Influenza: Difference between revisions
 
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==Background==
==Background==
*A history of influenza vaccination does not rule out influenza in an ill patient with clinical signs and symptoms compatible with influenza. Therefore, vaccination status should not impede the initiation of prompt antiviral treatment.
*Human Influenza type A and B cause majority of infections. Type A has more severe disease course.


===Transmission===
===Transmission===
*Occurs in 6ft radius around infected pt who is sneezing and/or coughing
*Occurs in 6ft radius around infected patient who is sneezing and/or coughing
*Viral shedding lasts ~5d (starts 24-48hr before onset of symptoms)
*Viral shedding lasts ~5d (starts 24-48hr before onset of symptoms)
**Longer duration of shedding occurs in children, elderly, pts w/ chronic illnesses  
**Longer duration of shedding occurs in children, elderly, patients with chronic illnesses  
**Shedding from asymptomatic individuals doesn't contribute significantly to transmission
**Shedding from asymptomatic individuals does not contribute significantly to transmission
*Use of either N95 or plain surgical mask by healthcare professionals caring for patients with proven influenza helps to decrease rates of provider contraction of influenza.<ref>SURGICAL MASK VS. N95 RESPIRATOR FOR PREVENTING INFLUENZA AMONG HEALTH CARE WORKERS Loeb, M., et al, JAMA 302(17):1865, November 4, 2009</ref>


===Risk Factors (for complicated course)===
===Risk Factors (for complicated course)===
*Age <2 years or >65 years
*Age <2 years or >65 years
*Pregnancy through 2 weeks after delivery
*[[Pregnancy]] through 2 weeks after delivery
*Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
*Chronic pulmonary (including [[asthma]]), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
*Immunosuppression, including that caused by medications or by HIV
*Immunosuppression, including that caused by medications or by HIV
*Persons younger than 19 years of age who are receiving long-term aspirin therapy
*Persons younger than 19 years of age who are receiving long-term aspirin therapy
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*Morbid obesity
*Morbid obesity
*Patients in nursing homes or chronic-care facilities
*Patients in nursing homes or chronic-care facilities
===Vaccination Status===
*A history of influenza vaccination does not rule out influenza in an ill patient with clinical signs and symptoms compatible with influenza.
*Therefore, vaccination status should not impede the initiation of prompt antiviral treatment.


==Clinical Features==
==Clinical Features==
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**[[Fever]]
**[[Fever]]
**[[Headache]]
**[[Headache]]
**Myalgias
**[[Myalgia]]s
**Malaise
**Malaise
*Respiratory
*Respiratory
**Non-productive cough
**Non-productive [[cough]]
**[[Sore throat]]
**[[Sore throat]]
**Rhinorrhea
**[[Rhinorrhea]]


===Cough and Fever===
===Cough and Fever===
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*Children < 5 yo - 64%
*Children < 5 yo - 64%
*Adults - unreliable predictors especially when older than 60 yo
*Adults - unreliable predictors especially when older than 60 yo
===Convalescence===
*Most gradually improve over 2-5d, although may last for one week or more
*Some have persistent weakness lasting several weeks (postinfluenza asthenia)


==Differential Diagnosis==
==Differential Diagnosis==
{{ILI DDX}}
{{Acute Fever DDX}}
{{Acute Fever DDX}}


==Diagnosis==
==Evaluation==
===Workup===
===Workup===
*Influenza PCR preferred for inpatients (sensitivity >95%)
*Influenza PCR preferred for inpatients (sensitivity >95%)
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*Rapid tests specific but not sensitive (cannot be used to rule-out)
*Rapid tests specific but not sensitive (cannot be used to rule-out)


