You have full access to this article via your institution. Download PDF We thank Dr. Greenberg for her comments on our study.1 As physicians and psychologists caring for pediatric patients

with Lyme disease and their families, we are grateful for the opportunity to respond and highlight several points raised, which were not possible within the scope of the initial publication.

We agree that larger studies with prospectively collected data, specifically in children, are necessary to further refine our study findings. The low number of participants with prolonged

symptoms for the outcomes in our study precluded the use of multivariable modeling. We recognize that our study design may have introduced differential response bias. However, it is not

terms of age and race, and not symptoms or stage of Lyme disease. Overall, our study results are similar to other pediatric studies which have shown that most children who are appropriately

treated for Lyme disease will have excellent long-term outcomes.2,3,4,5,6,7,8,9 It is important to make the distinction between definite sequelae and post-treatment Lyme disease symptoms, as

it was performed in the study by Skogman et al.10 For example, irreversible nerve damage can lead to persistent sequelae, as it is the case of incomplete resolution of facial palsy. These

sequelae should be differentiated from subjective nonspecific symptoms. Importantly, the study by Skogman et al.10 showed that children treated for neuroborreliosis had similar rates of

reported nonspecific symptoms, and their effect on daily activities and school performance, to matched controls. Regarding the study by Fallon at al.,11 it is important to note that the 28%

increase in the rate of mental disorder diagnoses is relative, and, as stated by the study, the absolute population risk is low. Interestingly, Lyme neuroborreliosis was not associated with

an increased risk of psychiatric illness, similarly to another population-based matched cohort study.12 Studies examining neuropsychiatric symptomatology in children treated for Lyme disease

have shown similar outcomes when compared to matched siblings controls13 and matched controls.14 Foremost, our findings provide an important starting point for health care professionals and

families to be made aware that most children do make full recovery, often within one or two months of diagnosis. It has been our experience in clinical practice that many children and

families who receive a diagnosis of early localized, early disseminated or late Lyme disease are fearful, due to the impression that there is not effective treatment available and that this

will be a lifelong illness. The lack of pediatric-specific information about outcomes, easily accessible to health care professionals and the general public, contributes to this belief. We

have found that publication of our study has provided many of our referred patients and families peace of mind on the knowledge that the odds are very much in favor for a full recovery with

appropriate treatment. Our study serves as a source of systematically collected and validated data documenting the spectrum of response to therapy in most children and is useful to not only

patients and their families but also those who are caring for them and addressing expectations for course of recovery. While most patients will recover, our study showed that full recovery

may take 6 months or longer in a significant subset of pediatric patients (22%). Our intention was never to dismiss this group of patients. In fact, one of the goals of our study was to

identify and operationalize a pediatric-specific description of post-treatment symptoms, potentially unique to children and their developmental stages. The finding that the majority recover

more quickly in no way diminishes the importance that children who are suffering from prolonged symptoms need our attention and care. Only by recognizing this entity and sharing this

information with health care professionals will these individuals be appropriately diagnosed and treated. Our collective clinical mission is not only to ensure that children receive the

correct diagnosis and treatment to optimize their outcome, but to also ensure that children with prolonged symptoms are appropriately identified and have access to effective treatments. We

agree that well-designed prospective studies looking at long term follow-up in youth with Lyme disease are needed to determine the persistence of and risk factors for different types of

symptomatology. The pathogenesis of these prolonged symptoms is not clear and is likely multifactorial. This is an active area of research by many different groups, thinking broadly in

scope. These studies must be scientifically rigorous and adequately powered to detect meaningful impact, or lack thereof, on patient outcomes. Furthermore, the broader concept of

infection-associated chronic illnesses, encompassing overlapping symptoms of unclear etiology occurring after different conditions, is a powerful paradigm for progress moving forward. To

this end, multicenter collaborative partnerships that leverage cross-disciplinary expertise, as well as geographic and demographic diversity, are the ideal platform to design and carry out

these studies, with crosstalk between clinicians, patients and scientists. We are committed to continued collaborative work toward the goal of identifying effective, safe, accessible and

affordable treatments for patients suffering from prolonged symptoms following _Borrelia burgdorferi_ infection. REFERENCES * Monaghan, M. et al. Pediatric Lyme disease: systematic

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FUNDING Funding This work was supported by the Clinical and Translational Science Institute at Children’s National (CTSI-CN) [Grant numbers UL1TR001876-05 and UL1TR001876-02S1] and the

Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to A.M.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of

Psychology and Behavioral Health, Children’s National Hospital, Washington, DC, USA Maureen Monaghan * Department of Pediatrics, The George Washington University School of Medicine and

Health Sciences, Washington, DC, USA Maureen Monaghan, Marcin Gierdalski, James E. Bost & Roberta L. DeBiasi * Center for Translational Research, Children’s Research Institute,

Washington, DC, USA Stephanie Norman, Marcin Gierdalski, James E. Bost & Roberta L. DeBiasi * Division of Biostatistics, Children’s National Hospital, Washington, DC, USA Marcin

Gierdalski & James E. Bost * Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

Adriana Marques * Division of Infectious Diseases, Children’s National Hospital, Washington, DC, USA Roberta L. DeBiasi * Department of Microbiology, Immunology and Tropical Medicine, The

George Washington University School of Medicine and Health Sciences, Washington, DC, USA Roberta L. DeBiasi Authors * Maureen Monaghan View author publications You can also search for this

author inPubMed Google Scholar * Stephanie Norman View author publications You can also search for this author inPubMed Google Scholar * Marcin Gierdalski View author publications You can

also search for this author inPubMed Google Scholar * Adriana Marques View author publications You can also search for this author inPubMed Google Scholar * James E. Bost View author

publications You can also search for this author inPubMed Google Scholar * Roberta L. DeBiasi View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS All authors drafted the response, revised it critically for important intellectual content, and provided final approval of the submitted manuscript. CORRESPONDING AUTHOR

Correspondence to Roberta L. DeBiasi. ETHICS DECLARATIONS COMPETING INTERESTS M.M. is currently employed by the National Institute of Diabetes and Digestive and Kidney Diseases, National

Institutes of Health. All data for this manuscript were collected prior to her employment at the National Institutes of Health. A.M. is employed by the National Institute of Allergy and

Infectious Diseases, National Institutes of Health; A.M. has a patent (US 8,926,989) and serves as an unpaid scientific advisor to the Global Lyme Alliance and the American Lyme Disease

Foundation. The other authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps

and institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Monaghan, M., Norman, S., Gierdalski, M. _et al._ Reply to

Correspondence. _Pediatr Res_ 95, 3–4 (2024). https://doi.org/10.1038/s41390-023-02790-0 Download citation * Received: 23 July 2023 * Accepted: 29 July 2023 * Published: 18 September 2023 *

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