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Tick-borne encephalitis (TBE) is a zoonotic flaviviral infection that is a growing public health concern in European countries. The aims of this research were to detect and characterize tick-borne encephalitis virus (TBEV) in Ixodes ricinus ticks at presumed natural foci in Serbia, and to determine seroprevalence of TBEV IgG antibodies in humans and animals. A total of 500 I. ricinus ticks were examined for the presence of TBEV by real-time RT-PCR, and conventional nested PCR and sequencing. To determine TBEV seroprevalence, 267 human sera samples were collected, as were 200 sera samples from different animal species. All sera samples were examined by ELISA for the presence of anti-TBEV antibodies. To exclude cross-reactivity, all sera samples were tested for anti-West Nile virus (WNV) antibodies and all human sera samples were also tested for anti-Usutu virus antibodies by ELISA. Results of this preliminary study indicated TBEV activity in Serbia at two microfoci. Several decades after the previous documentation of TBEV in Serbia, we have demonstrated the presence of TBEV in I. ricinus questing nymphs (prevalence 2% and 6.6% at the two different localities) and anti-TBEV antibodies in humans (seroprevalence 0.37%). Moreover, we show for the first time TBEV seroprevalence in several animal species in Serbia, including dogs (seroprevalence 17.5%), horses (5%), wild boars (12.5%), cattle (2.5%), and roe deer (2.5%). None of the goats tested was positive for anti-TBEV IgG antibodies. TBEV isolate from I. ricinus tick in this study belonged to the Western European subtype. To understand the true public health concern in Serbia, detailed epidemiological, clinical, virological, and acarological research are required. This is important for implementation of effective control measures to reduce the incidence of TBE in Serbia.

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AIM: To determine immediate risk factors of developing tuberculous meningitis, to assess the practical importance of clinical signs and findings in the cerebrospinal fluid (CSF) when opting for the specific therapy, and to predict the outcome of disease in relation to the beginning of treatment. METHODS: A retrospective clinical case series of nine patients with tuberculous meningitis who were treated from April 2001 until November 2010 at the Department of Infectious Diseases in Novi Sad, Serbia was presented. Data of patients' medical records and presentation of clinical and laboratory features, neuroradiologicalfindings and outcome were used. RESULTS: The factors of immediate risk/predisposition for the development of tuberculous meningitis were found in two (22.2%) patients. The duration of symptoms prior to admission was 9 days on average (from 3 to 20 days). The most frequent symptoms on admission were headache and fever in eight (88.9%) patients, whereas two patients (22.2%) were presented with stiff neck and photophobia. Consciousness was preserved in six patients (66.7%), two patients were somnolent and one was in coma. Two(22.2%) patients had concurrent pulmonary tuberculosis. Neuroradiological signs of the disease were present in two patients. CONCLUSION: The duration of symptoms before admission, clinical examination and CSF analysis can be helpful in identifying patients who are at high risk of developing tuberculous meningitis.

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BACKGROUND/AIM: Most infections caused by influenza A (H1N1) 2009 virus are presented by mild respiratory symptoms. However, some patients required admission to the intensive care unit (ICU). In this article we aimed to describe the clinical and laboratory characteristics of the patients with influenza A (H1N1) 2009, antiviral therapy use, the disease outcome and risk factors associated with the severe disease. METHODS: The patients with the signs and simptoms of novel influenza A (H1N1) 2009, admitted to the Clinic for Infectious Disease in Novi Sad, were evaluated. The study included 293 patients hospitalized between October 2009 and February 2010. Basic demographic data, underlying medical conditions, clinical signs and symptoms, duration of the disease before the admission, laboratory tests, radiographic findings, treatment, and the final outcome (survived, died) were all noted. Factors associated with severe disease requiring ICU admission were determined by comparing the ICU cases with control groups of the patients admitted to the hospital but not to ICU. RESULTS: The average age of the patients was 32.72 years. A total of 114 (38.9%) of the patients had an underlying medical condition. Asthma and chronic obstructive pulmonary disease were present in 44 (15.01%) of the patients, chronic cardiovascular diseases in 28 (9.56%), diabetes mellitus in 16 (5.46%), malignity in 15 (4.44%) of the patients and 11 (3.75%) of the patients were pregnant. Fever was registered in 282 (96.24%), myalgias in 119 (40.61%), headache in 48 (16.38%), cough in 240 (81.91%), sore throat in 25 (8.53%), runny nose and sneezing in 17 (5.8%) and dyspnea in 110 (37.54%) of the patients. A total of 192 (65.53%) had radiological findings that were consistent with pneumonia. A total of 154 (56.61%) of the patients received antiviral therapy within 48 h. A total of 280 (96.24%) patients were discharged and 13 (4.44%) were transferred to ICU. Fatal outcome was noticed in 2/13 (15.3%) ICU treated patients and 11/13 (84.7%) patients survived. The median time from the onset of illness to the initiation of antiviral treatment was 7.1 days for the patients admitted to ICU and 3.2 days for non-ICU patients (p < 0.05). Low blood oxygen saturation (SaO2 < or = 92%) was more common in ICU admitted patients, 10/13 (76,92%), compared to 28/280 (10%) non-ICU admitted ones (p < 0.01). Serum C-reactive protein (CRP) levels > 200 mg/L were noticed in 9/13 (69.23%) patients admitted to ICU and 85/280 (30.35%) patients who were not (p < 0.05). CONCLUSION: Most novel influenza A (H1N1) 2009 infections presented mild respiratory disease. Prompt antiviral therapy in patients with A (H1N1) virus infection seem to be the best approach to avoid serious form of the disease. Special attention should be payed to patients having low level of peripheral oxygen saturation and raised CRP serum level.

