INFLUENCEF STUDY: Epidemiology, Risk Factors and Clinical Phenotype of Headache Associated With Influenza Infection

Respiratory tract infections are the second global cause of disability-adjusted life years and represent a higher cost than illnesses such as heart failure, asthma, or migraine. The influenza virus is responsible for 11.5% of episodes of lower respiratory tract infections, causing 650,000 deaths per year. In Spain, in the period prior to COVID-19, the incidence rate of influenza infection was estimated in 2,069 cases per 100,000 inhabitants and year. Between 2001 and 2018, the seasonal transmissibility of influenza viruses has varied depending on diverse factors, such as the type/subtype of influenza, the dominant or codominance of multiple strains, and the timing of the epidemic. The diagnosis of the infection has evolved in the latest years, allowing to monitor the epidemics and elaborate sanitary programs that permit its control and management.

The Healthcare Sentinel Network of Castile and Leon - Red Centinela Sanitaria de Castilla y León (RCSCYL) carries out active influenza surveillance since the 1996-1997 season, and additionally, since the 2020 monitors other Acute Respiratory Infections (ARI) (VIGIRA system) in collaboration with the National Influenza Center of Valladolid (CNGV), the department of Microbiology of the University Clinical Hospital of Valladolid. This program works in collaboration with the National Influenza Surveillance System of Spain (SVGE), integrated into the European Influenza Surveillance Network (EISN). Active monitoring is done by 100 healthcare providers covering a 60,000 population.

The current VIGIRA program includes those patients who belong to a quota of a sentinel general practitioner or pediatrician that are evaluated in primary care (PC) setting due to an ARI. The World Health Organization (WHO) definition of ARI, as acute onset of at least one of the following four respiratory symptoms: cough, sore throat, shortness of breath, coryza, and a clinician's judgement that the illness is due to an infection. The definition states that ARIs may present with or without fever. During the 2021-2022 season, until June 12, 2022, the rate of ARIs has been of 43,841 cases per 100,000 population.

Influenza is defined as the clinical syndrome caused by influenza family viruses' infection. It is characterized by a combination of respiratory and systemic symptoms. Headache is one of the most frequent systemic symptoms, although the number of specific studies is very scarce. Up to now, only two studies that included 37 and 279 patients have shown prevalence rates for this symptom between 32.4% and 60%.

In 2008, the criteria that defines the influenza-like illness was modified, to an acute respiratory illness with onset during the last 7 days with at least one of the following general symptoms: fever or low-grade fever, malaise, headache and myalgia; and at least one of the following three respiratory symptoms: cough, odynophagia and/or dyspnea. The VIGIRA network registers the presence of headache consistently. During the 2021/2022 season, the prevalence rate of influenza-like illness was estimated in 758 per 100,000 inhabitants.