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ABSTRACT: To evaluate the association between human leukocyte antigens (HLA) class I and therapeutic response to interferon-alpha in Croatian patients with chronic hepatitis C.
HLA-A, -B, and -C genotyping was performed in 55 patients with sustained virological response and in 57 patients without sustained virological response to interferon-alpha therapy. Patients were treated in the period from 1998-2001 with interferon-alpha at a dose of 3 million units three times a week. Patients who became negative for hepatitis C virus RNA after 12 weeks of therapy completed 48 weeks of therapy.
There was no association between therapeutic outcome and frequency of HLA-A, as well as of HLA-B alleles. HLA-Cw7 was significantly more frequent in patients with than those without sustained virological response (27.0% vs 6.7%; P=0.011).
In Croatian patients with chronic hepatitis C, HLA-Cw7 is the predictor of sustained virological response to interferon-alpha therapy.
Croatian Medical Journal 01/2008; 48(6):807-13. · 1.80 Impact Factor
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ABSTRACT: Q fever is a common and acute but rare chronic zoonosis caused by Coxiella burnetii. Its acute form manifests as atypical pneumonia, flu-like syndrome, or hepatitis. Some authors observed symptoms of chronic fatigue in a small number of patients after the acute phase of Q fever; in many cases serological assay confirmed the activity of Coxiella burnetii infection. The effect of antibiotic therapy on post-Q-fever fatigue syndrome has not been studied in south-east Europe thus far.
Three patients are presented with post-Q-fever fatigue syndrome. All fulfilled the CDC criteria for chronic fatigue syndrome. IgA antibodies to phase I of the growth cycle of Coxiella burnetii were positive in two patients and negative in one. Two patients were treated with doxycycline for two weeks in the acute phase of illness and one with a combination of erythromycin and gentamycin. After 4-12 months they developed post-Q-fever fatigue syndrome and were treated with intracellular active antibiotics (fluoroquinolones and tetracycline) for 3-12 months. Efficacy of the treatment was observed in two patients, but in one patient the results were not encouraging.
These results suggest the possibility of the involvement of Coxiella burnetii infection in the evolution of chronic fatigue syndrome. This is the first report on post-Q-fever fatigue syndrome in Mediterranean countries. Evidence of IgA antibodies to phase I of the growth cycle of Coxiella burnetii is not a prerequisite for establishing a diagnosis of CFS. The recommendation of antibiotic treatment in post-Q-fever fatigue syndrome requires further investigation.
Medical science monitor: international medical journal of experimental and clinical research 08/2007; 13(7):CS88-92. · 1.70 Impact Factor
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ABSTRACT: Haemophilus parainfluenzae endocarditis is a rare acute or subacute disease. It is usually associated with dental and surgical procedures in the oral cavity. In a 23-year-old athlete admitted to Department of Infectious Diseases, Split University Hospital, the diagnosis of infective endocarditis was established based on Duke's criteria. The patient was not exposed to risky medical procedures nor he had a predisposing heart disease. The course of illness was characterized by peripheral embolizations (splinter hemorrhages and petechiae) and vegetation on the dorsal mitral valve. After seven days of incubation, blood cultures revealed Haemophilus parainfluenzae. The patient was treated intravenously with amoxicillin-clavulanic acid plus gentamicin for four weeks. Peroral therapy was continued with amoxicillin-clavulanic acid alone for two weeks. By the end of treatment, heart ultrasound showed disappearance of endocardial vegetation. Echocardiographic and clinical examinations performed at 3, 6 and 12 months of therapy showed no pathological aberrations.
Acta medica Croatica: c̆asopis Hravatske akademije medicinskih znanosti 05/2007; 61(2):219-22.
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ABSTRACT: Q fever shows a wide diversity of clinical manifestation. Q fever is endemic in northern Croatia, but the epidemiological and clinical characteristics of this disease in various ecological areas of southern Croatia are unclear.
From January 1985 to December 2002, acute Q fever cases hospitalized at Split University Hospital were analyzed. Acute Q fever was defined as fever (>38 degrees C) with clinical findings in lung and/or liver verified by serologic testing with Coxiella burnetii phase II antigen.