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INTRODUCTION: The aim of antimicrobial treatment of infections in the central nervous system (CNS) is to eradicate the bacterial cause. The choice of antibiotics should take into account its activity, pharmacokinetic properties, results of clinical trials, side effects and total treatment cost. Despite the fact that pharmacokinetics affects the ability of antibiotics to penetrate the blood brain barrier (BBB) significantly, the most important factor is that meningeal inflammation increases the permeability barrier. The selected antibiotic should have a bactericidal action and the achieved liquor concentration should be high above the minimal bactericidal concentration (MBC). ANTIBIOTIC THERAPY: Empirical antibiotic therapy should be started immediate after taking the sample to make the etiological diagnosis, taking into account the patient ' age. previous diseases and immune status. The specific or targeted antibiotic treatment is carried out according to the microbiological sensitivity test of antimicrobial agents isolated. Whenever possible, the preference should be given to a monotherapy except when it comes to a cause requiring synergistic combination of antibiotics. The length of treatment is individually assessed and is mainly based on experience. Numerous studies have shown that it is possible to reduce inflammatory response in subarachnoid space and thus improve the outcome of meningitis by using anti-inflammatory agents, along with the antibiotics. CONCLUSION: Today the increase in resistance to antibiotics is a leading medical problem in the 21st century. The most common micro organisms isolated from CSF (liquor) in our region are: Staphylococcus spp. coagulase negative. Haemophilus infuenzae, Neisseria meningitidis, serogroup B. Staphylococcus epidermidis, and Streptococcus beta haemoliticus. The resistance to antimicrobial drugs most frequently used in the treatment of bacterial meningitis is still not alarmingly. high in our country. Since there is a real possibility of development of high resistance in our area, the main recommendation is to rationalize the use of antibiotics.

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INTRODUCTION: Antibiotics are substances that possess bacteriostatic or bactericidal effect. Their administration is widespread in the treatment as well as in the prevention of many infections in general population, and especially in vulnerable groups. THE ELDERLY AND ANTIBIOTICS: Respiratory and urinary infections are the most common infections in the elderly. The initial empirical antibiotic therapy of pneumonia in older patients is directed to possible causative agents. Doxicicline is most frequently applied in ambulatory patients, followed by macrolides (azithromycin), fluorochinolone and amoxicillin with clavulanic acid. In the hospitalized patients, a wide spectrum of cephalosporins with macrolides is applied, as well as beta-lactamase inhibitors combined with macrolides or fluorochinolone only. Asymptomatic bacteriuria, a very common phenomenon in the elderly, is usually not treated. The antibiotic therapy of urinary infection in the older population is applied according to the causative agent. Polymicrobial infections occur in 30% of the patients, more often in those with urinary catheter. The wide spectrum antibiotics, especially cotrimoxazole and chinolone are applied in such cases. ANTIBIOTICS AND HIV/AIDS: In the HIV infected and AIDS suffering patients, antibiotics are used as a means of prophylaxis and treatment of the opportunistic infections. They occur during the terminal stage of illness, although they might be the first manifestation of the HIV illness. The treatment of the opportunistic infections in HIV/AIDS patients assumes the primary prophylaxis, then treatment of acute manifestations and the secondary prophylaxis. The aim of the treatment in this category is to prevent several opportunistic infections with a single antibiotic--the so called multiple prophylaxis. CONCLUSION: There are no general rules defining the choice of antibiotics for vulnerable groups, hence each and every patient should be considered as a separate individual and the most efficient antibiotic or a combination of antibiotics ant their optimal dosage should be selected taking into consideration all available facts.

