On target with Lyme disease: Understanding vector-borne infections

• Lyme disease was first recognized in the United States in the early 1970s as the cause of pediatric arthritis outbreaks in Lyme, 
Connecticut. 


• Lyme disease is a multisystem infection caused by the spirochete Borrelia burgdorferi, which exists in reservoir hosts, such as mice, squirrels, shrews, and other small vertebrates. The spirochete is transmitted to humans primarily by the black-legged deer tick, Ixodes scapularis. Infection will result only if the tick feeds on an infected animal host before feeding on a human host.


• The decision to administer prophylactic treatment after a tick bite depends on the species of tick, endemic population, the duration of tick attachment, and efficacy of tick removal. Risk for transmission of the pathogen is greater if the tick is engorged or was improperly removed.


• Oral doxycycline is the preferred treatment for all patients except women who are pregnant or nursing and children younger than 12 years. Alternative medications include amoxicillin, azithromycin, cefuroxime, clarithromycin, and erythromycin.


Incidence of Lyme disease, a vector-borne infectious disease, is reported to the CDC from every state in the United States; however, prevalence concentrates along the East Coast, in the central states, and in parts of California. This spirochete-mediated disease manifests with variable constitutional symptoms such as fever, myalgias, rash, neurologic symptoms, and joint pain that mimic many other disease processes. Although Lyme disease is treatable, late manifestation and inaccurate serologic confirmation can lead to long-term health concerns. Physician assistants, especially those practicing in endemic areas, should maintain a high index of suspicion in order to be able to recognize the risk factors and varied clinical presentations, provide initial management and referral, and counsel patients on disease prevention. 


EPIDEMIOLOGY


Lyme disease was first recognized in the United States in the early 1970s as the cause of pediatric arthritis outbreaks in Lyme, Connecticut. It is the most common vector-borne illness in North America. Voluntary surveillance statistics from the CDC show an estimated increase of 101% in the annual incidence of Lyme disease from 1992 to 2006.¹ This rise in incidence can be explained by the increased recognition of Lyme disease, the expansion of deer and tick populations, and the increased contact between ticks and humans as people encroach on forested habitats.² This marked surge in incidence is only an approximation, and statistics are probably sorely underestimated because of underreporting and early empiric treatment. 


The voluntary surveillance statistics from 1992 to 2006 also revealed that 93% of the 248,074 cases were from Connecticut, Delaware, Massachusetts, Maryland, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin.^1,2 In 1998, 76% of reported US cases of Lyme disease occurred in whites, and a bimodal age distribution affecting persons aged 5 to 9 years and 50 to 59 years was seen, while the lowest incidence was in persons aged 20 to 24 years.^1,2


ETIOLOGY AND PATHOPHYSIOLOGY


Lyme disease is a multisystem infection caused by the spirochete Borrelia burgdorferi, which exists in reservoir hosts, such as mice, squirrels, shrews, and other small vertebrates.¹ The spirochete is transmitted to humans primarily by the black-legged deer tick, Ixodes scapularis. The Ixodes tick becomes infected when it feeds on the blood of natural reservoir hosts. The tick has a 2-year life span and feeds once during each of three developmental stages—larva, nymph, and adult. The larval stage begins in summer, and the tick matures into a nymph the following spring. During these two stages, the tick is no bigger than a pinhead, and its preferred host is the common or white-footed field mouse. In the fall, the nymph becomes an adult; as such, it prefers the white-tailed deer as a host. Deer are not infected with B burgdorferi, but they play a role in transporting and maintaining tick populations.¹ Humans exposed to wooded habitats can become alternative hosts for nymphs and mature adult ticks. Nymphs are more likely to feed on human hosts and are responsible for spirochete transmission in 85% of cases during the spring and summer.² Infection will result only if the tick feeds on an infected animal host before feeding on a human host. 


After being acquired by the tick during feeding, the spirochete resides in the midgut of the tick. The bacteria multiply and migrate to the tick's salivary glands during the first 24 hours of the next feeding cycle. The tick injects the B burgdorferi spirochetes into the host at the end of feeding; therefore, a tick must be attached to a person for 2 to 3 days in order to transmit the infection. Some hosts may clear the infection without developing any manifestations, as demonstrated by patients who are asymptomatic but seropositive.² In others, the spirochete spreads throughout the body and induces an immune response in various organs. The incubation period is approximately 3 to 32 days; onset of symptoms occurs a few days to 1 month after the tick bite. Only 30% to 50% of patients recall being bitten by a tick.


STAGES AND CLINICAL MANIFESTATIONS


Lyme disease occurs in three stages, which reflect the in vivo maneuvering of the spirochete: stage 1, early disease; stage 2, disseminated disease; and stage 3, persistent disease. Stage 1 disease, or early Lyme disease, occurs up to approximately 1 month after the tick bite. B burgdorferi remains localized to the inoculation site, causing erythema migrans, the classic erythematous, expanding target-shaped (bull's-eye) lesion that averages 16 cm in diameter and may be pruritic or mildly painful (Figure 1).^2-4 The rash manifests in 60% to 80% of patients at the site of inoculation, commonly the thigh, popliteal area, groin, or axilla. An ulcerated or vesicular center to the rash may indicate coinfection with another vector-borne pathogen³ and may be associated with flulike symptoms. If left untreated, the flulike symptoms will persist for 2 to 3 weeks. Up to 20% of patients have recurrent episodes of a single bull's-eye lesion, and 40% of patients develop multiple lesions.² One-third of all patients with an erythema migrans lesion develop no further manifestations of Lyme disease, whereas the infection progresses to disseminated disease in the rest. 


Stage 2 disease marks early dissemination of the spirochete to distant organs. Disseminated disease primarily affects the skin, heart, joints, and nervous system (Table 1). Onset of symptoms occurs days to weeks after the tick bite, and symptoms may be intermittent, fluctuate, and eventually resolve. Arthropathy manifests during early Lyme disease as polyarthralgia; polyarthritis; or tendinitis most frequently involving the knee, ankle, and wrist. 


The migratory polyarticular process evolves into a monoarticular process in a weight-bearing joint, most commonly the knee, in stage 2 or 3 Lyme disease.^2,4 Acute Lyme arthritis manifests as a warm, red, swollen joint with painful range of motion but is usually not as severe as septic arthritis. In two-thirds of affected patients, the arthritis begins within 6 months of the rash and will persist for 1 week if untreated.² Recurrences of Lyme arthritis are common and resolve over 10 years. Cranial nerve palsies are the most common neurologic finding of Lyme disease, particularly bilateral facial nerve palsy, and last for less than 2 months. Lyme carditis is accompanied by fever and possibly syncope caused by atrioventricular (AV) heart block.² If the AV block persists for more than 1 week, a temporary pacemaker is required.