Bacteria, Viruses and Health
Organism, Transmission and Disease
Lyme disease is caused by the bacterium Borrelia burgdorferi in the United States, as well as Borrelia afzelii and Borrelia garinii in Europe. About 90% of the time it is transmitted through the bites of nymph ixodes ticks, more commonly known as deer ticks. Ticks are opportunistic, parasitic, arthropods that feed on the blood of their hosts. During a blood meal with a Lyme infected animal or human, the bacteria is transmitted from the host’s bloodstream into the tick’s stomach. The tick then becomes a mechanical vector of disease. During the next feeding, the B. burgdorferi spirochetes are transmitted between the tick and its host, passing on the bacteria and continuing its life cycle in a new host. This is a very effective method of transmission. ”The ticks’ saliva has components which disrupt the normal immune response to a bite and which afford protection to the infectious spirochaetes allowing them to establish themselves in the local area.” (Matthews, 2011)
An image demonstrating the size of a ixodes deer tick in its nymph stage when it is most likely to transmit B. burgdorferi bacteria to its host(s). Some ticks in their nymph stage are as small as the period at the end of a sentence.
Picture of a deer tick. N.d. MedicineNet. Web. 21 Mar. 2012.
Lyme disease pathology – infection with Borrelia burgdorferi sensu lato
Lyme disease pathology borellia bacteria infection. N.d. Lyme disease Guide. Web. 21 Mar. 2012.
This disease was first noted in 1975 in Lyme, Connecticut, a small, very rural town. Resident mothers received diagnoses of rheumatoid arthritis in their children, all of whom lived in close proximity of one another. The mothers reached out to researchers from Yale who noted the statistically improbable, unusual, grouping of cases occurring in this small, rural town. The investigation led Dr. Allen Steer, M.D. and his researchers to the discovery of the borrelial organism responsible for the illness officially designated as Lyme disease in 1982. They traced the cutaneous manifestations post tick bite inoculation, and their antibiotic responsiveness to the 1950s literature written by European researchers. The organism in the European literature was a different strain (B. afzelii) of the borrelial organism which was confirmed as the causative agent in the Connecticut epidemic. However, this was not the first literary incidence of the bacteria B. burgdorferi. In 1883, German physician Alfred Buchwald first described the dermatological manifestation known as acrodermatitis chronic atrophicans (ACA). In 1912, Swedish dermatologist Arvid Afzelius first described the “bull’s-eye” rash, erythema chronicum migrans (ECM) which is now known as erythema migrans. “In the 1920s, [Dr. Charles] Garin and [Dr. A.] Bujadoux described a patient with meningoencephalitis, painful sensory radiculitis, and erythema migrans following a tick bite, and they postulated the symptoms were due to a spirochetal infection. The neurologic manifestations and the association with lxodes ticks (also known as deer ticks) were recognized by the mid 1930s and were known as tick-borne meningoencephalitis. In the 1940s, [Dr. Alfred] Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythamatous skin lesions.” (Medscape, 2011)
Clinical manifestations of Lyme disease consist of:
- Acute Erythema Migrans Rash or the “bull’s-eye” rash appears within 24-48 hours. Cutaneous inflammation surrounds the initial site of the bite, then clears, with another circular pattern of inflammation in the localized area. However more than 1 in 4 patients never develop a rash in this stage.
Lyme disease initially affects the skin, causing an expanding reddish rash similar to a target or a bulls-eye
Lyme disease rash N.d. MedicineNet. Web. 21 Mar. 2012.
- Subacute flu-like syndrome with fever, general malaise, stiff neck, headache, and diffuse aches and pains in the early dissemination stage.
- In some, bacterial dissemination will result in a multicentric erythema migrans.
- Fewer than 5% of patients will develop cardiac conduction abnormalities.
- Others may develop a mild hepatitis or myositis, whereas some will develop arthralgias or frank arthritis.
- 10% to 15% of patients will develop nervous system involvement that typically consists of all or part of the triad of lymphocytic meningitis, cranial neuritis, and painful radiculitis.
