Viper envenomation in Central and Southeastern Europe: a multicentre study.

INTRODUCTION: Snakebite incidence varies across Europe. However, there is limited research from Central and Southeastern Europe. These regions are notable for the presence of the common European adder (Vipera berus) and the more venomous nose-horned viper (Vipera ammodytes). No standard European antivenom protocol exists. The aim was to assess the epidemiology and treatment of viper bites in this region, focusing on a comparison of bites from Vipera berus and Vipera ammodytes. METHODS: We conducted a prospective multicenter study in Central and Southeastern Europe from 2018 to 2020. This study included poison centres and toxicology-associated hospital wards in Poland, the Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, and Bulgaria. The following data were collected: age, gender, Vipera species, snakebite site, clinical picture, laboratory results, Audebert's clinical severity grading score, and antivenom therapy. RESULTS: The annual incidence of viper bites in Central and Southeast Europe was estimated at 2.55 bites per million population. Within their respective geographical distribution areas, the incidence of Vipera ammodytes bites (1.61 bites per million population) was higher than Vipera berus bites (1.00 bites per million population). Patients bitten by Vipera ammodytes more frequently reported local pain and developed thrombocytopenia. Antivenom treatment was more commonly administered in Vipera ammodytes bites (72%) compared to Vipera berus bites (39%). The incidence of Vipera ammodytes bites treated with antivenom within its geographical distribution area was three times higher than Vipera berus bites treated with antivenom (1.16 bites per million population versus 0.39 bites per million population). No deaths were reported. CONCLUSIONS: The estimated incidence of viper bites in Central and Southeastern Europe is at least 2.55 per million population. Vipera ammodytes bites are more common and severe, characterized by higher frequencies of pain and thrombocytopenia. Antivenom is needed more often for Vipera ammodytes bites. It is vital that enough European Medicines Agency-approved Vipera ammodytes antivenom is produced and offered affordably.

Antibody response and the clinical presentation of patients with COVID-19 in Croatia: the importance of a two-step testing approach.

According to anti-SARS-CoV-2 seroresponse in patients with COVID-19 from Croatia, we emphasised the issue of different serological tests and need for combining diagnostic methods for COVID-19 diagnosis. Anti-SARS-CoV-2 IgA and IgG ELISA and IgM/IgG immunochromatographic assay (ICA) were used for testing 60 sera from 21 patients (6 with severe, 10 moderate, and 5 with mild disease). The main clinical, demographic, and haemato-biochemical data were analysed. The most common symptoms were cough (95.2%), fever (90.5%), and fatigue and shortness of breath (42.9%). Pulmonary opacities showed 76.2% of patients. Within the first 7 days of illness, seropositivity for ELISA IgA and IgG was 42.9% and 7.1%, and for ICA IgM and IgG 25% and 10.7%, respectively. From day 8 after onset, ELISA IgA and IgG seropositivity was 90.6% and 68.8%, and for ICA IgM and IgG 84.4% and 75%, respectively. In general, sensitivity for ELISA IgA and IgG was 68.3% and 40%, and for ICA IgM and IgG 56.7% and 45.0%, respectively. The anti-SARS-CoV-2 antibody distributions by each method were statistically different (ICA IgM vs. IgG, p = 0.016; ELISA IgG vs. IgA, p < 0.001). Antibody response in COVID-19 varies and depends on the time the serum is taken, on the severity of disease, and on the type of test used. IgM and IgA antibodies as early-stage disease markers are comparable, although they cannot replace each other. Simultaneous IgM/IgG/IgA anti-SARS-CoV-2 antibody testing followed by the confirmation of positive findings with another test in a two-tier testing is recommended.

Omadacycline for Acute Bacterial Skin and Skin-Structure Infections.

