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In 1967, several workers involved in poliomyelitis vaccine development and production fell ill at three different locations in Europe with a severe and often lethal novel disease associated with grivets (Chlorocebus aethiops) imported from Uganda. This disease was named Marburg virus disease (MVD) after the West German town of Marburg an der Lahn, where most human infections and deaths had been recorded. Consequently, the Marburg episode received the most scientific and media attention. Cases that occurred in Frankfurt am Main, West Germany, were also described in commonly accessible scientific literature, although they were less frequently cited than those pertaining to the Marburg infections. However, two infections occurring in a third location, in Belgrade, Yugoslavia, have seemingly been all but forgotten. Due in part to their absence in commonly used databases and in part to the fact that they were written in languages other than English, the important articles describing this part of the outbreak are very rarely cited. Here, we summarize this literature and correct published inaccuracies to remind a younger generation of scientists focusing on Marburg virus and its closest filoviral relatives of this important historical context. Importantly, and unfortunately, the three episodes of infection of 1967 still represent the best in-depth clinical look at MVD in general and in the context of "modern" medicine (fully resourced versus less-resourced capacity) in particular. Hence, each individual case of these episodes holds crucial information for health care providers who may be confronted with MVD today.

Introduction. Juxtaglomerular cell tumor (JGCT) or reninoma is a very rare cause of curable hypertension among young people. The early diagnosis is the most important based on the clinical presentation, hormonal and radiological findings observed on computed tomography (CT) and/or magnetic resonance imaging (MRI). The final confirmation of the JGCT is the lateralization of the plasma renin activity (PRA) during the selective renal venous sampling. Case report. This report presents a typical case of young women with JGCT which was manifested for the first time with severe hypertension during the pregnancy and was the reason of fetal death. After the miscarriage, the diagnosis of JGCT was made by the CT scanning and confirmed by the selective renal venous sampling. After the partial nephrectomy, the blood pressure and serum potassium normalized without the medications. Conclusion. Reninoma should be considered in the differential diagnosis as a cause of severe hypertension in pregnancy and also should be suspected in young hipertensives (especially females) with hypokalemia and secondary hyperaldosteronism after the exclusion of other causes particularly renal artery stenosis. A dynamic contrastenhanced CT, MRI and selective renal venous sampling are the most important tools in the diagnosis of JGCT.

The disease caused by the West Nile virus (WNV) has been known since 1937 when it was described for the first time in Uganda. After spreading to Europe and the Middle East, the disease has changed its primary location. Today WN infection is a significant health problem in the world. As a result of the current epizootiological and epidemiological situation in Europe studies on the occurrence of WND were introduced in Serbia, also. The investigation on the presence of WNV antibodies was intensified in the period from 2008 to 2012. In this period a total of 3618 serum samples were tested from 18 localities (2736 animal sera from 8 different species and 882 human sera samples). The method applied was gel immunodiffusion and the representative samples were confirmed by the plaque reduction test (PRNT-90). Out of the total number of samples WNV antibodies were present in 3.97% horses, 0.93% dogs, 0.31% poultry and 1.36% man. In one horse serum sample there was a positive reaction with a positive control serum, thus indicating the presence of WNV antigen. The results have confirmed that WNV antibodies are present in 9 out of 18 tested locations in the Republic of Serbia. The percentage of seropositive samples varies from 0.42% in Pozarevac (horses and humans) up to 6.45% in Novi Pazar (dogs). Out of the investigated species the highest seropositivity was recorded in horses (3.97%), and lowest in poultry (0.31%). WNV is present and widespread in the Republic of Serbia, thus enabling distribution mapping. Bolest koju izaziva virus Zapadnog Nila (WNV) je poznata još od 1937. kada je po prvi put opisana u Ugandi. Posle širenja virusa u Evropu i na Bliski istok, bolest je promenila prvobitnu lokaciju. Danas je WN infekcija značajan zdravstveni problem u svetu. Kao rezultat trenutne epizootiološko-epidemiološke situacije u Evropi, uvedena su istraživanja prisustva WNV i u Srbiji. Istraživanja prisustva antitela za WNV intenzivirana su u periodu od 2008. do 2012. godine. U ovom periodu ukupno je ispitano 3618 seruma sa 18 lokaliteta (2736 seruma životinja, od 8 različitih vrsta i 882 seruma ljudi). Korišćen je metod imunodifuzije u gelu a reprezentativni uzorak potvrđen je testom neutralizacije plaka (PRNT- 90). Od ukupnog broja uzoraka na prisustvo antitela za WNV bilo je pozitivno 3,97% konja, 0,93% pasa, 0,31% domaće živine i 1,36% ljudi. U serumu jednog konja pojavila se pozitivna reakcija sa pozitivnim kontrolnim serumom, ukazujući na prisustvo antigena WNV. Dobijeni rezultati su potvrdili da su antitela za WNV prisutna u 9 od 18 ispitivanih lokacija u Republici Srbiji. Procenat seropozitivnih varira od 0.42% u Požarevcu (konji i ljudi) do 6,45% u Novom Pazaru (psi). Od ispitivanih vrsta najveća seropozitivnost je registrovana kod konja (3,97%), a najniža kod živine (0,31%). Raspoloživi podaci ukazuju da je WNV prisutan i značajno raširen u Republici Srbiji, što je omogućilo i mapiranje njegovog širenja.

