Influenza surveillance in the Autonomous Province of Vojvodina, Serbia, over ten consecutive seasons (2015/16–2024/25): epidemiological trends, fatal case characteristics, and vaccination

Mioljub Ristić; Aleksandra Patić; Nataša Nikolić; Gordana Kovačević; Vladimir Petrović

doi:10.2298/VSP250901080R

Mioljub Ristić Institute of Public Health of Vojvodina, Novi Sad, Serbia University of Novi Sad, Faculty of Medicine, †Department of Epidemiology, Novi Sad, Serbia
Aleksandra Patić University of Novi Sad, Faculty of Medicine, ‡Department of Microbiology with Parasitology and Immunology, Novi Sad, Serbia
Nataša Nikolić *Institute of Public Health of Vojvodina, Novi Sad, Serbia; University of Novi Sad, Faculty of Medicine, ‡Department of Microbiology with Parasitology and Immunology, Novi Sad, Serbia
Gordana Kovačević *Institute of Public Health of Vojvodina, Novi Sad, Serbia
Vladimir Petrović *Institute of Public Health of Vojvodina, Novi Sad, Serbia; University of Novi Sad, Faculty of Medicine, †Department of Epidemiology, Novi Sad, Serbia

DOI: https://doi.org/10.2298/VSP250901080R

Keywords: covid-19;, epidemiology;, influenza, human;, respiratory tract infections;, serbia;, vaccination; virology.

Abstract

Background/Aim. Influenza represents a significant public health concern. The aim of this study was to analyze indicators of influenza activity over ten consecutive seasons in the Autonomous Province of Vojvodina (APV), Serbia, including age-specific and weekly distribution, and characteristics of influenza-related mortality. In addition, influenza vaccination trends in APV over the past ten seasons were assessed. Methods. A retrospective study was conducted using data from sentinel surveillance of influenza-like illness (ILI) and acute respiratory infections (ARI) among outpatients, as well as severe acute respiratory infection (SARI) and acute respiratory distress syndrome (ARDS) among hospitalized patients with fatal outcomes, along with data on the number of individuals vaccinated against influenza in APV. Laboratory confirmation of influenza-related deaths was performed at the Virology Center, Institute of Public Health of Vojvodina, Novi Sad, Serbia. Results. ILI and ARI incidence varied seasonally, peaking typically between surveillance weeks 5 and 10. The 2020/21 season showed markedly low influenza virus activity, while the 2021/22–2024/25 seasons displayed patterns typical of influenza seasons. Throughout the surveillance period, children aged 0–4 and 5–14 exhibited the highest incidence rates. Over the ten seasons, 202 laboratory-confirmed influenza-associated deaths were recorded, predominantly among men aged 24–64 years, occurring mainly during winter months. None of the patients had been vaccinated. The most common influenza A subtype was A (H1N1)pdm09 (59.4%). Fatal cases were almost evenly distributed between SARI (49.0%) and ARDS (51.0%), with ARDS being more common in adults aged 24–64 years. No statistically significant difference in the distribution of fatal outcomes was observed between the pre- and post-coronavirus disease 2019 periods (p = 0.6870). Influenza vaccination coverage among high-risk populations remained low, peaking at 17.5% among individuals ≥ 65 years in the 2020/21 season. Among healthcare workers, coverage reached over 40.0% in 2020/21 but declined to 20.0–25.0% in the subsequent seasons. Conclusion. Integrated sentinel and hospital-based surveillance encompasses monitoring of outpatient, severe, and fatal influenza cases. A significant increase in influenza vaccination coverage among high-risk groups could reduce hospitalization rates, the frequency of complications, and influenza-related deaths.