BACKGROUND: Acute bacterial skin and skin-structure infections are associated with substantial morbidity and health care costs. Omadacycline, an aminomethylcycline antibiotic that can be administered once daily either orally or intravenously, is active against pathogens that commonly cause such infections, including antibiotic-resistant strains. METHODS: In this double-blind trial, we randomly assigned adults with acute bacterial skin and skin-structure infections (in a 1:1 ratio) to receive omadacycline (100 mg given intravenously every 12 hours for two doses, then 100 mg given intravenously every 24 hours) or linezolid (600 mg given intravenously every 12 hours). A transition to oral omadacycline (300 mg every 24 hours) or oral linezolid (600 mg every 12 hours) was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was an early clinical response at 48 to 72 hours, defined as survival with a reduction in lesion size of at least 20% without rescue antibacterial therapy. A secondary end point was an investigator-assessed clinical response at the post-treatment evaluation 7 to 14 days after the last dose, with clinical response defined as survival with resolution or improvement in signs or symptoms of infection to the extent that further antibacterial therapy was unnecessary. For both end points, the noninferiority margin was 10 percentage points. RESULTS: In the modified intention-to-treat population, omadacycline (316 patients) was noninferior to linezolid (311 patients) with respect to early clinical response (rate of response, 84.8% and 85.5%, respectively; difference, -0.7 percentage points; 95% confidence interval [CI], -6.3 to 4.9). Omadacycline also was noninferior to linezolid with respect to investigator-assessed clinical response at the post-treatment evaluation in the modified intention-to-treat population (rate of response, 86.1% and 83.6%, respectively; difference, 2.5 percentage points; 95% CI, -3.2 to 8.2) and in the clinical per-protocol population (96.3% and 93.5%, respectively; difference, 2.8 percentage points; 95% CI, -1.0 to 6.9). In both groups, the efficacy of the trial drug was similar for methicillin-susceptible and methicillin-resistant Staphylococcus aureus infections. Adverse events were reported in 48.3% of the patients in the omadacycline group and in 45.7% of those in the linezolid group; the most frequent adverse events in both groups were gastrointestinal (in 18.0% and 15.8% of the patients in the respective groups). CONCLUSIONS: Omadacycline was noninferior to linezolid for the treatment of acute bacterial skin and skin-structure infections and had a similar safety profile. (Funded by Paratek Pharmaceuticals; OASIS-1 ClinicalTrials.gov number, NCT02378480 .).

Mycoplasma pneumoniae in adult community-acquired pneumonia increases matrix metalloproteinase-9 serum level and induces its gene expression in peripheral blood mononuclear cells.

BACKGROUND: The objective of this study was to assess the concentration of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) in peripheral circulation and their mRNA expression in peripheral blood mononuclear cells (PBMCs) in patients with CAP caused by M. pneumoniae. MATERIAL/METHODS: We prospectively analyzed MMPs in 40 hospitalized patients with M. pneumoniae CAP on admission, and in the convalescent phase. Twenty healthy men were used as controls. Quantitative real-time PCR and ELISA tests were used. RESULTS: MMP-9 mRNA expression in PBMCs was increased in the acute phase of illness compared to the control group as well as in convalescent phase in which case it was statistically significant (Mann-Whitney; p=0.028). The same was found for MMP-9 plasma levels (Mann-Whitney test; p<0.001; p=0.001). Circulating MMP-2 concentration in acute patients was significantly lower than in the control group and convalescent phase (Mann-Whitney test; p=0.012; p=0.001), while no MMP-2 mRNA expression was found in PBMCs. The plasma level of MMP-9 correlated with leukocyte count in peripheral circulation (r=0.67, p<0.001). CONCLUSIONS: We conclude that M. pneumoniae in adult CAP induces activity of MMP-9 in peripheral blood circulation.

Electrocardiographic changes in hospitalized patients with leptospirosis over a 10-year period.