Variola (smallpox) virus is classified as class A of potential biological weapons, due to its microbiological, genetic, antigenic and epidemiological characteristics. The potential danger is more real because vaccination against smallpox has stopped since disease eradication in 1979. That is why we want to share our unique, rich experience and acquired knowledge in the fight against this highly contagious and deadly disease during the smallpox outbreak in ex-Yugoslavia in 1972. It was the largest postwar outbreak in Europe when there were officially registered 175 ill patients, 35 of them with lethal outcome. This outbreak was specific by the time of its occurrence, the affected territory, dimensions and some epidemiological characteristics, but also by the well-organized, synchronized and efficient reaction of the competent state services in the fight against it.

The disease caused by Influenza viruses has been well known for a very long time. In the recent period there has been noted an occurrence of pandemics caused by Influenza viruses type A with a high rate of mortality. The ongoing pandemic caused by avian influenza virus serotype H9N9 began in Hong Kong in 1992, and another pandemic caused by serotype H5N1 began in China (Hong Kong) in 1999. The world wide spreading of these viruses occurred due to migratory birds. Avian influenza was confirmed in Serbia in 2007. The goal of this study was to examine whether the avian influenza viruses type A circulate in the region of the Obedska bara marsh, which is a famous resort for many birds in Serbia, as well as many birds migrating from Europe to Africa and vice versa. The samples of blood sera of many animal species (123 samples from fowl, 64 samples from donkeys, 40 samples from horses) were tested by serologic reaction of inhibition of haemmaglutination (IHA) for the presence of antibodies to influenza A subtypes H5N1, H5N2, H5N3, H7N1 and H7N2. Also, the samples of blood sera of experimental chicken exposed to wild life in Obedska bara (sentinel species) were tested. Antibodies to subtypes H5N1, H5N2, H5N3, H7N1 and H7N2 were found in chicken from Dec, Boljevci, Petrovcic and Kupinovo villages but no antibodies were found in blood sera from hams from Dobanovci, Jakovo, Becmen and Surcin villages. From 23 samples from ducks antibodies were detected in 3 samples, and from 22 geese blood sera antibodies were found in 4 samples. From a total of 40 horse blood sera tested one was tested positive, and from 64 donkey sera 17 were positive for the presence of antibodies for avian influenza type A. In blood sera of experimental chicken antibodies were found by subtype H5N1 with corrections with H5N2 and H7N1. Bolest izazvana influenca virusima poznata je od davnina. U novije vreme, javljale su se pandemije izazvane influenca A-virusima sa visokom stopom smrtnosti. Sadašnja pandemija avijarne influence pojavila se u Hongkongu 1992. godine sa serotipom H9N9, a sa H5N1 počela je 1997. godine u Kini (Hongkong). Globalizaciju ove pandemije učinile su migracione ptice. Pojava bolesti registrovana je i u našoj zemlji 2007. godine. Cilj rada je bio da se ispita prisustvo virusa influence ptica tipa A kod životinja na lokalitetu Obedska bara, poznatom rezervatu brojnih ptica u Srbiji, kao i odmorištu ptica koje migriraju iz Evrope u Afriku i obrnuto. Reakcijom inhibicije hemaglutinacije (HI test) ispitivani su uzorci krvnih seruma raznih životinja (123 uzorka pernate živine, 64 seruma magaraca i 40 seruma konja) na prisustvo antitela za influencu A - podtipovi H5N1, H5N2, H5N3, H7N1 i H7N2. Takođe su ispitivani i uzorci seruma eksperimentalnih pilića izloženih kontaktu sa divljom prirodom (sentinel jedinke) na području Obedske bare. Specifična antitela za podtipove H5N1, H5N2, H5N3, H7N1 i H7N2 utvrđena su kod pilića u selima Deč, Boljevci, Petrovčić i Kupinovo, dok u serumima kokošaka poreklom iz Dobanovaca, Jakova, Bečmena i Surčina antitela nisu nađena. Od 23 uzorka krvnog seruma pataka, specifična antitela su utvrđena kod 3 uzorka i u 4 od 22 uzorka seruma gusaka. Od 40 ispitivanih uzoraka krvnih seruma konja antitela su ustanovljena u jednom uzorku, dok je u uzorcima seruma magaraca prisustvo specifičnih antitela utvrđeno u 17 od 64 ispitivana uzorka. U serumima eksperimentalnih pilića antitela su nađena za podtip virusa influence H5N1 sa koreakcijama sa antigenima podtipova H5N2 i H7N1. PR Projekat Ministarstva nauke Republike Srbije, br. TP 21047.

