Browsing by Author "Stevanovic, Goran (15059280200)"

Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.

Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.

The increasing incidence of fungal infections and antifungal resistance has prompted the search for novel antifungal drugs and alternative agents. We explored the antifungal activity of Myrtus communis essential oil (EO) against Malassezia sp. isolated from the skin of patients with pityriasis versicolor. These broad-spectrum antimicrobial activities of M. communis EO and its potent inhibiting activity on Malassezia growth deserve further research with aim to considerate this EO as candidate for topical use in treatment of skin diseases. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. Methodology: A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. Results: Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. Conclusion: Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings. © 2016 Zec et al.

Introduction: Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. Methodology: A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. Results: Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. Conclusion: Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings. © 2016 Zec et al.

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles. © Copyright © 2021 Kotur, Skakic, Klaassen, Gasic, Zukic, Skodric-Trifunovic, Stjepanovic, Zivkovic, Ostojic, Stevanovic, Lavadinovic, Pavlovic and Stankovic.

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles. © Copyright © 2021 Kotur, Skakic, Klaassen, Gasic, Zukic, Skodric-Trifunovic, Stjepanovic, Zivkovic, Ostojic, Stevanovic, Lavadinovic, Pavlovic and Stankovic.

Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.

Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1 %) were functionally independent at discharge (mRS 0-2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease. © 2014 Springer-Verlag Berlin Heidelberg.

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1 %) were functionally independent at discharge (mRS 0-2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease. © 2014 Springer-Verlag Berlin Heidelberg.

Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. These conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. The long-term prognosis for patients with CNPA and the potential complications of CNPA have not been well documented. The aim of this study was to review published papers that report cases of CNPA complications and to highlight risk factors for development of CNPA. The complications in conjunction associated with CNPA are as follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome, pulmonary Mycobacterium avium complex (MAC) disease, superinfection with Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still a challenge. Culture and histologic examinations of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals, even when the radiographic findings are unchanged. Early detection of intraluminal growth of Aspergillus and prompt antifungal therapy may facilitate the management of these patients and prevent development of complications. © 2017, Instituto de Medicina Tropical de Sao Paulo. All rights reserved.

The original version of this article unfortunately contained two mistakes in authors’ names. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40–50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient’s condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA. © 2023 by the authors.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40–50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient’s condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA. © 2023 by the authors.

Introduction: SARS-CoV-2 is fundamentally a respiratory pathogen with a wide spectrum of symptoms. The COVID-19 related pancreatitis is less considered than other clinical features. The purpose is to describe two cases of pancreatitis associated with COVID-19. Methodology: Patients' demographics, clinical features, laboratory, and instrumental findings were collected. Results: Two patients admitted to the hospital were diagnosed with COVID-19 and severe acute pancreatitis, according to the Atlanta criteria. Other causes of acute pancreatitis were excluded. Treatment included broad-spectrum antibiotics, proton pump inhibitors, and low molecular weight heparin. Steroids, oxygen, antifungal treatment, and pain killers were administered when appropriate. Both patients were asymptomatic, with normal vital parameters and blood exams, and were discharged in a good condition. Conclusion: It is recommendable to include lipase and amylase on laboratory routine tests in order to evaluate the need for the abdominal CT-scan and specific therapy before hospital admission of the patients with COVID-19 related life-threatening acute pancreatitis. Copyright © 2022 Fiore, Beretta, De Vito, Barac, Maida, Joeseph Kelvin, Piu, Lai, Madeddu, Rubino, Stevanovic, Korica and Babudieri.

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background: Tuberculosis (TB) remains a leading cause of mortality worldwide, particularly in low- and middle-income countries. The rise of multidrug-resistant TB (MDR-TB) poses significant challenges to global health. This study reviews the experience of the largest pulmonology center in Serbia, a country with low MDR-TB incidence, focusing on TB prevalence, resistance detection, and treatment strategies between 2012 and 2021. Methods: We retrospectively analyzed a total of 1239 patients who were diagnosed and treated for TB in the period from 2012 to 2021 at University Clinical Center of Serbia. Results: Drug resistance was identified in 21 patients (1.7%), with the highest resistance to rifampicin (1.4%) and isoniazid (1.3%). Pyrazinamide and streptomycin resistance were detected in only a few cases. Patients with resistant TB were younger on average, though the difference was not statistically significant (46.4 ± 19.1 vs. 53.6 ± 18.4, p = 0.079). Prior TB history was more frequent in the resistant group, almost reaching statistical significance (4 vs. 82, p = 0.052). Conclusions: These findings underscore the critical importance of sustained surveillance, particularly of latent and drug-resistant TB forms, in alignment with the World Health Organization’s (WHO) TB control strategy to preserve Serbia’s low-incidence status. Moreover, given Serbia’s strategic location on a major migration route, there is an elevated risk of new TB cases emerging and potential shifts in TB-drug-resistance patterns developing in the future. © 2025 by the authors.

Background: Tuberculosis (TB) remains a leading cause of mortality worldwide, particularly in low- and middle-income countries. The rise of multidrug-resistant TB (MDR-TB) poses significant challenges to global health. This study reviews the experience of the largest pulmonology center in Serbia, a country with low MDR-TB incidence, focusing on TB prevalence, resistance detection, and treatment strategies between 2012 and 2021. Methods: We retrospectively analyzed a total of 1239 patients who were diagnosed and treated for TB in the period from 2012 to 2021 at University Clinical Center of Serbia. Results: Drug resistance was identified in 21 patients (1.7%), with the highest resistance to rifampicin (1.4%) and isoniazid (1.3%). Pyrazinamide and streptomycin resistance were detected in only a few cases. Patients with resistant TB were younger on average, though the difference was not statistically significant (46.4 ± 19.1 vs. 53.6 ± 18.4, p = 0.079). Prior TB history was more frequent in the resistant group, almost reaching statistical significance (4 vs. 82, p = 0.052). Conclusions: These findings underscore the critical importance of sustained surveillance, particularly of latent and drug-resistant TB forms, in alignment with the World Health Organization’s (WHO) TB control strategy to preserve Serbia’s low-incidence status. Moreover, given Serbia’s strategic location on a major migration route, there is an elevated risk of new TB cases emerging and potential shifts in TB-drug-resistance patterns developing in the future. © 2025 by the authors.

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations. Copyright © 2022 Zecevic, Kotur, Ristivojevic, Gasic, Skodric-Trifunovic, Stjepanovic, Stevanovic, Lavadinovic, Zukic, Pavlovic and Stankovic.