Borrelia Burgdorferi: Lyme Disease
Borrelia burgdorferi
Overview:
Lyme disease was first recognized in the United States in 1975 by Dr. Allen Steere, following a mysterious outbreak of juvenile rheumatoid arthritis near the community of Lyme, Connecticut. The rural location of the Lyme outbreak and the onset of illness during summer and early fall suggested that the transmission of the disease was by an arthropod vector. Adult female Ixodes tick (deer tick) From Brown University In 1982, the causative agent of Lyme disease was discovered by Willy Burgdorfer, who isolated spirochetes belonging to the genus Borrelia from the mid-guts of the species Ixodes ticks. Spirochettes are pleomorphic. They appear spiral-shaped, but have evolved the capacity to hide …show more content…
in cysts and colonies, changing into a round ball and then back into a spiral. Lyme experts believe this is the way the bacteria move through the tissues and bloodstreams of the body.
Burgdorfer showed that these spirochetes reacted with immune serum from patients that had been diagnosed with Lyme disease. Subsequently, the etiologic agent was given the name Borrelia burgdorferi.
Classification
Domain: Bacteria Phylum: Spirochaetes Order: Spirochaetales Family: Spirochaetaceae Genus: Borrelia Species Borrelia burgdorferi
Strains of Borrelia
The borreliae causing Lyme disease are divided into several "genospecies", three of which have been firmly established and are well accepted:
I. Borrelia burgdorferi sensu stricto
II. Borrelia garinii
III. Borrelia afzelii
Disease
Lyme disease usually presents with a characteristic “bull’s eye rash”, erythema migrans, along with fever, fatigue, headache, muscle aches, and joint aches. The incubation period from infection to onset of the rash is typically 1-2 weeks. Some patients may be asymptomatic and present with only non-specific symptoms. B. burgdorferi is spread from the site of the tick bite through the blood stream. There are three clinical stages of Lyme disease: 1) the Localized Early (Acute) Stage, 2) the Early Disseminated Stage and 3) the Late Stage. The acute stage is characterized by a solid red or bull’s eye rash at the site of the bite, swelling of the lymph glands near the bite, generalized achiness and headache. The early disseminated stage is characterized by two or more; rashes not at the site of the bite, migrating pains in joints/tendons, headache, stiff neck, facial paralysis, tingling or numbness in the extremities, multiple enlarged lymph glands, abnormal pulse, sore throat, changes in vision, fever of 100 to 102 F, and severe fatigue. The late stage is characterized by arthritis of one or two large joints, disabling neurological disorders, and numbness in the extremities.
Biology of Spirochetes Borrelia burgdorferi, like the human pathogen Treponema pallidum, is a spirochete. Spirochetes are a group of phylogenetically-distinct bacteria that have a unique mode of motility by means of axial filaments (endoflagella). Spirochetes are widespread in viscous environments and are found in the intestinal tracts of animals and the oral cavity of humans. The spirochetes have a unique cell surface which accompanies their unique type of motility. The endoflagella are contained within the periplasmic space between a semi rigid peptidoglycan helix and a multi-layer, flexible outer membrane sheath. When the filaments rotate within this space, the spirochetes move in cork-screw fashion. This type of movement is thought to be an adaptation to viscous environments, such as aquatic sediments, biofilms, mucosal tissues and the intestinal tracts of animals. For pathogens, this allows the spirochetes to hide their flagella, which are normally antigenic, from the host immune defenses. Spirochetes are usually much longer than they are wide, and often their width is below the resolving power of the light microscope. Therefore, most spirochetes cannot be viewed using conventional light microscopy. Dark-field microscopy must be used to view spirochetes. Dark field microscopy utilizes a special condenser which directs light toward an object at a angle, rather than from the bottom. As a result, particles or cells are seen as light objects against a dark background. B. burgdorferi dark field illumination. American society for Microbiology. The spirochetes are not classified as either Gram-positive or Gram-negative. When Borrelia burgdorferi is Gram-stained, the cells stain a weak Gram-negative by default, as safranin is the last dye used. Borrelia, like most spirochetes, does have an outer membrane that contains an LPS-like substance, an inner membrane, and a periplasmic space which contains a layer of peptidoglycan. Therefore, it has a Gram-negative bacterial type cell wall, despite its staining characteristics.
Cell Structure and Metabolism B.
