Seroprevalence Study of Anti-HBs Antibodies in the General Population of Vojvodina, Serbia.

Background and Objectives: Hepatitis B (HB) is a major global health problem and a potentially life-threatening disease caused by the hepatitis B virus (HBV). Also, it is an important cause of morbidity and mortality worldwide. Thanks to serological surveys, testing hepatitis B surface antibodies (anti-HBs) allows for serological assessments of their prevalence. The presence of anti-HBs, which protects against HBV infection, can be attributed to HB vaccination or natural HBV infection. The aim of our study was to evaluate the prevalence of HB surface antibodies (anti-HBs) as an indicator of collective immunity against HBV in the general population of the Autonomous Province of Vojvodina, Serbia. In addition, to distinguish whether anti-HBs were induced by the vaccine or by infection, the presence of antibodies against the hepatitis B core antigen (anti-HBc) was tested among those who were anti-HBs-positive. Materials and Methods: A total of 3467 residual sera samples, collected according to the specifications of the European Sero-Epidemiology Network 2 (ESEN2) study, from April 2015 to March 2016, were screened for the presence of anti-HBs using a chemiluminescence immunoassay. The difference between categorical variables was tested using the chi-square test. Results: Overall, 1870 (53.9%, 95% CI: 52.3-55.6) participants tested positive for anti-HBs. The median age of the study participants was 17 years (IQR 9-35). The anti-HB seroprevalence decreased with age, ranging from 80.7% (95% CI: 78.9-82.4) in the 1-19-year-old group to 16.4% (95% CI: 12.0-20.9) in the ≥60 years' age group. A total of 71 (3.8%, 95% CI: 2.9-4.7) serum samples were also anti-HBc-positive. Higher prevalence, but not statistically significant, was noticed in women (4.1%, 95% CI: 2.8-5.4) compared with men (3.5, 95% CI: 2.4-4.8) (p = 0.542). Also, there was a significant difference across the age groups, where those ≥60 years old had a prevalence of 65.9% (95% CI: 51.9-79.9) and the age category of 1-19-year-olds had just 0.2% (95% CI: 0.0-0.4) (p < 0.001). Conclusions: This study provides a comprehensive assessment of the anti-HBs seroprevalence of the general population in Vojvodina and provides an opportunity to better shape the national preventive strategy related to HBV.

Pertussis Epidemiology in the Autonomous Province of Vojvodina, Serbia, 1948-2023.

Pertussis continues to be a significant public health concern. We aimed to examine the epidemiological characteristics of pertussis in Vojvodina, which accounts for almost a third of Serbia's population. Our aim was to determine the overall and age-specific incidence and mortality rates of pertussis in Vojvodina from 1948 to 2023, as well as the coverage of immunization against pertussis from 1960 to 2023. In the period 1948-2023, 42,259 cases of pertussis were reported. Following the introduction of the DTwP vaccine (1960) in Serbia, the reported incidence of pertussis began to decline. In 2001, for the first time since introduction of pertussis surveillance in Vojvodina, no pertussis cases were reported. Since 2012, the reported incidence of pertussis has once again increased, and peaked (41.1/100,000) in 2023, approaching the incidence rates recorded shortly after the introduction of DTwP vaccine. A shift in the age profile of pertussis from children aged 0-6 years to school-aged children (7-14 years) occurred between 2012 and 2023, when 48.3% of pertussis cases occurred in this age group. Although the incidence rates of pertussis among individuals aged 20 years and older were significantly lower than among younger age groups, there is evidence of an increasing trend in pertussis cases, particularly among those aged 40-49 years, since 2012. Based on the findings of this study, it is imperative to introduce additional booster doses of the aP vaccine for individuals aged 14 years, along with implementing maternal immunization strategies targeting women of childbearing age.

Seroepidemiology of Human Parvovirus B19 Infection among the Population of Vojvodina, Serbia, over a 16-Year Period (2008-2023).

