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Institute of Medicine (US) Forum on Microbial Threats. Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections, Workshop Summary. Washington (DC): National Academies Press (US); 2008.

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Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections, Workshop Summary.

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1Vector-Borne Disease Emergence and Resurgence

OVERVIEW

The once limited geographic and host ranges of many vector-borne diseases are expanding, spurred largely by anthropogenic factors. Epidemics of malaria, dengue, and other formerly contained vector-borne diseases are on the rise in the developing world, and in recent years the United States has witnessed the introduction of West Nile virus (WNV) in New York City and the emergence of previously unknown Lyme disease. Contributors to this chapter examine global, regional, and local phenomena associated with the emergence and resurgence of these and other vector-borne diseases, and explore the use of such information to predict future outbreaks and anticipate the geographic spread of vectors and pathogens.

The chapter begins with a summary of the workshop’s keynote address, which was presented by Duane Gubler of the University of Hawai‘i. Gubler describes the “dramatic global reemergence of epidemic vector-borne diseases” of the past three decades, in parallel with influential demographic, economic, and societal trends. He considers the changing epidemiology of malaria, plague, dengue, yellow fever, and WNV, identifies key factors in the emergence and spread of vector-borne disease, and discusses the implications of these trends for public health. In particular, he notes that advances in transportation, which centuries ago removed infectious disease barriers between the Old and New Worlds (that is, the eastern and western hemispheres), now drive the rapid, global dispersion of pathogens and their vectors. “If we hope to reverse the trend of emerging and reemerging infectious diseases,” Gubler insists, “the movement of pathogens and arthropod vectors via modern transportation must be addressed.”

In his presentation on anthropogenic factors in tick-borne pathogen emergence, Durland Fish of Yale University focused on the “steadily increasing” presence of tick-borne disease in the northeastern United States associated with the reversal of deforestation in that region (see Summary and Assessment subsection entitled “Reforestation and Tick-Borne Disease”). In addition to Lyme disease, which rose from obscurity to become the country’s most common vector-borne disease within the span of two decades, black-legged deer ticks (Ixodes scapularis) serve as the vector for Anaplasma phagocytophilum—a bacterium that causes a flu-like illness called human granulocytic anaplasmosis—and the protozoan Babesia microti can be spread by transfused blood from an infected human.

The adults of this tick species feed exclusively on white-tailed deer; only the nymphs feed on and transmit pathogens to humans. The decline of agriculture in the northeastern United States and the subsequent reforestation of this region over the past several decades have provided an ideal habitat for increasing numbers of white-tailed deer, their attendant ticks, and the pathogens they bear. This trend may well continue and gain momentum, Fish noted, since various non-native tick-borne arboviruses could infect any of several hundred human-feeding species of ticks present in the United States.

Although vector-borne plant diseases share many ecological and epidemiological features with their animal and human counterparts, they tend to be studied in isolation. In his contribution to this chapter, presenter Rodrigo Almeida of the University of California, Berkeley, argues that new insights on the nature of vector-borne diseases could be gained through the exchange of tools and ideas among disparate research communities. Plant systems, for example, “allow large experiments to be conducted, with multiple hosts, vector species and pathogen strains, which could be used to experimentally address ecological and evolutionary hypotheses on pathogen range and transmission efficiency,” he explains. In describing the rise of Pierce’s disease of grapevines in California following the recent introduction of a highly efficient insect vector for a local bacterial pathogen, Almeida explores a common pattern of vector-borne disease emergence from an agricultural perspective.

The final essays in this chapter address the profound influence of climate on vector-borne disease distribution and transmission. The first, by presenter Kenneth Linthicum of the U.S. Department of Agriculture’s (USDA’s) Agricultural Research Service (ARS) Center for Medical, Agricultural, and Veterinary Entomology and co-authors, focuses on the effects of regional variations in temperature and rainfall on vector-borne disease transmission. The primary driver of global climate variability, the periodic warming of the Pacific Ocean surface known as the El Niño/Southern Oscillation (ENSO), has been linked with outbreaks of a variety of arthropod-borne diseases, the authors note. In the case of Rift Valley fever (RVF), this association was sufficiently strong to permit them to develop risk maps that successfully predicted a major outbreak in Africa in 2006–2007, providing an early warning that reduced the impact and spread of the disease. Such forecasts, they conclude, may potentially predict risk for the spread of diseases on a global scale and offer health and agricultural authorities the possibility of targeting disease surveillance and control efforts, and thereby improve their cost-effectiveness.

Two consecutive contributions, from workshop speaker Jonathan Patz, of the University of Wisconsin, Madison, and co-authors, discuss the possible effects of global climate change on vector-borne disease emergence. The first paper, by Patz and S. H. Olson, comprises an overview of the effects of climate change on disease risk at both global and local levels. It is followed by an update, by Patz and C. K. Uejio, which presents detailed evidence for the effects of climate change on Lyme disease and WNV, the two most prevalent vector-borne diseases in North America.

Vector-borne pathogens are particularly sensitive to climatic conditions due to their influence on vector survival and reproduction, biting and feeding patterns, pathogen incubation and replication, and the efficiency of pathogen transmission among multiple hosts. The authors discuss evidence that an overall rise in global temperatures could enlarge the geographic range of malaria in Africa and increase the frequency of dengue outbreaks worldwide, but they place greater emphasis on opportunities for disease emergence in local environments driven by land use practices such as deforestation, cultivation, and dam construction. Given these influences, risk assessments for vector-borne diseases should incorporate appropriately scaled analyses of the effects of land use on microclimate and weather, habitat, and biodiversity, the authors conclude. The need for such considerations is clearly illustrated in their discussion of WNV distribution and transmission dynamics, which appear to be influenced by a broad and complex range of environmental factors.

THE GLOBAL THREAT OF EMERGENT/REEMERGENT VECTOR-BORNE DISEASES

Duane J. Gubler, Sc.D.1

University of Hawai‘i, Honolulu, Hawai‘i

Introduction

At the beginning of the 20th century, epidemic vector-borne diseases were among the most important global public health problems (Gubler, 1998, 2002a). Diseases such as yellow fever (YF), dengue fever (DF), plague, louse-borne Typhus, malaria, etc., caused explosive epidemics affecting thousands of people. Subsequently, other vector-borne diseases were identified as major causes of disease in both humans and domestic animals. As the natural history of these diseases became better understood, prevention and control measures, primarily directed at the arthropod vectors, were highly successful in controlling disease transmission. Effective prevention and control accelerated in the post-World War II years with the advent of new insecticides, drugs, and vaccines. By the 1960s, the majority of important vector-borne diseases had been effectively controlled in most parts of the world, and those that were not yet controlled were targeted for more intensive programs using new vaccines, drugs, and insecticides.

Unfortunately, “success led to failure”; some of the successful programs, such as the Aedes aegypti eradication program that effectively controlled epidemic YF and DF throughout the American tropics for over 40 years, and the global malaria eradication program that effectively controlled malaria in Asian and American countries, were disbanded in the 1970s because the diseases were no longer major public health problems (Gubler, 1989, 2004; Gubler and Wilson, 2005; IOM, 1992). Additionally, residual insecticides were replaced with less effective chemicals used as space sprays to control adult mosquitoes. The 1970s ushered in a 25-year period characterized by decreasing resources for infectious diseases, decay of the public health infrastructure to control vector-borne diseases, and a general perception that vector-borne diseases were no longer important public health problems. Coincident with this period of complacency, however, was the development of global trends that have contributed to the reemergence of epidemic infectious diseases in general, and vector-borne diseases in particular, in the past 25 years. In addition to the emergence of newly recognized diseases, there was increased incidence and geographic expansion of well-known diseases that were once effectively controlled (Gubler, 1989, 1998; IOM, 1992, 2003; Mahy and Murphy, 2005). This paper will briefly review the changing epidemiology of several of the most important vector-borne diseases and discuss the lessons learned from this global reemergence.

The Reemergence of Epidemic Vector-Borne Diseases as Public Health Problems

The earliest indications that epidemic vector-borne diseases might reemerge came in the early 1970s. Subsequent warnings were ignored by public health officials and policy makers because of competing priorities for limited resources (Gubler, 1980, 1987, 1989; IOM, 1992). The 1980s ushered in a period with increased epidemic vector-borne disease activity associated with expanding geographic distribution of both the vectors and the pathogens via modern transportation and globalization. It was not until the Institute of Medicine (IOM) report on emerging infectious diseases that policy makers took notice (IOM, 1992), and not until after the 1994 plague epidemic in India that new resources were allocated to emerging infectious diseases (Fritz et al., 1996; WHO, 1994).

Parasitic, bacterial, and viral pathogens may be transmitted by blood-sucking arthropods. Mosquitoes, which primarily transmit parasitic and viral diseases, are the most important arthropod vectors; ticks, which primarily transmit bacteria and viruses, are next in importance.

Parasitic Diseases

Of the parasitic infections transmitted by arthropods, malaria is by far the most important, although there has also been a reemergence of leishmaniasis and African trypanosomiasis. The principal problem area for malaria is Africa, where 95 percent of all global cases occur, most of them in children under 5 years of age (Gubler and Wilson, 2005). This disease is dealt with elsewhere and will not be considered further here.

Bacterial Diseases

Two newly recognized vector-borne bacterial diseases, Lyme disease, caused by Borrelia burgdorferi, and ehrlichiosis, caused by Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Ehrlichia ewingui, have emerged as important public health problems in the past three decades (Dumler et al., 2007; Steere et al., 2004). Both have small rodents as their natural vertebrate reservoir host, with hard ticks as their principal vectors. Both diseases are found primarily in temperate regions of the world, where emergence has been associated with environmental change. Figure 1-1 shows the dramatic increase in reported cases of Lyme disease in the United States since the Centers for Disease Control and Prevention (CDC) began surveillance in 1982. The increased transmission in the United States is directly related to reforestation of the northeastern United States, allowing the mouse and deer populations to increase unchecked, which in turn has allowed the tick population to increase. A final factor has been the trend in recent decades to build houses in woodlots where humans share the ecology with deer, mice, and ticks; thus most transmission to humans in the northeastern United States where the majority of cases of Lyme disease occur, is residential (Steere et al., 2004).

FIGURE 1-1. Reported Lyme disease cases by year, United States, 1982–2005.

FIGURE 1-1

Reported Lyme disease cases by year, United States, 1982–2005. SOURCE: Adapted from Gubler (1998) and CDC (2006), courtesy, Division of Vector-Borne Infectious Diseases, CDC, Fort Collins, CO.

Plague, caused by Yersinia pestis, is the most important reemergent bacterial vector-borne disease. The current global increase in case reports of plague is primarily due to outbreaks in Africa. However, it is the potential of plague to cause explosive epidemics of pneumonic disease, transmitted person-to-person and with high mortality, that makes it important as a reemergent infectious disease and as a potential bioterrorist threat. This was illustrated in 1994 when an outbreak of plague occurred in Surat, Gujarat, India (WHO, 1994). Although this was a small outbreak (most likely less than 50 cases) that should have been a relatively unimportant local public health event, it became a global public health emergency. The reasons for this are complicated and beyond the scope of this article, but it is a classic case of “success breeding failure.” Briefly, because the Indian Health Service had successfully controlled epidemic plague in India for over 30 years (the last confirmed human plague case prior to 1994 was in 1966), laboratory, clinical, and epidemiologic capacity to diagnose and control plague had deteriorated. Thus, when the Surat outbreak occurred, the clinical and laboratory diagnosis was confused, creating lack of confidence in public health agencies and ultimately panic when it was finally announced that the disease was pneumonic plague. Within a few weeks in early October 1994, an estimated 500,000 people fled Surat, a city of about 2 million people at that time. Many of these people traveled to other urban areas in India, and within days, newspapers were reporting plague cases in other cities. The World Health Organization implemented Article 11 of the International Health Regulations (WHO, 1983) for the first time in 33 years because it was thought that people with pneumonic plague might board airplanes in India and transport the disease to other urban centers around the world (Figure 1-2). Many countries stopped air travel and trade with India and most implemented enhanced surveillance for imported plague cases via airplane travel. This was the first global emerging infectious disease epidemic that impacted the global economy since infectious diseases were controlled in the 1950s. It is estimated that this small outbreak cost India US$3 billion (John, 1999) and the global economy US$5 to $6 billion. Fortunately, there were no cases of plague exported from India (Fritz et al., 1996), but this epidemic was the “wake-up call” that modern transportation and globalization were major drivers of pandemic infectious diseases. It was this epidemic that helped stimulate in the first funding of CDC’s Emerging Infectious Disease Program.

FIGURE 1-2. Suspected spread of pneumonic plague from India, 1994.

FIGURE 1-2

Suspected spread of pneumonic plague from India, 1994. SOURCE: Courtesy, Division of Vector-Borne Infectious Diseases, CDC, Fort Collins, CO.

Arboviral Diseases

Of the vector-borne diseases, it is the arboviruses that have become the most important causes of reemergent epidemic disease (Gubler, 1996, 2002a). In 2007, there are few places on Earth where there is no risk of infection with one or more of these viral diseases, most of which are transmitted by mosquitoes. The more important reemergent epidemic arboviral diseases are presented in Table 1-1. They include members of three families (Togaviridae, Flaviviridae, and Bunyaviridae). Three diseases—dengue fever, West Nile, and yellow fever—will be discussed as case studies to illustrate the changing epidemiology of arboviral diseases.

TABLE 1-1. Emergent/Reemergent Arboviral Diseases of Humans.

TABLE 1-1

Emergent/Reemergent Arboviral Diseases of Humans.

West Nile Virus2

West Nile virus (WNV) (Flaviviridae, genus Flavivirus), an African virus, belongs to the Japanese encephalitis virus (JEV) sero-group, which includes a number of closely related viruses, including JEV in Asia, St. Louis encephalitis virus in the Americas, and Murray Valley encephalitis virus in Australia. All have a similar transmission cycle involving birds as the natural vertebrate hosts and Culex species mosquitoes as the enzootic/epizootic vectors, and all cause severe and fatal neurologic disease in humans and domestic animals, which are generally thought to be incidental hosts, as well as in birds.

The clinical illness associated with WNV in humans ranges from asymptomatic infection to viral syndrome to neurologic disease (Hayes and Gubler, 2006), but historically it has been considered among the least virulent of the Japanese encephalitis sero-group viruses (Hayes, 1988); recent epidemics, however, have changed that perception.

From the time WNV was first isolated from the blood of a febrile patient in the West Nile province of Uganda in 1937 (Smithburn, 1940) until the fall of 1999, it was considered relatively unimportant as a human and animal pathogen. The virus was enzootic throughout Africa, West and Central Asia, the Middle East, and the Mediterranean, with occasional extension into Europe (Hayes, 1988). A subtype of WNV (Kunjin) is also found in Australia (Hall et al., 2002). A characteristic of WNV epidemiology during this 62-year history (1937–1999) was that it caused epidemics only occasionally, and the illness in humans, horses, and birds was generally either asymptomatic or mild; neurologic disease and death were rare (Marfin and Gubler, 2001; Murgue et al., 2001, 2002).

