Influenza Elisha Hall, PhD, RD Influenza is an infectious viral illness. The name “influenza” originated in 15th century Italy, from an epidemic attributed Influenza to “influence of the stars.” The first documented pandemic, or ● Viral illness worldwide epidemic, that clearly fits the description of influenza ● First pandemic in 1580 was in 1580. At least four pandemics of influenza occurred in ● Estimated 21 million deaths the 19th century, three in the 20th century, and one thus far worldwide in pandemic in the 21st century. The pandemic of “Spanish” influenza in of 1918-1919 1918–1919 caused an estimated 21 million deaths worldwide. ● Influenza A and B viruses Wilson Smith, Christopher Andrewes, and Patrick Laidlaw isolated in the 1930s isolated influenza A virus in ferrets in 1933, and Thomas Francis ● Inactivated vaccines first Jr. isolated influenza B virus in 1936. Also in 1936, Macfarlane developed and used in the Burnet discovered that influenza virus could be grown in late 1930s and 1940s embryonated hens’ eggs. This led to the study of the virus’s characteristics and the development and use of inactivated vaccines in the late 1930s and 1940s. The protective efficacy of these inactivated vaccines was demonstrated in the 1950s. The first live, attenuated influenza vaccine was licensed in 2003. A non-live, recombinant influenza virus vaccine not requiring isolation or growth in hen’s eggs was licensed in 2013. 12 Influenza Virus Influenza Virus Influenza is a single-stranded, helically shaped, RNA virus of the ● Single-stranded RNA virus orthomyxovirus family. Three types of influenza virus are known to affect humans: A, B, and C. Type A influenza has subtypes ● Orthomyxovirus family determined by the surface antigens hemagglutinin (HA) and ● Three types affect humans: neuraminidase (NA). There are 18 different H subtypes and 11 A, B, C different N subtypes. Eight H subtypes (H1, H2, H3, H5, H6, H7, ● Infection can be asymptomatic H9, H10) and six N subtypes (N1, N2, N6, N7, N8, and N9) have or result in mild to severe disease been detected in humans. Type B influenza is classified into two lineages: B/Yamagata and B/Victoria. Infection with influenza viruses can be asymptomatic or result in disease that ranges from mild to severe. Influenza B more commonly affects children. Influenza C is rarely Antigenic Changes reported as a cause of human illness, probably because most ● Antigenic drift cases are subclinical. Influenza C has not been associated ■ Small mutations over time with epidemic disease. that result in novel strain ■ Primary reason people Antigenic Changes can get influenza more Virus surface antigens hemagglutinin and neuraminidase than once continually change. Changes in influenza viruses can take the ■ May result in annual form of antigenic drift or antigenic shift. influenza epidemic Antigenic drift involves small mutations in the genes of ● Antigenic influenza viruses that lead to changes in HA and NA that ■ Abrupt, major change in accumulate over time, resulting in the emergence of novel surface antigen(s) strains that the human immune system may not recognize. These novel strains are the influenza virus’s evolutionary ■ May lead to pandemic (rare) adaptations to a strong population-wide immune response. 179 https://www.cdc.gov/vaccines/pubs/pinkbook/flu.html Aug 2021 Influenza Antigenic drift is the primary reason people can get influenza more than once and why it is necessary to annually review and update the composition of influenza vaccines. Antigenic drift, along with waning immunity, results in annual influenza epidemics, since the protection that remains from past exposures to similar viruses is incomplete. Drift occurs in all three types of influenza virus (A, B, C). Antigenic shift involves an abrupt, major change in one or both surface antigens (H or H-N combination). Antigenic shifts are probably due to genetic recombination (an exchange of a gene segment) between influenza A viruses that affect humans and/or animals. An antigenic shift may result in a worldwide pandemic if the virus is efficiently transmitted from person to person. Pandemics are rare; since the late 19th century, five antigenic shifts have led to pandemics in 1889-1891, 1918-1920, 1957-1958, 1968-1969, and 2009-2010. Influenza Pathogenesis Pathogenesis Following respiratory transmission, the virus attaches to and 12 ● Respiratory transmission penetrates respiratory epithelial cells in the trachea and bronchi. ● Replication in respiratory Viral replication occurs, which results in the destruction of the epithelium with subsequent host cell. Regeneration of epithelium takes about 3 to 4 weeks. destruction of cells Viremia, or presence of virus in the blood, has rarely been ● Viremia rarely documented