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The retrospective study (2002-2007) for human leptospirosis in Vojvodina was undertaken in order to describe the distribution of the disease in relation with some environmental factors. Regarding the presented results, the major detected number of leptospirosis cases concurs with stagnant waters, wetlands, fish pond areas and protected regions, which comprised the basis for mapping of the region in three risk zones: very high risk (incidence rate higher than 5.0), high risk (2.5-5.0) and medium risk of leptospirosis infection (1.0-2.5). During the investigated period, 97 cases were registered with an average of 13.85 cases per year: 2002, 32 cases; 2003, 7; 2004, 22; 2005, 16; 2006, 4 and 2007, 16. Out of these 97 cases only 5 were women. Serovars from 11 presumptive serogroups caused infection, with a predominance of Icterohaemorrhagiae and Bratislava, accounting for 72.72% of cases together. Icterohaemorrhagiae was the commonest infecting serogroup mostly connected with fish ponds. Case fatality ratio was 9.4%.

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INTRODUCTION: Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. AIM: To point out the immunomodulatory action of some antibiotics on certain components of immune system. METHODS AND RESULTS: The literature findings show that antibiotics express immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes), cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enhance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism, of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. CONCLUSION: There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.

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INTRODUCTION: Brucellosis is an acute, subacute or chronical disease, from the zoonosis group, caused by various types of bacteria belonging to genus Brucellae. It is transmitted to humans from domestic animals: goats, sheep, cattle, pigs and dogs. The course of the disease may either be asymptomatic, or produce a variety of clinical manifestations, ranging from light ones to extremely severe clinical forms. The aim of the study was to follow the clinical features of brucella infection in the hospital-treated patients, as well as its course and outcome. MATERIAL AND METHODS: The investigation included 15 patients, treated for brucella infection at the Clinic for Infectious Diseases during the last two years (2004 and 2005). RESULTS: All patients were adults, their age ranged from 18 to 71, 49.96 on average. The epidemiological questionnaire was positive in all patients, confirming contacts with the ailing animals, or consumption of cheese made from milk of diseased animals. They all exhibited the classic symptoms--increased body temperature and shiver, fever, sweating, malaise and headache, the so called flu like state. The serum agglutination test was positive in respect to brucellosis, the titre ranged from 1:80 to 1:1280. Eight patients suffered excessive back pain, accompanied with impeded walk. In half of them magnetic resonance imaging confirmed the spondylodiscitis diagnosis. Three patients had clinical features of knee arthritis, two had bronchopneumonia, one pancreatitis, and one developed the signs of an acute kidney insufficiency. The outcome was favourable in all patients. They recuperated or healed completely. In one patient a relapse occurred, leading to the chronic course of the illness. DISCUSSION: Although predominantly Mediterranean Brucellosis is a worldwide spread disease. During the last two years, an increased incidence of the disease has been observed. CONCLUSION: Due to the variety of clinical futures and the possibility of numerous complications and sequelae, brucella infection should be always taken into consideration while diagnosing undefined febrile states.

