Borrelia burgdorferi : Infectious substances pathogen safety data sheet
For more information on Borrelia burgdorferi, see the following:
Section I – Infectious agent
Name
Borrelia burgdorferi
Agent type
Bacteria
Taxonomy
Family
Borreliaceae
Genus
Borrelia
Species
afzelii, americana, andersonii, bavariensis, bissettii, burgdorferi sensu stricto, californiensis, carolinensis, garinii, japonica, kurtenbachii, lusitaniae, sinica, tanukii, turdi, spielmanii, valaisiana, yangtze, finlandensis and chilensis
Synonym or cross-reference
Formerly Borreliella burgdorferi, also known as Borrelia burgdorferi sensu lato; causative agent of Lyme disease, Lyme borreliosis, Lyme arthritis, tick-borne meningopolyneuritis, erythema migrans with polyarthritis, relapsing feverFootnote 1Footnote 2Footnote 3.
Characteristics
Brief description
Borrelia burgdorferi is a Gram-negative spirochete, a group of highly motile corkscrew-shaped bacteria, and a member of the family Borreliaceae within the order SpirochaetalesFootnote 2Footnote 3. It is microaerophilic, oxidase negative, and non-spore-forming, 10-30 µm in length and 0.2-0.5 µm in widthFootnote 2Footnote 4Footnote 5Footnote 6. The genome of B. burgdorferi consists of a linear chromosome approximately 950 kb in size, with a low G+C content of 28% and a variable complement of circular plasmids (cps) and linear plasmids (lps) that range in size from 9 to 62 kbFootnote 7. B. burgdorferi was identified as the causative agent of Lyme disease in 1982 but was only identified as a new Borrelia species in 1984Footnote 2Footnote 8. Molecular analysis has revealed that within the B. burgdorferi species, there are multiple genospecies, which are grouped together in the B. burgdorferi sensu lato complexFootnote 1Footnote 2. Several genospecies have been associated with human Lyme disease, including B. burgdorferi sensu stricto, B. afzelii, B. garinii, B. spielmanii, B. bavariensis, and B. bisettiiFootnote 1Footnote 7Footnote 9Footnote 10Footnote 11Footnote 12Footnote 13. B. burgdorferi sensu lato is maintained through a complex enzootic life cycle involving selected tick vectors and mammalian and avian hosts as its primary reservoirFootnote 3.
Properties
Certain circular and linear plasmids are essential for the enzootic cycle, including lp28-1, lp25 and some members of the cp32 familyFootnote 7. Other plasmids are essential for in vitro growth, such as cp26, which notably carries outer surface protein C (OspC), required for transmission from tick to vertebrate and infectivity in vertebratesFootnote 7. Virulence factors that contribute to persistence of infection with B. burgdorferi include the bacterium's ability to downregulate expression of specific immunogenic surface-exposed proteins, including OspC, and to alter rapidly and continually, by recombination of the antigenic properties, a surface lipoprotein known as variable major protein-like sequence expressed (VlsE)Footnote 1. Lyme Borrelia are not known to produce toxinsFootnote 1. Most tissue damage seems to result from host inflammatory reactions, with variable intensity in inflammatory response depending on the Borrelia genospecies implicated in infectionFootnote 1.
Section II – Hazard identification
Pathogenicity and toxicity
Lyme borreliosis causes multisystem disease that primarily affects the skin, joints, heart, and nervous systemFootnote 14Footnote 15. Other manifestations can include myalgia, arthralgia, lymphadenopathy, hepatosplenomegaly, congenital infections, and in rare cases, ophthalmic problemsFootnote 14Footnote 15. Disease presentation can vary based on the genospecies involvedFootnote 1. Effective treatment of the infection leads to rapid eradication of the bacteria with no additional symptoms. Untreated individuals may experience flares of infection for several years until their immune system successfully eliminates the bacteriaFootnote 16. Spirochaetal diseases generally occur in three overlapping stages with the following associated symptoms.
