Osh state university international medical faculty

Discussion

Brucellosis is a zoonotic disease, which is caused by organisms of the genus Brucella. Brucellosis is main- ly acquired by consumption of unpasteurized dairy products, and rarely by direct contact with infected animals through the skin, by inhalation of infected aerosols or inoculation into the conjunctiva1,3. In our case, there was a positive family history for brucellosis and consumption of cheese produced from unpasteur- ized milk.

Since the signs and symptoms of brucellosis are highly variable and non-pathognomonic, it may have a similar course with various multisystemic diseases. Due to these features, brucellosis is named as a “great imitator, major mimicker or disease of mistakes”4,5. The most common symptoms of brucellosis include fever of unknown origin, arthralgia, myalgia, weak- ness and night sweating6. Other symptoms that may be encountered are loss of appetite, fatigue, weight

Acta Clin Croat, Vol. 54, No. 1, 2015

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Childhood brucellosis with unusual features

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loss, abdominal pain and headache. Clinical features and history of our patient suggested brucellosis as an initial diagnosis.

Brucellosis may present with long lasting fever alone. Çiftdoğan et al. included 92 pediatric patients with fever of unknown origin in their study and re- ported Brucella as the most frequently encountered infectious agent7.

Focal involvement of brucellosis is mostly related to the osteoarticular system. Other focal involvements may be confined to the central nervous system, respi- ratory system, hematopoietic system and genitouri-

Table 1. General characteristics of laboratory test methods for the diagnosis of brucellosis4

test	Rose Bengal slide agglutination test	Serum agglutination test (Wright)	Indirect Coombs (antihuman globulin) test	Culture	Microagglutina- tion test	Brucellacapt (immunocapt)
time	5-10 min	24 h	48 ha	3-7 days	24 h	18-24 h
Pros	Rapid	titration possibility	Detects incomplete, blocking or non- agglutinating immunoglobulins	Gold standard	Uses smaller volumes of serum, can test multiple samples at the time	Single step, can detect blocking antibodies, prevent false positivity and false negativity
Cons	Has false positivity and false negativity	Cumbersome to set up, has false positivity and false negativity	two steps needed	time- consuming, hazardous, not sensitive, specialized well- equipped laboratories needed	Cumbersome to set up
False negativity	Chronic and complicated cases	Chronic and complicated cases, prozone phenomenon		Isolation rate of pathogen is 50%-90%	Chronic and complicated cases
False positivity	Cross reactionb	Cross reactionb		No	Cross reactionb
Studied antibody	IgM, IgG	IgA, IgM, IgG	IgG, IgA	-	IgM, IgG	IgA, IgM, IgG

a two-step test; first 24-hour incubation for serum agglutination test, second 24-hour for indirect Coombs test; bFranciella spp., Yersinia spp., Vibrio spp., Echerichia coli O:157 and lymphomas

nary system3,5,8. Among musculoskeletal manifesta- tions, sacroiliitis is the most common involvement in adult patients, while arthritis of the knee is the most common involvement in pediatric patients3,8-10. Spon- dylitis in brucellosis mainly affects patients above 40 years of age and occurs as a subacute or chronic in- fection of lumbar vertebrae11. The incidence of spon- dylitis and sacroiliitis in pediatric patients has been reported to be as low as 0.9%-4.5% and 0.3%-4.5%, respectively6,10. Musculoskeletal involvement of our patient manifested as sacroiliitis and spondylitis, both of which are quite rare in childhood.

Owing to the nonspecific nature of symptoms and since it may be confused with other multisys- temic diseases, serologic and microbiologic tests are crucial in the diagnosis of brucellosis. Isolation of Brucella spp. from the blood, bone marrow or other tissue fluids is the gold standard for the diagnosis but the isolation rate of this agent is generally low and variable. Therefore, serologic tests are the main tools in the diagnosis of brucellosis in routine practice4,12. In our case, in contrast to the initial negative serum agglutination test, the immunocapture agglutina- tion test performed later was found to be positive at a titer of 1/320. False negative serum agglutination test results may be seen in some conditions such as early phase of disease, chronic or complicated course of disease, existence of blocking antibodies or pro- zone phenomenon (excess of antibodies)4. Hence, it is recommended to try further dilutions or different agglutination tests in highly suspect cases with nega- tive initial serum agglutination tests. This approach may prevent delay in the diagnosis and treatment of brucellosis. table 1 shows the most common tests used in the diagnosis of brucellosis and their char- acteristics.

early radiological signs of brucellosis are nonspe- cific and destructive changes may not be detected on direct radiographs before the third month of the dis- ease, hence, the diagnosis of sacroiliitis or spondylitis may not be achieved. Contrast enhanced MRI is the most frequently advised method for the diagnosis and assessment of musculoskeletal involvement in brucel- losis13. MRI shows low-to-intermediate signal inten- sity on t1-weighted images of the intervertebral disc and low signal intensity in the adjacent vertebral bod- ies. The signals in these areas become hyperintense on t2-weighted MRI sequences11. Combined with the clinical features and laboratory results, MR im- ages of our patient were concordant with brucellosis infection.

trimethoprim/sulfamethoxazole, tetracycline, rifampicin, gentamicin and streptomycin are wide- ly used agents with various dose regimens, dura- tions and combinations in childhood brucellosis. In cases of osteomyelitis, meningitis and endocardi- tis, a triple combination of tetracycline, rifampicin and aminoglycoside should be used for at least 12 weeks2,14.

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Childhood brucellosis with unusual features