American Association for the Advancement of Science

Volume 260(5114) 11 June 1993 pp 1610-1616

The Biological and Social Phenomenon of Lyme Disease

Barbour, Alan G.; Fish, Durland

A. G. Barbour is in the Departments of Microbiology and Medicine, University of Texas Health Science Center, San Antonio, TX 78284. D. Fish is in the Medical Entomology Laboratory, Department of Community and Preventive Medicine, New York Medical College, Valhalla, NY 10595.

Outline

• Abstract

• The Origins of Lyme Disease in North America

• Maintenance of Borrelia burgdorferi in Nature

• Biology of Borrelia burgdorferi

• Dilemmas in Diagnosis and Case Management

• Surveillance for Lyme Disease

• Prevention Through Immunization

• Prevention Through Vector Control

• Conclusion

• REFERENCES AND NOTES

Graphics

• Figure 1

• Figure 2

Abstract

Lyme disease, unknown in the United States two decades ago, is now the most common arthropod-borne disease in the country and has caused considerable morbidity in several suburban and rural areas. The emergence of this disease is in part the consequence of the reforestation of the northeastern United States and the rise in deer populations. Unfortunately, an accurate estimation of its importance to human and animal health has not been made because of difficulties in diagnosis and inadequate surveillance activities. Strategies for prevention of Lyme disease include vector control and vaccines.

Lyme disease is a zoonosis, an inadvertent infection of humans with an animal pathogen. In

temperate regions of the Northern Hemisphere, ticks transmit the etiologic bacterium Borrelia

burgdorferi from its usual wildlife reservoirs to humans and domestic animals [1,2]. In the

United States, Lyme disease occurs primarily in suburban and rural areas [3]. Early infection of

humans is usually a self-limited, flu-like illness with a skin rash where the tick imbeds itself [4]

Figure 1. After a few weeks to several months, as many as 70% of untreated, infected patients

suffer the effects of bacterial invasion of one or more distant organs or systems, including the

brain, nerves, eyes, joints, and heart [5]. These late manifestations, particularly the dysfunction

of the central nervous system and chronic arthritis, are disabling but rarely fatal [5].

In the United States during 1991, 9465 cases of Lyme disease were formally reported, making it

by far the most common arthropod-borne disease [6]. The rising incidence and geographic spread

of this zoonosis have interested the general public [7]. Lyme disease probably ranks only behind

acquired immunodeficiency syndrome in media coverage of infectious diseases in the United

States over the last decade. News, public health programs, and patient advocacy groups have

informed the public of the symptoms of Lyme disease and of ways to avoid infection [8]. A less

salubrious consequence of the attention has been the attribution to B. burgdorferi of a number of

ills, only a fraction of which are likely to be Lyme disease [9,10]. Wisconsin had 545 reported

cases of Lyme disease in 1989; in the same year, 94,000 serum samples were received by

reference laboratories in the state for Lyme disease testing [11]. Georgia reported hundreds of

cases of Lyme disease until it was documented that there were few ticks bearing B. burgdorferi

in the state [12].

A provisional diagnosis of Lyme disease is often acceptable to patients with vexing, undefined

illnesses, not only because there is hope for a cure with antibiotics but also because Lyme

disease is acquired through what are generally perceived to be wholesome activities, such as

hiking and working out-of-doors [7]. The full extent to which people are being inappropriately

treated with antibiotics cannot be estimated at present, but it is likely that a large minority, if not

a majority, of the health care dollars expended on therapy for Lyme disease are for inaccurate

diagnoses of B. burgdorferi infection [9,10]. Some of these resources would better benefit the

community if directed toward methods of disease prevention, such as vector control. A zoonosis

can be characterized with respect to the microbiology of the agent, the ecology in relation to

vectors and reservoir hosts, and the epidemiology of human disease. Full description of the

phenomenon of Lyme disease will also require consideration of behavioral and economic factors

in the response to the disease's emergence. These social factors are still poorly understood.

