TICK-BORNE ENCEPHALITIS VIRUS INFECTION IN HUMANS.

INTRODUCTION: Tick-borne meningoencephalitis virus is a flavivirus that causes the most important vector-borne central nervous system infection in many countries of Europe and Asia. There are three subtypes of tick-borne encephalitis virus: European, Siberian and the Far-Eastern subtype. TRANSMISSION: In endemic areas, the virus remains in transmissive cycles between Ixodes ticks and small rodents. CLINICAL PICTURE: In most cases (70-98%) infection goes asymptomatically. In about one-third of meningitis cases, meningoencephalitis or meningomyelitis is developed. Postencephalytic syndrome may be the complication of the infection, presenting with neurological symptoms. DIAGNOSIS: Etiologic diagnosis of tick-borne meningoencephalitis is only made on basis of laboratory analyses. Reverse transcription-polymerase chain reaction is used for determining the presence of virus in the blood and cerebrospinal fluid. Antibodies in blood and cerebrospinal fluid can be detected by serological tests. PREVENTION: The most efficient way to control this potentially severe disease with possible serious long-term consequences is vaccination. It should be recommended to persons who live or travel to endemic areas. CONCLUSION: In Serbia, tick-borne encephalitis virus infection belongs to the list of reportable diseases; however, there are no reported cases because the diagnostics is not performed routinely. We believe that the significance of this zoonosis must be examined in our country and some of its parts because of preliminary positive serological findings found out in Vojvodina as well as because of reported cases in neighboring countries such as Hungary and Croatia and its worldwide distribution.

CHIKUNGUNYA - A SERIOUS THREAT FOR PUBLIC HEALTH.

INTRODUCTION: Chikungunya is a contagious disease caused by Chikungunya virus, an arbovirus from the Togaviridae family. This infection is mostly spread by mosquitoes from the genus Aedes, especially Aedes albopiclus, which have spread from Asia to America and Europe including some countries surrounding Serbia. EPIDEMIOLOGIC FEATURES: The outbreak of epidemics has been reported in Philippines, Sumatra, Java, Indonesia, West Africa region (from Senegal to Cameroon), Congo, Nigeria, Angola, Uganda, Guinea, Malawi, Central African Republic, Burundi, South Africa and India. At the beginning of the 21st century, large outbreaks were recorded on the island of Réunion. During 2006, 1.400.000 cases of chikungunya infection were recorded in India. Local transmission of infection in continental Europe was reported from Northeast Italy (254 suspected and 78 laboratory confirmed cases in Emilia-Romagna region) and France (two cases in 2010). From December 2013 to June 2014, 5.294 confirmed cases and more than 180.000 suspected cases of chikungunya were reported in the Caribbean. CLINICAL FINDINGS: The disease presents suddenly with fever, rush and arthralgia. In general, chikungunya is a mild self - limited disease. Less often, it may be presented with signs of meningoencephalitis or fulminant hepatitis, sometimes with fatal outcome. CONCLUSION: Fast developing international traffic and booming tourism as well as the vector spreading from its homeland make chikungunya a real threat to our country.

[The costs of urinary tract infection therapy with implementation of pharmacoeconomic guidelines at the Clinic for Infectious Diseases of the Clinical Center of Vojvodina].

BACKGROUND/AIM: The Serbian health system does not have strict guidelines for the treatment of bacterial infections. The choice of treatment is empirical which is not necessarily the same compared to the treatment guidelines from countries with a developed pharmacotherapeutic practice. In this study we compared the difference between the current treatment and the treatment taking into account the latest pharmacotherapeutic and pharmacoeconomic guidelines in order to estimate clinical efficiency of antibacterial drugs that were given as a therapy of urinary tract infections and to evaluate pharmacoeconomic aspect of this therapy as well. METHODS: Our study included 100 patients that were randomly chosen and divided into 2 groups. The first group was treated in an ordinary way, while the second one was treated strictly in accordance with the guidelines (British National Formulary - BNF, and Senford Guide). In both groups of the patients we compared length of hospitalization, combination of the used antibiotics, progress as a whole in clinical picture, laboratory analyses and the price of the whole treatment. RESULTS: Analyzing these values independently and according to statistical tests we proved that there were no significant differences between two groups with regard to the progress in a clinical picture as a whole and the length of hospitalization. According to this analysis, however suggested treatment based on guidelines showed a saving of 34.48% in comparison with the usual system of therapy. CONCLUSION: Efficacy of current treatment of urinary tract infection and the treatment according to foreign guidelines is the same, but the costs of the treatment are lower if the guidelines of developed health care systems are applied.