Author Biography

Nataša Nikolić, *Institute of Public Health of Vojvodina, Novi Sad, Serbia; University of Novi Sad, Faculty of Medicine, ‡Department of Microbiology with Parasitology and Immunology, Novi Sad, Serbia

Background/Aim. Influenza represents a significant public health concern. The aim of this study was to analyze indicators of influenza activity over ten consecutive seasons in the Autonomous Province of Vojvodina (APV), Serbia, including age-specific and weekly distribution, and characteristics of influenza-related mortality. In addition, influenza vaccination trends in APV over the past ten seasons were assessed. Methods. A retrospective study was conducted using data from sentinel surveillance of influenza-like illness (ILI) and acute respiratory infections (ARI) among outpatients, as well as severe acute respiratory infection (SARI) and acute respiratory distress syndrome (ARDS) among hospitalized patients with fatal outcomes, along with data on the number of individuals vaccinated against influenza in APV. Laboratory confirmation of influenza-related deaths was performed at the Virology Center, Institute of Public Health of Vojvodina, Novi Sad, Serbia. Results. ILI and ARI incidence varied seasonally, peaking typically between surveillance weeks 5 and 10. The 2020/21 season showed markedly low influenza virus activity, while the 2021/22–2024/25 seasons displayed patterns typical of influenza seasons. Throughout the surveillance period, children aged 0–4 and 5–14 exhibited the highest incidence rates. Over the ten seasons, 202 laboratory-confirmed influenza-associated deaths were recorded, predominantly among men aged 24–64 years, occurring mainly during winter months. None of the patients had been vaccinated. The most common influenza A subtype was A (H1N1)pdm09 (59.4%). Fatal cases were almost evenly distributed between SARI (49.0%) and ARDS (51.0%), with ARDS being more common in adults aged 24–64 years. No statistically significant difference in the distribution of fatal outcomes was observed between the pre- and post-coronavirus disease 2019 periods (p = 0.6870). Influenza vaccination coverage among high-risk populations remained low, peaking at 17.5% among individuals ≥ 65 years in the 2020/21 season. Among healthcare workers, coverage reached over 40.0% in 2020/21 but declined to 20.0–25.0% in the subsequent seasons. Conclusion. Integrated sentinel and hospital-based surveillance encompasses monitoring of outpatient, severe, and fatal influenza cases. A significant increase in influenza vaccination coverage among high-risk groups could reduce hospitalization rates, the frequency of complications, and influenza-related deaths.

References

World Health Organization. Vaccines against influenza WHO position paper – November 2012. Wkly Epidemiol Rec 2012; 47: 461–76.

Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 2018; 391(10127): 1285–300. Erratum in: Lancet 2018; 391(10127): 1262.

Fu X, Zhou Y, Wu J, Liu X, Ding C, Huang C, et al. A Severe Seasonal Influenza Epidemic During 2017–2018 in China Af-ter the 2009 Pandemic Influenza: A Modeling Study. Infect Microb Dis 2019; 1(1): 20–6.

World Health Organization Regional Office for the Eastern Mediter-ranean. Influenza surveillance. Geneva: WHO EMRO; 2025 [cited 2025 Aug 11; accessed 2025 Oct 10]. Available from: https://www.emro.who.int/health-topics/influenza/influenza-surveillance.html

World Health Organization. Global Influenza Surveillance and Response System (GISRS). Geneva: WHO; 2025 [cited 2025 Aug 11; accessed 2025 Oct 10]. Available from: https://www.who.int/initiatives/global-influenza-surveillance-and-response-system

Centers for Disease Control and Prevention (CDC). Monitoring for influenza viruses. Atlanta (GA): CDC; 2024 [cited 2025 Aug 11; accessed 2025 Oct 10]. Available from: https://www.cdc.gov/pandemic-flu/php/monitoring/index.html

Feldblyum TV, Segal DM. Seasonal and Pandemic Influenza Surveillance and Disease Severity. In: Shapshak P, Sinnott J, Somboonwit C, Kuhn J, editors. Global Virology I - Identifying and Investigating Viral Diseases. New York: Springer; 2015. pp. 761–89.

Chen Z, Yu H. Importance of integrating epidemiological and genomic surveillance of seasonal influenza viruses to monitor global circulation. Clin Transl Med 2024; 14(12): e70126.

Olsen SJ, Azziz-Baumgartner E, Budd AP, Brammer L, Sullivan S, Pineda RF, et al. Decreased Influenza Activity During the COVID-19 Pandemic - United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep 2020; 69(37): 1305–9.

Groves HE, Piché-Renaud PP, Peci A, Farrar DS, Buckrell S, Bancej C, et al. The impact of the COVID-19 pandemic on in-fluenza, respiratory syncytial virus, and other seasonal respira-tory virus circulation in Canada: A population-based study. Lancet Reg Health Am 2021; 1: 100015.

