|Year : 2015 | Volume
| Issue : 3 | Page : 294-297
Brucellar spondylodiscitis mimicking tuberculosis
Eshani Dewan1, Aroma Oberoi1, Bobby John2, Anuniti Mathias1, Dilip Abraham1
1 Department of Microbiology, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Orthopedics, Christian Medical College and Hospital, Ludhiana, Punjab, India
|Date of Web Publication||12-Jun-2015|
Dr. Eshani Dewan
Department of Microbiology, Christian Medical College Ludhiana - 141 001, Punjab
Source of Support: None, Conflict of Interest: None
Brucellosis is primarily a disease of domestic and wild animals that can be transmitted to humans (zoonosis). Infection with Brucella spp. continues to pose human health risk globally. Brucellosis in endemic and nonendemic regions remains a diagnostic puzzle due to misleading nonspecific manifestations and increasing unusual presentations. It may affect any organ of the body with clinical manifestations that include fever, joint pains, loss of weight, sweating, cough, sciatica, splenic enlargement, liver enlargement, orchitis, etc. Fewer than 10% of human cases of brucellosis may be clinically recognized and treated or reported. Routine serological surveillance is not practiced even in Brucella endemic countries. Whereas, this should be a part of laboratory testing coupled with a high index of clinical suspicion to improve the level of case detection. Rapid and reliable, sensitive and specific, easy to perform and semi-automated detection systems for Brucella spp. are urgently needed to allow early diagnosis and adequate antibiotic therapy in time to decrease morbidity and mortality.
Keywords: Automated blood culture system, BD BACTEC Blood Culture System, Brucella suis, brucellosis, spondylodiscitis, zoonosis
|How to cite this article:|
Dewan E, Oberoi A, John B, Mathias A, Abraham D. Brucellar spondylodiscitis mimicking tuberculosis. CHRISMED J Health Res 2015;2:294-7
|How to cite this URL:|
Dewan E, Oberoi A, John B, Mathias A, Abraham D. Brucellar spondylodiscitis mimicking tuberculosis. CHRISMED J Health Res [serial online] 2015 [cited 2020 Aug 14];2:294-7. Available from: http://www.cjhr.org/text.asp?2015/2/3/294/158721
| Introduction|| |
Brucellosis More Details is a worldwide zoonosis. In India, it is a very common but often neglected disease.  It is spread to humans by direct contact with infected tissue or by ingestion of infected animal products, most commonly milk or milk products. In developed countries, human brucellosis is primarily an occupation-related disease while it is known to occur more commonly among farmers, veterinarians and laboratory workers. In developing areas of the world, the ingestion of unpasteurized milk represents a common source of infection. Brucellosis is caused by aerobic, non-motile, Gram-negative, facultative intracellular, capnophilic, partially acid fast cocco-bacilli that lack capsules, flagella, endospores or native plasmids belonging to the genus Brucella More Details. The genus was named after David Bruce, who first isolated these bacteria in 1887 from soldiers with Malta fever More Details. Brucella genus has been divided into six species, four of which are known to produce disease in man: Brucella abortus, Brucella suis, Brucella canis and Brucella melitensis, the last being the most virulent. 
Human brucellosis may present with varied clinical manifestations that require broad differential diagnosis, including many infectious and noninfectious diseases. The onset of disease is insidious in approximately half of all cases. It is characterized by several somatic complaints such as fever, sweats, anorexia and weight loss. By contrast, there can be few abnormal physical findings.  Thus to an unaware physician, the diagnosis of brucellosis can be problematic.  It is a multisystem infection that most commonly leads to musculoskeletal system disorders. Osteoarticular involvement including spondylitis, sacroiliitis, osteomyelitis, peripheral arthritis, bursitis and tenosynovitis represents the most common complication of brucellosis affecting up to 85% of patients. 
Culture from the blood of a patient provides definite proof of brucellosis. In the past blood was cultured using the biphasic method of Castaneda, which uses both a solid and a liquid medium in the same container. This method circumvents the need for sub-culturing and is used to limit the risk of laboratory-acquired infections. Brucella however, is a slow growing organism and cultures are rarely positive before one to 3 weeks of incubation and should be kept for at least 45 days before the culture can be concluded to be negative for Brucella. The modern semi-automatic blood culture systems such as BACTEC have markedly improved the speed of detection and aids in rapid diagnosis. 