In stage I (early localized skin infection), a "bull's eye" shaped lesion, or an erythema chronicum migrans rash, typically appears at the site of the tick biteFootnote 1Footnote 16. A small red macule or papule appears as a rapidly expanding painless annular rash, which turns into a painless, hot, annular lesion. Other manifestations include acrodermatitis chronica atrophicans, a violaceous infiltration of the skin from which plaques or nodules are produced; lymphadenosis benigna cutis, a lymphocytic infiltration of the skin on ears, head or neck; morphoea, a localized scleroderma; and eosinophilic fasciitisFootnote 1Footnote 14Footnote 17Footnote 18. Depending on the study, up to 60% of persons with the disease show no cutaneous signs or symptomsFootnote 19.
Stage II (early disseminated infection) is characterized by multiple areas of erythema chronicum migrans rashes, accompanied by malaise, fatigue, headache, fever, and chillsFootnote 1Footnote 14Footnote 17Footnote 18. Neurological, musculoskeletal, or cardiac complications may occur. Although rare, cardiac involvement is seen in young male patients, and presents as myocarditis with conduction system abnormalities, syncope, palpitations, dyspnoea, atrioventricular blocks, and T wave abnormalitiesFootnote 1Footnote 14Footnote 17Footnote 18. Neurological effects include meningitis, cranial neuritis, radicular neuritis, encephalitis, and palsy. Oedema and erythema of the face may also occur.
In stage III (late or progressive infection), migratory polyarthropathy, which consists of intermittent attacks of arthritis in joints at the knees, shoulders, ankles, elbows, and the temporomandibular joints, can occur for a few weeks to months after onset, and is the most common clinical manifestationFootnote 14. Early symptoms (weeks after onset) show migratory musculoskeletal pain in joints, tendons, bursae, muscle, or bone with swellingFootnote 14. Months to years after onset, manifestations include intermittent arthritis, chronic synovitis with joint erosion and permanent disability. Encephalomyelitis, acrodermatitis chronica atrophicans, and encephalopathy have also been noted as clinical featuresFootnote 1. In children, this disease appears similar to juvenile rheumatoid arthritisFootnote 16.
Lyme borreliosis in domesticated animals is still poorly understood since clinical symptoms are often not present, and no distinctive rash seems to occurFootnote 20. The illness is best characterized in dogs, where arthritis and nephropathy appear to be the most common sequelae. Clinical signs attributed to Lyme borreliosis have also been reported in other species including horses and cattleFootnote 21Footnote 22.
Surveillance studies in dogs, using serologic evidence, detected high infection rates (25-90%) in endemic areas; but only 5-10% of infected dogs develop clinical diseaseFootnote 23Footnote 24. Experimentally infected pups and adult dogs developed symptoms of disease between 2-5 months following exposure, initially presenting with elevated body temperature, anorexia, warm and slightly swollen joints, and lameness, with recurrent mild polyarthritis following recoveryFootnote 23. A distinctive renal syndrome associated with B. burgdorferi infection has been described in dogs, histologically characterized by glomerulonephritis, tubular necrosis, and interstitial lymphoplasmacytic inflammation associated with a rapidly progressive and frequently fatal glomerular diseaseFootnote 24. In some dogs, central nervous system dysfunction and heart block secondary to myocarditis have been attributed to B. burgdorferi infectionFootnote 24.
Serologic evidence demonstrates infection in at least 20% of horses in endemic areas; however, it is uncommon to observe clinical manifestations of diseaseFootnote 23Footnote 24. Clinical signs of disease in horses are lethargy, low-grade fever, and stiffness and swelling in distal appendicular jointsFootnote 24. Neuroborreliosis, uveitis, lameness and swollen joints are the most common clinical symptoms of infected horses and cows; many also have fevers and abortionsFootnote 21Footnote 25.