The Origins of Lyme Disease in North America

The clinical syndrome of B. burgdorferi infection had been described in Europe [13] more than

six decades before Steere and colleagues in 1975 investigated an unusual cluster of childhood

arthritis in the coastal community of Lyme, Connecticut [14]. Soon after the Connecticut

investigation, the relation between the arthritis and a prior episode of the characteristic skin rash,

erythema migrans Figure 1, common in Europe, was noted [15]. The search for an etiologic

agent implicated a tick, Ixodes scapularis (I. dammini), as the vector on epidemiological grounds

[16]. The bite of a related species, I. ricinus, was known to cause erythema migrans in Europe

[17]. Identity between the two tick-borne conditions was established when B. burgdorferi was

first isolated from I. scapularis and I. ricinus and then from patients in the United States and

Europe with Lyme disease and erythema migrans [18].

The events leading to an epidemic of arthritis in residents of Lyme began several centuries

earlier. Infections from B. burgdorferi probably occurred in North America before the first

waves of European colonization. Erythema migrans, the hallmark of B. burgdorferi infection,

was already present in midwestern and Pacific states at the time Lyme disease was first described

in Connecticut [19]. Early descriptions of colonial forests, the abundance of deer, and ticks

annoying explorers suggest that the conditions for B. burgdorferi transmission were present in

the Northeast hundreds of years ago [20,21]. The generally benign nature of acute B. burgdorferi

infection relative to the debilitating and fatal effects of diseases plaguing North Americans

through the 19th century may have contributed to its obscurity until a cluster of cases of

childhood arthritis first brought it to wider attention on this continent.

The ecological changes in the northeastern and midwestern United States during this century are

responsible for the recent emergence of Lyme disease as a public health problem [1,22]. The

establishment of an endemic focus of B. burgdorferi in these areas is primarily dependent on

ecological conditions favorable for deer. The white-tailed deer is a keystone host for I. scapularis

populations, and the maintenance of B. burgdorferi is in turn dependent on the presence of I.

scapularis [23,24]. Deforestation of much of the Northeast during the 18th and 19th centuries

resulted in the near total elimination of deer, and presumably also of deer ticks [20,21].

However, deer were never totally eliminated from a few isolated areas, such as Long Island, New

York [20]. Both entomological collection records and polymerase chain reaction analysis of

museum specimens document the presence of B. burgdorferi and I. scapularis on Long Island 50

years ago [25].

The abandonment of farms in New England and in suburban metropolitan areas elsewhere in the

Northeast resulted in a change in the landscape through natural succession from open fields to

eastern deciduous forests. As the forests returned, so did the deer. The invasion by I. scapularis

of the increasingly reforested mainland from island refuges initiated the current epidemic of

Lyme disease in the Northeast; the closest mainland community from Long Island's

northernmost tip is Lyme. There is evidence that several independent mainland invasions by I.

scapularis took place, resulting in early Lyme disease foci in central New Jersey, mainland

Westchester County, New York, southeastern Connecticut, and eastern Massachusetts [26,27].

The population of I. scapularis in north-central states appears to be expanding its range

independently from an indigenous relict population [28].

The threat of Lyme disease in wooded, suburban residential communities such as Westchester

County [29,30] has resulted in a new sense of conflict between humans and nature. Because the

extremely small nymphs of I. scapularis commonly transmit B. burgdorferi to people, relatively

few cases of Lyme disease are associated with recognized tick bites [4]. The resulting fear of

nymphal I. scapularis in residential yards, school grounds, and nature preserves has had a

negative impact on public attitudes about deer and nature in some of the most desirable

residential areas of the Northeast [31].

Maintenance of Borrelia burgdorferi in Nature

Lyme disease occurs in environments where the distributions of competent vectors, B.

burgdorferi, and wildlife reservoir hosts overlap. Among Borrelia species, B. burgdorferi is

remarkable in the variety of tick and vertebrate hosts it can infect; the several species that cause

relapsing fever have much more limited ranges of hosts and vectors [32]. Competent vectors

involved in the transmission of B. burgdorferi to humans are members of the I. persulcatus group

of ticks, including I. scapularis and I. pacificus in eastern and western North America,

respectively, and I. ricinus and I. persulcatus of Europe and Eurasia, respectively [33,34]. Some

species outside this group have also been shown as competent enzootic vectors [35].