During the period of observation, 155 acute Q fever cases were hospitalized. The mean incidence of acute Q fever in the study region was 0.20/100,000/year (95%CI:0-0.78) in the coastal area and 4.64/100,000/year (95%CI:0.44-8.85) in the non-coastal areas, with a male predominance (chi2=60.0; p=0.0000) and a mean male to female ratio of 4.2:1. People of essentially all ages (4-76 years) were affected, the highest rate of infection being recorded in 20- to 49-year-old age groups. In contrast to adults, girls were more frequently affected than boys (2:1). No case of acute Q fever was recorded on any of the nearby islands. Clinically, acute Q fever most commonly presented with both pneumonia and hepatitis (60.0%), followed by pneumonia (25.8%), hepatitis (9.0%), and nonspecific febrile illnesses (5.2%).
C. burnetii is endemic in rural, coastal, and non-coastal areas of southern Croatia and is associated with stock breeding. In these areas, Q fever occurs sporadically and epidemically. Males 20-49 years of age were the prevalent cases.
Medical science monitor: international medical journal of experimental and clinical research 04/2006; 12(3):CR126-31. · 1.70 Impact Factor
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ABSTRACT: We present a case of a 22-month-old child with swollen upper part of the right arm and osteolytic lesion of the right humerus, which resembled a neoplastic process. Epidemiological history revealed no scratch marks on the skin or cutaneous papule or pustule. Presumptive diagnosis of hematogenous osteomyelitis was established, but treatment with fusidic acid was unsuccessful. Histological examination of the bioptic specimen of the soft tissue swelling showed a lymph node morphology, with numerous granulomas with central stellate necrosis. Indirect immunofluorescence assay for Bartonella henselae yielded positive results. New treatment included 15 days of trimetoprime and sulfamethoxazole, followed by azithromycin for 5 days. Four months later, swelling resolved and osteolytic lesion almost completely healed with formation of surrounding sclerosis. In conclusion, cat-scratch disease without positive epidemiological history and primary cutaneous papule or pustule may be a serious diagnostic problem, but can be solved by serological and histological examination.
Acta dermatovenerologica Croatica: ADC / Hrvatsko dermatolosko drustvo 02/2004; 12(2):92-5. · 0.36 Impact Factor
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ABSTRACT: To detect and isolate rickettsial strains from blood samples of patients with presumptive diagnosis of Mediterranean spotted fever (MSF) in the coastal region of south Croatia, and to compare the results with routine serology.
A "suicide" polymerase chain reaction (PCR), and a shell vial culture were done on samples of ethylenediamine tetra-acetic acid (EDTA) and citrate-anticoagulated blood samples. Indirect immunofluorescence was performed on sera collected from 17 patients clinically diagnosed with MSF during summer in three consecutive years, from 1998 to 2000.
The primers used in PCR amplified the expected part of the rickettsia genomic DNA and Rickettsia conorii grew from the shell vial-cultured blood of a single patient. In 13 patients, the diagnosis was confirmed serologically by paired sera, whereas in 4 patients the diagnosis remained presumptive, since no paired sera were available. Analyzing sequences of the ompA and citrate synthase gene, respectively, derived from the shell vial isolate, a 100% similarity with Rickettsia conorii, strain Seven (Malish), was found.
To the best of our knowledge, this is the first isolation of Rickettsia conorii from a human sample in Croatia, and the first proof of a causative agent of MSF in the country. Beside PCR-based methods and isolation, correct diagnosis of MSF could be still routinely reached by serology.
Croatian Medical Journal 11/2003; 44(5):630-4. · 1.80 Impact Factor
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ABSTRACT: To investigate the possibility of permanent renal function impairment and other organ lesions following hemorrhagic fever with renal syndrome (HFRS).
Data on 30/37 patients infected with HFRS, treated at the Department of Infectious Diseases, Split University Hospital, in 1995 were retrospectively analyzed. The data were collected three to six years following the appearance of HFRS. In 1998, 30/37 patients presented for control checkup, when their history data were collected, along with physical examination, hematology and biochemistry tests, and urinalysis. Creatinine clearance and sodium, potassium, chlorine, phosphorus, beta 2-microglobulin and N-acetyl-beta-D glucosaminase in 24-h urine were determined. In native urine, erythrocyturia was observed, with 10 erythrocytes per field were considered pathologic result. During the 1998-2001 period, renal scintigraphy by means of technetium labeled diethylene triaminopentacetic acid (99mTC DTPA) was performed in 13/30 patients.