===Evaluation===
===Diagnosis===
====Outpatients====
====Outpatients====
*Risk factors:
*Risk factors:
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*Do not send Point of Care influenza test
*Do not send Point of Care influenza test
*Send diagnostic test for influenza
*Send diagnostic test for influenza
**Influenza PCR preferred for inpatients (see Diagnosis section)
**Influenza PCR preferred for inpatients
*Empirically treat for influenza using antivirals
*Empirically treat for influenza using antivirals
**Most effective when administered when symptoms of influenza have occurred for < 48 hours
**Most effective when administered when symptoms of influenza have occurred for < 48 hours
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==Management==
==Management==
===[[Isolation Precautions]]===
*Droplet precautions
**If the patient is in an area in which they are in contact with other patients or need to be transported and thus may come in close contact (<3 feet) with staff, visitors, or other patients, the patient needs to wear a surgical mask (or N-95 respirator, if not available).
===Antiviral Treatment===
''Despite questions on efficacy and safety, CDC still recommends treatment for all hospitalized patients and outpatients at risk for complications<ref>Fiore AE, et al. Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). CDC. Recommendations and Reports. January 21, 2011. 60(RR01);1-24.</ref>''
''Despite questions on efficacy and safety, CDC still recommends treatment for all hospitalized patients and outpatients at risk for complications<ref>Fiore AE, et al. Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). CDC. Recommendations and Reports. January 21, 2011. 60(RR01);1-24.</ref>''
===[[Oseltamivir]] (Tamiflu)===
''Shorten duration of illness by 16.8 hrs while NNTH (number needed to harm) was 28 in regards to causing n/v, HA, and renal and psych syndromes<ref>Jefferson T, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348:g2545.</ref>''
*Greatest benefit if within 48hrs of symptom onset<ref>CDC Guidelines. 2015-2016. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm</ref>
**However, may be beneficial up to 4-5 days, including in pregnant patients
**Early treatment of hospitalized pts can reduce death
====Dosing====
*'''Age <1 year:''' 3mg/kg PO BID x 5 days
*'''<15kg:''' 30mg PO BID x 5 days
*'''15-23kg:''' 45mg PO BID x 5 days
*'''24-40kg:''' 60mg PO BID x5d
*'''Adult:''' 75mg PO BID x 5 days
===[[Zanamivir]] (Relenza)===
''Relatively contraindicated in patients with [[asthma]], [[COPD]], or [[pregnancy]]. Shorten duration of illness by 14.4 hrs with no reduction in flu-related complications<ref>Heneghan CJ, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports. BMJ. 2014; 348:g2547.</ref>''
====Dosing====
*'''Age >7yo:''' 10mg (2 inhalations) BID x 5d
*'''Prophylaxis:''' 10mg (2 inhalations) once daily x 7 days
**Not for age < 5yo
{| class="wikitable"
{| class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Antiviral Agent'''
| align="center" style="background:#f0f0f0;"|'''Antiviral Agent'''
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| align="center" style="background:#f0f0f0;"|'''Adverse Events'''
| align="center" style="background:#f0f0f0;"|'''Adverse Events'''
|-
|-
| Oseltamivir (Tamiflu®)
| [[Oseltamivir]] (Tamiflu®)
||
||
*Treatment: any age
*Treatment: any age
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*Adverse events: nausea, vomiting. Sporadic, transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults.
*Adverse events: nausea, vomiting. Sporadic, transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults.
|-
|-
| Zanamivir (Relenza®)
| [[Zanamivir]] (Relenza®)
||
||
*Treatment: >7 yrs
*Treatment: >7 yrs
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*Allergic reactions: oropharyngeal or facial edema.   
*Allergic reactions: oropharyngeal or facial edema.   
*Adverse events: diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose and throat infections.
*Adverse events: diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose and throat infections.
|-
|[[Baloxavir marboxil]] (Xofluza®)
||
*Treatment: >12 years
*Prophylaxis: not yet approved for this indication
||children less than 12 or weighing less than 40kg, pregnancy, breastfeeding
||
*Adverse Events: diarrhea, bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache
*Allergic reactions: oropharyngeal or facial edema
|}
|}


===[[Isolation Precautions]]===
===[[Oseltamivir]] (Tamiflu)===
*Droplet precautions
''Shorten duration of illness by 16.8 hrs while NNTH (number needed to harm) was 28 in regards to causing nausea/vomiting, headache and renal and psych syndromes<ref>Jefferson T, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348:g2545.</ref>''
**If the patient is in an area in which they are in contact with other patients or need to be transported and thus may come in close contact (<3 feet) with staff, visitors, or other patients, the patient needs to wear a surgical mask (or N-95 respirator, if not available).
*Greatest benefit if within 48hrs of symptom onset<ref>CDC Guidelines. 2015-2016. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm</ref>
**However, may be beneficial up to 4-5 days, including in pregnant patients
**Early treatment of hospitalized patients can reduce death
 
====Dosing====
*'''Age <1 year:''' 3mg/kg PO BID x 5 days
*'''<15kg:''' 30mg PO BID x 5 days
*'''15-23kg:''' 45mg PO BID x 5 days
*'''24-40kg:''' 60mg PO BID x5d
*'''Adult:''' 75mg PO BID x 5 days
 
===[[Zanamivir]] (Relenza)===
''Relatively contraindicated in patients with [[asthma]], [[COPD]], or [[pregnancy]]. Shorten duration of illness by 14.4 hrs with no reduction in flu-related complications<ref>Heneghan CJ, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports. BMJ. 2014; 348:g2547.</ref>''
 