- Late stage involvement may also cause chronic Lyme arthritis in the joints (particularly the knees), neurological symptoms consisting of facial palsies, confusion, numbness, pain or weakness in the limbs (peripheral neuropathy and peripheral radiculopathy), poor motor coordination, and heart problems which manifest as arrhythmias, palpitations, lightheadedness, fainting, chest pain, shortness of breath and heart failure.
(Halperin and Roos, 2011), (University of Maryland Medical Center, 2011)
“Variation in environmental and host conditions promotes different gene expression and changes in the composition of the membrane proteins of the spirochete. This adaptation is a critical step in the pathogenesis and transmission of Lyme disease.” (Medscape, 2011) During transmission, spirochetes take advantage of the protein plasmin found in ticks’ saliva. This protein prevents the first line of defenses, neutrophils, from congregating in the affected area. “The plasmin confounds the immune system’s efforts which are further obstructed by the spirochaetes ability to reduce the expression of surface proteins that would be targeted by such [B. burgdorferi] antibodies. This avoidance of detection involves alterations in the VIsE surface protein which effectively inactivates certain immune system components.” (Matthews, 2011) B. burgdorferi may also make it complicated for the immune system to target by positioning itself inconspicuously in the extracellular matrix.
Early Disseminated Lyme Disease Pathology
Over the days and weeks after a bite from an infected tick, the spirochaetes slowly enter the bloodstream from where they can gain access to almost every tissue in the body through the circulation. Infection can then spread quickly through the system and cause symptoms at places far away from the initial tick bite. The erythema migrans rash may now arise in other locations on the body as well as the original location as the spirochaetes cause other localised inflammation. Once again, the body’s normal response leading to the elimination of the spirochaetes through the action of neutrophils is inhibited by the pathogen’s use of the protease plasmin from the ticks’ saliva. The Borrelia bacteria are also adept at other tactics to avoid detection by the immune system. These tactics employed by the Lyme disease bacteria have potential ramifications for the development of autoimmune complications. Exposure to the spirochaetes creates a chronic inflammatory response which may begin to damage ordinary bodily tissues due to molecular mimicry employed by the bacteria to avoid detection. In their imitation of normal body cells the bacteria can confuse the immune system into attacking ordinary body tissues which goes some way to explaining the chronic symptoms of Lyme disease experienced by some patients even after eradication of the infection by antibiotics. Where the immune system has produced antibodies against its own cells it will continue to attack these cells even in the absence of the Borrelia bacteria, leading to persistent symptoms including joint pain. Effectively, Lyme disease may induce an autoimmune condition similar to rheumatoid arthritis which persists even after the causative agent, the Borrelia bacteria, is removed.
A Multisystem Effect
Borrelia burgdorferi s.l. infection creates multiple symptoms due to it multisytem effects. In a large number of those infected, the symptoms only go as far as an acute flu-like illness which is effectively fought by the body and which leads to no other persistent effects from the tick bite. Stage II, early disseminated Lyme disease, involves the cardiovascular system and/or the central nervous system, leading to myocarditis, meningoencephalitis, and polyradiculitis. The levels of inflammation during this stage are much higher in these tissues than anywhere else in the early acute stage and can lead to significant tissue damage if the infection continues unchecked. Progression into Stage III Lyme disease involves more bodily systems, including the joints, and exerts more serious effects such as dementia and transverse myelitis.
- L. Matthews, 2011
For the most part, rural areas provide the proper environment for deer ticks to thrive. Lyme endemic areas are mostly concentrated in the Northeastern United States but are also predominantly found in the Midwest and Pacific Northwest of the continental U.S. Colorado, Wyoming, Hawaii, Oklahoma, and South Dakota have the least cases reported according to the CDC in 2010, but Lyme has been reported in all 50 states. “Epidemiologic data suggest that the actual incidence of Lyme disease could be as much as 10 times higher than the CDC data indicate. This is probably a result of a restrictive case definition from the CDC, inevitable misdiagnosis, and the fact that physicians tend to underreport reportable diseases of all kinds.” (Medscape, 2011)
Lyme disease found in United States. N.d. MedicineNet. Web. 21 Mar. 2012.
