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 ~ Introduction
 ~ Case Report
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  Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 37  |  Issue : 1  |  Page : 123-126
 

Knee and the farm animals: An unusual presentation of Brucella melitensis masquerading as tuberculosis


1 Department of Microbiology, Indraprastha Apollo Hospitals, New Delhi, India
2 Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals, New Delhi, India

Date of Web Publication16-Aug-2019

Correspondence Address:
Dr. Raman Sardana
Department of Microbiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110 076
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_19_213

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 ~ Abstract 


In many developed countries, brucellosis has been successfully eradicated. However, brucellosis, with its myriad presentations, continues to be a clinical and diagnostic challenge in primarily agrarian countries such as India. We present a case of a rare manifestation of brucellosis i.e., septic arthritis of the knee joint associated with a lytic lesion of the proximal tibia. The patient belonged to a Brucella endemic country, and clinical features were of chronic reactive knee arthritis with synovial hypertrophy and effusion. Advanced diagnostic methods played a pivotal role in excluding the diagnosis of tuberculosis, and thus unnecessary administration of antitubercular therapy and initiating focused narrowed anti-Brucella management, achieving the goal of antimicrobial stewardship also.


Keywords: Antimicrobial stewardship, Brucella melitensis, brucellosis, knee, lytic lesion, septic arthritis, synovial hypertrophy


How to cite this article:
Sardana R, Vaish A, Merh A, Butta H, Vaishya R, Mendiratta L. Knee and the farm animals: An unusual presentation of Brucella melitensis masquerading as tuberculosis. Indian J Med Microbiol 2019;37:123-6

How to cite this URL:
Sardana R, Vaish A, Merh A, Butta H, Vaishya R, Mendiratta L. Knee and the farm animals: An unusual presentation of Brucella melitensis masquerading as tuberculosis. Indian J Med Microbiol [serial online] 2019 [cited 2019 Oct 21];37:123-6. Available from: http://www.ijmm.org/text.asp?2019/37/1/123/264491





 ~ Introduction Top


Brucellosis is a zoonotic disease with protean clinical manifestations. It is endemic in the Mediterranean region, Western and South Asia and parts of Africa and Latin America. Cattle and their products remain the primary source of infection, but Brucella melitensis has also emerged as an essential problem in some Southern European countries, Israel, Kuwait and Saudi Arabia.[1] The incidence of brucellosis is 10 in 100,000 in these endemic regions.[2] It is transmitted to humans through the consumption of unpasteurised dairy products of infected animals, directly through contact with infected animals or indirectly by environmental exposure.[3]

We present a unique presentation of Brucella infection of the knee joint in a 74-year-old male from Saudi Arabia, in which the only clinical features were of left knee pain, swelling and inflammation with flexion deformity. Brucella arthritis from the agrarian country, like India, is infrequently reported. Due to increasing medical tourism in India, it is necessary for the clinicians to be aware of the possibility of Brucella arthritis, to reach to prompt diagnosis and correct treatment, especially if the patient is reporting from endemic regions of Brucella.


 ~ Case Report Top


A 74-year-old resident of Saudi Arabia was referred in our hospital for total knee replacement with a history of left knee pain and swelling for the past 1 year. The knee pain was gradual in onset and progressed insidiously over the past 1 year. There was no history of cough, fever, weight loss or any other systemic complaints. The associated comorbid medical conditions included diabetes mellitus, hypertension and coronary artery disease. The patient was treated with antitubercular treatment based on the radiological and other investigations but with no clinical response. Hence, the patient was admitted to our hospital for further workup. A detailed clinical history was taken from the patient. The patient was a farmer by occupation and had a history of prolonged close contact with the sheep.

On local examination, the left knee was flexed in 45°, with further flexion present up to 90° only. There were associated synovial hypertrophy and effusion. Plain radiographs showed a reduction in medial joint space with a suspicion of an osteolytic lesion in the upper tibia [Figure 1] and [Figure 2]. The magnetic resonance imaging revealed a large cystic lesion, measuring 34.6 mm × 25.4 mm × 26.3 mm, in the proximal tibia, with surrounding bone marrow oedema and fluid filled in the cavity [Figure 3] and [Figure 4]. There was diffuse bone marrow oedema in the distal femur and proximal tibia with joint effusion and Grade III medial meniscal tear. Arthroscopic examination of the knee revealed diffuse proliferative synovitis, effusion, complex degenerative tear of the medial meniscus and chondropathy on the medial femoral condyle.
Figure 1: Anteroposterior radiograph of the knee showing a large osteolytic lesion in the proximal tibia (marked with arrows) and associated osteoarthritis

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Figure 2: Lateral radiograph of the knee showing a large osteolytic lesion in the proximal tibia (marked with arrows)