[Progress in antimicrobial therapy].

INTRODUCTION: Not so long ago, back in the 1900s, infectious diseases were the leading cause of death world wide. The doubling of our life span in the 20th century was achieved, first of all, by using bioactive natural products, their secondary metabolites or their derivates. These substances have prolonged our life span, reduced the pain and suffering and, at the same time, revolutionized medical science. HISTORY OF ANTIBIOTICS: Antibiotics are among the most important classes of bioactive products and as much as 78% of antimicrobial drugs are extracted from nature. This paper follows the history of progress of antimicrobial drugs, which runs parallel to the history of a man's struggle against the diseases.The golden age of progress of antimicrobial drugs went on between the 1940s and 1970s. Thereafter, there is a gradual decrease in the number of newly discovered antimicrobial drugs. During the time period between 2003 and 2007 only four antibiotics were registered. CONCLUSION: The current situation in the field of antimicrobial therapy should send off a global alarm .for the creation of a well coordinated, sound and all-encompassing monitoring of the resistance, consumption of antimicrobials and investment in the new trials.

[The choice of antimicrobial therapy by application of pharmacoeconomic principles in view of the most frequently isolated pathogens at the Clinic for Infectious Diseases of the Clinical Center of Vojvodina].

The research on the use of pharmaco-therapeutic/pharmacoeconomic guidelines in therapy of bacterial infections was carried out in all patients hospitalized at the Clinic for Infectious Diseases of the Clinical Center of Vojvodina in a three-month period. The overall antibiotic utilization in therapy of bacterial infections was determined. The total cost of all administered antibiotics was calculated as well as the defined daily dose/100 patient-days. The structure of bacterial causes and their resistance to standard antimicrobial therapy was established for all isolated strains. The results of bacterial resistance surveillance were the basis to lay down the guidelines for initial adequate antimicrobial therapy (according to the site of infection and pathogen), in view of resistance maps for bacterial strains isolated from the tested materials. The guidelines for choosing appropriate antibiotic therapy were based on pharmaco-therapeutic/pharmacoeconomic principles, taking into account the state of bacterial resistance, drug administration schedule, and lowest therapy cost. During the implementation of guidelines for appropriate initial antimicrobial therapy, large therapy cost savings of 1.275.576.9 dinars (33.9%.) were recorded, compared to the period before the implementation of the guidelines.

[Up-to-date knowledge of West Nile virus infection].

VIRUS: West Nile virus is a single-stranded RNA virus of the family Flaviviridae, genus Flavivirus. EPIDEMIOLOGY: West Nile virus is maintained in the cycle involving culicine mosquitoes and birds. Humans typically acquire West Nile infection through a bite from infected adult mosquito. Person to person transmission can occur through organ transplantation, blood and blood product transfusions, transplacentally and via breast milk. Human cases of West Nile infections were recorded in Africa, Israel, Russia, India, Pakistan. In Romania in 1996 West Nile fever occurred with hundreds of neurologic cases and 17 fatalities. First human cases in the United States were in New York City where 59 persons were infected and had fever, meningitis, encephalitis and flaccid paralysis. CLINICAL MANIFESTATION: Most human cases are asymptomatic. The majority of symptomatic patients have a self limited febrile illness. Fatigue, nausea, vomiting, eye pain, headache, myalgias, artralgias, lymphadenopathy and rash are common complaints. Less than 1% of all infected persons develop more severe neurologic illness including meningitis, encefalitis and flaccid paralysis. LABORATORY DIAGNOSIS: Diagnosis of West Nile virus infection is based on serologic testing, isolation of virus from patient samples and detection of viral antigen or viral genom. ELISA test and indirect immunofluorescence assay are used for detecting IgM and IgG antibodies in serum and cerebrospinal fluid. TREATMENT: In vitro studies have suggested that ribavirin and interferon alfa-2b may be useful in the treatment of West Nile virus disease. PREVENTION: The most important measures are mosquito control program and personal protective measures.