The northern form of I. scapularis, which is responsible for more than 80% of the Lyme disease

cases in North America, was described as a separate species, I. dammini, in 1979 [36]. Although

the northern and southern forms have distinguishable morphological and ecological

characteristics, the species status of I. dammini has recently been rejected because of mating

compatibility and genetic similarity between the two forms [37]. The immature stages, larvae

and nymphs, of the northern form feed on all terrestrial mammal species and on as many as half

of the bird species that occur in the eastern deciduous-forest ecosystem [38,39]. Many

mammalian and avian species are reservoir-competent and capable of infecting larvae with B.

burgdorferi during their 4-day feeding event. The white-footed mouse, Peromyscus leucopus, is

of primary importance as a reservoir species throughout the northern range of I. scapularis, but

other small and medium-sized mammals, as well as birds, can also be important locally

[27,38,40,41]. Engorged larvae molt and overwinter as nymphs, which seek hosts again the

following summer. Infected nymphs transmit spirochetes to reservoir-competent hosts just before

the maximum host-seeking activity of the next generation's larvae. The exploitation of reservoir

hosts for the transmittal of spirochetes between tick generations in the near absence of inherited

(transovarial) transmission results in infection rates that average 25% in unfed nymphs [1,41,42].

Spirochete prevalence in adult ticks averages 50%, in part because an adult has two chances of

acquiring an infectious blood meal, having fed as both a larva and a nymph. The prevalence of B.

burgdorferi infection in vector-competent ticks varies geographically and is a good predictor of

Lyme disease incidence.

The endemic cycle of B. burgdorferi, and the consequent epidemiology of Lyme disease, varies

among geographic locations. In the southern United States, immature I. scapularis feeds

primarily on lizards, which are reservoir-incompetent [43]. Consequently, nymphal and adult

infection rates are less than 1%, about the expected rate for transovarial passage [44]. Spirochete

infection rates are also 1 to 5% in I. pacificus. Although transovarial passage contributes to this

infection rate, it is not sufficient to explain the maintenance of endemic foci in the western

United States [45]. A transmission cycle involving I. neotomae and the dusky-footed woodrat

Neotoma fuscipes was found responsible for the maintenance of endemic foci in California.

Because I. neotomae is host-specific and not anthropophilic, the few larval and nymphal I.

pacificus that feed on reservoir-competent mammals rather than lizards are responsible for

transmitting B. burgdorferi to humans [33,46].

In Europe I. ricinus and in the former Soviet Union I. persulcatus have feeding ecologies similar

to that of northern I. scapularis: immatures feed primarily on mammals and birds [47].

Consequently, spirochete infection rates in these tick species can be as high as that found in I.

scapularis of the northeastern United States [48]. Reservoir-competent hosts reported for I.

ricinus include the mice Apodemus flavicollis and A. sylvaticus as well as a vole, Clethrionomys

glareolus [49]. The epizootiology of Lyme disease is more complex in Europe and Asia than in

the United States because of the greater diversity of landscapes and ecology. Enzootic cycles

involving the hedgehog tick, I. hexagonus, in Switzerland and the avian tick, I. uriae, in Sweden

have been described [50]. Recovery of organisms like B. burgdorferi from I. ovatus in Japan and

Haemaphysalis longicornis in China [51], both of which primarily parasitize man and domestic

animals, indicates even greater diversity of endemic cycles and vectors in Asia. A tick-associated

disease similar to Lyme disease has been described in Australia [52], but the agent has not yet

been successfully isolated from ticks, wildlife, or patients. There have been reports of B.

burgdorferi in other tick species in North America, including Dermacentor variabilis, I. cookei,

and Amblyomma americanum [53]. Although borrelias can be acquired by these species during

feeding, these ticks have not been shown to be competent for transmission of the borrelias to

other hosts [54]. The presence of spirochetes similar to B. burgdorferi in A. americanum in areas

where competent vectors are absent is inexplicable.

Biology of Borrelia burgdorferi

Like other spirochetes, B. burgdorferi has a wavy shape and flagella that lie between the outer

and inner membranes of the cell [32]. All Borrelia sp. are host-associated bacteria and usually

shuttle between a vertebrate and a hematophagous arthropod. They do not live in water, soil, or

plants and are not transmitted by aerosols or fecal contamination. Although spirochetes are

predominantly extracellular pathogens, they invade endothelial layers to pass into tissues,

including the brain [55]. Species of Borrelia differ from other spirochetes in that they have a

chromosome and several extrachromosomal elements that are linear rather than circular [56,57].

