Resurgence and Emergence of Human Vector-Borne Diseases

Infectious diseases transmitted by insects and other animal vectors have long been associated with significant human illness and death. In the 17th through early 20th centuries, human morbidity and mortality due to vector-borne diseases outstripped that from all other causes combined (Gubler, 1998). The early 20th century discovery that mosquitoes transmitted diseases such as malaria, yellow fever, and dengue led quickly to the draining of swamps and ditches where mosquitoes bred, and eventually to the use of pesticides, which reduced populations of these disease vectors. The adoption of vector control measures, including the application of a variety of environmental management tools and approaches,⁶ coupled with improvements in general hygiene, enabled much of the world to experience decades of respite from major vector-borne diseases in the first half of the 20th century. This success proved fleeting, however, and vector control programs waned due to a combination of factors including the development of pesticide resistance or—sometimes doomed by their own success—the loss of financial support when vector-borne diseases were no longer perceived as an important public health threat.

Today, vector-borne diseases are once again a worldwide concern and a significant cause of human morbidity and mortality, as Figure SA-1 illustrates (WHO, 2004c). Table SA-1 lists the disease burden (calculated in disability-adjusted life years, or DALYs) associated with each of several major human vector-borne diseases (WHO, 2004b).

FIGURE SA-1

Deaths from vector-borne diseases. SOURCE: Reprinted with permission from the World Health Organization (2004c).

TABLE SA-1

Estimates of the Global Burden of Disease Caused by Major Vector-Borne Diseases.

Malaria accounts for the most deaths by far of any human vector-borne disease. The causative agents, Plasmodium spp., currently infect approximately 300 million people and cause between 1 and 3 million deaths per year, mainly in sub-Saharan Africa (Breman, 2001). As described by keynote speaker Duane Gubler, of the University of Hawaii, malaria provides a particularly dramatic example of vector-borne disease reemergence (Gubler, 1998). As stated by Scott and Morrison (see Chapter 2), 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). Following the drastic depopulation of its vector, the anopheline mosquito, in the first half of the 20th century, malaria began its resurgence in Asia in the late 1960s. In Sri Lanka, where only 17 cases of malaria were reported in 1963, an epidemic of more than 440,000 cases erupted 5 years later after preventive vector control strategies were replaced with case-finding and drug treatment. Similarly, by the mid-1970s, millions of new post-control cases had occurred in India. In Africa, a recent upsurge in infection, punctuated by several major epidemics, has erupted in endemic areas (Nchinda, 1998).

Explosive epidemics have also marked the resurgence of plague, dengue, and yellow fever, a situation that Gubler characterized as particularly worrisome. Plague is carried by rodent fleas, which transmit the pathogen Yersinia pestis when they bite animals or humans (CDC, 2005a). Millions of people in Europe died from plague in the Middle Ages; today, antibiotics are effective against plague when administered promptly following infection. A 1994 plague epidemic in Surat, India, produced one of the first health emergencies that had a major documented impact on the global economy,⁷ Gubler said. When inadequate public health and government response to initial cases led to panic, nearly a quarter of the city’s population fled Surat to other Indian towns and cities, carrying the disease with them. For the first time in 33 years, the World Health Organization (WHO) implemented the International Health Regulations (IHR) to contain the potential pandemic, resulting in a ban on shipping and travel that cost India an estimated $3 billion and the global economy nearly twice that sum.

Dengue’s resurgence has been marked not only by epidemics, but also by the emergence of a more severe form of disease, dengue hemorrhagic fever (DHF) (Gubler, 1998). Ecological disruption in Southeast Asia, brought on by World War II, led to increased transmission of dengue and, eventually, a pandemic. As illustrated in Figure SA-2, dengue/DHF is one of the world’s fastest-growing vector-borne diseases (see Gubler in Chapter 1) (WHO, 2007a).⁸

FIGURE SA-2

Dengue/dengue hemorrhagic fever, average annual number of cases reported to WHO, 1955–2005. SOURCE: Courtesy of WHO.

The summer of 2007 brought the worst dengue epidemic in nearly a decade to Asia (Mason, 2007). By July—well before transmission was expected to have peaked—Indonesia alone had experienced over 100,000 infections and 1,100 deaths. The epidemic was apparently spurred by weather conditions: a period of drought, during which water stored around homes provided an ideal habitat for mosquitoes to breed. This was followed by unusually hot, humid weather, in which adult mosquitoes thrive (ProMed-Mail, 2007; Anyamba et al., 2006).

Yellow fever, which along with dengue was controlled in the Americas by a variety of mosquito abatement techniques through the mid-20th century, remains a constant threat, with concerns that it might make its first appearance in Asia (see Gubler in Chapter 1). Yellow fever virus has caused major epidemics in Africa and South America (Gubler, 2001; Monath, 2001), and sylvatic reservoirs in these areas provide an ongoing threat for its reintroduction into Aedes aegypti-infested metropolitan areas throughout the world. Ae. aegypti is also the principal vector of the dengue viruses (IOM, 2003). The virus was apparently carried by infected birds (and possibly mammals as well) abetted by a vast and diverse population of mosquitoes (see Gubler in Chapter 1 and Petersen in Chapter 2). Indeed, Gubler concluded, nearly all of the most important vector-borne human diseases have exhibited dramatic changes in incidence and geographic range in recent decades.

