Lyme Borrelia

Dr. Alan Steer and his colleagues first discovered Lyme disease and described its clinical manifestation in 1977 during the epidemic of solitary arthritis in three Connecticut communities. It is currently the leading cause of vector-borne diseases in the US, especially in the northeastern part of the US. Borrelia Burgdorferi are loosely coiled wave-like bodies and flagella that are transmitted by deer ticks called Ixodes Scapularis. Most borrelia species are obligate anaerobes. They are spiral shaped and have axial filaments that facilitate their movement. Borrelia is not the only spirochete. There are also Leptospira interrogans (leptospirosis), Treponema pallidum (agent of syphilis), and other Borrelia species that cause relapsing fever.  Compared to other spirochetes, Borrelia was relatively recently discovered in medicine as the bacterial agent of Lyme disease. It is also the only spirochete that is visible in light microscopy, using either Wright or Giemsa stains, due to their relatively larger size.

Borrelia has an outer membrane that contains many lipoproteins, including the outer surface proteins (Osp A through F), an inner membrane, and a peptidoglycan layer in the periplasmic space. Borrelia flagellum resides in the periplasmic space. Borrelia are gram-negative bacteria transmitted by deer ticks which are also a vector of transmission for Anaplasma species and the protozoa Babesia. The natural reservoir for Borrelia is the mice. Deers are the obligatory host. They do not get infected by the bacteria, but they are needed to continue the life cycle of the ticks.

Lyme Borrelia lacks many central metabolic pathways to produce nutrients. It is highly dependent on the host to survive. Borrelia changes the cellular metabolism of human immune cells and affects the host cell metabolism. Borrelia can induce changes in gene expression in the infected host. It will modulate its gene expression in response to different environments such as the tick midgut vs mammalian host digestive system. It has many complex immune evasion strategies. Data has shown that Borrelia is highly effective in suppressing innate and adaptive immunity to itself and other antigens. Data also suggests that Borrelia prevents CD4 T cells from mounting an effective immune response to infection. IgG and IgM can control tissue load of Borrelia, but they cannot clear them from the body. This causes persistent infection in some patients. Currently very few studies have focused on direct cell-cell interaction between the spirochete and the host. Further studies will be needed.

There are three stages of Lyme disease. In Stage one, an early localized erythema migrans is present and is represented by the expanding erythematous macular rash that has a target or bull’s eye appearance. Reports of an erythema migrans rash in people with Lyme ranged from 25% to 70%. Many might not even know that they are bitten. In addition to the rash, people may also experience nonspecific flu-like symptoms, such as fever and chills. In Stage two, the early disseminated stage, people may have carditis, AV heart block, facial nerve palsy, migratory myalgia and transient arthritis. In Stage three which is the disseminated state, it is often characterized by encephalopathy and chronic arthritis that usually affects the large joints such as the knees.

Borrelia can be grown in the lab. However the cultures are rarely positive. The diagnosis is often made serologically by detecting either IgM or IgG antibodies using Eliza. There is also a problem with Eliza regarding the sensitivity and specificity of these tests. Hence, the positive test results from Eliza are often confirmed with Western blotting. 

The treatment of choice for stage one disease or other mild manifestations is with antibiotics, either doxycycline or amoxicillin. Doxycycline is contraindicated in children less than 8 years of age and in pregnant women because it could cause permanent teeth stains in young children and enamel hypoplasia in fetuses. Amoxicillin is the treatment of choice for children and pregnant women. For more severe cases or late cases of Lyme disease, ceftriaxone is recommended.

There was a vaccine, LYMERix, in the past containing recombinant outer surface protein OspA for Borrelia developed by GSK. The vaccine was later discontinued in 2002 citing insufficient consumer demand. New vaccines for Lyme disease are in the pipeline. VLA15 is currently in phase 2 human trials. It is a multivalent , protein subunit vaccine that targets the outer face protein A (OspA) of Borrelia. It will protect against the European and North American strains of Lyme disease.

A human monoclonal antibody is also under development by MassBiologics, which is affiliated with University of Massachusetts Medical School. It is designed to be used as pre-exposure prophylaxis for Lyme disease. This will afford seasonal protection against Lyme disease and would likely be a single shot annually at the beginning of the Lyme season.