Lyme borreliosis is caused by a spirochete, Borrelia burgdorferisensu lato, that is transmitted by ticks of the Ixodes ricinus complex. The infection usually begins with a characteristic expanding skin lesion, erythema migrans (EM; stage 1, localized infection). After several days or weeks, the spirochete may spread to many different sites (stage 2, disseminated infection). Possible manifestations of disseminated infection include secondary annular skin lesions, meningitis, cranial neuritis, radiculoneuritis, peripheral neuritis, carditis, atrioventricular nodal block, or migratory musculoskeletal pain. Months or years later (usually after periods of latent infection), intermittent or persistent arthritis, chronic encephalopathy or polyneuropathy, or acrodermatitis may develop (stage 3, persistent infection). Most patients experience early symptoms of the illness during the summer, but the infection may not become symptomatic until it progresses to stage 2 or 3.
Lyme disease was recognized as a separate entity in 1976 because of geographic clustering of children in Lyme, Connecticut, who were thought to have juvenile rheumatoid arthritis. It became apparent that Lyme disease was a multisystemic illness that affected primarily the skin, nervous system, heart, and joints. Epidemiologic studies of patients with EM implicated certain Ixodes ticks as vectors of the disease. Early in the twentieth century, EM had been described in Europe and attributed to I. ricinus tick bites. In 1982, a previously unrecognized spirochete, now called Borrelia burgdorferi, was recovered from Ixodes scapularis ticks and then from patients with Lyme disease. The entity is now called Lyme disease or Lyme borreliosis.
B. burgdorferi, the causative agent of Lyme disease, is a fastidious microaerophilic bacterium. The spirochete's genome is quite small (~1.5 Mb) and consists of a highly unusual linear chromosome of 950 kb as well as 17–21 linear and circular plasmids. The most remarkable aspect of the B. burgdorferi genome is that there are sequences for more than 100 known or predicted lipoproteins—a larger number than in any other organism. The spirochete has few proteins with biosynthetic activity and depends on its host for most of its nutritional requirements. It has no sequences for recognizable toxins.
Currently, 13 closely related borrelial species are collectively referred to as Borrelia burgdorferisensu lato (i.e., B. burgdorferi in the general sense). The human infection Lyme borreliosis is caused primarily by three pathogenic genospecies: B. burgdorferi sensu stricto (B. burgdorferi in the strict sense, hereafter referred to as B. burgdorferi), Borrelia garinii, and Borrelia afzelii. B. burgdorferi is the sole cause of the infection in the United States; all three genospecies are found in Europe, and the latter two species occur in Asia.
Strains of B.burgdorferi have been subdivided according to several typing schemes, including one based on sequence variation of outer-surface protein C (OspC) and a second based on differences in the 16S–23S rRNA intergenic spacer region (RST or IGS). From these typing systems, it is apparent that strains of B. burgdorferi differ in pathogenicity. OspC type A (RST1) strains seem to be particularly virulent and may have played a role in the emergence of Lyme disease in epidemic form in the late twentieth century.
The 13 known genospecies of B. burgdorferisensu lato live in nature in enzootic cycles involving 14 species of ticks that are part of the I. ricinus complex. I. scapularis (Fig. 397-1) is the principal vector in the eastern United States from Maine to Georgia and in the midwestern states of Wisconsin, Minnesota, and Michigan. I. pacificus is the vector in the western states of California and Oregon. The disease is acquired throughout Europe (from Great Britain to Scandinavia to European Russia), where I. ricinus is the vector, and in Asian Russia, China, and Japan, where I. persulcatus is the vector. These ticks may transmit other diseases as well. In the United States, I. scapularis also transmits babesiosis and human anaplasmosis; in Europe and Asia, I. ricinus and I. persulcatus also transmit tick-borne encephalitis.
Ticks of the I. ricinus complex have larval, nymphal, and adult stages. They require a blood meal at each stage. The risk of infection in a given area depends largely on the density of these ticks as well as their feeding habits and animal hosts, which have evolved differently in different locations. For I. scapularis in the northeastern United States, the white-footed mouse and certain other rodents are the preferred hosts of the immature larvae and nymphs. It is critical that both of the tick's immature stages feed on the same host because the life cycle of the spirochete depends on horizontal transmission: in early summer from infected nymphs to mice and in late summer from infected mice to larvae, which then molt to become the infected nymphs that will begin the cycle again the following year. It is the tiny nymphal tick that is primarily responsible for transmission of the disease to humans during the early summer months. White-tailed deer, which are not involved in the life cycle of the spirochete, are the preferred host for the adult stage of I. scapularis and seem to be critical to the tick's survival.
Lyme disease is now the most common vector-borne infection in the United States and Europe. Since surveillance was begun by the Centers for Disease Control and Prevention (CDC) in 1982, the number of cases in the United States has increased dramatically. More than 25,000 new cases are now reported each summer. In Europe, the highest reported frequencies of the disease are in the middle of the continent and in Scandinavia.
Pathogenesis and Immunity
To maintain its complex enzootic cycle, B. burgdorferi must adapt to two markedly different environments: the tick and the mammalian host. The spirochete expresses outer-surface protein A (OspA) in the midgut of the tick, whereas OspC is upregulated as ...