burgdorferi is a helical shaped spirochete bacterium. It has an inner and outer membrane as well as a flexible cell wall. Inside the bacteria 's cell membranes is the protoplasm, which, due to the spiral shape of the bacteria, is long and cylindrical. Spirochete bacteria such as B. burgdorferi have a unique structural characteristic. The cell 's flagella are located inside the periplasm between the inner and outer cell membranes. The interactions between the flagella and cell cylinder allows the cell to travel through highly viscous fluids and materials. This adaptation is especially critical for the ability of B. burgdorferi to travel through the tissue of its infected host or vector, causing it to be highly …show more content…
invasive. Structure of Borrelia burgdorferi, Reprinted by permission from Nature Publishing Group: Nature Reviews Microbiology, copyright 2005 Another important cellular component of B. burgdorferi is its outer surface proteins. Researchers have investigated a variety of outer membrane surface proteins (Osp) and have found them to play important roles in transmission of the bacteria. The cell expresses different surface proteins, most notably OspA and OspC. When the bacteria is inside of an unfed tick, it produces mostly OspA. However, the bacteria that are inside of infected mammals express mostly OspC . This has led to the speculation that the bacteria produce specific outer surface proteins in order to successfully invade and inhabit certain organisms. For example, OspA may function to retain the bacteria in the tick stomach, while the presence of OspC may encourage the bacteria to enter the salivary glands and enter the host. OspA, OspC, and other outer surface proteins may play important roles in the ability of the bacteria to infect and survive inside their hosts. The genome sequencing of B. burgdorferi showed that it has genes for metabolism similar to other parasites. These bacteria have limited metabolic capabilities and rely on their host for energy. In ticks, it is believed that N-acetylglucosamine (NAG) is a major energy source as it is a main component of tick cuticle and is essential for in vitro growth of the bacteria. It produces ATP solely by using substrate-level phosphorylation and achieves reducing power using the pentose phosphate pathway.
Microbial Characteristics, Virulence and Pathogenicity B. burgdorferi can be cultivated on a modified medium. The spirochete grows more slowly than most other bacteria dividing once after 12-24 hours. B. burgdorferi resembles other spirochetes in that it is a highly specialized, motile, two-membrane, spiral-shaped bacteria which lives primarily as an extracellular pathogen. One of the most striking features of B.
burgdorferi as compared with other bacteria is its unusual genome, which includes a linear chromosome and numerous linear and circular plasmids. Long-term culture of B. burgdorferi results in a loss of some plasmids and changes in expressed proteins. The loss of plasmids results in the organism’s loss of ability to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.
Cultivation
Unlike Treponema pallidum, Borrelia burgdorferi can be cultivated in vitro. However, the bacterium is fastidious and requires a very complex growth medium. The medium used to grow Borrelia burgdorferi is called Barbour-Stoenner-Kelly (BSK) medium. It contains over thirteen ingredients in a rabbit serum base. Borrelia burgdorferi has an optimal temperature for growth of 32oC, in a microaerobic environment. Even under optimal conditions, the generation time is slow, about 12-24 hours. Borreliae from ticks and from the blood, skin, and cerebrospinal fluid of Lyme disease patients have been successfully cultivated in BSK medium. BSK solidified with 1.3% agarose allows the production of colonies from single organisms.
Outer Surface Proteins The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) and are thought to play a role in virulence. Osp A and Osp B are by far the most abundant outer surface
proteins.
Pathogenicity
B. burgdorferi invades the blood and tissues of various infected mammals and birds. The natural reservoir for B. burgdorferi is thought to be the white-footed mouse. Ticks transfer the spirochetes to the white-tailed deer, humans, and other warm-blooded animals after a blood meal on an infected animal. In humans, dogs, and many other animals, the infection with
B. burgdorferi results in the pathology of Lyme disease.
Transmission and Epidemiology Reports of Lyme disease have increased dramatically to the point that the disease has become an important public health problem in some areas of the United States. Today, Lyme disease is the most prevalent tick-borne illness in the United States. Lyme disease is spread through the bite of a blacklegged tick (Ixodes scapularis or Ixodes pacificus) that is infected with Borrelia burgdorferi. In the United States, most infections occur in the following endemic areas:
• Northeast and mid-Atlantic, from northeastern Virginia to Maine
• North central states, mostly in Wisconsin and Minnesota
• West Coast, particularly northern California Maps showing the distribution of human cases are based on where people live, which because of travel, is not necessarily where they became infected. Cases are sometimes diagnosed and reported from an area where Lyme disease is not expected, but they are almost always travel-related. Incidence of Lyme Disease in the United States, 1991-2006. Lyme disease is the most prevalent tick-borne illness in the United States. In 2006, there were 19,931 new cases reported. Between 1996 and 2001 the average number was about 17,000 new cases per year but increased to near or above 20,000 new cases per year in 2002, probably due to increased surveillance and reporting. CDC Field mice are the most important animal reservoir. The nymphal stage of the tick feeds on infected mice and is the mostly likely to infect humans. Even though adult ticks are about twice as likely to carry the bacterial pathogen. This is because nymphal ticks are small and less likely to be noticed before the infection is transmitted. Deer are important in the maintenance of the disease because ticks feed and mate on them. The tick feeds three times during its life cycle. The first and second feedings, as a larva and then as a nymph, are usually on a field mouse. The third feeding, as an adult, is usually on a deer. These feedings are separated by several months and the ability of the spirochete to remain viable in the disease-tolerant field mice is crucial to maintaining the disease in the wild. On humans, the ticks usually attach from a perch on shrubs or grass. They do not feed for about 24 hours, and it usually requires 2 or 3 days of attachment before transfer of bacteria and infection occur. The three-stage life cycle of the Ixodes tick. From the American Lyme Disease Foundation
