Influenza, also called flu, is a major viral respiratory disease that leads to frequent epidemics and severe clinical symptoms with significant mortality worldwide.
The disease occurs annually as outbreaks, resulting in about three to five million cases of severe illness with approximately 290,000 to 650,000 deaths. Influenza is a seasonal disease occurring mainly in winter in the temperate zone of the northern and southern hemispheres, and at any time of the year in some tropical counties. Influenza-associated mortality rates are higher in low-income countries mainly due to lack of access to adequate medical care, limited public health infrastructure, social factors, housing conditions and population density. Larger outbreaks due to novel emerging influenza virus strains are known as pandemics and can result in the death of millions.
Influenza is caused by members of the virus family Orthomyxoviridae divided into three major types (A, B and C). Type A viruses are the most frequent and virulent in humans, followed by the less common type B and C, the latter causing only mild disease in children.
Virus subtypes are defined by differences in the composition of the virus surface-proteins hemagglutinin (H) and neuraminidase (N). Currently, 18 hemagglutinin subtypes and 11 neuraminidase subtypes have been described. H1N1 or H3N2 are examples of influenza subtype A that circulate in the human population. Influenza viruses are constantly evolving as, during their replication, they accumulate genomic mutations (antigenic drift) and, due to their segmented genome, they can undergo re-assortment (exchange of combination of genome segments) between different virus subtypes (i.e. antigenic shift), thus leading to occurrence of new viruses with diversified antigenic composition. The variability of influenza viruses is further increased by circulation of influenza strains in several animal species (mainly avian, swine and bat), and adaption of those strains in humans can lead to the emergence of pandemic viruses.
Influenza infection causes from mild to severe illness and leads to significant mortality worldwide. Typical influenza symptoms include high fever, chills, fatigue, sore throat, muscle pains, nasal congestion and coughing. In children, especially influenza B, can cause mild to severe gastrointestinal symptoms such as nausea, vomiting, diarrhoea andabdominal pain. Most people recover from influenza but some, such as the elderly and young children, are at greater risk of developing complications such as pneumonia, bronchitis, sinus and ear infections, or worsening of other chronic health problems such as asthma or heart failure.
WHO estimates that around 5-10% of the world’s population is affected by seasonal influenza, resulting in an estimated 290,000 to 650,000 deaths per year, thus imposing a tremendous health and economic burden on the human population, which is more pronounced in middle- and low-income countries.
Vaccination is the most effective way to prevent infection and severe outcome caused by influenza viruses. Current vaccines either consist of inactivated viruses grown in chicken eggs, live attenuated viruses or recombinant hemagglutinin. As influenza viruses undergo continuous antigenic changes, current vaccines provide only limited protection against new epidemic or pandemic viruses. The composition of seasonal influenza vaccines has to be updated each year, and thus need to be administered annually. In consequence, continuous monitoring and selection of viruses, as well as production of vaccines, is necessary each year. A major limitation is therefore that the relatively long manufacturing and production time results in a vaccine that does not always contain the correct viruses to match the epidemic strains circulating in the community. Moreover, these vaccines are less or not at all affordable for low and middle-income populations.
A significant advance would be the development of a new generation of influenza vaccines that stimulate production of a robust, broadly neutralising immune response, not only to drifted variants of seasonal influenza viruses, but preferably also to potential pandemic strains. In addition “universal” influenza vaccines, that do not require annual immunisation, may be the best option for low and middle income populations, including those in subtropical and tropical regions.