A tick-borne, spirochetal, zoonotic disease characterized by a distinctive skin lesion, systemic symptoms and neurological, rheumatological and cardiac involvement occurring in varying combinations over months to years. Recent reports state that the optic nerve may be affected because of inflammation or increased intracranial pressure. Early symptoms are intermittent and changing. The illness more frequently occurs in late spring or in the summer following a tick bite, when nymphs are most active. The first manifestation in about 70 to 80% of patients is a red macule or papule that expands slowly in an annular manner, often with central clearing. This lesion is called erythema migrans or EM (formerly “erythema chronicum migrans”). EM may be single or multiple; to be considered significant for case surveillance purposes, the EM lesion must reach at least 5 cm in diameter. With or without EM, early systemic manifestations may include malaise, fatigue, fever, headache, stiff neck, myalgia, migratory arthralgias and/or lymphadenopathy, all of which may last several weeks in untreated patients. In central Europe and Scandinavia skin lesions called lymphadenosis benigna cutis and acrodermatitis chronica atrophicans are almost exclusively caused by Borrelia afzelii.
Within weeks to months after onset of the EM lesion, neurological abnormalities such as aseptic meningitis and cranial neuritis may develop in approximately 5% of untreated patients—including facial palsy, chorea, cerebellar ataxia, motor or sensory radiculoneuritis, myelitis and encephalitis. Symptoms fluctuate and may become chronic. Cardiac abnormalities (including atrioventricular block and, rarely, acute myopericarditis or cardiomegaly) may occur within weeks after onset of EM. Weeks to years after onset (mean, 6 months), intermittent episodes of swelling and pain in large joints (especially the knees) may develop in 60% of untreated patients, leading to chronic arthritis; this may recur for several years. Treatment-resistant Lyme arthritis is a rare complication that may be the result of cross reactivity between OspA and the human leukocyte function associated antigen-1 (hlFA-1) following natural infection with B. burgdorferi. Similarly, following latent infection, chronic neurological manifestations may develop and include encephalopathy, polyneuropathy or leukoencephalitis; the CSF often shows lymphocytic pleocytosis and elevated protein levels, while the electromyogram is usually abnormal.
The causative spirochete for Lyme disease in North America is B. burgdorferi, which was identified in 1982. Three genomic groups of B. burgdorferi have now been identified in Europe and named B. burgdorferi sensu stricto, B. garinii and B. afzelii. A few B. bissettii-like strains as well as B. valaisiana strains and one atypical A14S strain have been cultured from European patients with EM lesions.
Diagnosis is currently based on clinical findings supported by two-stage serological tests, IFA, ELISA and then Western immunoblotting. Serological tests are poorly standardized and must be interpreted with caution. They are insensitive during the first weeks of infection and may remain negative in people treated early with antibiotics. An ELISA for IgM antibodies that uses a recombinant outer surface protein C (rOspC) is more sensitive for early diagnosis than whole cell ELISA. VlsE (Vls locus expression site) or C6 recombinant antigens increase the sensitivity of IgG immunoblot. Test sensitivity increases when patients progress to later stages, but some chronic Lyme disease patients may remain seronegative. Cross-reacting IFA and ELISA antibodies may cause false-positive reactions in patients with syphilis, relapsing fever, leptospirosis, HIV infection, Rocky Mountain spotted fever, infectious mononucleosis, lupus or rheumatoid arthritis. The specificity of serological testing is enhanced by immunoblot testing of specimens that are positive or equivocal on IFA or ELISA. Diagnosis of nervous system Lyme disease requires demonstration of intrathecal antibody production. The causal agent is Borrelia burgdorferi sensu lato. The genotype present in North America, Borrelia burgdorferi sensu stricto, grows at 33°C (91.4°F) in the Barbour, Stoenner, Kelly (BSK) medium; other species causing Lyme-like disease may not grow well in this medium. Isolation from blood and tissue biopsies is difficult, but biopsies of the EM lesions may yield the organism in 80% of cases or more. PCR has identified B. burgdorferi genetic material sensu lato in synovial fluid, CSF, blood and urine, skin, and other tissues; the usefulness of PCR in routine management of Lyme disease cases has yet to be verified. Recent real-time assays combining DNA amplification with species-specific probes allow single step identification of spirochetal DNA to the species level.
Tick-borne; in experimental animals, transmission by I. scapularis and I. pacificus usually does not occur until the tick has been attached for 24 hours or more; this may also be true in humans. Borrelia survives in blood products: no blood donation should be accepted from people suspected to have Lyme disease.
For EM, 3 to 32 days after tick exposure (mean 7 to 10 days); early stages of the illness may be unapparent and the patient may present with later manifestations.
No evidence of natural person-to-person transmission. Despite rare case reports of congenital transmission, epidemiological studies have not shown a link between maternal Lyme disease and adverse outcomes of pregnancy.
Some ixodid ticks through trans-stadial transmission (no or very limited trans-ovarial transmission). Wild rodents, especially Peromyscus spp. in the northeastern and midwestern USA and Neotoma spp. and gray squirrels in the western USA, maintain the enzootic transmission cycle. Deer serve as important mammalian maintenance hosts for vector tick species. Larval and nymphal ticks feed on small mammals, and adult ticks feed primarily on deer. The majority of Lyme disease cases result from bites by infected nymphs. Research in Europe supports the possible role of birds in dispersing B. garinii and B. valaisiana. Other studies support a relationship between B. afzelii and European rodents, notably Clethrionomys voles.
