Influenza
Influenza is a viral respiratory infection causing fever,
coryza, cough, headache, and malaise. Mortality is possible during seasonal
epidemics, particularly among high-risk patients (eg, those who are
institutionalized, at the extremes of age, have cardiopulmonary insufficiency,
or are in late pregnancy); during pandemics, even healthy, young patients may
die. Diagnosis is usually clinical and depends on local epidemiologic patterns.
The influenza vaccine should be given annually to everyone aged ≥ 6 months who
does not have a contraindication. Antiviral treatment reduces the duration of
illness by about 1 day and should be specifically considered for high-risk
patients.
Influenza refers to illness caused by the influenza viruses,
but the term is commonly and incorrectly used to refer to similar illnesses
caused by other viral respiratory pathogens. Influenza viruses are classified
as type A, B, or C by their nucleoproteins and matrix proteins. Influenza C
virus infection does not cause typical influenza illness and is not discussed
here.
Influenza antigens
Hemagglutinin (H) is a glycoprotein on the influenza viral
surface that allows the virus to bind to cellular sialic acid and fuse with the
host cell membrane. Neuraminidase (NA), another surface glycoprotein,
enzymatically removes sialic acid, promoting viral release from the infected host
cell. There are 18 H types and 11 NA types, giving 198 possible combinations,
but only a few are human pathogens.
Epidemiology of Influenza
Influenza causes widespread sporadic illness yearly during
fall and winter in temperate climates (seasonal epidemics).
Seasonal epidemics are caused by both influenza A and B
viruses; since 1968, most seasonal influenza epidemics have been caused by H3N2
(an influenza A virus). Influenza B viruses may cause milder disease but often
cause epidemics with moderate or severe disease, either as the predominant
circulating virus or along with influenza A.
Most influenza epidemics are caused by a predominant
serotype, but different influenza viruses may appear sequentially in one
location or may appear simultaneously, with one virus predominating in one
location and another virus predominating elsewhere.
.
Pandemics are much less common. There have been 6 major
influenza pandemics, typically named after the presumed location of origin:
·
1889: Russian influenza (H2N2)
·
1900: Old Hong Kong influenza (H3N8)
·
1918: Spanish influenza (H1N1)
·
1957: Asian influenza (H2N2)
·
1968: Hong Kong influenza (H3N2)
·
2009: Swine influenza (influenza A [H1N1]pdm09)
In 2009–2010 an H1N1 flu pandemic occurred—the virus spread
to > 70 countries and to all 50 US states. The majority of the deaths
occurred in Mexico. The virus was initially referred to as a swine flu virus,
but it is a combination of swine, avian, and human influenza viruses. The
infection is not acquired through ingestion of pork and is acquired very rarely
by contact with infected pigs. Subsequently, the virus name was standardized to
influenza A(H1N1)pdm09 to denote the pandemic and distinguish the virus from
seasonal H1N1 strains and the 1918 pandemic H1N1 strain. Since 2009, influenza
A(H1N1)pdm09 has circulated as a seasonal influenza.
Influenza viruses can be spread by
·
Airborne droplets
·
Person-to-person contact
·
Contact with contaminated items
·
Airborne spread appears to be the most important
mechanism.
High-risk groups
·
Certain patients are at high risk of
complications from influenza:
·
Children < 5 years; children < 2 years are
at particularly high risk
·
Adults > 65 years
·
People with chronic medical disorders (eg,
cardiopulmonary disease, diabetes mellitus, renal or hepatic insufficiency,
hemoglobinopathies, immuodeficiency)
·
Women in the 2nd or 3rd trimester of pregnancy
·
Patients with disorders that impair handling of
respiratory secretions (eg, cognitive dysfunction, neuromuscular disorders,
stroke, seizure disorders)
·
Patients ≤ 18 years taking aspirin (because Reye
syndrome is a risk)
·
Morbidity and mortality in these patients may be
due to exacerbation of underlying illness, acute respiratory distress syndrome,
primary influenza pneumonia, or secondary bacterial pneumonia.
Symptoms and Signs of Influenza
·
The incubation period for influenza ranges from
1 to 4 days with an average of about 48 hours. In mild cases, many symptoms are
like those of a common cold (eg, sore throat, rhinorrhea); mild conjunctivitis
may also occur.
