Correspondence
Human Granulocytic Ehrlichiosis in Western Europe
N Engl J Med 1999; 340:1214-1216April 15, 1999
- Article
To the Editor:
Human granulocytic ehrlichiosis was first reported in the United States in 1994.1 Over the past five years at least several hundred cases have been reported, mostly in the upper Midwest and Northeast, regions where other diseases transmitted by Ixodes scapularis ticks, such as Lyme disease and babesiosis, are common. Four cases of human granulocytic ehrlichiosis have also recently been documented in Slovenia.2 We describe a case of human granulocytic ehrlichiosis in western Europe.
In September 1998, a 58-year-old Dutch man presented with a seven-day history of fever, chills, and diarrhea. He often camped in Gelderland, a region where Lyme disease is prevalent; however, a recent tick bite was not noted. He had not been out of the Netherlands during the six months before his illness. On examination, the temperature was 39.8°C and several petechiae were noted on the legs. Laboratory testing demonstrated leukopenia (3400 leukocytes per cubic millimeter) and thrombocytopenia (24,000 platelets per cubic millimeter). Levels of creatine kinase (1460 U per liter), aspartate aminotransferase (516 U per liter), alanine aminotransferase (208 U per liter), and lactate dehydrogenase (2970 U per liter) were elevated. Examination of a peripheral-blood smear revealed characteristic morulae containing the agent of human granulocytic ehrlichiosis in 7 percent of the polymorphonuclear leukocytes (Figure 1AFigure 1
Diagnosis of Human Granulocytic Ehrlichiosis.). The patient was treated with 200 mg of doxycycline orally per day for two weeks, and his symptoms resolved within a few days.The results of serologic and polymerase-chain-reaction (PCR) tests further supported the diagnosis of human granulocytic ehrlichiosis. An indirect immunofluorescence (IgG) assay in which HL-60 cells infected with human granulocytic ehrlichiosis were used as the antigen3 was initially negative and then became positive (serum dilution, up to 1:1000) at four weeks (Figure 1B). IgG antibodies to recombinant HGE-44, a 44-kd protein commonly recognized in cases of human granulocytic ehrlichiosis in the United States,4 were readily detected on immunoblotting at four weeks, at a serum dilution of up to 1:12,000 (Figure 1C). Neither the immunofluorescence assay nor immunoblotting detected IgM antibodies at either time. Human granulocytic ehrlichiosis DNA was detected by PCR with HGE-44 primers in peripheral blood obtained from the patient at presentation.4,5 Sequencing of 150 bp at the 5' region of the amplified HGE-44 DNA revealed 96 percent homology with the HGE-44 gene from an organism isolated in Massachusetts.4
These data demonstrate that human granulocytic ehrlichiosis occurs in western Europe and should be considered in the differential diagnosis when evaluating persons who are at risk for tick-borne diseases. Antibodies to HGE-44 develop during infection, and the identification of these antibodies may aid in the diagnosis of the disease in both the United States and Europe. As human granulocytic ehrlichiosis becomes more commonly recognized on various continents, the ecology and epidemiology of this emerging infection and the spectrum of clinical disease should become more completely understood.
5 ReferencesAart van Dobbenburgh, M.D.
Het Spittaal Hospital, 7207 BA Zutphen, the NetherlandsAlje P. van Dam, M.D., Ph.D.
University of Amsterdam, 1100 DE Amsterdam, the NetherlandsErol Fikrig, M.D.
Yale University School of Medicine, New Haven, CT 06520-80311
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