Symptoms and Signs The first symptom of Lyme disease is a characteristic “bull’s eye” rash that appears at the bite site. It is a red area that clears in the center as it expands to a final diameter of about 15 cm. This distinctive rash occurs in about 75% of the cases. Flulike symptoms appear in a couple of weeks as the rash fades. Antibiotics taken during this interval are very effective at limiting the disease. Classic bulls-eye rash (Erythema Migrans) caused by Borrelia.From the Hospital for Special Surgery
During a second phase, in the absence of effective treatment, there is often evidence that the heart is affected. In some cases, a pacemaker may become required if the heartbeat becomes extremely irregular. Incapacitating, chronic neurological symptoms, such as facial paralysis, meningitis, and encephalitis may be seen. In a third phase, months or years later, some patients develop arthritis that may affect them for years. Immune response to the prescence of the bacteria is probably the cause of joint damage. Many of the symptoms of long-term Lyme disease resemble those of later stages of syphilis, also caused by a spirochete. Diagnosis of Lyme disease depends partly on the symptoms and an index of suspicion based on the prevalence in the geographic area. It is recommended that serological tests must be interpreted in conjunction with clinical symptoms and the likelihood of exposure to infection. The initial ELISA or indirect fluorescent-antibody should be followed up and confirmed with a Western immunoblot test. Lyme symptoms can be confusing even to medical professionals and very difficult to diagnose. Treatment can be, and often is, long in coming, and in the meantime patients suffer. Tests are often inaccurate and not thoroughly conclusive. Symptoms manifest differently from patient to patient and depending on the stage of the disease. Not everyone who has Lyme disease develops the characteristic bull 's-eye rash, which is the commonly accepted evidence of the Borrelia infection, considered by many to be a classic Lyme symptom and indicating the need to move forward with treatment. Moreover, it is not yet known how long the Borrelia bacteria may lie dormant. Some people do not develop symptoms immediately after being infected, and some who have been exposed may never develop them. All these factors contribute to creating tricky grounds for a medical expert to reach a conclusive diagnosis. Due to the unfortunate combination of unreliable tests and the variety of symptoms, Lyme disease is frequently under-diagnosed and treatment delayed. It can be misdiagnosed as a number of other illnesses, such as multiple sclerosis, Chronic Fatigue Syndrome (CFS), Epstein-Barr virus, rheumatoid arthritis and even Alzheimer 's disease. Some Lyme experts estimate that up to fifty percent of patients diagnosed with autoimmune diseases have the Borrelia bacteria either as the cause of, or as a contributor to, their suffering. This is significant because Lyme can be treated with antibiotics. However, a misdiagnosed patient who is harboring undetected Lyme disease bacteria may go without treatment. Like CFS symptoms, indicants of a Lyme infection may include overall achiness, arthritic swelling of the knees and other joints, and crushing fatigue that is unrelieved with bed rest. However, Lyme does not only cause flu-like symptoms and severe joint pain.
Typically, the elimination organs are invaded: Kidneys, bladder, liver, skin and lymph glands. The Borrelia bacteria are capable of crossing the blood-brain barrier, affecting the brain. In addition, the heart can be affected. The Borrelia bacteria 's affect on the heart and the brain can cause an irregular heart beat, poor concentration, mood swings and depression.
• Cognitive symptoms include short-term memory loss, stammering, and the inability to finish a thought or comprehend a page of writing. Since these symptoms are also commonly associated with old age, they can easily be passed over by a doctor searching for a diagnosis. Again, treatment can be delayed.
• Cardiac symptoms such as arrhythmia, or an irregular heart beat, cause poor blood circulation especially to the extremities. Untreated cardiac symptoms are potentially dangerous and may lead to congestive heart failure. Additionally, patients commonly report some psychotic episodes, including hallucinations involving their sense of sight, smell and hearing. The list of symptoms is long and varied because the Borrelia bacteria affects every bodily system. Another factor making the disease hard to test for and diagnose is that negative clinical test results do not necessarily mean the patient is free of Lyme or its co-infections. The Borrelia burgdorferi bacteria are pleomorphic, which tends to complicate testing and treatment. The bacteria is capable of changing from its corkscrew or spiral shape into two, three, or more different shapes. It appears to do so in order to protect itself in a hostile environment, specifically, the body’s immune system and antibiotic therapy.
Although every case is different, if symptoms are left untreated, Lyme can be devastating. Unfortunately, the effect of a professional misdiagnoses results in many patients going untested for Lyme. Therefore, they remain untreated and their symptoms worsen.
However, some people who have the disease do not develop symptoms immediately after being infected. It may take years for some people to become symptomatic. Some who have been exposed may never develop Lyme disease symptoms, and further, is not yet known how long the bacteria may lie dormant.
Diagnosis and Treatment Diagnosis of Lyme disease should be made solely on clinical symptoms and the presence of a tick bite, and not blood tests, which can often give false results if performed in the first month after initial infection. Later on blood tests are considered more reliable. Antibiotics such as doxycycline or amoxicillin are administered for 3-4 weeks early in the disease. Cefuroxime, axetil or erythromycin are used for those who are allergic to penicillin or who can not take tetracylines. In the late stage of the disease patients may require treatment with intravenous ceftriaxone or penicillin for 4 or more weeks depending on disease severity. Most cases of Lyme Disease that are treated with antibiotics after the first few weeks of initial infection almost always results in a full cure. Treatment that is begun after the first three weeks will also likely provide a cure, but the rate decreases after treatment is prolonged.