World Health Organization. Flu in the context of COVID-19. Geneva: WHO; 2021. [cited 2025 Aug 11; accessed 2025 Oct 10]. Available from: https://www.who.int/europe/news-room/questions-and-answers/item/q-a-on-flu-in-the-context-of-covid-19

Del Riccio M, Caini S, Bonaccorsi G, Lorini C, Paget J, van der Velden K, et al. Global analysis of respiratory viral circulation and timing of epidemics in the pre-COVID-19 and COVID-19 pandemic eras, based on data from the Global Influenza Surveillance and Response System (GISRS). Int J Infect Dis 2024; 144: 107052.

Sinnathamby M, Meslé M I, Mook P; The European Region Influenza Network Group Authorship; Pebody R, Bino S, et al. Im-pact of the COVID‐19 Pandemic on Influenza Circulation During the 2020/21 and 2021/22 Seasons, in Europe. Influ-enza Other Respir Viruses 2024; 18(5): e13297.

Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, et al. Predic-tion of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study. Lancet Glob Health 2022; 10(11): e1612–22.

Ristić M, Stojanović VD, Milošević V, Radovanov J, Dugandžija T, Bjelica A, et al. Surveillance of influenza in the post-pandemic period in Vojvodina, Serbia, October 2010 – May 2015. Srp Arh Celok Lek 2017; 145(7–8): 387–93.

Ristić M, Štrbac M, Medić S, Petrović V. Estimation of influenza activity in Vojvodina (Serbia) for five consecutive influenza seasons. Vojnosanit Pregl 2018; 75(6): 589–97.

Official Gazette of the Republic of Serbia. Rulebook on immuniza-tion and method of protection with drugs. Beograd: Službeni glasnik RS; 2017 [cited 2025 July 15; accessed 2025 Oct 10]. Available from: https://pravno-informacioni-sistem.rs/eli/rep/sgrs/ministarstva/pravilnik/2018/14/1 (Serbian)

Official Gazette of the Republic of Serbia. Rulebook on the Pro-gram of Mandatory and Recommended Population Immuniza-tion against Certain Infectious Diseases. Beograd: Službeni glasnik RS; 2020 [cited 2025 July 15; accessed 2025 Oct 10]. Available from: https://www.paragraf.rs/propisi/pravilnik-o-programu-obavezne-i-preporucene-imunizacije-stanovnistva-protiv-odredjenih-zaraznih-bolesti.html (Serbian)

Institute for Public Health of Serbia "Dr. Milan Jovanović Batut". Expert-methodological instructions for the implementation of mandatory and recommended immunization of the population for 2025. Beograd: Institut za javno zdravlje Srbije; 2024 [cit-ed 2025 Aug 8; accessed 2025 Oct 10]. Available from: https://www.batut.org.rs/download/SMU%20za%20sprovo%C4%91enje%20imunizacije%202025.pdf (Serbian)

Petrović V, Seguljev Z, Cosić G, Ristić M, Nedeljković J, Dragnić N, et al. Overview of the winter wave of 2009 pandemic influen-za A(H1N1)v in Vojvodina, Serbia. Croat Med J 2011; 52(2): 141–50.

Adlhoch C, Mook P, Lamb F, Ferland L, Melidou A, Amato-Gauci AJ, et al. Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021. Euro Surveill 2021; 26(11): 2100221.

Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, et al. Comparing SARS-CoV-2 with SARS-CoV and influ-enza pandemics. Lancet Infect Dis 2020; 20(9): e238–44.

Kuitunen I, Renko M, Tapiainen T. Unusual late epidemic peak during influenza season 2021-2022: A nationwide register-based analysis in Finland. Influenza Other Respir Viruses 2022; 16(6): 1199–201.

Emborg HD, Vestergaard LS, Botnen AB, Nielsen J, Krause TG, Trebbien R. A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain, Denmark, 2021/22 influenza season up to 25 March 2022. Euro Surveill 2022; 27(15): 2200278.

