Lyme disease in humans is typically divided into 3 clinical
phases:
Early local disease (previously called Stage 1) is
manifest by fever, malaise, arthralgia (joint pain), myalgia (muscle
pain) and headaches. However, the most notable lesion is an "erythema
migrans" (EM) (previously referred to as "erythema
'chronicum' migrans").
- This is a bulls-eye-like, expanding, red skin lesion that
develops at the site of a tick bite.
- In many cases, people do not remember being bitten, and in
about ½ of cases, multiple smaller ECM-like lesions develop
elsewhere on the body (apparently due to spread of the organism
through the skin without additional preceding tick bites in these
locations).
Early disseminated disase (previously called Stage
2) occurs weeks to months after initial infection. At this
stage, multiple smaller EM-like lesions may develop elsewhere
on the body (apparently due to spread of the organism through
the skin without additional preceding tick bites in these locations).
People may also manifest neurologic disease (especially meningitis
and Bell's [facial nerve] palsy), myocarditis, and arthropathy
without joint effusion.
Late dissmeinated disease (previously called Stage
3) occurs months to years after initial infection. This stage
of disease is typified by chronic arthritis and/or encephalopathy
(sleep disturbances, fatigue, personality changes).
- Development of chronic arthritis may be associated with certain
MHC II types (HLA-DR2 and 4), as is the case with various autoimmune
diseases in humans.
- In this regard, it has been suggested that the chronic forms
of LD may represent examples of autoimmunity due to mimicry between
B. burgdorferi Ag and self Ag.
- Recent work suggests that the immunodominant epitope on the
B. burgdorferi ospA protein is homologous with a peptide
from human LFA-1, which, in addition to being expressed on immune
cells, is expressed on synoviocytes.
- In light of this possible autoimmune mechanism for chronic
Lyme arthritis, do we want to vaccinate against this disease?
Can humans be re-infected sequentially?
A report in 1998 (Golde et al.) confirmed that humans
can be infected more than once with B. burgdorferi.
- An individual developed EM lesions and constitutional symptoms
twice, 3 months apart, and B. burgdorferi was isolated
from skin biopsies on both occasions.
- The two isolates proved to be distinct strains of B. burgdorferi
sensu stricto, thus confirming that these were independent
infections.
In utero infection?
There have been cases of adverse fetal outcomes in women who
were infected with B. burgdorferi during pregnancy, including
neonatal deaths. There is also a report of in
utero infection in dogs, but transmission to the fetus
does not appear to occur in white-footed mice.
Vaccination against Lyme disease in humans:
A recombinant ospA vaccine (see Prevention
of Borrelia burgdorferi infection in dogs for a discussion
of ospA vaccines), LYMErix from SmithKline Beecham, was approved
for sale by the FDA in 1998.
- Its efficacy in preventing infection was 49-68% after 2 doses
the first year, but rose to 76-92% after a third dose is given
a year later.
- A growing issue in LD vaccination for humans is the fact
that there is substantial genetic and antigenic heterogeneity
among B. burgdorferi isolates, suggesting that multivalent
vaccines may be necessary to provide protection against a wide
range of geographically distinct strains.
- In 2002, this human vaccine was withdrawn from the market
because of poor sales.