This study aimed to estimate the serological status and dynamic changes in the prevalence of Parvovirus B19 (PVB19) antibodies within the general population residing in the northern part of the Republic of Serbia (Province of Vojvodina) during a 16-year period. Serum samples were analyzed for Human PVB19-specific IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Throughout the study period, the overall seroprevalence was 49.51%. Approximately 10% of patients exhibited a serologic profile positive for PVB19 IgM antibodies. Notably, seroprevalence varied significantly, ranging from 9.12% in the pediatric cohort (ages 1-4 years) to 65.50% in the adult demographic (40-59 years old). Seroprevalence was higher (51.88%) among women compared to men (42.50%). Immunologically naive pregnant women in the age groups 26-36 and 36-45 years had 45% (OR = 0.55, 95% CI: 0.31-1.00) and 52% (OR = 0.48; 95% CI: 0.24-0.94) lower odds of having negative IgM and IgG compared to those in age group 16-25 years old. Improved knowledge of the epidemiology of PVB19 may assist clinicians in the differential diagnosis of PVB19 clinical manifestations. The PVB19 detection is particularly important for monitoring individuals in risk groups such as women of reproductive age, medical staff, patients with hematological disorders, and those with immunodeficiency.

Knowledge of Healthcare Workers Regarding Road Traffic Child Safety in South Backa District, Serbia.

Introduction: Healthcare workers (HCW) can have an important role in educating parents about child road safety, but research on the topic shows that they usually do not have adequate knowledge. Thus, the aim of our study was to analyze their knowledge in the field of child road safety. Methods: The cross-sectional study was conducted among HCW from South Backa district, Serbia, using a specially created questionnaire for assessing knowledge on road traffic injuries in children. Results: The research involved the participation of 317 healthcare workers (86 physicians and 231 nurses). Healthcare workers from primary healthcare made up almost 70% of all respondents, followed by those from tertiary (21.8%) and secondary (11.3%) level institutions. The average percentage of correct answers on the knowledge test was 74.3% (mean=22.3, SD=4.0). Out of all respondents, HCWs employed in the paediatrics department had a significantly higher percentage of correct answers at 77.7% (mean=23.3, SD=3.4) compared to other health workers at 73% (mean=21.9, SD=4.1) (p=0.002). Association analysis demonstrated that HCW employed at paediatric departments on average scored 1.37 (95% CI: 0.40-2.33, p=0.006) points higher in comparison with other HCW. Conclusion: This research demonstrated an unsatisfactory level of knowledge on child road safety by HCW, and the variability across different question domains, which underlines the need for continuous educations in order to improve their knowledge. Our results may serve in planning additional public health measures and can provide a reference for future studies.

Overview of the Implementation of the First Year of Immunization against Human Papillomavirus across Different Administrative Units in Serbia and Montenegro.

Despite the availability of a safe and effective vaccination, uptake of human papillomavirus (HPV) vaccination remains low worldwide. We aimed to analyze the coverage of HPV immunization during the first year of the immunization program and the sociodemographic characteristics across different administrative units in Serbia and Montenegro. Coverage of HPV vaccination in Serbia for females aged 9-14 and 15-19 years was 5.5% and 5.9%, respectively. The coverage rate of immunization against HPV in Montenegro for girls aged 9-14 years was 22.1%. Within Serbia, only one administrative region (Moravica) had HPV immunization coverage in girls 9-19 years old above 10%, 11 districts had coverage from 5 to 10%, while 13 districts had coverage below 5%. As per Montenegro, two administrative units, Cetinje and Berane, reported the highest coverage, with 39% and 36.4% of vaccinated eligible girls, respectively. When we explored the coverage of HPV immunization among girls aged 9-19 years across different regions in Serbia, we observed that the level of coverage did not correlate with the number of pediatricians or with the population density. In Montenegro, we observed a similar situation. On the other hand, we noticed a statistically significant moderate negative correlation (r = -0.446; p = 0.026) between HPV immunization coverage and the percentage of illiterate women in the administrative units. Comparing the coverage between the two countries we found that the higher coverage in Montenegro corresponded with a smaller number of female populations aged 9-14 years, with higher average net monthly income, with smaller population density and smaller number of pediatricians, among divorced persons, and among those without formal education or incompletely primary education. Taking into account the experiences in Montenegro, increasing immunization coverage in Serbia could be achieved through a more vigorous educational campaign targeting schools, the general population, and healthcare workers as well as by additionally incentivizing those engaged in these activities.

Analysis of Cultured Gut Microbiota Using MALDI-TOF MS in COVID-19 Patients from Serbia during the Predominance of the SARS-CoV-2 Omicron Variant.

