We report on an ongoing measles outbreak in the Federation of Bosnia and Herzegovina with 141 cases notified between week 52 2023 and week 6 2024. Among those with known vaccination status, 97% were unvaccinated and the most affected group is children under the age of 5 years (n = 87) who were not vaccinated during the pandemic years. Sixty-eight cases were hospitalised, the most common complications were measles-related pneumonia and diarrhoea. The sequenced measles viruses from four cases belonged to genotype D8.

Aim To evaluate Helicobacter pylori (H. pylori) resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina, a region with no data on clarithromycin or quinolones resistance. Methods A prospective cross-sectional study was conducted at the Department of Gastroenterology and Hepatology at University Clinical Centre Tuzla between January 2021 and June 2022. The study included 99 patients who underwent esophagogastroduodenoscopy (EGDS) due to dyspepsia. In all patients biopsies were taken for rapid urease test (RUT) and histology findings, concomitantly with blood samples for IgG serology. All RUT positive patient samples were tested for clarithromycin and quinolones susceptibility with GenoType HelicoDr, a PCR method which detects point mutations in 23S rRNA and mutations in the gyrA gene. Results Out of 99 dyspeptic patients, 67 (67.7%) were serologically positive to H. pylori, 46 (46.4.%) were RUT positive, and 19 (19.2 %) had a positive histology finding. Antibiotic (AB) resistance was tested in the total of 46/99 (46.4%) patients. Resistance to clarithromycin was detected in 28.26% (13/46), quinolones resistance in 36.96% (17/46) , and resistance to both AB was detected in 8.69% (4/46) tested biopsies. Conclusions Due to high clarithromycin and quinolones resistance rates, we recommend the use of bismuth quadruple or non-bismuth concomitant quadruple therapy for H. pylori eradication in Tuzla Canton, Bosnia and Herzegovina.

Aim To evaluate clinical and epidemiological characteristics and outcome of patients with COVID-19, and impact of vaccine against COVID-19 on them. Methods This retrospective study included 225 patients treated from COVID-19 in the period from 1 to 30 September 2021 at the Clinic for Infectious Diseases, University Clinical Centre Tuzla (UCC Tuzla). For the diagnosis confirmation of Covid-19, RTPCR was used. Patients were divided in two groups: fully vaccinated with two doses of vaccine, and non-vaccinated or partially vaccinated. Results Of 225 patients, 120 (53.3%) were females, and 105 (46.7%) males. Mean age was 65.6 years. There were 26 (11.6%) fully vaccinated patients. Most common symptoms in unvaccinated patients were fatigue (70.9%), cough (70.4%) and fever (69.8%), and in vaccinated fever (76.9%), fatigue (69.2%) and cough (46.2%). Cough was more common in unvaccinated patients (p=0.013). Fatal outcome happened in 84 (37.3%) patients. Transfer to the Intensive Care Unit (ICU) and older age had a higher risk of death (p<0.001). Older age patients were more likely to have comorbidities like atrial fibrillation (p=0.017), hypertension (p<001) and diabetes mellitus (p=0.002). Atrial fibrillation (p<0.001), hypertension (p<0.001), diabetes mellitus (p=0.009) and history of stroke (p=0.026), were related to fatal outcome in unvaccinated patients, also did a shorter duration of illness prior to hospitalization (p<0.001) and shorter length of hospitalization (p=0.002). Conclusion Older patients with comorbidities, as well as those who were not vaccinated against COVID-19, were at higher risk for severe form of the disease and poor outcome.