Of subjective discomforts, 29/30 (96.7%) patients reported lumbar pain. Elevated blood pressure was found in 9/30 (30.0%), erythrocyturia in 4/30 (13.3%) and hepatic lesion in 4/30 (13.3%) patients. Decreased creatinine clearance values (< 1.2 ml/s) were found in 4 and increased values (> 2.35 ml/s) in 10 patients. Increased sodium in 24-h urine was recorded in 10/23 and increased beta 2-microglobulin in 6/23 (26%) patients. Proteinuria exceeding 150 mg/day was detected in 11/23 (47.8%) patients. Scintigraphy of the kidneys demonstrated reduced glomerular filtration (< 100 ml/min/1.72 m2) in 3/13 patients. Prolonged mean times (> 5 minutes) of radiopharmaceutical passage through the renal parenchymae were found in 7/13 (53.8%) patients.
Studies performed in 30 patients three years after they had recovered from HFRS revealed changes suggesting a mild to moderate impairment of the renal function. Hypertension found in 9/30 patients was a significant finding, considering the fact that all subjects were soldiers, thus having undergone through examinations to prove them completely healthy prior to joining army. Hypertension results were consistent with those reported from the USA. Although erythrocyturia points to urinary tract damage, its glomerular or postglomerular origin was not examined. Decreased creatinine clearance found in 4/23 patients suggested functional renal impairment. Increased natriuresis found in 10/23 patients implied tubular damage, i.e. reduced ability of tubular cells for sodium reabsorption from primary urine. Non-selective albuminuria detected in 11/23 patients indicated permanent lesion of the glomerular basal membrane. Increased beta 2-microglobulin found in 6/23 patients indicated that the lysosomal enzyme level was elevated only in the acute stage of the disease, but may have been an indicator of permanent lesion. No description of post-HFRS scintigraphic lesion of the kidneys was found in the literature. A decreased value of glomerular filtration, found in three patients, and especially the prolonged mean time of glomerular micropharmaceutical passage in 7/13 (53.8%) patients may have suggested glomerular damage. However, the possible reason may have also been a reduced passage of glomerular filtrate through the damaged lower parts of the nephrons. Transaminase increase during the acute stage of HFRS suggested the possible liver infection, maybe even hantavirus replication in hepatocytes. Even though biopsy confirmed the histologic picture of chronic hepatitis in one patient, the question remains whether it could have been caused by hantavirus.
Studies performed in 30 patients with a history of HFRS revealed renal function impairment, along with hypertension and damage to the liver parenchyma in some patients. The results obtained showed that the HFRS infection in Croatia may have entailed chronic sequels. To confirm this hypothesis, additional studies including a control group of hantavirus negative persons are needed.
Acta medica Croatica: c̆asopis Hravatske akademije medicinskih znanosti 01/2003; 57(5):365-8.
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ABSTRACT: To investigate the characteristics and determine risk factors for hantanvirus infection in natural focus of hemorrhagic fever with renal syndrome (HFRS) on the Dinara Mountain, where outbreak of disease emerged among Croatian soldiers in 1995, and to describe the features of HFRS acquired on the Dinara mountain and determine the scale of the largest HFRS epidemic so far in Croatia.
During 1996, small mammals were captured in the region of Dinara Mountain where infected Croatian soldiers had sojourned. By taxonomic classification of 42 captured small mammals, three species were determined: 23 yellow-necked mouse, 9 wood mouse, and 5 bank vole. Hantavirus antigen was determined in the lungs of the captured animals by means of direct immunofluorescence assay. The most important features of HFRS were retrospectively determined in 37 soldiers with HFRS treated in the Department for Infectious Diseases of the Split University Hospital. The degree of inapparent exposure to infection was determined by indirect immunofluorescence in 103 soldiers sojourning in this region of natural focus with no apparent signs of HFRS. Epidemiological questionnaire included 50 soldiers with negative serum antibodies, as well as 33 available out of total 37 soldiers with HFRS. Chi-square test was used to determine risk factors.
Hantavirus was found in the lungs of 5/42 (12%) captured animals. Mild form of the disease, with few hemorrhagic symptoms and pronounced renal insufficiency, was present in 19/37 patients. The epidemiological questionnaire determined the following risk factors for hantanvirus infection in this focus: service in artillery corps (p=0.040), sleep in wooden barracks (p=0.004), station in forest biotope (p=0.037), usage of natural camouflage (p=0.024), smoking (p=0.010), and the presence of rodents in the place of housing (p<0.001).
A new natural focus of HFRS in Croatia, and the first one in Dalmatia, was defined by seroepidemiologic, mamologic, and virologic analysis. The risk factors for infection in the new focus have been identified. Our patients suffered from a mild form of HFRS, which predominates in south-eastern Europe, without lethal outcome.
Croatian Medical Journal 10/2002; 43(5):576-80. · 1.80 Impact Factor