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INTRODUCTION: Infectious diseases are a part of the history of this region. Devastating epidemics of plague, smallpox, and cholera were frequent during the 18th and the 19th centuries. Other infectious diseases were a serious problem as well: alimentary tract infections, scarlet fever, diphtheria, whooping cough. Geographic position, climate, migrations, as well as the tradition and lack of medical staff and medications, affected the frequency and outcome of infections. THE HISTORY OF THE TREATMENT OF INFECTIOUS DISEASES: Patients with infectious diseases were first treated at home. Later, a hospital in Visarion street was opened as an isolation facility and a hospital for homeless patients. The development of science and the education of medical personnel exerted the greatest influence on the control and later treatment of infectious diseases. These measures resulted in the establishment of the first specialized medical institutions in Novi Sad during the cholera outbreak in 1884. After that, temporary pediatric units were organized for the treatment of scarlet fever, diphtheria and smallpox. A ward for infectious diseases was founded in the The Great City Hospital in the second half of the 19th century (1892). The 20th century was a period of control and eradication of infectious diseases in Vojvodina (smallpox, malaria, diphtheria, polio). MODERN INFECTIOUS DISEASES: Nowdays, major infectious deseases include respiratory, alimentary and parasitic infections. However, new diseases are being registered as well - hemorrhagic fevers, Lyme disease, HIV infection. The Infectologic Service in Novi Sad was developed from an Infectology Departement as part of the Departement of Internal Diseases in the new Provincial Hospital (1909) to the independent Departement for Infectious Diseases (1945). Today, Clinic of lnfectious Diseases is an integral part of the Clinical Center of Vojvodina. DEPARTMENT OF INFECTIOUS DISEASES: The Department of Infectious Diseases of the Faculty of Medicine in Novi Sad was founded in 1960. Undergraduate studies started in 1963/64 for students of medicine and in 1978/79 jor dentistry students. Today. the faculty of the Department takes part in undergraduate studies of medicine, dentistry, health care, as well as in graduate programs. The faculty members are also taking part in specialization programs at the Faculty of Medicine. Infectious disease physicians are involved in the activities of the Infectology Section (founded in 1979) of the Society of Physicians of Vojvodine of the Medical Society of Serbia. The first president of the Infectology Section was Dr. Vera Mudric, professor, infectologists, whereas Dr. Grozdana Canak, professor, was the vice-president from 2000-2004. The Infectology Section collaborates with various national and international societies for infectious diseases.

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INTRODUCTION: Animal infectious diseases which can be transmitted to humans are as old as the civilization itself. It is thought that 75% of all human infectious diseases are of zoonotic origin. Zoonoses are of significant public health importance, with major social and economic impact. GENERAL FACTS ABOUT ZOONOSES: Depending on their life cycle, four groups of zoonoses are distinguished: orthozoonoses, cyclozoonoses, metazoonoses and saprozoonoses. Some zoonoses are of bacterial or viral origin, some are caused by rickettsia or chlamydia, others are mycotic or parasitic infections, whereas some are caused by arthropods or prions. TRANSMISSION OF ZOONOSES TO HUMANS: Three stages are differentiated during the transmission of the causative agent to humans: excretion, presence in the environment and entry into the new host. There are two transmission mechanisms: transmissive (vector-borne) and non-transmissive (fecally-orally). CONCLUSION: Undoubtedly, new zoonoses will continue to emerge, and that is why we need to take seriously the warning of the Third Congress for the European Society for Emerging Infections "to expect the unexpected".

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EPIDEMIOLOGY: Aging is a natural process and a part of our lives, but nowadays there is an increase in the number of persons aged 65 and over. Today infectious diseases are still responsible for one-third of all deaths in the world. The elderly population is most vulnerable to serious infections and at greatest risk for death and complications. Among geriatric population pneumonia and influenza are the fourth most common cause of death. VACCINATION: One of the goals of preventive medicine is to reduce the rate of complications and mortality from infectious diseases by increasing immunization rates. Influenza and pneumococcal vaccines are indicated for persons aged 65 and over. Despite well-recognized benefit of such vaccination, less than 50% of eligible patients receive the vaccine each year. INFECTIONS: Older persons generally have increased susceptibility to infections because of multiple risk factors and they are the most vulnerable population to nosocomial and health-care associated infections. Older persons may manifest infectious diseases atypically, with acute confusion or delirium which can lead into delay in diagnosis and therapy. It is important to know that the older present with delayed or poor response to antimicrobial therapy and high rates of adverse reactions to drugs, including antibiotics. CONCLUSION: As elderly population is rapidly growing, majority of patients with serious or life-threatening infections are old. Geriatric issues have not typically been a focus of training in infectious diseases, but we must become aware of and knowledgeable about special and unique aspects of infections in this population.