In late August 1999, an astute physician in Queens, New York, identified a cluster of elderly patients with viral encephalitis (Asnis et al., 2000). Because of the age group involved and the clinical presentation, these cases were initially thought to be St. Louis encephalitis, but subsequent serologic and virologic investigation showed them to be caused by WNV (Lanciotti et al., 1999). The epidemic investigation, which focused only on neurologic disease, identified 62 cases with 7 (11 percent) deaths, all of them in New York City (Nash et al., 2001). Epidemiologic studies, however, showed widespread transmission throughout New York City, with thousands of infections (Montashari et al., 2001; Nash et al., 2001). The virus caused a high fatality rate in birds, especially those in the family Corvidae (Komar, 2003). Genetic sequence of the infecting virus suggested it was imported from the Middle East, most likely from Israel (Lanciotti et al., 1999). Although it will never be known for sure, epidemiologic and virologic evidence suggests the virus was introduced in the spring or early summer of 1999, most likely via infected humans arriving from Israel, which was experiencing an epidemic of WNV in Tel Aviv at the time (Giladi et al., 2001; Marfin and Gubler, 2001).

Over the next 5 years, WNV rapidly moved westward across the United States to the west coast (Figure 1-3), north into Canada, and south into Mexico, the Caribbean, and Central America. In 2002, it caused the largest epidemic of meningoencephalitis in U.S. history with nearly 3,000 cases of neurologic disease and 284 deaths. That same year, there was a large epizootic in equines with over 14,500 cases of neurologic disease and a case fatality rate of nearly 30 percent (Campbell et al., 2002). The epidemic curve for human cases in the United States is shown in Figure 1-4. In 2003, another large epidemic occurred, but the epicenter of transmission was in the plains states and the majority of the reported cases were not neurologic disease (Hayes and Gubler, 2006). Since 2003, the virus has persisted with seasonal transmission during the summer months, but at a lower level; the majority of cases have been in the plains and western states.

FIGURE 1-3. The sequential westward movement of West Nile virus in the United States by year, reported to CDC as of January 31, 2006.

FIGURE 1-3

The sequential westward movement of West Nile virus in the United States by year, reported to CDC as of January 31, 2006. Human infection was found in all states in the continental United States with the exception of Maine. SOURCE: Reprinted from Gubler (more...)

FIGURE 1-4. Epidemic West Nile virus in the United States, 1999–2006, reported to CDC as of May 2, 2007.

FIGURE 1-4

Epidemic West Nile virus in the United States, 1999–2006, reported to CDC as of May 2, 2007. SOURCE: CDC (2007).

WNV was first detected south of the U.S. border in 2001 when a human case of neuro-invasive disease was reported in the Cayman Islands (Campbell et al., 2002), and birds collected in Jamaica in early 2002 were positive for WNV-neutralizing antibodies (Komar and Clark, 2006). In 2002, WNV activity was reported in birds and/or equines in Mexico (in six states) and on the Caribbean islands of Hispaniola (Greater Antilles) and Guadeloupe (Lesser Antilles). Most likely, the virus was also present in Mexico in 2001, since a cow with WNV-neutralizing antibody was detected in the southern state of Chiapas in July of 2001 (Ulloa et al., 2003). In 2003, the virus was detected in 22 states of Mexico; in Belize, Guatemala, and El Salvador in Central America; and in Cuba, Puerto Rico, and the Bahamas in the Caribbean. In 2004, WNV activity was reported from northern Colombia, Trinidad, and Venezuela, the first reported activity in South America; in 2006, Argentina reported WNV transmission (Komar and Clark, 2006; Morales et al., 2006).

Migratory birds have likely played an important role in the spread of WNV in the western hemisphere (Owen et al., 2006; Rappole et al., 2000). This conclusion is supported by data on the movement of WNV in migratory birds in the Old World (Malkinson et al., 2002). Moreover, the westward movement of WNV across the United States and Canada can best be explained by introduction via migratory birds that fly south to Central and South America in the fall and north from those areas in the spring. Thus, the yearly movement westward in 2000, 2001, 2002, 2003, and 2004 shows very good correlation with the Atlantic, Mississippi, Central, and Pacific flyways of migratory birds (Figures 1-3 and 1-5). After introduction to an area, local dispersion of WNV likely occurred via movement of resident birds, which often fly significant distances. Interestingly, the major epidemic in each region of the country occurred the following year after introduction, with the exception of the 1999 New York outbreak.

FIGURE 1-5. Migratory bird flyways in the western hemisphere.

FIGURE 1-5

Migratory bird flyways in the western hemisphere. In the fall birds fly south to areas in tropical America where they spend the winter. In the spring, they fly north again, potentially carrying the virus with them each way. SOURCE: Reprinted from Gubler (more...)

The emergence of a WNV strain with greater epidemic potential and virulence was likely a major factor in the spread of WNV in both the Old and the New Worlds (Marfin and Gubler, 2001). The first evidence of this new strain of WNV was in North Africa in 1994, when an epidemic/epizootic of serologically confirmed WNV occurred in Algeria; of 50 cases with neurologic disease 20 (40 percent) were diagnosed as encephalitis and 8 (16 percent) died (Murgue et al., 2002). Over the next 5 years, epidemics/epizootics occurred in Morocco, Romania, Tunisia, Israel, Italy, and Russia, as well as jumping the Atlantic and causing the epidemic in Queens, New York (Figure 1-6). All of these epidemics/epizootics were unique from earlier epidemics in that they were associated with a much higher rate of severe and fatal neurologic disease in humans, equines, and/or birds. This virus most likely had better fitness and caused higher viremias in susceptible hosts, allowing it to take advantage of modern transportation and globalization to spread, first in the Mediterranean region and Europe, and then to the western hemisphere. This speculation is supported by sequence data documenting that the viruses isolated from these recent epidemics/epizootics are closely related genetically, most likely having a common origin; all belonged to the same clade (Lanciotti et al., 1999, 2002) (Figure 1-7). Moreover, experimental infection of birds has documented that viruses in this clade, represented by the New York 1999 isolate, have greater virulence than virus strains isolated earlier (Brault et al., 2004; Langevin et al., 2005).

FIGURE 1-6. Epidemics caused by West Nile virus, 1937–2007.

FIGURE 1-6

Epidemics caused by West Nile virus, 1937–2007. The red stars indicate epidemics that have occurred since 1994 and have been associated with severe and fatal neurologic disease in humans, birds, and/or equines. SOURCE: Reprinted from Gubler (2007). (more...)

FIGURE 1-7. Phylogenetic tree of West Nile viruses based on sequence of the envelope gene.

FIGURE 1-7

Phylogenetic tree of West Nile viruses based on sequence of the envelope gene. Viruses isolated during recent epidemics all belong to the same clade, suggesting a common origin. SOURCE: Reprinted from Gubler (2007).

The broad vertebrate host and vector range of WNV was another important factor in the successful spread of epidemic/epizootic WNV transmission. The virus has been isolated from 62 species of mosquitoes, 317 species of birds, and more than 30 species of non-avian hosts since it entered the U.S. in 1999 (CDC, 2007, unpublished data). The non-avian vertebrate hosts include rodents, bats, canines, felines, ungulates, and reptiles, in addition to equines and humans. It is unknown what role any of these non-avian species play in the transmission cycle of WNV, but the fact that so many mammal and opportunistic blood-feeding mosquitoes have been found infected suggests that there may be secondary transmission cycles involving mammals and mammal-feeding mosquitoes, putting humans and domestic animals at higher risk for infection.

Dengue/Dengue Hemorrhagic Fever3

The dengue viruses (DENVs) are also members of the family Flaviviridae; there are four dengue serotypes (DENV-1, DENV-2, DENV-3, DENV-4), which make up the dengue complex within the genus Flavivirus. While the DENVs have a primitive sylvatic maintenance cycle involving lower primates and canopy-dwelling mosquitoes in Asia and Africa, they have also established an endemic/epidemic cycle involving the highly domesticated Ae. aegypti mosquito and humans in the large urban centers of the tropics. They have become completely adapted to humans and current evidence suggests that the sylvatic cycle is not a major factor in the current emergence of epidemic disease (Gubler, 1997; Rico-Hesse, 1990).

The DENVs cause a spectrum of illness in humans ranging from inapparent infection and mild febrile illness to classic DF to severe and fatal hemorrhagic disease (WHO, 1997). All age groups are affected, but in endemic areas, most illness is seen in children, who tend to have either a mild viral syndrome or the more severe dengue hemorrhagic fever (DHF), a vascular leak syndrome. DENV infection has also been associated with severe and fatal neurologic disease and massive hemorrhaging with organ failure (Sumarmo et al., 1983).

Dengue is an old disease; the principal urban vector, Aedes aegypti, and the viruses were spread around the world as commerce and the shipping industry expanded in the 17th, 18th, and 19th centuries. Major epidemics of DF occurred as port cities were urbanized and became infested with Ae. aegypti. Because the viruses depended on the shipping industry for spread, however, epidemics in different geographic regions were sporadic, occurring at 10- to 40-year intervals. The disease pattern changed with the ecological disruption in Southeast Asia during and after World War II. The economic development, population growth and uncontrolled urbanization in the post-war years created ideal conditions for increased transmission and spread of urban mosquito-borne diseases, initiating a global pandemic of dengue. With increased epidemic transmission, and the movement of people within and between countries, hyperendemicity (the co-circulation of multiple DENV serotypes) developed in Southeast Asian cities, and epidemic DHF, a newly described disease, emerged (Gubler, 1997; Halstead, 1980; WHO, 1997). By the mid-1970s, DHF had become a leading cause of hospitalization and death among children in the region (WHO, 1997, 2000). In the 1980s and 1990s, dengue transmission in Asia further intensified; epidemic DHF increased in frequency and expanded geographically west into India, Pakistan, Sri Lanka, and the Maldives, and east into China (Gubler, 1997). At the same time, the geographic distribution of epidemic DHF was expanding into the Pacific islands in the 1970s and 1980s and to the American tropics in the 1980s and 1990s (Gubler, 1989, 1993, 1997; Gubler and Trent, 1994; Halstead, 1992).

Epidemiologic changes in the Americas have been the most dramatic. In the 1950s, 1960s, and most of the 1970s, epidemic dengue was rare in the American region because the principal mosquito vector, Aedes aegypti, had been eradicated from most of Central and South America (Gubler, 1989; Gubler and Trent, 1994; Schliessman and Calheiros, 1974). The eradication program was discontinued in the early 1970s, and the mosquito then began to reinvade those countries from which it had been eliminated. By the 1990s, Aedes aegypti had regained the geographic distribution it had before eradication was initiated (Figure 1-8). This was another classic case of “success breeding failure.”

FIGURE 1-8. Distribution of Aedes aegypti in American countries in 1930, 1970, and 2007.

FIGURE 1-8

Distribution of Aedes aegypti in American countries in 1930, 1970, and 2007. SOURCE: Courtesy, Division of Vector-Borne Infectious Diseases, CDC, Fort Collins, CO; adapted from Gubler (1998).

Epidemic dengue invariably followed after reinfestation of a country by Aedes aegypti. By the 1980s, the American region was experiencing major epidemics of DF in countries that had been free of the disease for more than 35 years (Gubler, 1989, 1993; Gubler and Trent, 1994; Pinheiro, 1989). With the introduction of new viruses and increased epidemic activity came the development of hyperendemicity in American countries and the emergence of epidemic DHF, much as had occurred in Southeast Asia 25 years earlier (Gubler, 1989). From 1981 to 2006, 28 American countries reported laboratory-confirmed DHF (Gubler, 2002b) (Figure 1-9).

FIGURE 1-9. Countries reporting confirmed DHF prior to 1981 and 1981 to 2007.

FIGURE 1-9

Countries reporting confirmed DHF prior to 1981 and 1981 to 2007. SOURCE: Courtesy, Division of Vector-Borne Infectious Diseases, CDC, Fort Collins, CO; adapted from Gubler (1998).

While Africa has not yet had a major epidemic of DHF, sporadic cases of severe disease have occurred as epidemic DF has increased in the past 25 years. Before the 1980s, little was known of the distribution of DENVs in Africa (Carey et al., 1971). Since then, however, major epidemics caused by all four serotypes have occurred in both East and West Africa (Gubler, 1997; Monath, 1994).

In 2007, dengue viruses and Ae. aegypti mosquitoes have a worldwide distribution in the tropics with 2.5 to 3.0 billion people living in dengue-endemic areas. Currently, DF causes more illness and death than any other arboviral disease of humans. The number of cases of DF/DHF reported to the World Health Organization (WHO) has increased dramatically in the past 3 decades (Figure 1-10). Each year, an estimated 100 million dengue infections and several hundred thousand cases of DHF occur, depending on epidemic activity (Gubler, 1997, 2002b, 2004; WHO, 2000).

FIGURE 1-10. Mean annual global reported cases of DEN/DHF to the World Health Organization, by decade, 1955–2005.

FIGURE 1-10

Mean annual global reported cases of DEN/DHF to the World Health Organization, by decade, 1955–2005. SOURCE: Adapted from MacKenzie et al. (2004).

Yellow Fever4

Yellow fever virus (YFV) was the first arbovirus to be isolated and the first shown to be transmitted by an arthropod. It is the type species of the family (Flaviviridae: genus Flavivirus) (Gubler et al., 2007). Its natural home is the rain-forests of sub-Saharan Africa where it is maintained in a cycle involving lower primates and canopy-dwelling mosquitoes (Monath, 1988). It was transported to the western hemisphere with the slave trade in the 1600s and became adapted to an urban cycle involving humans and Aedes aegypti mosquitoes, similar to dengue. It also established a sylvatic monkey cycle in the rain forests of the Amazon basin similar to the one in Africa.

The first recorded epidemic of YF occurred in 1648 and was followed by numerous epidemics in port cities of the New World, as far north as Boston (Monath, 1988). Urban epidemic transmission was effectively controlled in the Americas in the 1950s, 1960s, and 1970s by the Aedes aegypti eradication program (see earlier discussion) (Gubler, 1989; Schliessman and Calheiros, 1974) (Figure 1-8). The last known urban epidemic occurred in Brazil in 1942 (Monath, 1988). In Francophone countries of West Africa, YF was controlled by mass vaccination programs. The result was the disappearance of major urban epidemics of YF in both Africa and the Americas. In the mid-1980s, however, the urban disease reemerged in West Africa, with major epidemics in Nigeria and increased transmission in other countries (Gubler, 2004; Monath, 1988; Nasidi et al., 1989; Robertson et al., 1996). Kenya experienced its first epidemic in history in 1993 (Sanders et al., 1998). In the Americas, the reinfestion of most Central and South American countries by Aedes aegypti has put the urban centers of the American tropics at the highest risk for epidemic urban YF in more than 60 years (Gubler, 1989, in press). Thus, the disease continues to be an important public health problem in both Africa and the Americas.

The reemergence of epidemic YF in the past 30 years has not been as dramatic as that of DF/DHF. While there has been increased epidemic activity in both Africa and the Americas, the outbreaks have been limited and mostly associated with sylvatic cycles. Of concern is that several of the outbreaks in the Americas have occurred in or in close proximity to urban areas where Aedes aegypti occurs, greatly increasing the risk of urban transmission (Gubler, 2004; Van der Stuyft et al., 1999). Additionally, the recent increase in ecotourism without proper immunization has increased the risk of YF being introduced to urban areas where Aedes aegypti occurs (CDC, 2000).

Currently, the threat is that YFV will become urbanized in the American tropics and spread geographically much as DENVs have done over the past 25 years. The biggest concern is that it will be introduced to the Asia-Pacific region, where there are approximately 1.8 billion people living in large urban centers under crowded conditions in intimate association with large populations of Aedes aegypti mosquitoes, thus creating ideal conditions for increased urban transmission. While there is an effective, safe, and economical vaccine for YF, its supply is limited and it would take months to increase production to the point where adequate doses could be produced. By then YFV would likely be widely distributed in the region.