On a global scale, Lyme disease can be found in Canada, Scandinavia, Central Europe, Southern Europe, Western Europe, Russia, Japan, China and have even been reported in Australia.
Diagnosis begins with the observation of the skin for the erythema migrans rash that is typical in 70% to 80% of patients. However, many patients cannot recall being bitten by a tick due to their size and the location of the bite. For instance, a bite on the scalp can easily allow the tick to feed on its host without the host being aware of its presence. After considering the history of present illness, and ruling out other conditions during physical examination, the differential diagnosis can include other tick-borne illnesses such a babesiosis, Rocky Mountain Spotted Fever, “Spotless” Rocky Mountain Spotted Fever, bartonellosis, anaplasmosis, mycoplasmosis and ehrlichiosis which may be present as secondary and tertiary coinfections from the same bite. The differential diagnosis also can include autoimmune, rheumatoid, neurologic, and cardiac conditions, viral infections, and even clinical depression due to the array of nonspecific symptoms. To confirm or rule out a Lyme diagnosis, there are several diagnostic tests that can be done. Blood samples are subjected to ELISA or enzyme-linked immunosorbent assay and the Western Blot tests to detect B. burgdorferi antibodies but both tests can also provide false positive or false negative results so an ELISA is first performed and then confirmed with the Western blot test. Cerebrospinal fluid, urine, and fluid drawn from an infected joint can also be evaluated for IgG antibodies. Synovial fluid, which is drawn from the knee arthroscopically, can be subjected to a PCR or polymerase chain reaction test which detects bacterial DNA in the fluid. Positive serology is confirmed by a 2-tiered testing approach. “In patients with positive serologies and atypical disorders, or with negative serologies and typical syndromes, the diagnosis is possible but must be entertained with caution.” (Halperin and Roos, 2011)
Treatment and Prognosis
Oral antibiotics such as Doxycycline (Vibramycin) are the usual treatment for Lyme disease. For more involved infections, intravenous antibiotics consisting of Cefuroxime (Ceftin), Penicillin, Amoxicillin, Ceftriaxone (Rocephin) and Amoxicillin/Clavulanate (Augmentin) are administered. Chronic Lyme Arthritis is not well understood but is accepted by most of the medical community. However, long-term administration of antibiotics is discouraged if symptoms persist due to the negative side effects outweighing the benefits of prolonged treatment. Generally speaking people who contract Lyme disease have a very good prognosis with proper treatment during the early stages. When Lyme goes undetected for long periods of time and is allowed to enter late stages of the disease it has more permanent effects on the body. The neurologic, cardiac, and musculoskeletal effects of the disease can have serious complications in patients especially if multisystem involvement is present. Memory, cognition, and concentration can also become particularly difficult for Lyme sufferers. Despite the wealth of knowledge regarding tick-borne illnesses in humans and animals, many doctors are not aware of how to help Lyme patients beyond the usual battery of diagnostics and prescribed antibiotic therapy. There is still much to be learned about this illness and its long-term consequences for patients. Prevention is always the best method of treatment and you can protect yourself and your family from ticks, Lyme disease and other tick-borne illnesses by wearing long pants and sleeves when walking through heavily wooded or grassy areas, using insect repellents with DEET, pyrethroids or Permethrin on yourself and children above 3 years of age, tick-proofing your yard by clearing woodpiles, brush and leaves where ticks live, and by thoroughly checking yourself and your family for ticks each time you spend a day outdoors.
