Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease
Related Experiment Videos
S M Chen1, J S Dumler, J S Bakken
1Department of Pathology, University of Texas Medical Branch, Galveston 77555.
Abstract:
Six patients from northern Minnesota and Wisconsin with a febrile illness accompanied by granulocytic cytoplasmic morulae suggestive of ehrlichial infection were identified. Two patients died, and splenic granulocytes of one patient contained cytoplasmic vacuoles with organisms ultrastructurally characteristic of ehrlichiae. From one patient, a 1.5-kb DNA product was amplified by PCR with universal eubacterial primers of 16S rDNA. Analysis of the nucleotide sequence of the amplified product revealed 99.9 and 99.8% similarities with E. phagocytophila and E. equi, respectively, neither of which has previously been known to infect humans. From the variable regions of the determined sequence, a forward primer specific for three organisms (human granulocytic ehrlichia, E. phagocytophila, and E. equi) and a reverse primer for these ehrlichiae and E. platys were designed. By nested PCR with amplification by the universal primers and then reamplification with the specific primers described above, the expected 919-bp product was generated from the blood of the index patient and three additional patients. Blood from these four patients and two more patients with granulocytic morulae contained DNA which was amplified by nested PCR involving a combination of a universal primer and the human granulocytic ehrlichia-E. phagocytophila-E. equi-E. platys group-specific primer. This apparently vector-borne human granulocytic ehrlichia has only 92.5% 16S rDNA homology with E. chaffeensis. Nested PCR with group-specific primers did not amplify E. chaffeensis DNA, and E. chaffeensis-specific primers did not amplify DNAs of the human granulocytic ehrlichia. Thus, six patients were shown to be infected by an Ehrlichia species never previously reported to infect humans.
Insights
A novel ehrlichial infection, human granulocytic ehrlichia, was identified in six patients from the Midwest. This bacterium, distinct from Ehrlichia chaffeensis, caused severe illness and was detected using PCR.
Area of Science:
- Infectious Diseases
- Microbiology
- Molecular Biology
Background:
- Ehrlichial infections are tick-borne diseases that can cause significant morbidity and mortality.
- Previous research focused on Ehrlichia chaffeensis as the primary human pathogen in the United States.
Observation:
- Six patients in Minnesota and Wisconsin presented with febrile illness and granulocytic cytoplasmic morulae.
- Autopsy of one patient revealed ehrlichial organisms in splenic granulocytes.
- PCR amplification and sequencing of 16S rDNA identified organisms closely related to Ehrlichia phagocytophila and Ehrlichia equi.
Findings:
- A novel Ehrlichia species, provisionally named human granulocytic ehrlichia, was identified in six patients.
- This agent is genetically distinct from Ehrlichia chaffeensis, with only 92.5% 16S rDNA homology.
- Nested PCR assays were developed for specific detection of this new ehrlichial species.
Implications:
- This discovery expands the known spectrum of human ehrlichial pathogens in North America.
- The findings highlight the importance of considering novel ehrlichial agents in patients with unexplained febrile illnesses.
- Further research is needed to understand the transmission, pathogenesis, and treatment of this newly identified infection.