of California coastal forests. Human visitors to these forests—who pick up P. ramorum spores on their clothes and shoes, equipment, and companion animals—appear to be the main “vectors” for the spread of this pathogen over long distances. However, because the SOD pathogen was identified only 7 years ago, researchers are still learning about its disease cycle and transmission dynamics. As they probe the ecological context and epidemiology of SOD, Rizzo and colleagues are also working to manage the disease in natural ecosystems and in the nursery trade. To target monitoring efforts, they developed risk models based on findings from laboratory studies of the pathogen’s sporulation behavior, combined with data on the distribution of host species and climate. Areas identified by the models are investigated by various methods, including aerial imaging, plot-based monitoring, and sampling streams to determine whether the pathogen is present within a watershed. If the pathogen is detected at a sufficiently early stage, the affected vegetation may be clear-cut and burned in hopes of eradicating the disease. While this approach has not yet proven completely successful, Rizzo observed, it has significantly limited the spread of SOD. For areas where the pathogen is established, he and coworkers attempt to develop management schemes that avoid deleterious ecological consequences, such as the growth of invasive plant species following clear-cutting. In order to anticipate the potential effects of such management strategies, Rizzo collaborates with many ecologists. “Understanding the ecology of the forest is absolutely critical [to managing areas with established disease],” he said. “We’ve been doing a lot of work on how we can manipulate these [infected] forests, whether it’s reintroducing fire [or] removing some hosts [through clear-cutting], to figure out a way that we can live with this disease.”
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary LONGITUDINAL FIELD STUDIES WILL GUIDE A PARADIGM SHIFT IN DENGUE PREVENTION Thomas W. Scott, Ph.D.1 University of California Amy C. Morrison, Ph.D. University of California Introduction When done properly, vector control is a well-documented and effective strategy for prevention of mosquito-borne disease. Familiar examples of successful mosquito vector interventions include the worldwide reduction of malaria in temperate regions and parts of Asia during the 1950s and 1960s (Curtis, 2000; Rugemalila et al., 2006), yellow fever during construction of the Panama Canal, yellow fever throughout most of the Americas during the 1950s and 1960s (Soper, 1967), dengue in Cuba and Singapore (Ooi et al., 2006), and more recently dengue in parts of Vietnam (Kay and Nam, 2005). That these programs significantly improved public health is indisputable. Why then is disease burden from vector-borne diseases like malaria (Sachs and Malaney, 2002) and dengue increasing (WHO, 2006a)? Why has vector control not been effectively applied more often so that it reduces or appreciably minimizes disease? Unsuccessful programs are often attributed to a lack of resources, lack of political will, or ineffective implementation (Attaran, 2004; Gubler, 1989b; Halstead, 1993; Killeen et al., 2002). Just as responsible for control failures are deficiencies in understanding relationships between vector ecology and pathogen transmission dynamics, the most appropriate methods for assessing and responding to appreciable risk, and the failure to use existing knowledge or surveillance information to make informed control decisions. It is reasonable to conclude that despite more than a century of vector-borne disease investigation, fundamental concepts in disease prevention remain incompletely defined and underutilized. The goal of this paper is to illustrate the power of improved ecologic and epidemiologic understanding for increased effectiveness of vector control for dengue. The concepts and processes we discuss are not limited to dengue and, therefore, consideration should be given for their application to other vector-borne diseases. We assert that a better understanding of virus transmission dynamics, concepts, and tools and strategies for disease prevention will fundamentally change and significantly improve public health programs for dengue prevention. Current programs, which emphasize universally prescribed surveillance and control, have hindered development of an appropriate conceptual and factual foundation for 1 Department of Entomology, Davis, California. E-mail: firstname.lastname@example.org.