Tests and Diagnosis Currently, the recommended diagnostic tests for detecting Lyme disease are the Western Blot analysis, used to identify particular antibodies, and the ELISA, a general antibody test. Tests for the disease are unreliable. Negative clinical test results do not necessarily mean that the patient is free of Lyme or its co-infections. The bacteria appears to evade the body 's immune system, as it is capable of changing into two, three or more shapes as it spreads throughout the body. Unfortunately, it is common for people with Lyme to receive a misdiagnoses and thus remain untreated. The medical profession’s nickname for chronic Lyme disease is the Great Imitator, because symptoms mimic hundreds of other conditions including Multiple Sclerosis, Chronic Fatigue Syndrome, Epstein-Barr virus, and rheumatoid arthritis.
Lyme Treatment Lyme disease is treatable with antibiotics. However, the strength and length of prescription of antibiotics is at the core of controversy in the medical community. Antibiotics given immediately after infection seem to work for most Lyme patients. During later stages of the disease, some patients have responded to extended courses of antibiotics, but extended courses are not sanctioned by the Centers of Disease Control and Prevention (CDC) or the Infectious Diseases Society of America (IDSA). Current guidelines for treatment of Lyme published by the International Lyme and Associated Diseases Society (ILADS) state that it is reasonable to continue antibiotic therapy, in some cases, beyond the arbitrary 30-day course recommended by the IDSA. Experts familiar with the complicated nature of diagnosing Lyme advise that if a person has had a tick bite, or exhibits symptoms characteristic of Lyme, they consult a Lyme literate medical doctor (LLMD) and begin treatment, even if test results are negative or pending.
Alternative Medicine Increasingly, LLMDs are treating patients successfully with alternative protocols, such as pharmaceutical and herbal antimicrobials combined, and other non-invasive methods, such as hyperbaric oxygen therapy. Further, doctors are seeing fewer cases of relapse in patients who are treated with some of these alternative protocols.
Prevention
Prevention of infection of B. burgdorferi includes avoiding tick habitats such as brushy or overgrown grassy habitats especially in the spring and summer. When going into tick infested habitats wear light colored clothing so that ticks can be easily seen and removed. Wear long sleeve shirts and tuck pants into socks or boot tops. Wear rubber boots since ticks tend to be located closer to the ground.
Repel Ticks with DEET or Permethrin
• Use repellents that contain 20% or more DEET (N, N-diethyl-m-toluamide) on the exposed skin for protection that lasts up to several hours. Always follow product instructions. Parents should apply this product to their children, avoiding hands, eyes, and mouth.
• Use products that contain permethrin on clothing. Treat clothing and gear, such as boots, pants, socks and tents. It remains protective through several washings. Pre-treated clothing is available and remains protective for up to 70 washings.
• Other repellents registered by the Environmental Protection Agency (EPA) may be found at http://cfpub.epa.gov/oppref/insect/.
Preventing Ticks on Your Pets Dogs are very susceptible to tick bites and tickborne diseases. Vaccines are not available for all the tickborne diseases that dogs can get, and they don’t keep the dogs from bringing ticks into your home. For these reasons, it’s important to use a tick preventive product on your dog. Tick bites on dogs may be hard to detect. Signs of tickborne disease may not appear for 7-21 days or longer after a tick bite, so watch your dog closely for changes in behavior or appetite if you suspect that your pet has been bitten by a tick.
To reduce the chances that a tick will transmit disease to you or your pets:
• Check your pets for ticks daily, especially after they spend time outdoors.
• If you find a tick on your dog, remove it right away.
• Ask your veterinarian to conduct a tick check at each exam.
• Talk to your veterinarian about tickborne diseases in your area. Reduce tick habitat in your yard.
• Talk with your veterinarian about using tick preventives on your pet.
References
Brown University: Vector
Casjens, Sherwood, et al. 2000. A bacterial genome in flux: the twelve linear and nine circular extrachromasomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burdorferi. Molecular Microbiology, 35: 490-516.
Eggers, Christian H., et al. 2001. Transduction by phiBB-1, a bacteriophage of Borrelia Burdorferi. American Society for Microbiology, vol. 183: 4771-4778.
EUCALB: The Spirochete Borrelia Strains
Fraser, Claire M. et al. 1997. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature, vol. 390: 580-586.
EUCALB: The Spirochete Borrelia Strains
Health and Age: Lyme Disease and Related Tick-Borne Infection
Hospital for Special Surgery, Rheumatology Division: Lyme Disease of the Nervous System, Tracking the Elusive Spirochete
Hospital for Special Surgery, Rheumatology Division: Lyme Disease
National Center for Biotechnology Information: Borrelia burgdorferi
NCBI Coffee Break: What Do Lyme Disease and Syphilis Have in Common
Pichon B, Rogers M, Egan D, Gray J. "Blood-meal analysis for the identification of reservoir hosts of tick-borne pathogens in Ireland." Vector Borne Zoonotic Dis. 2005 Summer;5(2):172-180.
