WHO: Influenza Update N° 531
Published 18 June 2025 | For reporting Week 23, ending 08 June 2025
In the Southern hemisphere, influenza positivity continued to increase and was moderate to high (above 20%) in a few countries of Temperate South America (predominantly A(H1N1)pdm09). Influenza positivity was elevated (>10%) in countries of Tropical and Temperate South America (predominantly A(H1N1)pdm09), Southern Africa (predominantly A(H3N2)), Eastern Africa (predominantly A(H3N2)), South-East Asia (predominantly A(H3N2)) and Oceania (predominantly A(H1N1)pdm09).
In the Northern hemisphere, influenza activity remained stable or continued to decline in most countries with increases reported from a single country in Western Africa. Influenza positivity remained elevated in Central America and the Caribbean, Tropical South America and Western Africa (predominantly A(H1N1)pdm09), and Western, Southern and South-East Asia (predominantly A(H3N2)). Read More
Changes in influenza-associated excess mortality in China between 2012–2019 and 2020–2021: a population-based statistical modelling study
Infect Dis Poverty 2025;14,:52. https://doi.org/10.1186/s40249-025-01323-7
The seasonal cycle of the influenza virus causes substantial morbidity and mortality globally. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the circulation of influenza viruses can influence influenza-associated excess mortality. Given the few studies that have explored this topic, the objective of this study was to evaluate influenza-associated excess mortality in the Chinese mainland from 2012 to 2021 and quantify the changes from 2020 to 2021 compared with 2012–2019. Using data from national influenza surveillance report and disease surveillance points, the authors fitted a generalized additive model on all-cause (AC), pneumonia & influenza (P&I), and respiratory (R) mortality rates. In this model, we included data of influenza activity (A/H1N1, A/H3N2 and B), temperature, absolute humidity, the COVID-19 pandemic, and time trends. The excess mortality was estimated by subtracting the fitted baseline mortality from the predicted mortality, which set influenza activity to zero. The respiratory mortality model explained more than 90% of the variance, indicating the good performance. We found that the influenza-associated mortality was generally decreasing from 2020 to 2021, for instance, influenza A/H1N1-associated excess respiratory mortality (ERM) decreased from 2.62 per 100,000 persons (95% confidence interval: 0.16–5.21) to 0.31 (0.02–0.60) in the northern region and from 3.79 (0.09–7.05) to 0.24 (0.02–0.46) in the southern region between 2012–2019 and 2020–2021. A similar pattern was observed for A/H3N2-associated ERM. While the influenza B remained similar scale, for instance, the ERM was 2.90 (0.72–4.3) and 2.26 (1.76–2.76) in the southern region between 2012–2019 and 2020–2021, respectively. Distinct pattern was observed for the AC and P&I outcomes.
The authors concluded that the COVID-19 pandemic has reduced influenza-associated excess mortality, which may be a result of the reduced activity of the influenza virus caused by nonpharmaceutical interventions. Different patterns of regional differences differed for influenza-associated AC, P&I and R mortality. It should be noticed that the contribution of influenza B was generally similar when comparing 2012–2019 and 2020–2021, which highlighted the attention on the influenza B activity. Additional studies are needed to explore the changes in influenza-associated excess mortality afterwards. Read More
Portable lab-on-a-chip platform enabling multiplex recombinant enzyme polymerase amplification detection of H5/H7/H10 avian influenza virus subtypes
Poultry Science Available online 19 June 2025, 105463
The zoonotic nature of influenza pathogens creates substantial health security risks, jeopardizing the welfare of interconnected human and animal ecosystems. The H5/H7/H10 avian influenza virus (AIV) variants demonstrate persistent endemicity in poultry reservoirs and recurrent zoonotic jumps precipitating fatal human infections. Therefore, the innovation of multiplex diagnostic platforms integrating expedited processing, enhanced sensitivity, and subtype-specific discrimination has emerged as a pivotal strategy to curb epidemiological escalation. This research introduces a portable diagnostic device that uses temperature control and miniaturized fluid channels to detect and distinguish between H5, H7, and H10 bird flu subtypes at the same time. Based on the conserved sequences of the hemagglutinin (HA) gene of H5, H7, and H10 AIVs, three sets of primers and probes specific to the subtypes were developed. These were then combined with microfluidic microarray technology and a rapid gene-based amplification method that boosts detection accuracy. This combination aimed to create a method for the simultaneous detection of H5, H7, and H10 AIVs for differential diagnostic purposes. The method was distinguished by its specificity, sensitivity, accuracy, and its ability to detect these viruses in clinical samples. The specificity of the method showed that it could detect all strains of H5, H7 and H10 AIVs at the same time, with no cross-reactivity with other subtype influenza viruses or other avian pathogens. The the test was highly sensitive, able to detect very small amounts of the virus — as low as 2 copies per sample. The results of this method for 100 clinical samples were consistent with those produced by quantitative PCR. This integrated detection system for H5/H7/H10 AIV differentiation exhibits exceptional specificity, enhanced sensitivity, rapid turnaround, and streamlined operational procedures, representing a viable solution for prompt pathogen identification during outbreaks. Read More