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary adaptive disease prevention programs and help to explain why contemporary vector control programs too often fall short of public health expectations. Our principal recommendation is that enhancing dengue prevention will require locally adaptable tools and strategies. To accomplish this there is an urgent need for more comprehensive, longitudinal field studies of vector-borne diseases that (1) quantitatively define relationships between the most meaningful measures of risk and human infection and (2) use that information to direct public health measures that prevent or minimize disease. Information necessary to fill this knowledge gap should be obtained in the framework of interrelated longitudinal cohort studies that progressively build on one another, providing an increasingly detailed understanding of fundamental processes in pathogen transmission, epidemiology, and disease control. Based on our experience, critical missing knowledge of risk assessment and disease prevention can only be gained by carrying out integrative research that embraces the vector, pathogen, and human host. Too often vector-borne disease specialists study the arthropod vector, disease, or pathogen separately. Only by studying the system in total over a considerable period of time will we gain the greater insight into the complexity of interactions between components of transmission and disease that are essential for design, implementation, and evaluation of increasingly more successful disease prevention programs. In the case of dengue, until a vaccine or chemotherapy become available, control programs will continue to be limited to vector control, which in most cases means reducing mosquito vector populations. But do we understand Ae. aegypti and dengue virus (DV) transmission well enough to make specific recommendations for modifications in vector populations, short of vector eradication, that will result in a predictable public health outcome? Review of relevant literature clearly indicates that the answer to this critical question is no. Dengue Epidemiology and Ecology Worldwide, DV infections cause more human morbidity and mortality than any other arthropod-borne virus disease (Farrar et al., 2007; Gubler, 2002c, 2004; Gubler and Kuno, 1997; Kuno, 1995; MacKenzie et al., 2004; Monath, 1994). It is estimated that 2.5 to 3 billion people are at risk of infection in tropical parts of the world each year. In urban centers of Southeast Asia, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are among the leading causes of pediatric hospitalization. During the last 30 years dengue has emerged as a major international public health threat in the Americas (Rigau-Perez et al., 1998; WHO, 2006b). Dengue fever (DF), DHF, and DSS are caused by four closely related, but antigenically distinct, single-stranded RNA viruses (DV-1, DV-2, DV-3, and DV-4) in the genus Flavivirus, family Flaviridae. All four serotypes cause a range of human disease, including asymptomatic infections, undifferentiated fever, and classic DF (Gubler, 2002c, 2004; Gubler and Kuno, 1997; Rothman and Ennis,
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary 1999). Sequential infections with different serotypes are possible because infection with one serotype provides lifelong protection from a homologous infection, but is only briefly cross-protective against heterologous serotypes. The etiology of serious illness is not completely understood but is suspected to be due to immune enhancement and/or variation in virus virulence (Gubler, 2002c, 2004; Kochel et al., 2002; MacKenzie et al., 2004; Monath, 1994; Rothman and Ennis, 1999; Watts et al., 1999). It is estimated that annually there are between 50 and 100 million DF cases and 250,000 to 500,000 DHF/DSS cases worldwide. If untreated, the case fatality rate for DHF/DSS can approach 30-40 percent; with supportive therapy, less than 1 percent of severely ill patients die (Halstead, 1993). DVs generally persist in endemic foci by a horizontal Ae. aegypti-human transmission cycle (Gubler, 1989a; Rodhain and Rosen, 1997). After an incubation period of 3-15 days (typically 4-7 days) in the human, disease symptoms are first observed (Focks et al., 1995; Waterman and Gubler, 1989). Viremia often precedes fever, typically lasts ~5 days, and usually subsides in concert with the inability to detect virus in the blood (Vaughn et al., 2000). Mosquito vectors become infective after biting a viremic individual and surviving an extrinsic incubation period of 7-14 days (Watts et al., 1987). Although other mosquitoes in the subgenus Stegomyia have been incriminated as vectors, Ae. aegypti is the most important dengue vector worldwide (Gubler and Kuno, 1997). Once infective, Ae. aegypti can transmit virus each time it probes its mouthparts into a human or imbibe a blood meal (Putnam and Scott, 1995a,b). Ae. aegypti is uniquely adapted to a close association with humans and efficient transmission of DV. Immature forms develop primarily in artificial, man-made containers (Gubler, 1989a). Highly anthropophilic, females rest inside houses where they feed frequently and preferentially on human blood (Scott et al., 1993b, 2000b), which confers a fitness advantage (Scott et al., 1997; Morrison et al., 1999; Harrington et al., 2001a). Because food, mates, and substrates for laying eggs are readily available within the human habitations where female Ae. aegypti reside, dispersal beyond 100 m is not necessary and is detected in only a very small proportion of the adult population (Morland and Hayes, 1958; McDonald, 1977; Trpis and Hausermann, 1986; WHO, 1997, 1999; Edman et al., 1998; Harrington et al., 2001a,b, 2005). This indicates that most dispersal of DV occurs via movement of viremic human hosts. These features make Ae. aegypti an efficient vector and DV transmission can occur even when Ae. aegypti population densities are very low (Kuno, 1995). Dengue Control Presently, dengue control is dependent on the reduction or elimination of Ae. aegypti. Although dengue vaccines are a focus of attention (Pediatric Dengue Vaccine Initiative funded by the Bill and Melinda Gates Foundation2), currently 2 See http://www.pdvi.org.