Unfortunately there is no longer a vaccine to combat Lyme disease in humans, but there are Lyme vaccines for your family pets. In 1998 GlaxoSmithKline developed and released the human Lyme vaccine which was then pulled from the market in 2002 due to poor sales from lack of understanding of vaccination guidelines and side effects. However, the number of cases reported have been skyrocketing ever since and pharmaceutical manufacturers have yet to re-release it. This is a serious public health dilemma. “The vaccine was made from a single protein found on the surface of Borrelia burgdorferi, the bacterium that causes Lyme. When given to people, the vaccine prompted the production of antibodies that then entered ticks as they sucked vaccinated blood. Instead of killing pathogenic bacteria in the human body, like other vaccines do, these Lyme antibodies actually immunized the insects by killing bacteria in their bodies. The vaccine was shown to prevent Lyme in about 80 percent of exposed adults.” (Sohn, 2011) Due to the public outcry, “early clinical trials are underway for at least one new candidate vaccine. A combined phase 1/2 study is estimated to be completed in October 2013.” (The History of Lyme disease Vaccine, 2012)
Veterinary Testing, Vaccines and Prevention
A wide array of mammals are at risk of developing Lyme disease due to tick bite exposures. There have been many more advances in Lyme disease detection in the veterinary field and there are several diagnostic options available at this time. Depending upon the hypothetical or proposed timeline of tick bite inoculation, antibody titers which measure B. burgdorferi antibody levels, and multiplex testing which detect B. burgdorferi antigens in serum can be used. However, the most common testing for Lyme disease in companion animals such as canines consists of an in-house 4Dx Snap Test which can test serum, plasma or anticoagulated whole blood combined with conjugate for heartworm disease, ehrlichiosis, anaplasmosis and Lyme disease. ELISA, Western blot and PCR testing can be performed to rule out false positives and false negatives in the 4Dx tests. There is also an extremely effective vaccine for dogs which consists of a series of two killed, adjuvanted vaccine inoculations, given subcutaneously two weeks in succession of one another, and then it is continually boostered on an annual basis. There are also topical flea and tick repellent treatments for dogs and cats with varying mechanisms of action. Medicated shampoos and oral medications are more effective against fleas than ticks. In addition to topical treatments and vaccinations, physically checking your pets’ coat, underside and ears can help to reduce the incidence of Lyme disease and ensure that ticks are not being brought into your home.
CDC - Cases by State - Lyme disease. (n.d.). Centers for Disease Control and Prevention. Retrieved March 21, 2012, from http://www.cdc.gov/lyme/stats/chartstables/reportedcases_statelocality.html
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Littman, M., Goldstein, R., Labato, M., Lappin, M., & Moore, G. (n.d.). ACVIM Small Animal Consensus Statement on Lyme disease in Dogs: Diagnosis, Treatment, and Prevention. NC State College of Veterinary Medicine. Retrieved March 21, 2012, from www.cvm.ncsu.edu/vhc/documents/LymeconsstmtACVIM.pdf
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Lyme disease - MayoClinic.com. (n.d.). Mayo Clinic. Retrieved March 21, 2012, from http://www.mayoclinic.com/health/lyme-disease/DS00116/METHOD=print
Matthews, L. (n.d.). Lyme disease Pathology. Lyme disease. Retrieved March 21, 2012, from http://lymediseaseguide.org/lyme-disease-pathology
Sohn, E. (2011, June 17). Lyme disease: Where’s the Vaccine? : Discovery News. Discovery News: Earth, Space, Tech, Animals, History, Adventure, Human, Autos. Retrieved March 21, 2012, from http://news.discovery.com/human/lyme-disease-ticks-vaccine-110617.html
The American Animal Hospital Association. (n.d.). 2011 AAHA Canine Vaccination Guidelines. Retrieved March 21, 2012, from https://www.aahanet.org/PublicDocuments/CanineVaccineGuidelines.pdf
The History of the Lyme disease Vaccine - History of Vaccines. (n.d.). History of Vaccines - A Vaccine History Project of The College of Physicians of Philadelphia. Retrieved March 21, 2012, from http://www.historyofvaccines.org/content/articles/history-lyme-disease-vaccine