[Enterococcal endocarditis--a case report].

INTRODUCTION: Bacteria from genus Enterococcus may cause infections mostly in those who are immunocompromised and those who underwent endoscopic or surgical procedures. Endocarditis is caused by enterococci in 5-10% of cases. Its clinical presentation does not differ from endocarditis of other bacterial origin. Previous susceptibility testing is needed for appropriate choice of antibiotics against enterococci. The treatment recommendations for enterococcal endocarditis were given by American Heart Association recently. CASE REPORT: A case ofenterococcal endocarditis in a young female person hospitalised at Clinic for infectious diseases was reviewed. The disease was diagnosed during an extensive diagnostic procedure. Multiply repeated echocardiographic examination helped to find out bacterial vegetations on the mitral valve. Enterococcus species was isolated from several blood cultures. Despite powerful antibiotic treatment, the additional valvular replacement had to be done. DISCUSSION: A case of enerococcal endocarditis in a young female person was reviewed. The right diagnosis was based on a thorough clinical examination in cooperation with cardiologists using repeated transthoracic and transesophageal echocardiography. Echocardiography, even if it is transesophageal, has limited sensitivity and specificity, so it is sometimes necessary to be repeated for several times in diagnosing endocarditis. The source of endocarditis was not identified. The combined antimicrobial and surgical treatment led to the complete recovery of patient. CONCLUSION: Enterococcal endocarditis rarely occurrs in young females. Infective disease specialists sometimes face enterococcal endocarditis in their practice, mostly when they have to cope with fever of unknown origin. An appropriate approach to such conditions includes careful search for heart valve changes by repeated echocardiographic finding, if necessary.

[Significance of group A streptococcal infections in human pathology].

INTRODUCTION: Group A streptococci is the causative agent in 80 percents of human streptococcal infections. The only member of this group is Streptococcus pyogenes. CLINICALFEATURES OF GAS INFECTIONS: The various clinical entities and related complications caused by pyogenic streptococci are reviewed in the article. Pharyngitis, scarlet fever, skin and soft tissue infections (pyoderma, cellulitis, perianal dermatitis, necrotising fasciitis) and streptococcal toxic shock syndrome are described. DIAGNOSIS OF GAS INFECTIONS: The way of setting the diagnosis including epidemiological data, clinical features and the course of illness, laboratory findings and supportive diagnostic methods are represented in the article. DIFFERENTIAL DIAGNOSIS: The most important clinical entities which should be discussed in differential diagnosis of diseases caused by pyogenic streptococci are listed. TREATMENT OF GAS INFECTIONS: The major principles of etiologic treatment through widely accepted strategies related to first choice antibiotics and alternatives are reviewed.

[Mechanisms of bacterial resistance to antibiotics].

Development of bacterial resistance to antibiotics brought many problems among which the most important are infections caused by multiple resistant bacterial strains. Bacteria have amazing 'equipment' of biochemical and genetic mechanisms to ensure evolution and spread of antibacterial resistance genes. The results obtained from very important projects all around the world and in our country show that bacterial resistance to certain groups of antibiotics is very high (up to 100%), because of uncritical use of antibiotics out of these groups. Due to the development of resistant bacterial strains, we may soon run out of efficient antibiotics for some patients. Outcome of the race between science and pharmaceutical industry on one side, and bacterial adaptation trough acquisition of resistant genes on the other side, is very uncertain. Actions must be taken to slow down the evolution and spread of antibiotic resistance genes in which the major single factor is the proper use of antibiotics in human medicine, veterinary medicine and agriculture, respectively.

[Phamacoeconomic analysis of antibiotics use in the Clinical Center of Vojvodina].

