European Journal of Pediatrics

, Volume 168, Issue 8, pp 937–940

Ulceroglandular tularemia in a toddler in Germany after a mosquito bite

Authors

    • Department of Pediatrics and Adolescent MedicineUniversity Medical Center Freiburg
  • Joerg-Elard Otten
    • Department of Oral and Maxillofacial SurgeryUniversity Medical Center Freiburg
  • Reinhard Berner
    • Department of Pediatrics and Adolescent MedicineUniversity Medical Center Freiburg
  • Annerose Serr
    • Institute of Microbiology, Division of VirologyUniversity Medical Center Freiburg
  • Wolf Splettstoesser
    • German Reference Laboratory for TularemiaBundeswehr Institute of Microbiology
  • Christian von Schnakenburg
    • Department of Pediatrics and Adolescent MedicineUniversity Medical Center Freiburg
Original Paper

DOI: 10.1007/s00431-008-0862-3

Cite this article as:
Hanke, C.A., Otten, J., Berner, R. et al. Eur J Pediatr (2009) 168: 937. doi:10.1007/s00431-008-0862-3

Abstract

Introduction

Although tularemia is a long-known disease, its significance had diminished over the last decades in Middle Europe. However, over the past years, there is new evidence suggesting that tularemia has re-emerged in Germany. In 2007, the highest number of human cases for almost 50 years has been notified. Beside typical vectors, new ways of transmission seem to gain significance. So far, mosquito bite-transmitted tularemia has only been known from Scandinavia but not from Middle Europe.

Case report

We report the first case of a 1-year-old toddler from Southwestern Germany with mosquito bite-associated ulceroglandular tularaemia. The new and interesting features of this case are the young age of the patient and the unusual transmission route. The available data suggesting changes in the epidemiology for tularemia in Germany are reviewed. This is an interesting case of infantile tularemia with a very unusual transmission route, highlighting ongoing changes in the epidemiology of tularemia in Germany.

Keywords

TularemiaInfantFrancisella tularensis holarcticaMosquito biteGermanyEpidemiology

Introduction

Tularemia, a zoonosis typically affecting humans, rodents, and smaller vertebrates, has been known for about 100 years. In recent years, it regained significance due to fears for its putative use as a biological warfare agent [3]. In Germany, several lines of evidence indicate that tularemia has re-emerged since 2004. Besides outbreaks in primate facilities [13], the first outbreak in humans for more than 40 years has occurred in the vicinity of Darmstadt in late 2005 [6]. In 2007, the highest number of human cases for almost 50 years has been identified [14].

The causative agent of tularemia is Francisella tularensis (FT), a Gram-negative, pleomorphic coccobacillus. Two subspecies are notorious for causing human infection, F. tularensis tularensis (type A) and F. tularensis holarctica (type B). Types A and B can both be found in Northern America, whereas only type B is endemic in Europe, Russia, some Northern Asian countries, and Japan. Both subspecies are transmitted to humans by direct contact with infected rodents, rabbits, and hares. Ticks and deer flies are known vectors for type A, whereas mosquitoes transmit type B in Northern Europe [4]. So far, no mosquito-borne cases of tularemia have been reported from Germany. Furthermore, the few German cases that have come to medical attention during the last decades rarely included young children.

In the last decades, infected hares represented the main source of human infection in Germany, causing about 90% of all cases. But in 2007, more than 35% of the notified tularemia cases could not be attributed to contact with hares, and in many cases, the source of infection remained obscure [14].

In this report, we describe an unusual case of a toddler who developed ulceroglandular tularemia caused by F. tularensis holarctica after a mosquito bite in southwestern Germany. This first report of a putative mosquito-borne infection highlights current changes in the epidemiology of tularemia in Germany.

Case report

A 16-month-old and otherwise healthy boy developed fever and an unspecific rash in early October. No other clinical signs were apparent except of a lesion located laterally to the right eye attributed to a mosquito bite. After 5 days, the fever subsided, but the lesion increased and became tender to palpation (Fig. 1a). Additionally, swelling in the right parotid gland was noted. Due to abscess formation at the inoculation site, surgical incision was performed 2 days later. After an additional 10 days, skin ulceration developed at the periorbital abscess site (Fig. 1b). At that time, slowly increasing lymphadenopathy inferior to the abscess site developed. Antibiotic therapy with cefotiam was administered intravenously for 5 days followed by oral clindamycin. General condition remained well, but no clinical improvement of the inflammation was seen during antibiotic therapy. On follow-up visits, lymphadenopathy in the parotid gland area was increasing (Fig. 1c), leading to lymphatic abscess formation as confirmed by ultrasound and magnetic resonance imaging. Surgical incision with drainage of pus was performed 5 weeks after first symptoms.
https://static-content.springer.com/image/art%3A10.1007%2Fs00431-008-0862-3/MediaObjects/431_2008_862_Fig1_HTML.gif
Fig. 1

a Infected mosquito bite with abscess formation, 1 week after febrile illness. Preauricular swelling is already present. b Ulceration at the inoculation site after surgical incision, day 19 after first symptoms. Increased preauricular swelling. c Five weeks after first symptoms. Residual ulcer, increasing inflammation of preauricular lymph nodes with clinical redness and abscess formation on ultrasound

