Lyme Disease, Everything You Need to Know

Lyme Disease is a bacterial infection caused by Borrelia burgdorferi. This disease is transmitted to humans by ticks. Lyme arthritis was recognized as a clinical manifestation in 1976. Researchers at Yale University investigated a cluster of arthritis in children from the three contiguous communities of Old Lyme, Lyme, and East Haddam, Connecticut. If left untreated it can spread to other organs and cause permanent damage to joints, heart and nervous system. Lyme disease is diagnosed based on symptoms, physical findings, and the possibility of exposure to infected ticks. Laboratory testing is required to confirm the presence of Borrelia burgdorferi in the system of the host. Most cases of Lyme disease can be treated successfully with a few weeks of antibiotics. Steps to prevent Lyme disease include using insect repellent, removing ticks promptly, landscaping, and integrated pest management.

Microbiology:

Borrelia burgdorferi is a Gram negative bacteria belonging to the group of spirochete. It is a highly specialized, motile, two-membrane, spiral-shaped bacteria which lives primarily as an extracellular pathogen. It can survive inside the host for months even years. It has an unusual genome which consists of linear chromosomes and many linear and circular plasmids. 21 different plasmids were found, which represents the largest known complement of plasmids of all bacteria and constitutes one third of the spirochete's DNA.

Laboratory testing has confirmed that most of the virulence of the bacteria is linked to plasmids. After growing bacteria in cultures, results have shown that Borrelia loses some it’s plasmids and was unable to contract the disease in the laboratory animals. Borrelias plasmids encode for certain genes that play major role in its virulence. Borrelia burgdorferi has show susceptibility to antibiotics in vitro, but has shown more resistance to antibiotics used in vivo. The subdivision of this group of closely related organisms into the four distinct species B. burgdorferi sensu stricto. B. garinii, B. afzelii, and B. japonica. are found in Europe. In North America, all isolates of B. burgdorferi belong to the same species B. burgdorferi sensu stricto.

Diagnosis:

Lyme disease is diagnosed based on certain symptoms which can be determined by physical findings and a history of possible exposure to infected ticks. Laboratory tests are helpful in confirming the infection by Borrelia burgdorferi but is not recommended if the patient has erythema migrans. Erithema migrans is a localized manifestation of Lyme disease in it’s earlier form. It is localized on the same spot where the tick bite has occurred in form of a red rash resembling a bulls eye.
Physicians should be careful when determining Lyme disease infection because the symptoms can be similar to other bacterial infections. Not all patients with Lyme disease will develop the characteristic bulls-eye rash, and many may not remember having a tick bite. Laboratory testing is not recommended for persons who do not have symptoms of Lyme disease.


Picture 2: Infectious Cycle of Borrelia burgdorferi

Laboratory testing:

Serologic tests are insensitive during the first 1 or 2 weeks of infection because B. burgdorferi has a very slow reproduction rate. Confirming the infection depends mostly on detection of a positive IgM response, which may still represent a false-positive response.
There are several test that can be used in determining Lyme disease but thy are not all validated yet. The tests that are proven to be most effective are the blood tests which determine the presence of antibodies made during contact with the bacteria. There are two test recommended by the Center for Disease Control and Prevention in the form of the Elisa and

ELISA test:

The first test is the ELISA, This is a rapid test where antibody or antigen is linked to an enzyme as a means of detecting a match between the antibody and antigen. An antigen is a substance that induces the production of antibodies because it is recognized by the body as a threat. Antigens can be chemicals, bacteria, viruses, or pollen. The test is widely used in the medical laboratory for determining Lyme disease. It allows testing of your blood with an antigen to see if your immune system recognizes it, or tests your blood with an antibody to see if a particular substance or antigen is present in your system. This test is very sensitive and is positive for everyone with Lyme disease and some people that don’t as well. IgM antibodies become detectable 3–4 weeks after the infection and reaches it’s peak after 6–8 weeks and decline over the next 4 months. IgG antibodies appear 6–8 weeks after the infection and remain detectable for many years. If the test proves positive another test is required to confirm the findings.

Western blot test:

A western blot or immunoblot is a method to detect protein in a given sample of tissue. It uses gel electrophoresis to separate denatured proteins by mass. The proteins are then transferred out of the gel and onto a membrane typically nitrocellulose, where they are "probed" using antibodies specific to the protein. As a result, the amount of protein can be examined in a given sample and compare levels between several groups. Samples are taken from either tissue or from cell culture. The samples are cooled or frozen rapidly. They are homogenized using sonication or mechanical force. Samples are boiled from one to five minutes in a buffer solution. The proteins of the sample are separated according to molecular weight using gel electrophoresis. In order to make the proteins accessible to antibody detection, they are moved from within the gel onto a membrane made of nitrocellulose. Dr. Nelson has stressed the importance of formation of tiny black blotches, which indicate the presence of B. burgdorferi.

Symptoms:

Lyme disease has many signs and symptoms, but skin signs, arthritis and/or various neurological symptoms are often present. Like syphilis, the symptoms frequently seem to resolve, yet the disease progresses. Conventional therapy is with antibiotics. People who suspect they have been exposed to Lyme disease should consult a doctor with knowledge of the disease immediately.

Early symptoms are expressed in the form of: Erythema migrans, fever, fatigue , headache and muscle and joint soreness.
The late symptoms manifest in the form of: Neuropathy, Bell’s palsy, rheumatoid arthritis and other autoimmune reactions.

Treatment:

The first 24–72 hours of tick attachment is necessary for transmission of the spirochete. Removal of the tick within 24 hours of attachment is enough for prevention of Lyme disease. If an engorged tick is found, a single, 200-mg dose of Doxycycline usually is enough to prevent the development of Lyme disease. There is a high chance of reinfection if the patient was treated with antibiotics in the first weeks. Flu-like illness during summer is a more difficult issue. Most patients may have same symptoms as Lyme disease but are not caused by B. burgdorferi infection. Nevertheless, if we receive a patient with febrile illness followed by headaches and joint or muscle pain, without respiratory or gastrointestinal symptoms, antibiotic treatment is recommended. Early neurological symptoms should be treated with Ceftriaxone, 2 g/day intravenously for 2–4 weeks(4). Lyme arthritis should be treated for 30–60 days with Doxycycline 200 mg/day orally or with Ceftriaxone 2 g/day intravenously for 2–4 weeks. During my interview, Dr. Nelson has specified that there is a possibility of Lyme arthritis to persist even after therapy which indicates autoimmune reaction. In this case treatment needs to incorporate anti-inflammatory drugs.