INTRODUCTION: The investigation was performed in three phases and included all patients hospitalized at eight selected clinics known to be the biggest antibiotic spenders in the Clinical center of Vojvodina. MATERIAL AND METHODS: The first phase comprised retrospective evaluation of the total antibiotic use in therapy of all bacterial infections during a three-month period in 2006/2007. A total cost of all spent antibiotics was calculated, and a daily dose per 100 clinical day care was defined for each of investigated clinics. In the second phase, the structure of bacterial causes and their resistance to standard antimicrobial therapy was established for all isolated strains from each clinic. According to the the results of bacterial resistance surveilance, guidelines for initial adequate antimicrobial therapy were made (regarding localization and type of bacteria) considering resistance maps for isolated bacterial strains. The guidelines took into consideration all essential ellements: pharamcotherapeutic/pharmacoeconomic principles, bacterial resistance, patterns of antimicrobial prescriptions and lowest therapy costs. RESULTS AND CONCLUSION: In the third phase, (three-month period in 2007/2008), the guidelines were implemented in therapy of bacterial infections. In this period, only by implementing the guidelines for initial adequate antimicrobial therapy, the therapy costs savings were 2027018.52 dinars (12.8%) at four of eight investigated clinics, compared to the period before implementation of the guidelines. This was the first pharmacoeconomic study in Vojvodina.

[On the development of the infectology service in Novi Sad].

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.

[Avian influenza viruses--new causative agents of human infections].

INTRODUCTION: Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: A(H1N1), A(H2N2) and A(H3N2) have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H) and 9 neuraminidases (N). HUMAN CASES OF AVIAN INFLUENZA A: In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7). In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human cases (23 deaths) were reported in Viet Nam and Thailand. H5N1 virus-infected patients presented with fever and respiratory symptoms. Complications included respiratory distress syndrome, renal failure, liver dysfunction and hematologic disorders. Since 1999, 7 cases of human influenza H9N2 infection have been identified in China and Hong Kong. THE IMPORTANCE OF HUMAN INFECTION WITH AVIAN INFLUENZA VIRUSES: H5N1 virus can directly infect humans. Genetic reassortment of human and avian influenza viruses may occur in humans co-infected with current human A(H1N1) or A(H3N2) subtypes and avian influenza viruses. The result would be a new influenza virus with pandemic potential. All genes of H5N1 viruses isolated from humans are of avian origin. PREVENTION AND CONTROL: The reassortant virus containing H and N from avian and the remaining proteins from human influenza viruses will probably be used as a vaccine strain. The most important control measures are rapid destruction of all infected or exposed birds and rigorous disinfection of farms. Individuals exposed to suspected animals should receive prophylactic treatment with antivirals and annual vaccination.

[Clinical characteristics and prognostic significance of preherpetic neuralgia]. / Klinicke karakteristike i prognosticki znacaj preherpeticne neuralgije.

INTRODUCTION: Herpes zoster is a world-wide disease of older age commonly presenting with preherpetic pain. The aim of the study was to determine clinical characteristics of preherpetic neuralgia and its influence on occurrence of postherpetic neuralgia. MATERIAL AND METHODS: A prospective, controlled trial included 88 patients with preherpetic neuralgia. 44 herpes zoster patients without preherpetic neuralgia were included in the control group. All of them were clinically followed-up for three months after complete healing of skin lesions. RESULTS: Older age (> 60 years) was significantly predominant (59.1%) compared with other age groups (p < 0.01) as well as female sex (59.9%) compared with the male sex (p < 0.01). There was no significant predominance of any type of preherpetic neuralgia (stabbing, burning, itching, dull pain). More intense preherpetic pain (reported as "severe" and "moderate") was established more often than mild pain. The mean duration of preherpetic pain was 4.4 days (ranged between 1-20 days). Postherpetic neuralgia developed in 36/88 patients with preherpetic neuralgia (affecting predominantly older than 50 years of age--31/36), but there was no significant difference in proportion of postherpetic neuralgia (PHN) according to those without preherpetic neuralgia. DISCUSSION AND CONCLUSION: People older than 60 years are the most common age group among herpes zoster patients suffering from preherpetic neuralgia. Sex distribution of patients with preherpetic pain reveals highly significant predominance of female sex. Opposite to some other authors' reports, preherpetic neuralgia and its severity have not been proven as risk factors for postherpetic neuralgia in patients involved in our trial.