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INTRODUCTION: Lyme disease is a tick-borne disease caused by a spirochete Borrelia burgdorferi, which manifests as a multisystem disease of the skin, nervous system, heart and joints. Recently it is the most common vector-borne disease in Yugoslavia. NEW EPIDEMIOLOGICAL STUDIES: New epidemiological studies revealed that ticks can occasionally be infected not only by Borrelia burgdorferi, but also by some other microbes that can cause diseases in humans. Recently discovered the variable major protein-like sequence, antigenic variation of B. burgdorferi B 31 partly explains the ability of this organism to evade an active immune response. A key role in development of clinical symptoms associated with lyme disease belongs to the connection with ability of B. burgdorferi to induce and activate metallopeptidases and fibrinolytic enzymes, leading to extracellular matrix destruction. DIAGNOSIS AND TREATMENT: Diagnosis of Lyme borreliosis is made on the basis of clinical picture, exposure to ticks in endemic areas and serologic confirmation. It seems that polymerase chain reaction has little role in detection of B. burgdorferi in urine, blood, and spinal fluid samples, but it is most useful in evaluating the effectiveness of antibiotic therapy of Lyme arthritis. Infectious Diseases Society of America had prepared new guidelines for selective treatment of Lyme disease. Vaccination is still the best way of prevention for people living in high-risk areas.

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HISTORY: Anthrax has been known since ancient times. Besides some references in the Old Testament, there is evidence of plagues in ancient Egypt, as well as descriptions of the disease by the Roman poet Virgil. ETIOLOGY: Anthrax is caused by Bacillus anthracis, unmovable, aerobic, gram-positive rods. It forms spores, which can survive for years in the environment. PATHOGENESIS: Capsular polypeptide and anthrax toxin are the principal virulence factors of Bacillus anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor. It is thought that the inflammatory mediator--lethal factor is stored within the macrophage during the early stage of infection. It is rapidly released in large amounts into the blood stream and once the threshold for lysis is reached, it may be the cause of sudden death. EPIDEMIOLOGY: Grass-eating animals are usually infected by the bacilli from grass and ground. The disease is transmitted to people by contact with the sick animals or their products, such as wool, skin, meat etc. CLINICAL FEATURES: Two clinical forms exist: outer--cutaneous and inner, including inhalation and gastrointestinal anthrax. While cutaneous anthrax is easily cured, the inner forms have high mortality rates. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS: The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should arise suspicion of anthrax. THERAPY: Hospitalization of patients is mandatory. Bacillus anthracis is susceptible to a number of antibiotics, including penicillin, erythromycin, tetracyclines, cephalosporins etc. PREVENTION: General veterinary prevention including vaccination of livestock and control of products is very important. The vaccine consists of anthrax bacillus that is attenuated. The endangered population, such as animal workers and military personnel should be vaccinated. Annual schedule of booster immunization must be maintained. ANTHRAX AS A BIOLOGICAL WEAPON: Anthrax has been developed as a weapon of mass destruction since World War I. During accidental release from a biological warfare factory in the former Soviet Union, 68 people died. The ease of laboratory production and its dissemination via aerosol led to its adoption by terrorists, as shown by recent happenings in the USA. CONCLUSION: A good knowledge of anthrax, its transmission and potentials as a biological weapon is essential for timely prevention and protection.

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INTRODUCTION: Neurocysticercosis (NCC) is the most common parasitic disease with wide distribution which is caused by larval forms of Taenia Solium. Our aim was to: show the most common clinical manifestations of patients with NCC and their importance in diagnosing this disease; examine the value of serologic diagnostic methods in blood and cerebrospinal fluid; to emphasize the value of radiological diagnostic methods--CT and MRI of the brain, in relation to the applied protocol of therapy, as well as the impact of anti-parasitic therapy on the outcome of this disease. MATERIAL, METHODS AND RESULTS: 13 patients with NCC (from 35 to 63 years of age, median age 49; 61.5% male and 38.5% female) were treated at the Clinic of Infectious Diseases in Novi Sad during a five-year period. Two patients had a positive epidemic data of parasitic diseases of the intestinal tract in childhood. The most common clinical manifestation was headache in 61.5% of patients, and generalized convulsions and hemiparesis in 46.2%. Meningeal inflammation was present in 27.3% of patients. Two of five patients had positive ELISA test for cysticercosis in the serum and cerebrospinal fluid. CT and MRI findings confirmed parenchimal form of NCC in 30.8% of patients, while calcifications were found in 69.2% of patients. All patients were treated with Albendazole, 800 mg a day, in two doses, 30.76% of patients had a favorable outcome of the disease, 53.7% of patients were discharged with complications, and one patient died. CONCLUSION: The most common manifestation of NCC in our patients was headache, followed by general convulsions and hemiparesis. Radiological diagnostic methods--CT and MRI--proved to be most valuable both in diagnostics and follow-up of lesions. All our patients were treated with Albendazole; Dexamethasone was applied in patients with severe inflammatory reaction, and anti-convulsive drugs in patients with convulsions.

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