1103zu.qxd 10/9/2003 3:19 PM Page 1261 Zoonosis Update Lyme borreliosis Curtis L. Fritz, DVM, MPVM, PhD, DACVPM, and Anne M. Kjemtrup, DVM, MPVM, PhD n 1976, public health officials investigated a cluster and other animals, such as Leptospira and Treponema, Iof suspected juvenile rheumatoid arthritis cases that to which belong the agents of leptospirosis and occurred among residents of Lyme, Connecticut, and syphilis, respectively.8 Like other spirochetes, Borrelia neighboring communities.1 More than 50 residents spp are spiral shaped, gram-negative, and have an were evaluated for recurrent, usually short-lived (1 to outer sheath encasing endofibrils.9 Unique to Borrelia 2 weeks’ duration) attacks of swelling and pain in a few spp are a singular linear chromosome (with additional large joints. Clinical, laboratory, and epidemiologic evi- linear and circular plasmids) and life cycles that dence failed to substantiate an immune-mediated require both arthropod vectors and mammalian hosts.10 pathogenesis. An arthropod-transmitted bacterium was Borrelia spp may be generally grouped into those suspected as the etiologic agent, as many patients also that cause a relapsing fever-type illness (eg, B hermsii) had an expanding, red, annular rash that resembled and those that cause Lyme borreliosis.10 Spirochetes in erythema chronicum migrans (a lesion identified in the relapsing fever group typically utilize soft (ie, Europe in the early 20th century that was associated argasid) ticks as their vector. Some relapsing fever-type with tick bites and was responsive to penicillin).2,3 An Borrelia spirochetes have recently been recovered from infectious cause for the disease was confirmed when hard (ie, ixodid) ticks,11,12 but the pathogenic potential spirochetal bacteria isolated from Ixodes dammini (now of these isolates remains unknown. The Lyme borrelio- considered I scapularis) ticks4 and blood, CSF, and sis Borrelia complex is often divided into B burgdorferi other tissues of patients were shown to be identical.5-7 sensu stricto (B burgdorferi ss; those Borrelia geneti- The bacterium was named Borrelia burgdorferi, and the cally identical to the type-strain B31, recovered from multisystemic symptoms associated with infection an I scapularis tick from Long Island, NY13) and B were called Lyme disease or Lyme borreliosis (distin- burgdorferi sensu lato (B burgdorferi sl; all other guishing it from other forms of borreliosis caused by closely related Borrelia). Borrelia burgdorferi ss, B other Borrelia spp). Subsequently, B burgdorferi was afzelii, and B garinii cause Lyme borreliosis in humans identified in ticks in numerous regions of the United and animals in Europe and Japan.14,15 Only B burgdorferi States, and infection was associated with clinical illness ss is recognized as a cause of Lyme borreliosis in the in nonhuman animals, including dogs and horses. United States.16 Recently, B bissettii was recovered from 17 Findings of experimental, ecologic, epidemiologic, a human patient in Slovenia ; although B bissettii has 18 and clinical research conducted in the last 2 decades been identified in ticks in the United States, no infec- have tremendously expanded our scientific under- tion of mammals with this bacterium has been docu- standing of Lyme borreliosis. The genome of the mented. causative spirochete has been sequenced, ecologic A linear chromosome and 21 plasmids comprise 19 dynamics of its maintenance in nature have been the genome of the B burgdorferi B31 type strain. The described, effective diagnostic and treatment protocols genome codes for over 150 lipoproteins, some of which have been established, and vaccines have been devel- are key to the spirochete’s ability to transfer between oped. However, as coverage by the popular media of the tick vector and mammalian host. Several lipopro- this complex disease is often a farrago of fact, fallacy, teins that localize to the outer surface of the spirochete and opinion, familiarity with the current scientific (outer surface proteins [Osps]) are important in the body of knowledge on Lyme borreliosis is critical to transmission of Borrelia spirochetes to a vertebrate host enable practicing veterinarians to appropriately and the host’s subsequent immune response. While in the gut of the tick, the spirochete expresses chiefly Osp address concerns of their clients and to effectively 20 manage animals with the disease. A. The spirochete switches from Osp A to Osp C expression during a period of accelerated reproduction 20 Microbiology at the beginning of the tick’s blood meal. The variable The genus Borrelia is in the order Spirochetae, major protein-like sequence expressed (VlsE) Osp which contains genera that are pathogenic to humans has an invariable region conserved across many species of Borrelia and is highly immunogenic in mice, dogs, 21-24 From the California Department of Health Services, Division of and