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Figure 3: T2 (time relaxation)-weighted magnetic resonance imaging image of the knee (coronal section) showing a large cystic lesion in the proximal tibia, with surrounding bone marrow oedema and fluid filled in the cavity

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Figure 4: T2 (time relaxation)-weighted magnetic resonance imaging image of the knee (sagittal section) showing a large cystic lesion in the proximal tibia, with surrounding bone marrow oedema and fluid filled in the cavity

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His erythrocyte sedimentation rate was 21 mm at the end of 1 h, and C-reactive protein was raised to 35.0 mg/L. Tuberculosis (TB) gamma interferon assay was positive (antigen tube: 4.43 IU/ml, Nil tube: 0.08 IU/ml). The left knee aspiration yielded straw-coloured fluid, which was sent for various microbiological investigations. The Gram stain, acid-fast bacilli stain and real-time polymerase chain reaction for (TB-RT-PCR Assay) of knee aspirate were negative. Knee aspirate sent in blood culture bottle (BacT/Alert – Continuous Monitoring Blood Culture System) showed growth of Gram-negative coccobacilli after 72 h of incubation. These organisms were identified as Brucella species by matrix-assisted laser desorption ionisation-time of flight-mass spectrometry (MALDI-TOF-MS). This organism was further identified as B. melitensis by VITEK 2 Compact. The organism was found to be sensitive to gentamicin, tetracycline and trimethoprim-sulphamethoxazole. All the inoculation and identification procedures of the sample were performed in Class III Biosafety Cabinet using appropriate personal protective equipment. A blood sample was also collected for culture and RT-PCR for Brucella. RT-PCR for Brucella was found to be positive, but blood culture remained negative after 3 weeks of incubation. Brucella serology was negative.

The histopathological examination of the synovial biopsy retrieved by arthroscopy revealed hyperplastic synovial tissue with a focal area of stratification. The stroma contained granulation tissue formation, fibrosis, vascular proliferation and lymphoplasmacytic cell infiltration forming aggregates at places. No granuloma or malignancy was seen.

The patient was treated with tetracycline and co-trimoxazole (trimethoprim + sulphamethoxazole) for 12 weeks with proper monitoring. The patient showed complete resolution of pain and swelling with the improvement of range of knee movements.


 ~ Discussion Top


Brucellosis is a zoonotic disease caused by a Gram-negative bacillus, first described by Sir David Bruce, in 1887. The disease is transmitted from infected domestic animals such as cow, sheep and goat, by inoculation through cuts and abrasions in the skin or by ingestion of non-pasteurised raw milk and infected milk products.[3]

Brucellae are Gram-negative coccobacilli (short rods) measuring about 0.6–1.5 μm by 0.5–0.7 μm. They are non-sporing, non-capsulated and non-flagellated microorganisms. The outer cell membrane closely resembles that of other Gram-negative bacilli with a dominant lipopolysaccharide (LPS) component. There are three major species of B. melitensis, abortus and suis. These are differentiated by carbon dioxide requirement, production of urease, hydrogen sulphide, sensitivity to dye thionin and basic Fuchsin and cell wall antigens. Brucella requires multiple amino acids, thiamine, biotin, nicotinamide and pantothenic acid for growth. Their colonies become visible on suitable solid media in 2–3 days. The colonies of smooth strains are small, round and convex but dissociation, with loss of the O chains of the LPS, occurs readily to form rough or mucoid variants.[4] These organisms are killed after heating at 60°C for 10 min. Hence, these organisms are killed in milk by pasteurisation. Brucellosis is a systemic infectious disease with a broad spectrum of clinical presentation. It may vary from an acute febrile disease to a low-grade, ill-defined disease. The various complications of brucellosis include endocarditis, arthritis, meningitis, uveitis and epididymo-orchitis. The most common osteoarticular manifestation includes sacroiliitis and arthritis of a large peripheral joints such as knee (like in this case), hip and shoulder joints.[5] Monoarticular involvement of a large joint is a frequent osteoarticular manifestation.

Brucellosis may remain undiagnosed in non-endemic regions, due to its rarity and unawareness.[6] Hence, the awareness of this entity and a high index of suspicion is required to reach an early diagnosis and treatment. Its subclinical presentation, and in some chronic cases, microbiological and serological negativity, these cases can be easily missed. In this era of medical tourism, knowledge about the infections endemic in various regions is essential as also the travel history. Our patient belonged to Brucella endemic region but was diagnosed as a case of tubercular osteoarthritis. It could be because of the absence of systemic symptoms which could have given way to diagnose Brucella arthritis. Elzein and Sherbeeni reported four cases of Brucella septic arthritis from Brucella endemic country where all the patients have a history of either consumption of raw milk or contact with animals. Isolated focal symptoms were seen in only one patient, while the other three patients presented with systemic features along with joint pain.[7]

