Introduction
Brucellosis, a zoonotic infection, is an under-reported disease in India, although there are pockets where the disease is prevalent.1 Humans acquire brucellosis by consuming unpasteurized milk or exposure to infected animals and their products.2 It primarily affects the reticuloendothelial system but tends to have a multi-organ involvement. Musculoskeletal involvement is seen in 40-70% of patients.3 Brucella spondylodiscitis can mimic tuberculosis spine by having a similar presentation. Various modalities are available to diagnose brucellosis, such as blood culture, serological tests, and polymerase chain reaction (PCR). The automated blood culture method enables earlier diagnosis, especially in cases of fever of unknown origin. We are reporting a case series of brucellosis presented as a fever of unknown origin.
Case Presentation
Case 1
A 50-year-old man who is a farmer by occupation and worked in a sheep pen in the Middle East presented with a low-grade fever on and off with chills and rigors, night sweats, loss of appetite, arthralgia, loss of weight accompanied by low backache and bilateral lower limb pain for the past two months. He was treated elsewhere with a diagnosis of infective spondylodiscitis suspected of tubercular origin. His MRI revealed a cortical break in the L4-L5 region, with a pre-vertebral collection, which was ill-defined, and a mild diffuse bulge with the narrowing of the neural lamina (Figure 1). To relieve the pain, he was managed surgically by disc debridement and interbody fusion of the anterior lumbar was done. Postoperatively, he developed a high-grade fever, for which he was further evaluated. His total leukocyte count was 6,700/µl with neutrophil predominant of 75%. Haemoglobin was 6.6g/dl, so he was transfused two units of packed RBCs. Inflammatory markers like ESR 124mm/hour and CRP 95 mg/dl were also elevated, so a blood culture was sent by automated BacT/Alert bottle. After 75 hours of incubation, it flagged positive. Blood and chocolate agar showed minute moist colonies (Figure 2, Figure 3). This was identified as Brucella species by MALDI-ToF MS (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry), later speciated as Brucella melitensis by VITEK 2 (bioMérieux). The patient was started on Tab. Doxycycline 100 mg twice daily with Inj. Amikacin 500mg Q8H.The fever subsided gradually after two days of starting antibiotics, and he improved symptomatically. He was discharged and advised to continue Tab. Doxycycline 100 mg BD and Tab. Rifampicin 900mg OD for another 45 days. He completed the treatment and recovered completely.
Case 2
A 42-year-old male complained of fever associated with chills and rigors for four days. He is a shepherd by occupation. Routine investigations were sent, and all were normal. A tropical fever workup was done and found to be negative. He was a known case of hypertension and cerebrovascular accident (CVA). He was also an old case of rheumatic heart disease (RHD) with mitral valve replacement (since 2014) on Warfarin, so the possibility of infective endocarditis was considered and blood samples were sent for culture. A cardiology opinion was obtained, and 2D-ECHO was done, which showed normal valves and chambers, no regional wall motion abnormalities, good ventricular functions, and no vegetation. Three blood cultures were sent, all of which grew Brucella, and the standard agglutination test (SAT) was positive for Brucella abortus (Table 1). The patient was started on Tab. Doxycycline 100 mg BD with Inj. Gentamicin 300mg OD and Tab.Rifampicin 900mg OD as per Brucella endocarditis protocol, and he improved symptomatically; hence, he was discharged. The patient was advised to do Trans-oesophageal Echocardiography, which he could not do due to financial constraints. He completed the treatment and recovered completely.
Case 3
A 36-year-old male working in the Middle East in a camel farm complained of multiple joint pain, predominantly involving the large joints, on and off for two months. He had no history of fever, night sweats, loss of weight, or appetite. Blood culture and standard agglutination test were positive for Brucella abortus (Table 1). He was started on Tab. Doxycycline 100mg BD for six weeks and recovered completely.
Case 4
A 21-year-old female complained of lower back pain for three months and got aggravated for one month, for which she was evaluated in a private tertiary hospital. Her MRI showed spondylodiscitis of the D9 and D10 vertebra, suspected of infectious origin (probably TB spine). A CT-guided biopsy was done, and the result was negative for Gene Xpert. She came here for further management. She was evaluated for brucellosis. The standard agglutination test for Brucella abortus was positive, and the antibody titers were ≥1:320 (Table 1). The patient was started with Inj. Gentamicin 300mg OD for one week and advised to continue Tab.Rifampicin 900mg and Tab. Doxycycline 100 mg BD for 6 weeks.
Table 1 provides the relevant clinical details of patients (above four cases) with brucellosis.
