Respiratory infections are a leading cause of morbidity and mortality among children under the age of five, particularly in low- and middle-income countries [1]. Among these infections, seasonal influenza plays a significant role, contributing to a substantial global health burden [2]. Influenza, a highly contagious viral infection, affects millions of children annually, leading to widespread illness, hospitalizations, and, in severe cases, death. Young children are especially vulnerable due to their immature immune systems and limited prior exposure to influenza viruses [3] 

Despite the availability of vaccines and antiviral treatments, the burden of seasonal influenza in children under five remains a pressing public health challenge [4]. The clinical manifestations of influenza in this age group are often nonspecific, mimicking other respiratory infections, which complicates timely diagnosis and management [5]. Furthermore, influenza in children is associated with a high risk of complications, including pneumonia, otitis media, and secondary bacterial infections, contributing to the overall disease severity [6].

Globally, the impact of seasonal influenza is uneven, with disproportionate effects observed in resource-limited settings [7]. These regions often lack robust surveillance systems, limiting the accurate assessment of the disease burden and hindering the implementation of effective prevention and control measures [8]. This disparity underscores the need for a comprehensive understanding of the global burden of respiratory infections caused by seasonal influenza in this vulnerable population [9].

This review aims to synthesize current evidence on the epidemiology, clinical impact, and management of seasonal influenza in children under five years of age. By highlighting the challenges, gaps, and future directions, we hope to inform strategies that can mitigate the impact of this significant public health issue and improve outcomes for affected children worldwide [10].

Epidemiology and Global Burden

Seasonal influenza remains a significant contributor to the global burden of respiratory infections, particularly among children under the age of five [11]. Influenza epidemics occur annually, with varying severity influenced by the circulating viral strains, regional vaccination coverage, and healthcare infrastructure [12]. Understanding the epidemiology and burden of seasonal influenza is essential to designing effective prevention and management strategies for this vulnerable age group.

Global Prevalence and Incidence

Worldwide, an estimated 5–10% of adults and 20–30% of children are affected by influenza annually, with children under five years experiencing the highest attack rates [13]. Among this group, the annual incidence of influenza-associated respiratory infections ranges from 90 million to 150 million cases, as reported by the World Health Organization (WHO) [14]. The burden is particularly pronounced in developing countries, where a lack of access to vaccines and healthcare contributes to higher morbidity and mortality [15].

Studies have consistently shown that children under five years, especially infants under two years, are at increased risk of severe outcomes [16]. For instance, a global meta-analysis estimated that seasonal influenza causes approximately 870,000 hospitalizations and 28,000–111,500 deaths annually in this age group [17]. The burden is significantly higher in low-resource settings due to delayed diagnosis, limited treatment options, and inadequate vaccination coverage [18].

Regional Disparities

The burden of seasonal influenza varies markedly between high-income and low-income countries. In high-income countries, widespread vaccination programs and advanced healthcare systems contribute to lower mortality rates [19]. Conversely, in low- and middle-income countries (LMICs), the lack of comprehensive surveillance and vaccination coverage amplifies the disease burden [20]. For example, sub-Saharan Africa and Southeast Asia report some of the highest rates of influenza-associated morbidity and mortality in children under five [21]. In these regions, coexisting malnutrition, high rates of respiratory comorbidities, and limited healthcare infrastructure exacerbate the risk [22].

Mortality and Morbidity

Seasonal influenza is a significant cause of severe respiratory illness in children under five, often resulting in hospitalizations. According to WHO estimates, influenza-associated respiratory infections rank among the top causes of hospitalization in this demographic, with approximately 10%–15% of all acute respiratory infections attributed to influenza [23]. Additionally, influenza is a major contributor to pediatric intensive care unit (PICU) admissions, with complications such as viral pneumonia, secondary bacterial infections, and acute respiratory distress syndrome (ARDS) [24].

Globally, mortality due to seasonal influenza in children under five is concentrated in regions with limited healthcare access. For instance, studies from LMICs report case-fatality rates up to 10 times higher than those in high-income countries [25].

Diagnosis and Surveillance Systems

Current Diagnostic Methods

Diagnosing seasonal influenza in children under five involves clinical assessment and laboratory testing. Clinical diagnosis is often based on the presence of common symptoms such as fever, cough, and nasal congestion. However, these symptoms overlap with other respiratory infections, making laboratory confirmation essential for accurate diagnosis [1].