BACKGROUND: The aim of this study was to investigate the incidence and type of ECG changes in patients with leptospirosis regardless of clinical evidence of cardiac involvement. MATERIAL/METHODS: A total of 97 patients with serologically confirmed leptospirosis treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" in Zagreb, Croatia, were included in this retrospective study. A 12-lead resting ECG was routinely performed in the first 2 days after hospital admission. Thorough past and current medical history was obtained, and careful physical examination and laboratory tests were performed. RESULTS: Abnormal ECG findings were found in 56 of 97 (58%) patients. Patients with abnormal ECG had significantly elevated values of bilirubin and alanine aminotransferase, lower values of potassium and lower number of platelets, as well as more frequently recorded abnormal chest x-ray. Non-specific ventricular repolarization disturbances were the most common abnormal ECG finding. Other recorded ECG abnormalities were sinus tachycardia, right branch conduction disturbances, low voltage of the QRS complex in standard limb leads, supraventricular and ventricular extrasystoles, intraventricular conduction disturbances, atrioventricular block first-degree and atrial fibrillation. Myopericarditis was identified in 4 patients. Regardless of ECG changes, the most commonly detected infection was with Leptospira interrogans serovar Australis, Leptospira interrogans serovar Saxkoebing and Leptospira kirschneri serovar Grippotyphosa. CONCLUSIONS: The ECG abnormalities are common at the beginning of disease and are possibly caused by the direct effect of leptospires or are the non-specific result of a febrile infection and metabolic and electrolyte abnormalities. New studies are required for better understanding of the mechanism of ECG alterations in leptospirosis.

Zoonoses and vector-borne diseases in Croatia - a multidisciplinary approach.

Emerging and re-emerging infectious diseases create constant and serious concerns for public health. The majority of emerging infectious diseases (EID) are wildlife zoonotic diseases and vector-borne diseases. Croatia has a long tradition in the control, management and research of EID zoonotic diseases and vector-borne diseases. There has also been a long and advantageous tradition in the collaboration of different experts and professionals in EID research in Croatia involving physician clinicians in infectious diseases, microbiologists, pathologists, veterinarians and animal scientists, ecologists, forestry experts, wildlife scientists, public health specialists and epidemiologists and laboratory scientists. The University Hospital for Infectious Diseases in Zagreb established the Centre for Emerging and Re-emerging Infectious Diseases in liaison with national and international partners from Europe and the United States. This Centre is working in line with the 'One Health initiative' which recognises the inter-relationships between human, animal and environmental health.

Imported case of nephropathia epidemica--a case report.

A 41-year-oldpatient was hospitalized in hypotensive phase of nephropathia epidemica. The diagnosis was confirmed by serology. It is highly likely that the patient was exposed to infected aerosol of bank voles in endemic area of Sweden. The disease clinically manifested with fever, headache, abdominal and back pain, vision disturbances. Pathologic laboratory findings included thrombocytopenia, leukocytosis, increased values of C-reactive protein, blood urea and creatinine, abnormal chest X-ray and transient electrocardiogram abnormalities.

An unusual outcome in a child with hepatosplenic cat-scratch disease.

Typical cat-scratch disease (Bartonella henselae infection) in an immunocompetent child is usually associated with a history of scratch, bite or intimate contact with a cat. Most patients develop a non-tender papule in the scratch line after three to ten days. This may persist for only a few days or as long as two to three weeks. During the next two weeks or more, regional lymph nodes that drain the area gradually enlarge and then slowly resolve in more than 10% of patients. The nodes develop overlying erythema and may suppurate. Atypical forms of cat-scratch disease occur in a minority of cases and are characterized by ocular or neurological manifestations, hepatosplenic involvement, vertebral osteomyelitis, endocarditis etc. Immunocompromised individuals with B. henselae infection may develop bacillary angiomatosis, bacillary peliosis, and relapsing bacteremia. There have been several reports of hepatosplenic granulomas caused by B. henselae in immunocompetent children. We report a case of a 6-year-old boy with the hepatosplenic form of cat-scratch disease. Despite early diagnosis and long-term antimicrobial treatment, splenectomy could not be avoided.

Tuberculosis in HIV-infected patients in Croatia between 1986 and 2005.

A retrospective medical chart review was performed on 65 HIV-infected patients with tuberculosis hospitalized between 1986 and 2006 at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb. Thirty two patients presented with pulmonary involvement, 13 with extrapulmonary, and 20 patients had disseminated tuberculosis. Forty five patients had an abnormal chest X-ray. Mycobacterium tuberculosis was identified in 35 (53.9%) patients. Ten (15.3%) of 65 patients had already been receiving antiviral therapy, while another 31 (47.7%) initiated antiviral therapy after antituberculosis therapy. Tuberculosis-associated immune reconstitution inflammatory syndrome was observed in 11/27 (40.7%) patients. Forty one patient received the standard six month course of antituberculous therapy, while in 12 patients the therapy was prolonged. Twenty one patient (32%) experienced an adverse event to antituberculosis drugs. Twelve patients died (18.5%). After the introduction of highly active antiviral therapy (HAART) the mortality decreased. The incidence of tuberculosis in HIV-infected patients in Croatia is increasing, and tuberculosis is still an important opportunistic infection in our HIV-infected patients.

