Vol 43 # 3 September 2011 - Kma.org.kw

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206 KUWAIT MEDICAL JOURNAL September 2011 Original Article Complications of Brucellosis in Adults: An Experience from a State Hospital in Southeastern Anatolia Region of Turkey Mehmet Ulug, Nuray Can-Ulug Department of Infectious Diseases and Clinical Microbiology, Özel Ümit Hospital, Eskişehir, Turkey Department of Neurology, Özel Ümit Hospital, Eskişehir, Turkey Kuwait Medical Journal 2011; 43 (3): 206-212 ABSTRACT Objective: To evaluate the complications and systems involvement of acute Brucella infection in adults Design: Retrospective study Setting: Midyat State Hospital, Mardin, Turkey Subjects: Seventy-eight patients with acute brucellosis Interventions: Brucellosis treatment Main Outcome Measures: The frequency of complications and systems involvements Methods: This retrospective study was carried out at the Infectious Diseases and Neurology clinics between April 2007 and August 2008. The diagnosis of brucellosis was made with compatible clinical findings, positive Brucella agglutination 1/160 titers, and / or the isolation of Brucella species. Complication was defined as the presence of symptoms or physical signs of infection at a particular anatomic site in a patient with active brucellosis. Results: This study focuses on the frequency of complications in cases with brucellosis. Out of 78 patients, 46 (59%) were female and 32 (41%) were male. The mean age of patients was 36.4 ± 14.2 years. Skeletal complications were the most frequent, found in 26 (33.8%) cases, followed by hematological (n = 25, 32.1%), cutaneous (n = 3, 3.9%), nervous (n = 2, 2.6%), genitourinary (n = 2, 2.6%), respiratory (n = 1, 1.3%) and gastrointestinal system (n = 1, 1.3%). Conclusion: Brucellosis, whether in an endemic region or not, remains a diagnostic puzzle due to occasional misleading unusual presentations and non-specific symptoms. It is a systemic infection in which any organ or system of the body can be involved. Our data showed that brucellosis is a preventable disease. Knowledge and early diagnoses of the complications are especially important. KEY WORDS: adult, Brucella melitensis, Brucellosis, complication, osteoarticular, Turkey INTRODUCTION Brucella species are small, non-motile, non-sporeforming, encapsulated Gram-negative coccobacilli. There are seven species, of which only four can cause human brucellosis: Brucella aboruts, Brucella melitensis, Brucella suis, and Brucella canis [1,2] . Brucellosis is a systemic infectious disease and it is still an important public health problem throughout the world, but especially in the Mediterranean region, including Turkey [3,4] . Disease incidence and prevalence rates vary widely among nations. Due to variable reporting, true estimates in endemic areas are unknown. According to reports from the Turkish Ministry of Health, 37 cases were reported in 1970, with numbers rising to 18,408 cases in 2004 (incidence rate 25.67/100,000). It is frequent especially in the rural areas of the middle and southeastern regions, and B. melitensis is the most prevalent strain [5,6] . It is thought that this increase is a result of improvements in diagnosis and increased reporting, rather than a real increase in the prevalence of the disease. Humans are infected by direct contact with infected animals or their products or, indirectly, by ingesting infected milk or dairy products [1] . Following infection, the bacteria initially localize in the regional lymph nodes, and then disseminate hematogeneously to the organs of the reticuloendothelial system to multiply within phagocytic cells. The release of bacterial endotoxin from phagocytic cells produces the constitutional symptoms and signs of the disease [7] . Brucellosis can be an acute or chronic febrile illness and presents with a variety of manifestations after an incubation period, which can vary from one to six weeks or several months [8] . The most frequent symptoms are fever, chills or rigors, malaise, generalized ache, headache and fatigue. Gastrointestinal, skeletal, Address correspondence to: Dr. Mehmet Uluğ, Department of Infectious Diseases and Clinical Microbiology, Özel Ümit Hospital, Eskişehir, Turkey. Tel: (0532) 4475756, Fax: 0222 3350170 (Hospital), E-mail: mehmetulug21@yahoo.com
