Lyme Disease. By Mike Hughes. Name: Lyme Disease. Etiological Agent: Lyme disease is caused by the bacteria Borrelia burgdorferi.

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1 Lyme Disease Name: Lyme Disease By Mike Hughes Etiological Agent: Lyme disease is caused by the bacteria Borrelia burgdorferi. Transmission: Deer ticks transmit the pathogen by biting the host resulting in infection; thus this disease is ultimately passed through biological vector transmission. There are two different species of ticks known to pass Borrelia burgdorferi: Ixodes scapularis spreads Lyme disease in the northeastern all the way to the north- central part of the United States, while Ixodes pacificus transmits the disease in the northwest, though both are known as blacklegged ticks (1). It is the nymph growth stage when deer ticks infect most people, as they are small, hard to see and feed in the spring and summer (1). Deer ticks acquire Borrelia burgdorferi from biting and ingesting blood from animals already infected by the bacteria and in response, they themselves can become infected (1). Reservoirs: Borrelia burgdorferi is acquired by insects that have bitten animals that are infected by this bacterium, thus animals serve as the living reservoir for the zoonose Borrelia burgdorferi namely, white- footed mice and deer. In particular, the White- footed mouse serves as the largest reservoir of infection as many ticks in their larval and nymphal life stages are able to feed on it and become infected (2). In order for the blacklegged tick to proceed to the next life stage (of its four), it needs to have a blood meal, it s during these feeding times that the tick acquires the bloodborne pathogen, though it can acquire it from either a mammal, bird, reptile or amphibian (1). General Characteristics: Borrelia burgdorferi is a spirochete. Due to the small width of spirochetes compared to the resolving power of microscopes the Gram test doesn t usually effectively distinguish spirochetes, however due to the fact that Borrelia burgdorferi contains an outer lipopolysaccharide structure and a thin layer of peptidoglycan, it has a wall similar to a Gram- negative bacterial cell wall (3). Spirochetes achieve motility through the use of axial filaments called endoflagella. These endoflagella are located in the periplasmic space of the cell, between the semi rigid peptidoglycan helix and a multi- layer flexible outer membrane sheath (3). This allows the bacterium to move in a corkscrew- like motion through liquid and viscous material. Borrelia burgdorferi is microaerophillic and difficult to culture due to very specific requirements needed for it s growth medium (4). Due to the fact that the width of spirochetes is below the resolving power of light microscopes, a dark- field microscope is needed to view Borrelia burgdorferi or spirochetes, in general. Key tests for the identification Lyme disease (Borrelia burgdorferi): Serological tests are the initial tests used to determine the presence of possible antibodies indicating the potential presence of Lymes disease using either an ELISA test or an indirect fluorescent- antibody test though the presence of antibodies can persist for years after the bacteria has been eliminated sometimes interfering with diagnoses later on (5). The Western Blot test is used following an initial positive

2 test as the confirmatory test (5). Signs and Symptoms: The signs and symptoms of Lyme disease occur over a period of three stages. Early Localized Stage (3-30 days post- tick bite): After the initial infection is acquired, an erythema migrans a rash resembling a bull s eye can appear at the site of the bite after a delay of 3-30 days (6). This occurs in about 75% of cases and flulike symptoms appear a couple of weeks later as the rash disappears (5). These flulike symptoms include fever, joint pains, fatigue and chills (2). Early Disseminated Stage (days to weeks post- tick bite): As the disease progresses it can affect the peripheral nervous system causing tingling or numbness in extremities or facial palsy known as Bell s palsy (6). Additionally, severe headaches, neck stiffness due to swelling of the spinal chord, and pain and swelling in the large joints can occur (6). Late Disseminated Stage (months- to- years post- tick bite): Symptoms associated with this stage often include impairment of the CNS, causing cognitive disorders such as short- term memory loss and confusion (2) as well as bouts of arthritis (6). Historical Information: Lyme disease first came to the publics attention when during the 1970 s, several cases of rheumatoid arthritis occurred amongst children in the namesake town of Lyme, Connecticut including two neighboring towns (12). Researchers noted that majority of the cases occurred during the summer and in children who were playing near wooded areas that the bite was most likely caused by ticks and focused on finding a possible connection. It wasn t until the 1980 s however when a scientist in Hamilton, Montana named Willy Burgdorfer studying Rocky Mountain Spotted Fever had heard about the cases and wondered if the annular rashes associate with Lymes disease had any connection to the European rash called erythema migrans (12). After isolating the spirochete from the gut of ticks, the scientists were able to prove that it indeed caused Lyme disease. The bacteria was later given the species name burgdorferi in honor of Dr. Burgdorfer. Virulence Mechanisms: It has been noted that Borrelia burgdorferi produces two different lipoprotein coats depending on the their location within the blacklegged ticks, lipoprotein Osp A and lipoprotein Osp C. It was found that B. burgdorferi expressed of Osp A abundantly and downregulated Osp C when in the midgut of the tick however downregulated expression of the Osp A protein when the tick was feeding and upregulated Osp C protein expression (7). It has been found that these lipoprotein coats help protect the spirochetes from the host s acquired immune defenses (8). Though vaccines were created (and eventually pulled from the market) they were tested to target specifically Osp A and Osp C proteins, the Osp C vaccine proved less effective than the Osp A, indicating that genetic and antigenetic variation may also pose to be a limiting factor in protection against the pathogen (9). It s also been found that B. burgdorferi cloaks itself in a protein coating consisting of the protein Salp15 in which it drives the tick to overproduce in its saliva. This may contribute to the virulence of Lyme disease as this protein allows the bacteria to remain undetected by a human host s T- cells (10). B. burgdorferi also has the ability to survive in a hosts system without iron, a common element needed for production of cellular