Most U.S. isolates, as well as some strains from western Europe, are still included under the

original species designation B. burgdorferi [58]. Other strains, such as those from northern and

eastern Europe, Russia, and Asia, represent two other genomic groups, on the basis of DNA

relatedness and ribosomal RNA sequences [58]. A further justification for the division of extant

B. burgdorferi strains into two or more species would be consistent differences between strains

in their associated diseases. The most compelling evidence for this difference appears in the

infrequency of joint swelling and inflammation as sequelae of acute infection in northern and

eastern Europe as compared to the United States [59]. This difference does not seem to result

from acquisition bias. The absence of ``arthritogenic'' strains may help to explain the rarity of

chronic arthritis after erythema migrans in regions of Europe and Russia. Aside from its

taxonomic value, this difference in disease expression may provide insight into the pathogenesis

of other chronic arthritides, such as rheumatoid arthritis, for which an etiologic agent is not

known [60].

Two major contributors to antigenic distinctness of B. burgdorferi in North America are the

surface-exposed lipoproteins OspA, the focus of vaccine efforts, and OspB [61]. They or other

lipoproteins are anchored in an outer membrane that is more fluid than that of Gram-negative

bacteria [62]. In the least variable of the two proteins, OspA [63], there are three major groups

that differ from each other in their primary sequences by 21 to 23% [64]. Both OspA and OspB

are cotranscribed from an operon located on linear plasmids of about 50 kilobases [56]. The ends

of the linear plasmids are hairpins that most closely resemble in structure and sequence the

telomeres of poxviruses and the iridovirus that causes African swine fever [65]. The African

swine fever virus and a related Borrelia species, B. duttoni, live in the same tick vector,

Ornithodorus moubata, in Africa. The unusual genomic structure and organization of Borrelia

sp. may be the result of a trans-kingdom genetic exchange in the past [65].

Dilemmas in Diagnosis and Case Management

In an area where there is a high incidence of Lyme disease, such as Westchester County, the

presentation in July of a patient with low-grade fever, muscle aches, and erythema migrans

Figure 1 poses few diagnostic or therapeutic problems [66,67]. On clinical and epidemiologic

grounds, this condition would likely be early B. burgdorferi infection, and in most instances

prompt treatment with oral antibiotics such as amoxicillin or doxycycline would be curative

[65,68]. However, if a skin lesion is absent, a situation that may occur in 10% or more of

infections [4,5], nothing in the clinical presentation can clearly distinguish early Lyme disease

from other acute, febrile summer illnesses of temperate latitudes. Later manifestations of Lyme

disease, such as arthritis or carditis, can be attributed to other disorders. Neurologic symptoms,

especially those involving changes in cognitive functions, are especially difficult to interpret [69-

71]. Moreover, factors such as the premorbid personality and a tendency to somatization may

determine the length of convalescence and the response to postinfection fatigue and joint aches

[71,72]. Even if the original diagnosis of Lyme disease is undisputed, lingering or recurrent

symptoms, many of which are also characteristic of chronic fatigue syndrome or fibromyalgia,

may not be attributable to persistent infection [9,10,70,73].

In cases in which the hallmark skin rash is not observed, laboratory assays assume a more

important role in diagnosis [66,67]. A tentative diagnosis would be validated by isolation of the

agent from the patient, but this standard is seldom achieved in practice [7]. After a few weeks of

infection, B. burgdorferi is rarely if ever present in the blood; in other involved tissues, such as

joints or nerves, organisms are scarce [74]. The more commonly performed diagnostic procedure

is a serologic test, usually an enzyme-linked immunosorbent assay at a commercial laboratory,

for antibodies to B. burgdorferi at a single point in time. However, a positive serology result may

be incidental to the patient's disorder. In areas without Lyme disease, 1 to 2% of residents have

antibodies that sufficiently cross-react with B. burgdorferi antigens to give a false positive test

result [75]. In some endemic areas, 10% of healthy residents have serologic evidence of past

infection with B. burgdorferi [75]. Skepticism about serologic assays has also been raised by

surveys that show unacceptably high variation in results between different diagnostic

laboratories [76]. Test irreproducibility is attributable in part to lack of a standardized assay. In

the absence of leadership by the federal government in standardizing assays and assessing

proficiency, a cottage industry for Lyme disease testing has developed [7].

