The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity

Nigrovic, Lise E.; Lewander, David P.; Balamuth, Fran; Neville, Desiree N; Levas, Michael N.; Bennett, Jonathan E.; Garro, Aris

doi:10.1089/vbz.2019.2547

Cited by 9 publications

(7 citation statements)

References 11 publications

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“…Our findings of low sensitivity in CSF of patients with LNB are in concordance with previous studies [ 39 , 40 ]. However, in a recent study from Norway, a much higher sensitivity in pediatric LNB patients is reported with a Borrelia PCR positivity of 46% in CSF of patients defined as Definite LNB and 50% in CSF of patients defined as Probable LNB (i.e., symptoms attributable to LNB, pleocytosis in CSF, negative AI but presence of anti- Borrelia antibodies in either CSF or serum) [ 34 ].…”

Section: Discussionsupporting

confidence: 93%

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Lyme neuroborreliosis in Swedish children—PCR as a complementary diagnostic method for detection of Borrelia burgdorferi sensu lato in cerebrospinal fluid

Skogman

Wilhelmsson

Atallah

et al. 2021

Eur J Clin Microbiol Infect Dis

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The aim of this study was to evaluate polymerase chain reaction (PCR) as a diagnostic method for the detection of Borrelia burgdorferi s.l. in CSF of Swedish children with LNB. This study was performed retrospectively on CSF and serum samples collected from children evaluated for LNB (n = 233) and controls with other specific neurological disorders (n = 59) in a Swedish Lyme endemic area. For anti-Borrelia antibody index, the IDEIA Lyme Neuroborreliosis kit (Oxoid) was used. Two in-house real-time PCR assays targeting the 16S rRNA gene were evaluated (TaqMan® and LUX™). Among patients classified as LNB cases (n = 102), five children (5%) were Borrelia PCR-positive in CSF with the TaqMan® assay. In the Non-LNB group (n = 131), one patient was Borrelia PCR positive with the TaqMan® assay. Among controls (n = 59), all CSF samples were PCR negative. When amplifying and sequencing ospA, we found B. garinii (n = 2), B. afzelii (n = 2), B. bavariensis (n = 1), and one untypable (n = 1). With the LUX™ technology, all CSF samples were PCR negative. The TaqMan® assay could detect only few cases (n = 6) of B. burgdorferi s.l. in CSF among children with LNB and the sensitivity was very low (5%). However, using larger CSF volumes and centrifugation of samples, the PCR technique could still be useful as a complementary diagnostic method when evaluating LNB. Furthermore, detection of spirochete DNA in clinical matrices, including CSF, is the method of choice for studying epidemiological aspects of LNB, a tick-borne emerging disease.

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Section: Discussionsupporting

confidence: 93%

“…Furthermore, high levels of pleocytosis in CSF were found in the two B. garinii -infected LNB patients and in the one LNB patient with B. bavariensis. These two species are known to induce a prominent inflammatory response, whereas B. afzelii infections are associated with a lower level of inflammation in the CSF [ 35 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Lyme neuroborreliosis in Swedish children—PCR as a complementary diagnostic method for detection of Borrelia burgdorferi sensu lato in cerebrospinal fluid

Skogman

Wilhelmsson

Atallah

et al. 2021

Eur J Clin Microbiol Infect Dis

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“…Direct pathogen detection tests such as PCR identify the infecting pathogen rather than relying on host response to infection. Consistent with previous evaluations [ 14 , 27 ], the B burgdorferi blood PCR assay had inadequate sensitivity to be utilized clinically for evaluation of patients with potential Lyme disease. Similarly, Rickettsiae species infections are frequently limited to the vascular endothelium with few organisms circulating free in the bloodstream, which limits the sensitivity utility of PCR for these pathogens.…”

Section: Discussionsupporting

confidence: 53%

Multiplex High-Definition Polymerase Chain Reaction Assay for the Diagnosis of Tick-borne Infections in Children