Multivalent COBRA Hemagglutinin and Neuraminidase Influenza Vaccines Adjuvanted with TLR9 Agonist CpG 1018
Vaccines 2025, 13(7), 662; https://doi.org/10.3390/vaccines13070662
There is a need for effective seasonal influenza virus vaccines that provide broad and long-lasting protection against influenza virus infections. Methods: In this study, next-generation influenza hemagglutinin (HA) and neuraminidase (NA) vaccine candidates designed using the computationally optimized broadly reactive antigen (COBRA) methodology were formulated with the TLR9 agonist, CpG 1018. These adjuvanted COBRA HA/NA vaccines were administered intramuscularly or intranasally to mice with pre-existing anti-influenza immunity or immunologically naïve mice. Mice with pre-existing immune responses to historical influenza virus strains vaccinated intranasal (IN) with COBRA HA/NA vaccines adjuvanted with CpG 1018 had enhanced IgG titers in their bronchoalveolar lavages (BALF) compared to unadjuvanted vaccines. These mice also had increased serum IgG titers that were like antibody titers observed in mice that were vaccinated intramuscularly. Mice that were vaccinated intranasally with this adjuvanted vaccine also had antibodies with significantly higher hemagglutination inhibition activity against a broad range of H1N1 and H3N2 influenza viruses and more HA and NA specific antibody-secreting cells compared to unadjuvanted vaccine. Following the H1N1 influenza virus challenge, pre-immune mice that were vaccinated with the COBRA HA/NA vaccine with CpG 1018 were protected from morbidity and mortality and had no detectable viral lung titers. The authors conclude that overall, CpG 1018 adjuvanted COBRA HA/NA elicited enhanced protective antibodies compared to the unadjuvanted vaccine against several drifted H1N1 and H3N2 influenza viruses in pre-immune mice that were either intramuscularly or intranasally vaccinated with a balanced Th1/Th2 immune response. Read More
Global spread of H3 subtype avian influenza viruses with an accelerated evolution after interspecies transmission
Journal of Infection 2025; Published June 20, 2025:106542
The H3 subtype avian influenza virus (AIV) has been widely spread in birds and known as a natural source of mammalian influenza viruses. Based on data from public databases and our surveillance data, we analysed the ecology, evolution, and spread of H3 AIVs. Sublineages of H3 AIVs have been detected worldwide, infecting various birds, at least 90 species in wild birds and poultry. Important areas for large-scale and local dissemination of H3 AIVs were identified, such as Alaska, Central Asia, and Chinese provinces. The H3 viruses have elevated the HA gene substitution rate after introduction from wild birds to domestic poultry, and even faster in domestic chickens. Our results implied an evolutionary mechanism of H3 AIV cross-species transmission, that viruses from wild birds to domestic poultry have accelerated substitution rate by shorter generation time and host selection. Novel chicken H3 viruses, especially H3N8 G25 viruses that have spilled over to humans, require high attention. Read More
Vitamin D and Influenza: Immunological Insights and Therapeutic Potential for Respiratory Health
Nutrition Reviews, 2025;, nuaf086, https://doi.org/10.1093/nutrit/nuaf086
Influenza remains a significant global public health challenge, consistently contributing to high morbidity and mortality rates. Emerging research suggests that vitamin D plays a crucial role in modulating immune responses, a finding that may have implications for the prevention and control of influenza. In this review we explored the mechanisms through which vitamin D enhances both innate and adaptive immunity, emphasizing its role in managing inflammation and antiviral defenses, and we explored the current research on the immunomodulatory effects of vitamin D, highlighting its potential protective benefits against respiratory infections like influenza. Vitamin D, immunological modulation, influenza, viral infections, cytokine regulation, innate immunity, adaptive immunity, and respiratory viruses were among the keywords used, either singly or in combination, to search the PubMed, Web of Science, Scopus, and Google Scholar databases for this research. The inclusion criteria were full-length research publications published within the previous 12 years, observational studies, in vitro studies, and studies involving humans or animals, with the exception of groundbreaking earlier works that provided fundamental insights into the function of vitamin D in immunity. The capacity of vitamin D to regulate cytokine production, boost antimicrobial peptide activity, and influence cellular immune responses may help mitigate the severity of influenza infections and related complications, such as cytokine storms. Evidence from randomized trials and observational studies further supports the role of vitamin D supplementation in reducing the incidence and severity of influenza. Although these findings highlight the therapeutic promise of vitamin D for influenza management, further investigation is needed to address existing knowledge gaps before making clear recommendations for the use of vitamin D in viral respiratory infections. Read More