The currently dominant SARS-CoV-2 omicron variant, while causing mild respiratory symptoms, exhibits high transmissibility, drug resistance, and immune evasion. We investigated whether the presence of the SARS-CoV-2 affected the dynamics of fecal microbial composition isolated in culture in moderate COVID-19 patients. Blood, stool, and medical records were collected from 50 patients with confirmed SARS-CoV-2 infection. Two samples were taken per patient, at disease onset (within 5 days) and after symptom resolution (30-35 days). The part of the gut microbiota identifiable using MALDI-TOF MS was analyzed, and inflammatory cytokines and blood markers were measured in serum. The analysis identified 566 isolates at the species level, including 83 bacterial and 9 fungal species. Our findings indicate a change in the gut microbiota composition isolated in culture during the initial phase of infection, characterized by the proliferation of opportunistic bacteria such as Enterococcus spp. and Citrobacter spp., at the expense of beneficial commensal bacteria from the genus Bacillus and Lactobacillus. Additionally, the enrichment of fungal pathogens in fecal samples collected 30 days after the cessation of disease symptoms might suggest a prolonged disruption of the gut microbiota even after the resolution of COVID-19 symptoms. This study contributes to a growing body of evidence on the systemic effects of SARS-CoV-2 and highlights the importance of considering gastrointestinal involvement in the management and treatment of COVID-19.

Epidemiology of Q Fever in Southeast Europe for a 20-Year Period (2002-2021).

This study aimed to assess epidemiological trends of Q fever in six countries of Southeast Europe by analysing surveillance data for 2002-2021 period. In this descriptive analysis, we collected and analysed data on confirmed human Q fever cases, obtained from the national Public Health Institutes of Bosnia and Herzegovina, Croatia, Greece, Montenegro, North Macedonia and Serbia. Overall, 2714 Q fever cases were registered during the 20-year period. The crude average annual notification rate was 0.82 (± 2.06) (95% CI: 0.47-1.16) per 100,000 inhabitants, ranged from 0.06 (± 0.04) (95% CI: 0.04-0.08) /100,000 in Greece to 2.78 (± 4.80) (95% CI: 0.53-5.02) /100,000 in the Republic of Srpska (entity of Bosnia and Herzegovina). Significant declining trends of Q fever age standardized rates were registered in Croatia, the Federation of Bosnia and Herzegovina, North Macedonia and Serbia, with an average annual change of -30.15%; -17.13%; -28.33% and - 24.77%, respectively. An unequal spatial distribution was observed. The highest average age-specific notification rate was reported in the 20-59 age group (0.84 (± 0.40) (95% CI: 0.65-1.02) /100,000). Most cases (53.69%) were reported during the spring. Q fever remains a significant public health threat in this part of Europe. The findings of this study revealed the endemic maintenance of this disease in the including countries, with large regional and subnational disparities in notification rates. A downward trend was found in Q fever notification rates across the study countries with the average notification rate higher than in the EU/EEA, during the same period.

Motives and attitudes of parents toward HPV vaccination: Results from the initial period of HPV vaccine rollout in Serbia.

Human papillomavirus (HPV) infection is one of the most common viral infections in sexually active population worldwide, and is the main cause of cervical cancer, which is the fourth most common cancer among women. Serbia ranks third in incidence and mortality rate of cervical cancer in Europe. We conducted a cross-sectional study considering parents' motivation for the HPV vaccination of their children. Statistical analysis included descriptive statistics and a logistic regression model. We found that the strongest motive was "Recommendation from paediatrician" (20.2%), followed by the attitude that HPV vaccine protects against cancers in different localization (15.4%), the motive "It is better to vaccinate a child than expose them to potential risk of HPV infection" (13.3%) and "Feeling anxiety due to a possible infection and cancer in the child" (13.1%). For those parents that vaccinated their child for some other strongest motive, reasons like "Vaccine is free of charge", "Recommendation from friends and family" and motive "My child received all obligatory vaccines, so I want to receive this one as well", were significantly more frequently selected. In the group where paediatricians' recommendation was not a motive for accepting the HPV vaccine, the largest percentage of parents (89.6%) selected motive "HPV vaccine protects against cancers in different localization" and the motive "It is better to vaccinate a child than expose them to potential risk of HPV infection" (78.1%). Paediatrician's recommendation is very important for parents' decision to vaccinate, however, other motives also influenced and had significance in making the parents' decision to vaccinate their children against HPV. Encouraging trust in public health authorities in Serbia, highlighting the advantages of the HPV vaccine and further encouraging healthcare workers to give stronger recommendations can increase the HPV vaccine uptake. Finally, we provided the basis to create more targeted messages that will empower parents to vaccinate their children.

Incidence, Risk, and Severity of SARS-CoV-2 Reinfections in Children and Adolescents Between March 2020 and July 2022 in Serbia.

