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M. Hukić, S. Ahmetagić, N. Tihić, N. Mehinović, D. Tulumović, Mirza Ponjavić, P. Heyman

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

Ermina Iljazović, N. Mehinović, D. Ljuca, Z. Karasalihović, A. Adžajlić, F. Omeragić, S. Avdić

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

Ermina Iljazović, N. Mehinović, D. Ljuca, Z. Karasalihović, A. Adžajlić, F. Omeragić, S. Avdić

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

N. Mehinović, M. Popović, Selma Azabagić, Adnan Aljukić

Cilj ovog rada je da se prikaže trenutno stanje fizicko-hemijske i mikrobioloske ispravnosti vode s lokalnih izvorista i javnih cesmi na podrucju pet opcina Tuzlanskog kantona, te procijeni u kojoj mjeri stanovnistvo koristi alternativne izvore kao jedine izvore pitke vode, i kakav stav imaju o kvaliteti tih voda. Studijom presjeka anketirano je 400 ispitanika, starosti 30-70 godina, iz pet opcina Tuzlanskog kantona, izabranih metodom slucajnog izbora. Uzorci vode su prikupljeni sa 24 javne cesme iz istih opcina u kojima je vrseno anketiranje, te su izvrsene fizicko-hemijske i mikrobioloske analize vode prema važecim Pravilnicima. Rezultati ankete su pokazali da 52,54% ispitanika smatra da je voda iz javnih cesmi nesigurna jer se ne kontrolira redovito. 28,43% ispitanika ima stav da je voda s lokalnih izvorista „zdravija od vode iz vodovoda“, dok ih 19,04% smatra da je voda s lokalnih izvorista „bezbjedna za zdravlje“. Vise od trecine ispitanih (38,32%) koristi javne cesme i lokalna izvorista kao jedini izvor vode za pice, njih 35,79% koristi za pice vodu iz gradskog vodovoda, dok ih 25,89% konzumira flasiranu vodu. Od 24 ispitana uzorka vode, jedan uzorak ne zadovoljava fizicko-hemijske kriterije, dok je 16 bakterioloski neispravno. Mikrobioloska neispravnost se odnosi na fekalnu kontaminaciju.Prikazani rezultati upozoravaju da vode iz vecine izvorista ne zadovoljavaju propisane standarde, a needuciranost stanovnistva o rizicima koristenja nesigurnih izvora vode za pice dovodi do toga da ih jako veliki broj koristi upravo te vode kao jedine izvore pitke vode. Ovi rezultati trebaju biti podsticaj za nastavak istraživanja u cilju provođenja zastite izvorisnih podrucja, redovitog kontroliranja sastava voda te razvoja edukativnih programa u cilju podizanja nivoa znanja stanovnistva o koristenju sigurnih izvora vode za pice.

S. Ahmetagić, N. Tihić, A. Ahmetagic, A. Čustović, Arnela Smriko-Nuhanović, N. Mehinović, H. Porobic-Jahic

INTRODUCTION The prevalence of human brucellosis in Bosnia and Herzegovina and the Tuzla Canton reached its peak in 2008, with a reported total of 994 cases within country, and with 104 cases within the Tuzla Canton. AIM to analyze the clinical and epidemiological features of human brucellosis in patients hospitalized at the University Clinical Center Tuzla during the period from 01/01/2000 till the 31/12/2010. METHODS We retrospectively analyzed the clinical symptoms, the laboratory and X-ray findings, the treatments, and the course and outcome of the disease. The diagnosis of brucellosis was based on anamnesis, clinical presentation, in correlation with a positive blood-culture, and/or serological tests. RESULTS The majority of patients (93.18%) were from rural regions. There were more males (79.54%) than females. Most of the patients were aged between 30 to 39 years (21% cases). Contact with infected animals was registered for 83.40% of the patients. The main symptoms and signs were fever, joint-pains, night sweating, anorexia, headaches, and hepatosplenomegaly. The important laboratory findings were increased erythrocyte sedimentation rates, increased values of C-reactive protein, and anemia. Adult patients were treated with a combination of gentamicin or streptomycin with doxycycline, and the children with a combination of gentamicin, and trimethoprim-sulfametaxasol, over at least 6 weeks. Complications were documented in 20.45% of the patients. Relapses were observed in 14.20%, and a chronic form of brucellosis in 5.11% of patients. There were no cases with lethal outcomes. CONCLUSION Brucellosis is a growing public health problem, not only within the Tuzla Canton, but throughout Bosnia and Herzegovina.

M. Hukić, J. Hübschen, M. Šeremet, I. Salimović-Bešić, M. Mulaomerović, N. Mehinović, S. Karakaš, E. Charpentier et al.

SUMMARY A rubella outbreak involving 1900 cases was recorded in the Federation of Bosnia and Herzegovina between mid-December 2009 and the end of May 2010. Sera from 389 suspected rubella cases were examined for the presence of rubella-specific IgM and IgG antibodies. A total of 32 throat swabs from suspected rubella cases were tested by RT–PCR and were used to attempt virus isolation. Most patients (945/1900, 49·73%) had never received rubella vaccination or had an unknown vaccination status (563/1900, 29·63%). About 45% (178/389) of suspected rubella patients were IgM positive. From 13 of the throat swabs a virus isolate and E1 gene sequences attributed to genotype 2B were obtained. The rubella outbreak was due to failure to vaccinate during the war period (1992–1995) and emphasizes the need for additional vaccination opportunities.

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