"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.
- MeSH
- Anaplasmataceae classification genetics isolation & purification MeSH
- Genes, Essential MeSH
- Phylogeny MeSH
- Genetic Variation * MeSH
- Genotype * MeSH
- Anaplasmataceae Infections epidemiology microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Molecular Epidemiology methods MeSH
- Multilocus Sequence Typing methods MeSH
- RNA, Ribosomal, 16S genetics MeSH
- Aged MeSH
- Cluster Analysis MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Germany MeSH
- Sweden MeSH
BACKGROUND: Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. METHODS: We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. RESULTS: The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. CONCLUSIONS: 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.
- MeSH
- Aneurysm microbiology MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Autoimmune Diseases microbiology MeSH
- C-Reactive Protein metabolism MeSH
- DNA, Bacterial blood MeSH
- Hematologic Neoplasms microbiology MeSH
- Fever microbiology MeSH
- Anaplasmataceae Infections complications diagnosis drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Musculoskeletal Pain microbiology MeSH
- Tick-Borne Diseases complications diagnosis drug therapy microbiology MeSH
- Communicable Diseases, Emerging diagnosis drug therapy microbiology MeSH
- Delayed Diagnosis MeSH
- Pulmonary Embolism microbiology MeSH
- Aged MeSH
- Splenectomy MeSH
- Ischemic Attack, Transient microbiology MeSH
- Venous Thrombosis microbiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Hematooncologic patients often host rare or fastidious pathogens. Using 16S rDNA sequencing and transmission electron microscopy, we have identified 2 lymphoma patients infected with Candidatus Neoehrlichia mikurensis. In both individuals, the clinical presentation suggested ehrlichiosis-like syndrome. We believe that molecular techniques open new vistas in the field of pathogen detection.
- MeSH
- Anaplasmataceae classification genetics isolation & purification MeSH
- Molecular Diagnostic Techniques MeSH
- DNA, Bacterial genetics MeSH
- Ehrlichiosis diagnosis MeSH
- Microscopy, Electron MeSH
- Hematologic Neoplasms complications MeSH
- Fever of Unknown Origin diagnosis microbiology MeSH
- Immunocompromised Host MeSH
- Anaplasmataceae Infections complications diagnosis MeSH
- Ticks microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Polymerase Chain Reaction MeSH
- DNA, Ribosomal genetics MeSH
- Sequence Analysis, DNA MeSH
- Animals MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