Table 1
Relevant clinical details of patients with brucellosis
Discussion
Brucellosis is a zoonotic disease that affects individuals exposed to contaminated animal products or who consume unpasteurized milk and milk products.4 In our study, all of our patients had animal contact or had consumed unpasteurized milk products, which is a significant history of clinically suspected cases of brucellosis.
Among the extrapulmonary tuberculosis cases, Tuberculous spondylitis or Pott’s disease comprises around 5%.4 Brucella spondylodiscitis mimics spinal tuberculosis due to its similar clinical presentation and radiological and histopathological features, which is why it is often misdiagnosed.5 In our case series, two cases were suspected of TB Potts spine, and one was started on an anti-tubercular regime. Unfortunately, in a tuberculosis-endemic country like India, there is a high probability of misdiagnosing brucellosis due to its superimposed presentation.
Brucellosis has varied clinical presentations. To begin with, the constitutional symptoms such as fever accompanied by chills, myalgias, joint pain, headaches, and sweating. Osteoarticular involvement includes spondylitis, spondylodiscitis, sacroiliitis, and arthritis.1 Spondylitis and spondylodiscitis are the most frequent presentation of spinal brucellosis, apart from other complications.6 The spine involvement in brucellosis is seen in 2-54% of cases.7, 8
It is stated that brucellar spondylodiscitis accounts for 6%- 85%. The lumbar spine was the most common site (60%- 69%), followed by the thoracic or dorsal spine (19%) and cervical spine segments (6%- 12%).8, 9 In our study, two patients were diagnosed with spondylodiscitis. One patient had spondylodiscitis of lumbar vertebrae (L4-L5), and the other had spondylodiscitis of dorsal vertebrae (D9-D10).
At least two of the following findings are required for the diagnosis of spinal brucellosis:
Blood and/or bone marrow aspirate culture positive for Brucella.
Brucella standard agglutination test (SAT) titer of 1:160 or higher,
Radiography evidence (X-ray /MRI /CT scan) showing skeletal involvement like osteomyelitis or spondylodiscitis and,
Tissue biopsy showing non-caseating granulomatous tissue suggestive of brucellosis.9, 10 All four of our patients fulfilled these criteria.
Brucella endocarditis is a rare complication of brucellosis. Generally, it affects both native and prosthetic valves and leads to vegetation in the cardiac valves.11 The management requires surgical valve replacement and combined antimicrobial therapy.12 On the contrary, in this case series, we had one patient with a prosthetic valve who did not have vegetation or pulmonary hypertension. He was treated with a combined regimen, and his condition improved.
Laboratory investigations are essential tools in diagnosing brucellosis. It is observed that in brucellosis, the laboratory parameters like total leukocyte count (TLC) are within normal range, and a marginal rise seen in inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are correlating with the current study.13 All patients had anemia.
The isolation of organisms from bone marrow culture is the gold standard for diagnosing brucellosis. The positivity rate is high in blood and bone marrow cultures. It can range up to 70%.14 It is a gram-negative coccobacilli, an intracellular, aerobic, non-motile, and slow-growing organism that is often under-reported in resource-limited settings. Automated blood cultures facilitate earlier and more accurate diagnosis. In this study, three out of four patients had growth in blood culture (75%). The yield of blood culture positive is high during the acute phase. The tube agglutination assays are positive for acute and chronic diseases.15 This notion is seen in this case series as well.
According to WHO guidelines, the treatment regimen includes doxycycline 100 mg BD for 45 days plus streptomycin 1 g daily for 15 days. The other alternative therapy is doxycycline at 100 mg BD for 45 days, plus rifampicin at 15mg/kg/day for 45 days. WHO also suggests that streptomycin may be substituted with gentamicin 5mg/kg/daily for 7–10 days.16
There are specific guidelines for osteoarticular brucellosis, but various case reports suggest a triple regimen of Streptomycin (1g daily), Doxycycline (100mg BD), and Rifampin (15 mg/kg daily) will prevent relapses.17 Similarly, it has been followed in two spondylodiscitis cases.
In this case series, we had one acute brucellosis, two brucellar spondylodiscitis, and one case of Brucella endocarditis.
Conclusion
Brucellosis is a zoonotic infection transmitted by animals, and human brucellosis can lead to serious health consequences. In Brucella-endemic areas, a high index of suspicion and a detailed clinical history of occupation are necessary. Brucellosis is a great masquerader of tuberculosis and is often misdiagnosed, which leads to the unnecessary initiation of a long-term antitubercular regimen. Accurate diagnosis, timely management, and adherence to standard treatment protocols will aid in preventing brucellosis-related complications.
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