Unknown Fever and Back Pain Caused by Bartonella henselae in a Veterinarian After a Needle Puncture: A Case Report and Literature Review

Introduction

B artonella spp. are mainly transmitted by vectors such as fleas, ticks, and lice (Boulouis et al. 2005). The well-known agent of human cat-scratch disease (CSD), Bartonella henselae, is transmitted among cats via fleas, and humans acquire the infection through contaminated wounds after animal scratches and bites. Therefore, in general, only humans with a history of cat scratches and bites will be considered as suspected CSD cases. Unknown or nonspecific routes of the disease transmission may seriously delay diagnosis and appropriate treatment, and lead to serious clinical complications. We report a confirmed CSD patient who might have acquired the infection through an unusual route of transmission. This patient with persistent back pain was originally not suspected to be a CSD patient. However, after clinical investigations, contaminated wound after an accidental needle puncture was identified as the possible route of the disease transmission. This patient finally recovered after appropriate clinical treatments.

Case Report

The patient was a 32-year-old man working as a veterinarian in a private veterinary clinic. He sought for clinical help because of unknown fever and persistent back pain for at least a month. According to the patient's descriptions, the fever was undulant and right back flank pain not related to spondylitis was noted during fever bouts. Fever was improved after the use of analgesic, but soon exacerbated with chills for several hours. Because the clinical conditions did not improve, this patient was transferred to the Division of Infectious Disease, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan, for further clinical help.

After clinical examinations, the patient had fever (39.8°C) and right axillary lymphadenopathy. Blood pressure, heart rate, and respiratory rate were 139/80 mmHg, 98 beats/min, and 20 breaths/min, respectively. No obvious signs of blisters, rashes, or bites from insects or animals were noted on the patient's body. However, he clearly recalled that several days before the illness, he was accidentally injured on his right thumb by a clear needle stick when preparing injections for animal treatment. Complete blood cell count revealed hemoglobin level of 13.2 g/dL, 39.0% hematocrit, platelet count of 4.14 × 10⁵/mm³, RBC count of 4.44 × 10⁶/mm³, and leukocyte count of 9.4 × 10³/mm³ with 73.2% neutrophils, 19.6% lymphocytes, 6.3% monocytes, and 0.4% eosinophils. The C-reactive protein level was at 14.5 mg/dL. The serum levels of electrolytes and renal functions were normal. Routine blood cultures for bacteria or yeasts showed negative results. The chest X-rays and abdominal ultrasonography images showed no active lesions. The abdominal computed tomography scan revealed moderate splenomegaly. As this patient was a veterinarian, the illness might be caused by zoonotic infections. Therefore, this case was reported to Centers for Disease Control, Taiwan, for diagnoses of possible zoonoses. Serological tests for Q fever, brucellosis, and leptospirosis did not show positive results.

As the clinical findings such as unknown fever and lymphadenopathy were similar to those of Bartonella infection, a blood specimen from the patient was cultured for Bartonella and indirect immunofluorescence antibody assay using B. henselae as the antigen for CSD diagnosis was applied as previously described (Regnery et al. 1992). Although bartonellae isolation using whole blood was unsuccessful, the IgG titers by indirect immunofluorescence antibody assay tested at two different time points (more than 2 weeks' interval) were strongly positive for B. henselae (1:131,072 and 1:65,536, respectively). Molecular diagnosis using extracted DNA from the patient's whole blood and lymph node aspirates was negative after polymerase chain reaction (PCR) of the citrate synthase (gltA) gene for Bartonella (Norman et al. 1995). However, a positive result was obtained after further dot-blot hybridization for the PCR product with B. henselae–specific probe (Fig. 1). The dot-blot hybridization was analyzed using DIG hybridization system (Roche Diagnostics, Mannheim, Germany). The probe sequence used in this study was 5′-GCAAAAGATAAAAATGATTCTTTCCGYCTTATGGGTTTTGGTCATCGAGT-3′ (Ciervo and Ciceroni 2004). The hybridization was executed under the conditions established by Sander and Penno (1999) but with the hybridization temperature of 42°C (Kook et al. 2003). Further, single-step PCR of the 16S–23S intergenic region (Jensen et al. 2000) showed a unique fragment size (172 bp) of B. henselae, which was different from Bartonella clarridgeiae (154 bp), Bartonella quintana (157 bp), and Bartonella koehlerae (170 bp). After sequence comparison, the DNA similarity value of this specific PCR product was 100% with B. henselae, followed by 95.9% with B. koehlerae, 85.4% with B. quintana, and 77.9% with B. clarridgeiae. Therefore, after combining the results of serological and molecular diagnoses, this case was confirmed to be B. henselae infection. For the clinical therapy, the patient was treated intravenously with 2 g of ceftriaxone once a day for the initial 6 days. Thereafter, 100 mg of doxycycline twice a day and 500 mg of azithromycin once a day were given orally for 4 and 5 days, respectively. The patient was also given intravenously one shot of dexamethasone (4 mg) on the seventh day, followed by 15 mg of prednisolone (oral, two times a day) for 1 day and 10 mg of prednisolone (oral, two times a day) for the remaining 8 days. The pain and fever disappeared within 1 week.

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FIG. 1.

Dot-blot analysis with a specific probe for Bartonella henselae. N, negative control, sterile water substituted for DNA templates; NP, blood sample from a normal individual without cat-scratch disease (CSD); P, positive control, B. henselae ATCC49882; B1, the patient's blood sample before treatment for CSD; B2, the patient's blood sample after treatment for CSD; LN, lymph node aspirates from the patient before treatment for CSD.

As previously described by Vermeulen et al. (2008), low sensitivity of PCR for B. henselae diagnosis may result in false-negative reactions, especially when using whole-blood or serum samples. In this investigation, molecular detection of the gltA gene fragment amplified from the clinical specimen was negative. However, dot-blot hybridization with B. henselae–specific probe to increase the detection sensitivity showed a positive result. As further confirmed by the positive result of PCR-mediated amplification of the 16S–23S intergenic region, this CSD case was molecularly confirmed. The diagnosis was also supported by serological results. In this case, although it remains unknown, the very high level of antibody titers against B. henselae was unusual and could be considered as the main reason that induced the long-term clinical manifestations in this patient.

Since the identification of B. henselae as the agent of CSD in the early 1990s, a total of seven reports related to back pain caused by B. henselae that was confirmed by serology and/or molecular methods can be identified in PubMed (Table 1). Most of these patients were with a known history of cat exposure. These patients were mainly less than 10 years old, except two patients, who were 30 years old (one with HIV seropositivity). Our patient was a 32-year-old immunocompetent man with persistent back pain for at least a month. After appropriate treatments, he recovered without pain relapses. Among the seven previously reported cases in PubMed, one patient with a 3-month history of back pain relapsed despite treatment.

Humans acquire CSD infection mainly through wounds contaminated with infectious flea feces after animal scratches or bites (Boulouis et al. 2005). In Taiwan, the first human CSD patient was reported in 1998 (Lee et al. 1998), and an epidemiological study of CSD in cats and veterinary-associated populations has been conducted (Chang et al. 2006). In this case report, the patient did not recall any animal scratches or bites. However, without any wound care after an accidental needle stick injury, the patient kept on doing veterinary clinical work, which may in turn contaminated the wound through animal exposure and led him to acquire the infection. This event highlights the importance of wound management for CSD prevention, especially in a high-risk population such as veterinarians. Moreover, after ruling out other suspected infections, patients having unknown fever and back pain but with cat exposure and/or participating veterinary-associated professions should be considered for B. henselae infection.