Impact of Vector-Borne Animal and Plant Diseases

The majority of emerging, reemerging, and novel human infectious diseases are zoonoses (diseases that can be transmitted from animal reservoirs to humans), of which vector-borne diseases comprise a large percentage (IOM, 2003). Rift Valley fever (RVF), an acute mosquito-borne viral disease, primarily affects livestock (e.g., cattle, buffalo, sheep, goats) but can also be transmitted to humans through direct contact with the tissues or blood of infected animals, as well as by mosquito bites (see Linthicum et al. in Chapter 1 and Peters in Chapter 2) (CDC, 2007a). Outbreaks of RVF among animals can spread to humans; the largest reported human outbreak, which occurred in Kenya during 1997–1998, resulted in an estimated 89,000 infections and 478 deaths (CDC, 2007b). African trypanosomiasis, also known as African sleeping sickness, causes estimated losses in cattle production of more than $1 billion per year, and perhaps five times that amount in lost opportunities for development (FAO, 2007a). The disease currently affects an estimated 500,000 people in sub-Saharan Africa but threatens an estimated human population of 60 million, as well as 50 million head of cattle (FAO, 2007a). Given the rapid growth of human and domesticated animal populations, and their increasing contact with each other and with wild animals, the zoonotic disease threat is expected to increase (Karesh and Cook, 2005; Murphy, 1998; NRC, 2005).

Vector-borne diseases have the potential to cause enormous economic harm when they affect livestock and crops, and even the threat of infection can severely limit trade. For example, bluetongue, a viral disease transmitted among sheep and cattle by biting midges, results in annual losses of approximately $3 billion due to morbidity and mortality of animals, trade embargoes, and vaccination costs (see Osburn in Chapter 2) (FAO, 2007b; Osburn, 2007). Although considerable attention and resources have been committed to agriculturally important vector-borne diseases such as bluetongue, RVF, and African trypanosomiasis, relatively little is known about the vast majority of vector-borne disease-causing organisms that currently infect only wild animals. Yet such diseases can disrupt entire ecosystems and, under the right conditions, could potentially expand their host range to include livestock, pets, or humans (Marin/Sonoma Mosquito and Vector Control District, 2005).

Vector-borne plant diseases profoundly affect agricultural productivity and ecosystem dynamics (Gergerich and Dolja, 2006; Purcell, 1982; Weintraub and Beanland, 2006). Examples include the bacterium, Xylella fastidiosa, which damages a wide range of plant species; in grapevines, it causes Pierce’s disease, a significant threat to California’s table grape and wine industries (see Almeida in Chapter 1) (Fletcher and Wayadande, 2002; NRC, 2004). Emerging vector-borne viral and bacterial diseases of citrus, most of which were introduced into the Americas since 2000, threaten 85 percent of the world’s orange juice production, which resides in the United States and Brazil (Almeida, 2007; Woodall, 2007). Due in part to the difficulty of discerning whether damage to plants has been caused by disease, insects, or adverse weather conditions, the overall impact of vector-borne plant diseases cannot be accurately estimated (Almeida, 2007; Gergerich and Dolja, 2006); however, annual losses in crop quality and yield associated with certain vector-borne viruses are measured in the billions of dollars (Bowers et al., 2001; Gergerich and Dolja, 2006; Hull, 2002; Sherwood et al., 2003).

Vector-borne plant diseases also cause immeasurable damage to ecosystems, which may not be recognized until it threatens human health, safety, or prosperity. For example, Sudden Oak Death (SOD)—an emerging infectious disease that has been spread across wild lands by hikers, mountain bikers, and equestrians (i.e., human “vectors”)—was recognized after it caused widespread dieback of several tree species in West Coast forests (see subsequent section, “Lessons Learned: Case Studies of Vector-Borne Diseases” and Chapter 2) (California Oak Mortality Task Force, 2004; Rizzo and Garboletto, 2003). These losses are likely to reduce shelter and food sources for wildlife, increase fire frequency and intensity, and compromise water quality due to soil surface exposure. Moreover, such ecological effects can be long-lasting. For example, changes in forest composition in the Canadian Rocky Mountains, which resulted from the deaths of lodgepole pines due to an infestation of bark beetles, have persisted for as long as 65 years (Current Results, 2007; Dykstra and Braumandl, 2006).

Back to the Future

Infectious diseases have always accompanied humans, animals, plants, and goods in their travels. “Since the beginning of recorded history, disease epidemics have been associated with trade,” Gubler observed, noting that the plague epidemic that killed one in every four Europeans in the 14th century is believed to have been introduced to the continent by commercial trade with Asia. The rapid expansion of global trade and transportation since 1700 has been associated with the spread of mosquito-borne diseases such as yellow fever and dengue. Dutch Elm disease (so named because it was first described in Holland, in 1921) also originated in Asia and probably arrived in the United States on a shipment of lumber from Europe in the 1930s, after which it devastated American elms in forests and on city streets (Plant Disease Diagnostic Clinic, Cornell University, 2005; Riveredge Farms, 2004).

Today’s integrated global economy has accelerated the transnational flow of capital, knowledge, people, livestock and animal products, and plant materials, as well as the introduction of pathogens and their vectors to new hosts and geographic ranges. Presented with these opportunities, several vector-borne diseases considered most problematic 100 years ago, such as malaria, dengue, plague, and yellow fever, once again pose serious threats to public health. While we have gained considerable insights into the biology and management of certain vector-borne diseases over the past century, limited capacity exists to apply that knowledge. In addition, as many workshop participants observed, much remains to be learned about the ecology and epidemiology of a broad spectrum of vector-borne diseases, including those that have recently emerged. Subsequent sections of this summary therefore explore both what we know and what we most need to understand about the biology of vector-borne diseases, the factors that precipitate disease emergence and resurgence, discussion about key research areas needed to fill the current gaps, and strategies for disease detection and response.

Dynamics of Disease Transmission

A standard graphic representation of the ecology of infectious disease features host, pathogen, and environment as circles intersecting in a common zone that defines permissive conditions for disease transmission (see Figure SA-3).

FIGURE SA-3

The epidemiological triad. The familiar “epidemiological triad” concept (host-pathogen-environment), as illustrated in the famous diagram of Snieszko (1974), neatly illustrates the complex interplay of factors that result in disease at (more...)