Cure of Q fever pneumonia with moxifloxacin: case report.

In a 25-y-old hospitalized male, Coxiella burnetii pneumonia was confirmed serologically by enzyme-linked immunosorbent assay. Previous treatment with oral azithromycin was unsuccessful. In hospital the patient was treated with oral moxifloxacin for 10 d and was completely cured. To our knowledge, this is the first clinical report of Q fever pneumonia treated with moxifloxacin.

Electrocardiographic changes in patients with haemorrhagic fever with renal syndrome.

The purpose of the study was to assess the incidence, type and dynamics of electrocardiography (ECG) alterations in patients with haemorrhagic fever with renal syndrome (HFRS) according to different stages of the disease. 79 patients hospitalized at the University Hospital for Infectious Diseases in Zagreb during the large HFRS outbreak in Croatia in 2002 were retrospectively analysed. HFRS diagnosis was confirmed by enzyme-linked immunosorbent assay. A 12-lead resting ECG was obtained. 30 (38%) patients had abnormal ECG findings, most frequently in the oliguric stage. Increased levels of urea and creatinine were observed in all patients with abnormal ECG, along with abnormal chest X-ray in nearly 50% of cases. Sinus tachycardia was the most frequent ECG disorder in the febrile stage, and bradycardia in the oliguric stage. During the course of disease, some other ECG disorders were recorded: bundle branch conduction defects, non-specific ventricular repolarization disturbances, supraventricular and ventricular extrasystoles, prolonged QT interval, low voltage of the QRS complexes in standard limb leads, atrioventricular block first-degree, and atrial fibrillation. Myocarditis was present in 3 patients. In conclusion, abnormal ECG was found in more than one-third of HFRS patients with the most common findings during the oliguric stage. All ECG changes were transient.

[Laboratory findings in patients with hemorrhagic fever with renal syndrome]. / Analiza laboratorijskih nalaza u bolesnika s hemoragijskom vrucicom s bubreznim sindromom.

AIM: To examine the frequency and distribution of hematologic and biochemical laboratory findings in 94 patients with hemorrhagic fever with renal syndrome (HFRS) in the epidemic year 2002. PATIENTS AND METHODS: The following laboratory findings were retrospectively analyzed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, hematocrit, leukocyte count and differential percentage (segmented neutrophils, band neutrophils, atypical lymphocytes), platelet count, coagulation tests, blood urea nitrogen (BUN), creatinine, urine, potassium, bilirubin (BIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GT), alkaline phosphatase (ALP), and serum protein electrophoresis. The study included 94 HFRS patients treated at the Dr Fran Mihaljevic University Hospital for Infectious Diseases in Zagreb during 2002. RESULTS: ESR increase, mostly mild to moderate, was found in 86.2% of study patients. Increased CRP was recorded in 98.9% of study patients, however, one-fourth had CRP higher than 100 mg/L. Leukocytosis was recorded in 38.3% (10.1 +/- 4.2 x 10(9)/L), thrombocytopenia in 89.4% patients (68.2 +/- 48.3 x 10(9)/L), and severe thrombocytopenia (x 10(9)/L) in six patients. Three patients had abnormal coagulation tests. Increased values of BUN and creatinine were recorded in more than a half of patients, while only four patients had mild hyperkalemia. Only three patinets required hemodialysis. Mildly to moderately increased values of aminotransferases (AST, ALT, GT) were observed in more than 2/3; hypoalbuminaemia in nearly 1/3, and elevated alpha-2 fraction in more than 2/3 of patients. The majority of patients had pathologic urine findings. First laboratory abnormalities were usually found between day 5 and 7 of the disease (increased CRP level, thrombocytopenia, leukocytosis, and elevation of hemoglobin and hematocrit). Biochemical abnormalities(elevation of cratinine and urea, increased levels of aminotransferases) usually occurred at the beginning of the second week, and ESR increase in the second week of disease. CONCLUSION: The majority of our patients had laboratory findings characteristic of HFRS. Thrombocytopenia and increased level of CRP were the most common laboratory findings during the first week of the disease. Renal and liver impairment occurred at the beginning of the second week of the disease.