Importance: During the COVID-19 pandemic, children and adolescents were massively infected worldwide. In 2022, reinfections became a main feature of the endemic phase of SARS-CoV-2, so it is important to understand the epidemiology and clinical impact of reinfections. Objective: To assess the incidence, risk, and severity of pediatric SARS-CoV-2 reinfection. Design, Setting, and Participants: This retrospective cohort study used epidemiologic data of documented SARS-CoV-2 infections from the surveillance database of the Institute for Public Health of Vojvodina. A total of 32 524 children and adolescents from Vojvodina, Serbia, with laboratory-confirmed SARS-CoV-2 infection between March 6, 2020, and April 30, 2022, were followed up for reinfection until July 31, 2022. Main Outcomes and Measures: Incidence rates of documented SARS-CoV-2 reinfection per 1000 person-months, estimated risk of documented reinfection 90 days or more after laboratory confirmation of primary infection, reinfection severity, hospitalizations, and deaths. Results: The study cohort included 32 524 children and adolescents with COVID-19 (mean [SD] age, 11.2 [4.9] years; 15 953 [49.1%] male), including 964 children (3.0%) who experienced documented reinfection. The incidence rate of documented reinfections was 3.2 (95% CI, 3.0-3.4) cases per 1000 person-months and was highest in adolescents aged 12 to 17 years (3.4; 95% CI, 3.2-3.7). Most reinfections (905 [93.9%]) were recorded in 2022. The cumulative reinfection risk was 1.3% at 6 months, 1.9% at 9 months, 4.0% at 12 months, 6.7% at 15 months, 7.2% at 18 months, and 7.9% after 21 months. Pediatric COVID-19 cases were generally mild. The proportion of severe clinical forms decreased from 14 (1.4%) in initial episodes to 3 (0.3%) in reinfections. Reinfected children were approximately 5 times less likely to have severe disease during reinfection compared with initial infection (McNemar odds ratio, 0.2; 95% CI, 0.0-0.8). Pediatric reinfections rarely led to hospitalization (0.5% vs 1.3% during primary infections), and none resulted in death. Conclusions and Relevance: This cohort study found that the SARS-CoV-2 reinfection risk remained substantially lower for children and adolescents compared with adults as of July 2022. Pediatric infections were mild, and reinfections were even milder than primary infections.

Epidemiological Characteristics of COVID-19 during Seven Consecutive Epidemiological Waves (2020-2022) in the North Backa District, Serbia.

The COVID-19 pandemic continues to pose a threat to global public health. The purpose of this research was to determine the epidemiological characteristics of COVID-19 in the North Backa district while observing seven pandemic waves. The cross-sectional study was based on data from the COVID-19 surveillance database of the Institute for Public Health of Vojvodina during the period from March 2020 to December 2022. A total of 38,685 primary infections and 4067 reinfections caused by SARS-CoV-2 were notified. Pandemic waves caused by the Delta variant (cumulative incidence rate of 2482.37/100,000) and by the Omicron variant (cumulative incidence rate of 2994.45/100,000) emerged as significant focal points during the surveillance period. Over the course of three consecutive years (2020-2022), women were more affected (50.11%, 54.03%, and 55.68%, respectively). The highest incidence rates in age-specific categories were recorded in 2021 for the age group 40-49 (1345.32 per 10,000 inhabitants), while in 2022, they shifted towards the elderly population. Regarding vaccination status at the time of diagnosis, in 2021, around 15% of patients were vaccinated, while in 2022, the number increased to 37%. The most widely received vaccine was BBIBP-CorV (67.45%), followed by BNT162b2 (19.81%), Gam-COVID-Vac (9.31%), and ChAdOx1 nCoV-19 (3.42%) vaccine. The implementation of stringent public health measures and their mitigation, together with the emergence of new variants, influenced the dynamics of COVID-19 pandemic waves in the North Backa district. Notably, throughout the study period, the working-age population was the most affected, along with females, with a mild clinical presentation dominating. Reinfections were most frequently recorded during the latter pandemic waves. Dealing with this pandemic has provided some valuable lessons for the development of future strategies in the case of a similar public health crisis.

Early Effectiveness of Four SARS-CoV-2 Vaccines in Preventing COVID-19 among Adults Aged ≥60 Years in Vojvodina, Serbia.

