A Unique Case of Cardiac Hypereosinophilia With Recurrent Valve Thrombosis After Mechanical Mitral Valve Replacement in the Setting of a Supratherapeutic International Normalized Ratio.

Hypereosinophilia (HES) is a rare, but highly fatal, disease that results in excess eosinophils causing multiorgan damage, mainly manifesting as extensive inflammation contributing to fibrosis. Notably, cardiac involvement occurs in almost half the cases and can often lead to thrombus development. This is a unique case of HES contributing to recurrent cardiac thrombus formation on a mechanical mitral valve in the setting of a patient who had a supratherapeutic international normalized ratio (INR) while on coumadin. The rarity of this case is also displayed in the patient's negativity for one of the fusion genes that are highly suggestive of cardiac HES, the demographics of her female gender, and her first objective sign being T-wave inversions versus the usual heart failure signs and symptoms. This case raises awareness of the disorder but also the importance of keeping its potential exacerbations on the differential, even in the setting of atypical presentations. With this, it also begs the question of whether coumadin is the proper anticoagulant of choice in these patients and whether other parameters should be considered.

A Rare Case of I127V Heterozygous Transthyretin Amyloidosis With Atypical Transthoracic Echocardiogram Findings Presenting As Upper Extremity Sensorimotor Polyneuropathy.

Hereditary transthyretin amyloidosis (hATTR) is a class of disorders with various systemic clinical manifestations, most often cardiac and neurologic in origin. The I127V mutation is a known but uncommon type of hATTR that typically affects males in their sixth or seventh decade of life. We present a case of this rare genetic variant with an atypical presentation of upper, followed by lower extremity sensorimotor polyneuropathy, with an uncharacteristic transthoracic echocardiogram (TTE) pattern but strongly positive pyrophosphate (PYP) scan, confirming the amyloidosis (AL) diagnosis.

Antimicrobial resistance profiles of human Brucella melitensis isolates in three different microdilution broths: the first multicentre study in Bosnia and Herzegovina.

OBJECTIVES: Brucellosis is a ubiquitous emergent bacterial zoonotic disease causing significant human morbidity in Bosnia and Herzegovina. So far, a high rate of resistant Brucella has been found worldwide. This study prospectively analysed the rates of resistance among human Brucella melitensis strains isolated in Bosnia and Herzegovina. METHODS: This study included 108 B. melitensis isolates from 209 patients diagnosed at five medical centres in Bosnia and Herzegovina. The resistance profiles of the B. melitensis isolates for the 13 most commonly used antimicrobials were studied in standard Brucella broth (BB) and cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 4% lysed horse blood or 5% defibrinated sheep blood. RESULTS: Of the 209 patients, B. melitensis blood cultures were positive for 111 (53.1%). Among the 108 isolates investigated, 91 (84.3%) were resistant to trimethoprim-sulfamethoxazole on BB, but not on either CAMHB. Nearly all isolates (>90%) were resistant to azithromycin on BB and both CAMHBs. CONCLUSION: We observed a high rate of B. melitensis resistance to azithromycin. The high rate of resistance to trimethoprim-sulfamethoxazole that we observed was related to BB, so an alternative broth should be used, such as the enriched CAMHBs in this study, for evaluating resistance to trimethoprim-sulfamethoxazole. Whole-genome sequencing studies are needed to understand the development of antimicrobial resistance in B. melitensis strains isolated from humans.

Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches.

This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (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, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease.

The first report of Brucella melitensis Rev.1 human brucellosis in Bosnia and Herzegovina.

Brucellosis is an emergent and endemic zoonotic disease in Bosnia and Herzegovina. In this report we have diagnosed the first case of human brucellosis in Bosnia and Herzegovina, using molecular and microbiological tests, caused by live attenuated Brucella melitensis Rev.1 strain. The infection was caused through unintentional exposure to vaccination of small ruminants in Bosnia and Herzegovina and without any prior accidental self-injection of vaccine suspension.

Cytomegalovirus Seroprevalence and Birth Prevalence of Congenital CMV Infection in Bosnia and Herzegovina: A Single-Center Experience.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in developed countries. Although high cCMV rates have been reported in populations with high seroprevalence, the cCMV prevalence in low/middle-income countries in Europe has not been defined. OBJECTIVE: To determine cytomegalovirus (CMV) seroprevalence and the cCMV prevalence in Bosnia and Herzegovina. METHODS: Between March 2010 and February 2019, 5222 sera samples from patients seen at the University Clinical Hospital Mostar were tested for CMV IgG. The cord blood samples collected from 2091 infants between July 2011 and January 2013 were analyzed for CMV IgG and CMV DNA. The cCMV prevalence was determined by testing saliva swabs from 1293 infants between November 2015 and October 2016. RESULTS: The overall CMV IgG prevalence was 81.4% (95% confidence interval: 0.8-0.82). Significantly higher prevalence was observed among females (84.9%) than in males (77.0%), and the rate increased from 50.8% in the 1 to 5 years group to 97.7% in the group > 65 years old. Most cord blood samples (2091/1925, 92.1%) were CMV IgG positive, and 2 (0.1%) were CMV DNA positive. Of the 1293 saliva swabs, 8 (0.62%; 95% confidence interval: 0.3-1.2) were CMV positive. All 8 infected infants had asymptomatic cCMV, and none had SNHL at 18 months of age. CONCLUSIONS: In a highly CMV seropositive population, the prevalence of cCMV was lower compared with that reported from other low/middle-income countries populations. None of the infected infants had symptomatic infection or SNHL at 18 months.