The ecology and epidemiology of vector-borne diseases are particularly complex and often involve multiple disease cycles through alternate vectors and hosts, noted presenter Rodrigo Almeida of the University of California, Berkeley (see Chapter 1). His octagonal model, shown in Figure SA-4, depicts key influences on vector-borne plant disease; a similar diagram could illustrate the web of relationships governing animal and human vector-borne diseases. The inherently complex ecologies of individual vector-borne diseases are discussed in several case studies collected in Chapter 2.

FIGURE SA-4

Factors affecting plant disease outbreaks. SOURCE: Almeida (2007).

A confluence of risk factors for a vector-borne disease may result in an outbreak, according to speaker Ned Hayes of the Centers for Disease Control and Prevention (CDC). An outbreak is a condition defined by an increase over background of disease incidence within a subpopulation of potential hosts. 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 may frequently be influenced by environmental conditions and human behavior. To illustrate these connections, Hayes 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 (see Chapter 2 Overview).

Approximately 80 percent of vector-borne disease transmission typically occurs among 20 percent of the host population (Smith et al., 2005; Woolhouse et al., 1997). The distribution of the incidence of vector-borne diseases is grossly disproportionate, with the overwhelming impact in developing countries located in tropical and subtropical areas (CIESIN, 2007). Using his work on dengue as an example, presenter Thomas Scott of the University of California, Davis, described the challenges—as well as the potential rewards—of investigating the dynamic relationships between vector population density and risk for disease transmission. His findings, which are discussed in detail in Chapter 2 (see Scott and Morrison), as well as in a subsequent section of this summary, “Lessons Learned: Case Studies of Vector-Borne Diseases” support the notion that heterogeneity in exposure to infection can be exploited to optimize vector control. He cautioned, however, that such efforts cannot succeed unless they are tailored to the local epidemiological and ecological conditions that influence disease transmission.

Disease Prevention Strategies

Vector control is the primary means of preventing vector-borne disease. In the case of dengue, the goal of current public health policy is to prevent explosive epidemics by managing mosquito populations—a difficult proposition, given the intricacies of mosquito ecology and population biology, Scott said (see Scott and Morrison in Chapter 2). Seeking a more efficient alternative, he and colleagues used a simulation model to identify two important sources of heterogeneity in dengue transmission—age of infection and location—in their study area, the impoverished city of Iquitos, Peru. Based on these findings, they developed a cost-efficient spray plan that targeted those areas of the city that would have the largest impact; the timely implementation of this plan by local authorities appears to have averted an epidemic. This result, and those of similar studies, imply that careful modeling of transmission patterns and vector life cycles may suggest targeted interventions directed toward specific host subpopulations and locations associated with high rates of vector-borne infections. Such an approach may be far more effective than broad-spectrum, non-specific, vector control efforts (Getis et al., 2003; Morrison et al., 2004; Vanwambeke et al., 2006).

Recognition of shared features among vector-borne diseases—some broad, such as their ecological and epidemiological complexity; some narrow, such as a common vector—is prompting the development of guidelines for outbreak prevention and management. The purpose of these guidelines, as envisioned by Scott, would not be to prescribe universal solutions, but rather to help public health officials choose, apply, monitor, and evaluate pathogen detection and disease prevention methods that fit their particular circumstances. This is the underlying premise of decision support systems (DSSs) that have recently been launched for malaria and dengue and which could potentially be extrapolated to other vector-borne diseases, according to speaker Barry Beaty of Colorado State University. The development of both DSSs is supported by the Innovative Vector Control Consortium (IVCC), a private-public partnership funded by the Bill and Melinda Gates Foundation (see Eisen and Beaty in Chapter 2, and Beaty and Eisen in Chapter 3).¹⁰

Beaty, who has participated in efforts to establish the DSS for dengue, described it as a rationally designed, computer-based information system that serves three distinct purposes: to assist local and regional authorities in designing evidence-based vector control programs; to collect information on pesticide and insecticide resistance; and to provide proactive surveillance and modeling of dengue transmission. The malaria DSS, which is the predecessor and model for the dengue DSS, evolved from an interactive geographical information system (GIS) for insecticide resistance data that was developed to support malaria control in Africa (Coleman et al., 2006). The malaria DSS currently encompasses information on health and intervention management, entomology, geography, and surveillance.

Michael Coleman, a developer of the malaria DSS from the Medical Research Council of South Africa, focused on the crucial role of information on insecticide resistance in addressing malaria in his workshop presentation (see Coleman and Hemingway in Chapter 2 and the subsequent section, “Lessons Learned: Case Studies of Vector-Borne Diseases”). By way of introduction, he offered a concise rationale for the development of DSSs: vector control is difficult, but it can be made easier by providing resources for quality control, informed decisions, and evidence-based policy. In addition, workshop participants discussed the importance of predictive epidemiological models and the critical need for quality information that emphasizes strong surveillance, diagnostics, and evidence-based conclusions that are needed to support accurate modeling and/or DSS.

A Pandemic of Epidemics

Gubler described a “dramatic increase” in vector-borne disease epidemics over the past 30 years and identified several factors that underlie this trend (see Chapter 1).

Some recent epidemics have been associated with local surges in vector (particularly mosquito) density, but increased vector competence—a measure of a given vector’s intrinsic capacity to be infected by a pathogen, to replicate it, and to transmit it—has also fueled outbreaks. Epidemics have arisen in naïve host populations, whose opportunity for exposure to vector-borne diseases has increased with the globalization of travel and trade, as well as with declining vector control. For viruses such as WNV and dengue that have recently expanded their geographic range, increased transmission has driven selection for strains with increased epidemic potential (see also Petersen in Chapter 2), while increased gene flow among vector populations has been associated with higher viral transmission rates. Climate change may also have contributed to the emergence of some vector-borne diseases, Gubler said, but it has not played a central role in the reemergence of malaria or dengue.