We could diagnose the primary cause of Brucella infection, only because of comprehensive history taking and then getting the optimal investigations done. The various advanced and rapid diagnostic tests which were used in our case for the rapid and reliable detection of Brucella includes molecular tests and rapid culture techniques i.e., continuous monitoring automated blood culture systems (CMABS), rapid identification techniques such as MALDI-TOF-MS. Molecular tests such as RT-PCR assay is a genomic test which can detect Brucella in tissue, joint fluids and blood specimens. Culture is the gold standard test for any infection, and CMABS is a significant advancement and is a very useful tool to increase the culture yield of Brucella in joint aspirates. Other tests such as serum standard agglutination test and enzyme immunoassay are also used to diagnose Brucella infection. In our patient, Brucella serology was found to be negative (Titres <1:40). Hence, Brucella serology should not be considered as the only investigation to exclude Brucella infection. Çelik et al. also reported two cases of Brucella spondylodiscitis with negative Brucella serology.[8]

Various antibiotics either alone or in combination have been used for the treatment of brucellosis but with variable success, for example, ceftriaxone, ciprofloxacin/ofloxacin, co-trimoxazole, doxycycline/tetracycline, gentamicin/streptomycin and rifampicin (6). The treatment recommended by the World Health Organisation for acute brucellosis in adults is rifampicin 600–900 mg and doxycycline100 mg twice daily for a minimum of 6 weeks.[9] The choice and duration of treatment may be determined by the site of infection severity of infection, patient age and patient physiological factors. Tetracycline, gentamicin, rifampicin and co-trimoxazole, for 6–8 weeks have also been used for the conservative treatment.[10] Treatment with a single agent or combination of agents for <4 weeks is associated with a high risk of relapse.[11]

High suspicion for Brucella infection should exist in any patient coming from an endemic region with non-specific and chronic arthralgia. Improper or misdiagnosis may put treating surgeon in trouble by performing unnecessary surgery, which may be associated with post-operative infections and other complications.[12] Furthermore, unnecessary antitubercular treatment may be avoided, and this would serve as an antimicrobial stewardship component to minimise resistance in Mycobacterium tuberculosis. Thus, the role of advanced clinical microbiology laboratory is critical for early and accurate diagnosis which can, not only also avoid unnecessary surgeries and complications but also decrease the indiscriminate usage of antibiotics and focus on narrowed-specific antimicrobials.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
Wernaers P, Handelberg F. Brucellar arthritis of the knee: A case report with delayed diagnosis. Acta Orthop Belg 2007;73:795-8.  Back to cited text no. 1
    
2.
Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. The new global map of human brucellosis. Lancet Infect Dis 2006;6:91-9.  Back to cited text no. 2
    
3.
Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu YZ, Erol I, et al. Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement. AJR Am J Roentgenol 2006;187:873-80.  Back to cited text no. 3
    
4.
Baron S, editor. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7627/. [Last accessed on 2019 Apr 07].  Back to cited text no. 4
    
5.
Bosilkovski M, Krteva L, Caparoska S, Dimzova M. Osteoarticular involvement in brucellosis: Study of 196 cases in the republic of Macedonia. Croat Med J 2004;45:727-33.  Back to cited text no. 5
    
6.
Pandit DP, Pandit PT. Human brucellosis: Are we neglecting an enemy at the backyard? Med J DY Patil Univ 2013;6:350-8.  Back to cited text no. 6
  [Full text]  
7.
Elzein FE, Sherbeeni N. Brucella septic arthritis: Case reports and review of the literature. Case Rep Infect Dis 2016;2016:4687840.  Back to cited text no. 7
    
8.
Çelik AD, Yulugkural Z, Kilincer C, Hamamcioglu MK, Kuloglu F, Akata F. Negative serology: Could exclude the diagnosis of brucellosis? Rheumatol Int 2012;32:2547-9.  Back to cited text no. 8
    
9.
Mantur BG, Amarnath SK, Shinde RS. Review of clinical and laboratory features of human brucellosis. Indian J Med Microbiol 2007;25:188-202.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Solera J, Martínez-Alfaro E, Espinosa A. Recognition and optimum treatment of brucellosis. Drugs 1997;53:245-56.  Back to cited text no. 10
    
11.
Jalan D, Elhence A, Elhence P, Jain P. A case of acute septic arthritis hip caused by Brucella melitensis in an adolescent child. BMJ Case Rep 2015;2015. pii: bcr2015211678.  Back to cited text no. 11
    
12.
Erdogan H, Cakmak G, Erdogan A, Arslan H. Brucella melitensis infection in total knee arthroplasty: A case report. Knee Surg Sports Traumatol Arthrosc 2010;18:908-10.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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