Introduction:
Brucellosis, also called undulant fever or Malta fever, is one of the zoonotic diseases. It is caused by gram-negative coccobacilli of the genus Brucella (1,2). The bacteria primarily affect the cattle. However, it has the ability to cause disease in humans as a secondary infection (3). Bacteria enter the human body by ingesting animal products such as unpasteurised milk or uncooked meat (4). It is predominantly transmitted through the alimentary tract, respiratory tract, skin and mucosa (5). The blood, aerosols and body fluid of the infected person is the source of infection and contact with these substances can transmit the disease (6).
Osteoarticular involvement is the most frequently presented complication in brucellosis (6). The osteoarticular manifestations include arthritis, osteomyelitis, discitis, bursitis, tenosynovitis and spondylodiscitis (7). Sacroiliac and spinal joints are commonly affected areas (6,7). Spinal brucellosis is an inflammation of the spine. It usually begins at the disco-vertebral junction and starts spreading to the entire vertebrae and nearby vertebrae (6,8,9). It can affect any part of the vertebrae. The severe form of spinal brucellosis can result in motor weakness or paralysis (10).
The identification of spinal brucellosis is challenging, as it resembles other spinal diseases such as tuberculosis, pyogenic osteomyelitis, malignancy and intervertebral disc herniation (6). Spinal brucellosis can affect any parts of the vertebrae, disc space or spinal cord itself (7,10). The spinal cord or nerve root may be involved because of spondylitis, vasculitis, and arachnoiditis resulting in difficulty in movement and/or paralysis in lower limbs (6,7). Harboring Brucella bacteria in the lymphatic or reticuloendothelial system results in chronicity or relapsing of the brucellosis than untreated or mistreated patients (11).
The incubation period of brucellosis ranges from one to three weeks (12). Patients with spinal brucellosis usually present with fever and back pain (5,7,9). Other nonspecific clinical manifestations include malaise, profuse night sweats, weight loss, headache, pain in multiple joints and myalgia (5,7,9). These vague manifestations delay the patient seeking medical help in the early stage of the disease. Incidence of morbidity and mortality is directly proportional to the time of diagnosis (8,12). Long-term antibiotics with six weeks to 6 months duration are recommended to treat spinal brucellosis (13–15). Surgical decompression is reserved for persistent or progressive neurologic deficits (11,16).
Brucellosis is diagnosed by Agglutination titers of 1:160 or 1:80 for patients with or without a history of animal contact, respectively (13). Magnetic Resonance Imaging (MRI) is a promising test for detecting and following up on spinal brucellosis (7,11,16). Additionally, elevated erythrocyte sedimentation rate (ESR), positive enzyme-linked immunosorbent assay for IgG and IgM antibodies for Brucella and isolation of Brucella are valuable information (7,15,17).
Although plentiful evidence on epidemiology and clinical characteristics of brucellosis is presented in general, there is a dearth of information on spinal brucellosis. Therefore, this study aims to recognize the clinical characteristics of spinal brucellosis in a tertiary care center.
Methods
Setting and participants
The study adopted a retrospective cohort design with a quantitative approach. The study was conducted at a tertiary care hospital, southern India that has more than 2000 beds. The hospital has almost all super-specialties catering to the health needs of patients from Karnataka, Kerala and Goa. The hospital is certified by the International Organization for Standardization (ISO) 14001: 2015, ISO 50001:2011and accredited by National Accreditation Board for Hospitals & Healthcare Providers (NABH). Adult patients (> 18 years) of both genders treated in orthopedic wards as in-patients, from 1 January 2014 to 31 December 2016 (3 years) were included. The data were collected from the medical records of these patients.
Diagnosis
The spinal brucellosis was diagnosed based on the presenting history and physical examination, microbiological confirmation through Standard Agglutination Test (SAT), or blood culture growing Brucella spp. Patients also have undergone routine blood investigations such as complete blood counts, serum electrolytes, renal and liver function, ESR, C-reactive protein (CRP) and procalcitonin and urine analysis. Additionally, most of the patients have undergone MRI studies.
Ethical consideration
The study was approved by Institutional Review Board and Institutional Ethics Committee. Patient consent was waived off as it was a retrospective record review. However, administrative permission was sought from concerned authorities.