When opportunities or resources to confirm the presence of an infection by specific laboratory

tests are nonexistent or limited, antibiotics are often used empirically [77]. An inherent problem,

though, for this empirical approach is the lack of a clear endpoint for treatment. Late Lyme

disease is not likely to show a clear improvement within the time frame of the therapy, at least

not for the standardly recommended period. Not surprisingly, there is controversy about whether

the appropriate treatment duration for chronic Lyme disease is measured in weeks or months

[5,68,78]. When antibiotics are given parenterally for weeks, the direct and indirect costs of

administration of drugs are considerable for patients and thirdparty payers [79]. Studies of

antibiotics for Lyme disease therapy have often been funded by pharmaceutical companies; the

emphasis in these studies has been on antibiotics still under patent protection [80].

Decisions on diagnostic criteria, treatment strategies, research-funding allocation, and insurance

reimbursement are being made. Policy-makers are under pressure from some health professionals

and lay persons who believe that the spectrum of B. burgdorferi disease is broader than the limits

accepted by most peer-reviewed medical journals. The conditions in this larger set include

degenerative, inflammatory, and neuropsychiatric conditions not previously thought to be

ameliorated by antibiotics [81]. Alternative views of diagnostic criteria and treatment strategies

have been presented primarily at regional meetings sponsored by patient advocacy groups and in

newsletters devoted to Lyme disease. More recently, the influence of these points of view on the

last international scientific meeting on Lyme disease was such that several additional abstracts,

which had originally been rejected, were permitted presentation [82].

Surveillance for Lyme Disease

Misdiagnosis and inappropriate treatment could be lessened by improved surveillance of known

and emerging endemic foci. Clinical case distributions in the United States often do not coincide

with the known geographic distribution of endemic foci [83]. Travel to endemic foci accounts for

only a small fraction of the disparities. As with other vector-borne diseases, a history of exposure

to Lyme disease in an endemic area is an important consideration in diagnosis. Unfortunately,

the need for active surveillance of Lyme disease comes at a time when state and local

governmental budget cuts have reduced or eliminated many vector surveillance activities [84].

Current estimates of Lyme disease distribution are made principally from reports of human cases

Figure 2. However, inasmuch as humans are not involved in the natural maintenance cycle of B.

burgdorferi, the endemic status of this infection is not dependent on human involvement.

Spirochetes are far more frequent in wildlife and in ticks than in humans [67,85]. In terms of

surveillance, efforts to isolate the spirochete from ticks or reservoir hosts are more efficacious

than isolation attempts from patients [86]. Reservoir mice are particularly useful for surveillance

because B. burgdorferi can be cultured from their internal organs or ear punch biopsies, and they

are generally infected for life [87]. Polymerase chain reaction analysis will most likely replace

the use of cultures for this purpose [88].

Better knowledge of the geographic distribution and local abundance of vectors would improve

assessments of human risk. Although a national tick survey is only now under way in this

country [12], distribution maps for I. ricinus and I. persulcatus have been available for nearly 20

years in Europe and Russia [89]. Methods for quantitative assessment of vector abundance and

the application of remote sensing technology for the mapping of tick-borne disease distributions

are more advanced in central Europe and the former Soviet Union than in the United States

[28,90]. Decades of experience with and study of tick-borne viral encephalitis in Europe and

Asia have resulted in accurate knowledge of the geographic distributions of I. ricinus and I.

persulcatus.

The changing nature of the distribution and abundance of I. scapularis in the northern United

States complicates the surveillance of this vector. Invasions into areas previously free of I.

scapularis continue to occur [91], and establishment in new areas can be rapid and unpredictable

[92]; the ultimate limits of its distribution are uncertain. A steady increase in vector abundance at

a single location in Westchester County has been observed over a period of 5 years [27]. Such

changes in vector abundance can cause difficulties in the prediction of risk and in the assessment

of the efficacy of preventive measures, whether interventional or educational.

