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S. Ahmetagić

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Background: The corona virus is transmitted in three ways: by direct contact with an infected person, by droplets, and by air. Transmission control according to official guidelines can be prevented by keeping a distance, wearing a mask and washing hands. Sharing a space with several members of the immediate or extended family increases the risk of transmission in all three ways. In Traditional Bosnian families two or three generations live in one household. The family doctor is informed with living conditions of the residents and has the opportunity to monitor the rate of secondary transmission from the index case, and then recommend additional preventative and treatment measures. Objective: The aim of the study was to determine the first occurrence of the symptoms and to monitor possible intrafamilial transmission of the disease through clinical examinations and microbiological-serological tests. Methods: The study was conducted in a family medicine clinic in the region of northeastern Bosnia and Herzegovina from March to December 2020. Patients with symptoms that could indicate the presence of COVID-19 disease were registered. If COVID-19 was proven, the patient became an index case. The other members of the family would be monitored for the secondary transmission via laboratory (PCA SARS-CoV-2 and IgM and IgG antibodies) and clinical parameters. Results: Characteristics of 25 index cases were analyzed. All 25 of them were middle-aged men that worked outside the home. In 25 households, there was a total of 123 members that shared a home with the index patient. Secondary transmission developed in 76 out of 123 family members (61.8%). Only one patient had a severe form of the disease and was hospitalized. 2 patients died. Conclusion: Intrafamiliar transmission of Covid-19 in households of Bosnia and Herzegovina is high. The secondary attack rate of SARS- CoV-2 in households is 61,8%. In the surveyed households, family members use common rooms with an infected patient, and the customs of family gatherings are maintained, without the implementation of protective measures. The family medicine team has the opportunity to apply appropriate preventive action, education and early prehospital treatment as well as adequate selection for the hospital admission.

Introduction: Cytomegalovirus (CMV) infection is ubiquitous. It affects all age groups, and its clinical picture ranges from mild to severe, especially as a congenital infection in neonates. Aim: To determine frequency of CMV infection in pregnant women in Tuzla Canton (TC) and the risk factors that lead to the infection. Methods: This prospective study included 300 pregnant women from TC aged 18 to 42 years. CMV serology was performed on all participants, and in case of acute infection additionally IgG avidity test. Participants also completed the questionnaire on the risk factors for CMV infection. Results: The median age of the 300 women was 28 ±4.97 years. There were 161participants (53.6%) who classified their environment as urban and 295 (98.33%) were married. More than half of the women had completed secondary school 168 (56%). Positive IgG antibodies to CMV had 280 (93.0%) women. Positive IgM and IgG antibodies had 9 (3.0%) participants, but all of them had high IgG avidity, which indicates reinfection or recurrent CMV infection. There was a statistically significant higher number of seropositive participants living in rural areas than those living in urban areas (p= 0.048). Also, there was significantly higher percentage of positive anti-CMV IgG in pregnant women with lower education (p=0.04). Conclusion: In our region there is high seropositivity rates of IgG antibodies to CMV in pregnant women. No case of primary CMV infection was proven. The risk factors for CMV infection have been proven to be rural environment and lower level of education.

Introduction: Chronic HCV infection is chronic inflamatory liver disease caused by hepatitis C virus. Anti HCV prevalence among intravenous drug users (IVDU) is very high and it accounts 40% -90% (60%-90%) with the risk of 80% of developing the chronic infection. Aim: The aims of this study were: a) to compare clinical characteristics of chronic HCV infection among IVDU and non-users population and to detect their impact to treatment outcome; b) to investigate the treatment efficacy comparing sustained viral response (SVR) in these two populations in Tuzla Canton. Patients and methods: The study was retrospective-prospective and included 45 IVDU of both sexes from Tuzla Canton which were treated from chronic HCV infection with Pegilated interferon 2a/2b + ribavirin in the Clinic for Infectious Diseases and Clinic for Internal Disease of University Clinical Centre in Tuzla. The control group were presented by non-users who completed therapy in both Clinics. For statistical analyses it was used statistical package SPSS 20,0 (SPSS Inc, Chicago, IL, USA) with tests of descriptive statistics with measures of central tendency and dispersion. Quantitative variables were tested by t-test or by Mann-Whitney test. Qualitative variables were tested by hi-square test or by Fisher’s test. The standard analyse of level’s risk was used too. The analyse of predictive value of EVR for achieving the ETR and SVR was done by cross-tabulation. The impact of known factors for achieving the SVR was evaluated by logistic regression analyses. All tests were done with statistical level of significance of 95% (p=0,05). Results: Men were more dominant in the test group (93,3% / 61,7%), also younger age (p<0,001) and lower BMI (p=0,019). The test group had significant higher basal values of Le, Hb, Plt and ALT and tendency to lower stages of fibrosis (p=0,08). The difference in genotype frequencies was statistically significant (p=0,001) with clearly dominance of G3 and G4 among IVDU. Treatment was not complited by two patients in both groups (4,4% /3,3%). EVR was significantly higher in test group (p=0,001) so did the ETR (p=0,002) and SVR (p<0,001). Predictive factors for SVR were: age (negative predictive factor), male sex, absence of reduction of pegilated interferon and ribavirin, Metavir stage of fibrosis and presence of EVR. Conclusion: Population of IVDU were adherent to treatment protocol and with excellent treatment response they justified the hope of health care workers for success treatment of this population.

H. Erdem, A. Inan, E. Guven, S. Hargreaves, L. Larsen, G. Shehata, E. Pernicová, E. Khan, L. Baštáková et al.

H. Erdem, A. Inan, Emre Güven, S. Hargreaves, L. Larsen, G. Shehata, E. Pernicová, E. Khan, L. Baštáková et al.

mubidin mujić, S. Čavaljuga, A. Čustović, Rahima Jahić, S. Ahmetagić

Introduction: Rubella is an infectious disease of viral etiology. It occurs in two forms, as postnatal rubella and congenital rubella. Objective: The objective of this study is to assess the scope of the epidemic of rubella in Tuzla Canton (TK) in 2010, then the incidence of disease in certain segments of the population, spatial distribution and movement in time. Material and Methods: The target population of this retrospective study was people suffering from rubella in 2010 from the Tuzla Canton. Results and Discussion: From the topographical distribution of patients with rubella in Tuzla Canton there is a strikingly large difference in the number of affected municipalities. Temporal distribution of patients with rubella is congruent with the epidemiological characteristics of rubella in terms of reporting the same. Gender structure of patients showed significantly higher numbers in males with 437 patients (67.33%), while for women there were 212 cases (32.67%). According to the age structure, the majority of the persons infected were aged 15-19, 470 of them which makes 72.5% of the total number of patients. When it comes to the vaccination status of patients, 3.7% was fully vaccinated (got 2 doses of vaccine), 7.6% was incompletely vaccinated (got one dose of vaccine), 66.4% was unvaccinated and for 22.3% vaccine status is unknown.Conclusion: An outbreak of rubella in Tuzla Canton in 2010 and the emergence of a large number of people susceptible to rubella is a direct consequence of discontinuity of vaccination programs during the war from 1992 to 1995. Keywords: rubella, epidemic, Tuzla Canton

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

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