Serological Diagnostics of Lyme Borreliosis: Comparison of Universal and Borrelia Species-Specific Tests Based on Whole-Cell and Recombinant Antigens

Kodym, Petr; Kurzová, Zuzana; Berenová, Dagmar; Pícha, Dušan; Smíšková, Dita; Moravcová, Lenka; Malý, Marek

doi:10.1128/jcm.00601-18

Cited by 16 publications

(18 citation statements)

References 20 publications

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“…It is important to note that Borrelia undergoes several changes during host infections which require the production of new membrane proteins that could be used for immune evasion or adaptation to the new environment 38,42,43 . Multiple proteins identified herein are currently recognized as antigens in the standard serological test: OspC, Flagellin 44 . Among the Borrelia genus, the highest number of peptides were derived from species related to Lyme borreliosis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of pathogen specific urinary peptides in tick-borne illnesses

Magni

Almofee

Yusuf

et al. 2020

Sci Rep

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Mass spectrometry enhanced by nanotechnology can achieve previously unattainable sensitivity for characterizing urinary pathogen-derived peptides. We utilized mass spectrometry enhanced by affinity hydrogel particles (analytical sensitivity = 2.5 pg/mL) to study tick pathogen-specific proteins shed in the urine of patients with (1) erythema migrans rash and acute symptoms, (2) post treatment Lyme disease syndrome (PTLDS), and (3) clinical suspicion of tick-borne illnesses (TBI). Targeted pathogens were Borrelia, Babesia, Anaplasma, Rickettsia, Ehrlichia, Bartonella, Francisella, Powassan virus, tick-borne encephalitis virus, and Colorado tick fever virus. Specificity was defined by 100% amino acid sequence identity with tick-borne pathogen proteins, evolutionary taxonomic verification for related pathogens, and no identity with human or other organisms. Using a cut off of two pathogen peptides, 9/10 acute Lyme Borreliosis patients resulted positive, while we identified zero false positive in 250 controls. Two or more pathogen peptides were identified in 40% of samples from PTLDS and TBI patients (categories 2 and 3 above, n = 59/148). Collectively, 279 distinct unique tick-borne pathogen derived peptides were identified. The number of pathogen specific peptides was directly correlated with presence or absence of symptoms reported by patients (ordinal regression pseudo-R2 = 0.392, p = 0.010). Enhanced mass spectrometry is a new tool for studying tick-borne pathogen infections.

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Section: Discussionmentioning

confidence: 99%

Evaluation of pathogen specific urinary peptides in tick-borne illnesses

Magni

Almofee

Yusuf

et al. 2020

Sci Rep

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“…Variations in the PA, NA, or OA among the LD diagnostic tests is a rule rather than the exception, because several in vitro diagnostic test manufacturers utilize different Borrelia proteins [ 21 , 22 , 27 , 57 ]. For example, the positivity rate for LD patients with an Erythema Migrans rash can range from 18% to 53% for whole-cell antigen LD tests vs. 31% to 50% for recombinant antigen LD tests [ 57 ]. Generally, diagnostic test sensitivities improve from the early to late LD stages [ 21 , 22 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, the positivity rate for LD patients with an Erythema Migrans rash can range from 18% to 53% for whole-cell antigen LD tests vs. 31% to 50% for recombinant antigen LD tests [ 57 ]. Generally, diagnostic test sensitivities improve from the early to late LD stages [ 21 , 22 , 57 ]. In later LD stages like neuroborreliosis, the positivity rate can vary from 41% to 86% for whole-cell antigen LD tests and 49% to 81% for recombinant antigen LD tests [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Assessing the Need for Multiplex and Multifunctional Tick-Borne Disease Test in Routine Clinical Laboratory Samples from Lyme Disease and Febrile Patients with a History of a Tick Bite

Garg¹,

Jokiranta

Filén

et al. 2021

TropicalMed

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Human polymicrobial infections in tick-borne disease (TBD) patients is an emerging public health theme. However, the requirement for holistic TBD tests in routine clinical laboratories is ambiguous. TICKPLEX® PLUS is a holistic TBD test utilized herein to assess the need for multiplex and multifunctional diagnostic tools in a routine clinical laboratory. The study involved 150 specimens categorized into Lyme disease (LD)-positive (n = 48), LD-negative (n = 30), and febrile patients from whom borrelia serology was requested (n = 72, later “febrile patients”) based on reference test results from United Medix, Finland. Reference tests from DiaSorin, Immunetics, and Mikrogen Diagnostik followed the two-tier LD testing system. A comparison between the reference tests and TICKPLEX® PLUS produced 86%, 88%, and 87% positive, negative, and overall agreement, respectively. Additionally, up to 15% of LD and 11% of febrile patients responded to TBD related coinfections and opportunistic microbes. The results demonstrated that one (TICKPLEX® PLUS) test can aid in a LD diagnosis instead of four tests. Moreover, TBD is not limited to just LD, as the specimens produced immune responses to several TBD microbes. Lastly, the study indicated that the screening of febrile patients for TBDs could be a missed opportunity at reducing unreported patient cases.