Real-world evidence of the vaccine effectiveness (VE) of different COVID-19 vaccines is needed in order to better shape vaccine recommendations and policies and increase vaccine acceptance, especially among vulnerable populations such as the elderly. We analyzed the early effectiveness of four COVID-19 vaccines, namely BNT162b2, BBIBP-CorV, Gam-COVID-Vac and ChAdOx1 nCoV-19 in population aged ≥60 years for symptomatic, mild and severe COVID-19, in the period January-April 2021 in Vojvodina, a northern province of Serbia. Incidence rates of SARS-CoV-2 infection were calculated using data from the provincial COVID-19 surveillance registry, and vaccination coverage data were obtained from the nationwide registry of administered COVID-19 vaccines. During the observation period, 134,535 subjects aged ≥60 years were fully vaccinated, of whom 87.7% received BBIBP-CorV, 7.1% BNT162b2 and 5.2% Gam-COVID-Vac vaccines. The estimated VE in fully vaccinated persons was 86.9% (95% CI, 86-87.7) for BBIBP-CorV, 95% (95% CI, 92.4-96.7) for Gam-COVID-Vac and 99% (95% CI, 97.8-99.5) for BNT162b2, while VE after the first dose of ChAdOx1 nCoV-19 was 88.6% (95% CI, 80.5-93.4). Estimates were similar when stratifying the analyses to severe and mild SARS-CoV-2 infections. Our analysis provides evidence of high early effectiveness of BNT162b2, BBIBP-CorV, Gam-COVID-Vac and ChAdOx1 nCoV-19 in elderly people in preventing symptomatic, severe and mild COVID-19 disease, particularly after being fully vaccinated.

Immunogenicity of BNT162b2, BBIBP-CorV and Gam-COVID-Vac vaccines and immunity after natural SARS-CoV-2 infection-A comparative study from Novi Sad, Serbia.

BACKGROUND: Mass vaccination is the key element in controlling current COVID-19 pandemic. Studies comparing immunogenicity of different COVID-19 vaccines are largely lacking. We aimed at measuring anti-S antibody (Ab) levels in individuals fully vaccinated with BNT162b2, BBIBP-CorV and Gam-COVID-Vac, as well as in COVID-19 convalescents. METHODS: In this cross-sectional study, serum was collected from 400 age- and sex-matched participants, 100 fully vaccinated with BNT162b2, 100 with BBIBP-CorV and 100 with Gam-COVID-Vac on the 28th day after the second vaccine dose, and 100 recovered from COVID-19 at least 28 days after symptom(s) resolution. Sera were analyzed using the LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy). Wilcoxon rank-sum or Kruskal-Wallis tests was used for comparison of Ab levels. RESULTS: Highest mean value (210.11, SD = 100.42) was measured in the BNT162b2 group, followed by Gam-COVID-Vac (171.11, SD = 120.69) and BBIBP-CorV (68.50, SD = 72.78) AU/mL (p<0.001). Significant differences in antibody levels were found between BNT162b2 and BBIBP-CorV (p<0.001), BNT162b2 and Gam-COVID-Vac (p = 0.001), as well as BBIBP-CorV and Gam-COVID-Vac groups (p<0.001). Percentage of seropositive was 81% in the convalescent group, 83% in BBIBP-CorV vaccinated and 100% in BNT162b2 and Gam-COVID-Vac. When comparing measured antibody levels in vaccinated to those in COVID-19 recovered, significantly higher antibody levels were found for vaccinated with BNT162b2 (p<0.001), and with Gam-COVID-Vac (p<0.001), while for BBIBP-CorV there was no statistically significant difference (p = 0.641). CONCLUSIONS: All three investigated vaccines, BNT162b2, BBIBP-CorV and Gam-COVID-Vac, provide robust immune response 28 days after the second dose of vaccine, in the majority of participants. All individuals vaccinated with BNT162b2 and Gam-COVID-Vac seroconverted, while in vaccinated with BBIBP-CorV and COVID-19 recovered seroconversion rates were lower. Although less potent compared to other two vaccines, immune response after BBIBP-CorV was similar to response measured in convalescents. Challenge still remains to examine dynamics and durability of immunoprotection.

Seroepidemiology of SARS-CoV-2 Virus in Healthcare Workers before Circulation of the Omicron Sublineages BA.4/BA.5 in Vojvodina, Serbia.