European Centre for Disease Prevention and Control (ECDC). Sea-sonal influenza 2022−2023. Annual Epidemiological Report for 2023. Stockholm: ECDC; 2023 [cited 2025 Aug 12; ac-cessed 2025 Oct 10]. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/seasonal-influenza-annual-epidemiological-report-2022-2023.pdf

Ben Moussa M, Nwosu A, Schmidt K, Buckrell S, Rahal A, Lee L, et al. National Influenza Annual Report 2023-2024: A focus on influenza B and public health implications. Can Commun Dis Rep 2024; 50(11): 393–9.

Bancej C, Rahal A, Lee L, Buckrell S, Schmidt K, Bastien N. Na-tional FluWatch mid-season report, 2021-2022: Sporadic in-fluenza activity returns. Can Commun Dis Rep 2022; 48(1): 39–45.

Rankin DA, Spieker AJ, Perez A, Stahl AL, Rahman HK, Stew-art LS, et al. Circulation of Rhinoviruses and/or Enterovirus-es in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US. JAMA Netw Open 2023; 6(2): e2254909.

Lin Q, Lim JYC, Xue K, Yew PYM, Owh C, Chee PL, et al. San-itizing agents for virus inactivation and disinfection. View (Beijing) 2020; 1(2): e16.

Ristić M, Patić A, Miljković A, Nikolić N, Gavanski G, Kovačević G, et al. Sentinel surveillance of acute respiratory infections and distribution of SARS-CoV-2, influenza A and B, and res-piratory syncytial virus in the post-COVID-19 period. Vojno-sanit Pregl 2025; 82(8): 490–503.

Lomholt FK, Emborg HD, Nørgaard SK, Nielsen J, Munkstrup C, Møller KL, et al. Resurgence of Respiratory Syncytial Virus in the Summer of 2021 in Denmark-a Large out-of-season Epi-demic Affecting Older Children. Open Forum Infect Dis 2024; 11(3): ofae069.

Baker RE, Park SW, Yang W, Vecchi GA, Metcalf CJE, Grenfell BT. The impact of COVID-19 nonpharmaceutical interven-tions on the future dynamics of endemic infections. Proc Natl Acad Sci U S A 2020; 117(48): 30547–53.

Morgan R, Klein SL. The intersection of sex and gender in the treatment of influenza. Curr Opin Virol 2019; 35: 35–41.

Jensen-Fangel S, Mohey R, Johnsen SP, Andersen PL, Sørensen HT, Ostergaard L. Gender differences in hospitalization rates for respiratory tract infections in Danish youth. Scand J Infect Dis 2004; 36(1): 31–6.

Robinson DP, Hall OJ, Nilles TL, Bream JH, Klein SL. 17β-estradiol protects females against influenza by recruiting neu-trophils and increasing virus-specific CD8 T cell responses in the lungs. J Virol 2014; 88(9): 4711–20.

Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep 2010; 59(33): 1057–62.

Centers for Disease Control and Prevention (CDC). Influenza Hos-pitalization Surveillance Network (FluSurv-NET). Atlanta (GA): CDC; 2023 [cited 2025 Aug 11; accessed 2025 Oct 10]. Available from: https://www.cdc.gov/fluview/overview/influenza-hospitalization-surveillance.html

Serino M, Melo N, Caldas JP, Ferreira A, Garcia D, Lourenço P. Predictors of severity and in-hospital mortality in patients with influenza. Monaldi Arch Chest Dis 2021; 92(1).

Drăgănescu AC, Miron VD, Streinu-Cercel A, Florea D, Vlaicu O, Bilaşco A, et al. Circulation of influenza A viruses among pa-tients hospitalized for severe acute respiratory infection in a tertiary care hospital in Romania in the 2018/19 season: Re-sults from an observational descriptive epidemiological study. Medicine (Baltimore) 2021; 100(52): e28460.

Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk for severe or complicated influenza ill-ness: systematic review and meta-analysis. BMJ 2013; 347: f5061.

Puig-Barberà J, Tormos A, Sominina A, Burtseva E, Launay O, Ci-blak MA, et al. First-year results of the Global Influenza Hos-pital Surveillance Network: 2012-2013 Northern hemisphere influenza season. BMC Public Health 2014; 14: 564.