Epidemiological, Clinical and Molecular Characterization of Human Brucellosis in Bosnia and Herzegovina - An Ongoing Brucellosis Outbreak.

OBJECTIVE: The aim of this study was to evaluate an ongoing outbreak of brucellosis in southern region of Bosnia and Herzegovina (BIH) on the epidemiological, clinical and molecular level. PATIENTS AND METHODS: This study included 19 patients affected by brucellosis between 2015 and 2017, in Trebisevo (BIH). Out of 19 patients, 16 were admitted to and treated at the Department of Infectious diseases of the University Clinical Hospital Mostar, while three patients were treated in ambulatory care setting. Epidemiological, clinical and microbiological parameters were investigated. The Rose Bengal test (RBT) positive sera were serologically confirmed by complement fixation test (CFT). We also analyzed blood cultures, and isolates were additionally serotyped. Molecular analyses were performed with Bruce-ladder multiplex polymerase chain reaction (PCR) and multiple locus variable number of tandem repeat analysis of 16 loci (MLVA-16) assay. RESULTS: Fifteen out of 19 patients had been professionally exposed to the bacterium, while four patients acquired brucellosis without prior contact with infected animals. In seven out of eight (87.5%) patients with localized form of brucellosis, we detected significantly higher values of C-reactive protein (CRP) or erythrocyte sedimentation rate (P<0.001). B. melitensis was isolated from 13/16 (81.3%) blood culture samples, and additionally serotyped as biovar 3. Using MLVA16 assay, 11 isolates were genotyped. We observed complete genotype matches among 8/11 B. melitensis isolates, while 3/11 isolates differed in Bruce04 locus. CONCLUSION: Overall, our study confirms the usefulness of MLVA-16 method in the epidemiological and molecular research of brucellosis during epidemic that, most likely, originated from the same source.

Characteristics of Vancomycin-Resistant Enterococcus Strains in the West Balkans: A First Report.

Vancomycin-resistant enterococci are among the major causes of nosocomial infections and represent a growing problem in many European countries. Among the most common enterococcal isolates, Enterococcus faecium is considered to be the reservoir of VanA and VanB-mediated resistance to glycopeptides. Enterococci with VanA-mediated resistance can transfer resistance genes to other enterococci and gram-positive bacteria. Hence, monitoring and surveillance of vancomycin-resistant enterococci (VREs) are crucial for the prevention of the spread of glycopeptide resistance. No reports have yet been published that document the resistance rates and typization of VREs in the region of Bosnia and Herzegovina as well as Croatia. In this study, 64 clinical enterococcal strains that were isolated in clinical centers, Mostar, Sarajevo, and Zagreb, were studied and findings regarding characteristics of vancomycin-resistant strains found in the West Balkan region are reported for the first time. All of the strains were identified using conventional phenotypic methods, and the resistance to glycopeptides was determined using the disk diffusion method, Vitek 2, and genotypic Enterococcus assay. The results of genotyping showed that 40 strains were identified as VREs (30% Enterococcus faecalis and 70% E. faecium), while the sensitivity of the phenotypic methods was 87.5%. Furthermore, VanA and VanB resistance types were found in Bosnia and Herzegovina and Croatia, with slightly higher prevalence of the latter (72.5%) over the former (27.5%).

Prenatal stress and newborn telomere length.

BACKGROUND: The developmental origin of the health and disease hypothesis is based on the premise that many chronic diseases have their roots in fetal development. Specifically, maternal stress during pregnancy is associated with altered fetal development and many adverse long-term health outcomes. Although the mechanisms underlying this effect are currently unclear, at the cellular level 1 possible mediator is the regulation of telomere length. Telomere dynamics appear to play a role in disease progression, and an adverse intrauterine environment may contribute in the establishment of short telomeres in newborns. In accordance with this, it was recently reported that prenatal stress is significantly associated with shorter mean newborn telomere length. However, this finding has yet to be replicated, and currently we know nothing about whether different size classes of telomeres within the telomere length distribution are differentially affected by prenatal stress. Examining telomere length frequency distributions is important, because the shortest telomeres in the distribution appear to be the most indicative of telomere dysfunction and thus the best predictors of mortality and morbidity in humans. OBJECTIVE: We investigated the effects of intrauterine exposure to maternal stress over the whole course of gestation on newborn mean telomere length and telomere length frequency distributions. STUDY DESIGN: We conducted a prospective cohort study of 24 mother-newborn dyads at an urban teaching hospital. Pregnant women with nonanomalous, uncomplicated pregnancies were recruited and assessed in the third trimester of gestation. Maternal psychosocial stress was quantified using the Holmes and Rahe Stress Scale and categorized as high stress (≥300 points) or low stress (≤299 points) exposure. Newborn telomere length was measured from cord blood at delivery using the Telomere Restriction Fragment assay. RESULTS: We found a significant negative association between maternal stress and newborn telomere length (ß = -0.463, P = 0.04). Newborns whose mothers experienced a high level of stress during pregnancy had significantly shorter telomere length (6.98 ± 0.41 kb) compared to newborns of mothers with low stress (8.74 ± 0.24 kb; t = -3.99, P = .003). Moreover, the difference in newborn telomere length between high-stress and low-stress mothers was due to a shift in the telomere length distribution, with the high-stress group showing an underrepresentation of longer telomeres and an over-representation of shorter telomeres. CONCLUSION: Our findings replicate those of other recent studies and also show, for the first time, that the prenatal stress-associated difference in newborn mean telomere length is due to a shift in the overall telomere distribution.

