Globalization has made the world a more connected place. Bacterial and viral diseases transmitted by mosquitoes, ticks, and fleas continue to be an ever-present threat worldwide (Table 19-1). Some of these diseases have been present in the United States for a long time but others have emerged recently. These include some of the world’s most destructive diseases, many of which are increasing threats to human health as the environment changes and globalization increases.

Table 19-1

Examples of Vector-Borne Diseases

Vector	Disease	Pathogen	Distribution
Mosquitoes
Aedes triseriatus	California encephalitis	Virus	United States: Upper Midwest, Appalachian region
Aedes aegypti	Dengue fever West Nile encephalitis West Nile fever	Virus Virus	Worldwide: tropical regions United States; spreading nationwide Africa, Asia
Culiseta melanura	Eastern equine encephalitis	Virus	Eastern United States Central and South America, Caribbean
Culex spp.	St. Louis encephalitis Western equine encephalitis	Virus Virus	Eastern United States Central and South America Western United States Central and South America
Ticks
Deer tick, Ixodes spp.	Anaplasmosis (formerly human granulocytic ehrlichiosis)	Bacteria	Worldwide; Europe United States—Northeast, Upper Midwest, northern California
I. scapularis	Babesiosis	Protozoan parasite	United States—primarily northeastern states, rarely Pacific states
Lone star tick, Amblyomma americanum	Human monocytic ehrlichiosis	Bacteria	United States—Southeast, south central states
Dog tick, Rhipicephalus sanguineus	Mediterranean spotted fever	Bacteria	Europe, Africa, Central Asia
Tickborne, airborne vector	Q fever	Rickettsiae	Worldwide
Dog tick, wood tick, Dermacentor spp.	Rocky Mountain spotted fever Tick-associated rash, illness	Bacteria Bacteria	North and South America Southern
Ticks, various	Tickborne relapsing fever	Bacteria	Western United States (endemic^∗); Southern British Columbia; plateau regions of Mexico; Central and South America; Mediterranean, Central Asia, and much of Africa
Lice, Fleas, Mites
Human body louse; squirrel flea and louse	Epidemic typhus	Rickettsiae	United States, eastern
Rat flea, Xenopsylla cheopis	Murine typhus	Bacteria	Worldwide, where rats are abundant
Cat or dog fleas	Murine typhus–like febrile disease	Rickettsiae	Worldwide
Mites (chiggers)	Scrub typhus	Rickettsiae	South Asia to Australia, East Asia in recently disturbed habitat (e.g., forest clearings or other persisting mite foci infested with rats and other rodents)
Human body louse	Louse-borne relapsing fever Trench fever	Bacteria Rickettsiae	Africa Industrialized countries

^∗Most recent cases and outbreaks have occurred in rustic cabins at higher elevations (≥8000 ft) in coniferous forests in the western United States.

The discovery and surveillance of many of these vector-borne diseases (e.g., Lyme disease) can be accomplished by serologic testing. Travelers and military personnel may be at risk for exposure to vector-borne disease if they engage in activities that bring them into contact with habitats that support the vectors or the animal reservoir species associated with these diseases.

Some of the newly emerging infectious diseases in the United States include the following:

A few prominent examples of the more commonly occurring vector-borne diseases detectable by serologic methods are presented in this chapter.

Lyme disease (Lyme borreliosis) is caused by a spirochete bacterium. It is a cutaneous systemic infection generally transmitted by a hard-bodied tick (Fig. 19-1) and caused by Borrelia burgdorferi (Fig. 19-2). The causative agent of Lyme borreliosis currently consists of three pathogenic species—B. burgdorferi, Borrelia afzelii, and Borrelia garinii. Only B. burgdorferi strains have been found in the United States. In contrast, most of the illness in Europe is caused by B. afzelii, which is associated with the chronic skin condition acrodermatitis chronica atrophicans (ACA), and B. garinii, which is associated with neurologic symptoms. Only these two species have been found in Asia. The complete genome of B. burgdorferi (strain B31) has now been sequenced.