Adopting a broader frame of reference, Gubler traced the origins of emerging infections to human population growth, social organization, and technology. He identified demographic changes such as urbanization, along with human impacts on the environment and modern transportation, as principal drivers of the reemergence of vector-borne disease (see Figure SA-5). In his contribution to Chapter 1, Gubler presents case studies of three reemergent arboviral diseases—West Nile viral fever, dengue and DHF, and yellow fever—that illustrate the epidemiological effects of pristine populations and environmental change, which include animal and wildlife hosts.

FIGURE SA-5

The epidemiological effects of urbanization and environmental change. SOURCE: Adapted from Wilcox and Gubler (2005) with permission from Environmental Health and Preventive Medicine.

Trade and transportation have greatly contributed to the global spread of plant disease vectors, as described below, but as Almeida observes in his contribution to Chapter 1, many emerging infectious diseases of plants—and indeed of humans and animals as well—can also be viewed as a byproduct of agriculture. “The expansion of agricultural land and increased pesticide, irrigation, and fertilizer use have been the major controllable inputs to increase crop yield,” he states, but these gains have come at a price. “An increased human-natural vegetation interface may also result in new human and plant diseases, as pathogens may spill over from natural environments into new host organisms.” Reversing this trend through sustainable agricultural practices “may reduce the impact of human pathogens from individual to population levels,” Almeida concludes.

Follow the Vector

Where vectors go, diseases of both plants and animals follow. Norwegian rats, bearing plague-infected fleas from Asia, escaped from ships to deliver the Black Death to 14th century Europe.¹² In California, the emergence of Pierce’s disease in grapes followed the introduction of a highly competent vector for an endemic pathogen (see Almeida in Chapter 1). The pathogen in this case, Xylella fastidiosa, is a bacterium with a wide host range; it had caused low levels of disease in California grapevines for over a century, where until recently it was transmitted by the blue-green sharpshooter (Graphocephala atropuntata) (Fletcher and Wayadande, 2002). After a new vector species, the glassy-winged sharpshooter (Homalodisca coagulata), was introduced to California from the southeastern United States in the late 1980s, Pierce’s disease emerged as a major threat to the state’s viticultural industries. In his contribution to Chapter 1, Almeida describes a suite of characteristics that make the glassy-winged sharpshooter a highly efficient vector for X. fastidiosa. Similarly, the introduction of an efficient Asian aphid vector to the Americas prompted the regional emergence of citrus tristeza virus, decades after the pathogen was known to be present in South America (Anderson et al., 2004).

“The jet airplane provides the ideal mechanism by which pathogens of all kinds move around the world in infected humans, host animals, and vectors,” Gubler writes (see Chapter 1). For example, he noted, until recently, the African and American tropics had long been populated with single dengue viral serotypes, and multiple serotypes had only been present in Southeast Asia since the arrival of Allied and Japanese forces in World War II. Today, multiple dengue serotypes circulate throughout the tropics, where their ease of recombination, as well as the continued evolution, selection, and introduction of new serotypes and strains (Rico-Hesse, 2007), drives the evolution of viral strains with increased epidemic potential. In addition, the vectors themselves can also be transported. The used tire trade has recently been linked to the appearance of chikungunya in Italy, infecting almost 270 people in Ravenna province (Gale, 2007).

Land Use

As F. A. Murphy (1998) has observed, when ecosystems are altered, disease problems arise (Murphy, 1998). The usual vertebrate hosts for most vector-borne pathogens that infect humans are wild or domestic animals; people may also become infected when they intrude on habitats where pathogens exist (Marin/Sonoma Mosquito and Vector Control District, 2005). Similarly, many vector-borne diseases of wildlife have now spread to domestic animals. Bluetongue, for example, was first described after it devastated Merino sheep from Europe that were introduced to South Africa in the late 18th century (FAO, 2007b; Verwoerd and Erasmus, 1994). It is therefore not surprising that the initial human occupation of remote ecosystems has resulted in the emergence of vector-borne diseases, given the potential for such circumstances to introduce vector-borne pathogens to immunologically naïve hosts and vectors. Moreover, this is a two-way street: as vector-borne diseases emerge from formerly isolated locations, vector-borne pathogens enter new territories along with their human and animal hosts (Murphy, 1998).

Weather, Climate, and Prediction

Weather refers to short-term fluctuations in the atmosphere, whereas climate describes average weather over long periods of time (IOM, 2003: 64; NRC, 2001: 20). Climate tends to affect the geographic distribution of vector-borne diseases, while variations in weather such as temperature, rainfall, and humidity influence disease transmission dynamics, and thereby the timing and intensity of outbreaks (CIESIN Thematic Guide, 2007; Epstein et al., 1998; Gubler, 1998). Workshop participants considered both weather and climate effects on vector-borne diseases; they also discussed the development of models for outbreak prediction based on weather patterns and debated the usefulness of modeling the potential effects of climate change on disease transmission and spatial distribution.

Ocean Temperatures and Outbreaks

Other than the seasons, the El Niño/Southern Oscillation (ENSO)¹⁶ is the primary source of global variation in temperature and rainfall (Patz et al., 2005; Ropelewski and Halpert, 1987). Decades of observation indicate that ENSO-associated weather anomalies influence outbreaks of a variety of vector-borne diseases (see Table SA-2, and also Linthicum et al. in Chapter 1) (Anyamba et al., 2006).

TABLE SA-2

Studies Suggesting Links Between ENSO-Driven Variations in Temperature and Precipitation and Arthropod-Borne Infectious Diseases.