[Polymicrobial sepsis and perityphlic abscess: case report and review of literature]. / Polimikrobna sepsa i peritifliticki apsces: prikaz bolesnika i pregled literature.

AIM: To evaluate the safety and efficacy of conservative therapy of polymicrobial anaerobic sepsis and appendiceal mass. CASE REPORT: We report on an 18-year-old patient admitted for fever (38.8 degrees C), abdominal pain and vomiting. Leukocytosis with left shift maturation, and diarrhea were noted during hospital stay. A Fusobacterium species and Bacteroides ovatus were isolated from blood culture specimens. Radiologic examination with barium enema showed normal ileocecal region, while colonoscopy indicated terminal ileitis. Abdominal ultrasound and computed tomography showed appendiceal mass sized 6.5x5.5 cm in the right lower quadrant. The patient was treated with intravenous antibiotic therapy consisting of amoxicillin + clavulanic acid and metronidazole for 21 days. He was discharged from the hospital when control ultrasound indicated disappearance of the appendiceal mass. DISCUSSION: Acute appendicitis is the most common cause of urgent surgery in children. Bacterial enteritis limited to the ileocecal region appears to be responsible for an appreciable number of unnecessary appendectomies. On the other hand, diagnostic errors in appendicitis may delay early appendectomy and result in the formation of appendiceal mass. The advent of high-resolution real-time scanners and graded compression sonography has enabled not only an accurate diagnosis of acute appendicitis but also a reliable diagnosis of other diseases of the ileocecal region. Acute terminal ileitis has similar clinical and laboratory manifestations as acute appendicitis, thus presenting a common diagnostic problem in daily practice. Perforation occurs in 20% to 30% of children with acute appendicitis. Perforation may be difficult to diagnose by sonography. The most common complications are peritonitis and intraperitoneal abscesses. The management of appendiceal mass remains controversial, such as interval appendectomy after nonoperative treatment. CONCLUSION: Successful conservative treatment for polymicrobial anaerobic sepsis and appendiceal mass in an 18-year-old patient is described. The case report is followed by review of the literature on the appendiceal mass management.

[Spontaneous rupture of the spleen in infectious mononucleosis: case report and review of the literature]. / Spontana ruptura slezene u infekcioznoj mononukleozi: prikaz bolesnika uz pregled literature.

OBJECTIVE: Spontaneous splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. Abdominal pain is uncommon in infectious mononucleosis, and splenic rupture should be strongly considered whenever abdominal pain occurs. The onset of pain may be insidious or abrupt. The pain is usually in the left upper quadrant. AIM: To indicate that infectious mononucleosis is not always the innocent kissing disease, but could be complicated with splenic rupture as a life-threathenig condition. CASE-REPORT: Our first case is described and a short literature review is provided. We report on the case of a 27-year-old man with infectious mononucleosis who had spontaneous splenic rupture that was successfully managed by splenectomy. On admission, he was febrile (38.5 degrees C) with hepatosplenomegaly, and had a blood pressure of 100/70 mm Hg. Six hours later, the patient complained of increasing abdominal pain. Abdominal ultrasound and computed tomography showed a 16.5 cm heterogeneous splenomegaly with subcapsular hematoma as well as free ascites. Laparotomy confirmed spontaneous rupture of the splenic capsule with active abdominal bleeding. Splenectomy was performed with a good clinical response. Examination of the spleen revealed a ruptured capsule with a subcapsular hematoma. DISCUSSION: Infectious mononucleosis is the most common infectious disease to result in spontaneous spleen rupture. The prognosis is favorable when diagnosis is made on time and correct treatment is started immediately. Although splenectomy was advocated as definitive therapy in the past, numerous recent reports have documented good outcomes with non-operative management. Based on the literature review, an approach to the management of a spontaneously ruptured spleen secondary to infectious mononucleosis is suggested. Non-operative management can be successful in hemodynamically stable patients, i.e. in patients with subcapsular hematoma without overt rupture of the capsule to avoid complications of splenectomy (e.g. post-splenectomy sepsis). CONCLUSION: We report on a 27-year-old man with infectious mononucleosis who had spontaneous splenic rupture that was successfully managed by splenectomy.