Aims: The aims of this study was to investigate the susceptibility of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae clinical isolates to antibiotics and essential oils - Origanum compactum, Origanum majorana and Thymus serpyllum. Study Design: Study included 30 isolates of Klebsiella pneumoniae obtained from clinical material provided from the University Clinical Center Tuzla. Place and Duration of Study: Department of Biology, Faculty of Science, University of Tuzla, BiH, between September 2019 to September 2020. Methodology: Antibiotic susceptibility testing was performed by the Kirby-Bauer disk diffusion method. The following commercially available antibiotic discs were used: amoxicillin (30µg), cefalexin (30 µg), gentamicin (10 µg), amikacin (30 µg), imipenem (10 µg), piperacillin (75µg), ampicilin (10 µg), meropenem (10 µg), ciprofloksacin (10 µg), ceftazidim (30 µg), cefotaksim (30 µg), ceftriaxone (30 µg), cefepime (30 µg) and aztreonam (30 µg). The antibacterial effect of the essential oils was tested for ESBL K. pneumoniae isolates using the diffusion method according to Clinical laboratory standards institute (CLSI) guidelines. Results: O. compactum and O. majorana essential oils showed the same antimicrobial activity with 80.0% effect on ESBL K. pneumoniae isolates, Thymus serpyllum EO showed antimicrobial activity of 60.0%. The lowest MIC value had the O. compactum essential oil (MIC 6 mg/ml-10.5 mg/ml), followed by the T. serpyllum (MIC 17.2 mg/ml-43 mg/ml), while the O. majorana essential oil showed MIC values in range from 11 mg/ml to 39 mg/ml. Conclusion: The results of the study showed the exceptional sensitivity of ESBL K. pneumoniae clinical isolates to the essential oils from Origanum and Thymus genera, which highly suggests their potential application in the struggle against these pathogens in the future.

Background : As antibiotic resistance  in microorganisms is  increasing and becoming a global problem, essential oils should be considered as new chemical substances with potenial therapeutic effects. Aim of the study : Determine the susceptibility of beta-lactamase clinical isolates of Pseudomonas aeruginosa to antibiotics and essential oils, define the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for tested oils. Material and Methods : This study included 120 P. aeruginosa isolates from clinical material. A disc diffusion method was used to for determination of antibiotic and essential oil susceptibility profile. For the phenotypic detection of beta-lactamase isolates, a disk diffusion method was used according to the CLSI guidelines with clavulanic acid. MIC was determined by microdilution test in broth. MBC was recorded after determination of MIC, it was corresponded to the lowest concentration of the essential oil yielding negative subcultures after incubation at appropriate temperature for 24 h. Results : Of the three tested oils, Origanum compactum had the strongest antimicrobial effect (MIC 6.4 mg/ml - 9.3 mg / ml) on P. aeruginosa isolates followed by Thymus serpylum (MIC 13 mg / ml to 78 mg / ml) and Origanum majorana ( MIC 21,5 mg/ml do 43 mg/ml ). Conclusion : Beta-lactamase producing P. aeruginosa isolates resistant to third and forth genetration of cephalosporin antibiotics, showed susceptibility against tested essential oils.

Aim To characterize methicillin-resistant S. aureus (MRSA) strains phenotypically and genotypically and to determine their clonal affiliation, representation and antibiotic resistance profile. Methods A total of 62 randomly selected MRSA isolates of different clinical samples collected from 2009 to 2017 were phenotypically and genotypically analysed. Phenotypic analyses were performed by standard microbiological procedures, and using VITEK 2/AES instrument as well as MALDI-TOF (matrix-assisted laser desorption/ionization) technology. Genotypic characterization included spa, MLST (multilocus sequence typing) and SCCmec typing, and detection of the Panton-Valentine leukocidin (PVL) and other enterotoxin encoding genes. Results The largest number of isolates, 21 (33.87%) belonged to ST228-MRSA-I, spa type t041, t1003 and t001. Other major clones were: ST239-MRSA-III, spa type t037 and t030 (27.41%); ST8-MRSA-IV, spa type t008 and t121 (12.9%); ST247-MRSA-I, spa type t051 (4.83%). PVL was detected in 10 isolates (SCCmec IV/V). During 2009 and 2010 the most frequent MRSA strain was South German clone, ST228-MRSA-I (80% and 90%, respectively), while in later years it was replaced with Brazilian-Hungarian clone ST239-MRSA-III (75% in 2015 and 2016). The South German clone, spa type t041 in 90.48% of cases was resistant to clindamycin, ciprofloxacin, erythromycin, cefoxitin, gentamicin, kanamycin, tobramycin and penicillin, while 70.58% samples of the Brazilian-Hungarian clone spa type t037 were additionally resistant to tetracycline and rifampicin. Conclusion This research can supplement the existing knowledge about the clonal distribution of MRSA in Bosnia and Herzegovina and their sensitivity to antibiotics in order to improve the national control of these infections.

Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.

Aim To present combined measles cases data and phylogenetic analysis of the virus circulated in 2018 in the Federation of Bosnia and Herzegovina (FB&H, the entity of Bosnia and Herzegovina), in order to analyse endemic transmission patterns of circulating strains and its implications for elimination efforts. Methods The data were derived from epidemiological case investigations and laboratory diagnoses based on serology, molecular detection and genotyping of the measles virus. Results During 2018 16 measles cases were reported in FB&H, of which five were classified as laboratory confirmed cases, one was an epidemiologically linked case and 10 were clinically compatible cases. Among them 12 (75.00%) cases were unvaccinated or had unknown vaccination status. The most affected population was up to 14 years of age (13/16; 81.25%). None of the cases was fully vaccinated. Viruses of other genetic lineages had been introduced in FB&H in the recent period. Two virus lineages of genotype B3 were identified. Phylogenetic analysis indicated the presence of a unique sequence of measles B3 virus in FB&H (Sarajevo). Conclusion Further strengthening of measles surveillance system and renewed efforts to increase vaccination levels are necessary to prevent disease and for elimination setting.

Objectives: To assess the prognostic value of pentraxin 3 (PTX3) in patients with ST-elevation myocardial infarction (STEMI) after bare-metal stent (BMS) implantation. Methods: In this prospective study, PTX3, interleukin (IL-6), IL-10, high-sensitivity c-reactive protein (hsCRP), and cardiac troponin I (cTnI) plasma values were determined before and 24hours after BMS implantation in 97 consecutively enrolled patients with STEMI who were admitted to University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina between February 2016 and February 2017. Patients were followed for 24 months to assess major adverse cardiovascular events (MACEs). Results: At 24 hours after percutaneous coronary intervention (PCI), plasma values of PTX3, IL-6, hsCRP, and cTnI were significantly increased; and IL-10 levels were significantly decreased compared with the values determined before PCI. Patients with MACEs had significantly higher plasma PTX3 levels at 24 hours after BMS-PCI than in patients without MACEs. Patients with PTX3 plasma values ≥5042 ng/ml had a significantly higher risk of MACEs than patients with PTX3 levels <5.042 ng/mL. Pentraxin 3 levels exhibited strong and significant correlations with IL-6 and IL-10 levels. Pentraxin 3, cTnI, and IL-6, but not hsCRP levels have showed independent association with MACEs, according to the multivariate Cox regression analysis. Conclusion: Pentraxin 3 might be better serum prognostic marker than IL-6, IL-10 or high sensitivity CRP for MACEs after BMS-PCI. It might help to make better risk stratification of those patients who are undergoing BMS-PCI.

Received: 17.12.2017 Accepted: 25.01.2018 Department of 1Otorhinolaryngology, 2Chest Disease, 3Surgery, 4Radiology, 5Clinic for Microbiology, Tuzla University Clinical Center, Tuzla, Bosnia and Herzegovina, 6Faculty of Education and Rehabilitation. University of Tuzla, Bosnia and Herzegovina Yazışma adresi: Sekib Umihanic, ENT Clinic. UCC Tuzla. Bosnia and Herzegovina e-mail: sekib.umihanic@gmail.com INTRODUCTION