Upon recognizing, some 25 years ago, that RVF outbreaks were associated with periods of heavy rainfall, speaker Kenneth Linthicum and colleagues discovered through a series of field and laboratory studies that Aedes mosquito vectors of RVF lay virus-infected eggs in moist soil after heavy rains and flooding. These eggs can remain viable and infected in dry soil for extended periods of time, allowing the virus to persist for years in an area during dry years. When the next heavy rainfall event produces flooding of egg habitats infected Aedes mosquito populations are produced and can infect domestic animals. If immature mosquito habitats remain flooded for a month or more secondary Culex mosquito vector populations will surge and become infected after feeding on viremic domestic animals, and potentially cause an epizootic and/or epidemic. With this information, the researchers developed an operational model capable of predicting RVF outbreaks based on ocean temperatures, rainfall anomalies, and vegetation characteristics.

After the U.S. National Oceanic and Atmospheric Administration (NOAA) issued an unscheduled El Niño advisory in September 2006, Linthicum’s team monitored the developing temperature and rainfall anomalies and soon issued alerts for a variety of diseases, including RVF in East Africa, based on its operational model. When RVF activity was detected in Kenya in December 2006, a broad range of governmental, nongovernmental, and international agencies responded to the imminent epidemic that included a ban on animal slaughter, distribution of mosquito nets, insecticidal spraying of vector habitats, and domestic animal vaccination (CDC, 2007b). While the application of these measures limited the spread and severity of RVF in Kenya—compared to the 1997–1998 outbreak—they did not prevent the recurrence of this disease. Speaker C. J. Peters of the University of Texas Medical Branch in Galveston observed, however, that had the many organizations responding to the 2006–2007 outbreak been better coordinated, their efforts would have been more effective.

These events illustrate the potential uses of vector-borne disease forecasting in reducing the impact and limiting the spread of disease. Environmental models may one day be used to identify imminent outbreaks of specific vector-borne diseases by tracking and integrating factors critical to disease transmission, Linthicum said. “It’s important for prevention and preparation to know that we can forecast,” he concluded, “and then when we do forecast, it’s important that we mobilize.”

Climate and the European Emergence of Bluetongue

That many infectious diseases are strongly influenced by seasonal or anomalous changes in weather suggests that they would also be influenced by longer-term climatic changes (Patz et al., 2000). Climate can affect disease transmission through its influence on the replication and movement (and perhaps, the evolution) of disease microbes and vectors; less directly, climate shapes ecology and human behavior, which in turn control pathogen behavior.

Climatic warming appears to have precipitated the emergence of bluetongue in northern Europe, where it was identified for the first time in 2006 (see Osburn in Chapter 2) (Institute for Animal Health, 2007a). There it caused a series of localized outbreaks, infecting more than 2,000 sheep and cattle, of which 30 percent and 10 percent of cases, respectively, proved fatal. While the source of blue-tongue introduction into Europe remains unknown, recent increases in regional temperatures appear to favor its establishment and transmission (European Food Safety Authority, 2007). The summer of 2006 was the warmest on record in northern Europe, where temperatures have been logged since the late 17th century. As speaker Bennie Osburn of the University of California, Davis, pointed out, temperatures in northern Europe remained warm into early November in 2006, rendering the season not only unusually hot, but abnormally long as well.

On June 13, 2007, a sentinel animal in Germany was announced to have displayed evidence of bluetongue infection during April. This was the first indication that the virus strain responsible for the outbreak in northern Europe last year might have successfully overwintered in the region. As of late August 2007, clinical and subclinical cases of bluetongue have been reported in sheep and cattle on hundreds of farms in Germany, Belgium, France, the Netherlands, and Luxembourg (Institute for Animal Health, 2007b). According to the European Commission (2007), bluetongue has now been found in the United Kingdom, where hundreds of thousands of sheep and tens of thousands of cattle—all immunologically naïve to the virus—will present a vulnerable target for arriving midges (Institute for Animal Health, 2007a). Since April 2007, bluetongue has made its way across the English Channel to threaten livestock in the UK and most of northern Europe (see Figure SA-6).

FIGURE SA-6

Map of the distribution of bluetongue throughout Europe as of November 28, 2007. SOURCE: Copyright European Communities (2007).

Because the few species of the midge Culicoides known to transmit blue-tongue lived in habitats with narrow temperature ranges, Osburn noted that the disease was long thought to be restricted to a band between 40° north and 35° south of the equator; any Culicoides blown north of this zone by the wind were not expected to reproduce, or perhaps even to survive. However, with the onset of a span of warm years stretching from 1998 to the present, the bluetongue vector Culicoides imicola staged a surprising incursion into Greece (1999) and Italy (2002) and continued to move north; it became established as far north as 45º by 2005, and found at 52º in 2006. “Bluetongue is emerging only … where expansion of the virus’s range appears to be the consequence of spread of competent insect vectors as the result of climate change,” conclude Osburn and co-author N. James MacLachlan (MacLachlan and Osburn, 2006).

Surveillance and Detection

As is true for all infectious diseases, the early detection of vector-borne disease outbreaks is essential to their control. In Mexico, for example, the detection of initial cases of dengue fever by syndromic surveillance¹⁷ alerts health workers to impose vector control measures immediately in order to mitigate an outbreak that will arrive within days, Beaty reported. Surveillance of pesticide resistance in vector populations informs the choice of control strategies; this is particularly true for malaria-carrying mosquitoes, which are rapidly developing resistance to existing insecticides (see Coleman and Hemingway in Chapter 2). In order to improve surveillance for insecticide resistance and pathogen infection, and thereby malaria and dengue control, the IVCC is developing survey kits for vector testing in the field (see Eisen and Beaty in Chapter 2). Results from field surveys should greatly enhance the IVCC’s aforementioned DSSs for malaria and dengue.

Even as field surveillance methods become faster, more accurate, and less costly, “laboratory-based surveillance must be improved and maintained, not only in the United States but especially in developing countries where a lot of vector-borne diseases will reemerge,” Gubler observed. Ultimately, surveillance systems will enable global tracking of vector-borne and other infectious diseases.