3 proteins and enzymes. The bacterium is able to use manganese to produce an essential enzyme, allowing it to avoid immune defenses that attempt to starve pathogens of iron (11). Control/Treatment: Treatment in the early stages of Lyme disease commonly requires the use of antibiotics taken by mouth such as amoxicillin, doxycycline or cefuroxime axetil twice a day for two weeks. If the disease is found in later stages, use of antibiotics is usually extended to four weeks (13). If late cardiac or neurological forms of Lyme disease are found with damage to the central or peripheral nervous system, adults are treated intravenously with ceftriaxone for 2 to 4 weeks. If there s evidence of development of rheumatoid arthritis, non- steroidal anti- inflammatory agents, intra- articular injections of corticosteroids, or disease- modifying antirheumatic drugs (DMARDs) may also be used to ease swelling (13). Approximately 10 to 20% of people who have been treated for Lyme disease have reported lingering symptoms of joint and muscle aches, fatigue and pain leading to a diagnosis of Post- treatment Lymes Disease Syndrome (PTLDS). It has been found though that prolonged use of antibiotics hasn t been effective at alleviating PTLDS and clinical studies ro find the cause of PTLDS are ongoing (1). Prevention/Vaccine: Ultimately though, limiting contact with vector ticks. It is usually recommended to wear long clothing that fully covers limbs and exposed skin, tucking pants into socks, wearing light colored clothing and changing clothes after having been outside. Also check for ticks daily during spring and summer seasons to avoid any prolonged exposure. If a tick is found and removed within 24 hours of exposure, one s chances of getting Lyme disease is greatly reduced (1). The use of tick and bug repellents is also effective in avoiding contact when walking near potential sites of exposure. A vaccine called LYMERix was developed in 1998, however was withdrawn from the market after 905 reports, including 66 classified as serious, were found to have been caused after the administration of the vaccine resulting in negative media attention and ultimately negative public opinion (14). Cases and Outbreaks: Lyme disease is the most commonly reported vectorborn disease in the United States and is endemic in the northeast and upper Midwest (15). In 2012, 22,014 confirmed cases were reported in the United States including another 8,817 probable cases. Eleven states of the northeast and 2 state of the upper Midwest containing 95% of those reported cases (15). Though Lyme disease is endemic in the United States, it has been isolated in all the other continents except for Antarctica and cases still commonly occur in the United Kingdom and Europe. As of now, Lyme disease has been found in over 80 different countries, though there haven t been any global outbreaks (15). Bibliography: 1. Centers for Disease Control and Prevention, Division of Vector- Borne Diseases. (2013). Lyme Disease Transmission. Retrieved May 6, 2014 from

4 2. American Lyme Disease Foundation (2010, April 26). Lyme Disease. Retrieved May 5, 2014 from 3. Kenneth Todar, PhD. (2008). Todar s Online Textbook of Bacteriology. Borrelia burgdorferi and Lyme Disease. Retrieved May 5, 2014 from 4. Hyde, J.A., Trzeciakowski, J.P., Skare, J.T. (January, 2007). Borrelia burgdorferi Alters Its Gene Expression and Antigenic Profile in Response to CO2 Levels. Journal of Bacteriology, 189, Retrieved May 6, 2014 from 5. Case, C.L., Funke, B.R., Tortora, G.J. (2013). Microbiology: An Introduction. 11th ed. San Francisco: Pearson. 6. Centers for Disease Control and Prevention, Division of Vector- Borne Diseases. (2013). Signs And Symptoms of Lyme Disease. Retrieved May 6, 2014 from 7. Yang, X., Goldberg, M.S., Popova, T.G., Schoeler, G.B., Wikel, S.K., Hagman, K.E., Norgard, M. V. (September, 2000). Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi. Molecular Microbiology, 37, Retrieved May 5, 2014 from 8. Battisti, J.M., Bono, J.L., Rosa, P.A., Schrumpf, M. E., Schwan, T.G., Policastro, P.F. (September, 2008). Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector. Infection and Immunity, 76, Retrieved May 6, 2014 from 9. Probert, W.S., Crawford, M., Cadiz R.B., LeFebvre R.B. (February, 1997). Immunization with outer surface protein (Osp) A, but not OspC, provides cross- protection of mice challenged with North American isolates of Borrelia burgdorferi. The Journal of Infectious Diseases, 175, Retrieved May 5, 2014 from Howard Hughes Medical Institute. (November, 2009). Tick Saliva: New Target for Lyme Disease Vaccine. Retrieved May 5, 2014 from saliva- new- target- lyme- disease- vaccine 11. Lippsett, L., (2013, March 21). Lyme Disease Bacteria Have Quirky Needs. Retrieved May 5, 2014 from find- surprising- lyme- disease- bacteria- has- quirky- needs

5 12. National Institute of Health, National Institute of Allergy and Infectious Diseases. (2008). Finding the Cause of Lyme Disease. Retrieved May 6, 2014 from Wormser, G.P., Dattwyler, R.J., Shapiro, E.D., Halperin, J.J., Steere, A.C., Klempner, M.S., Krause, P.J., Bakken, J.S., Strle, F., Stanek, G., Bockenstedt, L., Fish, D., Dumler, J.S., Nadelman, R.B. (2006). The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases, 43, Retrieved May 5, 2014 from The History of Vaccines, A Project of the College of Physicians of Philadelphia. (2014, January 23). The History of the Lyme Disease Vaccine. Retrieved May 6, 2014 from lyme- disease- vaccine 15. Centers for Disease Control and Prevention, Division of Vector- Borne Diseases. (2013). Lyme Disease Data. Retrieved May 6, 2014 from