Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
Abstract:Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
“…Neoehrlichia mikurensis" strains observed in this study may be that the samples were all derived from humans, with all of them being immunocompromised. These patients were selected because they exhibited very high loads of bacteria in their blood (12), which allowed for the DNA sequence-based analyses of multiple genes. One of the challenges of this study was to select accurate genotyping markers for "Ca.…”
Section: Discussionmentioning
confidence: 99%
“…The study was performed in accordance with the declaration of Helsinki. Neoehrlichiosis was diagnosed by the analysis of EDTA-plasma samples using a specific real-time PCR targeting the groEL sequence and confirmed by panbacterial PCR assays with subsequent sequencing of the genes (10,12,20,25).…”
Section: Methodsmentioning
confidence: 99%
“…twice daily for 2 weeks) and recovered completely within 1 week. Details of the clinical pictures and outcome of the remainder of the patients have been reported previously (10,12,20,24,25).…”
Section: Patientsmentioning
confidence: 99%
“…MLSA can map the genetic changes in these housekeeping genes and can serve as a reliable method for the study of epi-demiological relationships (23).We have analyzed clinical "Ca. Neoehrlichia mikurensis" strains derived from 12 immunocompromised neoehrlichiosis patients from Sweden, Germany, and the Czech Republic; nine of these cases have been published already (10,12,20,24,25).We also report on three new cases of neoehrlichiosis diagnosed in Sweden during 2014 and the associated strains that were typed with this new assay.…”
mentioning
confidence: 97%
“…Neoehrlichiosis, the human infectious disease caused by "Ca. Neoehrlichia mikurensis," is believed to be transmitted via tick bites (11) and may present as a severe febrile illness with thromboembolic events in immunocompromised patients (12). "Ca.…”
h "Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n ؍ 9), the Czech Republic (n ؍ 2), and Germany (n ؍ 1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
“…Neoehrlichia mikurensis" strains observed in this study may be that the samples were all derived from humans, with all of them being immunocompromised. These patients were selected because they exhibited very high loads of bacteria in their blood (12), which allowed for the DNA sequence-based analyses of multiple genes. One of the challenges of this study was to select accurate genotyping markers for "Ca.…”
Section: Discussionmentioning
confidence: 99%
“…The study was performed in accordance with the declaration of Helsinki. Neoehrlichiosis was diagnosed by the analysis of EDTA-plasma samples using a specific real-time PCR targeting the groEL sequence and confirmed by panbacterial PCR assays with subsequent sequencing of the genes (10,12,20,25).…”
Section: Methodsmentioning
confidence: 99%
“…twice daily for 2 weeks) and recovered completely within 1 week. Details of the clinical pictures and outcome of the remainder of the patients have been reported previously (10,12,20,24,25).…”
Section: Patientsmentioning
confidence: 99%
“…MLSA can map the genetic changes in these housekeeping genes and can serve as a reliable method for the study of epi-demiological relationships (23).We have analyzed clinical "Ca. Neoehrlichia mikurensis" strains derived from 12 immunocompromised neoehrlichiosis patients from Sweden, Germany, and the Czech Republic; nine of these cases have been published already (10,12,20,24,25).We also report on three new cases of neoehrlichiosis diagnosed in Sweden during 2014 and the associated strains that were typed with this new assay.…”
mentioning
confidence: 97%
“…Neoehrlichiosis, the human infectious disease caused by "Ca. Neoehrlichia mikurensis," is believed to be transmitted via tick bites (11) and may present as a severe febrile illness with thromboembolic events in immunocompromised patients (12). "Ca.…”
h "Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n ؍ 9), the Czech Republic (n ؍ 2), and Germany (n ؍ 1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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