An example of such a surveillance system, called ArboNET, was created in response to the introduction of WNV to the United States in 1999 (see Petersen in Chapter 2 and Nasci in Chapter 3). It was the first national integrated human-animal disease surveillance system (there are now similar national [HHS, 2007] and international [WHO, 2007b] systems for influenza surveillance in birds and humans), according to speaker Lyle Petersen of the CDC, which administers the network. ArboNET is a real-time electronic reporting system that captures data on WNV in humans, dead birds, mosquitoes, horses, and live captive sentinel animals (chickens) (Gubler et al., 2000).

ArboNET analyses of data—which are collected and reported to CDC by health departments across the country—have revealed a number of significant trends; among them, that WNV activity moved across the country with migrating birds, a finding that anticipated an enzootic¹⁸ WNV outbreak that occurred in the southeastern United States in 2001 (CDC, 2001). Because human WNV epidemics have arisen rapidly under such conditions, a key goal of ArboNET is to better predict when human outbreaks will occur, Petersen said. Ecological surveillance offers some promise in this regard, he added, since outbreaks in birds and sometimes other species (e.g., horses) tend to precede those in humans—but only by a few weeks, so response must be rapid to prevent or mitigate human disease.

An important, and under-recognized, impact of the emergence of WNV in the United States is the threat it poses to the nation’s blood supply. Within 3 years of its arrival, Petersen said, WNV had become the most common transfusion-transmissible viral agent¹⁹ due to its high incidence of infection in donor populations (Biggerstaff and Petersen, 2002; Pealer et al., 2003; Petersen, 2008). The cost of screening donated blood for WNV is approximately three times the current CDC budget for surveillance, prevention, and control of the virus (Custer et al., 2005; Korves et al., 2006; Petersen, 2008). By late July 2007—weeks away from the annual disease peak, in which 90 percent of cases typically occur—nearly four times as many WNV cases had been reported as compared with the previous year (Grady, 2007), suggesting a need for increased vigilance on the part of the health care community.

Outbreak Prediction

Weather patterns and anomalies, and ENSO events in particular, are associated with outbreaks of several arthropod-borne diseases, as previously noted (see “Factors in Emergence,” as well as Linthicum et al. in Chapter 1). Speaker Charles Calisher of Colorado State University discussed findings that suggest ENSO influences outbreaks of HPS, a rodent-borne viral disease of which the first human epidemic was reported in the spring of 1993 (see Calisher in Chapter 2). This outbreak, and a subsequent one in 1998, occurred in the Four Corners region of the continental United States, where the borders of Utah, Colorado, New Mexico, and Arizona meet.

Prior to each HPS outbreak, ENSO had brought a warm, wet winter to the region, which in turn prompted an abrupt rise in local populations of the deer mouse Peromyscus maniculatus, the vertebrate host of the Sin Nombre virus (SNV) that causes HPS (Calisher et al., 2005). Humans can always become infected with hantavirus, but risk of human exposure increases (and human cases increase) with the expansion of the deer mouse population, Calisher explained; thus, in order to understand the dynamics of SNV and thereby predict HPS outbreaks, he and colleagues monitored populations of deer mice—as well as of other rodents that share their environment, and which also carry other types of hantaviruses—at three ecologically diverse locations in the Four Corners region over nearly 6 years.

The researchers identified both seasonal and interannual meteorological influences on the population dynamics of these diverse rodent species, but these factors did not entirely explain variations in rodent populations (Calisher et al., 2005). “Much longer-term studies will be required to discern the effects of truly rare phenomena or to identify trends or cycles that have a multiyear periodicity, such as the El Niño southern oscillation,” Calisher and colleagues wrote. The results of these studies, they observed, “have important implications for those attempting to model population dynamics of rodent populations for purposes of predicting disease risk.”

Vector Control

The control of disease vector populations by habitat modification, a mainstay of early 20th century public health, was replaced by chemical methods when they became relatively inexpensive and widely available. Pesticides remain the primary means to prevent or mitigate most vector-borne diseases, but resistance has increasingly limited the effectiveness of this strategy. Because insecticide resistance poses an especially significant barrier to controlling malaria and dengue, and because vector control measures could potentially reduce the incidence of additional vector-borne diseases, IVCC supports the development of novel insecticides and deployment methods as one of its foremost goals (see Eisen and Beaty in Chapter 2).

Profits drive manufacturers to produce more innovative insecticides for golf courses than to protect people from vector-borne diseases, just as they encourage pharmaceutical companies to develop more drugs to combat aging and obesity than malaria. Thus, Beaty explained, IVCC attempts to help for-profit companies market insecticides that they have already discovered that show promise for public health applications, but which may have been dropped from development due to their unsuitability for commercial purposes. An insecticide that breaks down in ultraviolet light would not be effective for spraying fields, for example, but if incorporated into bed-nets and curtains, it might control mosquitoes inside houses and other buildings. Several such novel products in IVCC’s pipeline will be made available to developing countries upon their approval, Beaty said.

“Our focus [at IVCC] is the control of vectors in and around the house,” he explained, because most dengue virus mosquito-borne human disease transmissions occur indoors. In addition to supporting the development of inexpensive domestic products such as pyrethroid-impregnated bamboo curtains and mats, IVCC encourages their combined use in an approach known as casa segura (“safe house”). Scott also advocated the casa segura strategy for vector control and advised that market analyses of both households and ministries of health be conducted in order to guide product development.

Emphasis on controlling mosquitoes indoors was one of several targeted vector control strategies discussed by workshop participants. As previously mentioned, Scott and coworkers took advantage of spatial and temporal heterogeneities in dengue-carrying mosquito populations in order to increase the efficiency of control efforts (see “Hallmarks of Vector-Borne Disease,” as well as Chapter 2). Based on a simulation model designed to predict the effect of dengue vaccine in various outbreak scenarios, he suggested that combining immunization (should an effective vaccine be developed) with vector control would be advantageous. By contrast, controlling dengue solely through immunization could cause significant problems, such as more severe disease following infection with heterotypic strains of dengue, or perhaps greater rates of morbidity among older persons with waning immunity.

