Lyme disease test kits and limitations
 

Key points

• Serologic test results are
supplemental to the clinical
diagnosis of Lyme disease and
should not be the primary basis for
making diagnostic or treatment
decisions.

• Lyme disease test kits have
sensitivity and specificity
limitations.

• Health care professionals should
be aware of these limitations and
are encouraged to report
suspected incidents, including
false-positive and false-negative
results, to Health Canada.

Lyme disease test kits are class II (IV
being the highest risk class) in vitro
diagnostic devices. The devices are
intended for the detection of antibodies
to Borrelia burgdorferi in human serum,
plasma or cerebrospinal fluid.1 They are
used to provide serologic evidence of
B. burgdorferi exposure.1 Infection can
result in dermatologic, neurologic,
cardiac and musculoskeletal disorders.2
Serologic testing is the only
standardized type of laboratory
investigation available to support the
clinical diagnosis of Lyme disease in
North America.3 The public health
agencies of Canada and the United
States recommend a two-tiered
approach for blood testing when Lyme
disease is suspected.3–7 The first tier
consists of an enzyme immunoassay,
such as an enzyme-linked
immunosorbent assay (ELISA), or an
indirect immunofluorescent assay. If the
result of first-tier testing is negative, the
sample is reported to be negative for
antibodies to B. burgdorferi and is not
tested further. If the result is positive or
indeterminate, second-tier testing with
a standardized Western blot is then
performed.3–5
As of June 2012, Health Canada
received one incident report of
false-negative serologic test results for
24 patients that may have delayed
treatment. Timely recognition of Lyme
disease and treatment are imperative to
facilitate recovery and prevent longterm
sequelae.2,7,8
The currently available Lyme disease
test kits have been found to have
limitations of sensitivity and specificity,
particularly when used on patients with
acute infection, which is usually easily
treated with antibiotics.7,9 Even when
the conventional two-tiered testing
approach is used, the sensitivity and
specificity of the combined test results
can be less than optimal.9–11 In a
comprehensive study of 280 serum
samples from well-characterized Lyme
disease patients, the sensitivity of the
two-tiered approach was as low as 38%
for the sera of patients who had
erythema migrans during the acute
phase and 67% during their
convalescence after antimicrobial
treatment.10 In late Lyme disease, the
sensitivity increased to 87% for the
sera of patients with early
neuroborreliosis and to 97% for the
sera of patients with Lyme arthritis.10
Many factors contribute to falsenegative
or false-positive serologic test
results for Lyme disease.1,7,9,11–14 In
general, false-negative results have
been attributed to (a) a slow antibody
response early in the course of the
disease, (b) genetic diversity of
B. burgdorferi and (c) treatment with
antibiotics. False-positive results have
been attributed to (a) cross-reacting
antibodies due to other conditions or
infections and (b) the persistence of
antibodies after disease resolution.
Variability in serologic test results for
Lyme disease may also be related to
interlaboratory differences and lack of
interassay standardization. 9,13,14
In contrast to the known HIV
serologic testing using the two-tiered
algorithm to confirm diagnosis, the
Lyme disease test kits are not designed
to screen patients or to establish a
clinical diagnosis.9,12 A positive test
result does not necessarily indicate
current infection with B. burgdorferi,
and a negative result, especially early
in the course of infection, does not
exclude B. burgdorferi infection as
the cause of illness.9–12 Serologic test
results should be used to support a
clinical diagnosis of Lyme disease and
should not be the primary basis for
making diagnostic or treatment
decisions.1,11 Diagnosis should be based
on patient history, which includes
symptoms and exposure to the tick
vector, and physical findings.4,11,15
Health care professionals should be
aware of the limitations of Lyme
disease test kits and are encouraged to
report suspected incidents, including
false-positive and false-negative results,
to Health Canada (www.hc-sc.gc.ca
/dhp-mps/medeff/report-declaration
/index-eng.php).
Rana Filfil, PhD, Health Canada

See full Article here:
http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v22n4-eng.php