Figure 19-1 Deer tick. (From Habif TP: Clinical dermatology, ed 2, St Louis, 1990, Mosby.)

Figure 19-2 *Borrelia* organisms present in the blood of a patient with endemic relapsing fever (Giemsa stain, 1000x magnification). (From Murray PR et al: Medical microbiology, ed 5, Philadelphia, 2005, Mosby.)

The spirochete is transmitted by certain ixodid ticks that are part of the Ixodes ricinus complex. These include Ixodes scapularis (formerly classified as Ixodes dammini) in the northeastern and Midwestern United States, Ixodes pacificus in the western United States, Ixodes ricinus in Europe, and Ixodes persulcatus in Asia. The vector has not been identified in Australia. Ixodid ticks are also indigenous to Africa and South America. The lone star tick, Amblyomma americanum, does not transmit Lyme disease.

In the United States, the preferred host for larval and nymphal stages of I. scapularis is the white-footed mouse, Peromyscus leucopus. White-tailed deer, which are not involved in the life cycle of the spirochete, are the preferred host for the I. scapularis adult stage and they seem to be critical to tick survival. Ixodid ticks have also been found on at least 30 types of wild animals and 49 species of birds. Illness is not known to develop in wild animals, but clinical Lyme disease does occur in domestic animals, including dogs, horses, and cattle.

Spirochetes are transmitted from the gut of the tick to human skin at the site of a bite and then migrate outwardly into the skin. This migration causes the unique expanding skin lesion, erythema migrans (EM). Subsequent dissemination of spirochetes to secondary sites may cause major organ system involvement in humans. In dogs, the most common symptom is arthritis.

Epidemiology

Currently, Lyme disease is a global illness. Cases have been reported on all continents except Antarctica. Since its original description more than 25 years ago, Lyme disease has become the most commonly reported (95%) vector-borne illness in the United States. This infection has emerged as a major health hazard for human beings and domestic animals. In 2011, it was the sixth most common nationally notifiable disease. It is endemic in more than 15 states in the United States and in Europe and Asia.

In some patients, Lyme disease may be transitory and of little consequence, but in others it may become chronic and severely disabling. Accurate diagnosis is therefore essential, although better laboratory techniques are still needed.

Retrospectively, the first symptom of Lyme disease apparently was recognized as early as 1908 in Sweden. In the decades that followed, the rash produced by the disease erythema chronicum migrans (ECM) was noted elsewhere in Europe, as were other symptoms that seemed to follow ECM’s eruption. Secondary symptoms, such as impairment of the nervous system, were described in France, Germany, and again in Sweden.

In the United States the European rash was almost unknown until 1969, when a case of a physician bitten by a tick while hunting in Wisconsin was reported. Although a few ECM cases were seen in Americans who had traveled to Europe, there were no further native American cases until 1975, when physicians at the U.S. Navy base in Groton, Connecticut, reported seeing four patients with a rash similar to that of ECM. At the same time, an epidemiologist at the Connecticut State Department of Health and a rheumatologist at Yale University were notified of an unusual cluster of cases of arthritis occurring in children in Lyme, Connecticut.

It was not until 1982 that Burgdorfer and Barbour isolated a previously unrecognized spirochete, now called B. burgdorferi, from I. scapularis ticks, and Lyme disease became a recognized vector-borne, infectious disease. Two factors influence the chance that a bitten patient will contract the disease, the likelihood that local ixodid ticks carry the Lyme spirochete and the likelihood of infection after a bite by an infected tick. The probability of infection after an ixodid tick bite in an area of endemic disease is about 3%, but varies in different regions from less than 1% to as high as 5%. It has been suggested that human leukocyte antigen (HLA)–DR4 (HLA-DR4) and, secondarily, HLA-DR2, may increase the risk that Lyme arthritis will become chronic and fail to respond to antibiotics.