The Lyme Disease Guide: Tick Life Cycle
Samuels DS; Radolf, JD (2010). Borrelia: Molecular Biology, Host Interaction and Pathogenesis http://www.brown.edu/Courses/lyme_disease/organism.htm http://www.cdc.gov/ncidod/dvbid/lyme/index.htm http://www.cdc.gov/ncidod/dvbid/lyme/ld_Borreliaburgdorferi.htm http://emedicine.medscape.com/article/786767-overview
Overview:
Lyme disease was first recognized in the United States in 1975 by Dr. Allen Steere, following a mysterious outbreak of juvenile rheumatoid arthritis near the community of Lyme, Connecticut. The rural location of the Lyme outbreak and the onset of illness during summer and early fall suggested that the transmission of the disease was by an arthropod vector. Adult female Ixodes tick (deer tick) From Brown University In 1982, the causative agent of Lyme disease was discovered by Willy Burgdorfer, who isolated spirochetes belonging to the genus Borrelia from the mid-guts of the species Ixodes ticks. Spirochettes are pleomorphic. They appear spiral-shaped, but have evolved the capacity to hide …show more content…
in cysts and colonies, changing into a round ball and then back into a spiral. Lyme experts believe this is the way the bacteria move through the tissues and bloodstreams of the body.
Burgdorfer showed that these spirochetes reacted with immune serum from patients that had been diagnosed with Lyme disease. Subsequently, the etiologic agent was given the name Borrelia burgdorferi.
Classification
Domain: Bacteria Phylum: Spirochaetes Order: Spirochaetales Family: Spirochaetaceae Genus: Borrelia Species Borrelia burgdorferi
Strains of Borrelia
The borreliae causing Lyme disease are divided into several "genospecies", three of which have been firmly established and are well accepted:
I. Borrelia burgdorferi sensu stricto
II. Borrelia garinii
III. Borrelia afzelii
Disease
Lyme disease usually presents with a characteristic “bull’s eye rash”, erythema migrans, along with fever, fatigue, headache, muscle aches, and joint aches. The incubation period from infection to onset of the rash is typically 1-2 weeks. Some patients may be asymptomatic and present with only non-specific symptoms. B. burgdorferi is spread from the site of the tick bite through the blood stream. There are three clinical stages of Lyme disease: 1) the Localized Early (Acute) Stage, 2) the Early Disseminated Stage and 3) the Late Stage. The acute stage is characterized by a solid red or bull’s eye rash at the site of the bite, swelling of the lymph glands near the bite, generalized achiness and headache. The early disseminated stage is characterized by two or more; rashes not at the site of the bite, migrating pains in joints/tendons, headache, stiff neck, facial paralysis, tingling or numbness in the extremities, multiple enlarged lymph glands, abnormal pulse, sore throat, changes in vision, fever of 100 to 102 F, and severe fatigue. The late stage is characterized by arthritis of one or two large joints, disabling neurological disorders, and numbness in the extremities.
Biology of Spirochetes Borrelia burgdorferi, like the human pathogen Treponema pallidum, is a spirochete. Spirochetes are a group of phylogenetically-distinct bacteria that have a unique mode of motility by means of axial filaments (endoflagella). Spirochetes are widespread in viscous environments and are found in the intestinal tracts of animals and the oral cavity of humans. The spirochetes have a unique cell surface which accompanies their unique type of motility. The endoflagella are contained within the periplasmic space between a semi rigid peptidoglycan helix and a multi-layer, flexible outer membrane sheath. When the filaments rotate within this space, the spirochetes move in cork-screw fashion. This type of movement is thought to be an adaptation to viscous environments, such as aquatic sediments, biofilms, mucosal tissues and the intestinal tracts of animals. For pathogens, this allows the spirochetes to hide their flagella, which are normally antigenic, from the host immune defenses. Spirochetes are usually much longer than they are wide, and often their width is below the resolving power of the light microscope. Therefore, most spirochetes cannot be viewed using conventional light microscopy. Dark-field microscopy must be used to view spirochetes. Dark field microscopy utilizes a special condenser which directs light toward an object at a angle, rather than from the bottom. As a result, particles or cells are seen as light objects against a dark background. B. burgdorferi dark field illumination. American society for Microbiology. The spirochetes are not classified as either Gram-positive or Gram-negative. When Borrelia burgdorferi is Gram-stained, the cells stain a weak Gram-negative by default, as safranin is the last dye used. Borrelia, like most spirochetes, does have an outer membrane that contains an LPS-like substance, an inner membrane, and a periplasmic space which contains a layer of peptidoglycan. Therefore, it has a Gram-negative bacterial type cell wall, despite its staining characteristics.
Cell Structure and Metabolism B.
burgdorferi is a helical shaped spirochete bacterium. It has an inner and outer membrane as well as a flexible cell wall. Inside the bacteria 's cell membranes is the protoplasm, which, due to the spiral shape of the bacteria, is long and cylindrical. Spirochete bacteria such as B. burgdorferi have a unique structural characteristic. The cell 's flagella are located inside the periplasm between the inner and outer cell membranes. The interactions between the flagella and cell cylinder allows the cell to travel through highly viscous fluids and materials. This adaptation is especially critical for the ability of B. burgdorferi to travel through the tissue of its infected host or vector, causing it to be highly …show more content…
invasive. Structure of Borrelia burgdorferi, Reprinted by permission from Nature Publishing Group: Nature Reviews Microbiology, copyright 2005 Another important cellular component of B. burgdorferi is its outer surface proteins. Researchers have investigated a variety of outer membrane surface proteins (Osp) and have found them to play important roles in transmission of the bacteria. The cell expresses different surface proteins, most notably OspA and OspC. When the bacteria is inside of an unfed tick, it produces mostly OspA. However, the bacteria that are inside of infected mammals express mostly OspC . This has led to the speculation that the bacteria produce specific outer surface proteins in order to successfully invade and inhabit certain organisms. For example, OspA may function to retain the bacteria in the tick stomach, while the presence of OspC may encourage the bacteria to enter the salivary glands and enter the host. OspA, OspC, and other outer surface proteins may play important roles in the ability of the bacteria to infect and survive inside their hosts. The genome sequencing of B. burgdorferi showed that it has genes for metabolism similar to other parasites. These bacteria have limited metabolic capabilities and rely on their host for energy. In ticks, it is believed that N-acetylglucosamine (NAG) is a major energy source as it is a main component of tick cuticle and is essential for in vitro growth of the bacteria. It produces ATP solely by using substrate-level phosphorylation and achieves reducing power using the pentose phosphate pathway.
