Global, regional, and national burden of influenza-associated lower respiratory infections, 1990–2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality, with influenza viruses being a significant cause. Despite advances in vaccination and antiviral therapies, the burden of influenza-associated LRIs remains high, particularly in low-income regions and high-risk populations. Understanding long-term trends and regional disparities is crucial for developing effective prevention strategies. METHODS: Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed age-standardized mortality rates (ASMR), and disability-adjusted life years (DALYs) for influenza-associated LRIs across 21 global regions and 204 countries and territories from 1990 to 2021. Joinpoint regression was utilized to analyze temporal trends in the disease burden of influenza-associated LRIs. The relationship between influenza-associated LRIs burden and the socio-demographic index (SDI) was examined using a smoothing spline model. Frontier analysis was employed to estimate achievable outcomes based on development levels. RESULTS: Globally, ASMR declined from 5.87 (95% UI: 5.33-6.40) per 100,000 population in 1990 to 1.30 (0.98-1.66) per 100,000 population in 2021, with an average annual percent change (AAPC) of -0.69% (1990-2019) and - 49.74% (2019-2021). Despite declining rates, absolute deaths increased by 0.85% annually from 1990 to 2019, reflecting population growth and aging. In 2021, Central Sub-Saharan Africa had the highest ASMR (10.84/100,000 population) and ASDR (271.71/100,000 population), while high SDI regions (e.g., High-income Asia Pacific) approached near-zero mortality. Age-specific analysis revealed bimodal burdens: children under 5 and adults ≥ 70 years faced the highest risks. CONCLUSIONS: Influenza-associated LRIs remain a significant global health challenge, particularly in low-income and high-risk populations. While global trends indicate progress, regional disparities and the impact of demographic factors highlight the need for tailored interventions. Targeted strategies-including equitable vaccine access, healthcare system strengthening, and integrated surveillance-are critical to mitigating burden in high-risk regions and populations.