primates. An understanding of the kinetics of Communicable Disease Control, Vector-Borne Disease Section, PO these and other expressed proteins (eg, decorin bind- Box 942732, MS 7307, Sacramento, CA 94234-7320. ing proteins and flagellin) is important for diagnosis Address correspondence to Dr. Fritz. (measurement of mammalian antibody response to JAVMA, Vol 223, No. 9, November 1, 2003 Vet Med Today: Zoonosis Update 1261 1103zu.qxd 10/9/2003 3:19 PM Page 1262 bacterial proteins) and prevention (identification of States (typically > 50%).44 Birds also may play a role in potential vaccine candidates) of Lyme borreliosis. the transmission cycle of B burgdorferi in specific habi- tats in the western United States.45 Ecology and Transmission The multiple species of Borrelia that exist world- Borrelia burgdorferi is maintained in nature in a wide and the broad host range of their vector ticks con- cycle that involves hard ticks of the Ixodes genus as tribute to complex life cycles for agents of Lyme borre- vectors and small mammals or birds as reservoir hosts. liosis in other areas of the world.46 Each of the Borrelia Ixodes spp are 3-host ticks that attach to a host and take genotypes in Europe is associated with a specific verte- a blood meal at each life stage (larva, nymph, and brate host: B burgdorferi ss and B afzelii with small adult), then drop off the host to molt in the environ- rodents47,48 and B garinii with birds.48,49 In Japan, I persul- ment.25 Larval and nymphal stages of Ixodes spp are catus is the primary vector tick that maintains B afzelii, found in moist, protected areas, such as under leaf lit- B garinii, and B burgdorferi ss in enzootic cycles; this ter in humid hardwood forests. The principal hosts of species of tick also transmits these agents to humans immature Ixodes ticks are small rodents, lizards, and and domestic animals.50 All 3 genospecies of B burgdor- ground-feeding birds. The immature ticks typically feri sl have been documented in both rodents and require 2 to 4 days of attachment to the host to com- birds.50-52 plete a blood meal. At the adult stage, an Ixodes tick In all vector ticks, the Borrelia spirochetes under- climbs to the tips of grasses, where it waits (or quests) go both quantitative and qualitative changes prior to for a large mammal host to brush against it. Adult ticks and during an infected tick’s blood meal. When a larval feed typically for 5 to 7 days. The abundance and activ- or nymphal Ixodes tick ingests B burgdorferi from an ity of each life stage differ by season and are dependent infected host, the spirochetes localize to the gut and on weather, sunlight, and host availability.26,27 multiply until the tick molts, at which time the num- In the northeastern and upper midwestern United ber of spirochetes decreases greatly, resulting in quest- States, I scapularis (commonly known as the deer tick ing nymphs or adults with few spirochetes.53,54 Once or black-legged tick) is the principal vector of B the infected nymphal or adult tick attaches to a new burgdorferi. Larval and nymphal I scapularis acquire B host, spirochetes multiply rapidly in the lumen of the burgdorferi primarily from infected white-footed mice midgut, and there is a change in Osp expression from (Peromyscus leucopus).5,28,29 Borrelia burgdorferi is trans- Osp A (hypothesized to be an adhesion for spirochete mitted trans-stadially from larva to nymph and from attachment to the midgut)55 to Osp C.56 The expression nymph to adult. Ixodes scapularis that become infected of Osp C is subsequently decreased in spirochetes that as larvae or nymphs can subsequently transmit the are in the salivary glands of ticks.20 Thus, Osp C is agent as nymphal and adult ticks when they feed in the thought to facilitate the transmission step wherein the summer and fall, respectively.30 Transovarial transmis- spirochetes migrate from the midgut to the hemocele sion (adult female to egg) is rare and inefficient.25,31,32 and finally to the salivary glands, from which they can White-tailed deer (Odocoileus virginianus) are the pre- be transmitted to the host.20 The spirochetes’ develop- ferred hosts of adult I scapularis; however, because they ment and migration take approximately 2 to 3 days; are poor reservoirs for B burgdorferi,33 they serve chiefly therefore, transmission to the mammalian or avian to maintain the population of ticks and not that of B host is relatively inefficient until 48 hours after tick burgdorferi. Furthermore, birds may introduce infected attachment.57 Feeding by ticks is a dynamic process I scapularis into previously nonendemic areas or serve involving the release of many immunologically active as reservoir hosts for B burgdorferi.34,35 substances from the ticks’ salivary glands. The host’s The transmission cycle of B burgdorferi in the initial immune response temporarily delays the spiro- western United States is slightly more complicated.