documented. Virus is shed in respiratory secretions for 5 to 10 days, with a peak of 1 to 3 days following illness onset. ● Virus shed in respiratory secretions for 5–10 days Clinical Features The incubation period for influenza is usually 2 days but Influenza Clinical Features can vary from 1 to 4 days. Influenza illness can range from ● Incubation period 2 days (range, asymptomatic to severe infection. On average, about 8% of the 1–4 days) U.S. population gets sick from influenza each season (range between 3% and 11%). ● About 8% of U.S. population gets sick each season Onset of influenza symptoms is sudden. Respiratory symptoms ● Sudden onset of symptoms include cough, sore throat, and runny or stuffy nose. Systemic symptoms generally include fever, chills, headache, malaise, ■ Respiratory: cough, sore throat, runny or stuffy nose and myalgia. Vomiting and diarrhea may also occur, especially in children. Recovery is rapid; fever usually resolves within 3 ■ Systemic: fever, chills, to 4 days and other symptoms within approximately 7 days. headache, malaise, myalgia Some patients may have lingering asthenia (lack of strength or ■ Gastrointestinal: vomiting, energy) for several weeks. More information can be found at: diarrhea www.cdc.gov/flu/symptoms/symptoms.htm. ● Rapid recovery Influenza symptoms (e.g., pain and fever) can be controlled with medications such as aspirin, ibuprofen, or acetaminophen. Aspirin and salicylate-containing products should not be used for children or adolescents because it may increase the risk for developing Reye syndrome. 180 Influenza Complications Influenza Complications People most at risk of developing serious influenza-related complications include people age 65 years and older, people ● Secondary bacterial pneumonia with chronic medical conditions (e.g., heart disease or diabetes), ● Exacerbations of underlying pregnant women, and young children, especially those younger respiratory conditions than age 2 years. More common complications of influenza ● Otitis media include secondary bacterial pneumonia (e.g., Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus), ● Laryngotracheobronchitis exacerbations of underlying respiratory conditions, otitis media, ● Bronchitis laryngotracheobronchitis, and bronchitis. ● Other less common complications may occur Other complications may include primary pneumonia, encephalitis, aseptic meningitis, transverse myelitis, myocarditis, pericarditis, Guillain-Barré syndrome, and Reye Syndrome. Reye syndrome is a complication that occurs almost exclusively in children taking aspirin, primarily in association with influenza B virus (or varicella zoster virus), and presents with severe vomiting and confusion, which may progress to coma due to swelling of the brain. Most deaths due to influenza typically occur among persons 12 age 65 years and older. Laboratory Testing Influenza is usually suspected based on characteristic clinical findings, particularly if influenza has been reported in the community. Influenza virus testing is not required to make a clinical diagnosis but can inform clinical management when results may influence decisions to initiate antiviral treatment, perform other diagnostic testing, or implement infection and prevention control measures. Diagnostic tests include: • Molecular assays (i.e., rapid molecular assays, reverse transcription polymerase chain reaction (RT-PCR), and other nucleic acid amplification tests) • Antigen detection tests (i.e., rapid influenza diagnostic tests and immunofluorescence assays) Approved respiratory tract specimens differ among the FDA-cleared influenza tests, so clinicians should refer to the specific test’s package insert for approved respiratory specimens. In addition to diagnostic testing for only influenza virus, the Flu SC2 Multiplex Assay is a real-time RT-PCR test that detects and differentiates RNA from SARS-CoV2, influenza A virus, and influenza B virus in upper or lower respiratory specimens. Serology testing is no longer used for clinical diagnosis of influenza but is still used for research studies. 181 Influenza Information for health care providers on influenza virus testing can be found at www.cdc.gov/flu/professionals/diagnosis/index. htm. Details about the laboratory diagnosis of influenza are available at www.cdc.gov/flu/symptoms/testing.htm. Medical Management Vaccination is the principal means for preventing influenza- related morbidity and mortality, however antiviral agents may be indicated in some situations for preventing and/or treating influenza. Current recommendations and a decision tree for clinicians is available for making antiviral decisions: https://www.cdc.gov/flu/professionals/antivirals/summary- clinicians.htm Influenza Epidemiology ● Reservoir Epidemiology