If YF was introduced to the Asia-Pacific, the initial cases would most likely be misdiagnosed as DHF, leptospirosis, rickettsiosis, hantavirus disease, or malaria, thus potentially allowing it to spread and become established in widespread areas before it was identified. Thus, YF virus could be introduced and become established in Asia-Pacific countries weeks to months before it was recognized. Even after it is diagnosed, it is not likely that an effective control program could be mounted because most countries in the region do not have effective Aedes aegypti control programs. Once recognized as YF, it would likely cause overreaction and panic on the part of the press, the public, and health officials. Regardless of whether YF virus caused a major epidemic in this region, there would be a major public health emergency, creating social disruption and great economic loss to all countries of the region, making the Indian plague epidemic of 1994 (Fritz et al., 1996; John, 1999; WHO, 1994) and the 2003 SARS epidemic (Drosten et al., 2003) pale by comparison.

It is not known whether YFV would become established in Asia (Downs and Shope, 1974; Gubler, 2004; Monath, 1989). YFV was most likely introduced sporadically to the Pacific and Asia in the past (Usinger, 1944), but secondary transmission has never been documented. There are several possible explanations why there have not been YF epidemics in the Asia-Pacific region (Monath, 1989). First, logistics: during the time when major YF epidemics were occurring in the Americas, the virus and the mosquitoes depended on ocean vessels to be transported to new geographical locations. The probabilities of the virus being introduced to Asia were low because the Panama Canal had not been built, and there was not as much commerce between Caribbean, Central and South American counties and Asia, as there was with the United States and Europe. Moreover, YF epidemics were not common in East Africa, thus decreasing the probability of introduction to India. Second, the high heterotypic flavivirus antibody (DENV-1, DENV-2, DENV-3, DENV-4, JEV, and many other flaviviruses of lesser importance) rates in Asian populations, while not protecting against YF infection, could possibly modulate the infection and down-regulate viremia and clinical expression, as has been shown in monkeys (Theiler and Anderson, 1975), thus decreasing the likelihood of secondary transmission by mosquitoes. Third, there has been some suggestion that Asian strains of Aedes aegypti mosquitoes are less susceptible to YFV than American strains (Gubler et al., 1982). Finally, it is possible that evolutionary exclusion may prevent YFV from becoming established in areas where closely related flaviviruses are endemic. Most likely, a combination of these factors has contributed to preventing YF from becoming established in Asia in the past.

The reason why urban YF has not occurred in the American tropics, despite the high risk in recent years, is not known. As noted for Asia, the high seroprevalance rates for the DENVs and other flaviviruses in most Central and South American countries could down-regulate viremia and illness, thus decreasing the risk of secondary transmission and clinical diagnosis. Additionally, the enzootic YFV may require adaptation to Aedes aegypti and humans, before becoming highly transmissible in the urban environment. If it does become adapted, however, it is important to remember that the logistic and demographic factors that influence arbovirus spread at the beginning of the 21st century are very different from past centuries. First, tens of millions of people travel by jet airplane between the cities of tropical America and the Asia-Pacific region every year; this provides the ideal mechanism for people incubating YFV to transport it to new geographic locations. There has been an increase in ecotourism in recent years, and since 1996, at least six tourists have died in the United States and Europe as a result of infection with YFV acquired during travel to YF endemic countries without vaccination (CDC, 2000; Gubler, 2004; Gubler and Wilson, 2005). If urban epidemic transmission of YF begins in the Americas, there could be thousands of YFV infected people traveling to Asia-Pacific countries where Aedes aegypti exposure is high, thus dramatically increasing the probability that epidemic YF transmission will occur in Asia.

Why Has There Been Such a Dramatic Resurgence of Vector-Borne Diseases?5

The dramatic global reemergence of epidemic vector-borne diseases in the past 25 years is closely tied to global demographic, economic, and societal trends that have been evolving over the past 50 years. Complacency and deemphasis of infectious diseases as public health problems in the 1970s and 1980s resulted in a redirection of resources and ultimately to a decay of the public health infrastructure required to control these diseases. Coincident with this trend, unprecedented population growth, primarily in the cities of the developing world, facilitated transmission and geographic spread. This uncontrolled urbanization and crowding resulted in a deterioration in housing accompanied by a lack of basic services (e.g., water, sewer, and waste management). Population growth has been a major driver of environmental change in rural areas as well (e.g., deforestation, agriculture land use, and animal husbandry practice changes). All of these changes contributed to increased incidence of vector-borne infectious diseases.

Many urban agglomerations (population >5 million) have emerged in the past 50 years, and most have an international airport through which millions of passengers pass every year (Wilcox et al., 2007). In addition, globalization has insured an equally dramatic increase in the movement of animals and commodities between population centers. The jet airplane provides the ideal mechanism by which pathogens of all kinds move around the world in infected humans, vertebrate host animals, and vectors. A classic example of how urbanization combined with globalization has influenced the geographic expansion of disease is illustrated by the DENVs (Figure 1-11). In 1970, only Southeast Asian countries were hyperendemic with multiple virus serotypes co-circulating, as a result of World War II. The rest of the tropical world was hypoendemic with only a single DENV serotype circulating, or nonendemic (Figure 1-11A). In 2007, the whole of the tropical world is hyperendemic as a direct result of urbanization, lack of mosquito control, and increased movement of viruses in people via modern transportation (Figure 1-11B). The result has been increased frequency of larger epidemics, and the emergence of the severe and fatal form of disease, DHF, in most tropical areas of the world. Globalizaton and modern transportation were also responsible for the recent spread of WNV to and throughout the western hemisphere (Figure 1-6). Increased transmission is a major driver of genetic change in all of these viruses, which can result in virus strains with greater virulence or epidemic potential being spread around the globe. The concern is that YF or RVF will be the next vector-borne diseases to spread because of globalization and modern transportation.

FIGURE 1-11. The global distribution of dengue virus serotypes, (A) 1970 and (B) 2007.

FIGURE 1-11

The global distribution of dengue virus serotypes, (A) 1970 and (B) 2007. SOURCE: Adapted from Mackenzie et al. (2004).

There are many other vector-borne diseases that have the potential for geographic spread. As an illustration of movement of infectious disease pathogens, Table 1-2 lists some of the exotic diseases introduced into the United States in recent years. It should be noted that the majority of these pathogens are vector-borne, zoonotic, and viruses. In addition, five species of exotic mosquitoes have been introduced and have become established in the country in the past 25 years. Some of the more important epidemic vector-borne diseases affecting humans at the beginning of the new millennium and which have the potential to spread via modern transportation are shown in Table 1-3. Again, it should be noted that most are zoonotic viral diseases. There is reason to believe that, sooner or later, one or more known or unknown pathogens will cause devastating epidemic disease.

TABLE 1-2. Exotic Infectious Diseases That Have Recently Been Introduced to the United States.

TABLE 1-2

Exotic Infectious Diseases That Have Recently Been Introduced to the United States.

TABLE 1-3. Principal Epidemic Vector-Borne Diseases Affecting Humans at the Beginning of the 21st Century.

TABLE 1-3

Principal Epidemic Vector-Borne Diseases Affecting Humans at the Beginning of the 21st Century.

Lessons Learned and Challenges to Reverse the Trend6

At the dawn of the 21st century, epidemic infectious diseases have come “full circle” in that many of the diseases that caused epidemics in the early 1900s, and which were effectively controlled in the middle part of the 20th century, have reemerged to become major public health problems. Complacency and competing priorities for limited resources have resulted in inadequate resources to continue prevention and control programs when there is no apparent disease problem. Only when an epidemic occurs do policy makers respond by implementing emergency response plans, but by then it is usually too late to have any impact on transmission.

In today’s world of modern transportation and globalization, we have learned to expect the unexpected: that old diseases will reemerge and new diseases will emerge, and that modern transportation and globalization will disperse them around the world. Once introduced and established, it is unlikely that zoonotic disease agents can be eliminated from an area.

We have learned that international cooperation and collaboration are critical to developing and maintaining effective early warning disease detection and emergency response systems. Unfortunately, while elaborate epidemic preparedness and response plans are often drawn up, these plans are most often not implemented until it is too late to impact disease transmission because the decision to declare an emergency is one that often has important political and economic implications. As a result, public health problems that should remain localized have the potential to become more widespread because of modern transportation and the mobility of people.

We have learned that we must emphasize prevention. Local public health infrastructure must be rebuilt and maintained in order to contain disease outbreaks as local public health events instead of letting them spread around the world via modern transportation. The public and the press require accurate and reliable information in order to prevent panic and overreaction.

We have learned that most newly emergent infectious diseases will likely be caused by zoonotic pathogens, and those that cause major regional or global epidemics that impact the global economy will likely originate in Asia. This has been the case for the past 25 years, and demographic, societal, and economic trends suggest this trend will continue for the indefinite future (Table 1-4). Thus, it is projected that most of the world’s population growth will occur in the cities of Asia in the next 25 years, and most of the world’s economic growth will occur in Asian countries. Changes in animal husbandry and agricultural practices, combined with regional human behavior and cultural practices, and increased trade, will all facilitate the emergence of exotic zoonotic pathogens in a region where people from rural areas continue to migrate to large urban centers, and from which the movement of people, animals, and commodities increase the risk of dispersal via modern transportation and globalization.

TABLE 1-4. Pathogens of Tomorrow: From Whence They Will Come?

TABLE 1-4

Pathogens of Tomorrow: From Whence They Will Come?

Finally, if we hope to reverse the trend of emerging and reemerging infectious diseases, the movement of pathogens and arthropod vectors via modern transportation must be addressed. This problem has important political and economic implications, but if it is not dealt with, the long-term costs will far exceed those required to proactively address the problem. Local public health infrastructure, including laboratory and epidemiologic capacity, must be developed in all countries, but especially in those tropical developing countries where new diseases may emerge. Effective laboratory-based, active disease surveillance systems are needed in every country, as are public health personnel that can respond rapidly and effectively to control epidemic transmission before it spreads. We need new tools (vaccines, drugs, insecticides, diagnostic tests, etc.), and finally, we need to better understand the ecology of newly emerging diseases in order to develop effective prevention strategies; drugs or vaccines will likely not be developed for most of these pathogens.

WHY WE DO NOT UNDERSTAND THE ECOLOGICAL CONNECTIONS BETWEEN THE ENVIRONMENT AND HUMAN HEALTH: THE CASE FOR VECTOR-BORNE DISEASE

Durland Fish, Ph.D.7

Yale University

New challenges in addressing the global rise of human disease burden due to emerging and reemerging infectious diseases have resulted in increased interest in the environmental determinants of disease risk and the underlying ecological processes that are involved (Guernier et al., 2004; Morens et al., 2004). Vector-borne diseases are exquisitely sensitive to environmental change because of the complex ecological processes that regulate the distribution and abundance of vectors in the environment, their contact with humans, and often also nonhuman reservoir hosts of infection for vectors (Sutherst, 2004). No other infectious disease threats of humans exhibit such extensive dependence upon ecological complexity. Progress in successfully addressing the problem of global vector-borne disease will rely upon our willingness and ability to understand this complexity to the extent that intelligent mitigation measures can be planned and implemented. Such progress has been hampered by an imbalance of research disciplines and allocated resources that have been applied to the problem, which favors reductionistic disciplines over holistic or organismic disciplines. A new interdisciplinary approach to the understanding of vector-borne diseases is long overdue.

The science of understanding how organisms, including human pathogens, interact with the environment lies squarely within the discipline of ecology. Yet, in the United States, the formal discipline of ecology is divorced from the realm of biomedical sciences, both in academia and in government agencies. Evidence for this is supported by the absence of formal training programs in ecology within medical schools and schools of public health, the exclusion by MEDLINE of all five journals published by the Ecological Society of America from its database (only two are just now indexed from 2006), and the absence of a specific study section within the National Institute of Allergy and Infectious Diseases (NIAID) to peer review extramural research proposals in ecology. These, as well as other intellectual and cultural barriers, have effectively alienated the discipline of ecology from the mainstream of biomedical science.

Historically, successful vector-borne disease prevention has relied upon the management or elimination of vector populations within the environment. Early concrete examples include louse-borne epidemic typhus during World War II (Raoult et al., 2004), mosquito-borne malaria in the Tennessee Valley (Patterson, 2004), and tick-borne encephalitis in Siberia (Uspensky, 1999). Prior to our dependence on insecticides for vector population control, an emphasis was placed on ecological studies of vectors as well as their parasites and predators for biological control. Wetlands and water management for mosquito control and malaria prevention depended on knowledge of habitat specificity for egg laying and larval development (Herms and Gray, 1944). The use of larvivorus fish for mosquito-borne arbovirus control depended on ecological knowledge of both predator and prey species (Geiger and Purdy, 1919). Host-specific hymenopterous parasitoids8 were discovered and deployed against ticks for prevention of Rocky Mountain spotted fever (Smith and Cole, 1943). The rapid success of chemical insecticides for reducing a broad range of vector populations virtually eliminated the need for continued ecological studies. Consequently, the emphasis on ecological studies of vectors, which dominated vector-borne disease research activities in the early 20th century, has yet to be restored despite the serious limitations of insecticide dependence resulting from vector resistance and adverse environmental impact (Busvine, 1978; Patterson, 2004).

Rather than returning to ecological studies that would provide a better understanding of the complex relationships among vectors, reservoir hosts and pathogens, and the environment that could potentially reveal alternative intervention strategies for vector-borne diseases, research emphasis was placed instead on reductionistic disciplines that promised to develop novel approaches for vector population suppression or elimination, such as genetic manipulation (sterility, translocation, conditional lethal genes, etc.) (Baker et al., 1978; Busvine, 1978; Seawright et al., 1978) and interruption of the physiological processes involved in the conversion of host blood into egg production (Borovsky et al., 1993; Hagedorn, 1974; Shapiro, 1980). These basic genetic and biochemical studies dominated vector biology research for more than two decades (1970s and 1980s). The extensive research on reproductive physiology has yet to produce a product or strategy that would impact vector-borne disease and the only apparent outcome of genetic manipulation studies so far has been the controversial use of sterile insect releases (Molyneux, 2001; Enserink, 2007), a technology developed in the 1950s (Bushland et al., 1955).

Throughout the most recent decade, research in vector biology has been dominated by the discipline of molecular biology with the ultimate goal of manipulating vector populations through the introduction of genes that will reduce vector competence for specific pathogens, thereby eliminating the need for population suppression (Aldhous, 1993; Alphey et al., 2002; Kramer, 2004; Speranca and Capurro, 2007; Nene et al., 2007). This approach has received wide acceptance as a promising area of research and has benefited from generous support from the World Health Organization (WHO), the National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation. While novel and extremely productive in understanding the molecular mechanisms of vector/pathogen interactions, this purely reductionistic approach is generally not viewed as having an immediate impact on vector-borne disease prevention (Spielman, 1994; Aultman et al., 2001; Enserink, 2002; Knols and Scott, 2002; Scott et al., 2002; Tabachnick, 2003; Toure and Manga, 2004). The many technical and logistic barriers to the practical implementation of transgenic vectors for disease control will likely delay the use of this technology for several more decades.