“Vector control, in essence, slows the force of infection and makes the delivery of vaccine more effective,” Scott concluded. “Therefore an integrated program with vector reduction and immunization will more effectively prevent epidemic dengue and is more sustainable than either strategy alone.” However, he noted, implementing such programs will take “a change in mind set to start to get people who are working on vaccines to think about working together with people who are working on vector control.”

Multidisciplinary Research and Management

Research on infectious diseases must often be conducted in the midst of epidemics and in concert with management efforts. This challenging process was described by speaker David Rizzo of the University of California, Davis, who has worked to understand and mitigate the effects of SOD in California since shortly after its emergence there in the mid-1990s (see also Chapter 2 Overview). Caused by the fungus-like water mold Phytopthora ramorum, SOD kills several oak species and causes nonfatal leaf disease in many other plants, including rhododendrons and California bay laurel (California Oak Mortality Task Force, 2004; Faden, 2004). P. ramorum thrives in the cool, wet climate of California coastal forests—where it has caused substantial mortality in tanoak and several oak species—and has also been detected in the United Kingdom and a number of other European countries. SOD is not, strictly speaking, a vector-borne disease because it is not transmitted by arthropods; instead, humans (in the form of hikers, mountain bikers, and equestrians, who unknowingly carry P. ramorum spores on their clothes, shoes, equipment, and companion animals) appear to be the main vehicle for spreading this pathogen over long distances.

Because the SOD pathogen was only identified in 2000, researchers are still learning about its disease cycle and transmission dynamics. As they probe the ecological context of SOD and refine epidemiological models, Rizzo and colleagues are also working to manage the disease in natural ecosystems as well as 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, the researchers attempt to develop management schemes that avoid deleterious ecological consequences.

In all of their efforts, Rizzo and colleagues collaborate with a multidisciplinary team, the California Oak Mortality Task Force.²⁰ This group brings together plant biologists, anthropologists, entomologists, and ecologists from research and educational institutions, as well as representatives from interested public agencies, nonprofit organizations, and private interests (e.g., the nursery trade). The task force coordinates research, management, monitoring, and public policy efforts with regard to oak mortality and, as Rizzo noted, educates its broad constituency on developments in the understanding and management of SOD.

Integrating Disciplines and Systems

In the course of a panel discussion on integrating strategies for surveillance, diagnosis, and response, the four discussants—who represented the CDC, the National Institute of Allergy and Infectious Disease of the National Institutes of Health (NIAID/NIH), and the U.S. Department of Agriculture (USDA)—emphasized the importance of multidisciplinary efforts toward understanding and addressing individual vector-borne diseases, as well as groups of diseases that share a common vector (see Chapter 3). Roger Nasci, chief of the Arboviral Diseases Branch at CDC’s Division of Vector-Borne Infectious Diseases, described multidisciplinary teams as “essential” to addressing international health problems, but also noted the difficulties in coordinating such teams (e.g., the previously discussed response to RVF in Kenya).

Panelists described existing multidisciplinary programs of limited scope, such as CDC field teams that respond to vector-borne outbreaks and research groups that address West Nile encephalitis and plague (see Nasci in Chapter 3), and advocated a wider adoption of this approach. “We have to provide an environment to foster [multidisciplinarity] in training, as well as in research,” said David Morens of NIAID; for example, by changing the current paradigm of highly compartmentalized Ph.D. programs and instead emphasizing interdisciplinary studies in global health (see Chapter 3) (Hotez, 2004). Similarly, Forum member Lonnie King observed that working at the interface of different scientific cultures is a learned skill that needs to be taught. Panelist Sherrilyn Wainwright (see Chapter 3), a veterinary epidemiologist with the USDA currently working at Colorado State University, suggested that involvement in multidisciplinary research trains scientists to better integrate their distinct cultures in other circumstances, such as outbreak response.

Participants in the ensuing open discussion urged the expansion of multidisciplinary research and response and encouraged the development of “transdisciplinary” programs that integrate diverse disciplines in a meaningful fashion, rather than simply involving representatives of different fields. Some also advocated expanding the range of disciplines brought to bear on vector-borne diseases beyond public health, ecology, and the biomedical sciences, to include professionals such as urban planners, hydrologists, ecologists, and engineers.

ArboNET, a pioneer among integration disease surveillance systems, provides a model for the collection and organization of information on zoonotic diseases, according to Nasci (see Chapter 3, Petersen in Chapter 2, and previous discussion in “Lessons Learned: Case Studies of Vector-Borne Diseases”). This environmental surveillance program could be harnessed for broader use, as is currently being explored in an experimental ArboNET/plague surveillance system designed to test models that could provide early warning of plague outbreaks. In addition to gathering surveillance on vector-borne diseases, it would be useful to integrate and disseminate data that have already been accumulated, King observed, because to a large extent, “we don’t know what we know.” For example, as Nasci pointed out, data from the USDA’s equine arbovirus monitoring program could be integrated into ArboNET.

Knowledge Gaps

The need to understand better the ecology of vector-borne diseases, a central theme of workshop discussions (see Fish in Chapter 1), was identified as critical to a host of purposes:

• Targeting surveillance and control efforts
• Minimizing surveillance costs over large areas
• Forecasting risk and anticipating expansion of disease range (including globalization)
• Designing containment or exclusion strategies

In addition, basic questions remain to be answered about most important vector-borne diseases (see Chapter 2 and Fish in Chapter 1). The following information was deemed essential by workshop presenters:

• Quantitative descriptions of endemic and epidemic disease cycles in all hosts
• Measurements of disease transmission potential by known and potential vectors
• Timing, distribution, and abundance of disease-competent vectors
• Mechanisms of host infection
• Mechanisms of pathogenesis
• Mechanisms of transovarial transmission
• Spatial and temporal distributions of vectors and environmental conditions in settings at risk for disease emergence

Field studies of vectors are crucial to answering many of these questions; however, as several participants who engage in such research attested, this work is not well funded. For example, Fish has written, “Some research is being done on methods for reducing the risk of Lyme disease through tick population suppression and other field intervention strategies, but this effort has been meager compared to that already invested in vaccines [that were withdrawn from the market]. One can only imagine what impact [the money invested in developing the discontinued Lyme vaccine, conservatively estimated at $200 million] would have [had] upon research to answer some basic questions about tick ecology, such as what limits the geographic distribution of Lyme disease vectors” (Fish, 2001a).