• Rapid Influenza Diagnostic Tests (RIDTs): RIDTs detect influenza antigens within 15–30 minutes, making them a convenient option in clinical settings. While their speed is advantageous, these tests have moderate sensitivity (50–70%) and high specificity, leading to a risk of false-negative results, particularly during low influenza activity periods [2].
• Reverse Transcriptase Polymerase Chain Reaction (RT-PCR): RT-PCR is considered the gold standard for influenza diagnosis due to its high sensitivity and specificity. It can identify and differentiate between influenza types and subtypes. However, its use is limited in resource-constrained settings due to high costs, the need for specialized equipment, and longer turnaround times [3].
• Other Methods: Viral culture and immunofluorescence are less commonly used in routine diagnostics but are valuable in research and surveillance to monitor viral evolution and resistance patterns [4].

Challenges in Diagnosing Influenza in Children

Diagnosing influenza in children under five presents unique challenges. Infants and young children often exhibit nonspecific symptoms such as irritability, poor feeding, or lethargy, which can delay diagnosis [5]. Additionally, co-infections with other pathogens like respiratory syncytial virus (RSV) or bacterial pneumonia can obscure the clinical picture, further complicating diagnosis [6].

Resource limitations in low- and middle-income countries exacerbate these challenges, as access to advanced diagnostic tools like RT-PCR is often unavailable. Over-reliance on clinical diagnosis or RIDTs in such settings may lead to underdiagnosis or misdiagnosis, hindering appropriate treatment and prevention efforts [7].

Role of Surveillance in Understanding the Burden

Surveillance systems are critical for monitoring the burden of seasonal influenza and guiding public health interventions. The World Health Organization (WHO) coordinates the Global Influenza Surveillance and Response System (GISRS), which collects and analyzes data from over 100 countries [8]. Surveillance activities include tracking circulating strains, assessing vaccine effectiveness, and identifying potential pandemic threats.

In many low-resource settings, surveillance infrastructure is inadequate, resulting in underreporting and a lack of reliable data on influenza burden. Strengthening surveillance systems in these regions is essential to provide accurate burden estimates, inform vaccine formulation, and guide resource allocation [9]. Integrating influenza surveillance into existing respiratory disease monitoring programs can improve data collection and ensure sustainable operations [10].

Prevention and Management Strategies

Vaccination

Vaccination is the cornerstone of preventing seasonal influenza in children under five, significantly reducing the risk of severe illness, hospitalization, and death [1]. Current influenza vaccines include inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). These vaccines are formulated annually to match circulating strains, ensuring optimal efficacy.

• Efficacy and Coverage in Children Under 5: Studies suggest that influenza vaccines reduce the risk of laboratory-confirmed influenza by 40–60% in children under five, depending on the vaccine match to circulating strains [2]. However, vaccine efficacy is lower in children under two years, highlighting the need for improved formulations or adjunctive interventions [3]. Despite the proven benefits, vaccination coverage remains suboptimal, with only 30–50% of eligible children vaccinated annually in many regions [4].
• Global Vaccination Programs and Success Rates: Initiatives such as the WHO’s Global Influenza Strategy aim to improve vaccine access in low- and middle-income countries (LMICs) [5]. High-income countries report better vaccination rates due to established immunization programs, while LMICs face challenges related to cost, logistics, and vaccine hesitancy [6]. Targeted campaigns during peak influenza seasons have shown promise in increasing coverage.

Antiviral Treatments

Antiviral medications, such as oseltamivir and zanamivir, play a crucial role in managing influenza, especially in severe cases or high-risk populations.

• Availability and Limitations: Oseltamivir, a neuraminidase inhibitor, is the most commonly used antiviral, effective in reducing symptom severity and duration when administered within 48 hours of onset [7]. However, access to antivirals is limited in LMICs due to high costs and insufficient healthcare infrastructure. Resistance to antivirals is also an emerging concern, necessitating the development of new drugs [8].

Supportive Care

Supportive care remains essential in managing influenza in children under five, especially in resource-limited settings.

