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population has limited immunity
, leading to increased transmission , and may be associated with a pandemic . 7 , 8
PANDEMICS
INFLUENZA A viruses are the only influenza viruses known to cause global influenza pandemics . Table 1 lists the major influenza A pandemics since 1918 . The influenza A / H1N1 virus that caused the most severe pandemic of modern times ( 1918-19 ) was likely an adaptation of an avian virus to human infection . It is estimated that about one-third of the world ’ s population ( about 500 million people ) were infected , with at
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Jung HE , Lee HK Viruses 2020 / CC BY 4.0 / bit . ly / 4eS8inI |
Table 2 . Clinical observations in 24 seronegative children examined during H3N2 influenza ( A / Port Chalmers ) infection
Condition / event
Number of patients (%) with H3N2 influenza A / Port Chalmers infection
Coryza 22 / 24 ( 91.7 )
Fever ( temperature above 38.4 ° C [ above 101 ° F ])
21 / 24 ( 87.5 )
Cough 21 / 24 ( 87.5 )
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least 50 million deaths worldwide . 7 , 9
The most recent influenza pandemic occurred in 2009-10 with a new H1N1 virus , designated ( H1N1 )
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Pharyngitis / sore throat
20 / 24 ( 83.3 )
Irritability 20 / 24 ( 83.3 )
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pdm09 . It was first detected in the spring of 2009 in the US and spread quickly across the world . The virus had two genes from influenza viruses that normally circulate in pigs in |
Figure 1 . The structure of the influenza A virus . |
Fever ( temperature above 39.5 ° C [ above 103 ° F ])
13 / 24 ( 54.2 )
Anorexia 12 / 24 ( 50 )
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Europe and Asia , three genes that normally circulate in North Amer- |
Tonsillitis 8 / 24 ( 33.3 ) |
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ican pigs , as well as genes from influenza viruses from birds and humans . 10 While few young people had any existing immunity ( as detected by antibody response ) to ( H1N1 ) pdm09 , nearly one-third of |
Vomiting 7 / 24 ( 29.2 )
Otitis 6 / 24 ( 25 )
Pneumonia 6 / 24 ( 25 )
Diarrhoea 6 / 24 ( 25 )
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those over 60 had antibodies against this virus , likely from prior exposure |
Hoarseness 4 / 24 ( 16.7 ) |
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to an H1N1 virus . Vaccination with seasonal influenza vaccines offered little cross-protection against infec- |
Croup 1 / 24 ( 4.2 )
Source : Wright PF et al 22
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tion with this virus , even though they contained H1N1 strains . 10 Worldwide , an estimated 284,400 peo- |
gastrointestinal symptoms can occur |
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ple ( range 151,700 to 575,400 ) died from infection during the first year . 11 Globally , 80 % of deaths were esti- |
22 , 23 , 24 in up to 28 %. Presentations may be subtle or altered in extremes of age and |
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mated to have occurred in those under 65 . 10 This differs from typical seasonal influenza epidemics , when |
immunocompromise . This group may present without fever and with fewer typical symptoms such as sore |
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70-90 % of deaths are estimated to occur in those 65 or over . 10 In Australia , more than 59,000 notifications |
Figure 2 . Life cycle of a virus . |
throat and myalgias . Predominant symptoms may be non-specific , such as anorexia , malaise , weakness |
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were reported to the NNDSS , almost |
or dizziness . |
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10 times the five-year mean , peaking at nearly 30,000 notifications in July 2009 ( see figure 3 ). 12
TRANSMISSION
INFLUENZA virus spreads primarily via person-to-person respiratory transmission , aided by the coughing and sneezing that occur with infection . There are three transmission methods ; aerosol , large droplets and self-inoculation of the mucosa
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Table 1 . Antigenic subtypes of influenza A virus associated with pandemics or epidemics since 1918
Years Subtype Extent of outbreak
1918-19 H1N1 ( formerly HswN1 # ) Severe pandemic
1933-35 H1N1 ( formerly H0N1 # ) Mild epidemic
1946-47 H1N1 Mild epidemic
1957-58 H2N2 Severe pandemic
1968-69 H3N2 Moderate pandemic
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in clearance of an infection and reliably develops 8-10 days after exposure . T-cells have been proposed to play a role in protection against influenza acquisition . 7
PRESENTATION
INFLUENZA is primarily a respiratory illness with the clinical manifestations of cough , sore throat , and rhinorrhoea or nasal congestion ( see figure 4 ). The degree of accom-