Prevention Through Immunization

Until recently there was no consensus that a human vaccine against Lyme disease was a realistic

prevention strategy, let alone profitable for a company to produce. A vaccine for a more

frequently fatal tick-borne disease, Rocky Mountain spotted fever, was taken off the market for

lack of use [93]. Moreover, human and animal studies indicate that the pathologic changes in

Lyme disease are determined in part by the host's immune response [94]. Until disease

pathogeneis and immunity are better understood, the risk of provoking disease through

vaccination cannot be accurately predicted. Because Lyme disease is rarely fatal, societal

tolerance of untoward reactions from the vaccine would probably be low.

Despite these discouraging considerations, demand for preventive measures against Lyme

disease has prompted efforts to develop a human vaccine for the disease [95]. One justification

for this effort is the accumulated evidence over the last decade that the morbidity from B.

burgdorferi infection in highly endemic areas is considerable; in some areas, 10% of the

population has been infected [96]. Some patients with Lyme disease involving the joints or

nervous system do not improve substantially even after parenteral antibiotic therapy [69-71,97].

Although doubts remain about many diagnoses of chronic Lyme disease, the specter of a large

number of persons with unrelieved disabilities prompts further consideration of a B. burgdorferi

vaccine for high-risk populations, such as outdoor workers and residents of endemic areas.

The feasibility of a human vaccine was demonstrated with experimental infections of animals.

Passive and active protection against homologous challenge was obtained in hamsters

immunized with killed B. burgdorferi cells [98]. These findings were the basis for the

commercially developed vaccine for dogs, which in an experimental infection study provided

evidence of protection [99]. However, because of concerns about the safety of whole-cell

vaccines, the initial focus for a human vaccine has been on recombinant DNA products. Most

work has been done on the OspA lipoprotein. The ability of recombinant OspA to induce an

immune response against B. burgdorferi was first demonstrated with rabbits and subsequently

with mice and hamsters [100,101]. Mice immunized with recombinant OspA were protected

against challenge from borrelias that were delivered by syringe and by tick [101,102]. The lipid

moiety of OspA is necessary for protection in mice when no adjuvants or adjuvants approved for

human use are used [103]. Phase I human trials of recombinant OspA lipoprotein have begun

[104].

Prevention Through Vector Control

Most vector-borne diseases are prevented through vector control and not by vaccines for humans.

However, relatively few methods to control ticks that influence public health have been

developed, in contrast to measures of mosquito control, for instance. Consequently, reduction of

the risk of Lyme disease through reduction of tick exposure has been limited to insecticide use

and personal protection measures. In regions where tick infection rates are low or where

exposure is elective and occasional, personal protection measures may be adequate to minimize

risk. However, in regions where tick infection rates are high and exposure is unavoidable, as in

many suburban environments in the northeastern United States, the use of insecticides is the only

effective means available to lower the risk of Lyme disease.

Ticks are susceptible to several chemical insecticides that are suitable for use in the environment

or on hosts. Application of an insecticide directly to a tick-infested area is the most common

method of control. However, because of the tick's life cycle of two or more years and the

redistribution of ticks between each host-feeding event, several applications of an insecticide

over a large area are necessary to suppress significantly tick populations of the I. persulcatus

complex [105]. Large area applications of DDT were successfully used to reduce morbidity from

tick-borne encephalitis in Siberia [106], but only insecticides with the persistence of DDT

provide long-term control. Although single insecticide applications reduced the abundance of

nymphal I. scapularis on high-risk residential properties in Westchester County and Lyme,

acceptance by the public and health agencies of such well-targeted insecticide use has been slow

because of environmental concerns [107]. Nevertheless, because of the prevalence of Lyme

disease in suburban areas of the Northeast, the benefit of reduced tick abundance through annual

insecticide application to lawns may outweigh potential environmental costs.