====Dosing====
*'''Age >7yo:''' 10mg (2 inhalations) BID x 5d
*'''Prophylaxis:''' 10mg (2 inhalations) once daily x 7 days
**Not for age < 5yo
 
===Baloxavir marboxil (Xofluza)===
''Only approved for patients >12 years old and >40kg in weight, no current safety data exists for pregnancy and breastfeeding.<ref>https://www.cdc.gov/flu/treatment/baloxavir-marboxil.htm</ref> More expensive but one time dosing. Genentech, its creator, states a recent phase III trial has shown it to be effective for prophylaxis but not currently FDA indicated for this.<ref>https://www.gene.com/download/pdf/xofluza_prescribing.pdf</ref>
 
====Dosing====
*'''Weight between 40-80kg:''' 40mg PO once (20 mg tab x2)
*'''Weight >80kg:''' 80mg PO once (40mg tab x2)
*'''Prophlyaxis:''' not yet approved for this indication by CDC or FDA
 
===NOT Indicated===
*Amantadine and other M2 viral proton channel blockers are '''no longer indicated for influenza treatment''' due to nearly 100% resistance
 
==Disposition==


==Complications==
==Complications==
*[[Pneumonia]]
*[[Pneumonia]]
**Primary influenza PNA
**Primary influenza pneumonia
***Most severe and least common type of PNA
***Most severe and least common type of pneumonia
***Rare in otherwise healthy adults
***Rare in otherwise healthy adults
***Consider in pts w/ persistent and worsening symptoms (esp high fever, SOB, cyanosis)
***Consider in patients with persistent and worsening symptoms (esp high fever, shortness of breath, cyanosis)
***CXR shows b/l opacities w/ or w/o superimposed consolidation
***[[CXR]] shows bilateral opacities with or with out superimposed consolidation
**Secondary bacterial PNA
**Secondary bacterial pneumonia
***Exacerbation of fever and respiratory symptoms after initial improvement
***Exacerbation of fever and respiratory symptoms after initial improvement
****Higher fever, productive cough, radiographic evidence of infiltrates
****Higher fever, productive cough, radiographic evidence of infiltrates
***Microbiology
***Microbiology
****[[Pneumococcus]], [[S. aureus]] (including [[MRSA]]), H. flu
****[[Pneumococcus]] and [[S. aureus]] (including [[MRSA]]) most common (35% and 28%, respectively)<ref>Klein EY, Monteforte B, Gupta A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394-403. doi:10.1111/irv.12398</ref>
*****[[MRSA]] associated with necrotizing cavitary infections with high mortality rate in previously healthy young people<ref>Centers for Disease Control and Prevention (CDC). Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza--Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep. 2007;56(14):325-329.</ref><ref>Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006;12(6):894-899. doi:10.3201/eid1206.051141</ref>
*[[Otitis Media]]
*[[Otitis Media]]
**More common in children
**More common in children
*Myositis and [[rhabdo]]
*[[Myositis]] and [[rhabdomyolysis]]
**More common in children
**More common in children
**Extreme tenderness of affected muscles (most commonly in the legs)
**Extreme tenderness of affected muscles (most commonly in the legs)

Latest revision as of 21:51, 1 February 2021

Background

  • Human Influenza type A and B cause majority of infections. Type A has more severe disease course.

Transmission

  • Occurs in 6ft radius around infected patient who is sneezing and/or coughing
  • Viral shedding lasts ~5d (starts 24-48hr before onset of symptoms)
    • Longer duration of shedding occurs in children, elderly, patients with chronic illnesses
    • Shedding from asymptomatic individuals does not contribute significantly to transmission
  • Use of either N95 or plain surgical mask by healthcare professionals caring for patients with proven influenza helps to decrease rates of provider contraction of influenza.[1]

Risk Factors (for complicated course)

  • Age <2 years or >65 years
  • Pregnancy through 2 weeks after delivery
  • Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
  • Immunosuppression, including that caused by medications or by HIV
  • Persons younger than 19 years of age who are receiving long-term aspirin therapy
  • American Indians and Alaska Natives
  • Morbid obesity
  • Patients in nursing homes or chronic-care facilities

Vaccination Status

  • A history of influenza vaccination does not rule out influenza in an ill patient with clinical signs and symptoms compatible with influenza.
  • Therefore, vaccination status should not impede the initiation of prompt antiviral treatment.