Because of fever, high erythrocyte sedimentation rate (ESR) and osteomyelitis of the vertebral bodies it is often misdiagnosed and treated as tubercular spondylitis. Brucellosis is also known to produce chest radiographic features similar to tuberculosis.  We hereby present a case of Brucellar spondylodiscitis which mimicked spinal tuberculosis and presented in the orthopedic OPD at Christian Medical College, Ludhiana, Punjab.
| Case Report|| |
A 50-year-old farmer presented with a 2 month history of fever, progressive malaise and painful lower back. The fever was of moderate grade and continuous in nature. There was an associated history of weight loss (10 kg) and decreased appetite. No history of trauma was recorded. There was a history of constant contact with cattle and pigs as well as consumption of raw cow milk.
Liver and spleen were not enlarged. ESR (72 mm/h)and C-reactive protein (23.5 mg/dl) were raised, other biochemical tests and liver enzyme were within normal range.
Based on the history of animal contact and prolonged fever serum was tested for anti Brucella IgG antibodies by slide agglutination Rose Bengal (RB) test and was found to be positive. Blood culture was also done by incubation in semi-automated BD BACTEC 9120 system. Positive growth was detected within 48 hours. The sample was subjected to Gram-stained smear microscopy and sub-cultured on sheep blood agar and MacConkey agar, incubated at 37°C. Gram-negative coccobacilli, nonencapsulated and nonmotile were observed. Brucella was identified and differentiated from other Gram-negative genera on the basis of tiny, transparent, low convex with entire edge, soft and easily emulsifiable colonies on MacConkey and blood agar (Small grayish white and nonhemolytic) with absence of X and V factor dependence [Figure 1]. The isolate was oxidase, catalase, nitrate reductase and urease positive (within 15 min), producing acid from xylose in oxidative fermentative medium. H 2 S production was also positive. The organism did not grow on Serum Dextrose agar with Basic Fuchsin or have special CO 2 requirement for growth. Based on the results of the tests the organism was identified as B. suis.
|Figure 1: Colonies of Brucella suis on sheep blood agar and Gram-stain of the bacteria|
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Magnetic resonance imaging (MRI) spine revealed findings consistent with Infective Spondylodiscitis involving L4-L5 level with canal stenosis [Figure 2].
|Figure 2: Magnetic resonance imaging spine images showing spondylodiscitis of L4-L5 level along with canal stenosis|
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The patient was initially started on DOTS Category I - Intensive phase of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) administered thrice weekly on alternate days for 2 months (24 dosages), followed by a continuation phase of H and R thrice weekly on alternate days for 4 months (18 weeks, 54 dosages). This was later modified to T. Doxycycline (100 mg) for 6 weeks in combination with streptomycin (1 g/day) intramuscularly for 2-3 weeks with monitoring of renal function. This regime was preferred since there are lesser chances of a relapse. The patient was symptomatically relieved at the time of discharge and has improved since. He is on regular follow-up and was last reviewed in October 2014.
| Discussion|| |
Brucellosis is a re-emerging worldwide zoonosis and has been reported in at least 56 countries; but it is especially prevalent in the Mediterranean basin, the Arabian peninsula, the Indian subcontinent, Mexico and Central and South America.  Brucellosis has been present for thousands of years and has managed to elude eradication even in the most developed countries.  WHO has declared only 17 countries to have eradicated animal brucellosis.  There have been numerous reports of cases from isolated areas from India in the literature and an acknowledged prevalence of animal brucellosis, but official data of the incidence of human disease is lacking. 
Brucella abortus, B. suis and B. melitensis are the common human pathogens.  Brucella has no predilection for any organ system and can infect both sexes and at all ages.  Brucella species are capable of evading host defense mechanisms, surviving as intracellular organisms and are able to cause prolonged morbidity, relapses and long-term sequelae. 
Human brucellosis is traditionally described as a disease of protean manifestations and the demographic and clinical characteristics are wide with an unexpected spectrum of this disease. In addition to a multitude of somatic nonspecific complaints such as fever, sweats, anorexia, fatigue, weight loss, symptoms and signs related to a single system occasionally predominate when the disease is localized.  The characteristics of fever vary and can be spiking and accompanied by rigors, or may be relapsing, mild or protracted. The name "undulant fever" has been attached to brucellosis because of the periodic nocturnal fever that may occur over weeks, months or even years.  Dissemination via the bloodstream can result in involvement of almost any organ and the clinical presentation can be misleading.  The most commonly localized form of human brucellosis is the osteoarticular form including spondylitis, osteomyelitis, peripheral arthritis, bursitis, and tenosynovitis, affecting up to 85% of patients. Out of these manifestations, spondylitis is the commonest and most important musculoskeletal complication of brucellosis and its reported incidence is 6-58%.  The regional distribution of the spondylitis lesions shows a predilection to the lumbar spine (L-4 mostly).  Clinically, back pain is the most common complaint in patients with spinal involvement, as seen in our patient, due to invasion of the richly innervated periosteum. 