Puig-Barberà J, Tormos A, Trushakova S, Sominina A, Pisareva M, Ciblak MA, et al. The Global Influenza Hospital Surveillance Network (GIHSN): a new platform to describe the epidemi-ology of severe influenza. Influenza Other Respir Viruses 2015; 9(6): 277–86.

Li Y, Wang LL, Xie LL, Hou WL, Liu XY, Yin S. The epide-miological and clinical characteristics of the hospital-acquired influenza infections: A systematic review and meta-analysis. Medicine (Baltimore) 2021; 100(11): e25142.

European Centre for Disease Prevention and Control (ECDC). In-fluenza virus characterization - Summary Europe, September 2024. Stockholm: ECDC; 2024 [cited 2025 Aug 14; accessed 2025 Oct 10]. Available from: https://www.ecdc.europa.eu/en/publications-data/influenza-virus-characterization-summary-europe-september-2024

Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009; 361(20): 1935–44.

Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza; Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010; 362(18): 1708–19. Erratum in: N Engl J Med 2010; 362(21): 2039.

Institute for Public Health of Vojvodina. Health status of the population of Vojvodina in 2020. Srbija: Institut za javno zdravlje Vojvodine; 2021. [cited 2025 August 15; accessed 2025 Oct 10]. Available from: https://izjzv.org.rs/?lng=lat&cir=0&link=4-21 (Serbian)

De la Cámara MÁ, Fernández de Larrea-Baz N, Pastor-Barriuso R, Larrauri A, Fernández-Navarro P, Pollán M, et al. Influenza Vaccination Coverage and Determinants of New Vaccinations During the COVID-19 Pandemic in Spain (ENE-COVID): Nationwide Population-Based Study. JMIR Public Health Surveill 2025; 11: e60658.

De Fougerolles TR, Baïssas T, Perquier G, Vitoux O, Crépey P, Bartelt-Hofer J, et al. Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives. BMC Public Health 2024; 24(1): 1222.

Scardina G, Ceccarelli L, Casigliani V, Mazzilli S, Napoletano M, Padovan M, et al. Evaluation of Flu Vaccination Coverage among Healthcare Workers during a 3 Years' Study Period and Attitude towards Influenza and Potential COVID-19 Vac-cination in the Context of the Pandemic. Vaccines (Basel) 2021; 9(7): 769.

Bianchi FP, Cuscianna E, Rizzi D, Signorile N, Daleno A, Migliore G, et al. Impact of COVID-19 pandemic on flu vaccine up-take in healthcare workers in Europe: a systematic review and meta-analysis. Expert Rev Vaccines 2023; 22(1): 777–84.

Petrović V, Šeguljev Z, Nedeljković J, Ristić M. Seroprevalence study in Vojvodina (Serbia) following 2009 pandemic influen-za A(H1N1)V. Srp Arh Celok Lek 2012; 140(11–12): 751–5.

Radovanov J, Milošević V, Hrnjaković I, Petrović V, Ristić M, Elez I, et al. Influenza A and B Viruses in Population of Vojvodina, Serbia. Arch Biol Sci 2014; 66(1): 43–50.

Ristić M, Petrović V. Evaluation of the diagnostic utility of case definitions to detect influenza virus infection in Vojvodina, Serbia. Srp Arh Celok Lek 2020; 148(1–2): 100–5.

Radovanov J, Ristic M, Medic S, Kovacevic G, Dopud N, Nikolic N, et al. Genetic variability of the neuraminidase gene of influen-za A(H1N1)pdm09 viruses circulating from the 2012/2013 to 2017/2018 season in Vojvodina Province, Serbia. Mol Cell Probes 2020; 52: 101557.

Radovanov J, Hrnjaković-Cvjetković I, Nikolić N, Jovanović-Galović A, Kovačević G, Patić A, et al. Risk factors for severe influenza A virus infections in post-2009 pandemic period. Srp Arh Celok Lek 2016; 144(11–12): 626–32.

Miljković A, Patić A, Petrović V, Nikolić N, Kovačević G, Pustahija T, et al. Diagnostic Significance of Influenza Symptoms and Signs, and Their Variation by Type/Subtype, in Outpatients Aged ≥ 15 Years: Novi Sad, Serbia. Viruses 2025; 17(2): 272.