Data collection
The data were collected from medical records of patients using structure data collection tolls. Demographic proforma and a dichotomous checklist on presenting clinical manifestations, diagnostic measures and treatment modalities were included. Experts validated the tools and the validation index was 0.96. The reports of ESR, CRP, white blood cell (WBC) count and procalcitonin (PCT) level were retrieved and transferred to the investigation reporting form. The reports were retrieved and radiologists and orthopedic surgeons interpreted MRI studies. Both the tools were pre-tested.
Statistical analysis
The collected data were coded and entered in SPSS 16.0 version. The statistical analysis was done using the same SPSS software. The data were categorized into spinal brucellosis and other brucellosis. Chi-square or Fisher’s exact test was used to compare these groups. The reports of blood investigations are given in mean and standard deviation.
Results
Patients’ characteristics
During the study period, 107 brucellosis patients were treated in the hospital and among them, 28 (26.17%) had spinal brucellosis. The mean age of patients with brucellosis was 41.39±18.04 years and 57 (53.3%) were men. Among 28 spinal brucellosis patients, the mean age was 44.68±16.8 years and 23 (82%) were men.
Clinical manifestations
The history, co-morbidities and clinical manifestations are compared between brucellosis in general and spinal brucellosis (Table 1).
Table 1: Comparison of clinical manifestations and treatment modalities between spinal brucellosis and brucellosis in general |
| Characteristics |
Spinal Brucellosis (N=28) |
Brucellosis in general (N=79) |
p-value |
Frequency |
Parentage |
Frequency |
Parentage |
|
History |
Drug abuse |
0 |
0 |
2 |
1.87 |
1 |
Previous surgical history |
3 |
10.71 |
10 |
9.35 |
1 |
Weight loss |
12 |
42.86 |
35 |
32.71 |
0.8946 |
Comorbidity |
Malignancies |
0 |
0 |
2 |
1.87 |
1 |
Diabetes mellitus |
8 |
28.57 |
8 |
7.48 |
0.0187* |
Pulmonary tuberculosis |
1 |
3.57 |
2 |
1.87 |
1 |
HIV |
2 |
7.14 |
2 |
1.87 |
0.2798 |
Hypertension |
5 |
17.86 |
8 |
7.48 |
0.282 |
Clinical manifestations |
Skin infection |
0 |
0 |
1 |
0.93 |
1 |
Respiratory tract infections |
4 |
14.29 |
11 |
10.28 |
1 |
Muscle spasm |
8 |
28.57 |
13 |
12.15 |
0.1654 |
Back pain |
21 |
75 |
24 |
22.43 |
0.0001* |
Feeling of lump or mass along the spine |
0 |
0 |
12 |
11.21 |
0.0335* |
Irritability |
5 |
17.86 |
18 |
16.82 |
0.5855 |
Fever |
21 |
75 |
64 |
59.81 |
0.4988 |
Pain while moving |
9 |
32.14 |
10 |
9.35 |
0.0204* |
Loss of bladder control |
1 |
3.57 |
7 |
6.54 |
0.6776 |
Paralysis of the extremities- complete/incomplete |
0 |
0 |
1 |
0.93 |
1 |
Altered sensation of lower limbs/ upper limbs |
7 |
25.00 |
2 |
1.87 |
0.0011* |
Spinal deformities - Torticollis/ Kyphosis/ Scoliosis |
2 |
7.14 |
4 |
3.74 |
0.6508 |
Night sweats |
10 |
35.71 |
30 |
28.04 |
0.8318 |
| *statistically significant (p<0.05) |
Fever was the presenting symptom in patients with brucellosis (75% Vs. 59.8%). Backache was more common in patients with spinal brucellosis (75%, p=0.0001). Weight loss presented by spinal brucellosis patients was slightly higher (42.85%) than patients with brucellosis in general (32.7%) though there was no statistical significance (p=0.89). Spinal brucellosis also resulted in pain while walking (p=0.02) and altered sensation of lower limbs (0.001). Although patients had co-morbidities such as diabetes mellitus, pulmonary tuberculosis, hypertension, patients with spinal brucellosis had diabetes as significant co-morbidity (p=0.018). No patients gave a history of immunosuppression therapy. The other notable symptoms were night sweats and muscle spasms. However, none of the patients with spinal brucellosis experienced dysphagia and bladder disturbances.
