Positive 2-Tiered Lyme Disease Serology is Uncommon in Asymptomatic Children Living in Endemic Areas of the United States

Garro, Aris; Bennett, Jonathan E.; Balamuth, Fran; Levas, Michael N.; Neville, Desiree N; Branda, John C.; Maulden, Alexandra B.; Lantos, Paul M.; Nigrovic, Lise E.

doi:10.1097/inf.0000000000002157

Cited by 10 publications

(6 citation statements)

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“…Therefore, our findings should not be applied to children with nonspecific constitutional symptoms, a clinical situation in which Lyme disease testing is not routinely recommended (12). Second, we lack a definitive gold standard for the diagnosis of Lyme disease, as the clinical features are not pathognomonic unless a classical bulls-eye skin rash is present, and Lyme disease serology can produce both false-positive and false-negative test results (18,19). We relied on CDC criteria for interpretation of serologic testing.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

2019

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Conventional two-tiered testing (CTTT) for Lyme disease includes a first-tier enzyme immunoassay (EIA) followed by a supplemental immunoblot, and modified two-tiered testing (MTTT) relies on two different sequential EIAs without the inclusion of an immunoblot. MTTT has shown promising results as an alternative strategy for the diagnosis of Lyme disease in adults but has not yet been evaluated in children. We performed a cross-sectional study of children and adolescents ≤21 years of age undergoing clinical investigation for suspected Lyme disease. Serum specimens were analyzed with both a whole-cell sonicate (WCS) and a C6 EIA, with a supplemental immunoblot if either EIA was positive or equivocal. We compared CTTT (WCS EIA followed by supplemental immunoblot) to MTTT (WCS EIA followed by C6 EIA) using McNemar’s test to evaluate for agreement beyond chance alone. We then used a kappa statistic to measure level of the agreement between testing strategies. We included 1,066 serum specimens, of which 156 (14.6%) had a positive CTTT and 165 (15.5%) had a positive MTTT. There were no significant differences between MTTT and CTTT (P = 0.16). Although the overall agreement between MTTT and CTTT was high (kappa, 0.88; 95% confidence interval, 0.84 to 0.92), 33 children had discordant test results. In a cohort of children and adolescents undergoing investigation for suspected Lyme disease, CTTT and MTTT results agreed in most cases. Since immunoblots are time-consuming, laborious, and challenging to interpret, MTTT provides a promising alternate Lyme disease testing strategy for children.

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Section: Discussionmentioning

confidence: 98%

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

2019

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“…A false positive test, however, should be differentiated from the concept of an asymptomatic patient [ 39 , 40 ]. Asymptomatic seroconversion, that is, the development of a serological response for B. burgdorferi without specific signs of the disease, is increasingly being reported; its incidental finding varies from 2.6 to 15% among children in endemic areas [ 39 , 41 , 42 ]. In our cohort, we found only one positive two-tier testing result in a child referred for an asymptomatic tick bite.…”

Section: Discussionmentioning

confidence: 99%

Pediatric Lyme Disease in Northern Italy: An 18-Year Single-Center Case Series

Forlanini,

Di Tonno,

Caiazzo

et al. 2024

Microorganisms

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Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary.

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“…Fourth, all study enrollment sites were located in urban areas. However, many families bypass local care sites to seek care for their children at regional pediatric centers [ 30 ]. Fifth, we only performed short-term clinical follow-up (1 month after enrollment) and may not have identified subtle symptoms in children with an identified coinfection.…”

Section: Discussionmentioning

confidence: 99%

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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Positive 2-Tiered Lyme Disease Serology is Uncommon in Asymptomatic Children Living in Endemic Areas of the United States

Cited by 10 publications

References 10 publications

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

Pediatric Lyme Disease in Northern Italy: An 18-Year Single-Center Case Series

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

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