Such reductionistic and narrowly focused research agendas have contributed little to a broader understanding of the interactions between vectors and their physical or biological environment(s), which is essential for a complete understanding of vector-borne disease epidemiology and the development of other novel approaches for vector-borne disease prevention. Consequently, progress in our understanding of basic vector ecology has seriously lagged over many decades compared to that in fields of genetics, biochemistry, and molecular biology, which are the more traditional biomedical disciplines. Evidence for this lies in the relative paucity of vector-related publications in top-ranked ecology journals compared to top journals in traditional biomedical disciplines, and the progressive decline in the academically trained professional workforce specializing in vector ecology (see later discussion).

The scope of basic ecological processes that are poorly understood about vectors is extraordinary considering their importance in human disease transmission. Far more is known about how parasites, predators, and pathogens influence the abundance of insect species of agricultural importance than for most vectors of human disease (Service, 1983). The processes by which larval mosquitoes acquire nutrients in aquatic environments lag behind our knowledge of nutrient procurement for common aquatic stream insects (Merritt et al., 1992, 1996). Nutrient procurement is critical to the understanding of animal (and plant) ecology, yet significant studies have been conducted on only a very few of the more than 3,000 known mosquito species (Fish and Carpenter, 1982; Walker et al., 1988, 1991; Smith et al., 1998; Kaufman et al., 2006). Manipulation of the aquatic microfauna upon which mosquito larvae depend would seem to have tremendous potential for exploitation. However, this essential aspect of mosquito ecology is tragically understudied compared to the ongoing effort on transgenic vectors.

Natural mechanisms of animal population regulation were a prime topic in ecology during the 1950s and 1960s, but such studies applied to vector species are exceedingly rare (Evans and Smith, 1952; Southwood et al., 1972). Consequently, we know very little about the natural limits of population growth for vector populations and efforts to reduce population density of vectors are not based on knowledge of the regulatory processes already operative in nature. For holometabolous9 insect vectors, such knowledge would direct intervention efforts to either larval or adult populations (Herms and Gray, 1944). For tick populations, knowledge of the relative importance of on-host versus off-host mortality would provide intelligent choices for host reduction or habitat modification in population suppression efforts (Fish, 1993). Ignorance concerning the procurement of carbohydrate resources by adult mosquitoes, an essential daily requirement compared to the few life-time blood meals a female needs for reproduction (Foster, 1995), prevents its exploitation for control or surveillance applications. The fact that larval habitats for most species of sand fly vectors of leishmaniasis, Carrion’s disease, and phleboviruses are totally unknown to science (Tesh and Guzman, 1996; Feliciangeli, 2004) adds to the long list of astounding gaps in our basic knowledge of vector ecology.

In contrast, recent advances in genomic sciences have resulted in the ability to do complete genome sequencing for vectors and vector-borne pathogens (Gardner et al., 2002; Holt et al., 2002). These expensive projects are generally considered to be landmark accomplishments in the effort against global vector-borne diseases. While much basic research on vectors and pathogens is certain to ensue at the molecular level, there is no clear path to applications and its future impact upon vector-borne disease is uncertain (Enserink, 2002; Tabachnick, 2003). Basic research in all biological disciplines is essential for progress and innovation, but the disciplines of environmental science and ecology have not received a fair share of research support or recognition in biomedical science. This short-sightedness has limited our understanding of important connections between the environment and vector-borne disease and has weakened our overall effort to combat global vector-borne disease.

Imbalance in the total research effort among biological disciplines participating in vector-borne diseases is likely to continue for some time until a workforce is trained in interdisciplinary sciences that include ecology and environmental sciences. Concerns about this imbalance were articulated in a previous report published by the National Research Council in 1983 (NRC, 1983). Many subsequent articles and editorials on this subject have since appeared (Edman, 1993; Fish, 2001b; Gubler, 2001; Spielman, 2003, 2006), but with no apparent impact upon the status quo. Consequently, the workforce of academic professionals trained in the field aspects of vector biology and vector-borne disease has diminished to such a critical point that the capacity for such training is now endangered.

The recent epidemics of Lyme disease and West Nile virus in the United States have demonstrated our inability to effectively respond to vector-borne disease threats in our own backyard (literally). The traditional biomedical response of supporting basic research on diagnostics, therapeutics, and vaccines (Fauci et al., 2005) has had little, if any, impact on the natural courses of these epidemics (Fish, 2001a; Edman, 2005). Precise measures of environmental surveillance that identify populations at risk are inadequate for both diseases and prevention measures for both still depend primarily upon the controversial use of broad spectrum insecticides. Efforts to contain these epidemics through novel intervention directed at vectors or their reservoir hosts have been hampered by decades of inadequate basic research support on the environmental determinants of vector-borne disease risk coupled with an inadequate workforce with interdisciplinary training. A recent effort by the Centers for Disease Control and Prevention (CDC) to support academic training specifically in response to these recent vector-borne disease threats has not been sustained (Fish, 2007).

New technologies that have tremendous potential for improving our understanding of relationships between the environment and vector-borne disease risk include remote sensing by Earth-orbiting satellites, geographic information systems, and spatial statistics (Fish, 1996). A constellation of satellites continuously acquires a broad range of environmental data on vegetation, water, atmosphere, land use, and weather on a global scale that are archived and available for research and applications in vector-borne diseases (Beck et al., 2000). Geographic information systems provide powerful tools for capturing and analyzing spatially explicit data (Ostfeld et al., 2005). New statistical methods are being developed to determine spatial patterns in environmental data that reveal relationships between cause and effect. These powerful new tools are just beginning to be applied to vector-borne diseases and other human health problems (Hay et al., 2000, 2007). Courses in these topics are now being taught in schools of public health as well as in the environmental sciences.

The bridging of environmental sciences and infectious disease epidemiology through this common technology offers some immediate hope for broadening the realm of scientific disciplines participating in vector-borne disease research (Fish, 2002). Such new technologies combined with the wealth of existing basic knowledge and theories of contemporary ecology will do much to improve our understanding of the complex relationships among the environment and vectors, pathogens, reservoir hosts, and, consequently, human health.

While other emerging disease threats, such as directly transmitted zoonotic pathogens and, to a lesser extent, directly transmitted human pathogens, also are dependent upon the environment, vector-borne diseases have the greatest potential for advancing the integration of ecology and environmental science into the mainstream of infectious disease epidemiology. Such integration is long overdue, and it will fill a significant void in the spectrum of biological disciplines currently contributing to human health.

ECOLOGY OF EMERGING VECTOR-BORNE PLANT DISEASES

Rodrigo P. P. Almeida, Ph.D.10

University of California, Berkeley

Individuals, populations, communities, and ecosystems are impacted by pathogenic organisms at different levels. During epidemics, high mortality may result in temporary or permanent perturbations of ecological networks within communities (Daszak et al., 2000). Alterations in community structure can significantly impact habitats driving ecosystem change. On the other hand, anthropogenic environmental changes may have catastrophic consequences to natural communities and populations, in some cases resulting in pathogen spill over to humans (e.g., Daszak et al., 2000; Patz et al., 2004; Power and Mitchell, 2004). Therefore, reducing the social, economic, and environmental impacts of diseases requires in-depth knowledge of pathogen, host, and vector biology and ecology.

The increasing number of emerging diseases and epidemics in recent decades has stimulated interest in understanding how new diseases arise and previously rare diseases increase in incidence. However, most of the research linking diseases with environmental change has been limited to human and animal pathogens (e.g., Daszak et al., 2000; Patz et al., 2004). In this essay I will argue that there are important connections and similarities between human diseases and plant diseases, focusing on those occurring in agricultural systems. I will also discuss similarities among vector-borne diseases and present an example of how the introduction of an invasive vector species has dramatically modified the ecology of a bacterial pathogen of previous limited importance. One of my main goals is to emphasize that much could be gained in our understanding of the ecology of vector-borne human and animal diseases from work done with agricultural systems, and vice versa. Unfortunately, to this date researchers in these two domains remain largely unaware of each other.

Emerging Vector-Borne Diseases

The number of disease epidemics has dramatically increased in recent years, as have the threat of emerging new diseases and the reemergence of other diseases. Although biological factors such as pathogen mutations have been demonstrated to be associated with recent epidemics (Anishchenko et al., 2006), surveys have suggested that most diseases can be linked to anthropogenic activities (Woolhouse and Gowtage-Sequeria, 2005). A growing body of literature exists on pathogens disseminated without the aid of vectors, such as primate viruses “jumping” to human hosts primarily due to bush meat hunting activities (Wolfe et al., 2005).

Commerce, frequency and speed of transportation, invasive species, pesticide resistance, urbanization, climate change, and many other factors have been linked to emerging human diseases (Woolhouse and Gowtage-Sequeria, 2005). Anderson et al. (2004) conducted the only survey that systematically studied factors driving emerging plant diseases. Although introductions (56 percent) and weather (25 percent) were determined to be responsible for most emerging plant diseases, other factors were also found to be of importance. Interestingly, it was observed that viruses composed 47 percent of all emerging plant diseases. A similar trend was found in human emerging diseases (Woolhouse and Gowtage-Sequeria, 2005). Therefore, emerging human and plant diseases share driving factors, and approaches to control either one might be instructive to researchers working with both groups of pathogens.

Human Health, Environmental Change, and Plant Diseases

One of the challenges for this century will be to sustainably produce enough food for an exponentially growing world population. In 2006, 6.5 billion people inhabited the planet; the World Health Organization estimates that number will increase to 9 billion by 2050 (UN, 2007). Increasing crop yield with sustainable agricultural approaches that are not detrimental to the environment will be challenging. Approximately 40 percent of the world’s yield is currently lost due to pests (pre- and post-harvest) (Agrios, 1997). Because malnutrition and poverty are directly linked to human health, sustainably producing increased quantities of food to populations around the world will be a global challenge for future generations.

The increased technological inputs for agriculture and the expanding scale of monocultures provide continual change in challenges for producing food. The expansion of agricultural land and increased pesticide, irrigation, and fertilizer use have been the major controllable inputs to increase crop yield. These alternatives have various detrimental effects on the environment and human and animal health. Furthermore, the long-term sustainability of these strategies is questionable due to the environmental impact of current agricultural technology (Altieri and Nichols, 2005). To increase farm land one must explore new regions, infiltrating into forest, grassland, or other habitats that may provide important ecosystem services. 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 (Power and Mitchell, 2004). To reduce losses and increase yield per unit area, pesticides and fertilizers must be applied in increasing quantities. The environmental and health impacts of pesticides have been highly publicized. Fertilizers have a similar reputation, for example their role in driving toxic algal blooms caused by agricultural runoff in waters throughout the world (Gilbert et al., 2006). Because food production is tightly connected to human health, promoting sustainable agricultural practices may reduce the impact of human pathogens from individual to population levels. Quantitatively determining the importance of plant health in the maintenance of a healthy human population and a sustainable environment would certainly be an interesting exercise.

Contrasting Plant and Animal Vector-Borne Diseases

A large diversity of organisms transmits plant pathogens. The most common vectors are insects, but mites, nematodes, and fungi are also important (Agrios, 1997). Insects transmit plant-pathogenic viruses, bacteria, fungi, nematodes, and protozoa. Among insects, sap-sucking hemipterans such as aphids, leafhoppers, planthoppers, and whiteflies are the major vectors. Of those, aphids are the most important group, as they are responsible for disseminating 70 percent of vector-borne plant viruses (Nault, 1997). Like vector-borne animal pathogens, vector-plant pathogen interactions can be classified based on several characteristics, such as requirement for circulation and/or propagation within vector and temporal characteristics of transmission and pathogen retention (Gray and Banerjee, 1999; Ng and Perry, 2004). Molecular determinants of vector transmission have been well explored for only a few plant disease systems compared to numerous animal disease systems (e.g., Gray and Gildow, 2003).

In addition to commonalities in transmission biology, the ecology of vector-borne diseases of plant and humans also share important similarities. Human vector-borne pathogens are generally categorized as the etiological agents of anthroponotic (human-centered) diseases such as malaria or zoonotic (having an animal reservoir) diseases such as Lyme disease, in relation to their ecology (Eldrige and Edman, 2000). This is an important distinction with epidemiological implications, as the involvement of animal hosts in addition to humans in zoonotic diseases must be well understood to devise control strategies to reduce pathogen spread. A similar scenario occurs with plant pathogens. Some insect vectors are host-specific (e.g., certain aphid species), whereas others can have broad host ranges (e.g., sharpshooter leafhoppers). The host range of plant pathogens is largely dependent on the degree of vector specificity required for efficient dissemination and on the host range of the vectors, as usually there are no other means of spread. Pathogens transmitted by species with narrow host ranges tend to be plant specific, whereas those transmitted by polyphagous insects may infect many plants and cause disease in several crops or weeds. Some phloem-limited bacteria (mollicutes) of maize, for instance, only colonize species in the plant genus Zea (maize and teosintes) and are spread by a few oligophagous leafhopper vectors that have co-evolved with those host plants (Nault, 1990). In contrast, insect transmission of the bacterium Xylella fastidiosa has low vector specificity, being transmitted by several sharpshooter leafhoppers and the more distantly related spittlebugs. Both of these insect groups tend to be polyphagous (Redak et al., 2004). In consequence, this pathogen could colonize hosts in at least 94 species tested in 28 different plant families (Hill and Purcell, 1995a). Therefore, plant pathogens with a very narrow host range behave ecologically as anthroponotic diseases, whereas those with a wide host range behave more similarly to zoonotic ones.

Nevertheless, several relevant differences must be kept in mind when extrapolating concepts from animal to plant systems or vice versa. Host movement is significantly different in these systems. The host immune response of plants is very different from that of animals. Host genetic diversity may be high in animal systems, but is usually extremely low in crops. Moreover, the spatial, age structure, and population densities of crop plants differ dramatically from those of animals. In addition, plant disease epidemics often are not categorized as such unless at least thousands of individuals are infected. Therefore, host social networks, movement, immune response, and recovery are not considered of importance in plant epidemiology. Conversely, other approaches that incorporate the availability of large numbers of static susceptible hosts are more useful for plant systems.

The Plant Pathogenic Bacterium Xylella fastidiosa as a Case Study

The xylem-limited bacterium X. fastidiosa is present throughout the Americas and causes disease in many crops of economic importance, including Pierce’s disease of grapevines (PD), almond leaf scorch (ALS), and citrus variegated chlorosis (CVC) (Purcell, 1997). X. fastidiosa is disseminated among plants by sharpshooter leafhoppers (Hemiptera: Cicadellidae) and spittlebugs (Hemiptera: Cercopidae), both of which specialize in feeding on the sap in plant xylem (water-conducting tissue) (Severin, 1949, 1950). Sharpshooter leafhoppers are considered the most important vectors in epidemics examined so far. Transmission is not specific, as different strains of X. fastidiosa are transmitted by different vector species. There is no transmission of X. fastidiosa from parent to offspring and no required latent period (Freitag, 1951; Purcell and Finlay, 1979). However, the bacterium multiplies in the foregut of vectors and is persistent in adult insects but is lost when immature insects molt (Hill and Purcell, 1995b; Purcell and Finlay, 1979). The inoculum of X. fastidiosa for plant inoculation is located in the canals leading to the sucking pump (cibarium) of the foregut of vectors (Almeida and Purcell, 2006; Purcell et al., 1979). Transmission efficiency, however, varies dramatically depending on the combination of host plant, bacterial strain, and vector species. The factor most clearly associated with transmission efficiency is bacterial densities within plants, with higher cell numbers resulting in increased transmission rates (Hill and Purcell, 1997). The ecology of X. fastidiosa shares similarities with complex zoonotic diseases with multiple host species. X. fastidiosa has a very wide host range (Hill and Purcell, 1995a), with colonization patterns varying from systemic pathogenic plant-strain associations to infections that die out over time (Purcell and Saunders, 1999). The host range of sharpshooter vectors can also be very large, with up to a few hundred plants listed for certain species (Redak et al., 2004). Because X. fastidiosa has such a wide host range and is vectored without specificity by a group of insects that tends to be polyphagous, the resulting diseases have complex epidemiology.