September 2011 KUWAIT MEDICAL JOURNAL 207 cardiovascular, genitourinary and hematological manifestations are well-known. Neurobrucellosis, peritonitis, pericarditis, pancytopenia are unusual manifestations of brucellosis [6] . If the disease is not well recognized and not included in the differential diagnosis, a treatable disease will be missed [3] . In this study, all patients were investigated in more detail with respect to complications in adult cases in southeastern Anatolia region of Turkey. SUBJECTS AND METHODS This study was retrospectively carried out at Midyat State Hospital, Departments of Infectious Disease and Neurology, between April 2007 and August 2008. For its size, Midyat, a small and mostly rural county of approximately 75,000 inhabitants, had an unusually high annual incidence of brucellosis due to poor preventive measures and inadequate public health policies. Brucellosis was diagnosed according to the case definition and treatment guidelines of the Turkish Ministry of Health [9] ; isolation of microorganisms in blood, other body fluids or tissue samples, or the presence of compatible clinical symptoms such as arthralgia, fever, sweating, chills, headache, myalgia and malaise combined with a serum antibody titer 1/160 or at least a fourfold increase in this titer by the standard tube agglutination (STA) test in a two or three weeks interval. B. abortus S99 antigens (Seromed Laboratory Products, Turkey) were used for the STA. The BACTEC 9240 system (Becton-Dickinson, Maryland, USA) for initial blood and other body fluids cultures with subculturing onto chocolate blood agar at 37 ºC in CO 2 was used. All of the cultures were done in Biosafety Class II cabinets. Smears from colonies that grew were stained with Gram stain. The isolates of Gram-negative cocco-bacilli were identified with use of conventional biochemical tests (e.g., motility; oxidase, catalase and urease tests; effect to glucose and production of H 2 S), and Sceptor system (Becton- Dickinson, Maryland, USA). Patients who were known to have any chronic or acute systemic disease other than brucellosis, or were younger than 15 years of age were excluded from the study. Focal form or complication was defined as the presence of symptoms or physical signs of infection at a particular anatomic site in a patient with active brucellosis. Osteoarticular involvement was diagnosed in instances of tenderness, restriction of movement and swelling in any peripheral joint, or by unrelieved pain at rest together with radiological alterations. However, swelling was not essential for the diagnosis of hip, spine or sacroiliac arthritis. Diagnoses of spondylitis and sacroiliitis were confirmed by computerized tomography (CT) or magnetic resonance imaging (MRI). Neurobrucellosis was defined as: isolation of Brucella spp. from cerebrospinal fluid (CSF) of patients with suspected findings for brucellosis or isolation of Brucella spp. from bone marrow or blood cultures of patients with abnormal CSF findings with or without STA positivity of any titer in CSF with abnormal findings. Hematologic involvement was defined as hematologic abnormalities in laboratory and clinical findings (epistaxis, bleeding, petechiae, purpura, disseminated intravascular coagulation, and thrombophlebitis), excluding asymptomatic or poorly symptomatic cytopenias or coagulation disturbances. Anemia, thrombocytopenia and leucopenia were defined as hemoglobin level < 120 g/dl in females, < 135 g/dl in males, a platelet count of < 142,000/mm 3 and leukocyte count of < 4600/mm 3 , respectively. Hepatic complications were defined as the presence of a five-fold or greater rise in normal levels of aspartate aminotransferase or alanine aminotransferase, or jaundice. In addition, completed history and physical examination of all patients were reviewed: tests for complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor and blood chemistry profile were performed in all patients. In suspected cases the following tests were performed: lumbar puncture, CT and / or MRI for meningitis, routine chest X-ray and thorax CT for pneumonia, scrotal doopler ultrasonography (USG) for epididymoorchitis and abdominal USG for hepatitis. Patients were treated with various combinations of antibiotics. The regimens included the following: oral doxycycline (100 mg every 12 h), oral rifampin (300 or 600 mg every 24 h), intramuscular streptomycin (1 g every 24 h), and co-trimoxazole (80/400 or 160/800 every 12 h). The choice depended on several conditions: clinical presentation, pregnancy, drug side effects, tolerability and co-morbidity; in addition, in regions with scarce resources, therapeutic decisions are also determined by treatment costs and drug availability. In neurobrucellosis, pregnant women and patients with relapses and drug side effects intravenous ceftriaxone (2 g per day) was added to the regimen initially for two to four weeks and other antimicrobials were given for at least six weeks. When required, the duration of therapy was extended. Patients were followed up fortnightly until the end of the treatment period, monthly for three months, and thereafter every three months for one year. Relapse was assessed by a recurrence of symptoms and signs of the disease, a positive blood culture or rising antibody titer after treatment, in the absence of re-exposure to infection. RESULTS In this study, 78 patients (46 female and 32 male) with brucellosis were analyzed. The female / male
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