Page 425 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 28 Host Defenses to Spirochetes 405

Treatment
During early stages of Lyme disease, such as that during which
erythema migrans is present, oral administration of doxycycline
(100 mg twice daily) or amoxicillin (500 mg three times a day)
for approximately 2 weeks is recommended. Doxycycline has
the advantage of being effective against Anaplasma phagocyto-
philum, which may also be transmitted by ticks. In areas where
B. burgdorferi infection is prevalent, some experts recommend
antibiotic therapy for individuals who served as hosts to I.
scapularis ticks that were attached longer than 40–48 hours—the
time required for transmission of the spirochete. It is extremely
difficult, however, to consistently make accurate determinations
of the species of tick and the degree of engorgement. Furthermore,
randomized double-blind clinical trials involving individuals
who were bitten by I. scapularis ticks led to the conclusion that
antibiotic treatment of all individuals who had vector ticks
FIG 28.2 Erythema migrans caused by infection with Borrelia removed is probably not warranted.
burgdorferi, the Lyme disease agent. (Courtesy of Gary Wormser,
MD.) Venereal Syphilis
Infection with the agent of syphilis, T. pallidum subspecies pal-
lidum, occurs worldwide. T. pallidum is an obligate human parasite
that is almost exclusively transmitted when contact with infectious
exudates from lesions of the skin and mucous membranes of
more commonly found in the United States, whereas patients infected individuals occurs. Clinically, this treponemal infection
in Europe tend to show higher incidence of skin and nervous is first characterized by the formation of a hardened and painless
system involvement. This may be attributed to the heterogeneity ulcer at the initial site of infection. This primary lesion, called
of the B. burgdorferi sensu lato genospecies that cause the disease. a chancre, forms after invasion of the bloodstream by the spi-
In the United States, in the large majority of cases, B. burgdorferi rochete. Four to 6 weeks after infection, the edges of the chancre
sensu stricto is involved, whereas in Europe infections by B. afzelii roll inward and upward and, in most cases, a secondary eruption
and B. garinii predominate. appears, often accompanied by a rash on the palms of the hands
and the soles of the feet. The secondary manifestations resolve
Diagnosis within weeks to a year after the development of a vigorous
A detailed clinical history and comprehensive physical examina- cell-mediated immune response. Long periods of latency followed
tion are critical for the accurate diagnosis of Lyme disease. by late lesions of skin, bone, and viscera, as well as the cardio-
Appropriate laboratory testing, however, is a valuable diagnostic vascular system and the CNS, can occur despite clearance of the
aid. A two-tiered approach is standard for the serodiagnosis of majority of the treponemes, which coincides with the resolution
Lyme disease. Using this approach, serum is first tested for the of the primary syphilitic lesion.
presence of B. burgdorferi–specific antibodies by using a sensitive
method, such as enzyme-linked immunosorbent assay (ELISA) Diagnosis
or immunofluorescent assay (IFA). Sera testing negative for Much like Lyme disease, the diagnosis for syphilis is based on
antibodies generally need not be tested further; however, those the clinical presentations of the disease and serological tests. In
found to be positive or equivocal are further evaluated by the addition, dark-field microscopy can be used for the identification
more specific immunoblotting for immunoglobulin M (IgM) of T. pallidum in the serous exudates of the chancre. This
and IgG antibodies. The detection of at least two of three specific approach, however, is limited by the number of live treponemes
bands in IgM or five of 10 specific bands in IgG is considered in the exudates and by the presence of nonpathological trepo-
positive. Patients with early Lyme disease often report to a nemes in oral and anal lesions; as such, negative examinations
physician during the first few days of infection, at which time a on three independent days are required before a lesion is con-
detectable humoral response may not have developed. Conse- sidered negative for T. pallidum.
quently, the two-tiered approach is considered highly sensitive Infection with T. pallidum leads to the production of non-
during the later stages of the disease (>90%) and less sensitive specific antibodies, which is the basis for other diagnostic tests,
during very early infection. Furthermore, a positive serological such as the traditional nontreponemal serological tests, including
test, particularly IgG, is evidence of exposure to B. burgdorferi, the Venereal Disease Research Laboratory (VDRL) and rapid
but it does not necessarily indicate active infection. All serological plasma reagin (RPR) tests. Because these tests are nonspecific,
tests must then be evaluated in conjunction with a clinical false-positive reactions can occur as a result of pregnancy,
assessment by the attending physician. Other diagnostic methods, autoimmune disorders, or infections. Therefore treponemal-
such as culture and polymerase chain reaction (PCR) detection specific tests, which detect antibodies to various antigens of T.
of B. burgdorferi, may be very useful to detect active infection, pallidum, are often used to confirm the results of a nonspecific
particularly of skin, joints, and the central nervous system (CNS). test. Interestingly, treponemal-specific tests are just as sensitive
Culture, however, is generally limited to research laboratories, as nontreponemal tests; however, they are much more difficult
and the sensitivity and specificity of PCR can vary greatly among and expensive to perform, which limits their use. These tests
testing centers. include, but are not limited to, the enzyme immunoassay (EIA)