Although X. fastidiosa has been present in California for over 100 years, only three large epidemics have occurred in that period of time, all of which were associated with grapevine hosts (PD) (reviewed by Hopkins and Purcell, 2002). The first one occurred in the late 1800s in Southern California, which decimated the incipient grape industry in the region. In the 1930s to 1940s an epidemic in the Central Valley associated with infected sharpshooters migrating from alfalfa fields was also of importance and resulted in several breakthroughs in our understanding of X. fastidiosa diseases by researchers at the time. In recent decades, however, the disease has been constantly present at low incidence in the wine grape growing coastal valleys of Napa and Sonoma. The third, and current, epidemic emerged after the introduction of a polyphagous invasive vector species, Homalodisca vitripennis (glassy-winged sharpshooter; Hemiptera: Cicadellidae) (Sorensen and Gill, 1996), into Southern California in 1989 (Blua et al., 1999). This invasive species is the driving factor of PD epidemics in Southern California and the southernmost region of the Central Valley. It is also responsible for several emerging X. fastidiosa diseases in California, such as oleander leaf scorch. I will discuss the current hypothesis on how H. vitripennis has increased the incidence of PD and how it may be responsible for the emergence of new diseases.

An Invasive Vector Driving the Emergence of a Rare Disease

PD epidemics have occurred in different regions of California, although much of Southern California and the Central Valley have been largely disease free in the last decades. The introduction of H. vitripennis into the state dramatically changed this scenario. In 1999, reports of PD outbreaks in the small wine region of Temecula Valley resulted in very high infection rates in just a few years after the epidemic began (Purcell and Feil, 2001); a similar situation occurred in Kern County, the southernmost area of the Central Valley, starting in 2000 (Hopkins and Purcell, 2002). A large area-wide monitoring, control, and research project is in place to address this problem and temporarily limit the distribution of H. vitripennis. The driving factor associated with the outbreak was the presence of extremely large numbers of H. vitripennis in vineyards. This vector overwinters in large number on citrus, up to thousands per plant, and has a larger dispersal range than that of typical sharpshooters. Therefore, it has been suggested that sheer numbers of an invasive species, not under biological control by native parasitoids, predators, or parasites, was the main factor driving the epidemic. Two cycles of pathogen spread could occur in this scenario, one of primary spread by infective vectors migrating from citrus to grape in early spring, and a second cycle with a new generation of vectors on grape that could acquire the pathogen from plants infected earlier in the year and transmit it to new plants during the summer and fall. Because citrus does not serve as a host of X. fastidiosa strains causing disease in grape in the United States, it has been suggested that secondary spread is responsible for the outbreak, a hypothesis dubbed “vine-to-vine spread” (Hopkins and Purcell, 2002).

Although the ecological factors responsible for these outbreaks are not well understood, it is clear that large vector populations are an important component of this system. H. vitripennis is a poor vector of X. fastidiosa to grape when compared to other species (Almeida and Purcell, 2003). Therefore, its ecology and behavior seem to offset low transmission rates. In addition, H. vitripennis can infect dormant vines under field conditions, opening a new window of time for new infections, when infective insects on citrus may migrate to vines in warm days during the winter (Almeida et al., 2005). That may be important because H. vitripennis overwinters on citrus and moves to vines in early spring when young shoots are present, remaining in vineyards until the winter (Park et al., 2006). Furthermore, H. vitripennis can also inoculate the woody tissue of vines, which are closer to tissues of the plant that are not pruned off during the winter, possibly resulting in a larger number of infections late in the growing season that persist through to the next year (Almeida and Purcell, 2003). On the other hand, evidence demonstrated that some late infections recover by a yet to be determined plant physiological mechanism during dormancy (Feil et al., 2003). In summary, PD epidemics in the presence of H. vitripennis in California seem to be driven primarily by an invasive vector species that compensates for poor transmission efficiency by having large populations in and near citrus, and behavioral and ecological characteristics that promote pathogen spread within vineyards.

Emergence of New X. fastidiosa Diseases

There are many strains, or genetic clusters, of X. fastidiosa isolates (Schuenzel et al., 2005). Like other bacterial pathogens, the difficulty in defining species boundaries, or what a bacterial species is, has plagued the taxonomy of X. fastidiosa. Nevertheless, this is a pathogen primarily limited to the Americas, with only one exception in Asia (pear disease) and a report from Europe (Purcell, 1997). Diversity studies have focused on diseased crops, biasing sample collection towards pathogenic isolates occurring in a limited number of host plants (e.g., Hendson et al., 2001; Schuenzel et al., 2005). Pathogenicity studies, linking genetic diversity to host species susceptibility, have not been widely conducted, limiting the interpretation of molecular diversity results. Studies in the United States have provided an idea of X. fastidiosa’s diversity, primarily because it causes disease in many host plants in the country compared to Brazil, for example, where it is documented to cause disease in only three crops. If environmental samples from alternative, nonsymptomatic hosts were included in such surveys, it is reasonable to assume that a much larger number of genetic clusters could be identified. As previously mentioned, this is a pathogen transmitted by several polyphagous sharpshooters with very wide plant host ranges. Thus, this pathogen has the potential to diverge and maybe have a high rate of genetic recombination among isolates in different environments and host plants.

Oleander leaf scorch (OLS) emerged in the mid-1990s in Southern California, and was tightly associated with the presence of H. vitripennis (Purcell et al., 1999). OLS is caused by what at the time was a new strain of X. fastidiosa. It is possible that this strain of X. fastidiosa was present in alternative host plants in the region, with limited dispersal by native vector species occurring in low numbers and without feeding preference for oleander; an alternative hypothesis is that this strain was an introduction into California. It can be hypothesized that H. vitripennis, present in high numbers and with feeding preference for oleander, could have acquired this strain from an alternative host and transferred it to oleander where it was maintained by the presence of susceptible hosts by a vector occurring in high number on the same host. A similar mechanism may be responsible for the emergence of X. fastidiosa diseases in many host plants in the presence of H. vitripennis in recent years, including mulberry, sweet gum, and olive (Wong et al., 2006).

A model for the emergence of new diseases after the introduction of a new vector into a region could be valid for vector-borne diseases in which pathogens are maintained in the environment in hosts of marginal epidemiological importance by vector species with little or no preference for feeding on humans or animals of interest. In this situation, pathogens have the opportunity to not only be maintained in endemic cycles, but also diverge and evolve into new strains, as different vector species may have associations with hosts of variable degrees of specificity. The introduction of a new vector species may result in pathogen acquisition from such cycles and its transfer to new disease cycles where it may be self-maintained (Figure 1-12).

FIGURE 1-12. Model illustrating a hypothesis on how newly introduced vectors may drive new disease epidemics.

FIGURE 1-12

Model illustrating a hypothesis on how newly introduced vectors may drive new disease epidemics. On the left, different strains of a pathogen (labeled with different letters) are maintained in endemic disease cycles in alternative habitats by different (more...)

Concluding Remarks

Human, animal, and plant vector-borne pathogens share several biological, ecological, and epidemiological similarities, but important differences exist. Unfortunately, scientists studying these systems rarely exchange ideas or are aware of each other’s research contributions. Plant scientists, for example, could incorporate tools and concepts from studies on human diseases that integrate pathogen spatial and temporal distribution and molecular population genetics to develop disease spread and evolution models. On the other hand, plant systems allow large experiments to be conducted, with multiple hosts, vector species, and pathogen strains, which could be used to experimentally address ecological and evolutionary hypotheses on pathogen range and transmission efficiency. Finally, ecological hypotheses based on either system may be useful in building models that can be tested for the development of disease control strategies.

Acknowledgments

I thank Matt Daugherty, Joao Lopes, and Sandy Purcell for helpful discussions, insights, and suggestions to this manuscript.

ECOLOGY OF DISEASE: THE INTERSECTION OF HUMAN AND ANIMAL HEALTH

Kenneth J. Linthicum, Ph.D.11, 12

USDA-ARS Center for Medical, Agricultural, and Veterinary Entomology

Seth C. Britch, Ph.D.12

USDA-ARS Center for Medical, Agricultural, and Veterinary Entomology

Assaf Anyamba, Ph.D.13

NASA Goddard Space Flight Center

Jennifer Small13

NASA Goddard Space Flight Center

Compton J. Tucker, Ph.D.13

NASA Goddard Space Flight Center

Jean-Paul Chretien, M.D., Ph.D.14

Department of Defense-Global Emerging Infections System

Ratana Sithiprasasna, Ph.D.15

Armed Forces Research Institute of Medical Sciences

Introduction

President John F. Kennedy stated in the early 1960s in reference to the world community, “For in the final analysis, our most basic common link, is that we all inhabit this small planet, we all breathe the same air, we all cherish our children’s futures, and we are all mortal.” More than 40 years later it is evident that on this small planet we also share the same animal and human vector-borne infectious diseases, as evidenced by the global spread of emerging diseases such as West Nile virus (Hayes et al., 2005).

Population growth, frontier agricultural expansion, and urbanization transform the landscape and the surrounding ecosystem, affecting climate, diseases, and interactions between animals and humans. Additionally, the earth’s oceans serve as the engine of the earth’s climate and ecosystems, and they are closely linked (NASA, 1999). Epstein (2002) described how climate variability has a direct impact on infectious diseases, and increased disease transmission has been linked to the El Niño/Southern Oscillation (ENSO)-driven global climate anomalies (Checkley et al., 2000; Pascual et al., 2000). Outbreaks of vector-transmitted diseases such as Murray Valley encephalitis, bluetongue, Rift Valley fever (RVF), African horse sickness, Ross River virus disease, and malaria also have been associated with ENSO phenomena (Anyamba et al., 2006). In this work we briefly address (1) the effect of ecology on vector-borne disease, (2) the role of ecology and global climate in disease forecasting, and (3) the potential use of forecasting to reduce impact and limit spread of vector-borne disease.

Effect of Ecology on Vector-Borne Diseases

Several examples will be used to demonstrate that we share a global environment that strongly influences vector-borne disease transmission. First, we will describe how temperature plays a major role in the ability of Aedes aegypti to transmit dengue virus in Southeast Asia and possibly chikungunya virus in Africa. Second, we will describe how rainfall affects the ability of Aedes and Culex species to transmit RVF in sub-Saharan Africa. Third, we will describe how modifications to environment such as the construction of a dam and development of rice irrigation projects affect the ability of Culex species to transmit RVF in Mauritania and Senegal. During periods of elevated transmission there is a significantly increased risk of globalization of these and other arboviruses. The ability to predict periods of high risk might permit us to design better prevention, containment, or exclusion strategies to limit globalization of these and other pathogens.

Temperature

The Ae. aegypti mosquito is the principal vector of dengue viruses in Southeast Asia and most of the world’s tropics. Dengue virus infection in humans can produce classical dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), and these diseases are endemic in Southeast Asia. DHF and DSS cases are reported to the Ministry of Health in Thailand by health care professionals, clinics, and hospitals; however, classic dengue fever is so common that it is not reported to the Ministry of Health. Cases of DHF represent approximately 1 percent of the total dengue infections (Gubler, 1988). The spatial distribution of DHF between years is highly variable and not well understood. The incidence of DHF is affected by temperature-induced variation in the vectorial capacity of mosquitoes (Watts et al., 1987) and other factors including the virus and human hosts. Vectorial capacity is dependent upon the extrinsic incubation period of the virus in the mosquito vector the time from virus ingestion to the time that virus infects the salivary glands of the mosquito.

Global climate is significantly affected by the variability of sea surface temperatures (SSTs). Due to its location, the climate in Southeast Asia is influenced by the variability in both the Pacific and Indian Ocean temperatures. The impacts of the interannual variability in SSTs in these oceans is revealed in atmospheric circulation through outgoing longwave radiation (OLR) measurements. These satellite-derived measurements are a proxy indicator of cloudiness and hence rainfall. When expressed as anomalies with respect to reference long-term means, negative OLR anomalies in the tropics represent regions of precipitating clouds, whereas positive OLR anomalies are associated with dry conditions. Through such measurements the impacts of such phenomena as ENSO on global cloudiness and rainfall patterns can be observed. Various climate indicators, such as SST and OLR, can be measured with instruments on Earth-orbiting satellites (Anyamba et al., 2006). Large-scale variability in the climate regime producing either floods or droughts has the effect of enhancing the emergence and propagation of various disease vectors.

DHF incidence data, calculated per 100,000 population, were examined for all provinces in Myanmar (1981–1988) and Thailand (1979–1998) and compared to OLR anomalies over those two countries, respectively. There was a positive correlation, with a several-month lag, between OLR anomalies and reported DHF cases in 1987 and 1990–1991 in Myanmar, and in 1980, 1984–1985, 1987, 1988–1989, and 1997–1998 in Thailand. This indicates that hot and dry conditions, which characterize warm ENSO episodes in this region, preceded increased DHF occurrence (Linthicum, unpublished observations). Drought conditions in Southeast Asia are associated with the occurrence of warm ENSO episodes. The relationship between dengue incidence in Thailand and OLR anomalies is depicted in Figure 1-13. Dengue incidence data were obtained from Nisalak et al. (2003). Recently, warm dry conditions associated with a warm ENSO event in 2006–2007 led to elevated transmission, and the government of Indonesia reported that it considered the DHF outbreak in April 2007 to be “an extraordinary situation” (ProMed-Mail, 2007).

FIGURE 1-13. Dengue incidence calculated per 100,000 population for Thailand from 1973 to 1999 plotted against OLR anomalies from 1979 to 2000.

FIGURE 1-13

Dengue incidence calculated per 100,000 population for Thailand from 1973 to 1999 plotted against OLR anomalies from 1979 to 2000. Increase and peaks in dengue incidence is preceded by hot and dry periods indicated by positive OLR anomalies. Drought conditions (more...)

Chikungunya virus, which causes febrile illness and joint pain, is also transmitted by Ae. aegypti and other Aedes species in Africa. Epidemics of chikungunya fever affected hundreds of thousands of people in the Indian Ocean basin from 2005 to 2007, and the initial outbreak occurred in coastal Kenya in 2004 (Chretien et al., 2007). They demonstrated, analyzing satellite-derived normalized difference vegetation index (NDVI) data anomalies and rainfall measurements, that the chikungunya outbreak began in June 2004 following unusually dry and warm conditions, especially in May 2004 (Figure 1-14). Widespread water storage and elevated temperatures, thus increasing habitat for container-breeding Ae. aegypti, were thought to have contributed to this outbreak along the coast to Kenya.

FIGURE 1-14. NDVI (dashed line) and rainfall anomalies (bars) for Lamu, Kenya, between 1998 and 2006.

FIGURE 1-14

NDVI (dashed line) and rainfall anomalies (bars) for Lamu, Kenya, between 1998 and 2006. Negative NDVI and rainfall anomalies indicate unusually dry conditions. SOURCE: Chretien et al. (2007).