Influenza vaccination coverages in Italy from 1999/00 to 2023/24: a joinpoint regression analysis
Journal of Infection and Public Health. Available online 18 June 2025, 102875
Influenza is a contagious respiratory viral infection with significant health and economic impacts, causing millions of cases and hundreds of thousands of deaths annually worldwide. In Italy, annual epidemics affect approximately 8% of the population. Vaccination remains the most effective prevention strategy, yet coverage in Italy is low and consistently below the WHO-recommended threshold of 75% in elderly. This study aims to analyze trends in influenza vaccination coverage in Italy from 1999/2000 to 2023/2024 through joinpoint regression analysis. Data on influenza vaccination coverage were obtained from the Italian Ministry of Health, covering the general population and specific age groups. The analysis included data from the 1999/2000 season to the 2023/2024 season. Joinpoint regression was used to identify significant changes in coverage trends over time, calculating Annual Percentage Change (APC) and Average Annual Percent Change (AAPC). Coverages vary between and within age groups over the study period. The pediatric population showed the lowest values, never exceeding 10% except for the COVID-19 pandemic years. Similar trends, albeit with higher coverage, were observed in the adult population. In the elderly population, the WHO target of 75% was never reached, obtaining the highest value of 68.3% in 2005/2006. Trends show increasing AAPC coverages for all groups except 15-17 years. During the pandemic, increases in coverages are observed in all age groups, but these decline to pre-pandemic values during the following seasons. The authors conclude that vaccination coverage in Italy falls below target thresholds, particularly in high-risk age groups, with a significant decreasing trend observed in the years following the pandemic across almost all age groups. Despite the proven efficacy and safety of the vaccine, hesitancy has gained momentum in Italy, resulting in persistently low coverage rates. Our findings highlight the need for a multifaceted approach, including expanding free vaccination programs, implementing school-based initiatives, strengthening healthcare worker engagement, and enhancing public awareness campaigns. Read More
Recombinant quadrivalent influenza vaccine (RIV) induces robust cell-mediated and HA-specific B cell humoral immune responses among healthcare personnel
Vaccine Volume 61, 13 August 2025, 127361
Egg-free influenza vaccines, specifically cell culture-based inactivated influenza vaccine (ccIIV) and recombinant influenza vaccine (RIV), represent a significant advancement over traditional egg-based inactivated influenza vaccines (IIV), particularly for populations with extensive vaccination histories. This comprehensive immunological study investigated the comparative efficacy of ccIIV, IIV, and RIV in healthcare personnel (HCP) with repeated vaccination histories, examining both cellular and humoral immune responses through multiple analytical approaches. Our investigation employed a multi-faceted analytical framework, combining serological assessments via hemagglutination inhibition (HI) and microneutralization (MN) assays with detailed cellular immune response analysis. We utilized advanced flow cytometry techniques with recombinant hemagglutinin (HA) probes to evaluate both circulating specialized immune cells that help the body produce antibodies after vaccination. The results revealed RIV’s superior immunogenicity profile, demonstrating significantly elevated levels of both cTfh and HA-specific B cells compared to ccIIV and IIV. RIV’s enhanced performance was particularly evident in its response to influenza A components, with notably higher immunogenicity against both A(H3N2) and A(H1N1) strains. This superiority was reflected in higher levels of protective antibodies and stronger immune responses. compared to traditional vaccines. While RIV also demonstrated enhanced HA-specific B cell responses against influenza B components compared to ccIIV, interestingly, HI titers remained comparable across all vaccine groups for these strains. These findings underscore the critical importance of comprehensive immune response evaluation in vaccine assessment. The disparity between cellular and serological responses, particularly for influenza HA-specific B cells, highlights that traditional serological measures alone may not fully capture the breadth and depth of vaccine-induced immunity. The findings suggest that evaluating how well vaccines activate immune cells — not just antibodies — is important for understanding their effectiveness. Read More
The Influence of the COVID-19 Pandemic on Influenza Vaccination Refusal and Patient Satisfaction.
