Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study

Rosa Maja Møhring Gynthersen; Mette Frimodt Hansen; Lukas Frans Ocias; Andreas Kjaer; Randi Føns Petersen; Sisse Rye Ostrowski; Lene Harritshøj; Søren Jacobsen; Ulrik Overgaard; Karen Angeliki Krogfelt; Anne Mette Lebech; Helene Mens

doi:10.1186/s12941-023-00571-5

Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study

Rosa Maja Møhring Gynthersen^*, Mette Frimodt Hansen^*, Lukas Frans Ocias, Andreas Kjaer, Randi Føns Petersen, Sisse Rye Ostrowski, Lene Harritshøj, Søren Jacobsen, Ulrik Overgaard, Karen Angeliki Krogfelt, Anne Mette Lebech, Helene Mens

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Background: The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods: Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher’s exact test. Results: Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 – 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8–11.5%) and 11/192 (5.7%, 95%: CI 3.2–10.0%). Conclusion: In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.

Original language	English
Article number	20
Journal	Annals of Clinical Microbiology and Antimicrobials
Volume	22
Issue number	1
ISSN	1476-0711
DOIs	https://doi.org/10.1186/s12941-023-00571-5
Publication status	Published - 20 Mar 2023

Bibliographical note

Funding Information:
The project was partially supported by the Interreg North Sea Region programme, NorthTick, Grant no. J-No.: 38-2-7-19 and by Danish National Research Foundation, Grant no.: 126, Aase og Ejnar Danielsens Fond and Funding Copenhagen University Hospital, Rigshospitalet.

Keywords

B-cell depleting therapy
Biological treatment
Immunocompromised patients
Neoehrlichia mikurensis
Neoehrlichiosis
Tick-borne disease
diagnostics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort studyFinal published version, 1.2 MBLicence: CC BY

Cite this

Gynthersen, R. M. M., Hansen, M. F., Ocias, L. F., Kjaer, A., Petersen, R. F., Ostrowski, S. R., Harritshøj, L., Jacobsen, S., Overgaard, U., Krogfelt, K. A., Lebech, A. M., & Mens, H. (2023). Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study. Annals of Clinical Microbiology and Antimicrobials, 22(1), Article 20. https://doi.org/10.1186/s12941-023-00571-5

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title = "Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study",

abstract = "Background: The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods: Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher{\textquoteright}s exact test. Results: Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 – 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8–11.5%) and 11/192 (5.7%, 95%: CI 3.2–10.0%). Conclusion: In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.",

keywords = "B-cell depleting therapy, Biological treatment, Immunocompromised patients, Neoehrlichia mikurensis, Neoehrlichiosis, Tick-borne disease, diagnostics, B-cell depleting therapy, Biological treatment, Immunocompromised patients, Neoehrlichia mikurensis, Neoehrlichiosis, Tick-borne disease, diagnostics",

author = "Gynthersen, {Rosa Maja M{\o}hring} and Hansen, {Mette Frimodt} and Ocias, {Lukas Frans} and Andreas Kjaer and Petersen, {Randi F{\o}ns} and Ostrowski, {Sisse Rye} and Lene Harritsh{\o}j and S{\o}ren Jacobsen and Ulrik Overgaard and Krogfelt, {Karen Angeliki} and Lebech, {Anne Mette} and Helene Mens",

note = "Funding Information: The project was partially supported by the Interreg North Sea Region programme, NorthTick, Grant no. J-No.: 38-2-7-19 and by Danish National Research Foundation, Grant no.: 126, Aase og Ejnar Danielsens Fond and Funding Copenhagen University Hospital, Rigshospitalet.",

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doi = "10.1186/s12941-023-00571-5",

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Gynthersen, RMM, Hansen, MF, Ocias, LF, Kjaer, A, Petersen, RF, Ostrowski, SR, Harritshøj, L, Jacobsen, S, Overgaard, U, Krogfelt, KA, Lebech, AM & Mens, H 2023, 'Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study', Annals of Clinical Microbiology and Antimicrobials, vol. 22, no. 1, 20. https://doi.org/10.1186/s12941-023-00571-5

TY - JOUR

T1 - Neoehrlichia mikurensis in Danish immunocompromised patients

T2 - a retrospective cohort study

AU - Gynthersen, Rosa Maja Møhring

AU - Hansen, Mette Frimodt

AU - Ocias, Lukas Frans

AU - Kjaer, Andreas

AU - Petersen, Randi Føns

AU - Ostrowski, Sisse Rye

AU - Harritshøj, Lene

AU - Jacobsen, Søren

AU - Overgaard, Ulrik

AU - Krogfelt, Karen Angeliki

AU - Lebech, Anne Mette

AU - Mens, Helene

N1 - Funding Information: The project was partially supported by the Interreg North Sea Region programme, NorthTick, Grant no. J-No.: 38-2-7-19 and by Danish National Research Foundation, Grant no.: 126, Aase og Ejnar Danielsens Fond and Funding Copenhagen University Hospital, Rigshospitalet.

PY - 2023/3/20

Y1 - 2023/3/20

N2 - Background: The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods: Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher’s exact test. Results: Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 – 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8–11.5%) and 11/192 (5.7%, 95%: CI 3.2–10.0%). Conclusion: In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.

AB - Background: The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods: Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher’s exact test. Results: Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 – 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8–11.5%) and 11/192 (5.7%, 95%: CI 3.2–10.0%). Conclusion: In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.

KW - B-cell depleting therapy

KW - Biological treatment

KW - Immunocompromised patients

KW - Neoehrlichia mikurensis

KW - Neoehrlichiosis

KW - Tick-borne disease

KW - diagnostics

KW - B-cell depleting therapy

KW - Biological treatment

KW - Immunocompromised patients

KW - Neoehrlichia mikurensis

KW - Neoehrlichiosis

KW - Tick-borne disease

KW - diagnostics

U2 - 10.1186/s12941-023-00571-5

DO - 10.1186/s12941-023-00571-5

M3 - Journal article

AN - SCOPUS:85150877105

SN - 1476-0711

VL - 22

JO - Annals of Clinical Microbiology and Antimicrobials

JF - Annals of Clinical Microbiology and Antimicrobials

IS - 1

M1 - 20

ER -