Mustafa Kasım Karahocagil

Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature.

INTRODUCTION Brucellosis is the most prevalent bacterial zoonosis worldwide. In this study, we aimed to compare our 1028 brucellosis cases with other big series in the literature in view of epidemiological, clinical, and laboratory findings and therapeutic features. METHODS A total of 1028 brucellosis cases admitted to the Department of Infectious Diseases and Clinical Microbiology over a 10-year period were included in the study. A retrospective analysis was undertaken and patient files were reviewed for history, clinical and laboratory findings, and therapeutic features, as well as complications. RESULTS Of the 1028 patients, 539 (52.4%) were female and 489 (47.6%) were male. The mean age of patients was 33.7+/-16.34 years and 69.6% of cases were aged 13-44 years. Four hundred and thirty-five cases (42.3%) had a history of raising livestock and 55.2% of the cases were found to have no occupational risk for brucellosis. Six hundred and fifty-four of the cases (63.6%) had a history of raw milk and dairy products consumption. The most frequently seen symptoms were arthralgia (73.7%) and fever (72.2%), while the most common clinical findings were fever (28.8%) and hepatomegaly (20.6%). The most frequent laboratory finding was a high C-reactive protein level (58.4%). The standard tube agglutination (STA) test+Coombs STA test was positive in 1016 cases (98.8%). Focal involvement was present in 371 (36.1%) cases. The most frequent involvement was osteoarticular involvement with 260 cases (25.3%). The overall relapse rate for patients with brucellosis was 4.7%. The highest relapse rate, 8.5%, was observed in the group of patients with osteoarticular involvement. Regimens including doxycycline and streptomycin with or without rifampin appeared more effective than other regimens in osteoarticular involvement. CONCLUSIONS In humans, brucellosis may lead to serious morbidity, and it continues to be a major health problem in Turkey. There is no recommended treatment protocol for complicated brucellosis. Large multicenter studies are needed to determine the most appropriate treatment choices and durations in complicated brucellosis.

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

ABSTRACT No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

A familial outbreak of fascioliasis in Eastern Anatolia: a report with review of literature.

AIM To present the results of a cross-sectional epidemiological analysis of a familial outbreak of fascioliasis in Eastern Anatolia and to discuss the clinical, diagnostic and therapeutic properties of the patients. MATERIALS AND METHODS A screening group consisting of 92 individuals from the same family with a history of watercress ingestion and a control group consisting of 30 individuals from neighboring families were included in the study. In both groups, full blood count, erythrocyte sedimentation rate, liver function tests and total IgE levels were assessed. Stool analysis was performed on three consecutive days with native, lugol and sedimentation methods. The diagnosis was based on the detection of parasite ova in the stool or alternatively based on consistent clinical, laboratory, and radiological findings or positive clinical findings in combination with a positive ELISA test. Abdominal ultrasonography and computerized tomography scans were performed on all patients. RESULTS 24 patients (21 women and 3 men) were diagnosed with fascioliasis. The mean age was 24.5±18.6 years (range, 5-64 years). All cases had a history of watercress ingestion, malaise, fatigue, lack of appetite, and abdominal pain. Clinical features included: weight loss was present in 18 cases (75%), dyspepsia in 12 (50%), headache in 11 (45.8%), sweating in 10 (41.7%), fever and dyspnea each in 8 (33.3%), nausea and vomiting in 6 (25%), and itching in 4 (16.75). The most common laboratory abnormalities were total IgE elevation in 19 cases (79.2%) and eosinophilia in 17 (70.8%). The eosinophilia was >20% in 14 cases (58.3%) and the total IgE was >500IU/ml in 15 cases (62.5%). Stool examination for ova was positive in 11 cases. 10 patients had positive clinical, laboratory and radiological findings. A further three patients were diagnosed based on their clinical findings and their ELISA results. All cases had positive ELISA results. All patients, except one pregnant woman, were treated with 10mg/kg triclabendazole. Two patients required a second treatment course of triclabendazole 20mg/kg in two divided doses due to persistence of ova in the stool. One patient who developed acute urticaria as a side effect of the drug was given three additional courses of 10mg/kg triclabendazole in combination with prednisolone and antihistamines. The pregnant woman initially received four courses of 25mg/kg praziquantel treatment for 1 week. As ova were still detected in her stool following delivery, she was subsequently treated with triclabendazole. CONCLUSIONS One case of fascioliasis may indicate a familial outbreak. In the acute stage radiological investigations can assist in confirming the diagnosis. ELISA testing is a reliable and sensitive method for the diagnosis of fascioliasis during any stage of the disease and may also be useful during follow-up.