• Role of Healthcare Access and Infrastructure: Access to healthcare facilities capable of providing oxygen therapy, intravenous fluids, and management of complications like pneumonia is critical [9]. In LMICs, weak healthcare infrastructure contributes to high mortality rates. Strengthening primary healthcare systems and training healthcare workers in early identification and treatment of influenza can significantly improve outcomes [10].

Public Health Interventions

Public health strategies aim to complement vaccination and treatment efforts by reducing transmission and building community resilience.

• Education and Hygiene: Promoting hand hygiene, respiratory etiquette, and the use of masks in crowded settings can reduce transmission rates [11]. Education campaigns targeting parents and caregivers about influenza symptoms and prevention strategies are vital, especially in rural and underserved areas [12].
• Community-Level Strategies: Community-level interventions, such as establishing vaccination clinics, distributing antivirals, and improving surveillance, have shown effectiveness in managing outbreaks [13]. Partnerships with local organizations can help overcome logistical challenges in LMICs.

Challenges and Gaps in Current Knowledge

Lack of Data from Low- and Middle-Income Countries

Seasonal influenza burden data from LMICs is scarce, largely due to inadequate surveillance systems and underreporting [14]. Most available studies are from high-income countries, creating a skewed understanding of the global burden. Reliable data from LMICs is crucial for developing region-specific strategies and allocating resources effectively.

Gaps in Vaccination and Treatment Accessibility

Vaccination rates in LMICs remain significantly lower than in high-income countries, driven by financial constraints, logistical challenges, and vaccine hesitancy [15]. Similarly, access to antiviral medications is limited, with availability often restricted to urban centers. These gaps leave large portions of the population vulnerable to severe outcomes.

Variability in Surveillance and Reporting Systems

Surveillance systems for influenza vary widely in quality and coverage across regions [16]. Many LMICs lack the infrastructure and trained personnel to implement robust surveillance programs, resulting in underestimation of disease burden. Standardizing surveillance protocols and integrating them into existing public health programs could improve data accuracy and inform global strategies.

Addressing these challenges requires global collaboration, investment in healthcare infrastructure, and innovative approaches to vaccination and treatment delivery.

Future Directions and Recommendations

Research Priorities

Advancing vaccine innovation is a critical research priority to address the limitations of current influenza vaccines. Efforts should focus on developing universal influenza vaccines that provide long-lasting immunity across multiple strains and seasons [1]. Additionally, exploring adjuvants to enhance vaccine efficacy in young children and those with weakened immune systems is vital [2]. Diagnostic advancements, such as affordable point-of-care tests with higher sensitivity and specificity, are equally important to enable timely and accurate influenza detection in low-resource settings [3].

Policy Recommendations

Policymakers should prioritize equitable access to vaccines and antiviral treatments, particularly in low- and middle-income countries (LMICs). Subsidizing vaccine costs, expanding immunization programs, and addressing vaccine hesitancy through community engagement are essential steps [4]. Strengthening global influenza surveillance systems by standardizing protocols and integrating real-time reporting can improve burden estimation and resource allocation [5]. Collaboration between governments, non-governmental organizations, and international agencies is necessary to ensure coordinated responses to influenza outbreaks.

Integration of Influenza Prevention in Broader Child Health Programs

Influenza prevention efforts should be integrated into existing child health initiatives, such as routine immunization schedules, nutrition programs, and maternal and child health services [6]. This integration can maximize the reach and impact of prevention strategies while addressing other health determinants. Promoting multi-sectoral approaches that include education, hygiene promotion, and access to healthcare services can build resilience against influenza and other childhood illnesses.

Seasonal influenza remains a significant global health challenge, disproportionately affecting children under five, particularly in low-resource settings. The high burden of morbidity, mortality, and economic impact underscores the need for urgent action to reduce its global impact.

Prevention through vaccination, coupled with early diagnosis, effective antiviral treatments, and supportive care, offers the best strategy for managing the disease. However, challenges such as vaccine accessibility, diagnostic limitations, and weak healthcare infrastructure in LMICs hinder progress. Addressing these gaps through innovative research, policy reforms, and integration of influenza prevention into broader health programs is critical.

By strengthening global and local efforts, we can mitigate the burden of seasonal influenza and improve health outcomes for vulnerable pediatric populations worldwide.

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