Journal of Clinical Microbiology, December 2001, p. 4591-4592, Vol. 39, No. 12
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.12.4591-4592.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
First European Pediatric Case of Human Granulocytic
Ehrlichiosis
Maja
Arne
,1,*
Miroslav
Petrovec,2
Stanka
Lotri
-Furlan,1
Tatjana
Avsic
Zupanc,2 and
Franc
Strle1
Department of Infectious Diseases, University
Medical Center Ljubljana, Japljeva 2, 1525 Ljubljana,1 and Institute of
Microbiology and Immunology, Medical Faculty, University of
Ljubljana, Zalo
ka 4, 1000 Ljubljana,2
Slovenia
Received 21 June 2001/Returned for modification 26 August
2001/Accepted 5 October 2001
 |
ABSTRACT |
Herein we report on the first confirmed pediatric case of
acute human granulocytic ehrlichiosis in Europe. Presentation in this
11-year-old girl was comparable to clinical findings seen in adult
European patients with human granulocytic ehrlichiosis; i.e., she had
self-limited febrile illness with leukopenia, thrombocytopenia, and
elevated serum C-reactive protein concentration. It is of interest that
the patient not only had a fourfold change in antibody titer to
Ehrlichia phagocytophila but also developed antibodies to Ehrlichia chaffeensis and that her PCR test result
was positive on the third as well as on the 22nd day after the onset of
illness, that is, 16 days after spontaneous defervescence.
 |
CASE REPORT |
On February 21, 2001, an 11-year-old girl was
admitted to the Department of Infectious Diseases, University Medical
Center Ljubljana, Ljubljana, Slovenia, with a 3-day history of high
fever, fatigue, headache, nausea, and abdominal pain. She had no known chronic illnesses, had not been vaccinated against tick-borne encephalitis (TBE), and had not traveled outside Slovenia. The patient
had received a tick bite on her neck 9 days before the onset of the
illness, during a trip to the southwestern part of Slovenia. The region
is known to be an area of endemicity for TBE and Lyme borreliosis; an
adult patient diagnosed recently with proven human granulocytic
ehrlichiosis (HGE) had received tick bites in this area. Tick bites in
February are highly unusual in this part of Central Europe; however,
the winter of 2001 was exceptionally mild. The patient's physical
examination was notable for fever (38.8°C), conjunctivitis,
erythematous throat, and right upper quadrant abdominal tenderness.
Meningeal signs were absent. Initial laboratory findings revealed
normal erythrocyte sedimentation rate, serum electrolyte
concentrations, and transaminase and alkaline phosphatase activities.
The serum C-reactive protein value was 39 mg/liter (normal value, <5
mg/liter), the total leukocyte count was 2.3 × 109/liter (16% band forms, 28% segmented, 41%
lymphocytes, 15% monocytes), and the platelet count was 90 × 109/liter, while red cell counts were normal. The
girl was treated symptomatically. On the third day of hospitalization
(sixth day of illness) fever and all other signs and symptoms
disappeared. The child remained well during the whole observational
period of 2 months; the results of control laboratory examinations were in the normal range.
Indirect fluorescent-antibody assays for immunoglobulin M (IgM)
and IgG antibodies to Borrelia burgdorferi sensu lato (whole cells of a local isolate of Borrelia afzelii were used as
an antigen) as well as enzyme-linked immunosorbent assays (Dade
Behring) for the presence of TBE IgM and IgG antibodies in acute- and
convalescent-phase serum samples were negative. PCR testing of DNA
extracted from the leukocyte fraction of blood yielded positive
results. Subsequent sequence analysis of the amplified portion (1,256 bp) of the GroESL gene of Ehrlichia phagocytophila revealed
complete identity to those previously amplified from HGE patients in
Slovenia (6). PCR results and serum antibody titers to
E. phagocytophila (the causative agent of HGE) and
Ehrlichia chaffeensis (the etiologic agent of human
monocytic ehrlichiosis) at the time of acute illness and during
convalescence are presented in Table 1.
It is of interest that our patient developed a fourfold increase of
antibody titer to E. phagocytophila but also developed
low-titer antibodies to E. chaffeensis. The significance of
this finding is still unclear, but it probably represents only a low
level of cross-reactivity as previously reported from the United States
and Europe (1, 6).