Open Forum Infectious Diseases Accepted Manuscript 2025; Available online.
The authors retrospectively analyzed influenza vaccination records of adult primary care patients in Southwestern Minnesota during two 3-year phases: Pre-Pandemic (1/1/2017—2/28/2020) and Pandemic-Plus (3/1/2020—12/31/2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently vaccinated” (IV) for seasonal influenza. Standardised patient experience surveys were used to determine patient dissatisfaction. In the Pandemic-Plus phase, 7.0% (n=3,556) of the Pre-Pandemic AV and 48.7% (n=16,710) of the Pre-pandemic IV never received another influenza vaccine. Compared to AV, IV and NV patients were more likely to reside in areas with greater socioeconomic deprivation [odds ratio (95% confidence interval): 1.58 (1.53-1.62); 1.99 (1.94—2.05), respectively], have a high school education or less [2.86 (2.74-2.98); 3.38 (3.23-3.53)], and report greater healthcare disengagement [1.59 (1.55-1.64); 4.21 (4.09-4.33)]. After adjusting for area deprivation index and medical comorbidities, the odds ratio of healthcare disengagement increased among the NV versus AV between phases [3.33 (3.24-3.41); 4.23 (4.10-4.35)]. In a multivariable subgroup analysis of patients who completed satisfaction surveys, those with severe health comorbidities were less likely AV [NV vs AV 1.21 (1.14-1.27)] and more likely to report healthcare dissatisfaction [NV vs AV 1.25 (1.18-1.33)]. The authors conclude that the COVID-19 pandemic altered vaccination behaviors and healthcare satisfaction, especially among those at high risk of developing influenza-related complications. Medical providers and public health officials should be aware of factors associated with vaccine refusal to better target interventions. Read More
Low and inequitable influenza and COVID-19 vaccination coverage among pregnant women in Norway: Nationwide population-based cohort study
Vaccine 2025; 13 August, 2025, 127386
Many countries recommend vaccination against influenza and COVID-19 during pregnancy, but surveillance of coverage is often lacking. In this sudy the authors aim to quantify nationwide coverage of influenza and COVID-19 vaccination during pregnancy in Norway and identify its sociodemographic correlates. They combined nationwide individual-level registry data on childbirth, vaccinations and sociodemographic factors for all pregnancies in Norway between 1 September 2021 and 31 December 2022. They estimated maternal influenza and COVID-19 vaccination coverage and its correlates among women whose only indication for vaccination was pregnancy, i.e., during the second and third trimester.
Among 52,833 women eligible for influenza vaccination during pregnancy in the 2021/2022 influenza season, 27.7 % (n = 14,646) received the influenza vaccine. Similarly, among 50,108 women eligible for COVID-19 vaccination during pregnancy in the study period, 31.8 % (n = 15,951) received the COVID-19 vaccine. Coverage estimates were lower among mothers with immigrant background, low education, low income, low maternal age, multiple children, those living rurally and those outside the workforce. The lowest coverage was observed among immigrant women (14.5 % for influenza, 16.0 % for COVID-19 vaccination), with corresponding relative risks (RR) compared to native Norwegian women of 0.44 (95 % CI: 0.42, 0.46) and 0.41 (95 % CI: 0.39, 0.43). The highest coverage was observed among women with the highest education (38.2 % for influenza, 43.6 % for COVID-19), with corresponding RRs compared to women with the lowest education of 2.47 (95 % CI: 2.33, 2.62) and 2.36 (95 % CI: 2.24, 2.49). The authors conclude that the coverage of maternal vaccination against influenza and COVID-19 is insufficient. Additionally, there is high and consistent inequity in uptake. Timely and comprehensive surveillance of maternal vaccination programs should be prioritized to ensure that program performance can be adequately assessed and improved. Read More