First name
Desiree
Middle name
N
Last name
Neville

Title

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

Year of Publication

2023

Number of Pages

ofad121

Date Published

04/2023

ISSN Number

2328-8957

Abstract

BACKGROUND: ticks can carry species as well as other pathogens that cause human disease. The frequency of tick-borne infections and coinfections in children with suspected Lyme disease is unknown, creating clinical uncertainty about the optimal approach to diagnosis.

METHODS: We enrolled children aged 1-21 years presenting to 1 of 8 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 multiplex high-definition polymerase chain reaction (HDPCR) panel to identify 9 bacterial or protozoan pathogens associated with human disease. We compared the frequency of tick-borne coinfections 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- tick-borne infections: (2), (1), and (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% confidence interval, 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 coinfections in children.

DOI

10.1093/ofid/ofad121

Alternate Title

Open Forum Infect Dis

PMID

37089773
Featured Publication
No

Title

Racial Differences in the Diagnosis of Lyme Disease in Children.

Year of Publication

2023

Number of Pages

1129-1131

Date Published

03/2023

ISSN Number

1537-6591

Abstract

Black children with Lyme disease compared with children of other races were less likely to have an erythema migrans lesion diagnosed (adjusted odds ratio, 0.34; 95% confidence interval, .14-.79) but more likely to have a swollen joint (adjusted odds ratio, 3.68; 95% confidence interval, 2.13-6.36) after adjustment for age and local Lyme incidence.

DOI

10.1093/cid/ciac863

Alternate Title

Clin Infect Dis

PMID

36314085
Featured Publication
No

Title

Empiric antibiotics for children with suspected Lyme disease.

Year of Publication

2022

Number of Pages

101989

Date Published

06/2022

ISSN Number

1877-9603

Abstract

In our prospective cohort of children undergoing evaluation for non-cutaneous Lyme disease, 02 (13.9% of those with Lyme disease) were not initially treated with an appropriate antibiotics and 356 (13.3% without Lyme disease) received potentially unnecessary antibiotics. Rapid and accurate diagnostics are needed to further improve initial antibiotic treatment decisions.

DOI

10.1016/j.ttbdis.2022.101989

Alternate Title

Ticks Tick Borne Dis

PMID

35759989

Title

A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions.

Year of Publication

2022

Number of Pages

225-234

Date Published

05/2022

ISSN Number

1097-6760

Abstract

STUDY OBJECTIVE: Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI.

METHODS: We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort.

RESULTS: Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%).

CONCLUSION: A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children.

DOI

10.1016/j.annemergmed.2022.04.009

Alternate Title

Ann Emerg Med

PMID

35643775

Title

Seasonality of Acute Lyme Disease in Children.

Year of Publication

2021

Date Published

2021 Nov 09

ISSN Number

2414-6366

Abstract

<p>Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year.</p>

DOI

10.3390/tropicalmed6040196

Alternate Title

Trop Med Infect Dis

PMID

34842846

Title

Electrocardiogram as a Lyme Disease Screening Test.

Year of Publication

2021

Date Published

2021 Jul 12

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVE: </strong>To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease.</p>

<p><strong>STUDY DESIGN: </strong>We performed an eight-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease with the presence of an erythema migrans lesion or a positive two-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and AV block or any ECG evidence of carditis.</p>

<p><strong>RESULTS: </strong>Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis of which 24 had atrioventricular (AV) block (20 first degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (odds ratio 4.7, 95% confidence interval 1.8-12.1) and any ECG evidence of carditis (odds ratio 2.3, 95% confidence interval 1.2-4.3) were both associated with diagnosis of Lyme disease.</p>

<p><strong>CONCLUSIONS: </strong>ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.</p>

DOI

10.1016/j.jpeds.2021.07.010

Alternate Title

J Pediatr

PMID

34265339

Title

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

Year of Publication

2021

Date Published

2021 May 13

ISSN Number

1535-1815

Abstract

<p><strong>OBJECTIVE: </strong>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 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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>Of the 543 eligible children, 13 had septic arthritis (2.4%), 234 Lyme 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], 62.8%-100%; specificity, 68.1%; 95% CI, 63.6-73.3; negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1097/PEC.0000000000002455

Alternate Title

Pediatr Emerg Care

PMID

34160185

Title

Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis.

Year of Publication

2021

Number of Pages

306-309

Date Published

2021 Apr 01

ISSN Number

1532-0987

Abstract

<p><b>BACKGROUND: </b>The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease.</p><p><b>METHODS: </b>We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis.</p><p><b>RESULTS: </b>Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%).</p><p><b>CONCLUSIONS: </b>The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.</p>

DOI

10.1097/INF.0000000000003003

Alternate Title

Pediatr Infect Dis J

PMID

33710975

Title

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

Year of Publication

2019

Date Published

2019 Dec 10

ISSN Number

1557-7759

Abstract

<p>The Lyme PCR is a direct detection test, but has not been rigorously evaluated in children undergoing evaluation for acute Lyme disease. We performed a six-center prospective cohort study of children aged 1 to 21 years undergoing acute evaluation for Lyme disease. For this planned secondary analysis, we limited our cohort to children undergoing evaluation for Lyme disease who had any Lyme PCR test obtained by a treating clinician (blood, synovial fluid, or cerebrospinal fluid). We defined a case of Lyme disease with a positive two-tier Lyme disease serology: a positive or equivocal enzyme immunoassay followed by a positive supplemental immunoblot interpreted using standard criteria. We report the test characteristics of Lyme PCR for the diagnosis of Lyme disease. We identified 124 children of whom 54 (43.5%) had Lyme disease. Overall, 23 had a positive PCR test (sensitivity 41.8%; 95% confidence interval [CI] 29.7-55.0; specificity 100%, 95% CI: 94.2-100). All children with a positive Lyme PCR also had a positive two-tiered Lyme disease serology. The Lyme disease PCR test did not improve the diagnosis of children undergoing evaluation for acute Lyme disease. Given the additional costs of this low utility test, clinicians should not order Lyme PCR testing in the acute care setting.</p>

DOI

10.1089/vbz.2019.2547

Alternate Title

Vector Borne Zoonotic Dis.

PMID

31821110

Title

A minority of children diagnosed with Lyme disease recall a preceding tick bite.

Year of Publication

2019

Number of Pages

694-696

Date Published

2019 Apr

ISSN Number

1877-9603

Abstract

<p>Of 1770 children undergoing emergency department evaluation for Lyme disease, 362 (20.5%) children had Lyme disease. Of those with an available tick bite history, only a minority of those with Lyme disease had a recognized tick bite (60/325; 18.5%, 95% confidence interval 14.6-23.0%). Lack of a tick bite history does not reliably exclude Lyme disease.</p>

DOI

10.1016/j.ttbdis.2019.02.015

Alternate Title

Ticks Tick Borne Dis

PMID

30853264

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