Microbial Characteristics, Virulence and Pathogenicity B. burgdorferi can be cultivated on a modified medium. The spirochete grows more slowly than most other bacteria dividing once after 12-24 hours. B. burgdorferi resembles other spirochetes in that it is a highly specialized, motile, two-membrane, spiral-shaped bacteria which lives primarily as an extracellular pathogen. One of the most striking features of B.
burgdorferi as compared with other bacteria is its unusual genome, which includes a linear chromosome and numerous linear and circular plasmids. Long-term culture of B. burgdorferi results in a loss of some plasmids and changes in expressed proteins. The loss of plasmids results in the organism’s loss of ability to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.
Cultivation
Unlike Treponema pallidum, Borrelia burgdorferi can be cultivated in vitro. However, the bacterium is fastidious and requires a very complex growth medium. The medium used to grow Borrelia burgdorferi is called Barbour-Stoenner-Kelly (BSK) medium. It contains over thirteen ingredients in a rabbit serum base. Borrelia burgdorferi has an optimal temperature for growth of 32oC, in a microaerobic environment. Even under optimal conditions, the generation time is slow, about 12-24 hours. Borreliae from ticks and from the blood, skin, and cerebrospinal fluid of Lyme disease patients have been successfully cultivated in BSK medium. BSK solidified with 1.3% agarose allows the production of colonies from single organisms.
Outer Surface Proteins The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) and are thought to play a role in virulence. Osp A and Osp B are by far the most abundant outer surface
proteins.
Pathogenicity
B. burgdorferi invades the blood and tissues of various infected mammals and birds. The natural reservoir for B. burgdorferi is thought to be the white-footed mouse. Ticks transfer the spirochetes to the white-tailed deer, humans, and other warm-blooded animals after a blood meal on an infected animal. In humans, dogs, and many other animals, the infection with
B. burgdorferi results in the pathology of Lyme disease.
Transmission and Epidemiology Reports of Lyme disease have increased dramatically to the point that the disease has become an important public health problem in some areas of the United States. Today, Lyme disease is the most prevalent tick-borne illness in the United States. Lyme disease is spread through the bite of a blacklegged tick (Ixodes scapularis or Ixodes pacificus) that is infected with Borrelia burgdorferi. In the United States, most infections occur in the following endemic areas:
• Northeast and mid-Atlantic, from northeastern Virginia to Maine
• North central states, mostly in Wisconsin and Minnesota
• West Coast, particularly northern California Maps showing the distribution of human cases are based on where people live, which because of travel, is not necessarily where they became infected. Cases are sometimes diagnosed and reported from an area where Lyme disease is not expected, but they are almost always travel-related. Incidence of Lyme Disease in the United States, 1991-2006. Lyme disease is the most prevalent tick-borne illness in the United States. In 2006, there were 19,931 new cases reported. Between 1996 and 2001 the average number was about 17,000 new cases per year but increased to near or above 20,000 new cases per year in 2002, probably due to increased surveillance and reporting. CDC Field mice are the most important animal reservoir. The nymphal stage of the tick feeds on infected mice and is the mostly likely to infect humans. Even though adult ticks are about twice as likely to carry the bacterial pathogen. This is because nymphal ticks are small and less likely to be noticed before the infection is transmitted. Deer are important in the maintenance of the disease because ticks feed and mate on them. The tick feeds three times during its life cycle. The first and second feedings, as a larva and then as a nymph, are usually on a field mouse. The third feeding, as an adult, is usually on a deer. These feedings are separated by several months and the ability of the spirochete to remain viable in the disease-tolerant field mice is crucial to maintaining the disease in the wild. On humans, the ticks usually attach from a perch on shrubs or grass. They do not feed for about 24 hours, and it usually requires 2 or 3 days of attachment before transfer of bacteria and infection occur. The three-stage life cycle of the Ixodes tick. From the American Lyme Disease Foundation
Symptoms and Signs The first symptom of Lyme disease is a characteristic “bull’s eye” rash that appears at the bite site. It is a red area that clears in the center as it expands to a final diameter of about 15 cm. This distinctive rash occurs in about 75% of the cases. Flulike symptoms appear in a couple of weeks as the rash fades. Antibiotics taken during this interval are very effective at limiting the disease. Classic bulls-eye rash (Erythema Migrans) caused by Borrelia.From the Hospital for Special Surgery
