Page 72 - Human Lyme Neuroborreliosis

56 David S. Younger

mg/kg/day for 9.5 weeks after infection, a dosage considered low to moderate
to render them immunocompromised, while two other NHP remained
immunocompetent. The two immunocompetent underwent postmortem
examination 9.5 p.i. while the immunocompetent NHP were studied at 13
weeks p.i. The MIT, culture, PCR and antibodies studies of the CSF obtained
at the time of inoculation prior to infection were negative in all animals. A
previous study determined that CNS invasion did not occur before 3 weeks p.i.
in NHP [5] but was positive for infection at 3.5 weeks with one or more of the
four tests in 14 of 16 (88%) among all four animals, and notably positive in 7
of 8 (88%) CSF specimens from immunocompromised NHP. The MIT test
was the only positive test in 2 of 8 (25%) CSF samples from the
immunocompromised NHP. CSF antibody measured by ELISA was negative
in the CSF of the immunocompromised NHP despite a low level of specific
antibody that appeared in the blood and steadily rose by the time of
postmortem examination. None of the immunocompromised NHP CSF
displayed lymphocytic pleocytosis although sera from the immuno-
compromised NHP had a number of B. burgdorferi-specific IgG bands on
Western blot. None of the CSF samples had 5 or more IgG-specific bands
fulfilling the criteria for positive seroconversion in CSF. Borrelia-specific
antibody was present in the CSF of immunocompetent NHP 5.5 weeks p.i.
with CSF pleocytosis, and much high serum antibody levels, with IgG and
IgM Western blot positivity in the serum. The MIT outperformed culture in
samples of CNS tissue in the immunocompromised NHP, while MIT and PCR
were concordant for the majority of tissue samples. Thus, in the
immunocompetent NHP, B. burgdorferi-specific antibody in the CSF was a
successful assay for detection of CNS invasion however false negatives were
frequent especially early in the course of the infection or with transient
immunosuppression. The latter can occur with Lyme coinfections. In
immunocompetent NHP, the window of opportunity for CNS invasion prior to
development of CSF antibody was brief and the chance of detection of
spirochetes by any of the three techniques was low. In this group,
measurement of CSF antibody was generally diagnostic. In immuno-
compromised NHP, intrathecal antibody production was delayed and thus
falsely negative, requiring PCR, culture or MIT for diagnosis at 3.5 to 9.5
weeks after infection. The appearance of anti-B. burgdorferi antibody in the
CSF can be delayed when there is interference by anti-B. burgdorferi immune
responses. The chance of detecting spirochetes by culture, PCR and MIT was
least likely to be successful when the anti-B. burgdorferi antibody was present.

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