[The biggest epidemic of hemorrhagic fever with renal syndrome in Croatia]. / Najveca epidemija hemoragijske vrucice s bubreznim sindromom u Hrvatskoj.

INTRODUCTION: The largest outbreak of hemorrhagic fever with renal syndrome (HFRS) to date occurred in Croatia in the year 2002. The epidemic started in winter, lasted throughout spring to summer months, ending not earlier than November. AIM: The aim of this study was to investigate and analyze the basic epidemiologic and clinical features of HFRS in Croatia by uniform and standardized prospective-retrospective analysis of all patients affected by the epidemic. PATIENTS AND METHODS: When the epidemic started, a patient questionnaire with questions on the basic demographic data, site of infection and other epidemiologic characteristics, clinical symptoms, disease severity and laboratory results was designed. Data on 401 patient with a clinical diagnosis of HFRS were collected. The etiologic diagnosis of the disease was confirmed by ELISA, and in some patients by indirect immunofluorescence test (IFT). The results were analyzed using a descriptive statistical method. RESULTS: HFRS was clinically diagnosed in 401 patients from all over Croatia. A total of 320 (79.8%) cases were reported to the Epidemiology Service of the National Institute of Public Health. The majority of patients (n = 128) were registered in June. Males were three times more affected than females. Apart from its long duration, this epidemic was characteristic for the involvement of general population, with only a small number of the affected from the potential risk groups (forestry workers 28, soldiers 14, farmers 18). The epidemic spread almost throughout inland Coratia. At least 44 patients were infected in the Plitvice Lakes area, 32 in Slunj, 27 on Sljeme, 24 in Velika, and at least 19 in the area of Kutjevo. The youngest patient was aged 4 and the oldest 80 years. The majority of patients were treated in Zagreb (University Hospital for Infectious Diseases--110, Zagreb University Hospital Center--3), followed by Karlovac (71 inpatients and 39 outpatients), Pozega (n = 79), and Rijeka (n = 37). Serologic analysis (ELISA method) detected Puumala virus in 161 and Dobrava virus in only 17 patients. The disease was confirmed by immunofluorescence method in 53 patients (mostly in Kariovac). During the 2002 outbreak, HFRS clinically manifested mostly in a milder form with general symptoms and transitory renal insufficiency, while hemorrhages were rarely recorded. According to our disease severity score, a mild form of the disease was recorded in 65%, moderately severe in 28%, severe in 5% and extremely severe form in 2% of the patients. One patient died. Two thirds of the patients were hospitalized during the febrile stage of the disease. All patients had fever, whereas headache and pain in the lumbar region were recorded in more than 90% of cases, polyuria in 75%, oliguira and vomiting in approximately 50%, respiratory symptoms in 35%, and hemorrhages (mostly on the skin and mucous membranes), vision disturbances, conjunctivitis and diarrhea in approximately 25% of patients. ESR was elevated in 64% and CRP in 93% of patients. Leukocytosis was recorded in 25% and thrombocytopenia in 70% of patients. Increased values of urea and creatinine and signs of liver damage were recorded in approximately 50% of the patients. CONCLUSION: The largest outbreak of HFRS occurred in Croatia in 2002, with more than 400 diseased throughout Croatia. This epidemic confirmed our previous assumption that the whole Croatia, apart from its narrow coastline area and islands, is a natural focus of HFRS with different causative types of hantaviruses. Efforts should be made to conduct a comprehensive ecologic and mammologic study on hantaviruses and their biologic characteristics in these areas.

[Clinical and epidemiologic characteristics of hemorrhagic fever with renal syndrome in patients treated at the Dr. Fran Mihaljevic Clinic for Infectious Diseases in Zagreb]. / Klinicke i epidemioloske znacajke hemoragijske vrucice s bubreznim sindromom u bolesnika lijecenih u Klinici za infektivne bolesti "Dr. Fran Mihaljevic" u Zagrebu.