During a second phase, in the absence of effective treatment, there is often evidence that the heart is affected. In some cases, a pacemaker may become required if the heartbeat becomes extremely irregular. Incapacitating, chronic neurological symptoms, such as facial paralysis, meningitis, and encephalitis may be seen. In a third phase, months or years later, some patients develop arthritis that may affect them for years. Immune response to the prescence of the bacteria is probably the cause of joint damage. Many of the symptoms of long-term Lyme disease resemble those of later stages of syphilis, also caused by a spirochete. Diagnosis of Lyme disease depends partly on the symptoms and an index of suspicion based on the prevalence in the geographic area. It is recommended that serological tests must be interpreted in conjunction with clinical symptoms and the likelihood of exposure to infection. The initial ELISA or indirect fluorescent-antibody should be followed up and confirmed with a Western immunoblot test. Lyme symptoms can be confusing even to medical professionals and very difficult to diagnose. Treatment can be, and often is, long in coming, and in the meantime patients suffer. Tests are often inaccurate and not thoroughly conclusive. Symptoms manifest differently from patient to patient and depending on the stage of the disease. Not everyone who has Lyme disease develops the characteristic bull 's-eye rash, which is the commonly accepted evidence of the Borrelia infection, considered by many to be a classic Lyme symptom and indicating the need to move forward with treatment. Moreover, it is not yet known how long the Borrelia bacteria may lie dormant. Some people do not develop symptoms immediately after being infected, and some who have been exposed may never develop them. All these factors contribute to creating tricky grounds for a medical expert to reach a conclusive diagnosis. Due to the unfortunate combination of unreliable tests and the variety of symptoms, Lyme disease is frequently under-diagnosed and treatment delayed. It can be misdiagnosed as a number of other illnesses, such as multiple sclerosis, Chronic Fatigue Syndrome (CFS), Epstein-Barr virus, rheumatoid arthritis and even Alzheimer 's disease. Some Lyme experts estimate that up to fifty percent of patients diagnosed with autoimmune diseases have the Borrelia bacteria either as the cause of, or as a contributor to, their suffering. This is significant because Lyme can be treated with antibiotics. However, a misdiagnosed patient who is harboring undetected Lyme disease bacteria may go without treatment. Like CFS symptoms, indicants of a Lyme infection may include overall achiness, arthritic swelling of the knees and other joints, and crushing fatigue that is unrelieved with bed rest. However, Lyme does not only cause flu-like symptoms and severe joint pain.
Typically, the elimination organs are invaded: Kidneys, bladder, liver, skin and lymph glands. The Borrelia bacteria are capable of crossing the blood-brain barrier, affecting the brain. In addition, the heart can be affected. The Borrelia bacteria 's affect on the heart and the brain can cause an irregular heart beat, poor concentration, mood swings and depression.
• Cognitive symptoms include short-term memory loss, stammering, and the inability to finish a thought or comprehend a page of writing. Since these symptoms are also commonly associated with old age, they can easily be passed over by a doctor searching for a diagnosis. Again, treatment can be delayed.
• Cardiac symptoms such as arrhythmia, or an irregular heart beat, cause poor blood circulation especially to the extremities. Untreated cardiac symptoms are potentially dangerous and may lead to congestive heart failure. Additionally, patients commonly report some psychotic episodes, including hallucinations involving their sense of sight, smell and hearing. The list of symptoms is long and varied because the Borrelia bacteria affects every bodily system. Another factor making the disease hard to test for and diagnose is that negative clinical test results do not necessarily mean the patient is free of Lyme or its co-infections. The Borrelia burgdorferi bacteria are pleomorphic, which tends to complicate testing and treatment. The bacteria is capable of changing from its corkscrew or spiral shape into two, three, or more different shapes. It appears to do so in order to protect itself in a hostile environment, specifically, the body’s immune system and antibiotic therapy.
Although every case is different, if symptoms are left untreated, Lyme can be devastating. Unfortunately, the effect of a professional misdiagnoses results in many patients going untested for Lyme. Therefore, they remain untreated and their symptoms worsen.
However, some people who have the disease do not develop symptoms immediately after being infected. It may take years for some people to become symptomatic. Some who have been exposed may never develop Lyme disease symptoms, and further, is not yet known how long the bacteria may lie dormant.
Diagnosis and Treatment Diagnosis of Lyme disease should be made solely on clinical symptoms and the presence of a tick bite, and not blood tests, which can often give false results if performed in the first month after initial infection. Later on blood tests are considered more reliable. Antibiotics such as doxycycline or amoxicillin are administered for 3-4 weeks early in the disease. Cefuroxime, axetil or erythromycin are used for those who are allergic to penicillin or who can not take tetracylines. In the late stage of the disease patients may require treatment with intravenous ceftriaxone or penicillin for 4 or more weeks depending on disease severity. Most cases of Lyme Disease that are treated with antibiotics after the first few weeks of initial infection almost always results in a full cure. Treatment that is begun after the first three weeks will also likely provide a cure, but the rate decreases after treatment is prolonged.
