Dr William Naughton Infectious diseases and general medicine physician , Alice Springs Hospital , Central Australia Health Service , NT .

First published online on 7 March 2024

BACKGROUND

INFLUENZA is a common presentation

to both primary care and hospital . It causes significant morbidity and mortality , accounting for minor or major epidemics of seasonal influenza most years . Patterns of influenza activity vary geographically . In temperate climates , seasonal epidemics typically occur during winter months ( April to September in the Southern Hemisphere ) with interpandemic influenza A outbreaks usually beginning abruptly , peaking over 2-3 weeks and lasting 3-5 months . In tropical and subtropical climates , activity may occur year-round with peaks during cooler or rainy season months . 1

In Australia , seasonal influenza results in more than 300,000 GP consultations , 18,000 hospitalisations and 3500 deaths each year . 2 The Australian Influenza Surveillance Program monitors influenza activity and severity in the community . While the 2023 season was considered to be of low overall clinical severity , it led to 252,296 notifications of laboratory-confirmed influenza , 3696 admissions with confirmed influenza to sentinel hospitals , and 376

influenza-associated deaths notified to the National Notifiable Diseases Surveillance System ( NNDSS ). 3

Globally , seasonal influenza-associated respiratory deaths are estimated to range between 291,243 to 645,832 ( 4.0 to 8.8 per 100,000 individuals ) annually with a peak mortality rate among people older than 75 ( 17.9 to 223.5 per 100,000 individuals ) and in sub-Saharan Africa ( 2.8- 16.5 per 100,000 individuals ) and South-East Asia ( 3.5-9.2 per 100 000 individuals ). 4

This How to Treat covers the assessment and management of influenza in Australia with a focus on diagnosis , risk stratification , treatment , and prevention of acquisition and complications . It aims to ensure GPs can identify those likely to have influenza , those at higher risk of poor outcomes from influenza and those most likely to benefit from antivirals and vaccination .

PATHOPHYSIOLOGY

INFLUENZA viruses are members of the Orthomyxoviridae family . Influenza viruses A , B and C can infect humans , though influenza C is an uncommon cause of respiratory

illness . 5 The designation of influenza virus type ( A , B or C ) is based on the antigenic characteristics of the nucleoprotein and matrix ( M ) protein antigens . Further subdivision of influenza A virus is based on the surface haemagglutinin ( H ) and neuraminidase ( N ) glycoproteins . The virus binds to sialic acid cell receptors in the respiratory tract using haemagglutinin ( see figure 1 ), while the neuraminidase degrades the receptor and plays a role in the release of the virus from infected cells after replication ( see figure 2 ). 6 Influenza A has 18 distinct H subtypes and 11 distinct N subtypes . Epidemics of human disease have been associated with subtypes H1 , H2 , H3 , N1 , and N2 . Influenza B and C do not receive subtype designations as intratypic variations in influenza B antigens are less extensive than in influenza A viruses and may not occur with influenza C . 7

Humans are the primary reservoir for seasonal influenza , while birds , pigs , horses and other mammals are natural hosts for influenza A virus . Animal reservoirs are potential sources of new human subtypes and risk of transmission to humans

occurs particularly when people interact closely with livestock . 2

Influenza A is a constantly evolving pathogen with a propensity for periodic antigenic variation . This underpins the capacity for extensive and severe outbreaks of disease . Antigenic variation may involve H alone or both H and N . There are two major mechanisms for antigenic change : antigenic drift and antigenic shift . Point mutations in the viral genome lead to minor changes at key viral epitopes , causing antigenic drift , which account for local outbreaks as influenza evades host immune responses .

Antigenic shift only occurs among influenza A viruses because of their extensive animal reservoirs , the sources of antigenically distinct viruses , and is a consequence of the segmented nature of the influenza A genome . 8 The opportunity for reassortment of these segmented genes during infection is high and may occur on co-infection of a single cell with two influenza viruses . Gene segment exchange can occur between viruses and result in a complete exchange of H and or N genes . The result is a virus to which the