AIM: The aim of the study was to examine and analyze the main epidemiologic and clinical data of 94 patients with hemorrhagic fever with renal syndrome (HFRS) hospitalized at the University Hospital for Infectious Diseases in Zagreb during the HFRS outbreak in Croatia in 2002. PATIENTS AND METHODS: A total of 110 patients with clinical diagnosis HFRS were treated at the University Hospital for Infectious Diseases in Zagreb. In 110 of HFRS suspected patients, the clinical diagnosis was verified serologically in 94 patients and they were included in the retrospective study. In 93 patients the diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA), and in one patient by indirect immunofluorescence assay (IFA). Results were analyzed by the use of descriptive statistics. RESULTS: Puumala (PUU) virus infection was verified in 80 (85.1%), Dobrava (DOB) infection in 8 (8.5%) and cross-reactive antibodies to both PUU and DOB viruses in 5 (5.3%) HFRS patients. In one patient who was confirmed by IFA the hantavirus serotype causing HFRS could not be determined. The localities of the presumed HFRS patient exposure to hantaviruses were mostly in the Zagreb area. Most patients were aged 21-50 (83.0%) and male (76.6%). The majority of HFRS cases occurred between May and August (75.5%). A high proportion of HFRS cases were found in the general population from Zagreb and its surroundings (78.7%). The majority of patients were hospitalized in the febrile stage of the disease (70.2%). The main symptoms were: fever (100%), headache (88.3%) and backache (87.2%). Oliguria was recorded in 56.4% and, anuria in 7.5% of patients, however, only three (3.2%) patients required hemodialysis. Six patients developed hemorrhagic manifestations, especially petechiae on the skin and mucosa. One patient in the convalescent stage had subarachnoidal bleeding. Six patients had pathologic electroencephalogram (EEG) findings and two developed epileptic seizures. Lumbar puncture was performed in 12 patients without inflammatory changes in the cerebrospinal fluid. Pathologic ECG findings were recorded in 30/79 (38.0%) patients, primarily including mild and translent disturbances such as sinus tachycardia, sinus bradycardia, nonspecific alteration of the final complex and incomplete right bundle branch block. Conventional chest radiography revealed abnormal findings in 23/84 (27.4%) patients. The abnormalities consisted of interstitial infiltrates and/or pleural effusions and atelectasis. The patients were divided into 4 groups according to the disease severity: mild in 74 (78.7%), moderate in 15 (16.0%), severe in 4 (4.2%), and very severe in one (1.1%) patient. The latter developed multiorgan failure and died. CONCLUSION: The largest outbreak of HFRS to date was recorded in Croatia in 2002. Ninety-four patients with clinical and serologically verified HFRS were treated at the Dr. Fran Mihaljevic University Hospital for Infectious Disease, Zagreb. The majority of patients were hospitalized between May and August. Most patients had mild form of the disease primarily caused by PUU virus.

[The Brill-Zinsser disease still occurs in Croatia: retrospective analysis of 25 hospitalized patients]. / Brill-Zinsserova bolest jos se pojavljuje u Hrvatskoj: retrospektivna analiza 25 hospitaliziranih bolesnika.

The article presents epidemiological, clinical, laboratory and therapeutic characteristics of Brill-Zinsser disease (BZD). A total of 25 cases of BZD were retrospectively analyzed during the period from January 1, 1980 through December 31, 2000, and etiology was confirmed by rickettsial complement-fixation test (CFT). The majority of cases 15 (60%) quoted history of primary attack of epidemic typhus during or after the World War II. During the course of the disease in our patients different organic systems were involved. Aseptic meningitis was verified in 21 (84%) patients, rash in 17 (68%), liver lesion in 14 (56%), pneumonitis in 7 (28%), myopericarditis in 7 (28%) and 5 (20%) had renal lesion. Not a single clinical symptom or finding of disease has a diagnostic particularity. However, long term fever, headache, rash and aseptic meningitis, or information of infestation with lice in childhood, or a history of epidemic typhus should arouse a suspicion of this disease, which still occurs in Croatia.