Diagnosis of spinal brucellosis is established if the patient presents at least two of the following findings: (1) Blood and/or bone marrow aspirate culture positive for Brucella, (2) Brucella agglutination titer of 1:160 or higher, (3) bone scan, radiographs and/or a tomography scan showing skeletal involvement characteristic of osteomyelitis and (4) biopsy suggestive of brucellosis demonstrating noncaseating granulomatous tissue. 
The rate of isolation ranges from 15% to more than 90% depending on the methods used. , Most laboratories now use semi-automated blood culture systems (e.g. BACTEC or BacT/Alert) that has improved the time to isolation and have obviated the need for biphasic media techniques that need continuous-monitoring.  The mean time-to-detection could be ≤5 days, which is considered rapid enough for starting appropriate evidence-based treatment in an endemic setting.  Prior use of antibiotics is associated with reduced incidence of positive blood cultures but does not affect the bone marrow culture. 
A variety of tests have been applied to the serologic diagnosis of brucellosis, of which the serum agglutination test (SAT) is the most widely used. RB and a new dipstick test are useful for screening.  The sensitivity of RB is very high (>99%) but the specificity can be disappointingly low (60.78%). As a result, the positive predictive value of the test is low and a positive test result thus requires confirmation by a more specific test. Since the negative predictive value of RB is high, a negative test results excludes active brucellosis with a high degree of certainty. For confirmation of RB test the, Wright or SAT or in more sophisticated and equipped laboratories enzyme linked immunosorbent assay (ELISA) may be used.  Positive results (titers of antibodies to Brucella of 1:160 by standard tube agglutination test) are common, although low titers determined by standard tube agglutination tests have been reported. In rare cases, patients with brucellosis can have positive blood cultures but negative serology. More recently, the Brucella ELISA test has been introduced into clinical laboratories for the diagnosis of brucellosis. It is reported to be rapid, highly sensitive and specific for detecting the Brucella-specific IgG, IgM and IgA antibodies.  It may be positive when other tests are negative, no single titer is always diagnostic; however, most cases of active infection have titers of 1:160. Brucella antibody titers have been recommended to assess the therapeutic response and the resolution of the disease. 
Polymerase chain reaction is fast and can be performed on any clinical specimen. Although it is very promising, standardization of extraction methods, infrastructure, equipment and expertise are lacking, also a better understanding of the clinical significance of the results is still needed. Therefore, its use in Brucella endemic areas needs to be explored before application. 
Unfortunately, imaging is invaluable in the differential diagnosis of spinal brucellosis, particularly for tuberculosis of the spine. MR imaging is the method of choice for the diagnostic assessment and follow-up of the spinal brucellosis. 
The successful treatment of brucellosis requires prolonged chemotherapy regimen with a combination of antibiotics. World Health Organization has issued guidelines for the treatment of human brucellosis. The guidelines recommend two regimens, both involved doxycycline (6 weeks) in combination with either streptomycin (2-3 weeks) or rifampin (6 weeks). Both regimens are the most popular treatments worldwide, although they are not used universally.  Various antibiotics, such as tetracycline, ciprofloxacin, trimethoprim-sulfamethoxazole and aminoglycoside are also used. Hence, the treatment regimen is not standardized and treatment failure in brucellar spondylitis is high.  The eradication of infection from the bone is difficult and relapse may occur especially if only short-term treatment is given. Therefore, long-term anti-brucellar antibiotic treatment should be prescribed immediately after the diagnosis. If the treatment is extended for longer than previously recommended (6 weeks), it would result in an incidence of relapse significantly lower than that for shorter courses of treatment. 
Because of the deceptive nature of the clinical signs and symptoms of brucellosis, the disease may be easily misdiagnosed as tuberculosis. Therefore, alertness of practitioners as well as the availability of laboratory facilities for rapid diagnostic testing is essential.  Studies are ongoing to develop an effective vaccine against B. suis.  Till then the lack of human vaccines and effective control measures make it necessary to practice high clinical suspicion especially where there is history of animal contact due to occupation, sub-febrile fever, consumption of raw, unpasteurized milk, travel to endemic regions, etc.  Pre-exposure prophylaxis in the form of control and elimination of the infection in animals, pasteurization of milk and vaccination of cattle is the need of the hour. As well as post-exposure prophylaxis: Doxycycline 100 mg twice daily and rifampin 600 mg once daily for 3 weeks should be stringently followed. 
In conclusion; in endemic regions, brucellar spondylodiscitis should be included as a differential diagnosis in patients who have back pain with or without neurological deficits. As it is now easily and rapidly established on the basis of laboratory testing and responds well to appropriate medical therapy if diagnosed early.
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[Figure 1], [Figure 2]