Comparative Evaluation of Commercial Test Kits Cleared for Use in Modified Two-Tiered Testing Algorithms for Serodiagnosis of Lyme Disease.

BACKGROUND: Modified 2-tiered testing (MTTT) for Lyme disease utilizes automatable, high throughput immunoassays (AHTIs) in both tiers without involving western immunoblots, offering performance and practical advantages over standard 2-tiered testing (STTT; first-tier AHTI followed by immunoglobulin M (IgM) and immunoglobulin G (IgG) western immunoblots). For MTTT, Centers for Disease Control and Prevention recommends using AHTI test kits that have been cleared by Food and Drug Administration (FDA) specifically for this intended use. We evaluated performance of FDA-cleared MTTT commercial test kits from 3 manufacturers by comparing with STTT results. METHODS: We performed MTTT (total antibody AHTI with reflex to separate IgM and IgG AHTIs) using test kits from Diasorin, Gold Standard Diagnostics (GSD), and Zeus Scientific on 382 excess serum samples submitted to the clinical laboratory for routine Lyme disease serologic testing in July 2018, measuring agreement between MTTT and STTT using the κ statistic. RESULTS: Overall agreement with STTT was 0.87 (95% confidence interval [CI], .77-.97) using Diasorin assays (almost perfect agreement), 0.80 (95% CI, .68-.93) using GSD assays (substantial agreement) and 0.79 (95% CI, .68-.90) using Zeus assays (substantial agreement). For detection of IgM reactivity, agreement between MTTT and STTT was 0.70 (.51-.90; substantial), 0.63 (95% CI, .44-.82; substantial) and 0.56 (95% CI, .38-.73; moderate), respectively. For detection of IgG reactivity, MTTT/STTT agreement was 0.73 (95% CI,.58-.88), 0.78 (95% CI, .62-.94), and 0.75 (95% CI, .60-.90), respectively (substantial agreement in all cases). CONCLUSIONS: MTTT results obtained using commercial test kits from 3 different manufacturers had substantial to almost perfect agreement with STTT results overall and moderate to substantial agreement for IgM and IgG detection independently. Commercial MTTT tests can be used broadly for the diagnosis of Lyme disease.

Predictors of Invasive Bacterial Infection in Febrile Infants Aged 2 to 6 Months in the Emergency Department.

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2-6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing.

Utility of Synovial Fluid Biomarkers for Culture-Positive Septic Arthritis in a Lyme Disease-Endemic Region.

OBJECTIVE: To evaluate the performance of synovial fluid biomarkers to identify children with culture-positive septic arthritis. METHODS: We identified children 6 months to 18 years old presenting to a single emergency department between 2007 and 2022 undergoing evaluation for septic arthritis defined by having a synovial fluid culture obtained. Our primary outcome was septic arthritis defined by a positive synovial fluid culture. We evaluated the ability of synovial fluid biomarkers to identify children with septic arthritis using area under the receiver operating characteristic curve (AUC) analyses. We measured the sensitivity and specificity of commonly used synovial fluid biomarkers. RESULTS: We included 796 children, of whom 79 (10%) had septic arthritis. Compared with synovial white blood cell count (AUC, 0.72; 95% confidence interval [CI], 0.65-0.78), absolute neutrophil count (AUC, 0.72; 95% CI, 0.66-0.79; P = 0.09), percent neutrophils (AUC, 0.66; 95% CI, 0.60-0.71; P = 0.12), and glucose (AUC, 0.78; 95% CI, 0.67-0.90; P = 0.33) performed similarly, whereas protein (AUC, 0.52; 95% CI, 0.40-0.63, P = 0.04) had lower diagnostic accuracy. Synovial fluid white blood cell count ≥50,000 cells/µL had a sensitivity of 62.0% (95% CI, 50.4%-72.7%) and a specificity of 67.0% (95% CI, 63.4%-70.4%), whereas a positive synovial fluid Gram stain had a sensitivity of 48.1% (95% CI, 36.5%-59.7%) and specificity of 99.1% (95% CI, 98.1%-99.7%) for septic arthritis. CONCLUSIONS: None of the routinely available synovial fluid biomarkers had sufficient accuracy to be used in isolation in the identification of children with septic arthritis. New approaches including multivariate clinical prediction rules and novel biomarkers are needed.

Mapping the distribution of Lyme disease at a mid-Atlantic site in the United States using electronic health data.

Lyme disease is a spatially heterogeneous tick-borne infection, with approximately 85% of US cases concentrated in the mid-Atlantic and northeastern states. Surveillance for Lyme disease and its causative agent, including public health case reporting and entomologic surveillance, is necessary to understand its endemic range, but currently used case detection methods have limitations. To evaluate an alternative approach to Lyme disease surveillance, we have performed a geospatial analysis of Lyme disease cases from the Johns Hopkins Health System in Maryland. We used two sources of cases: a) individuals with both a positive test for Lyme disease and a contemporaneous diagnostic code consistent with a Lyme disease-related syndrome; and b) individuals referred for a Lyme disease evaluation who were adjudicated to have Lyme disease. Controls were individuals from the referral cohort judged not to have Lyme disease. Residential address data were available for all cases and controls. We used a hierarchical Bayesian model with a smoothing function for a coordinate location to evaluate the probability of Lyme disease within 100 km of Johns Hopkins Hospital. We found that the probability of Lyme disease was greatest in the north and west of Baltimore, and the local probability that a subject would have Lyme disease varied by as much as 30-fold. Adjustment for demographic and ecological variables partially attenuated the spatial gradient. Our study supports the suitability of electronic medical record data for the retrospective surveillance of Lyme disease.