Obstacles to Scientific Education and Training

The introduction of WNV into the United States resulted in an unprecedented demand for expertise in mosquito surveillance and control operations throughout most of the country, Fish observed in a 2001 editorial (Fish, 2001b). However, there is a strong perception among those in the field that—after three decades of decline in mosquito-borne disease in the United States, the dismantling of training programs, and a loss of employment opportunities for vector biologists and medical entomologists—positions went unfilled, and few academic institutions were capable of providing such training. The CDC briefly financed training in medical entomology at four institutions with the new funds provided to it for WNV, but that funding has since been cut, and the programs are slated for termination (Fish, 2007).

Panelist Adriana Costero, Vector Biology Program Officer at NIAID/NIH, described the Institute’s programs, which fund basic and translational research and training in the United States and in disease-endemic countries (see Chapter 3). However, several participants expressed discouragement at the lack of research funding targeted specifically for vector ecology and the resulting dearth of expertise—as well as the persistence of knowledge gaps—in this field. Various causes were postulated for this deficit, from the broad (funding trends that favor solutions to well-defined problems, preferably posed by the “disease du jour,” over descriptive studies of infectious diseases) to the specific (the organization of NIH study sections [Spielman, 2003]). However, as Forum member Stephen Morse observed, every scientific specialty complains of insufficient funding, a symptom of a scientific establishment focused on specialized research programs that compete for limited funds.

Multidisciplinary approaches offer a solution to this dilemma by creating unified communities, synergies of expertise, and economies of scale commensurate with problems as complex and wide-ranging as the prevention and mitigation of vector-borne disease. Such efforts, it was suggested, might be most expediently funded if they capitalized on the “disease du jour,” and also if they offered near-term benefits for public health (e.g., how best to use existing pesticides in disease control and prevention).

Barriers to Implementation

There is a general lack of infrastructure for implementing vector-borne disease interventions in most settings, Morens observed, whether they are cities in the United States—as revealed by the introduction of Lyme disease—or impoverished countries where vector-borne diseases cause major morbidity and mortality. “Many folks were shocked to discover [upon the arrival of WNV] that there were state health departments in the United States that had no vector people anymore,” he said. The domestic situation has improved somewhat, he added, but the same cannot be said for developing countries, where infrastructures for infectious disease control lack far more than vector biologists. Moreover, legal and bureaucratic barriers increasingly impede international research on and response to vector-borne disease. Because many vector-borne infectious agents have been classified as “Select Agents,” they are subject to rules associated with the USA Patriot Act²¹ that substantially limit the ability of foreign scientists to work on U.S.-funded research efforts even within their own countries. In addition, U.S. air transportation regulations and bans on the international transport of biological specimens by nations experiencing disease outbreaks slow and sometimes stop the vital exchange of biological materials (see Morens in Chapter 3).

Meanwhile, 8 years after the introduction of WNV, the U.S. response to the threat of vector-borne disease is fading, as illustrated by recent funding reductions that will shrink the CDC’s WNV program by nearly 50 percent over the next 2 years (Fish, 2007). “These cuts will force big reductions in federal support for the surveillance and control of WNV in 57 state and local jurisdictions,” Fish noted in an editorial in the May 27, 2007, New York Times: “While federal financing for biosecurity and public health preparedness has … become a priority, in fact little has been learned from the WNV experience,” he continued. WNV is certainly not the last mosquito-borne virus that will invade the United States, Fish predicted, but without sustained federal support for surveillance and control of such diseases, “we will again be vulnerable to threats, accidental or not, and incapable of prompt action that could curb or prevent epidemics.”

Reflecting on this situation, Forum member George Korch wondered aloud how governments and industry might be convinced to invest in addressing vector-borne diseases. “What is the product that medical entomology and infectious disease studies provide?” he inquired. A major common goal for countries, or cultures, is to have a productive and healthy workforce that translates into the well-being of the entire community, he suggested. Thus, in order to convince the pharmaceutical industry, as well as governments, that vector-borne diseases are worth solving, researchers will need to provide evidence of economic benefit and opportunities for strategic investment. Even training is a short-term solution unless it fits into a grand matrix of vector-borne disease control, Korch said.

Conclusions

While acknowledging the global burden of vector-borne diseases, as well as the daunting obstacles to much-needed research on their control, prevention, and treatment, Forum chairman Fred Sparling also expressed optimism and excitement in the pursuit of solutions. Recalling that the final recommendation in the 2003 report Microbial Threats to Health advocated the creation of interdisciplinary centers for infectious disease research, he applauded the development of such a center—albeit a “virtual” one—at Colorado State University, in close association with the nearby CDC Division of Vector-Borne Infectious Diseases.²²

Other universities (e.g., Vanderbilt, Duke, Johns Hopkins, and the University of Washington, Seattle²³) are creating centers for global health. These initiatives are driven, in large part, by the promise of funding from the Bill and Melinda Gates Foundation and other public and private sources, Sparling said. In such a climate, and in such interdisciplinary venues, he encouraged vector biologists to look for opportunities and synergies and, thereby, support for their field. Like vector-borne diseases themselves, he concluded, research in this area is rife with thorny problems, but also abundant with opportunity.