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“…ELISA is the most commonly used assay today since it is easy to perform, is relatively cheap, and has high diagnostic sensitivity 212 . Another benefit in using ELISA compared to IFA is the while assays based on a whole-cell antigen mixture generated high diagnostic sensitivity but lower diagnostic specificity due to cross-reactivities to other diseases and pathogens 239,247 .…”

Section: Difference Between Various Serological Methods -Limitationsmentioning

confidence: 99%

Molecular and serological tools for clinical diagnostics of Lyme borreliosis - can the laboratory analysis be improved?

Lager

2020

Linköping University Medical Dissertations

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Lyme borreliosis (LB) is caused by spirochetes within the Borrelia burgdorferi sensu lato complex and is the most common tick-transmitted disease in the northern hemisphere. The transmission of the spirochetes to humans in Europe is done by the Ixodes ricinus ticks, which can also transmit the relapsing fever species Borrelia miyamotoi. LB may cause clinical manifestations in the skin, in the central nervous system, in joints, and in the heart. Diagnosis of LB is mainly based on the patient´s medical history, self-described symptoms, and clinical signs in combination with the detection of Borrelia-specific antibodies (serological methods). In some cases/issues, detection of Borrelia-specific deoxyribonucleic acid (molecular methods) may be used as a complement to serology. All diagnosed LB infections are treated with antibiotics to prevent disease progression, and most patients fully recover without further sequelae. The overall aims of this thesis were to evaluate molecular and serological tools for laboratory diagnosis of LB, with a special focus on Lyme neuroborreliosis (LNB), and to identify potential improvements. The results presented in this thesis showed that the immunoglobulin (Ig) G assays, currently in use in northern Europe for detection of antibodies in serum, had high diagnostic sensitivity (88 %) together with comparable results both between and within assays. For the IgM assays, the diagnostic sensitivity was lower (59 %) with more heterogeneous results. Small variations in diagnostic performance for IgM and IgG were mainly presented for samples within the borderline zone. These results support the theory that separate testing of IgM antibodies in serum has low diagnostic value. However, simultaneous detection in serum and cerebrospinal fluid (CSF) for both IgM and IgG antibodies was essential for the diagnosis of LNB, at least for certain assays. So far (to our knowledge), no systematic evaluation and optimisation of the pre-analytical handling of CSF samples before molecular testing has been performed. By use of the precipitate concentrated by moderate centrifugation, extraction of total nucleic acid followed by reversetranscription to complementary deoxyribonucleic acid, in combination with the absence of Abstract polymerase chain reaction (PCR) inhibitors, detection of Borrelia garinii, Borrelia afzelii, Borrelia burgdorferi sensu stricto, and B. miyamotoi was possible. These four species are all known to be pathogenic to humans. The results revealed a high analytical sensitivity and specificity for the optimised pre-analytical conditions. The thesis also presents results showing that the real-time PCR protocols currently used in Scandinavia have high analytical sensitivity, specificity, and concordance. This indicates that the low diagnostic sensitivity for detection of Borrelia in CSF was not a result of poorly designed and evaluated PCR protocols, but was possibly due to the low number of spirochetes in the samples. However, to further evaluate the diagnostic performance for detection of Bo...

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Serological Diagnostics of Lyme Borreliosis: Comparison of Universal and Borrelia Species-Specific Tests Based on Whole-Cell and Recombinant Antigens

Cited by 16 publications

References 20 publications

Evaluation of pathogen specific urinary peptides in tick-borne illnesses

Evaluation of pathogen specific urinary peptides in tick-borne illnesses

Assessing the Need for Multiplex and Multifunctional Tick-Borne Disease Test in Routine Clinical Laboratory Samples from Lyme Disease and Febrile Patients with a History of a Tick Bite

Molecular and serological tools for clinical diagnostics of Lyme borreliosis - can the laboratory analysis be improved?

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