Healthcare workers (HCWs) are a vulnerable and critical population in the ongoing response to the SARS-CoV-2 pandemic. We aimed to estimate the seroprevalence in HCWs considering all of their previous contacts with the SARS-CoV-2 virus and/or the immunity acquired through their immunization against COVID-19 before the advent of the Omicron variants BA.4/BA.5. Serum samples were collected from 28 March to 10 June 2022. We covered 25% out of all the people who worked in some of the government healthcare centers (primary, secondary, and tertiary level) across the entire Autonomous Province of Vojvodina (Northern Serbia). Two serological tests (Anti-SARS-CoV-2 QuantiVac ELISA and LIAISON® SARS-CoV-2 TrimericS) were used to detect anti-spike IgG antibodies. The overall prevalence of the SARS-CoV-2 antibody among the 6936 HCWs was 92.96% [95% CI 92.33−93.55]. Regarding the type of serological test, there was a statistically significant (p = 0.0079) difference of the seropositivity obtained by the LIAISON® SARS-CoV-2 TrimericS (93.87%, 95% CI 92.97−94.69) and Anti-SARS-CoV-2 QuantiVac ELISA (92.23%, 95% CI 91.34−93.06) tests. Seropositivity to SARS-CoV-2 significantly (p < 0.0001) increased with the number of SARS-CoV-2 infections combined with the number of doses of the SARS-CoV-2 vaccines received. A vast majority of the HCWs in Vojvodina had detectable levels of antibodies to the spike protein of SARS-CoV-2, but despite this high seropositivity, it is unknown whether this herd immunity among HCWs is protective against the new variants of concern. Further research should evaluate the rates of reinfections and the associated severity of COVID-19 caused by the Omicron sublineages and/or new variants of SARS-CoV-2 among HCWs.

Pneumococcal carriage in adults aged 50 years and older in outpatient health care facility during pandemic COVID-19 in Novi Sad, Serbia.

BACKGROUND: Data related to carriage of Streptococcus pneumoniae (Spn) and antimicrobial resistance patterns in middle-aged and older adults are limited. We assessed the carriage of Spn, and its antibiotic resistance patterns, among participants ≥50 years of age living in the city of Novi Sad during the second year of COVID-19 pandemic. METHODS: Analysis of prospectively collected data among participants with or without symptoms of upper respiratory tract infection who visited their elected physicians in the Primary Health Care Centre of Novi Sad (outpatient facility) was conducted from May 18, 2021 to December 7, 2021. Both nasopharyngeal (NP) and oropharyngeal (OP) samples from each participant were collected. RESULTS: A total of 1042 samples from 521 study subjects (1 NP and 1 OP sample from each person) were collected. Sixteen samples from the same number of persons (3.1%, 95% confidence interval: 1.76%-4.94%) were culture positive for the presence of Spn. Overall, the median age of study participants was 71 years (range, 50-93 years; 90th percentile, 77 years), and most (197/521, 37.8%) of them were 70-79 years of age. A majority of the study subjects were: females (324/521; 62.2%), sampled during May and June 2021 (376/521, 72.2%), those who did not have contact with children aged 0-10 years in the family (403/521; 77.4%), without smokers in the household (443/521; 85.0%), and those who did not receive vaccine against Spn (519/521; 99.6%). Out of 16 Spn positive samples, for six participants, Spn carriage serotypes were obtained and there were four vaccine (6A, 11A, 15B, and 18C) serotypes, and two (6C and 35F) non-vaccine serotypes. Remaining 10 (62.50%) samples were non-typeable isolates of pneumococci. Among four vaccine serotypes, two (6A and 18C) were represented in PCV13, and 18C along with the other two (11A and 15B) in PPSV23 vaccine. The highest level of resistance of Spn isolates was observed for erythromycin, (10 or 62.50%), and tetracycline, (7 or 43.75%), one isolate showed resistance to penicillin, ampicillin, and amoxicillin/amoxicillin-clavulanic acid, while none of them were resistant to ceftriaxone, trimethoprim/sulfamethoxazole and levofloxacin. There were three multi-drug resistant isolates; one was identified as 6C (non-vaccine serotype), and two other were non-typeable isolates of Spn. CONCLUSIONS: In this first study conducted in Serbia on Spn carriage in adults ≥50 years of age, we found low prevalence of Spn carriage and identified 6 serotypes of Spn, four of which were represented in vaccines. These results may support future Spn colonization studies among middle-aged and older adults.

Immunogenicity of BNT162b2, BBIBP-CorV, Gam-COVID-Vac and ChAdOx1 nCoV-19 Vaccines Six Months after the Second Dose: A Longitudinal Prospective Study.