Lyme disease does not occur nationwide and is concentrated heavily in the northeast and upper midwest. The highest number of confirmed cases of Lyme disease to date was 29,959 in 2009 (Fig. 19-3). Persons of all ages and both genders are equally susceptible. In 2011, 96% of Lyme disease cases were reported from 13 states (Fig. 19-4):

Figure 19-3 Reported cases of Lyme disease—United States, 1996-2010. (Courtesy Centers for Disease Control and Prevention, Atlanta.)

Figure 19-4 Reported cases of Lyme disease—United States, 2011. (Courtesy Centers for Disease Control and Prevention, Atlanta.)

Lyme disease is considered an emerging infectious disease because of the impact of changing environmental and socioeconomic factors, such as the transformation of farmland into suburban woodlots favorable for deer and deer ticks. Although pets may represent a spirochete reservoir, it is unlikely that humans can be infected directly by them. In areas of endemic Lyme disease, however, both adult and nymphal ticks, carried into the household by dogs and cats, may infect humans.

Signs and Symptoms

The basic features of Lyme disease are similar worldwide, but there are regional variations, primarily between the illness in America and that in Europe and Asia. In at least 60% to 80% of U.S. patients, Lyme disease begins with a slowly expanding skin lesion, EM, which occurs at the site of the tick bite. The skin lesion is frequently accompanied by flulike symptoms.

The Centers for Disease Control and Prevention (CDC) clinical case definition for Lyme disease includes the presence of EM or at least one objective, late manifesting sign of musculoskeletal, neurologic, or cardiovascular disease and a positive serologic test for antibodies to B. burgdorferi. Many misdiagnosed patients actually have chronic fatigue syndrome or fibromyalgia, both of which can cause similar symptoms, such as joint stiffness or pain, fatigue, and sleep disturbance.

Lyme borreliosis is a multisystem illness that primarily involves the skin, nervous system, heart, and joints (Table 19-2). Lyme disease usually begins during the summer months with EM and flulike symptoms and may be accompanied by right upper quadrant tenderness and a mild hepatitis (stage 1). This stage is followed weeks to months later by acute cardiac or neurologic disease in a minority of untreated individuals (stage 2) and then by arthritis and chronic neurologic disease (stage 3) in many untreated patients weeks to years after disease onset. There is considerable overlap of these stages, but Lyme disease is best characterized as an illness that evolves from early to late disease without reference to an arbitrary staging system. However, a patient may have one or all of the stages, and the infection may not become symptomatic until stage 2 or 3. Most affected patients have EM and 25% manifest arthritis; neurologic manifestations and cardiac involvement are uncommon.

Table 19-2

Clinical Features of Lyme Disease

Stage	Duration	Signs and Symptoms
I	4 wk (median) after injection	Cutaneous manifestations (erythema migrans) or other skin eruptions, flulike syndrome, neurologic symptoms
II	Follows a variable latent period	Target organs and systems include nervous system, heart, eyes, and skin, all of which can manifest abnormalities
III	Weeks to years after infection	Arthritis, late neurologic complications, acrodermatitis chronica atrophicans

Arthritis

Arthralgia and myalgia are common features of early Lyme disease, but frank arthritis during EM is unusual. Arthritis is a well-described complication of Lyme disease and characteristically occurs months to years after Borrelia infection. Therefore, cases of Lyme arthritis occur during every month of the year. Lyme arthritis and parvovirus B19 arthritis can occur in the absence of other symptoms, such as the characteristic rash. Some suspected cases of Lyme arthritis might be caused by parvovirus B19, particularly those occurring during the parvovirus B19 season.

Arthritis in patients with chronic Lyme disease may be associated with a long-standing infiltration of the joints by B. burgdorferi spirochetes, along with a local inflammatory response. It may not be triggered simply by the presence of circulating immunoglobulin G (IgG) antibodies against outer surface proteins.

Cutaneous Manifestations

Cutaneous manifestations can be demonstrated as early ECM (Fig. 19-5), secondary lesions (disseminated lesions and lymphocytoma), and late lesions (ACA). Except for the late lesions, cutaneous manifestations generally resolve spontaneously over weeks to months. The red papule at the site of the tick bite is most often located on the thigh, groin, or axilla. Facial EM is seen more frequently in children.