Cattle appear to be less frequently affected than dogs and horses, and only occasional cases of clinical borreliosis have been describedFootnote 22Footnote 26. Seroconversion of cattle to Lyme Borrelia has been reported in several studies, with seropositivity rates of 9.8-21.8% reported from areas with high incidence of Lyme borreliosis, such as Slovenia Footnote 26. In cattle, borreliosis usually occurs as a herd problem in first-calving heifers, with acute signs of disease including fever, stiffness, and swollen joints, and decreased milk productionFootnote 27. Laminitis, chronic weight loss, uveitis and abortions have also been reportedFootnote 27. Two cows from distinct herds in tick-infested areas of Switzerland initially presented with poor appetite, reduced milk production, swollen joints, as well as erythema, warmth, swelling, and hypersensitivity of the ventral skin of the udder, which developed into erythematous udder lesions that healed with dark sloughing scabs within a few weeksFootnote 26Footnote 27. Experimental infection of cattle resulted in immunological responses suggestive of short-term subclinical infection, but clinical symptoms were not detectedFootnote 26. Wild and domestic ruminants appear to be incompetent reservoirs and may help reduce the prevalence of infected ticks by clearing spirochetes from infected ticks feeding on ruminantsFootnote 26Footnote 28.
Erythema migrans skin lesions, polyarthritis and carditis have been reported in experimentally infected rabbitsFootnote 29.
Although 5-47% of cats are seropositive in surveys, cases of naturally occurring disease have not been published. Conflicting results have been seen in experimental infections: in one study, cats remained asymptomatic while, in another, they developed fever, lethargy, stiffness and arthritisFootnote 20.
Epidemiology
B. burgdorferi infections occur worldwideFootnote 16. Lyme borreliosis is one of the most prevalent vector-borne diseases in North America, with 20,000 new cases reported annually in the United StatesFootnote 30. Most Lyme borreliosis cases in the United States occur in states along the Northeastern seaboard and in the Midwest (e.g., Wisconsin and Minnesota). In Canada, the disease appears to be emerging primarily in temperate regions of central and eastern Canada but has been on the increase in Western CanadaFootnote 31Footnote 32. Foci of infected ticks have been reported in Manitoba, particularly in the southeastern part of the province. Lyme borreliosis is also present throughout parts of Europe, China and RussiaFootnote 14Footnote 18Footnote 32. All four genospecies of Borrelia burgdorferi have been isolated from patients in Europe. Onset of disease is most frequently reported during the spring and summer months corresponding to peak activity of the nymphal stage of the relevant tick vectors. The presence of deer is associated with an increase in the number of Ixodes (deer) ticks which increases the infection risk for humansFootnote 33.
In the United States, the age distribution of Lyme borreliosis is typically bimodal, with peaks among children 5-15 years of age and adults 45-55 years oldFootnote 34. The incidence of Lyme borreliosis in the United States is higher among men than women in those below 60 years of age, but the sex ratio is nearly equal or slightly higher in older age groupsFootnote 34. In Canada, adults aged 55-79 years accounted for 46% of reported cases in 2019, while 11% of reported cases occurred in children aged 5-14 years of ageFootnote 35. Frequently in children, tick bites occur on the head and infection is more often associated with lymphocytic meningitisFootnote 36.
Case reports have suggested that adverse outcomes of pregnancy may be complicated by maternal Lyme borreliosisFootnote 36. However, the risk of transplacental transmission of B. burgdorferi is minimal when appropriate antibiotics are given to pregnant women, with Lyme borreliosis and congenital Lyme borreliosis syndrome having not been reportedFootnote 36. Besides abortion, malformations such as syndactyly, ventricular septum defect, and heart rate defects have been described in case reports of B. burgdorferi infection during pregnancyFootnote 37.
Within an endemic area, the risk of human infection by B. burgdorferi is determined by the local abundance and infection rate of vector ticks and by human behaviours that affect the likelihood of being bittenFootnote 34. Occupations and hobbies that increase tick exposure (e.g., forestry workers, hunters, and hikers) are associated with an increased risk of infection. Where homes are situated in tick-infested areas, exposure occurs primarily in the peridomestic environment that is influenced by the amount of suitable tick habitat, the density of ticks and deer, landscaping practices that promote tick survival and the undertaking of outdoor activities, such as gardeningFootnote 34.
Disease has increased in incidence and expanded its geographic range to include the Eastern United States and southeastern CanadaFootnote 35Footnote 38. Risk of exposure to B. burgdorferi is emerging in Canada, and geographic range expansion is predicted to accelerate with climate changeFootnote 31. Most cases of Lyme borreliosis occur from June to AugustFootnote 34.