Rainfall

Outbreaks of RVF are known to follow periods of widespread and heavy rainfall associated with the development of a strong intertropical convergence zone over East Africa (Davies et al., 1985). Rainfall has a significant effect on the ability of various Aedes and Culex species to transmit RVF in sub-Saharan Africa. Excessive rainfall is thought to precipitate RVF virus outbreaks by flooding mosquito breeding habitats and producing a hatch of primary (RVF-vertically-infected Aedes spp.) and increase in secondary (Culex spp.) vectors (Linthicum et al., 1985). Additionally, there are strong linkages between ENSO events and outbreaks of RVF as depicted in Figure 1-15 (Linthicum et al., 1999). These linkages have permitted us to develop a monitoring and risk mapping system using a suite of satellite-derived measurements including SST, OLR, rainfall, and NDVI to map areas with potential for an RVF outbreak (Anyamba et al., 2002).

FIGURE 1-15. Southern Oscillation Index (SOI) anomalies between January 1950 and 2006.

FIGURE 1-15

Southern Oscillation Index (SOI) anomalies between January 1950 and 2006. Periods of RVF activity in Kenya are depicted by black bars. Monthly SOI values are shown as standardized deviations based on the 1951–1980 mean. Outbreaks of RVF coincide (more...)

Environmental Modifications

An RVF virus epizootic/epidemic occurred in West Africa in the Senegal River basin in October and November 1987 (Jouan et al., 1988). Severe hemorrhagic disease was observed in the human population of the area, accompanied by a high incidence of abortion and disease in their livestock (Ksiazek et al., 1989). More than 200 strains of RVF virus were isolated from patients in the local hospital in Rooso, Mauritania.

Unlike other sub-Saharan RVF epizootics, which occurred during periods of very heavy rainfall, this outbreak occurred during a period of only average rainfall. Immediately prior to the outbreak, however, a series of ecological modifications to the Senegal River were instituted by the Mauritanian and Senegalese governments in cooperation with internationally sponsored programs. These modifications included the construction of two dams on the Senegal River (one at Diama in the delta region and one 1,200 km up river at Manantelli in Mali). Dams and dikes were also constructed along the river to control the natural flooding.

The controlled management of the river resulted in several dramatic changes in the ecology of the river basin. Although not designed to impound water, the Diama dam caused extensive flooding and vegetation growth in Senegal and Mauritania (Figure 1-16). This flooding peaked in October 1987, coinciding with the RVF outbreak (Linthicum et al., 1994). New areas of increased rice agricultural development were identified in satellite data along the river where we observed intense Culex species mosquito immature development as late as January 1988. Subsequent RVF activity in this region has tended to cluster along the Senegal River, indicating that landscape modification can contribute to endemism of diseases.

FIGURE 1-16. Diama Dam on Senegal River (left), and resulting flooding (center) and vegetation development (right) in Mauritania in January 1988 after the closure of dam.

FIGURE 1-16

Diama Dam on Senegal River (left), and resulting flooding (center) and vegetation development (right) in Mauritania in January 1988 after the closure of dam.

The association between RVF activity and alterations in the ecology of the region suggests that the development of new ecological habitats for potential Culex species mosquito vectors may have caused and/or enhanced the epidemic. Just as new technological developments, like irrigation projects, can enhance or in some cases cause disease outbreaks, new technologies, like satellite remote sensing, can now help in the prediction and possible control of these same outbreaks.

Knowledge of Global Climate and Ecology to Forecast Disease

ENSO is the most well-known phenomenon influencing global climate variability. Important aspects of interannual variability in global weather patterns are linked to ENSO. El Niño refers to a large-scale ocean-atmosphere climate phenomenon that is linked to periodic warming of SSTs across the central equatorial Pacific. Because of the large size of the Pacific Ocean, changes in SST patterns and gradients across the basin influence global atmospheric circulation.

There is building evidence suggesting links between ENSO-driven climate anomalies and infectious disease, particularly those transmitted by arthropods, such as Murray Valley encephalitis (Nicholls, 1986), bluetongue (Baylis et al., 1999), RVF (Linthicum et al., 1999), Ross River virus (Woodruff et al., 2002), dengue (Linthicum et al., unpublished), malaria (Bouma and Dye, 1997; Bouma et al., 1996), and chikungunya (Chretien et al., 2007).

The link established between ENSO and RVF, based on ecological studies (Anyamba et al., 2002), was used to establish in 2000 an operational RVF risk mapping system for sub-Saharan Africa, the Nile Valley, and the Arabian Peninsula.16 The convergence of a Pacific El Niño event and the warming of the western Indian Ocean led to widespread and persistent rainfall in semiarid lands of East Africa. As described earlier under “Rainfall,” flooding of mosquito habitats introduce RVF-infected Aedes mosquitoes into the environment and vegetation develops providing ecological microhabitats conducive for mosquito survival and propagation. Ocean temperatures, rainfall, and vegetation development are monitored and this information is used to produce RVF risk maps monthly.

In July to October 2006, anomalous positive SSTs in the equatorial east Pacific, indicative of the typical development of El Niño conditions, were observed. In October 2006, SSTs 2°C and 1°C above normal developed in the equatorial eastern Pacific Ocean and equatorial western Indian Ocean, respectively, suggesting the development of heavy rainfall in East Africa (Figure 1-17). Additionally, negative OLR anomalies were observed over the equatorial Indian Ocean and East Africa indicating elevated convective activity and heavy rainfall. The persistence of these conditions eventually produced extremes in global-scale climate anomalies similar to those observed in previous years, and RVF risk maps predicted the outbreak that occurred in December 2006 and continued until May 2007 (Anyamba et al., 2006).

FIGURE 1-17. SST anomalies for October 2006 (top) and OLR anomalies for October 2006 (bottom).

FIGURE 1-17

SST anomalies for October 2006 (top) and OLR anomalies for October 2006 (bottom). SSTs are shown in degrees Celsius, and OLR is shown as watts per square meter. Positive (negative) SST anomalies in the western equatorial Indian Ocean are associated with (more...)

Disease Forecasting to Reduce Impact and Limit Spread

The prediction of the 2006–2007 RVF in East Africa and subsequent observations of response activities can give us an insight about how disease forecasting based on ecological conditions might help reduce the impact and spread of vector-borne diseases. Between September and November 2006, several alerts were provided to the international public health and agricultural communities, presentations were made in scientific forums, and news media were notified. The World Health Organization (WHO) notified appropriate representatives and officials in East African countries, and the Food and Agriculture Organization (FAO) issued an Emergency Prevention System for the Transboundary Animal Diseases (EMPRES) Watch in November 2006 (FAO, 2006). The EMPRES program provides, at an international level, an overall initiative for coordination of the RVF-Early Warning System, where data integration and analysis are performed before being disseminated to recipient countries, international organizations, and key stakeholders in the form of RVF bulletins and risk assessments. Regional task forces in Kenya were alerted, and field assessment was promoted in flooded areas.

The U.S. Army Research Unit based in Nairobi, Kenya (USAMRU-K) and the Kenya Medical Research Institute were alerted and started mosquito surveillance of mosquitoes in northeastern Kenya in flooded areas in November. RVF was isolated in December in conjunction with the first report of human cases. WHO, FAO, the government of Kenya, USAMRU-K, and the U.S. Centers for Disease Control and Prevention (CDC) mobilized response teams and resources in an attempt to identify the extent of the outbreak and provide control and containment operations. The government of Kenya banned slaughter of livestock in eastern and northeastern Kenya and started a public education campaign, and various organizations became involved in distribution of mosquito nets and personal protection measures, application of insecticides to mosquito habitats, domestic animal vaccination, and other control measures. The response to the 2006–2007 RVF outbreak was 1 to 1.5 months earlier than that which occurred in the 1997–1998 outbreak in the same part of Africa. It appears likely that the early warning contributed to a reduced impact of the disease and limited its geographical spread.

Advance knowledge of an RVF, dengue, or chikungunya outbreak in their endemic areas might be used to prevent globalization of the disease by assessing favorable conditions in other parts of the world where suitable mosquito vectors, potential domestic animal hosts, and likely habitats for disease exist. Knowledge of vector-borne disease activity in endemic areas can be used to trigger monitoring of trade, and movement of people and mosquitoes on aircraft between sites of disease outbreaks and other places in the world where introduction might occur. For example, early planning and active monitoring of ships and containers arriving from endemic ports and dispersed into the wide network of inland container facilities in the United States could potentially detect and eliminate introduced RVF threats before these threats reach suitable human, animal, or mosquito hosts (Figure 1-18). Early detection of RVF in human or mosquito hosts could provide early warning in the United States or other nonendemic regions or countries before ecological conditions become optimal for elevated mosquito populations, thus permitting targeted implementation of mosquito control, animal quarantine, and vaccine strategies in time to reduce or prevent animal and human diseases (Linthicum et al., 2007). Additionally, the RVF risk mapping system in operation in Africa could be adapted for use in the United States and neighboring countries.

FIGURE 1-18. Shipping lanes entering eastern U.S. ports and inland container facilities from offshore destinations.

FIGURE 1-18

Shipping lanes entering eastern U.S. ports and inland container facilities from offshore destinations. The figure is based on data from the U.S. Bureau of Transportation Statistics.

Conclusions

Understanding the ecology of vector-borne viral disease transmission is critical and can provide linkages between the environment, including climate, and mosquito densities. These linkages can be evaluated with spatial and temporal statistics, generating risk maps to inform the community at risk. This information can provide a powerful tool to public health and agricultural authorities, enabling them to target disease surveillance/control efforts, minimize cost of surveillance over large areas, design better containment or exclusion strategies to limit disease spread, and predict risk and permit anticipation of globalization of vector-borne diseases.

CLIMATE CHANGE AND HEALTH: GLOBAL TO LOCAL INFLUENCES ON DISEASE RISK17

Jonathan A. Patz, M.D., M.P.H. 18

University of Wisconsin

Sarah H. Olson18

University of Wisconsin

The World Health Organization has concluded that the climatic changes that have occurred since the mid 1970s could already be causing annually over 150,000 deaths and five million disability-adjusted life-years (DALY), mainly in developing countries. The less developed countries are, ironically, those least responsible for causing global warming. Many health outcomes and diseases are sensitive to climate, including: heat-related mortality or morbidity; air pollution-related illnesses; infectious diseases, particularly those transmitted, indirectly, via water or by insect or rodent vectors; and refugee health issues linked to forced population migration. Yet, changing landscapes can significantly affect local weather more acutely than long-term climate change. Land-cover change can influence micro-climatic conditions, including temperature, evapo-transpiration and surface run-off, which are key determinants in the emergence of many infectious diseases. To improve risk assessment and risk management of these synergistic processes (climate and land-use change), more collaborative efforts in research, training and policy-decision support, across the fields of health, environment, sociology and economics, are required.

In the past half-century, global mean temperature has risen by 0.6°C, sea level has risen by a mean of 1–2 cm/decade, and ocean heat content has also measurably increased (Figure 1-19). The rate of change in climate is faster now than in any period in the last 1,000 years. Between 1990 and 2100, according to the United Nations Intergovernmental Panel on Climate Change (IPPC), mean global temperatures will increase by 1.4–5.8°C and sea level will rise by 9–88 cm, with mid-range estimates of 3°C and 45 cm, respectively (Houghton et al., 2001). However, additional greenhouse-gas releases from warmer oceans (CO2) and warmer soils (CO2 and methane) will increase the estimated warming from human-induced emission another 2°C by the end of the century (Torn and Harte, 2006). Extremes of the hydrological cycle (e.g., floods and droughts) are expected to accompany the global warming.

FIGURE 1-19. Variations in the mean surface temperatures recorded (using thermometers) across the planet in the past 140 years (a) and (using a combination of tree-ring, coral, and ice-core analysis and, for recent decades, thermometers) in the northern hemisphere over the past 10,000 years (b).

FIGURE 1-19

Variations in the mean surface temperatures recorded (using thermometers) across the planet in the past 140 years (a) and (using a combination of tree-ring, coral, and ice-core analysis and, for recent decades, thermometers) in the northern hemisphere (more...)

Non-Infectious Diseases

Heat Waves

Extremes in air temperature, both hot and cold, are associated with higher levels of human morbidity and mortality than seen within an intermediate or ‘comfortable’ range of temperatures. The relationship between temperature and mortality is typically ‘J-shaped,’ indicating asymmetry, with a steeper slope at higher temperatures (Curriero et al., 2002). In the U.S.A., heat waves are more deadly than hurricanes, floods and tornadoes combined.

The extreme heat wave that hit much of Europe in 2003 is estimated to have killed up to 45,000 people in just 2 weeks (Walker, 2004; Kosatsky, 2005). The summer of 2003 was probably Europe’s hottest summer in >500 years, with mean temperatures 3.5°C above normal (Beniston, 2004; Luterbacher et al., 2004; Schar et al., 2004). Although the level of temperature-related mortality seems to vary with geographical location, the temperature-mortality relationship found in European and North-American cities appears similar to that in São Paulo, a developing Brazilian city with sub-tropical conditions (Gouveia et al., 2003). The results of the relevant studies conducted so far indicate a clear vulnerability to heat in the relatively cool, temperate regions, and tropical regions may show similar sensitivity as location-specific temperatures rise.

Built environments markedly modify the intensity of ambient temperatures, in a phenomenon known as the ‘urban heat island effect.’ Black asphalt and other dark surfaces (on roads, parking lots or roofs) reduce albedo (reflectivity) and consequently increase the heat retention of the surface. In addition, the loss of trees in urban areas diminishes the cooling effect of evapotranspiration. During heat waves, when stagnant atmospheric conditions may persist, air pollution often compounds the effects of the elevated air temperatures (Frumkin, 2002). Urban areas may therefore suffer from both global and localized warming.

Severe Storms and Rise in Sea Level

Floods, droughts and extreme storms have claimed millions of lives during the recent past, and have adversely affected the lives of many more people. On average, disasters killed 123,000 people world-wide each year between 1972 and 1996. Africa suffers the highest rate of disaster-related deaths, even though 80 percent of the people affected by natural disasters are in Asia (Loretti and Tegegn, 1996). Disaster-related mental disorders, such as post-traumatic-stress disorder (PTSD), may substantially affect population well-being, depending upon the unexpectedness of the impact, the intensity of the experience, the degree of personal and community disruption, and the long-term exposure to the visual signs of the disaster.

Hurricanes only form in regions where sea surface temperatures exceed 26°C, and sea-surface warming by slightly more than 2°C intensifies hurricane wind speeds by 3–7 m/s (or 5 percent-12 percent) (Knutson et al., 1998). Records indicate that sea-surface temperatures have steadily increased over the last 100 years, and more sharply over the last 35 years. The highest mean sea-surface temperatures ever recorded occurred between 1995 and 2004 (Trenberth, 2005). During the first half of this period, there was a doubling in the overall hurricane activity in the North Atlantic and a five-fold increase in such activity in the Caribbean (Goldenberg et al., 2001). The North Atlantic Oscillation (NAO) was in its warm phase at this time, making it difficult to attribute the extra hurricanes to the long-term trends in warming. Sea-surface temperature is, however, correlated with hurricane intensity, and the frequency of higher-category storms has increased in many other parts of the world (Figure 1-20).

FIGURE 1-20. The increasing trend in strong tropical storms seen over the last 50 years.