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Older adults are also more likely to present with altered mental status , which may be their only symptom of influenza . 23 , 25 In a US Centers for Disease Control and Prevention ( CDC ) study of adult transplant patients the criteria for influenza-like illness ( ILI ), defined as fever and either cough or sore throat , were poorly predictive of PCR-positive cases . 26 A report of an influenza outbreak in an ambulatory stem cell transplant centre noted |
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of the eyes , nose or mouth by hands contaminated by respiratory secretions . 15 The role of contact transmission relative to droplet and aerosol spread is unclear . 16
The typical incubation period ( the time between exposure and the appearance of the first symptoms ) ranges from 1-4 days , with an average of two days . 17 The serial interval ( the time between the onset of
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1977-78 H1N1 Mild pandemic
2009-10 H1N1 Mild to moderate pandemic *
#
Haemagglutinins formerly designated as Hsw and H0 are now classified as variants of H1 . * During the 2009-10 H1N1 influenza A pandemic , mortality was relatively high among individuals under 65 and relatively low among those 65 or older . 14 Table adapted from Neuzil KM , Wright PF . Emergence of antigenic subtypes of influenza A virus associated with pandemic or epidemic disease . In : Loscalzo J ( editor ), et al . Harrison ’ s Principles of Internal Medicine . McGraw Hill Education , New York , 2022 7
including obesity . The role of asymp-
Infection spreads to the lungs ,
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panying fatigue , myalgia , malaise , fever and chills helps to distinguish influenza from most other respiratory viral illnesses , noting that SARS- CoV-2 is the exceptional respiratory virus associated with a significant systemic presentation . 7
Table 2 lists the manifestations of influenza caused by an H3N2 virus in 24 young seronegative children . While these data involve children
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that only 7 % of cases met the CDC ILI definition , with fever present in eight of 31 ( 26 %) patients . 27
Infants and young children may present with a wide range of signs and symptoms . Young children may not be able to vocalise their symptoms , they may have higher fevers , febrile seizures , less prominent respiratory findings , and more gastrointestinal complaints such as nausea , vomiting ,
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illness in an index patient and the |
tomatic or presymptomatic infected |
remaining confined to the epithe- |
and a viral strain circulating in 1974- |
diarrhoea and anorexia at the time of |
onset of illness in a household con- |
people in the transmission of influ- |
lial layer . Systemic manifestations of |
75 , this is a representative picture |
presentation . Fever , though it may be |
tact ) is 3-4 days . 18 |
enza viruses is unclear , but is |
fever , malaise , and myalgia are pre- |
of influenza , noting that irritability |
absent , and malaise may be the only |
Infectiousness is usually equated to the presence of virus shedding . In immunocompetent hosts , viral shedding occurs at or just before symptom onset ( 0-24 hours ), peaks at |
16 , 20 , 21 believed to be uncommon .
PATHOGENESIS AND IMMUNITY
Influenza infection is initiated in
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sumed to be mediated by cytokines , with excess cytokine production implicated in the toxicity of highly pathogenic influenza viruses . 7
The host immune response to
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in a young child is more specifically recognised as malaise , myalgia and headache in an adult . 22
The spectrum of clinical manifestations and severity of infection vary
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23 , 28 recognised manifestations .
There is usually a paucity of physical examination findings . Patients may appear unwell with sweating , coughing , non-purulent
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24-48 hours , and swiftly declines . There is usually little or no detectable virus after 5-10 days . 19 Viral shedding may be prolonged , lasting weeks to months , in immuno- |
the upper respiratory tract via aerosolised virus , with the primary site of infection within the ciliated cells . Symptoms are likely secondary to subsequent denudation of superficial |
influenza virus incorporates both T- and B-cells . B- cell responses are directed primarily toward antigenic epitopes on the two surface glycoproteins H and N . T-cell responses |
with different strains , for example , during the 2009-10 H1N1 influenza pandemic , vomiting and diarrhoea were common among adults . Diarrhoea is usually more common |
conjunctivitis , and diffuse pharyngeal erythema ( see figure 5 ). Mild cervical lymphadenopathy ( see figure 6 ) may be present , more commonly in younger patients . Physical |
compromised patients , adults over |
epithelium , which may predispose |
remain unclear ; however , T-cell |
among infants , young children , |
examination of the lungs is gener- |
65 and those with chronic illnesses , |
to secondary bacterial infections . |
immunity is thought to play a role |
and school-aged children , where |
ally unremarkable but may identify |