Host range
Natural host(s)
Primary hosts include larger mammals, predominantly white-tailed deer, but also cattle, sheep, dogs, cats, horses, and bearsFootnote 24Footnote 39. Secondary hosts include small rodents (e.g., mice, voles, chipmunks, shrews, squirrels), lizards, and birdsFootnote 39. Humans are considered dead-end hostsFootnote 40. Other natural hosts include raccoons, red foxes, raccoon dogs, European badgers, pine martens and stone martensFootnote 41.
Other host(s)
Experimental infection with B. burgdorferi has been induced in hamsterFootnote 42 and Rhesus monkey modelsFootnote 43.
Infectious dose
Unknown for humans. In experimentally infected mice, the ID50 ranges from ~30 organisms for B. burgdorferi derived from replete nymphs to ~500 organisms cultivated in vitroFootnote 44. An ID50 of approximately 107 organisms has been reported in experimentally infected hamstersFootnote 42.
Incubation period
Erythema migrans appears in most people after 2-30 daysFootnote 17. In cases of disseminated disease, stage II occurs weeks to months after the erythema migrans rash, if untreated, and stage III can occur months to years, with considerable overlap with stage IIFootnote 14.
Communicability
Transmitted by bites from selected species of ticksFootnote 1Footnote 17. Human-to-human transmission of the disease has not been described; however, there is a theoretical risk of transmission of B. burgdorferi via blood transfusionFootnote 42.
Studies in both human and animal models have established that B. burgdorferi can cross the placenta, presumably during the period of initial spirochetemia, and that the likelihood of transplacental infection is likely higher at the beginning of pregnancy than in subsequent stagesFootnote 36Footnote 37. However, these studies indicated that an adverse fetal outcome resulting from maternal infection with B. burgdorferi at any point during pregnancy in humans is, at most, extremely rare.
Section III – Dissemination
Reservoir
There are a wide range of potential reservoirs but typically selected species of small rodents (e.g., mice, voles, shrews, and squirrels), and bird species are the primary reservoirsFootnote 18Footnote 45Footnote 46. Birds, mice, deer, voles, and lizards are major reservoirsFootnote 47. The white-footed mouse, Peromyscus leucopus, is the natural reservoir for B. burgdorferiFootnote 48Footnote 49. These mice are easily infected and harbor the pathogen for months, reintroducing the disease to the tick population, demonstrating reservoir competence. Deer are principal hosts for adult ticks and help maintain the tick population but are considered incompetent reservoirsFootnote 50.
Zoonosis
None.
Vectors
The primary vectors for Lyme disease in North America are Ixodes scapularis and I. pacificus, while in Europe and Asia, I. ricinus and I. persulcatus are the most prevalent vectorsFootnote 10Footnote 13Footnote 51Footnote 52. Several other species of ticks (e.g., I. uriae, I. angustus, I. spinipalpis and others) are capable of acting as enzootic vectors, transmitting the infection amongst reservoir hosts; however, because these species rarely bite humans they are not considered as important vector species.
Section IV – Stability and viability
Drug susceptibility/resistance
In most cases, Lyme borreliosis is treated successfully with antimicrobial therapyFootnote 50. Sensitivity has been established for macrolides, tetracyclines, semisynthetic penicillins, and late second and third generation cephalosporinsFootnote 18Footnote 53. Doxycycline, amoxicillin, and cefuroxime axetil are the most common oral antibiotics used clinically, and are highly effective and preferred treatmentsFootnote 1Footnote 18. Intravenous ceftriaxone is used for late stage and central nervous system disease (chronic Lyme borreliosis)Footnote 54Footnote 55. Doxycycline should not be used in the treatment of children aged <10 years or in pregnant womenFootnote 1Footnote 36. Erythema migrans resolves without treatment; however, oral antibiotic treatment is recommended to prevent dissemination and development of later sequelae.
Resistant to trimethoprim, sulfamethoxazole, cotrimoxazole, rifampin, ciprofloxacin, quinolones, and aminoglycosidesFootnote 3Footnote 52Footnote 56. Certain strains show resistance to erythromycinFootnote 56.
