Tick-Related Infections

Ticks are the vectors of at least 10 clinically significant zoonotic illnesses in the United States (Box 1). These illnesses may be caused by bacterial, viral, or parasitic pathogens, some of which may occur simultaneously during the bite of a single tick. Humans are often an accidental host to these increasingly recognized conditions by virtue of our intrusion into the natural habitat of the ticks and their reservoirs, the white-footed mouse and whitetail deer. Geographically distinct areas exist for most of the vectors, reservoirs, and diseases; however, recreational travel into these regions may result in illness for nonresidents. Continued encroachment into forested and uncultivated areas will likely lead to a further increase in the incidence of tick-related infections. Many of these infections may be contracted in urban or semirural areas as well. Therefore, they should not be viewed as occurring only in remote or rural regions.

The common arthropod vectors are listed in Table 1. Each has the potential to carry more than one pathogen. The illnesses they cause often have a nonspecific manifestation that requires astute physician recognition. A careful history and physical examination, with particular attention to travel and recreational activities, may be lifesaving. Early recognition, diagnosis, and treatment result in fewer complications and less morbidity and death. Seroconversion is often delayed; therefore, empirical therapy is frequently necessary. A dated but useful overview of these infections has been given by Spach and colleagues.¹

Table 1 Tick Vectors

Vector	U.S. Location
Ixodes scapularis	East, Northeast, Midwest
Ixodes pacificus	West, Northwest
Dermacentor variabilis (dog tick)	East, Midwest
Dermacentor andersoni (wood tick)	West
Amblyoma americanum (Lone Star Tick)	South, Central

LYME DISEASE

Lyme disease is currently the most common vector-borne disease in the United States. It was described in Lyme, Connecticut, in the 1970s and also exists in Europe with a different clinical presentation. Although rarely fatal and seldom a serious illness, Lyme disease has been widely publicized, frequently overdramatized, and sometimes linked to unproven conditions. Borrelia burgdorferi, a gram-negative spirochete, is the causative organism. Ixodes scapularis ticks in the eastern and midwestern regions of the United States and I. pacificus in the northern Pacific areas carry this bacterium. The white-footed mouse is the natural reservoir. Although Lyme disease has been reported in nearly every state, it is considered endemic to the northeast coastal, mid-Atlantic, upper Midwest, northern California, and Pacific northwest regions (Fig. 1), with seasonal peaks of infection occurring in May through August.

Figure 1 Lyme disease, reported cases by county, United States, 2000.

The total number of cases from these counties (marked in green) represented 90% of all cases reported in 2000.

(From the Centers for Disease Control and Prevention.)

Ixodes tick attachment for 48 to 72 hours is generally required for infection.² After an incubation period of 7 to 10 days (range, 3-30 days), the illness may evolve through three stages. Other than erythema migrans (EM), the characteristic rash of Lyme disease, symptoms of Lyme disease are nonspecific. Stage 1, or early localized disease, is characterized by EM in approximately 90% of cases. EM is a rapidly expanding erythematous macule varying in size from 5 to 70 cm. It is generally solid, especially in the early period, but may show central clearing or a target-like appearance (Fig. 2). EM may resolve without therapy; it is usually asymptomatic but may be associated with fever, malaise, arthralgia, myalgia, or headache. Occasionally, the lesion may be pruritic. A history of a tick bite or exposure and the development of EM are diagnostic for Lyme disease.

Figure 2 Erythema migrans (EM).

This is the characteristic rash of Lyme disease.

Stage 2, early disseminated disease, may occur if stage 1 was not treated. It may manifest as multiple EM lesions (generally smaller) 3 to 5 weeks after the bite. Cranial nerve palsies (especially cranial nerve VII, or Bell’s, palsy), meningitis, or carditis (variable atrioventricular block) may also occur.

Stage 3, late disease, may evolve if stage 2 was not treated. Monoarticular or oligoarticular arthritis is the most common manifestation of stage 3. The knee is the most commonly involved joint. It is likely an autoimmune arthritis, which does not respond well to antibiotic therapy. Encephalitis, encephalopathy, and polyneuropathy may be late-stage sequelae, but are uncommon.

Diagnosis is best accomplished by recognition of EM and the compatible history in stage 1 or 2. Culture of the organism, most often from an EM lesion, is the standard of diagnosis but is technically slow and difficult.³ Serology detects antibodies but does not establish the diagnosis by itself because other spirochetes (e.g., syphilis, relapsing fever, oral spirochetes) as well as varicella, cytomegalovirus, Epstein-Barr virus, and parvovirus may cause false-positive test results. In addition, rheumatoid arthritis and systemic lupus may cause erroneous serologic results. Serology is best performed as a two-step process using an enzyme-linked immunosorbent assay (ELISA; high sensitivity) as the first step, followed by a Western blot test for confirmation (high specificity). Immunoglobulin M (IgM) antibodies may be detected in only 20% to 30% of cases during the first 2 weeks; however, 70% to 80% of cases develop IgM antibodies by 1 month. IgG antibodies will be present by 6 to 8 weeks. Early antibiotic therapy may delay, blunt, or block the antibody response, making the clinical diagnosis even more important.

Therapy is well established and defined (Table 2). There appears to be no indication for prolonged therapy. Shorter courses may be as effective as the current recommendations. Stage 1 is treated with oral antibiotics for 14 to 21 days with doxycycline, amoxicillin, or cefuroxime. Stage 2 disease may be treated with the same regimens as for stage 1 unless meningitis or severe carditis occurs, in which case ceftriaxone, 100 mg/kg/day (maximum, 2 g/day) for 14 to 28 days, is recommended. Stage 3 arthritis may be treated with oral doxycycline or amoxicillin for 14 to 21 days. If it recurs, therapy with ceftriaxone would be used for 14 to 28 days. Late-stage neurologic disease is also treated with ceftriaxone.⁴

Table 2 Treatment of Lyme Disease

Human Lyme disease vaccine is no longer available in the United States (it is available in Europe), but animal vaccine is still used. Also, Lyme vaccine results in reactive ELISA (but negative Western blot) results.

ROCKY MOUNTAIN SPOTTED FEVER

Rocky Mountain spotted fever (RMSF) is caused by the obligate intracellular, pleomorphic, gram-negative rod Rickettsia rickettsii. Although it is considered the most common rickettsial disease in the United States, its declining incidence (Fig. 3) may yield this position to ehrlichiosis. RMSF occurs in the south Atlantic coastal, south central, and western regions, being most concentrated in North and South Carolina, Tennessee, and Oklahoma. The tick vectors are Dermacentor variabilis in the East and D. andersoni in the West.

Figure 3 Rocky Mountain spotted fever, reported cases/100,000 population in the United States by year, 1970 to 2000.

(From the Centers for Disease Control and Prevention.)

Infection can occur year-round but is most commonly encountered from April through September. Most cases occur in children with exposures to dogs and wooded areas. Tick attachment of 6 to 10 hours is required for transmission, followed by an incubation period of 5 to 7 days (range, 2-14 days) until infection is manifest. Only 60% to 70% of patients recall a tick bite.

The classic triad of fever, rash, and headache occurs in a minority of cases, particularly early in the course. The vasculitic rash, which often begins on the wrists and ankles and then spreads centrally (Fig. 4), is uncommon during the first 3 days of illness; however, 10% of patients may not develop a rash. When it occurs, it may first have a maculopapular appearance, which progresses to a petechial rash. Abdominal symptoms of nausea, vomiting, and diarrhea may be present in one third of cases.⁵ Myalgia, arthralgia, and confusion may also be parts of the clinical picture.