Influenza, one of the most common infectious diseases, is a

highly contagious airborne disease that occurs in seasonal

epidemics and manifests as an acute febrile illness with variable
degrees of systemic symptoms, ranging from mild fatigue to
respiratory failure and death. Influenza causes significant loss of
workdays, human suffering, and mortality. The World Health
Organization estimates that worldwide annual influenza
epidemics result in about 3-5 million cases of severe illness and
about 250,000-500,000 deaths. The Centers for Disease Control
and Prevention (CDC) estimates that flu-associated deaths in the
United States ranged from about 3000 to 49,000 annually
between 1976 and 2006. During the 2017-2018 flu season,
900,000 people were hospitalized and 80,000 died in the United
States.

Which of the following is accurate regarding influenza transmission and infection?

Influenza B is generally more pathogenic than influenza A

Adults typically shed the influenza virus longer than children

Transmission of influenza from asymptomatic persons is possible

Eating poultry or pork infected with influenza may still transmit infection, even
when properly cooked

Influenza viruses spread from human to human via aerosols

created when an infected individual coughs or sneezes. Infection
occurs after an immunologically susceptible person inhales the
aerosol. As in other viral infections, systemic symptoms result
from release of inflammatory mediators. The incubation period of
influenza ranges from 1 to 4 days. Aerosol transmission may
occur 1 day before the onset of symptoms; thus, it may be
possible for transmission to occur from asymptomatic persons or
persons with subclinical disease who may be unaware that they
have been exposed to the disease.
Influenza results from infection with one of three basic types of
influenza virus: A, B, or C. Influenza A is generally more
pathogenic than influenza B. Epidemics of influenza type C have
been reported, especially in young children and military recruits;
however, the disease course is usually less severe than that
associated with influenza A. Fever is less prominent with type C.
Viral shedding occurs at the onset of symptoms or just before the
onset of illness (0-24 hours). Shedding continues for 5-10 days.
Young children may shed virus longer, placing others at risk of
contracting infection. In highly immunocompromised persons,
shedding may persist for weeks to months.
Transmission of influenza from poultry or pigs to humans
appears to occur predominantly as a result of direct contact with
infected animals. The risk is especially high during slaughter and
preparation for consumption; eating properly cooked meat poses
no risk.

Which of the following is accurate regarding the presentation and physical examination
of patients with influenza?

Diarrhea associated with influenza infection is more commonly seen in adults

than in children

Fever associated with influenza infection is generally lower in young adults than
in elderly patients

Nasal discharge is present in most patients with influenza, and rhinitis is

commonly the chief symptom

Onset of influenza symptoms can occur suddenly or can progress more slowly,
and patients who received vaccine may have milder symptoms

The presentation of influenza virus infection varies; however, it

usually includes many of the symptoms described below.
Patients with influenza who have preexisting immunity or who
have received vaccine may have milder symptoms. Onset of
illness can occur suddenly over the course of a day, or it can
progress more slowly over the course of several days. Typical
signs and symptoms include (not necessarily in order of
prevalence):
 Cough and other respiratory symptoms
 Fever
 Headache
 Myalgias
 Nasal discharge
 Red, watery eyes
 Sore throat
 Tachycardia
 Weakness and severe fatigue
Cough and other respiratory symptoms may be initially minimal
but frequently progress as the infection evolves. Patients may
report nonproductive cough, cough-related pleuritic chest pain,
and dyspnea. In children, diarrhea may be a feature.
The general appearance varies among patients who present with
influenza. Some patients appear acutely ill, with some weakness
and respiratory findings, whereas others appear only mildly ill.
Upon examination, patients may have some or all of the
following findings:
 Fever of 100-104°F; fever is generally lower in elderly
patients than in young adults
 Tachycardia, which most likely results from hypoxia, fever,
or both
 Pharyngitis—Even in patients who report a severely sore
throat, findings may range from minimal infection to more
severe inflammation
 Eyes may be red and watery
 Skin may be warm to hot, depending on core temperature
status; patients who have been febrile with poor fluid intake
may show signs of mild volume depletion with dry skin
 Pulmonary findings may include dry cough with clear lungs
or rhonchi, as well as focal wheezing
 Nasal discharge is absent in most patients
 Fatigued appearance
Which of the following is accurate regarding the workup of
patients with suspected influenza?

Rapid influenza diagnostic tests tend to be more sensitive in

adults than in children and better at detecting influenza B than
influenza A

Because they are more sensitive in detecting influenza than

culture methods, direct immunofluorescent tests on fresh
specimens are recommended

Chest radiography performed early on during an influenza

infection typically reveals extensive bilateral symmetrical patch
infiltrates

The criterion standard for confirming influenza virus infection

remains reverse transcription-polymerase chain reaction or viral
culture of nasopharyngeal or throat secretions