Cutaneous anthrax in Eastern Turkey: a review of 85 cases

Background.  Anthrax is a zoonotic disease diminishing worldwide. Although a very rare disease in developed countries, anthrax is still endemic in developing countries.

Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection.

Objective The aim of this study was to demonstrate the relation between intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels and the other HBV replicative intermediates and hepatocyte expression of HBV antigens. Patients and methods Patients with hepatitis B surface antigen (HBsAg) positivity, hepatitis B early antigen negativity, serum HBV DNA levels 104 copies/ml or more, and constantly or intermittently increased alanine aminotransferase levels were included. Results Fifty-nine patients were included. There was a good correlation between the levels of IH HBV cccDNA and serum HBV DNA (P<0.001). Serum HBsAg levels were weakly correlated with IH HBV cccDNA levels and moderately correlated with serum HBV DNA (r=0.322, P=0.017; r=0.489, P=0.001, respectively). There were no significant correlation between serum HBsAg level and histologic activity index groups (P=0.691), but stage 0, 1, and greater than 2 fibrosis groups were positively correlated with serum HBsAg levels (P=0.019). IH cccDNA and serum HBV DNA were significantly different in hepatitis B core antigen staining groups (P=0.008 and <0.001, respectively) but there was no significant correlation between HBsAg staining groups and HBV replication markers. There was a weak correlation between serum HBsAg levels and IH HBsAg and hepatitis B core antigen levels (r=0.333, P=0.012; r=0.366, P=0.006, respectively). In multivariate analysis, alanine aminotransferase, age, fibrosis stage, and serum HBsAg quantitation were the most important factors predicting IH HBV cccDNA level. Conclusion Histopathologic damage, serum HBV DNA levels, and IH HBV replication markers have a more complex and dynamic process. However, both serum and IH HBV replication markers provide important knowledge about the activity of the disease.

An outbreak of botulism in a family in Eastern Anatolia associated with eating süzme yoghurt buried under soil

Cases of botulism in a family in eastern Anatolia were studied. In late September 2005, an outbreak of botulism developed in our region, first in 2 patients, a teenage boy and his mother, in whom the disease culminated in respiratory insufficiency and death. An additional 8 cases of botulism were identified later; most of them presented to our medical centre the next d. These patients with milder symptoms recovered gradually. All the patients received anti-botulinum toxin. The investigation of the source of the outbreak showed an unexpected vehicle for botulism infection in the these patients, süzme (condensed) yoghurt buried under soil. Type A botulinal toxin was detected in the yoghurt sample. The clinical diagnosis was also confirmed by a mouse bioassay performed with the serum samples of the patients. The most common symptoms were dry mouth, difficulty in speaking and swallowing, and change in voice quality. The 10 identified patients with botulism constitutes the largest-ever outbreak of botulism reported in Turkey to date. The present study shows the importance of considering a diagnosis of botulism soon after patients present with acute cranial nerve dysfunction and of promptly treating suspected cases with antitoxin.

Diagnosis of chronic brucellar meningitis and meningoencephalitis: the results of the Istanbul-2 study

No detailed data exist in the literature on the accurate diagnosis of chronic brucellar meningitis or meningoencephalitis. A multicentre retrospective chart review was performed at 19 health centres to determine sensitivities of the diagnostic tests. This study included 177 patients. The mean values of CSF biochemical test results were as follows: CSF protein, 330.64 ± 493.28 mg/dL; CSF/ blood-glucose ratio, 0.35 ± 0.16; CSF sodium, 140.61 ± 8.14 mMt; CSF leucocyte count, 215.99 ± 306.87. The sensitivities of the tests were as follows: serum standard tube agglutination (STA), 94%; cerebrospinal fluid (CSF) STA, 78%; serum Rose Bengal test (RBT), 96%; CSF RBT, 71%; automated blood culture, 37%; automated CSF culture, 25%; conventional CSF culture, 9%. The clinician should use every possible means to diagnose chronic neurobrucellosis. The high seropositivitiy in brucellar blood tests must facilitate the use of blood serology. Although STA should be preferred over RBT in CSF in probable neurobrucellosis other than the acute form of the disease, RBT is not as weak as expected. Moreover, automated culture systems should be applied when CSF culture is needed.