·
Typical influenza in adults is characterized by
sudden onset of chills, fever, prostration, cough, and generalized aches and
pains (especially in the back and legs). Headache is prominent, often with
photophobia and retrobulbar aching. Respiratory symptoms may be mild at first,
with scratchy sore throat, substernal burning, nonproductive cough, and
sometimes coryza. Later, lower respiratory tract illness becomes dominant;
cough can be persistent, raspy, and productive.
·
Gastrointestinal symptoms may occur and appear
to be more common with the 2009 pandemic H1N1 strain. Children may have
prominent nausea, vomiting, or abdominal pain, and infants may present with a
sepsis-like syndrome.
·
After 2 to 3 days, acute symptoms rapidly
subside, although fever may last up to 5 days. Cough, weakness, sweating, and
fatigue may persist for several days or occasionally for weeks.
Complications
Pneumonia is suggested by a worsening cough, bloody sputum,
dyspnea, and rales. Secondary bacterial pneumonia is suggested by persistence
or recurrence of fever and cough after the primary illness appears to be
resolving.
Encephalitis, myocarditis, and myoglobinuria, sometimes with
renal failure, develop infrequently after influenza A or B infection. Reye
syndrome—characterized by encephalopathy; fatty liver; elevation of liver
enzymes, ammonia, or both; hypoglycemia; and lipidemia—often occurs during
epidemics of influenza B, particularly in children who have ingested aspirin.
Diagnosis of Influenza
Clinical evaluation
Sometimes rapid antigen or conventional reverse
transcriptase-polymerase chain (RT-PCR) tests
Pulse oximetry and chest x-ray for patients with severe
respiratory symptoms
The diagnosis of influenza is generally made clinically in
patients with a typical syndrome when influenza is known to be present in the
community.
Prognosis for Influenza
Most patients recover fully, although full recovery often
takes 1 to 2 weeks. However, influenza and influenza-related pneumonia are
important causes of morbidity or mortality in high-risk patients. Prompt
antiviral treatment in these patients can reduce the incidence of lower
respiratory disease and hospitalization. Appropriate antibacterial therapy
decreases the mortality rate due to secondary bacterial pneumonia.
Overall, the case fatality rate is low (eg, < 1%), but
because incidence of disease is high, the total number of deaths can be
significant. The Centers for Disease Control and Prevention (CDC) estimates
that in the US from 2010 to 2020, hospitalizations resulting from seasonal
influenza ranged from 140,000 to 710,000 annually, and deaths ranged from
12,000 to 52,000 annually (1). Rates of hospitalization and death are highest
in patients > 65 years. During typical seasonal influenza epidemics, about
80% of deaths are estimated to occur in patients > 65 years; however, 80% of
H1N1-related deaths were estimated to have occurred in people < 65 years during
the first 12 months of the 2009 H1N1 pandemic. (2, 3).
Prevention of Influenza
Influenza infections can largely be prevented by
Annual vaccination
Sometimes chemoprophylaxis (ie, with antiviral drugs)
Current commercially available influenza vaccines protect
against seasonal H3N2, pandemic H1N1 influenza A, and influenza B. A vaccine
for H5N1 avian influenza has been approved for people > 18 years at high
risk of H5N1 exposure but is available only through public health officials. No
vaccines are currently available for the other avian influenza viruses rarely
associated with human disease (H7N7, H9N2, H7N3, and H7N9).
Prevention is indicated for all patients but is especially
important for high-risk patients and health care practitioners.
Key Points
·
Minor antigenic drift in H and/or NA antigens
produces strains that cause seasonal epidemics; rare antigenic shifts resulting
in new combinations of H and NA antigens can cause a pandemic with significant
mortality.
·
Influenza itself may cause pneumonia, or
patients with influenza may develop secondary bacterial pneumonia.
·
Diagnosis is usually clinical, but sensitve and
specific RT-PCR assays can differentiate influenza types and subtypes and thus
help select antiviral therapy and determine whether outbreaks of respiratory
disease are due to influenza.
·
Treat most patients symptomatically.
·
Antiviral drugs given early can slightly
decrease duration and severity of symptoms but are typically used only in
high-risk patients; different influenza types and subtypes are resistant to
different drugs.
·
Vaccinate annually everyone aged ≥ 6 months who
does not have a contraindication; antiviral drugs can be used for prevention in
immunocompromised patients (who may not respond to vaccination) and patients
with contraindications to vaccination.