Genotypic and phenotypic characteristics of Methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated on three different geography locations.

Staphylococcus aureus is a major cause of hospital-acquired infections worldwide. Increased frequency of methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients and possibility of vancomycin resistance requires rapid and reliable characterization of isolates and control of MRSA spread in hospitals. Typing of isolates helps to understand the route of a hospital pathogen spread. The aim of this study was to investigate and compare genotypic and phenotypic characteristics of MRSA samples on three different geography locations. In addition, our aim was to evaluate three different methods of MRSA typing: spa-typing, agr-typing and GenoType MRSA.  We included 104 samples of MRSA, isolated in 3 different geographical locations in clinical hospitals in Zagreb, Mostar, and Heidelberg, during the period of six months. Genotyping and phenotyping were done by spa-typing, agr-typing and dipstick assay GenoType MRSA. We failed to type all our samples by spa-typing.  The most common spa-type in clinical hospital Zagreb was t041, in Mostar t001, and in Heidelberg t003.We analyzed 102/104 of our samples by agr-typing method. We did not find any agr-type IV in our locations. We analyzed all our samples by the dipstick assay GenoType MRSA. All isolates in our study were MRSA strains. In Zagreb there were no positive strains to PVL gene. In Mostar we have found 5/25 positive strains to PVL gene, in Heidelberg there was 1/49. PVL positive isolates were associated with spa-type t008 and agr-type I, thus, genetically, they were community-associated MRSA (CA-MRSA). Dipstick assay GenoType MRSA has demonstrated sufficient specificity, sensibility, simple performance and low cost, so we could introduce it to work in smaller laboratories. Using this method may expedite MRSA screening, thus preventing its spread in hospitals.

Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus (MRSA) by pulsed-field gel electrophoresis (PFGE).

Staphylococcus aureus has long been recognized as one of the leading cause of hospital infections all over the world. Increased frequency of methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients and possibility of vancomycin resistance requires rapid and reliable characterization of isolates and control of MRSA spread in hospitals. Typing of isolates helps to understand pathogenesis and route of the hospital pathogen spread. In this study, in the analysis of an outbreak of MRSA infections in one surgical ward, we used pulsed-field gel electrophoresis (PFGE) as a method of typing. PFGE revealed one epidemic strain type A in 13 out of 16 patients, and another two types (type B in two patients and type C in one patient). Discussing the typing results in the ward has changed the admission policy of patients with infected vascular ulcers who were then cured as outpatients, and admitted for surgery after that. This policy resulted with the stopping of the outbreak; during next 2.5 year there was no further MRSA outbreak in the ward. PFGE also showed subtypes which enabled the insight into dynamics of MRSA strain changes during the outbreak. PFGE could be recommended as a screening method in the MRSA outbreak analysis. Because of it's high discriminatory power still remains the gold standard for MRSA typing.

Tonsillar colonization is unlikely to play important role in Helicobacter pylori infection in children.

OBJECTIVE: To determine (i) seroprevalence of Helicobacter pylori (HP) infection in children undergoing tonsillectomy, (ii) possible HP colonization on tonsils of children and its importance in HP transmission, and (iii) if four examined socio-economic factors are the risk factors for HP transmission and HP colonization on tonsils in children. METHODS: Rapid urease test (RUT) of tonsils, and serologic blood tests for HP were performed in 77 children (aged 4-14 years) in Bosnia and Herzegovina (B-H), undergoing tonsillectomy. RUT positive tonsils were cultured for HP. RUT positive children were tested using (13)Carbon-urea breath test ((13)C-UBT). Information about socio-economic potential risk factors was obtained from the parents. RESULTS: Out of 139 pharyngeal and palatine tonsils, 17 palatine tonsils in 14 children were RUT positive and had negative HP culture. Eight children had positive both RUT and (13)C-UBT. There was no significant difference between children with hypertrophy and those with recurrent tonsillitis comparing their serologic tests results. There was no significant difference between seronegative (n=61) and seropositive (n=16) children comparing their age, sex, parental education level, owning a family courtyard, attending a children's collective, and owning a pet cat. CONCLUSIONS: The results in this prospective study do not support the notion that tonsils are an important reservoir for HP transmission in children in B-H. The examined socio-economic factors did not enhance HP seropositivity rate in children.