Definition
A.An acute respiratory illness caused by the influenza virus, an orthomyxovirus.
Incidence
A.3 to 5 million severe cases and 250,000 to 500,000 deaths annually worldwide.
B.Annually, since 2010, in the United States.
1.Between 9.2 and 35.6 million related illnesses.
2.Hospitalization rate between 140,000 and 710,000.
3.Death rates range between 12,000 and 56,000.
Pathogenesis
A.A single-stranded RNA virus attaches to the epithelial cells in the respiratory tract and replicates inside of them. Ongoing destruction and eradications of these cells occurs.
B.Infectious particles are released through budding,
causing rapid invasion of neighboring cells and a cyclical process.
Predisposing Factors
A.All individuals are at risk. Influenza vaccination can decrease risk. However, this decrease changes annually, pending vaccination efficacy.
B.Those at higher risk for complications include children younger than 5 years of age, adults older than 65 years old, pregnant women, long-term care facility residents, Alaskan Natives, and American Indians.
C.Other high risk groups include patients with underlying neurological, cardiac, or pulmonary conditions; immunosuppressed individuals (with conditions such as hypogammaglobulinemia, HIV, or cancer); obese patients; and those with other significant comorbid conditions.
Subjective Data
A.Common complaints/symptoms.
1.Fever.
2.Diffuse myalgias.
3.Fatigue.
4.Cough and respiratory symptoms, including rhinorrhea and sore throat.
5.Headache.
B.Common/typical scenario.
1.Symptoms: Abrupt in onset; some patients may remember exact time.
2.Abrupt onset of fever with myalgia and respiratory symptoms during influenza season (late fall to early spring): High likelihood for influenza.
C.Family and social history.
1.Positive comorbid conditions or hereditary immunodeficiencies.
2.Recent exposure to individuals with symptoms of influenza: Symptoms generally appear 2 days after exposure (airborne, touching contaminated surfaces).
3.Crowded environments.
D.Review of systems.
1.Neuro: Anorexia, dizziness, or weakness.
2.Gastrointestinal (GI) symptoms: Uncommon in adults.
3.Respiratory: Nonproductive cough (productive cough is more common in pneumonia).
4.HEENT: Runny nose, sore throat.
Physical Examination
A.Relatively benign, with nonspecific findings.
B.Constitutional: Ill appearing, fatigued appearing.
C.Fever: Usually 100°F–104°F; rarely much higher other than in complicated cases.
D.Possible hyperemia or cervical lymphadenopathy (more common in younger patients).
E.Mild tachycardia from hypoxia, dehydration, and fever.
F.Pharyngitis.
G.Conjunctivitis.
H.Pulmonary findings: Possibly dry cough, focal wheezing, or rhonchi.
I.Skin: May appear flushed, warm to hot, with diaphoresis depending on the core body temperature.
Diagnostic Tests
A.Clinical diagnosis in patients with influenza symptoms during influenza season or during outbreaks. The combination of fever with cough, sore throat, and myalgia can improve diagnostic accuracy. In periods of outbreak, patients with combinations of any of these symptoms may be reasonably treated with neuraminidase inhibitors without testing.
B.Rapid influenza tests.
1.Polymerase chain reaction (PCR): Most sensitive and specific and can differentiate subtypes.
2.Rapid antigen tests: Result obtained in 15 minutes; less sensitive.
3.Gold standard: Viral culture; may take 72 hours to obtain results.
Differential Diagnosis
A.HIV.
B.Pneumonia.
C.Cytomegalovirus (CMV).
D.Legionnaires’ disease.
E.Hantavirus pulmonary disease.
F.Acute respiratory distress syndrome (ARDS).
G.Other viral upper respiratory infections (URIs).
H.Tick- and mosquito-borne illnesses.
1.However, these tend to present in different seasons or patients have exposure history or travel history.
Evaluation and Management Plan
A.General plan.
1.Usually self-limited; duration can be shortened with the use of neuraminidase inhibitors.
2.Airborne isolation.
3.Supportive care.
B.Patient/family teaching points.
1.Handwashing is key to help prevent spread.
2.Annual influenza vaccines for all those who can receive them (most individuals).
C.Pharmacotherapy.
1.Neuraminidase inhibitors.
a.Oseltamivir (Tamiflu).
i.Most commonly used agent; can cause nausea and vomiting.
ii.Treatment: 75 mg BID for 5 days, starting within 48 hours of symptom onset.
iii.Prophylaxis: 75 mg daily for 10 days within 48 hours of contact with infected person.
b.Zanamivir (Relenza).
i.Inhaled agent that should not be used in patients with pulmonary disease.
ii.Should be avoided in lactose intolerant patients (powder mixture contains lactose/milk proteins).
c.Peramivir (Rapivab).
i.Intravenous formulation for those who cannot use oral route.
ii.Treatment: 600 mg IV 1 dose.
d.Laninamivir.
i.Still under development: Nasal spray.
e.All neuraminidase inhibitors: Can cause neuropsychiatric effects based on their mechanism of action. Less commonly, they may cause skin reactions, including erythema multiforme or Stevens–Johnson syndrome.
f.Adamantane antivirals (amantadine and rimantadine).
i.Target M2 protein of influenza A and therefore not active against influenza B; little to no activity against current influenza A strains.
ii.Amantadine and rimantadine not currently recommended for treatment of influenza A, due to high levels of resistance among many circulating strains of influenza.
iii.Amantadine and rimantadine are safe in children older than 1 year of age.
g.Ribavirin.
i.Nucleoside analog active against influenza A and B.
ii.Not Food and Drug Administration (FDA) approved; rarely used except with consultation of infectious disease specialists via inhaled route.
h.Baloxavir marboxil.
i.FDA approved.
ii.Influenza treatment 40 to less than 80 kg: 40 mg as a single dose within 48 hours of onset of influenza symptoms.
iii.80 kg: 80 mg as a single dose within 48 hours of onset of influenza.
Follow-Up
A.Follow-up other than regular visits with primary care physician is usually not required.
Consultation/Referral
A.If hospitalized, consider consultation with infectious disease and pulmonary specialists.
B.If illness is significant, a critical care specialist may be required.
C.In general, influenza tends to be an outpatient illness cared for by primary care and urgent care providers.
Special/Geriatric Considerations
A.Annual influenza vaccination is indicated in all patients who are at least 6 months of age except:
1.Patients who have had a severe allergic reaction to prior influenza vaccine (this does not include minor flu-like symptoms).
2.Those with a severe allergic reaction to egg proteins if receiving the live attenuated vaccine (nasal).
B.Immunocompromised patients, pregnant women, and patients 50 years of age or older should not receive live attenuated vaccine.
C.Adults under the age of 65 with no significant comorbidities generally have self-limiting disease.
D.Children younger than 5 years of age, but especially under 2 years, are at higher risk of influenza complications.
E.Patients older than 65 years have an increased risk of developing complications.
Bibliography
Centers for Disease Control and Prevention. (2016). National and state healthcare associated infections progress report. Retrieved from http://www.cdc.gov/HAI/pdfs/progress-report/hai-progress-report.pdf
Centers for Disease Contro and Prevention. (2019, February 19). Disease burden of influenza. Retrieved from https://www.cdc.gov/flu/about/disease/burden.htm
Longo, D., Fauci, A., Kasper, D., Hauser, S., Jameson, J., & Loscalzo, J.(Eds.). (2015). Harrison’s principles of internal medicine (19th ed.). New York, NY: McGraw Hill.