We assayed the presence of antibodies specific for Rickettsia typhi, R. akari, and R. conorii in sera of persons from several localities in Serbia with different geographic, climatic, and lifestyle characteristics. Sera from 140 patients with unclear clinical symptoms and 273 healthy persons were tested for the presence of rickettsiae-specific antibodies by indirect immunofluorescence assay. In this study, for the first time we detected the presence of rickettsiae from the spotted fever group in Serbia. We detected the presence of antibodies against R. conorii in the samples from all tested localities. The proportion of positive cases was low in the plain agricultural areas but reached up to 23% in the mountain areas. We also observed a significant number of cases positive for antibodies against R. akari. Antibodies specific for the antigens of R. typhi were detected in only 2 samples from the municipality of Pec (Kosovo region). These findings contribute to the prevalence of Rickettsia species in Southeast Europe. Our study also revealed a dramatic lack of awareness of rickettsioses among medical personnel and pointed to the need for urgent measures that would help improve the current situation in the region.

SUMMARYHantaviruses are endemic in the Balkans, particularly in Serbia, where sporadic cases and/or outbreaks of hantaviral human disease have been reported repeatedly, and evidenced serologically. Here, we present genetic detection of Dobrava-Belgrade virus (DOBV) hantaviral sequences in wild rodents trapped in central Serbia. All the animals were pre-screened serologically by indirect immunofluorescence (IF) test and only those with a positive finding of hantaviral antigens were further tested by polymerase chain reaction. Of the total of 104 trapped animals, 20 were found to be IF positive and of those three were positive for hantaviral RNA: one Microtus arvalis for Tula virus, and one each of Apodemus agrarius and Glis glis for DOBV. Phylogenetic analysis of the obtained sequences implies putative DOBV spillover infection of A. agrarius and G. glis from Apodemus flavicollis. However, future investigations should help to identify the most common natural host and geographical distribution of DOBV in its reservoir hosts in Serbia.