Nigrovic

Neville

Chapman

et al. 2023

Open Forum Infectious Diseases

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Background Ixodes scapularis ticks can carry Borrelia species as well as other pathogens that cause human disease. The frequency of tick-borne infections and co-infections in children with suspected Lyme disease is unknown, creating clinical uncertainty about the optimal approach to diagnosis. Methods We enrolled children aged 1 to 21 years presenting to one of eight Pedi Lyme Net emergency departments for evaluation of Lyme disease. We selected cases with serologically or clinically diagnosed Lyme disease (erythema migrans or early neurologic disease) matched by symptoms, age, gender and center to control subjects without Lyme disease. We tested whole blood samples collected at the time of diagnosis using a high-definition multiplex polymerase chain reaction (HDPCR) panel to identify 9 bacterial or protozoan pathogens associated with human disease. We compared the frequency of tick-borne co-infections in children with Lyme disease to matched controls. Results Of the 612 selected samples, 594 (97.1%) had an interpretable multiplex HDPCR result. We identified the following non-Borrelia tick-borne infections: Anaplasma phagocytophilum (2), Ehrlichia chaffeensis (1) and Babesia microti (12). Children with Lyme disease were more likely to have another tick-borne pathogen identified than matched controls [15/297 (5.1%) Lyme cases vs. 0/297 (0%); difference 5.1% 95% CI 2.7, 8.2%). Conclusions Although a substantial minority of children with Lyme disease had another tick-borne pathogen identified, either first-line Lyme disease antibiotics provided adequate treatment or the coinfection was subclinical and did not require specific treatment. Further studies are needed to establish the optimal approach to testing for tick-borne co-infections in children.

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“…Third, study patients did not have a synovial fluid polymerase chain reaction (PCR) testing performed. Although Lyme PCR has low diagnostic yield, 25 bacterial PCR testing can identify pathogens missed by synovial fluid culture 26 . Fourth, children with distal femoral or proximal tibial osteomyelitis who may have a reactive arthritis were not included in the primary outcome 27 .…”

Section: Discussionmentioning

confidence: 99%

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area

et al. 2021

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In Lyme disease endemic areas, Lyme and septic arthritis often present similarly. A published septic knee arthritis clinical prediction rule includes 2 high-risk predictors: absolute neutrophil count of 10,000 cells/mm 3 or greater and erythrocyte sedimentation rate of 40 mm/h or greater. The objective of the study was to externally validate this prediction rule in a multicenter prospective cohort. Methods:We enrolled a prospective cohort of children with knee monoarthritis undergoing evaluation for Lyme disease at 1 of 8 Pedi Lyme Net emergency departments located in endemic areas. We defined a case of septic arthritis with a positive synovial fluid culture or a synovial fluid white blood cell count of 50,000 or greater per high powered field with a positive blood culture and Lyme arthritis with a positive or equivocal C6 EIA, followed by a positive supplemental immunoblot. Other children were classified as having inflammatory arthritis. We report the performance of the septic arthritis clinical prediction rule in our study population.Results: Of the 543 eligible children, 13 had septic arthritis (2.4%), 234Lyme arthritis (43.1%), and 296 inflammatory arthritis (54.5%). Of the 457 children (84.2%) with available laboratory predictors, all children with septic arthritis were classified as high risk (sensitivity, 100%; 95% confidence interval [CI], 77.2%-100%; specificity, 68.1%; 95% CI, negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis. Conclusions:The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures.

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The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity

Cited by 9 publications

References 11 publications

Lyme neuroborreliosis in Swedish children—PCR as a complementary diagnostic method for detection of Borrelia burgdorferi sensu lato in cerebrospinal fluid

Lyme neuroborreliosis in Swedish children—PCR as a complementary diagnostic method for detection of Borrelia burgdorferi sensu lato in cerebrospinal fluid

Multiplex High-Definition Polymerase Chain Reaction Assay for the Diagnosis of Tick-borne Infections in Children

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area

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