FIGURE 1-20

The increasing trend in strong tropical storms seen over the last 50 years. For the plot, the power dissipation indices (PDI) for the Atlantic Ocean and Western Pacific were adjusted (by multiplying them by a factor of 5.8610213) so that they could be (more...)

Rise in sea level Warmer oceans also cause sea levels to increase, primarily as the result of the thermal expansion of salt water. Even if the mid-range predictions of climate change are correct and sea levels in the 2080s are, on average, ‘only’ 40 cm higher than the current values, the coastal regions at risk of storm surges will become much greater and the population at risk will increase from the current 75 million to 200 million (McCarthy et al., 2001). Rising sea levels will result in the salination of coastal freshwater aquifers and the disruption of stormwater drainage and sewage disposal. A case study for Bangladesh (Nicholls and Leatherman, 1995) indicates that >15 percent of the total population would be adversely affected by a 1.5-m rise in sea level (Figure 1-21).

FIGURE 1-21. The potential impact of sea-level rise on Bangladesh.

FIGURE 1-21

The potential impact of sea-level rise on Bangladesh. If sea levels rose by 1.5 m, 17 million people (15 percent of the population) and an area of 22,000 km2 would be affected. This figure is adapted from one produced by the United Nations Environment (more...)

Droughts That droughts cause famines is well recognized. Malnutrition remains one of the largest health crises world-wide, with approximately 800 million people—close to half residing in Africa—currently undernourished (WHO, 2002). Droughts and other climate extremes not only have direct impacts on food crops but can also indirectly influence food supply by altering the ecology of plant pathogens. While projections of the effect of climate change on global food-crop production appear to be broadly neutral, such change will probably exacerbate regional inequalities in the food supply (Parry et al., 2004). As there is a breakdown in sanitation as water resources become depleted, droughts can also increase the incidence of diarrhoea and diseases, such as scabies, conjunctivitis and trachoma, associated with poor hygiene (Patz and Kovats, 2002).

Air Quality and Climate

Air temperature affects the problems posed by air pollutants. Ground-level ozone smog tends to become worse with increasing air temperature but the relationship is nonlinear, with a strong correlation only seen at temperatures above 32°C. In their recent study, Bell et al. (2006) predicted that, because of global warming, the mean number of days exceeding the health-based “8-h ozone standard” will increase by 60 percent in the eastern U.S.A.—from 12 to almost 20 days per summer—by the 2050s.

Pollen levels in the air may also increase with global warming, as higher levels of CO2 promote growth and reproduction by many plants. When, for example, ragweed (Ambrosia artemisiifolia) plants were experimentally exposed to high levels of CO2 they increased their pollen production several-fold; this response is perhaps part of the reason for rising levels of ragweed pollen observed in recent decades (Ziska and Caulfield, 2000; Wayne et al., 2002). Ziska et al. (2003) found that ragweed grew faster, flowered earlier and produced more pollen in urban locations than in rural locations, presumably because of the relatively high air temperatures and CO2 levels in the urban areas.

Finally, if the frequency of flooding increases, significant exposure to moulds may also pose respiratory health risks during the post-flood clean-ups (Patz et al., 2001).

Infectious Diseases

Water- and Food-Borne Diseases

Water shortages, as mentioned above, contribute to diarrhoeal disease through poor hygiene, especially in poor countries. On the other hand, flooding can contaminate drinking water with run-off from sewage lines, containment lagoons (such as at animal-feeding operations), or conventional (non-point-source) pollution from across watersheds.

The parasites in the genus Cryptosporidium are usually associated with domestic livestock but can contaminate water intended for human consumption, especially during periods of heavy precipitation. In 1993 a cryptosporidiosis outbreak in Milwaukee, which killed more than 50 people and potentially exposed over 400,000 more to Cryptosporidium, coincided with unusually heavy spring rains and run-off from melting snow (Mac Kenzie et al., 1994). A review of outbreaks of any water-borne disease in the U.S.A. over a 50-year period demonstrated a distinct seasonality, a spatial clustering in the key watersheds, and a strong association with heavy precipitation (Curriero et al., 2001).

Certain food-borne diseases are also affected by fluctuations in temperature. Across much of continental Europe, for example, an estimated 30 percent of reported cases of salmonellosis occur when air temperatures are 6°C above the mean (Kovats et al., 2004). In the U.K., the monthly incidence of food poisoning is strongly correlated with air temperatures in the previous 2–5 weeks (Bentham and Langford, 1995).

Coastal waters One type of phytoplankton, the dinoflagellates, thrive in warm waters with adequate nitrogen, and they are the primary component of toxic “red tides.” They can cause acute paralytic, diarrhoeic, and amnesiac poisoning in humans, as well as extensive die-offs of fish and shellfish and the marine mammals and birds that depend on the marine food-web. The frequency and global distribution of toxic algal incidents and the incidence of human intoxication from algal sources appear to be increasing (Van Dolah, 2000).

Vibrio species also proliferate in warm marine waters. Zooplankton that feed on algae can serve as reservoirs for Vibrio cholerae and other enteric pathogens of humans. In Bangladesh, cholera follows the seasonal increase in sea-surface temperatures that can enhance plankton blooms (Colwell, 1996). During the El Niño event in 1997–1998, winter temperatures in Lima increased to >5°C above normal, and the number of daily admissions for diarrhoea rose to levels that were twice as high as recorded, over the same months, in the previous 5 years (Checkley et al., 2000). Although long-term studies of the El Niño Southern Oscillation (ENSO) have shown a consistent association with cholera and other diarrhoeal diseases, the oscillation appears to have played an increasing role in cholera outbreaks in recent years, perhaps because of concurrent climate change (Rodo et al., 2002). A detailed understanding of the inter-annual cycles of cholera and other infectious diseases, however, requires the combined analyses of both environmental exposure and the host’s intrinsic immunity to a disease. When they considered these factors together, Koelle et al. (2005) found that the inter-annual variability seen in cholera in Bangladesh was strongly correlated, across periods of <7 years, with sea-surface temperatures in the Bay of Bengal, ENSO and the extent of flooding in Bangladesh, and, across longer periods, with the monsoon rains and the discharge of the Brahmaputra river.

Vector-Borne Diseases

As the human pathogens transmitted indirectly by insect or rodent vectors spend considerable time outside of their vertebrate hosts, they may easily be affected by environmental conditions. The range of suitable climatic conditions within which each vector-borne pathogen and its vector can survive and reproduce is limited. The incubation time of a vector-borne infective agent within its vector is typically very sensitive to changes in temperature and humidity (Gubler et al., 2001). Table 1-5 shows some examples of temperature thresholds.

TABLE 1-5. Temperature Thresholds of Some Human Pathogens and Their Vectors.

TABLE 1-5

Temperature Thresholds of Some Human Pathogens and Their Vectors.

Malaria Between 700,000 and 2.7 million people—mostly children in sub-Saharan Africa—die each year of malaria (www.cdc.gov/malaria), and, thanks to climate and land-use change, drug resistance, ineffective control efforts, and various socio-demographic factors, there is no evidence that malaria-attributable mortality is falling. Malaria is an extremely climate-sensitive tropical disease, making the assessment of the potential change in malarial risk, caused by past or projected global warming, one of the most important topics in the field of climate change and health (Patz et al., 2005). The incidence of malaria varies seasonally in highly endemic areas, and malaria transmission has been associated with temperature anomalies in some African highlands (Zhou et al., 2005). In the Punjab region of India, excessive monsoon rainfall and the resultant high humidity have been recognized for years as major factors in the occurrence of malaria epidemics. More recently in the region, the frequency of malaria epidemics was observed to increase approximately five-fold during the year following an El Niño event (Bouma and van der Kaay, 1996). In Botswana, Thomson et al. (2006) recently showed that indices of El Niño-related climate variability can serve as the basis of malaria-risk prediction and early warning.

Highland malaria Air temperatures decrease by a mean of 6°C for every 1,000 m gained in elevation. In areas where human malaria is endemic, this effect usually precludes the transmission of malarial parasites at high altitudes, partly because the parasites cannot produce sporozoites in mosquitoes living at low temperatures. The minimum temperatures for the sporogony of Plasmodium falciparum and P. vivax, for example, are approximately 18°C and 15°C, respectively (Figure 1-22). As seen in the African highlands (Bodker et al., 2003), mosquito abundance tends to decrease with increasing altitude. Global warming is likely to result in an increase in the altitudes at which no malaria transmission occurs. In Africa, Tanser et al. (2003) estimated that the risk of exposure to malaria, measured in person months, will be 16 percent–28 percent higher in 2100 than at present. Having compared climate suitability maps for malaria in the topographically diverse country of Zimbabwe, Ebi et al. (2005) concluded that the warming predicted from global-climate models could make the country’s entire highland area climatologically suitable for malarial transmission by 2050. The highland areas of Africa that are not currently endemic for malaria but are, as the result of global warming, at high risk of becoming areas where transmission occurs are shown in Figure 1-23. Pascual et al. (2006) recently reported that the East African highlands had generally become warmer since 1950, over a period in which malaria incidence had also increased. There are well-recognized non-linear and threshold responses of malaria to the effect of regional temperature changes. In a form of biological ‘amplification,’ the response of mosquito populations to warming can be more than an order of magnitude larger than the measured change in temperature, an increase of just 0.5°C translating into a 30 percent–100 percent increase in mosquito abundance (Pascual et al., 2006). In the African highlands, where mosquito populations are relatively small compared with those in lowland areas (Minakawa et al., 2002), such biological responses may be especially significant in determining the risk of malaria.

FIGURE 1-22. As this graph produced by MacDonald (1957) illustrates, air temperature has a marked effect on the extrinsic incubation periods (EIPs—the times taken by the parasites to produce sporozoites in their mosquito vectors) of Plasmodium falciparum and P. vivax.

FIGURE 1-22

As this graph produced by MacDonald (1957) illustrates, air temperature has a marked effect on the extrinsic incubation periods (EIPs—the times taken by the parasites to produce sporozoites in their mosquito vectors) of Plasmodium falciparum and (more...)

FIGURE 1-23. Areas of the African highlands that, though currently nonendemic, are probably vulnerable to malaria as the result of climate warming ().

FIGURE 1-23

Areas of the African highlands that, though currently nonendemic, are probably vulnerable to malaria as the result of climate warming (Image ch1fu1.jpg). These areas, which are at altitudes of .1000 m, have ratios of precipitation to potential evapo-transpiration that (more...)

Malaria and local effects on climate from land-use change Changing landscapes can significantly affect local climate more acutely than long-term global warming. Land-cover change, for example, can influence the micro-climatic conditions, including temperature, evapo-transpiration and surface run-off (Foley et al., 2005), that are key to determining mosquito abundance and survivorship. In Kenya, Afrane et al. (2005) observed that open treeless habitats had warmer mean midday temperatures than forested habitats, and that deforestation also affected indoor hut temperatures (Figure 1-24). As a result, the gonotrophic cycle of female Anopheles gambiae s.l. during the dry and rainy seasons was found to be 2.6 days (52 percent) and 2.9 days (21 percent) shorter, respectively, in the deforested sites than in the forested. Similar findings have been documented in Uganda, where temperatures in communities bordering cultivated fields have been found higher than those in communities adjacent to natural wetlands, and the number of An. gambiae s.l./house has been found to increase with increasing minimum temperature, after adjustment for potentially confounding variables (Lindblade et al., 2000). In Kenya, mosquito breeding sites in farmland have been found to be relatively warm and this warmth speeds up the development of the immature insects (Munga et al., 2006). Increased canopy cover in western Kenya is negatively associated with the presence of larval An. gambiae s.l. and An. funestus in natural aquatic habitats (Minakawa et al., 2002). In artificial pools, survivorship of the larvae of An. gambiae s.s. in sunlit open areas was 50-fold higher than that in forested areas, and also related to assemblages of predatory species (Tuno et al., 2005). In short, deforestation and cultivation of natural swamps in the African highlands creates conditions favourable for the survival of An. gambiae larvae, making an analysis of the effects of land-use change on local climate, habitat, and biodiversity key to any malaria-risk assessments.

FIGURE 1-24. Comparison of the maximum (○), mean (□) and minimum (▵) temperatures recorded within huts in deforested agricultural lands with the corresponding maximum (●), mean (▪) and minimum (▴) temperatures recorded within huts in forests.

FIGURE 1-24

Comparison of the maximum (○), mean (□) and minimum (▵) temperatures recorded within huts in deforested agricultural lands with the corresponding maximum (●), mean (▪) and minimum (▴) temperatures recorded (more...)

Deforestation has also affected malaria in other regions, such as the Amazon basin (Guerra et al., 2006). Vittor et al. (2006) found a strong association between the biting rates of An. darlingi and the extent of deforestation in the Amazon; after controlling for the variation in human population densities, the biting rates of An. darlingi were still >200-fold higher in sites experiencing >80 percent deforestation than in sites with <30 percent deforestation.

Human activities have the capacity to shift the biodiversity of local ecosystems rapidly, intentionally and unintentionally increasing or decreasing malarial risk factors by altering the environment and mosquito habitat. The direction of the trend depends heavily on the Anopheles species present and on local conditions (Guerra et al., 2006). In north–eastern India, expansive deforestation has caused the numbers of An. dirus and An. culicifacies to decline (Dev et al., 2003). The effects of changing land-use patterns on the regulation of malaria (or other infectious disease) across a large area are species and site-specific, and therefore cannot be generalised.

Arboviruses Although Aedes aegypti is known to be strongly affected by ecological and human ‘drivers’ in urban settings, this species is also influenced by climate, including variability in temperature, moisture and solar radiation. Similar to the extrinsic incubation periods of malarial parasites (Figure 1-22), the rate of replication of dengue virus in Ae. aegypti increases directly with air temperature, at least in the laboratory. Biological models have been developed to explore the influence of projected temperature change on the incidence of dengue fever. These models indicate that, given viral introduction into a susceptible human population, relatively small increases in temperature could significantly increase the potential for epidemics of dengue (Patz et al., 1998). In addition, for relatively small countries with presumably some climate uniformity, a climate-based dengue model has been developed that strongly correlates with the inter-annual variability seen in the incidence of dengue reported at the national level (Figure 1-25; Hopp and Foley, 2003).

FIGURE 1-25. Correlation between simulated, climate-driven variations in Aedes aegypti mosquito density (○) and observed variations in the annual numbers of cases (•) of dengue, including dengue haemorrhagic fever, in three countries.

FIGURE 1-25

Correlation between simulated, climate-driven variations in Aedes aegypti mosquito density (○) and observed variations in the annual numbers of cases (•) of dengue, including dengue haemorrhagic fever, in three countries. Using a computer (more...)

Certain other arboviruses, such as Saint Louis encephalitis virus (SLEV), are also associated with climatic factors. In Florida, the appearance of SLEV in sentinel chicken flocks is preceded by a wet period followed by drought (Shaman et al., 2002). It has been suggested that spring drought forces the mosquito vector, Culex nigripalpus, to converge with immature and adult wild birds in restrictive, densely vegetated, hammock habitats. This forced interaction of mosquito vectors and avian hosts then creates an ideal setting for rapid transmission and amplification of SLEV. Once the drought ends and water sources are restored, the infected vectors and hosts disperse and transmit SLEV to a much broader geographical area (Shaman et al., 2002).

Climate variability may also have an effect on West Nile virus (WNV), a pathogen only recently introduced into the New World. Reisen et al. (2006) found that the strain of WNV that entered New York, during the record hot July of 1999, differed from the South African strain in that it required warmer temperatures for efficient transmission. It seems likely that, during the epidemic summers of 2002–2004 in the U.S.A., epicentres of WNV were linked to above-average temperatures.