Introduction Ehrlichiosis is a bacterial zoonosis transmitted by hematophagous arthropods - ticks. In humans, it occurs as monocytic, granulocytic, and ewingii ehrlichiosis. Pathological process is based on parasitic presence of Ehrlichia organisms within peripheral blood cells - monocytes and granulocytes. Case Outline Fifty-two year old patient was admitted to hospital due to high fever of over 40°C that lasted two days, accompanied with chills, muscle aches, malaise, loss of appetite, headache, confusion, breathing difficulties, and mild dry cough. The history suggested tick bite that occurred seven days before the onset of disease. Doxycycline was introduced and administered for 14 days, causing the disease to subside. Indirect immunofluorescence assay was used to analyze three serum samples obtained from this patient for Ehrlichia chaffeensis antibodies, and peripheral blood smear was evaluated for the presence of Ehrlichia and Ehrlichia aggregation into morulae. Conclusion Ehrlichiosis should be considered in each case where there is a history of tick bite together with the clinical picture (high fever, chills, muscle aches, headache, generalized weakness and malaise, and possible maculopapular rash). The presence of Ehrlichia chaffeensis antibodies was confirmed in a patient with the history of tick bite, appropriate clinical picture and indirect immunofluorescence assay. This confirmed the presence of human monocytotropic ehrlichiosis, a disease that is uncommonly identified in our country. Uvod Erlihioza je bakterijska zoonoza koja se prenosi hematofagnim artropodama - krpeljima. Kod ljudi se javlja kao monocitna, granulocitna i ewingii erlihioza. Patološki proces je posledica unutar ćelijskog parazitiranja erlihije u monocitima i granulocitima periferne krvi. Prikaz bolesnika Bolesnik star 52 godine primljen je na odeljenje zbog visoke dvodnevne febrilnosti (preko 40°C) koja je praćena drhtavicom, bolovima u mišićima, malaksalošću, gubitkom apetita, glavoboljom, konfuznošću, otežanim disanjem i oskudnim suvim kašljem. U anamnezi je dobijen podatak o ujedu krpelja sedam dana pre prijema. Laboratorijski nalazi su ukazali na trombocitopeniju, leukopeniju, anemiju i povećanje aktivnosti transaminaza u serumu. Bolesnik je lečen doksiciklinom 14 dana, nakon čega su se tegobe povukle. Metodom indirektne imunofluorescencije analizirana su tri uzorka seruma ovog bolesnika na prisustvo antitela na bakteriju Ehrlichia chaffeensis i pregledan je uzorak razmaza periferne krvi na prisustvo erlihija i konglomerata erlihije u morule, koje predstavljaju citoplazmatske vakuole. Zaključak Kod bolesnika s podatkom o ubodu krpelja, odgovarajućom kliničkom slikom i serološkim testom indirektne imunofluorescencije dokazana su antitela za bakteriju Ehrlichia chaffeensis, što ukazuje na humanu monocitotropnu erlihiozu, bolest koja se kod nas retko dokazuje. Na erlihiozu treba misliti kada uz kliničku sliku (visoka febrilnost, groznica, bolovi u mišićima, glavobolja, opšta slabost i malaksalost, eventualno makulopapulozna ospa) postoji podatak o ubodu krpelja.

Introduction. Balloon valvuloplasty (BVP) is one of the primary therapies for congenital aortic stenosis in children and adolescents. The aim of this interventional procedure is to gain time before possible surgical therapy (aortic valve replacement) until adulthood. Objective. The aim of this study was to evaluate the efficacy, safety and mid-term results of transcatheter BVP in children and adolescent in our Center. Methods. From 2004 to 2011, 50 patients, aged 18 days to 18 years (mean 6.3 years) underwent BVP. Retrospective analysis of the echocardiographic and hemodynamic parameters were performed before and after procedure, especially peak pressure gradient (PG) across the aortic valve, semiquantification of the aortic regurgitation (AR) after the BVP as well as the left ventricle dimensions and functions. Results. The mean peak PG in the whole group decreased from 74.80±27.72 mm Hg to 27.86±13.04 mm Hg (p

The Dobrava-Belgrade virus (DOBV) is a member of the Bunyaviridae family, genus Hantavirus, possessing a single-stranded RNA genome consisting of three segments, designated L (large), M (medium) and S (small). In this study, we present phylogenetic analysis of a newly detected DOBV strain isolated from Apodemus agrarius. Analysis was based on partial L and S segment sequences, in comparison to previously published DOBV sequences from Serbia and elsewhere. A phylogenetic tree based on partial S segment revealed local geographical clustering of DOBV sequences from Serbia, unrelated to host (rodent or human). The topology of the phylogenetic tree was confirmed with a high percent of completely or partially resolved quartets in likelihood-mapping analysis, whereas no evidence of possible recombination in the examined S segment data set was found.