At that point, serologic testing for bartonellosis and a tuberculin skin test was negative, but polymerase chain reaction (PCR) for eubacterial DNA from the drained specimen raised suspicion of an infection with F. tularensis. Tularemia could be confirmed by real-time PCR and testing of the serum mentioned above. The latter test showed a single highly positive reaction in enzyme-linked immunosorbent assay (ELISA) as well as immunoblot (Seramun, Dolgenbrodt, Germany [12]. All PCR assays were performed according to published protocols (Table 1) including a commercially available, standardized test kit (Tib MolBiol, Berlin, Germany [13]). Further differentiation by PCR revealed F. tularensis holarctica (type B). Thus, the diagnosis of tularemia was made 6 weeks after initial presentation. Primary and secondary abscesses were successfully drained, and the child clinically recovered. At this stage, a specific antibiotic therapy was not considered to be necessary.
Table 1

Laboratory confirmation of the F. tularensis infection

Clinical sample

Methods

Target

Results

Reference

Pus (drained abscess)

Eubacterial PCR

16S rRNA gene

+

[10]

Real-time PCR

16S rRNA gene

+

[13]

Real-time PCR

fopA gene

+

[5]

RD1 PCR, gel- based

Chromosomal region RD1

924 bp fragment

[1]

30 bp deletion PCR, gel-based

Chromosomal region Ft-M19

220 bp fragment

[2]

Pus (drained abscess)

Culture

Cysteine heart agar, prolonged cultivation

[12]

Serum

ELISA

Anti-F. tularensis lipopolysaccharide antibodies

+++

[9]

Western Blot

+++

DNA from F. tularensis holarctica could be amplified using different PCR techniques. Both serological assays, detecting anti-F. tularensis specific antibodies, were strongly positive five weeks after onset of symptoms

Discussion

We present the rare case of ulceroglandular tularemia in a 1-year-old boy, who is, to the best of our knowledge, the youngest tularemia patient ever described in Germany. The mode of transmission is most likely a mosquito bite, several of which had occurred at the time the primary lesion was noticed. The infection occurred in early October, a warm autumn period in which mosquitoes were still abundant in the upper Rhine Valley at the vicinity of Fribourg. At that time point, the mother had mosquito bites as well. No previous contact with pet animals, hares, or their excrements and no tick bites could be elicited as the toddler had been supervised indoors at home. There had been no signs of rodents in the family house in a suburban area. The family had not been traveling recently.

Generally, the clinical course of tularemia type B is often milder than with type A. However, clinical courses of type B tularaemia in children are more severe than in adults [15], and pulmonary involvement might be more common. Still, the ulceroglandular form of tularemia is most frequent, and lymphadenopathy and initial fever are typical symptoms in children with tularemia type B. Transmission of type B tularemia via mosquito bite has been repeatedly described from Scandinavia but not from Central Europe. The first isolation of F. tularensis from a child in Denmark was reported in 2005 and could be attributed to a tick bite [2]. In our patient, transmission by a mosquito bite is most likely, as inflammation began at the respective lesion, and no other known potential modes of transmission could be identified in this patient. In Germany, only three to five human cases of tularemia per year used to be reported on average. In late 2005, the first outbreak for more than 40 years has been registered in participants of a hare hunt [6]. In 2007 an increase to 21 reported cases was observed, of which 11 occurred in the southwestern state of Baden-Wuerttemberg [14]. However, none of the other cases was directly linked to a mosquito bite. In one adult case, frequent stays in a forestal area were reported as the sole risk factor for acquiring the infection. Interestingly, this case was reported from the same county as our young patient.

The second reason making this case unusual is the young age of the affected boy. So far, no cases of infants have been reported in Germany, and generally few patients have been younger than school age [8]. On the other hand, lymphadenopathy is very frequently observed in this age group, and routine workup does usually not include a specific test for F. tularensis. Blood cultures often remain negative. Serological testing has high sensitivity and specificity but is not widely established. In recent years, detection of FT by PCR has become another option, but again, availability is limited, and choosing the right primers is crucial [11]. Both diagnostic tools were used in this presented case and brought conclusive positive results. However, the reason for specifically testing for tularemia came initially from an unspecific PCR test screening for eubacterial DNA in a swab from the incised lymph node. Hence, this might be a first diagnostic step but requires suitable specimen for testing.

The initial antibiotic treatment used in our patient was insufficient. Aminoglycosides have been the drugs of choice, but ciprofloxacin seems to be a very effective alternative for type B tularemia, even for very young patients [7]. Our patient showed excellent recovery after surgical incision. Therefore, no further antibiotic treatment was initiated.

Conclusion

The presented case describes an uncommon presentation of tularemia in a very young child in Germany. Transmission seems to have occurred by mosquito bite, a vector that so far was known almost exclusively from Scandinavia. Diagnosis was delayed until surgical incision, but recovery occurred despite inadequate antibiotic treatment. The benign course was probably attributable to type B infection with only localized, ulceroglandular manifestation. Concerns remain whether this type of transmission will be seen more often in the future in Germany or other Central European countries. Medical professionals should therefore be aware of this diagnosis when treating young patients with lymphadenopathy and additional signs of infection.

Ethical Standards

This report complies with the ethical standards laid down in the 1964 Declaration of Helsinki.

Conflict of Interest

The authors declare that they have no conflict of interest.

Copyright information

© Springer-Verlag 2009