The criterion standard for confirming influenza virus infection is

reverse transcription-polymerase chain reaction or viral culture of
nasopharyngeal or throat secretions. Rapid diagnostic tests for
influenza are available and are becoming more widely used.
These tests have high specificity but only moderate sensitivity.
The US Food and Drug Administration has waived federal
Clinical Laboratories Improvement Amendments (CLIA)
requirements and cleared for marketing 7 rapid influenza
diagnostic tests that directly detect influenza A or B virus-
associated antigens or enzyme in throat swabs, nasal swabs, or
nasal washes. These tests can produce results within 30
minutes. A meta-analysis examining the accuracy of rapid
influenza diagnostic tests found a pooled sensitivity of 62% and
specificity of 98%. The tests tended to be more sensitive in
children (67%) than in adults (54%) and better at detecting
influenza A (65%) than influenza B (52%).
Some laboratories offer direct immunofluorescent tests on fresh
specimens, but these tests are labor- and personnel-intensive
and less sensitive than culture methods. In order to overcome
the expensive and time-consuming obstacle of culturing, several
serologic tests have become available. In reality, many of these
are not bedside tests; generally, 30-60 minutes is required to
perform the tests' multiple steps. Test sensitivities generally
range from 60% to 70%.
In elderly or high-risk patients with pulmonary symptoms, chest
radiography is indicated to exclude pneumonia. Early
radiographic findings include no or minimal bilateral symmetrical
interstitial infiltrates. Later, bilateral symmetrical patch infiltrates
become visible. Focal infiltrates indicate superimposed bacterial
pneumonia.
For more on the workup of influenza, read here.
Which of the following is accurate regarding influenza
vaccination?

In the Northern Hemisphere, all persons aged 6 months or older

should receive influenza vaccine annually, by the end of October,
if possible

Vaccination becomes effective against influenza rapidly, within 3-

4 days after administration

Influenza vaccination is contraindicated in persons with a history

of egg allergy who have experienced only hives after exposure to
eggs

Influenza vaccination is contraindicated in women who are

beyond the first trimester of pregnancy

In the Northern Hemisphere, all persons aged 6 months or older

should receive influenza vaccine annually, by the end of October,
if possible. Influenza vaccination should not be delayed to
procure a specific vaccine preparation if an appropriate one is
already available. Influenza vaccine provides reasonable
protection against immunized strains. The vaccination becomes
effective 10 to 14 days after administration.
Persons with a history of egg allergy who have experienced only
hives after exposure to egg should receive influenza vaccine.
Inactivated influenza vaccine or trivalent recombinant influenza
vaccine (RIV3) should be used. RIV3 may be used for persons
aged 18 years or older who have no other contraindications.
A CDC analysis stressed the importance of vaccinating pregnant
womenregardless of trimester and prompt treatment with a
neuraminidase inhibitor (ie, within 2 days of symptom onset) if
influenza occurs during pregnancy. Vaccination of high-risk
pregnant patients also provides some protective immunity for
newborns and reduces subsequent hospitalizations in the
infants.
For more on influenza vaccination, read here.
Which of the following is accurate regarding antiviral
pharmacologic therapy?

Neuraminidase inhibitors have activity against influenza A only,

whereas adamantanes have activity against influenza A and B

Antiviral medications for influenza include oseltamivir, zanamivir,

and baloxavir marboxil, and clinicians should monitor local
antiviral resistance surveillance data

Antiviral agents should be initiated only within the first 48-72

hours after symptoms first appear

Treatment with antiviral drugs is contraindicated in pregnant

women with influenza

Recently, the FDA approved baloxavir marboxil tablets for the

treatment of acute uncomplicated influenza in people aged 12
years and older who have been symptomatic for no longer than
48 hours. This drug is the first new antiviral flu treatment with a
novel mechanism of action to be approved by the FDA in
approximately 20 years.
The CDC has made the following recommendations regarding
the use of antiviral drugs in influenza:
 Antiviral treatment is recommended as soon as possible for
patients with confirmed or suspected influenza who have
severe, complicated, or progressive illness or who require
hospitalization
 Antiviral treatment is recommended as soon as possible for
outpatients with confirmed or suspected influenza who are
at higher risk for influenza complications on the basis of
their age or underlying medical conditions; clinical
judgment should be an important component of outpatient
treatment decisions
 Currently recommended antiviral medications include
oseltamivir and zanamivir
 Oseltamivir may be used for treatment or
chemoprophylaxis of influenza in infants younger than 1
year, when indicated
 Antiviral treatment also may be considered on the basis of
clinical judgment for any outpatient with confirmed or
suspected influenza who does not have known risk factors
for severe illness, if treatment can be initiated within 48
hours of illness onset
 Because antiviral resistance patterns can change over
time, clinicians should monitor local antiviral resistance
surveillance data
The neuraminidase inhibitors (oseltamivir, peramivir, and
zanamivir) have activity against influenza A and B viruses
(including H1N1), whereas the adamantanes (amantadine and
rimantadine) have activity against influenza A viruses only. Since
2006, only the neuraminidase inhibitors have been
recommended because of widespread resistance to the
adamantanes among influenza A (H3N2) virus strains.
Oseltamivir resistance emerged in the United States during the
2008-2009 influenza season.
To be effective as treatment, these agents must be administered
within 48 hours of symptom onset. These agents are most
effective if started within the first 24 hours of symptoms and less
effective if begun 24 to 48 hours after symptoms appear.
Prompt use of antiviral drugs during the 2009 H1N1 influenza
pandemic improved survival among severely ill pregnant
women. A CDC study of 347 pregnant women (including 272
who required ICU admission but survived and 75 who died) and
15 severely ill postpartum women (9 of whom died) found that
94.8% of survivors received antiviral treatment with oseltamivir or
zanamivir compared with 86.1% of those who died, a statistically
significant difference. Baloxavir marboxil, an oral cap-dependent
endonuclease inhibitor that blocks influenza virus proliferation by
inhibiting the initiation of mRNA synthesis, has received approval
in Japan for the treatment of influenza and is under study in the
United States.