Susceptibility to disinfectants
Octenidine hydrochloride (0.01%) for 5 minutes has shown bactericidal activity against two B. burgdorferi sensu lato genospecies (B. afzelii, B. garinii)Footnote 57.
Physical inactivation
B. burgdorferi in platelet concentrates is sensitive to photochemical treatment with amotosalen and long-wavelength ultraviolet lightFootnote 58. Temperatures between 50 to 70°C successfully inactivate the bacteria. B. burgdorferi cultures heated at 55°C for 20 minutes experience a 5-fold decrease (based on log most probable number (MPN)/ml for determining low concentrations of organisms), whereas heating at 65°C results in a comparable decrease after approximately 3 minutesFootnote 59.
Survival outside host
Under experimental conditions, B. burgdorferi can survive for 48 days in blood products processed for transfusion when stored at 4°CFootnote 42. Survival at 20 to 24°C in platelet concentrates and at -18°C in fresh-frozen plasma has been reportedFootnote 60.
Section V – First aid/medical
Surveillance
Acute disease is primarily diagnosed based on history of exposure to tick vectors and clinical symptomsFootnote 1Footnote 17Footnote 18. Clinical diagnosis is most often supplemented by serological testing targeted at detection of IgM and IgG antibodies in blood using ELISAs and Western blots. Direct detection methods, such as bacterial culture or PCR, are less sensitive and infrequently used in routine clinical practiceFootnote 13.
Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.
First aid/treatment
Treatment with antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) can aid in lessening the severity of diseaseFootnote 17. Length of treatment, dose and route of treatment can vary depending on the stage of infection.
Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.
Immunization
No human vaccine currently available in Canada. A vaccine was developed and approved for use in the USA but is no longer in production after being withdrawn from the market for lack of demand and safety concerns at the timeFootnote 61.
Several canine Lyme disease vaccines are currently available, including Merilym, Lymevax, Galaxy Lyme, and Biocan BFootnote 62. OspA subunit vaccines, such as ProLyme and Recombitek Lyme, are also used. The efficacy of these vaccines has not been validated.
Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.
Prophylaxis
Use of antimicrobial prophylaxis for the prevention of Lyme borreliosis after a recognized tick bite is currently recommended where tick infection prevalence is greater than 20%Footnote 63. In Lyme disease-endemic areas, treatment with a single dose of 200 mg of doxycycline within 72 hours after a bite from a vector tick (I. scapularis) may prevent the development of Lyme diseaseFootnote 64.
Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.
Section VI – Laboratory hazard
Laboratory-acquired infections
None reported.
Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.
Sources/specimens
Blood, cerebrospinal fluid, synovial fluid, urine, retinal and vitreous specimens, skin biopsy specimens; naturally or experimentally infected mammals, vector ticks and their infected tissuesFootnote 18Footnote 50Footnote 65Footnote 66.
Primary hazards
Accidental parenteral inoculation and exposure to ticks or tissues from infected animals are the primary hazards associated with exposure to B. burgdorferiFootnote 17.
Special hazards
Work with ectoparasites (ticks) on laboratory animals can present a special hazardFootnote 67.
Section VII – Exposure controls/personal protection
Risk group classification
B. burgdorferi is a Risk Group (RG) 2 Human Pathogen and RG 2 Animal PathogenFootnote 68.
Containment requirements
Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.
Protective clothing
The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, post-mortem rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.
Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.
Other precautions
A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.
Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.
Additional information
For diagnostic laboratories handling primary specimens that may contain B. burgdorferi, the following resources may be consulted:
Section VIII – Handling and storage
Spills
Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (Canadian Biosafety Handbook).
Disposal
All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).
Storage
The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.
Section IX – Regulatory and other information
Canadian regulatory information
Controlled activities with Borrelia burgdorferi require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada.
The following is a non-exhaustive list of applicable designations, regulations, or legislations:
- Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
- Health of Animals Act and Health of Animals Regulations
- Transportation of Dangerous Goods Regulations
- National notifiable disease (human)
Last file update
March 2023
Prepared by
Centre for Biosecurity, Public Health Agency of Canada.
Disclaimer
The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.
Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.
Copyright © Public Health Agency of Canada, 2024, Canada
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