A novel approach to reduce the risk of Lyme disease through insecticides includes a self-delivery

system for mice [108]. Cotton, treated with permethrin insecticide and provided in paper tubes, is

used for nesting material by the white-footed mouse. The application system is designed to

render mice tick-free during the entire enzootic transmission season and, thus, prevent immature

I. scapularis from either transmitting or acquiring B. burgdorferi. Although this technique was

effective in one study in Massachusetts, it did not reduce risk measurably in three field tests in

Connecticut and New York [109]. The diversity of reservoir-competent host species that help to

maintain endemic foci of Lyme disease may limit the usefulness of any method that targets a

single reservoir species. An imaginative strategy, not yet evaluated in the field, to reduce the

prevalence of infected ticks and wildlife through vaccination of reservoir hosts against B.

burgdorferi may suffer from the same limitation [102]. A host-targeted insecticide applied to

deer may be more effective in reducing the incidence of Lyme disease [108]. Because of the

narrow host range of adult I. scapularis, topical applications of an insecticide to deer would limit

tick reproduction and eventually reduce the total tick population in the affected area. However,

identification of appropriate insecticides, provision of effective delivery systems, and better

knowledge of deer behavior in suburban environments are problems to be solved before a deer-

targeted strategy can be put into practice.

The potential for biological means of tick control through natural enemies is relatively

unexplored. Few natural predators or pathogens are known for ticks [110]. The obligatory blood-

feeding nature of ticks suggests that there may be limited opportunities for the acquisition of

pathogens or parasites directly from the environment. An insect parasite of I. scapularis has been

found in the Elizabeth Islands, Massachusetts [109], but its impact on risk has not been

determined. Laboratory colonies of the parasite appear to be easily established, and sustained

releases from colonized stock may ultimately help to reduce risk in isolated situations.

The total nutritional dependency of ticks on vertebrate hosts affords an opportunity to reduce the

abundance of Lyme disease vectors through limits in the availability of hosts. Such restriction

can be accomplished either directly by affecting host abundance or indirectly by making hosts

unavailable for tick feeding through topical application of repellents or insecticides or by

vaccination against ticks [108,111]. Again, deer would be the most suitable target. An attempt to

reduce the population of I. scapularis on a Massachusetts island by the removal of deer was only

successful when nearly all the deer were eliminated [24]. Thus, traditional deer management

practices alone are not likely to decrease significantly the risk of Lyme disease. Any alternative

to the elimination of deer would probably also have to approach 100% effectiveness. A

combination of host reduction, habitat modification, and area insecticide application was

successfully used in a control program for a pest tick, A. americanum [112], but the general

suitability of such integrated control techniques for Lyme disease prevention remains to be

determined.

Personal protection measures are the most frequent recommendation provided by public health

agencies to reduce the risk of Lyme disease [3]. These measures include the wearing of light-

colored clothing, taping the tops of socks over trouser cuffs, and the use of insect repellents on

clothing and exposed skin. Such recommendations are easy to make because they place

responsibility for prevention on the individual. However, personal protection measures may

actually have limited effectiveness in suburban areas with high tick density. Clearly, public

health agencies will have to take a more active role in prevention than providing simple cautions

if their efforts are to reduce the incidence of B. burgdorferi infection.

Conclusion

Ironically, the emergence of Lyme disease as a health problem is attributable in part to the

``greening'' of the United States: forests are regaining those lands formerly devoted to

agriculture. Citizens value ever more highly the propinquity of wildlife to their residences. Deer,

once close to elimination in many parts of the United States, are now as commonly noted as

squirrels in some suburban communities. A cost of this otherwise welcomed development is

Lyme disease. Living close to nature may have more public health consequences in the future as

other known zoonotic diseases expand their ranges, and as perhaps others are discovered [113].

The history of Lyme disease also shows that a newly recognized disease may be defined as much

by individuals and groups outside of academic and governmental institutions as by those within

them. Consequently, a mix of opinion has formed about what Lyme disease is and how it should

be managed.

REFERENCES AND NOTES

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114. Supported by National Institutes of Health grants A129731, A124424 (A.G.B.), and A128956 (D.F.); Centers

for Disease Control Contract U50/CCU20662601 (D.F.); USDA grant 58-1265-2119 (D.F.); and grants from the

Lyme Borreliosis Foundation (A.G.B.), American Lyme Disease Foundation, and G. Harold and Leila Y. Mathers

Charitable Foundation (D.F.).

Figure 1. Erythema migrans of the skin of patients at the Lyme Disease diagnostic Center,

Westchester County Medical Center, New York [Photograph courtesy of G.P. Wormser]

Figure 2. Human cases of lyme disease in the United States in 1990 by county. Counties with

two or more cases of Lyme disease by criteria of the Centers for Disease Control [83], Fort

Collins, Colorado.