Rodent-Borne Diseases

Hantavirus is transmitted to humans largely by exposure to infectious rodent excreta, and may then cause serious disease, with a high level of mortality. In the emergence of hantavirus pulmonary syndrome in the southwestern U.S.A., in 1993, it was the weather conditions, especially El Niño-driven heavy rainfall, that appear to have led to a growth in rodent populations and subsequent viral transmission (Glass et al., 2000).

Extreme flooding or hurricanes can lead to outbreaks of leptospirosis. In 1995, an epidemic of this disease occurred in Nicaragua after heavy flooding, and a major risk factor for the disease was found to be walking through the flood waters (Trevejo et al., 1998).

Attribution of Disease Burden Resulting from Climate Change

The World Health Organization (WHO) has examined the global burden of disease already attributable to anthropogenic climate change up to the year 2000 and made model-based forecasts of the health risks from global climate change up to the year 2030 (McMichael et al., 2004). Conservative assumptions were made about climate-health relationships (e.g., that socio-economic conditions would prevent a climate-driven spread of vector-borne disease from endemic tropical regions to temperate regions) and many plausible health impacts were excluded for lack of quantitative models. The results indicate that the current burden from climate-sensitive diseases such as diarrhoea, malaria and malnutrition is so large that even the subtle climatic changes that have occurred since the mid-1970s could already be causing >150,000 deaths and approximately 5 million disability-adjusted life-years (DALY) each year. Although climate change is a global threat to public health, the WHO’s assessment also revealed that the poorer regions of the world may be the most vulnerable (Figure 1-26). When the WHO’s estimates of morbidity and mortality caused by human-induced climate change were extrapolated to 2030, it was found that the climate-change-induced excess risk of the various health outcomes considered could more than double by that year (McMichael et al., 2004).

FIGURE 1-26. The World Health Organization’s estimates of mortality attributable to climate change by the year 2000 (no estimate could be made for Western Sahara or French Guiana because of a lack of data).

FIGURE 1-26

The World Health Organization’s estimates of mortality attributable to climate change by the year 2000 (no estimate could be made for Western Sahara or French Guiana because of a lack of data). The Intergovernmental Panel on Climate Change’s (more...)

Conclusions

The health outcomes from climate change are diverse and occur via multiple pathways of exposure. Whereas some disease resurgence has been attributed to recent warming trends, some of the long-term and complex problems posed by climate change may not be readily discernible from other causal factors. Accordingly, expanded efforts are required in both classical and future-scenario-based risk assessment, to anticipate these problems. In addition, the many health impacts of climate change must be examined in the context of many other environmental and behavioral determinants of disease. Increased disease surveillance, integrated modelling, and the use of geographically-based data systems will enable more anticipatory measures by the public-health and medical communities.

There are clear ethical challenges. The regions with the greatest burden of climate-sensitive diseases are often the regions with the lowest capacity to adapt to the new risks. Many of the regions most vulnerable to climate change are also those least responsible for causing the problem. Africa, for example, is thought to harbour about 70 percent of all malaria cases but has the lowest per-capita emissions of the ‘greenhouse’ gases that cause global warming. In today’s globalized world, with its international trade and travel, an increase in disease anywhere on the globe can affect every country.

Health is just one of the many sectors expected to be affected by climate change. It represents just a part of the interconnected context in which decision makers must implement strategies to prevent or reduce the adverse effects of such change. To achieve the greatest disease prevention, “upstream” environmental approaches, rather than assaults on single agents of disease, must form part of any intervention. If the truly global public-health challenge of climate change is to be adequately addressed, an unprecedented co-operation between natural and social/health scientists, as well as between rich and poor countries, must occur.

CLIMATE CHANGE AND VECTOR-BORNE DISEASE: UPDATE ON CLIMATE EFFECTS ON LYME DISEASE AND WEST NILE VIRUS IN NORTH AMERICA

Jonathan A. Patz, M.D., M.P.H.19

University of Wisconsin

Christopher K. Uejio, M.A.

University of Wisconsin

Introduction

Global climate change is expected to have broad health impacts. These could occur through various exposure pathways, such as the frequency or intensity of extreme heat waves, floods, and droughts. Warmer air temperatures could also influence local and regional air pollutants and aeroallergens. Less direct health impacts may result from climate-related alteration of ecosystems or water and food supplies, which in turn could affect infectious disease incidence and nutritional status. Finally, sea level rise could potentially lead to massive population displacement and economic disruption. Positive effects may include fewer winter-related deaths in some regions.

Changes in temperature, humidity, rainfall, and sea level rise could all affect the incidence of infectious diseases. Mosquitoes, ticks, and fleas are cold-blooded and thus sensitive to subtle temperature and humidity changes. But vector-borne diseases are also dependent on many other interacting factors. Although there has been a resurgence of infectious diseases in recent years, it is unclear that climate change has played a significant role. Other factors such as the movement of human and animal populations, the breakdown in public health infrastructure, changes in land use, and the emergence of drug resistance have been contributory.

The transmission of infectious diseases is strongly influenced by temperature, humidity, and rainfall (see Box 1-1). The distribution and seasonality of important infectious diseases are likely to be affected by climate change. Diseases transmitted by insect or rodent vectors have life cycles where much time is spent outside the human host, and therefore are more influenced by ambient conditions. There is a limited range of climatic conditions within which each such infective or vector species can survive and reproduce.

Box Icon

BOX 1-1

Some Effects of Weather and Climate on Vector-and Rodent-Borne Diseases. Vector-borne pathogens spend part of their life cycle in cold-blooded arthropods that are subject to many environmental factors. Changes in weather and climate that can affect transmission (more...)

Mosquito-borne virus transmission is largely governed by vector population abundance, vector host-seeking behavior, and the dissemination of the virus through the vector’s body to the salivary glands. The environment can be thought of as contextually providing suitable conditions for the persistence of infectious disease agents or more directly driving the variability of vector and host populations and interactions. Environmentally mediated mechanisms explaining vector and host dynamics focus on nonlinear changes to time before an infectious mosquito can retransmit a virus or extrinsic incubation period (EIP), vector population explosions, or changing host-seeking behavior (Jupp et al., 1986; Kilpatrick et al., 2006; Reisen et al., 2006).

For a full discussion of the topic, refer to Patz and Olson (2006) earlier in this chapter. Next, we provide an update on the two most prevalent vector-borne diseases in North America: Lyme disease and West Nile virus.

Lyme Disease

Lyme disease, Rocky Mountain spotted fever, ehrlichiosis, and tick-borne encephalitis are the most common vector-borne diseases in temperate zones in the northern hemisphere. Climate affects tick habitat, host and reservoir species, the interval between blood meals, and pathogen transmission.

Lyme disease is the most prevalent tick-borne disease in North America for which there is new evidence of an association with temperature (Ogden et al., 2006) and precipitation (McCabe and Bunnell, 2004). In the field, temperature and vapor pressure contribute to maintaining populations of the tick Ixodes scapularis, which, in the United States, is the microorganism’s secondary host. A monthly average minimum temperature above −7°C is required for tick survival (Brownstein et al., 2003).

The northern boundary of tick-borne Lyme disease is limited by cold temperature effects on the tick, Ixodes scapularis. Linking to future projections of climate via global climate models (GCMs), the northern range limit for this tick could shift north by 200 km by the 2020s, and 1,000 km by the 2080s. Plausible tick geographic ranges were developed from the Coupled Global Climate Model version 2 (CGDM2) and Hadley Centre Coupled Model, version 3 (HadCM3) models using the A2 Intergovernmental Panel on Climate Change Special Report on Emissions Scenario (Ogden et al., 2006).

West Nile Virus

Climate variability has been shown to affect West Nile virus (WNV), a disease only recently introduced into the New World in 1999. The summer adult WNV vector Culex spp. monthly abundance across diverse U.S. and Canadian biomes is largely controlled by antecedent moisture and temperature conditions (Raddatz, 1986; Day and Curtis, 1989; Andreadis et al., 2004). Optimal temperatures increase the rates of juvenile mosquito maturation, adult females biting, virus replication (decreases the extrinsic incubation period), and the total amount of virus transmitted (Madder et al., 1983; Buth et al., 1990; Rueda et al., 1990; Turrell et al., 2001; Dohm et al., 2002). Temperature’s influence on vector abundance is place specific, dependent upon local conditions and time during the mosquito season. Mild winter, spring, and warmer early summer season conditions foster enhanced vector survival and replication (Takeda et al., 2003; Degaetano, 2005).

WNV vector abundance in mid-latitude locations generally increases directly with moisture variables such as precipitation or river run-off levels over the preceding month (Wegbreit and Reisen, 2000; Degaetano, 2005). Mosquitoes are r-strategists20 with a competitive ecological advantage to preferentially reproduce in novel habitats created or activated by excessive precipitation. The wettest spring and summer in 100 years was significantly associated with increased WNV vectors abundance in the central United States (Vandyk and Rowley, 1995). Conversely, drought over the preceding year’s summer season may also induce a mosquito population explosion by suppressing competitor and/or predator development (Chase and Knight, 2003).

Absolute and relative departures from summer long-term average temperature and precipitation conditions are hypothesized to be similarly important WNV transmission and epidemic drivers. High summer temperature and positive temperature anomalies have been observed in South Africa, Russia, and the United States (McIntosh et al., 1976; Jupp et al., 1986; Platonov et al., 2001; Reisen et al., 2006). Drought-like conditions or below-average summer or spring precipitation are common threads of Romanian, Russian, and French WNV outbreaks (Despommier, 2001; Han et al., 1999; Platonov et al., 2001). Abnormal or suitable moisture conditions conversely influence disease transmission in climatically sensitive South Africa. Extreme seasonal precipitation, subsequent breeding site creation, and normally hot temperatures coupled with existing irrigation and land use practices fueled two widespread South African epidemics (McIntosh et al., 1976). In the neighboring semiarid region, summer season average temperatures 1.1°C above normal and average precipitation may similarly have triggered the 1984 WNV epizootic (Jupp et al., 1986). A combination of antecedent winter/spring drought and above-average summer moisture controls vector and avian host aggregation and resulting virus amplification (Shaman et al., 2005). Human activities such as degraded housing infrastructure, which spawned abnormal vector population levels, also influence WNV transmission dynamics (Han et al., 1999).

Efficient transmission of the New York WNV strain is greatly reduced at low average temperatures compared to African isolates (Cornel et al., 1993; Reisen et al., 2006). The efficiency of WNV transmission from an infected Cx. pipiens to another vector directly increases as average temperatures rise from 18–30°C, (Figure 1-27). A mosquito’s period of infectivity is sensitive to temperature such that relatively small seasonal temperature changes (1.3°C) may double WNV infection risk (Reisen et al., 2006). WNV transmission and epidemic genesis may therefore be more temperature limited in higher latitude locations. During WNV’s march westward across the continental United States, above-average or average monthly temperatures qualitatively coincided with northern latitude regional epicenters (Figure 1-28) (Reisen et al., 2006). A straightforward model uses vector EIP to classify counties into “high” or “low” WNV transmission risk areas (Zou et al., 2007). Current temperature information drives the spatial explicit model, which has moderate but variable levels of over-and underprediction (Zou et al., 2007).

FIGURE 1-27. Decrease in the time before an infectious mosquito can retransmit a virus or extrinsic incubation period from laboratory experiments.

FIGURE 1-27

Decrease in the time before an infectious mosquito can retransmit a virus or extrinsic incubation period from laboratory experiments. SOURCE: Dohm et al. (2002). Reprinted with permission from the Entomological Society of America. Copyright 2002.

FIGURE 1-28. (A) Long-term climatological average summer (June–September) temperatures for the United States and (B–D) anomalies for each summer from 2002 to 2004.

FIGURE 1-28

(A) Long-term climatological average summer (June–September) temperatures for the United States and (B–D) anomalies for each summer from 2002 to 2004. National epicenters with relatively high numbers of recorded human cases are encapsulated (more...)

Land use and land cover metrics contain interrelated information on biophysical conditions and vector and host community assemblages that influence WNV transmission. Urban/suburban study sites consistently exhibit a modest positive association with infected avian hosts (Gibbs et al., 2006). Predominately white, moderately high income, suburban areas with housing built from 1940 to 1960 and moderate vegetation experienced as high as 3 to 8 times the WNV risk as the safest land use classification in two WNV epicenter cities (Ruiz et al., 2007). WNV vector infection prevalence tended to be lower in wetlands with greater community avian diversity than forest, shrub, or developed study sites (Ezenwa et al., 2007).

Conclusions

Climate change may affect the distribution and transmission intensity of a number of infectious diseases. Many of the linkages are complex and a range of other social, behavioral, and environmental factors also affect the health outcomes in question. Therefore, enhanced integrated assessment is required to identify threshold conditions and to improve disease predictions. Due to the cross-cutting nature of risks posed by climate change, determining more upstream environmental risk factors should be of high priority, in addition to the ever-present need for improved surveillance and early warning.

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Footnotes

1

Director, Asia-Pacific Institute for Tropical Medicine and Infectious Diseases; Professor and Chair, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine.

2

Reprinted in part with permission from Gubler (2008). Copyright 2008.

3

Reprinted in part with permission from Gubler (2008). Copyright 2008.

4

Reprinted in part with permission from Gubler (2008). Copyright 2008.

5

Reprinted in part with permission from Gubler (2008). Copyright 2008.

6

Reprinted in part with permission from Gubler (2008). Copyright 2008.

7

Yale School of Public Health; Yale School of Forestry and Environmental Studies; Yale Center for EcoEpidemiology.

8

Parasitic wasps such as those commonly used for biological control of insect pests.

9

Insects that undergo complete metamorphosis (larva, pupa, and adult stages).

10

Department of Environmental Science, Policy and Management.

11

Corresponding author. Agricultural and Veterinary Entomology, 1600 S.W. 23rd Drive, Gainesville, FL 32608. Phone: (352) 374-5700; Fax: (352) 374-5850; E-mail: vog.adsu.sra@mucihtniL.htenneK.

12

Mosquito and Fly Research Unit.

13

Biospheric Sciences Branch.

14

Division of Preventive Medicine, Walter Reed Army Institute of Research.

15

Department of Entomology

16
17

Reprinted with permission from Maney Publishing. Copyright Liverpool School of Tropical Medicine, 2006. This article was originally published in Annals of Tropical Medicine and Parasitology 100(5–6):535–549 (2006). See http://www​.maney.co.uk/journals/atmp and http://www​.ingentaconnect​.com/content/maney/atmp.

18

Center for Sustainability and the Global Environment (SAGE), the Nelson Institute and Department of Population Health Sciences.

19

Associate Professor and Director, Global Environmental Health, Center for Sustainability and the Global Environment (SAGE), Nelson Institute for Environmental Studies and Department of Population Health Sciences, 1710 University Avenue, Madison, WI 53726. Phone: (608) 262-4775; Fax: (608) 265-4113; E-mail: ude.csiw@ztap; Website: http://www​.sage.wisc.edu.

20

The term r-strategist heuristically characterizes species that develop rapidly, produce abundant offspring, and have small body sizes. K-strategists conversely develop slowly and invest more resources in a larger body size and a small number of progeny (MacArthur and Wilson, 1967).

Copyright © 2008, National Academy of Sciences.
Bookshelf ID: NBK52945

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