Diagnostic workup
Blood investigations
Some of the important blood investigations retrieved are presented in Table 2.
| Table 2: Mean and standard deviation (SD) of blood investigations among patients with spinal brucellosis |
| Blood investigations |
Normal values |
N |
Mean |
SD |
Testing method |
ESR (mm/hr) |
0-20 |
23 |
49.22 |
24.35 |
RBC aggregometry Westergren's |
CRP mg/L |
0-5 |
15 |
50.62 |
37.28 |
Immunoturbidimetric |
WBC (x103/µL) |
4-10 |
26 |
8.93 |
2.81 |
Impedance |
Procalcitonin mcg/L |
<0.5 |
20 |
0.222 |
0.043 |
Brahms PCT Kryptor |
MRI studies
Among 28 spinal brucellosis patients, 19 (67.86%) had abnormal MRI studies showing infective spondylitis/spondylodiscitis (figure 1 and figure 2). According to MRI reports, four (14%) patients had cervical vertebrae involvement (2 cervical and 2 cervical & lumbar) and the most commonly affected area in the cervical spine was C4-C5 level. Eight (29%) patients had infective signs in the lumbar region, predominantly at the L4-L5 level. Another six (21%) patients had lumbosacral (L5-S1) involvement. MRI also showed nerve root compression in eight (29%) patients. Furthermore, two (7%) patients had degenerative changes in their spine. A total of 35 intervertebral discs involvement was noted from 28 patients indicating multiple areas affected in some patients. The disease was presented in 11 cervical, 17 lumbar, six lumbosacral and one in sacral area. No patients had thoracic vertebrae involvement.
Treatment
All (100%) patients received antibiotics. The other pharmacological therapy for symptom management is given in figure 3. One-fourth of the cohort had undergone a decompression procedure.
 |
Figure 3: Bar diagram showing treatment modalities |
Discussion
Spinal brucellosis is an important source of morbidity and mortality, predominantly in endemic regions (11). Spinal brucellosis was identified in 28 (26%) patients in three years and 82% of men were affected. Spinal involvement in brucellosis is not homogenous across the globe and the recorded rate is 2% to 65% (18). Previous reports also show that men are affected more frequently than women (11,18).
The lumbar spine is the most frequently affected area, particularly at the L4 and L5 levels. A similar trend is noticed in the previous studies (6,7). The lumbar region has a rich blood supply and a greater probability of endplate degeneration. Involvement of cervical vertebrae is highly dangerous since it can cause life-threatening impediments, such as tetraplegia. Another affected location is the thoracic spine (6,19,20). However, the present study did not find thoracic involvement.
Destructive brucellar lesions of the spine are generally described in adults and can develop in any spinal area at single or multiple levels (11,19,20). In the present study, 35 discs were infected from 28 patients, which suggests multiple vertebrae involvement.
Plain radiography has low sensitivity, specifically in the initial phases of Brucella spondylitis (7,11). Low sensitivity is because of the slow progression of Brucella spondylitis. MRI is considered the best imaging device for diagnosis and follow-up among patients with any spinal infections (4,18,21). MRI has higher sensitivity and specificity (20–22). MRI helps identify the soft tissue components, including intervertebral discs, epidural space, paraspinal soft tissues, nerve roots, spinal cord and spinal canal. Nineteen patients had abnormal findings in MRI.
Patients with Brucella spondylitis present in focal and diffuse forms, generally in patients aged above 50 years, specifically in endemic areas (23). Contradicting to this, it occurred in early ages in the current study setting. Besides, degenerative spinal changes were identified in MRI in two patients.
Though the history of animal contact or consuming unpasteurized dairy products was missing in our study, most of our patients are from rural areas and animal contact and consuming non-posturized milk is possible.
Conclusion
Fever and backache were the predominant clinical manifestations presented by the patients with spinal brucellosis. The other symptoms such as weight loss and night sweats are common in brucellosis, affecting any part of the body. The diagnosis of spinal brucellosis is difficult. Yet, it is essential to provide proper treatment. Radiologic evaluations have increased significantly in the diagnosis, evaluation, and treatment monitoring of spinal brucellosis.
Acknowledgment: The authors acknowledge the support of MRD staff.
Funding:
None
Conflict of Interests:
Authors declare no conflict of interests.
References
- McDermott J, Grace D, Zinsstag J. Economics of brucellosis impact and control in low-income countries. Revue Scientifique et Technique (International Office of Epizootics). 2013 Apr;32(1):249-261. DOI: 10.20506/rst.32.1.2197
- WHO. Brucellosis: Facts. World Organisation for Animal Health. 2021. p. 1–2.