All persons are probably susceptible. Re-infection has occurred in those treated with antibiotics for early-stage disease.
In the USA, endemic foci exist along the Atlantic coast, in Wisconsin and Minnesota, and in some areas of California and Oregon; increasing recognition of the disease has led to reports from 47 states and from Ontario and British Columbia in Canada, as well as from Europe, Russia, China and Japan.
The distribution of most cases coincides with the distribution of the black-legged tick, Ixodes scapularis (formerly I. dammini), in the eastern and midwestern USA; the western black-legged tick, I. pacificus, in western USA; I. ricinus (sheep tick) in Europe; and I. persulcatus in Asia. Initial infection occurs primarily during late spring or summer, with a peak in June and July, but may occur throughout the year, depending on the seasonal abundance of the tick locally. Dogs, cattle and horses develop systemic disease that may include the articular and cardiac manifestations seen in human patients. The explosive repopulation of the eastern USA by white-tailed deer, on which adult ticks feed, has been linked to the spread of Lyme disease in this region.
a) Educate the public about the mode of tick transmission and the means for personal protection.
b) Avoid tick-infested areas when feasible. To minimize exposure, wear light-colored clothing that covers legs and arms so that ticks may be more easily seen; tuck trousers into socks and apply tick repellent such as diethyltoluamide to the skin and/or permethrin (repellent and contact acaricide) to sleeves and trouser legs.
c) If working or playing in an infested area, examine the total body area daily. Do not neglect hairy areas. Remove ticks promptly; these may be very small, especially larvae or nymphs. Remove ticks by using gentle, steady traction with forceps (tweezers) applied close to the skin, so as to avoid leaving mouth parts in the skin; protect hands with gloves, cloth or tissue when removing ticks. Following removal, cleanse the attachment site with soap and water.
d) Measures designed to reduce tick populations on residential properties (host management, habitat modification, chemical control) are usually impractical on a large-scale basis.
e) During the late 1990s, two Lyme disease vaccines were developed for protection of humans using recombinant B. burgdorferi stricto sensu lipidated outer-surface protein A (rOspA) as an immunogen. In late 1999, one of these vaccines was licensed in the USA for administration on a 3-dose schedule of 0, 1, and 12 months, and was found to be safe and 76% effective in preventing overt Lyme disease after 3 doses. After license of the vaccine, anecdotal reports of joint reactions associated with vaccination, accompanied by lawsuits, led to discontinuation of distribution in February 2002 due to low demand and sales.
i) Vaccine-induced anti-rOspA antibodies routinely cause false-positive ELISA results for Lyme disease. Experienced laboratory workers can usually discriminate between B. burgdorferi infection and previous rOspA immunization, because anti-OspA antibodies do not develop after natural infection.
ii) Lyme disease vaccine did not protect all recipients against infection with B. burgdorferi and offers no protection against other tick-borne borrelioses.
iii) Risk assessment should include consideration of the geographic distribution of Lyme disease. The areas of highest risk in North America are concentrated within some northeastern and north-central states and provinces. In Europe, sporadic areas of transmission occur in areas where animal vectors are found. However, risk for Lyme disease differs even within counties and townships. Detailed information about the distribution of Lyme disease risk within specific areas is best obtained from public health authorities.
iv) In areas of moderate to high risk, immunization had until 2002 been considered for persons aged 15–70 years who engaged in activities (recreational, property maintenance, occupational or leisure) resulting in frequent or prolonged exposure to tick-infested habitats. Future availability of vaccines against Lyme disease is uncertain.
a) Report to local health authority: Case report obligatory in some countries, Class 3.
b) Isolation: Not applicable.
c) Concurrent disinfection: Carefully remove all ticks from patients.
d) Quarantine: Not applicable.
e) Immunization of contacts: Not applicable.
f) Investigation of contacts and source of infection: Studies to determine source of infection when cases occur outside a recognized endemic focus.
g) Specific treatment: For adults, the EM stage can usually be treated effectively with doxycycline (100 mg twice daily) or amoxicillin (500 mg 3–4 times daily)—though tetracycline and doxycyline cannot be used in children less than eight years of age. For localized EM, 2 weeks of treatment usually suffice; for early disseminated infection, 3–4 weeks. Children under 9 can be treated with amoxicillin, 50 mg/kg/day in divided doses, for the same period of time as adults. Cefuroxime axetil or erythromycin can be used in those allergic to penicillin or who cannot receive tetracyclines. Lyme arthritis can usually be treated successfully with a 4-week course of the oral agents. However, objective neurological abnormalities, with the possible exception of isolated facial palsy, are best treated with IV ceftriaxone, 2 grams once daily, or IV penicillin, 20 million units in 6 divided doses, for 3–4 weeks. Treatment failures may occasionally occur with any of these regimens and retreatment may be necessary.
In hyper-endemic and infested areas, identify tick species involved, if possible.
WHO Collaborating Centres provide support as required. More information can be found at: http://www.who.int/collaboratingcentres/database/en/
Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.