Tularemia is a vector-borne zoonosis with a complex epidemiology caused by Francisella tularensis. F. tularensis is a non-motile, obligatory aerobic, facultative intracellular Gram-negative coccobacillus. The bacterium has a broad host range, i.e. mammals, birds and invertebrates. Two types (A, B) and four subspecies (F. tularensis subsp. tularensis (type A), F. tularensis subsp. holarctica (type B), F. tularensis subsp. mediasiatica and F. tularensis subsp. novicida.) are known today. Types A and B are of importance as they cause disease in humans and animals. Type A is present almost exclusively in North America and type B is found all over the Northern hemisphere. F. tularensis is considered to be a class A biological warfare agent, it is notoriously difficult to recognize infections in non-endemic regions and was produced as a weaponized agent by several countries in the 1960ties and 70ties. Humans can acquire tularemia by inhaling dust or aerosols contaminated with F. tularensis bacteria, this type of exposure can result in pneumonic tularemia, one of the most severe forms of the disease. especially farming involving machines that disperse remains of infected animals or carcasses. Rarely, water can become tularemia contaminated through contact with infected animals. Humans who drink contaminated and untreated water may contract oropharyngeal tularemia. The tularemia outbreak in B&H in 1995 showed an unusual number of oropharyngeal cases. As all aspects of this particular tularemia epidemic were not thoroughly investigated and the possible intentional use of agents of biological warfare remained a possibility, we reviewed all available data in order to assess whether the outbreak was natural. Correspondence to: Mirsada Hukić, Institute for Biomedical Diagnostic and Research Nalaz, Sarajevo Bosnia and Herzegovina, Tel: +387-33-651 371; E-mail: mirsadahukic@yahoo.com Received: May 23, 2017; Accepted: June 20, 2017; Published: June 22, 2017 Introduction Tularemia is a vector-borne zoonosis with a complex epidemiology caused by Francisella tularensis. F. tularensis is a non-motile, obligatory aerobic, facultative intracellular Gram-negative coccobacillus. The bacterium has a broad host range, i.e. mammals, birds and invertebrates. Four subspecies are known today; F. tularensis subsp. tularensis (type A), F. tularensis subsp. holarctica (type B), F. tularensis subsp. mediasiatica and F. tularensis subsp. novicida. Types A and B are of importance as they cause disease in humans and animals. Type A is present almost exclusively in North America and type B is found all over the Northern hemisphere [1]. Infections due to tick and deer fly bites usually take the form of ulceroglandular or glandular tularemia. F. tularensis bacteria can also be transmitted to humans via the skin when handling infected animal tissue. This can occur when hunting or skinning infected rodents like rabbits, muskrats and other rodents. Many animals have also been known to become infected and clinically ill from tularemia. Domestic cats are very susceptible and can transmit the bacteria to their owners. Therefore, care should always be taken when handling sick or dead animals. Infection due to handling animals can result in glandular, ulceroglandular and oculoglandular tularemia. Eating of under-cooked meat of infected animal’s tularemia can also result in oropharyngeal tularemia [2]. Humans can acquire tularemia by inhaling dust or aerosols contaminated with F. tularensis bacteria, this type of exposure can result in pneumonic tularemia, one of the most severe forms of the disease. especially farming involving machines that disperse remains of infected animals or carcasses. Rarely, water can become tularemia contaminated through contact with infected animals. Humans who drink contaminated and untreated water may contract oropharyngeal tularemia [3]. Transmission from person to person has so far not been reported. Inhalational tularemia following intentional release of a virulent strain of F. tularensis would have the greatest adverse human Hukić M (2017) Recognizing the possibility of bioterrorism in the face of emerging and reemerging zoonotic pathogens in Bosnia and Herzegovina during the war (1992-1995) Volume 1(3): 2-7 Virol Res Rev, 2017 doi: 10.15761/VRR.1000113 consequence because of its very high infectivity if delivered as an aerosol. It has been estimated that an aerosol dispersal of 50 kg of virulent F. tularensis over a metropolitan area with 5 million inhabitants would result in 250 000 incapacitating casualties, including 19,000 deaths. Outbreaks of pneumonic tularemia, particularly in low incidence areas, should prompt consideration of bioterrorism. F. tularensis has long been considered a potential biological weapon. It was one of the agents studied the Japanese germ warfare research units in Manchuria, China between 1932 and 1945; it was also considered for military purposes in the West [4]. An outbreak of tularemia