Tula hantavirus (TULV) belongs to Bunyaviridae family, with negative sense RNA genome. Segmented nature of hantaviral genome allows for genetic reassortment, but the evidence of homologous recombination also exists. In this study we analyzed TULV sequences isolated in Serbia on different occasions and from different rodent hosts: 1987 strain from Microtus subterraneus and 2007 strain from Microtus arvalis. Phylogenetic analysis of both L and S segment sequences is suggestive of geographically related clustering, as previously shown for majority of hantaviruses. Reconstruction of phylogenetic tree for TULV S segment showed that both sequences from Serbia clustered together with sequences from East Slovakia, which had previously been shown to be recombinants (Kosice strain). Exploratory recombination analysis, supported by phylogenetic and amino acid pattern analysis, revealed the presence of recombination in the S segment sequences from Serbia, resulting in mosaic-like structure of TULV S segment similar to the one of Kosice strain. Although recombination is considered a rare event in molecular evolution of negative strand RNA viruses, obtained molecular data in this study support evidence of recombination in TULV, in geographically distant regions of Europe. (C) 2013 Elsevier B.V. All rights reserved. Ministry of Education and Science Republic of Serbia {[}175024]

During an outbreak of haemorrhagic fever with renal syndrome (HFRS) in 1989, five children (3 girls, 2 boys, aged 6.8-16 years) with severe clinical form of the disease, were treated at the Institute of Mother and Child Health of Serbia; four of them were followed-up 22-28 months thereafter. The main clinical features were: fever, headache, myalgia, abdominal and back pains, and vomiting in all, and haemorrhagic syndrome in three; renal syndrome with severe acute renal failure in all five patients. All the patients recovered. Serological confirmation by an indirect immunofluorescence assay, enzyme immunoassay for IgM antibodies, and by plaque reduction neutralization test revealed that the infection was caused by Belgrade virus in three, and by Hantaan virus in two patients. It was not possible to differentiate these two serogroups on the basis of clinical features. This finding gave further evidence of circulation of different hantaviruses causing severe HFRS in Serbia.

From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3-12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Children's Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2-3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fetal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS.

Five hundred and forty-four rodents and small mammals were trapped in various regions of Yugoslavia and examined. Antihantaviruses, immunofluorescent (IF) antibodies were detected in the blood samples of 129 animals. Antigens were detected in the lung samples of 139 animals. Sixty-seven animals tested positive for both the presence of antibodies in the sera and antigens in the lungs. Hantaviral antibodies and/or antigens were detected most in the yellow-necked mouse (Apodemus flavicollis) (88/189), the wood mouse (Apodemus sylvaticus (28/146), the striped field mouse (Apodemus agrarius) (10/64), house mouse (Mus musculus) (14/29), and the Norway rat (Rattus norvegicus) (14/21). Five other species of rodents and insectivora were infrequently infected. Hantavirus infection in small mammals, according to age, gender, location and species indicated a disparity from region to region prior to and during the epidemic. RA 1; HFRS; Ecology; Human Disease; BD.

Five hundred and forty four rodents and small mammals were trapped in various regions of Yugoslavia and examined. Antihantaviruses, immunofluorescent (IF) antibodies were detected in the blood samples of 129 animals. Antigens were detected in the lung samples of 139 animals. Sixty-seven animals tested positive for both the presence of antibodies in the sera and antigens in the lungs. Studies on the immune status of healthy people in various HFRS endemic areas were conducted. Blood samples from over 700 forest workers, farmers, and other individuals with considerable outdoor exposure were collected and tested serologically for antibodies to hantaviruses. Approximately 336 individuals possessed hantaviral antibodies. In 1989, an HFRS epidemic occurred throughout Yugoslavia, over 600 individuals were hospitalized and 15 deaths occurred. The epidemic occurred in all six republics and two provinces of Yugoslavia, in both previously recognized and newly recognized foci areas.