Host-pathogen interactions in Lyme disease and their application in diagnostics
||Department of Medical Microbiology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
||B. burgdorferi has a wide variety of
strategies to hide from the host immune system. Complement regulatory
binding proteins have been described for almost all complement resistant B.
burgdorferi sl, except for the complement resistant B. bavariensis, one of the
species that is known to frequently cause Lyme neuroborreliosis.
In chapter 2 it is attempted to identify CRASP-1 proteins in B. bavariensis,
formerly known as B. garinii OspA serotype 4. Potential CRASP-1 proteins will be
cloned and studied for their ability to interact with host derived fluid phase
regulators of complement.
The specific role of complement resistance in early effective infection and
dissemination of B. burgdorferi sl has not been well investigated. Can
complement resistance lead to a better and more effective infection and
dissemination? In chapter 3 an in vivo experiment in which the infectivity and
dissemination patterns of complement sensitive and complement resistant B.
burgdorferi sl in a C3 deficient mouse model is described.
After effective transmission from the tick to the host the next challenge in B.
burgdorferi infection is rapid and accurate detection of the pathogen.
Diagnostics of Lyme disease is often compromised due to specific pathogen
properties combined with technical shortcomings of bacterial serology.
Two indirect detection methods which can aid in diagnosing patients suffering
from Lyme neuroborreliosis were studied. In chapter 4 the performance of the
C6-peptide ELISA for detecting antibodies in CSF in Lyme neuroborreliosis
patients is studied. While in chapter 5 levels of CXCL13 in several patient
populations as a potential biomarker for the diagnosis of Lyme neuroborreliosis
For both indirect markers of presence of B. burgdorferi the specificity in
clinically resembling and neuroinfectious diseases is of key importance. Several
other infectious and inflammatory diseases that have a clinical presentation
that can resemble Lyme disease are included in the analysis.
Diagnosing Lyme disease can be difficult in some populations, first because
Lyme disease is a relatively rare infection, resembling a large spectrum of other
autoimmune and inflammatory diseases. Clinicians could often consider testing
for Lyme disease. It is also important to do this in specific preselected
populations, because the positive predictive value of a test, but specifically
indirect tests such as serology, in a random population, is low.In chapter 6 all patients that present with complaints of arthritis at the early
arthritis clinic are tested for Lyme arthritis. The prevalence of B. burgdorferi
seropositivity in this population is studied. Another aim is to identify clinical
factors which should urge the doctor to test, or explicitely not test, for Lyme
disease in a patient presenting with arthritis in Europe.
In chapter 7 a case of an HIV positive patient presenting with a meningoencephalitis
caused by B. burgdorferi is described. The literature on HIV and
Lyme neuroborreliosis co-infections is also reviewed.
||Promotor: A.C.M. Kroes, Co-Promotor: A.P. van Dam
With Summary in Dutch
||Burgel, N.D. van, 2013, Doctoral Thesis, Leiden University