Renal involvement in Brucella infection.

OBJECTIVES To examine our patients with brucellosis and renal involvement. Although brucellae have been recovered from the urine of patients with brucellosis, renal involvement is uncommon. METHODS The data from 15 patients (8 males and 7 females, mean age 43 +/- 18.9 years, range 16 to 80), who had been admitted to our hospital with the diagnosis of brucellosis with renal involvement from 1998 to 2006, were retrospectively evaluated. RESULTS In almost all cases, urinalysis revealed hematuria and variable amounts of proteinuria; some of the patients had pyuria. Of the 15 patients, 14 had renal failure. The etiology of renal failure was prerenal azotemia in 1, acute tubular necrosis because of nonsteroidal anti-inflammatory drug use in 1, anuric tubulointerstitial nephritis due to rifampin use in 1, nephritis accompanied by brucellar endocarditis in 3, brucellar endocarditis and tubulointerstitial nephritis-associated vasculitis in 1, brucellar membranoproliferative glomerulonephritis in 1, and brucellar tubulointerstitial nephritis clinically in 6 patients. Hemodialysis was required in 5 patients. Chronic renal failure developed in 1 patient, 2 patients were lost to follow-up, and renal function completely recovered in 11 patients. Two patients underwent renal biopsy and membranoproliferative glomerulonephritis with intraglomerular infiltration of histiocytes was identified in 1 patient and chronic tubulointerstitial nephritis associated with vasculitis and immune complex nephritis features was identified in the other. CONCLUSIONS In areas endemic for brucellosis, this infection can be associated with hematuria, proteinuria, and renal failure. In addition, many diverse etiologies can play a role in the renal involvement associated with Brucella infection.

Toxic-febrile neurobrucellosis, clinical findings and outcome of treatment of four cases based on our experience.

Central nervous system (CNS) involvement is uncommon in brucellosis. Neurological complications of brucellosis may be divided into 2 major groups: 1) those related to the acute-febrile state that occurs in acute disease (toxic-febrile neurobrucellosis), and 2) those related to actual invasion and localization of the pathogen in the CNS (classical neurobrucellosis). In this paper, we present 4 cases of toxic-febrile neurobrucellosis and discuss clinical findings and outcome of treatment in these cases. All patients had fever, headache, stupor or coma with neuropsychiatric symptoms such as hallucination, delirium, convulsion, dysarthria, psychosis, and night raving. Peripheral and cranial vasculitis was present in case 3 and bilateral sensorioneural hearing loss in case 4. Neither pleocytosis nor hyperproteinorrachia was present in any patient in lumbar puncture. Brucella melitensis was isolated in case 3 from bone marrow, and in case 4 both from blood and bone marrow. All patients received combined treatment consisting of ceftriaxone, rifampicin, and doxycycline. They were discharged from the hospital with full recovery. No recurrence or any complaint was observed during the follow-up. In conclusion, despite the rapid course and serious complications, outcome from febrile-toxic neurobrucellosis is excellent especially when effective antimicrobial therapy is started early in the course of illness.

Serum myeloperoxidase activity and oxidative stress in patients with acute brucellosis

OBJECTIVES The role of infection in the pathogenesis of atherosclerosis has been increasingly discussed. Previous studies have suggested that increased myeloperoxidase activity plays an important role in the pathogenesis of atherosclerosis. The aim of this study was to investigate the serum myeloperoxidase activity and catalase activity along with lipid hydroperoxide (LOOH) levels in patients with acute brucellosis. DESIGN AND METHODS Thirty-two patients with brucellosis and 33 healthy controls were enrolled. Serum myeloperoxidase activity, catalase activity and LOOH levels were determined. RESULTS Serum myeloperoxidase activity and LOOH levels were significantly higher in patients with brucellosis than controls (p<0.05, p<0.001), while catalase activity were significantly lower (p<0.001). LOOH levels were found to be significantly positively correlated with MPO activity (r=0.297, p=0.016) in patients. CONCLUSIONS These results indicate that increased myeloperoxidase activity and decreased catalase activity is associated with increased oxidative stress, which may have a role in atherosclerotic processes in brucellosis patients.