- Lai S, Chen Q, Li Z. Human Brucellosis: An Ongoing Global Health Challenge. China CDC Weekly. 2021 Feb 5;3(6):120-3.
- Musallam II, Abo-Shehada MN, et al. Systematic review of brucellosis in the Middle East: disease frequency in ruminants and humans and risk factors for human infection. Epidemiology & Infection. 2016 Mar;144(4):671-85.
- Zheng R, Xie S, Lu X, et al. A systematic review and meta-analysis of epidemiology and clinical manifestations of human brucellosis in China. BioMed
Research International. 2018 Apr 22;2018.
- Adetunji SA, Ramirez G, Foster MJ, et al. A systematic review and meta-analysis of the prevalence of osteoarticular brucellosis. PLoS Neglected Tropical Diseases. 2019 Jan 18;13(1):e0007112.
- Esmaeilnejad-Ganji SM, Esmaeilnejad-Ganji SMR. Osteoarticular manifestations of human brucellosis: A review. World Journal of Orthopedics. 2019 Feb 18;10(2):54.
- Koubaa M, Maaloul I, Marrakchi C, et al. Spinal brucellosis in South of Tunisia: review of 32 cases. The Spine Journal. 2014 Aug 1;14(8):1538-44.
- Ledbetter LN, Salzman KL, Sanders RK, et al. Spinal neuroarthropathy: pathophysiology, clinical and imaging features, and differential diagnosis. Radiographics. 2016 May;36(3):783-99.
- Colmenero JD, Ruiz-Mesa JD, et al. Clinical findings, therapeutic approach, and outcome of brucellar vertebral osteomyelitis. Clinical Infectious Diseases. 2008 Feb 1;46(3):426-33.
- Tali ET, Koc AM, Oner AY. Spinal brucellosis. Neuroimaging Clinics. 2015 May 1;25(2):233-45.
- Gokhale YA, Ambardekar AG, Bhasin A, et al. Brucella spondylitis and sacroiliitis in the general population in Mumbai. The Journal of the Association of Physicians of India. 2003 Jul 1;51:659-66.
- Pericherla S, Gupta N, Saravu K. Clinical profile and treatment outcomes of patients with brucellosis: a hospital-based cohort study from Southern India. Headache. 2021 Mar 1;22:23-4.
- Mirnejad R, Jazi FM, Mostafaei S, et al. Epidemiology of brucellosis in Iran: A comprehensive systematic review and meta-analysis study. Microbial Pathogenesis. 2017 Aug 1;109:239-47.
- Ali S, Nawaz Z, Akhtar A, et al. Epidemiological investigation of human brucellosis in Pakistan. Jundishapur Journal of Microbiology. 2018 Jul 31;11(7).
- Cho C, Goto M. Spinal brucellosis. New England Journal of Medicine. 2018 Oct 25;379(17):e28.
- Mohseni K, Mirnejad R, Piranfar V, et al. A comparative evaluation of ELISA, PCR, and serum agglutination tests for diagnosis of Brucella using human serum. Iranian Journal of Pathology. 2017;12(4):371.
- Ceran N, Turkoglu R, Erdem I, et al. Neurobrucellosis: clinical, diagnostic, therapeutic features and outcome. Unusual clinical presentations in an endemic region. The Brazilian Journal of Infectious Diseases. 2011 Jan 1;15(1):52-9.
- Aktuğ-Demir N, Kolgelier S, Özçimen S, et al. Diagnostic clues for spondylitis in acute brucellosis. Saudi Medical Journal. 2014; Vol. 35 (8):816-20.
- Bouaziz MC, Ladeb MF, Chakroun M, et al. Spinal brucellosis: a review. Skeletal Radiology. 2008 Sep;37(9):785-90.
- Ulu Kilic A, Metan G, Alp E. Clinical presentations and diagnosis of brucellosis. Recent Patents on Anti-infective Drug Discovery. 2013 Apr 1;8(1):34-41.
- Liang C, Wei W, Liang X, et al. Spinal brucellosis in Hulunbuir, China, 2011–2016. Infection and Drug Resistance. 2019;12:1565.
- Raptopoulou A, Karantanas AH, Poumboulidis K, et al. Brucellar spondylodiscitis: noncontiguous multifocal involvement of the cervical, thoracic, and lumbar spine. Clinical Imaging. 2006:30(3): 214-7
|
