To the Editors,
Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum and transmitted by Ixodes ricinus ticks. To date, only 2 cases of HGA in European children younger than 15 years were reported.1,2
A 14-year-old boy was admitted to our department in June, 2011 with a 3-day fever up to 39.7°C accompanied by chills, headache, neck and lumbar pain and passing of dark urine. The patient lived in a rural area and reported being bitten by numerous ticks in the preceding month. He had no underlying illnesses and at the age of 12 had completed a 3-dose basic tick-borne encephalitis (TBE) vaccination.
On admission, he was afebrile with jaundice and a discrete maculopapular rash on the trunk and neck. A systolic murmur was heard in the precordium, and the abdomen was tender to palpation below the right costal margin and in the right flank region. Elevated C-reactive protein (10.1 mg/dL), normal white blood cells count (4300/mm3) with 19% band forms, thrombocytopenia (91,000/mm3), elevated transaminases (aspartate aminotransferase, 1.96; alanine aminotransferase, 1.47; gamma-glutamyltransferase, 1.96 μkat/L; normal values, <0.58, <0.74 and <0.92 μkat/L, respectively), lactate dehydrogenase (8.67 μkat/L; normal level < 4.13) and bilirubin (total, 64 μmol/L; direct, 18 μmol/L; upper normal values, 17 and 5 μmol/L, respectively) as well as prolonged prothrombin time (0.63, international normalized ratio, 1.32) were found. Serum electrolytes, urea and creatinine were normal.
The patient was given cefotaxime and flucloxacillin for suspected sepsis but remained febrile. Because blood, urine and stool cultures were negative, white blood cells (nadir 1600/mm3) and platelet (53,000/mm3) counts further decreased and transaminase levels increased (maximum values aspartate aminotransferase, 3.59; alanine aminotransferase, 3.05 and γ-GT, 3.80 μkat/L) and tests for A. phagocytophilum infection [demonstration of morulae in peripheral blood smear, detection of A. phagocytophilum genome in blood with polymerase chain reaction (PCR) and immunofluorescence assay for detection of A. phagocytophilum antibodies] were performed on day 3 of hospital stay. Based on a positive specific PCR result, treatment with doxycycline 100 mg/12 hours was accompanied by prompt defervescence and normalization of laboratory values. Differential diagnoses included tests for hantavirus infection (serology) and infection with Leptospira sp. (PCR in urine) that were negative, whereas serology for TBE was compatible with postvaccination levels (positive IgG and negative IgM). The patient made an uneventful recovery after 10 days of doxycycline treatment. The test results for A. phagocytophilum and Ehrlichia chaffeensis infection are shown in Table 1.
HGA is rare in Europe and affects predominately adults with only 2 cases described in children.1,2 In a prospective study, on fever within 6 weeks after a tick bite in Slovenian children <15 years, a tick-transmitted infection was detected in 28 (53%) of 53 children with TBE being most frequent (18 cases, 64%) and only 1 case (4%) of probable HGA (presence of antibodies without a subsequent 4-fold increase).5 A seroprevalence study among 143 children and young adults in Slovenia demonstrated the presence of antibodies to A. phagocytophilum in 15.4% of study subjects,6 whereas study on vectors revealed that 3.2% of the I. ricinus ticks contained nucleotide sequences of portions of the bacterial groESL heat shock operon identical to those previously determined for human patients with HGA from Slovenia.3 Although rare, HGA should be suspected in a child with fever after a tick bite, especially when leukopenia and/or thrombocytopenia, elevated C-reactive protein levels and increased liver function tests are present and treatment with doxycycline should be given in microbiologically confirmed cases.
Marko Pokorn, MD
Department of Infectious Diseases University Medical Centre Ljubljana
Tatjana Avšič Županc, PhD
Institute of Microbiology and Immunology Medical Faculty, University of Ljubljana
Franc Strle, MD, PhD
Department of Infectious Diseases University Medical Centre Ljubljana Ljubljana, Slovenia
1. Arnež M, Petrovec M, Lotrič-Furlan S, et al. First European pediatric case of human granulocytic ehrlichiosis. J Clin Microbiol. 2001;39:4591–4592
2. Psaroulaki A, Koliou M, Chochlakis D, et al. Anaplasma phagocytophilum
infection in a child. Pediatr Infect Dis J. 2008;27:664–666
3. Petrovec M, Sumner JW, Nicholson WL, et al. Identity of ehrlichial DNA sequences derived from Ixodes ricinus
ticks with those obtained from patients with human granulocytic ehrlichiosis in Slovenia. J Clin Microbiol. 1999;37:209–210
4. Lotric-Furlan S, Petrovec M, Avsic-Zupanc T, et al. Comparison of patients fulfilling criteria for confirmed and probable human granulocytic ehrlichiosis. Scand J Infect Dis. 2004;36:817–822
5. Arnez M, Luznik-Bufon T, Avsic-Zupanc T, et al. Causes of febrile illnesses after a tick bite in Slovenian children. Pediatr Infect Dis J. 2003;22:1078–1083
6. Čižman M, Avsic-Zupanc T, Petrovec M, et al. Seroprevalence of ehrlichiosis, Lyme borreliosis
and tick-borne encephalitis infections in children and young adults in Slovenia. Wien Klin Wochenschr. 2000;112:842–845