Many available SARS-CoV-2 vaccines demonstrated good humoral response, but studies directly comparing their immunogenicity in the general population are lacking. We evaluated the medium−term kinetics of anti-S SARS-CoV-2 antibodies (Abs) at one and six months after the second dose of BNT162b2, BBIBP-CorV, and Gam-COVID-Vac. Immunogenicity at six months was directly compared between BNT162b2, BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 nCoV-19. Participants ≥ 20 years old from Novi Sad, Serbia, without prior SARS-CoV-2 infection, were included. Anti S1/S2 IgG antibodies were measured using quantitative LIAISON SARS-CoV-2 assay. A total of 368 participants were included: 231 (62.77%) had sera collected at two time points. Two doses of BNT162b2 were received by 37.50% of participants, followed by BBIBP-CorV (22.01%), Gam-COVID-Vac (21.47%), and ChAdOx1 nCoV-19 (19.02%). Mean Ab levels at the 28th day and 6 months were 216.55 (SD = 105.73) AU/mL and 75.68 (SD = 57.30) for BNT162b2, 194.38 (SD = 140.24) and 90.53 (SD = 111.30) for Gam-COVID-Vac, and 72.74 (SD = 80.04) and 24.43 (SD = 38.43) for BBIBP-CorV group (p < 0.01, between two time points across all three groups), with a significant difference between women and men (p < 0.01, for both sexes). At the sixth month post-vaccination, the highest mean Ab level was detected in Gam-COVID-Vac group (91.28 AU/mL, SD = 95.96), followed by BNT162b2 (85.25 AU/mL, SD = 60.02), ChAdOx1 nCoV-19 (64.22 AU/mL, SD = 65.30), and BBIBP-CorV (25.26 AU/mL, SD = 36.92) (p < 0.01). Anti-spike IgG persistence was demonstrated six months post-vaccination with a significant decline in Ab levels. These results suggest a lower protection against SARS-CoV-2 over time. Our findings support the introduction of additional (booster) doses.

Pneumococcal nasopharyngeal carriage in children under 5 years of age at an outpatient healthcare facility in Novi Sad, Serbia during the COVID-19 pandemic.

Objectives: To assess whether pneumococcal nasopharyngeal carriage among children aged 24-60 months reduced during the coronavirus disease 2019 (COVID-19) pandemic in Novi Sad, Serbia, and to investigate the overall prevalence of carriage, serotype distribution and dominant serotypes 2-3 years after the introduction of pneumococcal conjugate vaccine 10. Design and methods: This prospective, observational study was conducted in February-March 2020, September-November 2020 and April-June 2021, enabling the comparison of results in the pre-pandemic/early pandemic period with two periods during the COVID-19 pandemic. Pneumococci were identified by standard microbiological methods. Serotype identification was performed using conventional multiplex polymerase chain reaction assays. Results: Among 1623 children tested, 515 (31.7%, 95% confidence interval 29.4-34.0%) carried pneumococci. A significant increase in prevalence was found between February-March 2020 and September-November 2020 (P=0.0085), with no difference found between September-November 2020 and April-June 2021 (P=0.0524). Pneumococcal colonization was significantly higher in children who were fully vaccinated and among children who attended day care centres. The dominant serotypes were 15B, 6B, 19F, 11A, 6C, 6A, 3, 23F and 19A, representing 66.4% of all isolates. Conclusions: This study found that pneumococcal nasopharyngeal carriage in children aged 24-60 months was high before the COVID-19 pandemic, and then increased during the pandemic. This rules out a major role of COVID-19 in the suppression of carriage and, probably, transmission.