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary there is no licensed vaccine. Developing a dengue vaccine is a challenge because it will need to be tetravalent to avoid the risk of immune enhancement. Even after a vaccine or drug is available, we expect that vector control will remain important. The benefits of a vaccine will be limited by its safety profile, efficacy, cost, and capacity for delivery (DeRoeck et al., 2003; Shepard et al., 2004). Although a variety of dengue vaccines are being developed and there are promising leads for antidengue drugs at the time of this writing (Farrar et al., 2007), none of the vaccine candidates have been evaluated in Phase III trials, and licensing is not imminent for clinical use of prospective drugs. Critical information on efficacy and cost was, therefore, not available. Even with superior efficiency, which considering the complexity of dengue disease we can not assume without rigorous evaluation, a dengue vaccine will clearly not protect against infection with other mosquito-borne viruses. Furthermore, in order for there to be widespread application of a dengue vaccine in endemic countries the cost would need to be low (no more than $0.50 per dose) and preferably applied in a single dose (DeRoeck et al., 2003). In a best-case scenario there will be perfect protection against all DVs and perhaps some cross-protection for other Ae. aegypti-borne viruses in the genus Flavivirus (i.e., yellow fever). A dengue vaccine will not protect against infection with nonflaviruses and, realistically, complete vaccine coverage seems unlikely. Conversely, effective vector control reduces risk of infection for all Ae. aegypti-borne arboviruses (e.g., dengue, yellow fever, and chikungunya) across the human population. This alone is a compelling reason for continuing Ae. aegypti control after an effective DV vaccine becomes available. Current vector control methodologies for Ae. aegypti surveillance and control emphasize techniques that were developed for mosquito eradication to prevent yellow fever (see “Measuring Mosquito Density,” below). Although those programs were initially successful in helping to define the role of vector eradication in disease prevention, the approach taken provided little insight into quantitative relationships between mosquito abundance and DV transmission (PAHO, 1994; Gubler and Kuno, 1997; Reiter and Gubler, 1997; Scott and Morrison, 2003). For a variety of reasons, mostly changing urban environments and limited economic resources, in 1994 the Pan American Health Organization (PAHO) departed from the eradication paradigm and declared eradication of Ae. aegypti an unattainable goal (PAHO, 1994). The new goal of dengue control programs is cost-effective utilization of limited resources to reduce vector populations to levels at which they are no longer of significant public health importance (Gubler, 1989b; PAHO, 1994). Aedes aegypti control programs worldwide vary widely, in many cases driven by country-specific economic constraints on local health agencies. Most countries use a combination of vector surveillance, chemical treatment of Ae. aegypti larval habitats, and either regular or emergency applications of ultra low volume (ULV) space sprays. Aerosol insecticides are effective if they reach female Ae. aegypti resting indoors, where they otherwise avoid insecticide contact (Reiter and Gubler, 1997). This means that space sprays need to be applied inside houses
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary using backpack applicators rather than from high-profile trucks moving down city streets or from airplanes flying over houses. Farther up the product development pipeline, disease control based on genetic manipulation of mosquito vectors is being investigated in the laboratory (Beaty, 2000; James, 2005) and will require extensive field evaluation before it can be deployed (Scott et al., 2002; Louis and Knols, 2006). Successful dengue vector control programs in Singapore and Cuba (Ooi et al., 2006), promising results from trials with insecticide-treated materials in Latin America (Kroeger et al., 2006), and cost-effective larval control in Cambodia (Suaya et al., 2007) fortify the notion that properly done vector control effectively prevents dengue disease. Enhancing tools and strategies for vector surveillance and control should be a priority in the fight against dengue. The PAHO strategy emphasizes vector surveillance, with the objectives of maintaining Ae. aegypti populations below or close to transmission thresholds, slowing DV transmission, and accordingly, reducing sequential infections with heterologous serotypes that can increase the incidence of serious disease (Vaughn et al., 2000). Although intuitively reasonable, this approach has not been systematically validated and the implication is that controlling serious disease rather than all disease is a viable public health goal. No well-controlled field studies have been published that clearly define the key relationships between vector density and human