Tests and Diagnosis Currently, the recommended diagnostic tests for detecting Lyme disease are the Western Blot analysis, used to identify particular antibodies, and the ELISA, a general antibody test. Tests for the disease are unreliable. Negative clinical test results do not necessarily mean that the patient is free of Lyme or its co-infections. The bacteria appears to evade the body 's immune system, as it is capable of changing into two, three or more shapes as it spreads throughout the body. Unfortunately, it is common for people with Lyme to receive a misdiagnoses and thus remain untreated. The medical profession’s nickname for chronic Lyme disease is the Great Imitator, because symptoms mimic hundreds of other conditions including Multiple Sclerosis, Chronic Fatigue Syndrome, Epstein-Barr virus, and rheumatoid arthritis.
Lyme Treatment Lyme disease is treatable with antibiotics. However, the strength and length of prescription of antibiotics is at the core of controversy in the medical community. Antibiotics given immediately after infection seem to work for most Lyme patients. During later stages of the disease, some patients have responded to extended courses of antibiotics, but extended courses are not sanctioned by the Centers of Disease Control and Prevention (CDC) or the Infectious Diseases Society of America (IDSA). Current guidelines for treatment of Lyme published by the International Lyme and Associated Diseases Society (ILADS) state that it is reasonable to continue antibiotic therapy, in some cases, beyond the arbitrary 30-day course recommended by the IDSA. Experts familiar with the complicated nature of diagnosing Lyme advise that if a person has had a tick bite, or exhibits symptoms characteristic of Lyme, they consult a Lyme literate medical doctor (LLMD) and begin treatment, even if test results are negative or pending.
Alternative Medicine Increasingly, LLMDs are treating patients successfully with alternative protocols, such as pharmaceutical and herbal antimicrobials combined, and other non-invasive methods, such as hyperbaric oxygen therapy. Further, doctors are seeing fewer cases of relapse in patients who are treated with some of these alternative protocols.
Prevention
Prevention of infection of B. burgdorferi includes avoiding tick habitats such as brushy or overgrown grassy habitats especially in the spring and summer. When going into tick infested habitats wear light colored clothing so that ticks can be easily seen and removed. Wear long sleeve shirts and tuck pants into socks or boot tops. Wear rubber boots since ticks tend to be located closer to the ground.
Repel Ticks with DEET or Permethrin
• Use repellents that contain 20% or more DEET (N, N-diethyl-m-toluamide) on the exposed skin for protection that lasts up to several hours. Always follow product instructions. Parents should apply this product to their children, avoiding hands, eyes, and mouth.
• Use products that contain permethrin on clothing. Treat clothing and gear, such as boots, pants, socks and tents. It remains protective through several washings. Pre-treated clothing is available and remains protective for up to 70 washings.
• Other repellents registered by the Environmental Protection Agency (EPA) may be found at http://cfpub.epa.gov/oppref/insect/.
Preventing Ticks on Your Pets Dogs are very susceptible to tick bites and tickborne diseases. Vaccines are not available for all the tickborne diseases that dogs can get, and they don’t keep the dogs from bringing ticks into your home. For these reasons, it’s important to use a tick preventive product on your dog. Tick bites on dogs may be hard to detect. Signs of tickborne disease may not appear for 7-21 days or longer after a tick bite, so watch your dog closely for changes in behavior or appetite if you suspect that your pet has been bitten by a tick.
To reduce the chances that a tick will transmit disease to you or your pets:
• Check your pets for ticks daily, especially after they spend time outdoors.
• If you find a tick on your dog, remove it right away.
• Ask your veterinarian to conduct a tick check at each exam.
• Talk to your veterinarian about tickborne diseases in your area. Reduce tick habitat in your yard.
• Talk with your veterinarian about using tick preventives on your pet.
References
Brown University: Vector
Casjens, Sherwood, et al. 2000. A bacterial genome in flux: the twelve linear and nine circular extrachromasomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burdorferi. Molecular Microbiology, 35: 490-516.
Eggers, Christian H., et al. 2001. Transduction by phiBB-1, a bacteriophage of Borrelia Burdorferi. American Society for Microbiology, vol. 183: 4771-4778.
EUCALB: The Spirochete Borrelia Strains
Fraser, Claire M. et al. 1997. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature, vol. 390: 580-586.
EUCALB: The Spirochete Borrelia Strains
Health and Age: Lyme Disease and Related Tick-Borne Infection
Hospital for Special Surgery, Rheumatology Division: Lyme Disease of the Nervous System, Tracking the Elusive Spirochete
Hospital for Special Surgery, Rheumatology Division: Lyme Disease
National Center for Biotechnology Information: Borrelia burgdorferi
NCBI Coffee Break: What Do Lyme Disease and Syphilis Have in Common
Pichon B, Rogers M, Egan D, Gray J. "Blood-meal analysis for the identification of reservoir hosts of tick-borne pathogens in Ireland." Vector Borne Zoonotic Dis. 2005 Summer;5(2):172-180.
The Lyme Disease Guide: Tick Life Cycle
Samuels DS; Radolf, JD (2010). Borrelia: Molecular Biology, Host Interaction and Pathogenesis http://www.brown.edu/Courses/lyme_disease/organism.htm http://www.cdc.gov/ncidod/dvbid/lyme/index.htm http://www.cdc.gov/ncidod/dvbid/lyme/ld_Borreliaburgdorferi.htm http://emedicine.medscape.com/article/786767-overview