COVID-19 Breakthrough Infections among Patients Aged ≥65 Years in Serbia: Morbidity and Mortality Overview.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 have shown effectiveness in the prevention of COVID-19. Breakthrough infections occur, and age has been shown to be one of the dominant risk factors for poorer outcome. This research focuses on characteristics of breakthrough infections in older adults. METHODS: This retrospective study was conducted for four months (March−June 2021) in the autonomous province of Vojvodina in Serbia on 11,372 patients using reverse-transcription polymerase chain reaction or antigen-detection rapid diagnostic tests verifying COVID-19 in those aged ≥65 years. Demographics, comorbidities, disease severity, and final outcomes were evaluated in fully vaccinated compared to unvaccinated individuals. Individuals were divided into younger-old (65−74 years) and older-old (≥75 years) age groups and differences between those groups were further evaluated. Binary logistic regression was performed to identify independent predictors of poor outcome. RESULTS: By the end of the research, 51.3% of the population of APV 65−74 years, as well as 46.2% of those older than 74 years, were vaccinated. From the acquired sample, 17.4% had breakthrough infection. Asymptomatic forms were higher in both age groups of vaccinated vs. unvaccinated (3.9%­younger-old, 6.3%­older-old vs. 2.9%­younger-old, 3.9%­older-old). The same results were registered with mild symptoms (82.1%­younger-old, 68.1%­older-old vs. 76.3%­younger-old, 57.5%­older-old) (p < 0.001). The case fatality ratio of the vaccinated population was smaller than the unvaccinated population in both groups (3.1% vs. 7.9%­younger-old; 11.4% vs. 22.5%­older-old) (p < 0.001). The odds ratio for poor outcome in unvaccinated individuals was 2.3 (95% confidence interval, p < 0.001) for the total sample. CONCLUSIONS: An increase in asymptomatic and mild forms, as well as decrease in severe or critical forms and poor outcomes, were noted in the vaccinated population. Choosing to avoid vaccination against SARS-CoV-2 may increase the chance of poor outcome in older individuals.

Risk and severity of SARS-CoV-2 reinfections during 2020-2022 in Vojvodina, Serbia: A population-level observational study.

Background: Data on the rate and severity of SARS-CoV-2 reinfections in real-world settings are scarce and the effects of vaccine boosters on reinfection risk are unknown. Methods: In a population-level observational study, registered SARS-CoV-2 laboratory-confirmed Vojvodina residents, between March 6, 2020 and October 31, 2021, were followed for reinfection ≥90 days after primary infection. Data were censored at the end of follow-up (January 31, 2022) or death. The reinfection risk was visualized with Kaplan-Meier plots. To examine the protective effect of vaccination, the subset of individuals with primary infection in 2020 (March 6-December 31) were matched (1:2) with controls without reinfection. Findings: Until January 31, 2022, 13,792 reinfections were recorded among 251,104 COVID-19 primary infections (5.49%). Most reinfections (86.77%, 11,967/13,792) were recorded in January 2022. Reinfections were mostly mild (99.17%, 13,678/13,792). Hospitalizations were uncommon [1.08% (149/13,792) vs. 3.66% (505/13,792) in primary infection] and COVID-19 deaths were very rare (20/13,792, case fatality rate 0.15%). The overall incidence rate of reinfections was 5.99 (95% CI 5.89-6.09) per 1000 person-months. The reinfection risk was estimated as 0.76% at six months, 1.36% at nine months, 4.96% at 12 months, 16.68% at 15 months, and 18.86% at 18 months. Unvaccinated (OR=1.23; 95%CI=1.14-1.33), incompletely (OR=1.33; 95%CI=1.08-1.64) or completely vaccinated (OR=1.50; 95%CI=1.37-1.63), were modestly more likely to be reinfected compared with recipients of a third (booster) vaccine dose. Interpretation: SARS-CoV-2 reinfections were uncommon until the end of 2021 but became common with the advent of Omicron. Very few reinfections were severe. Boosters may modestly reduce reinfection risk. Funding: No specific funding was obtained for this study.

Detection and Molecular Characterization of Rotavirus Infections in Children and Adults with Gastroenteritis from Vojvodina, Serbia.

Rotaviruses (RV) are the leading cause of gastroenteritis in infants, young children, and adults, responsible for serious disease burden. In the period 2012-2018, a cross-sectional study was conducted using stool samples collected from patients with acute gastroenteritis from Vojvodina, Serbia. We described age and gender distribution, as well as seasonal patterns of RV prevalence. Out of 1853 included stool samples, RV was detected in 29%. Hospitalized children between 1-2 years old were especially affected by RV infection (45%). The highest prevalence of infection was observed during the colder, winter/spring months. We compared sequenced representative G and P genotypes circulating in Serbia with vaccine strains and determined their genetic similarity. Genotype combination G2P[4] was the most prevalent (34.6%), followed by G2P[8] (24.1%) and G1P[8] (21.1%). Given that several epitopes were conserved, neutralization motifs among circulating strains can be characterized as sufficiently matching vaccine strains Rotarix™ and RotaTeq™, but existing antigenic disparities should not be overlooked. The present results contribute to a better insight into the prevalence of rotavirus infection in our region and point out the need for epidemiological surveillance of rotaviruses before the introduction of vaccines. These data can help formulate future vaccine strategies in Serbia.