infection. There is an urgent need for entomological and epidemiological data that refine understanding of relationships among entomological risk factors, incidence of human infection, and clinical disease manifestations. This has rarely been done for any vector-borne disease, exceptions being arbovirus studies of western and St. Louis encephalitis viruses in southern California by Reeves and his colleagues (Reeves, 1971; Olson et al., 1979). Yet reduction of vector populations remains a prominent, underlying premise of many current public health recommendations for control of a long list of vector-borne diseases, including dengue. Prospective studies are urgently needed to test and refine fundamental assumptions of this strategy for dengue control. Establishing Goals for Dengue Prevention Programs A fundamental observation in dengue prevention is that there is no single method or approach that works in all situations (Scott and Morrison, 2003). Ecology and epidemiology of virus transmission vary from one place and/or time to another. To help establish dynamic goals for disease prevention programs that can be adapted across the diversity of situations in which dengue exists, we developed four interrelated questions that assist in goal setting. The concepts discussed are not limited to dengue, and therefore, can be applied to other vector-borne diseases.3 Location-specific answers to these questions are important steps in the development of adaptive dengue control programs. 3 See Scott and Morrison (2003) for additional discussion on each topic.
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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections - Workshop Summary What is an acceptable level of dengue risk? This is a complex question. The answer will be situation- and location-specific depending on historical patterns of local DV transmission, available resources, and competing public health priorities. In order to reach properly informed decisions, entomologic and epidemiologic data will need to be considered. That will require appropriate coordination, sharing of relevant information, and teamwork among different public health entities (e.g., vector control and epidemiology departments) (Ooi et al., 2006). Goals will likely change as epidemiologic conditions and public health expectations change. This implies that the definition of what constitutes acceptable risk will vary from eradication of all clinically apparent dengue cases to “living with dengue but not DHF.” Consideration of this issue is an important part of the paradigm shift away from universally prescribed control actions and toward local experts developing a dynamic system for repeatedly reevaluating what are the most effective control tools, strategies, and application protocols for their particular situation. What are the mosquito densities (thresholds) necessary to meet agreed upon risk goals? The new policy for dengue control implies that although there may be some DV transmission, properly applied vector control will reduce or eliminate severe disease (Gubler, 1989b; PAHO, 1994). The objective, therefore, is to lower the force of infection and thus minimize severe disease by managing the density of mosquito vector populations. This is a tricky proposition. How does one know when vector populations have been reduced to levels at which they are no longer significant? What constitutes no longer significant? What exactly are the epidemiological objectives that guide this approach? Control strategies that do not aim for vector eradication, like this one, require surveillance (entomological and epidemiological) that informs disease prevention responses. In this case, the objective is to identify an entomological threshold below which there will be no epidemic transmission. Values above the thresholds will trigger control actions. Although the concept is straightforward, implementation is challenging. Without the appropriate knowledge and analytical tools, it can be difficult to distinguish between the mere presence of a vector species and situations when vector control is required to prevent an epidemic (Peterson and Higley, 2002). Operationally friendly systems for estimating action thresholds from locally available surveillance, weather, and human population data would be a significant addition to the armature against dengue. Thresholds for DV transmission can fluctuate depending on mosquito density, overall immunity of the local human population (i.e., herd immunity), introduction of novel virus serotypes or genotypes, the nature of contact between mosquito vectors and human hosts, human density, and weather (Scott and Morrison, 2003). Temperature is particularly important because of its inverse relationship with extrinsic incubation. Even after key parameters have been identified, estimation can require acquisition of data that are hard to obtain (e.g., site-specific herd immunity) or can be encumbered by complicated assumptions (e.g., spatially and
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