reported in Soviet and German soldiers during the second world war may have been the result of intentional release [5]. F. tularensis has been studied, weaponized and stockpiled by several countries, including Japan, the USSR and the US [4]. Pathogenesis Francisella tularensis can infect humans through the skin, mucous membranes, gastrointestinal tract, and lungs. The major target organs are the lymph nodes, lungs and pleura, spleen, liver, and kidney. Bacteremia is common in the early phase of infection. The initial tissue reaction to infection is a focal, suppurative necrosis. Suppurative lesions become granulomatous, typical of other granulomatous conditions, i.e. tuberculosis or sarcoidosis. Humans with inhalational exposure also develop early in the course of illness hemorrhagic signs and inflammation of the airways which usually evolves to bronchopneumonia. Clinical manifestations The primary clinical forms of tularemia vary in severity and presentation according to virulence of the infecting organism, the dose, and way of administration. Primary disease presentations can be glandular, ulceroglandular, oculoglandular, oropharyngeal, pneumonic, typhoidal, and septic forms. The onset of tularemia is usually abrupt, with fever (38°C-40°C), headache, chills and rigors, generalized body aches (lower back pain) and sore throat. A dry or slightly productive cough frequently occurs with or without signs of pneumonia. Nausea, vomiting, and diarrhea sometimes occur. Sweats, fever and chills, malaise, progressive weakness and weight loss characterize the continuing illness. In untreated tularemia, symptoms often persist for several weeks or months. Any form of tularemia may be complicated by hematogenous spread, resulting in secondary pleura-pneumonia, sepsis, and meningitis. Prior to the administration of antibiotics, the overall mortality with the more severe type A strains is of 5% to 15%, and in the case of untreated pneumonic and severe systemic forms fatality rates as high as 30% to 60% were reported. Type B infections are in contrast rarely fatal. Ulceroglandular tularemia, after handling a contaminated carcass or due to an infective arthropod bite, a local cutaneous papule appears at the inoculation site together with the onset of generalized symptoms, becomes pustular, and ulcerates within a few days. The ulcer is tender may show an eschar. Antibiotic treatment does not prevent the affected nodes from becoming fluctuant and rupture. Oculoglandular tularemia, which follows direct contamination of the eye, ulceration occurs on the conjunctiva, accompanied by pronounced chemosis, vasculitis, and regional lymphadenitis. Glandular tularemia is characterized by lymphadenopathy without an ulcer. Oropharyngeal tularemia is acquired by drinking contaminated water, ingesting contaminated food, or by inhaling contaminated droplets or aerosols. Affected persons may develop stomatitis but more commonly develop exudative pharyngitis or tonsillitis, sometimes with ulceration. Tularemia pneumonia is the direct result of inhaling contaminated aerosols. Inhalational exposures commonly result in an initial clinical picture of systemic illness without prominent signs of respiratory disease. The earliest pulmonary radiographic findings of inhalational tularemia may be peribronchial infiltrates, typically advancing to bronchopneumonia in one or more lobes. Pulmonary infection can sometimes rapidly progress to severe pneumonia, respiratory failure, and death. Lung abscesses occur infrequently. Typhoidal tularemia is used to describe systemic illness when the site of inoculation or the localization of infection is unclear. Tularemia sepsis is severe and potentially fatal. As in the case of typhoidal tularemia, fever, abdominal pain, diarrhea, and vomiting may be prominent early in the course of illness. The patient typically appears toxic and may develop confusion and coma. Unless treated promptly, septic shock and other complications of systemic inflammatory response syndrome may develop with hemorrhagic signs, acute respiratory distress syndrome and organ failure [4]. The war in Bosnia and Herzegovina (B&H) (1992-1995) As in all conflicts, the inhabitants of Bosnia and Herzegovina were under extreme pressure during the war that took place 1992-1995. Due to the nature of the conflict that sometimes involved hostilities amongst neighbors, there was minimal respect for human rights and civilians, children and old people as well as soldiers suffered the consequences. In particular the weakest individuals, namely women and children suffered the most. Horrific ethnic cleansing campaigns between 1992 and the end of 1995 killed thousands and violently displaced more than two million people in much of B&H. International intervention into the Bosnian conflict led finally to a peace agreement in late 1995 (the Dayton Accords). The Dayton agreement finally ended the war in B&H. In 1995, the conflict between multiple factions was ag