View this table:
[in this window]
[in a new window]
|
TABLE 1.
Serum antibody titers to E. chaffeensis and
E. phagocytophila and E. phagocytophila PCR
findings in an 11-year-old girl from Slovenia
|
|
Three tick-transmitted ehrlichial diseases were discovered
during the last 15 years in the United States: human monocytic ehrlichiosis, caused by E. chaffeensis, was reported for the
first time in 1987 (7); HGE was first reported in 1994 (3); and the disease caused by Ehrlichia
ewingii was first reported in 1999 (2). The first
confirmed European HGE case was discovered in 1996 in Slovenia
(8). More than 600 patients with HGE were reported until
2000, the large majority being from the United States (1).
Clinically, HGE is manifested by fever, headache, myalgias, and
arthralgias, and it is often accompanied by laboratory findings such as
thrombocytopenia, leukopenia, mildly elevated liver transaminases,
and/or elevated serum C-reactive protein concentrations
(1). The clinical characteristics in children are assumed
to be similar to those in adults (5). However, the
clinical information on HGE in children is limited to individual case
reports and is completely restricted to data from the United States
(4, 5).
Our patient represents the first European child with confirmed HGE. Her
presentation was comparable to clinical findings seen in our adult
patients with HGE (6), with the exception of abdominal pain, which is probably not specific for HGE in childhood because it is
seen quite often also in several other infectious diseases in children
but only exceptionally in adults.
 |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Infectious Diseases, University Medical Center, Japljeva 2, 1525 Ljubljana, Slovenia. Phone: 386 1 2310 558. Fax: 386 1 2302 781. E-mail: maja.arnez{at}kclj.si.
 |
REFERENCES |
| 1.
|
Bakken, J. S., and J. S. Dumler.
2000.
Human granulocytic ehrlichiosis.
Clin. Infect. Dis.
31:554-560[CrossRef][Medline].
|
| 2.
|
Buller, R. S.,
M. Arens,
S. P. Hmiel,
C. D. Paddock,
J. W. Sumner,
Y. Rikihisa,
A. Unver,
M. Gaudreault-Keener,
F. A. Manian,
A. M. Liddell,
N. Schmulewitz, and G. A. Storch.
1999.
Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis.
N. Engl. J. Med.
341:148-155[Abstract/Free Full Text].
|
| 3.
|
Chen, S. M.,
J. S. Dumler,
J. S. Bakken, and D. H. Walker.
1994.
Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease.
J. Clin. Microbiol.
32:589-595[Abstract/Free Full Text].
|
| 4.
|
Gershel, J. C.
2000.
Human granulocytic ehrlichiosis presenting as abdominal pain.
Pediatrics
106:602-604[Abstract/Free Full Text].
|
| 5.
|
Jacobs, R. F., and G. E. Schutze.
1997.
Ehrlichiosis in children.
J. Pediatr.
131:184-192[CrossRef][Medline].
|
| 6.
|
Lotri -Furlan, S.,
M. Petrovec,
T. Avsic Zupanc,
W. L. Nicholson,
J. W. Sumner,
J. E. Childs, and F. Strle.
1998.
Human granulocytic ehrlichiosis in Europe: clinical and laboratory findings for four patients from Slovenia.
Clin. Infect. Dis.
27:424-428[Medline].
|
| 7.
|
Maeda, K.,
N. Markowitz,
R. C. Hawley,
M. Ristic,
D. Cox, and J. E. McDade.
1987.
Human infection with Ehrlichia canis, a leukocytic rickettsia.
N. Engl. J. Med.
316:853-856[Medline].
|
| 8.
|
Petrovec, M.,
S. Lotric Furlan,
T. Avsic Zupanc,
F. Strle,
P. Brouqui,
V. Roux, and J. S. Dumler.
1997.
Human disease in Europe caused by a granulocytic Ehrlichia species.
J. Clin. Microbiol.
35:1556-1559[Abstract].
|
Journal of Clinical Microbiology, December 2001, p. 4591-4592, Vol. 39, No. 12
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.12.4591-4592.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.