Clinical Features

Cough and Fever

Odds that acute cough and fever are due to flu during flu season:[2]

  • Adolescents ≥ 12 yo - 79-88%
  • Children 5-12 yo - 71-83%
  • Children < 5 yo - 64%
  • Adults - unreliable predictors especially when older than 60 yo

Convalescence

  • Most gradually improve over 2-5d, although may last for one week or more
  • Some have persistent weakness lasting several weeks (postinfluenza asthenia)

Differential Diagnosis

Influenza-Like Illness

Fever

Infectious

Non-infectious

Evaluation

Workup

  • Influenza PCR preferred for inpatients (sensitivity >95%)
  • RSV/Flu/metapneumovirus test low sensitivity for adults (48-60%) and children (62-72%), with turnaround time <24 hours
  • The Viral Respiratory Panel (influenza, RSV, adenovirus, parainfluenzavirus) discouraged (sensitive 70-90%) with 3-5 days turnaround
  • Rapid tests specific but not sensitive (cannot be used to rule-out)

Diagnosis

Outpatients

  • Risk factors:
    • Yes
      • Do NOT send Point of Care influenza test
      • Do NOT send diagnostic test for influenza
      • Empirically treat for influenza using antivirals if symptoms for <48 hours
    • No
      • Do NOT send Point of Care influenza test.
      • Do NOT send diagnostic test for influenza.
      • May consider treating with anti-influenza antivirals if symptoms <48 hours

Admitted Patients

  • Do not send Point of Care influenza test
  • Send diagnostic test for influenza
    • Influenza PCR preferred for inpatients
  • Empirically treat for influenza using antivirals
    • Most effective when administered when symptoms of influenza have occurred for < 48 hours
    • May be benefit when initiated in severely ill inpatients with 48 hours to 5 days of symptoms
    • No evidence of benefit after 5 days of symptoms
  • Treat empirically promptly with oseltamavir unless there is an alternative diagnosis
  • Droplet precautions (see below)

Management

Isolation Precautions

  • Droplet precautions
    • If the patient is in an area in which they are in contact with other patients or need to be transported and thus may come in close contact (<3 feet) with staff, visitors, or other patients, the patient needs to wear a surgical mask (or N-95 respirator, if not available).

Antiviral Treatment

Despite questions on efficacy and safety, CDC still recommends treatment for all hospitalized patients and outpatients at risk for complications[3]

Antiviral Agent Recommended For Not Recommended With Adverse Events
Oseltamivir (Tamiflu®)
  • Treatment: any age
  • Prophylaxis: >3 months
 N/A
  • Adverse events: nausea, vomiting. Sporadic, transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults.
Zanamivir (Relenza®)
  • Treatment: >7 yrs
  • Prophylaxis >5 years
 Underlying respiratory disease (e.g., asthma, COPD)
  • Allergic reactions: oropharyngeal or facial edema.
  • Adverse events: diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose and throat infections.
Baloxavir marboxil (Xofluza®)
  • Treatment: >12 years
  • Prophylaxis: not yet approved for this indication
 children less than 12 or weighing less than 40kg, pregnancy, breastfeeding
  • Adverse Events: diarrhea, bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache
  • Allergic reactions: oropharyngeal or facial edema

Oseltamivir (Tamiflu)

Shorten duration of illness by 16.8 hrs while NNTH (number needed to harm) was 28 in regards to causing nausea/vomiting, headache and renal and psych syndromes[4]

  • Greatest benefit if within 48hrs of symptom onset[5]
    • However, may be beneficial up to 4-5 days, including in pregnant patients
    • Early treatment of hospitalized patients can reduce death

Dosing

  • Age <1 year: 3mg/kg PO BID x 5 days
  • <15kg: 30mg PO BID x 5 days
  • 15-23kg: 45mg PO BID x 5 days
  • 24-40kg: 60mg PO BID x5d
  • Adult: 75mg PO BID x 5 days

Zanamivir (Relenza)

Relatively contraindicated in patients with asthma, COPD, or pregnancy. Shorten duration of illness by 14.4 hrs with no reduction in flu-related complications[6]

Dosing

  • Age >7yo: 10mg (2 inhalations) BID x 5d
  • Prophylaxis: 10mg (2 inhalations) once daily x 7 days
    • Not for age < 5yo

Baloxavir marboxil (Xofluza)

Only approved for patients >12 years old and >40kg in weight, no current safety data exists for pregnancy and breastfeeding.[7] More expensive but one time dosing. Genentech, its creator, states a recent phase III trial has shown it to be effective for prophylaxis but not currently FDA indicated for this.[8]

Dosing

  • Weight between 40-80kg: 40mg PO once (20 mg tab x2)
  • Weight >80kg: 80mg PO once (40mg tab x2)
  • Prophlyaxis: not yet approved for this indication by CDC or FDA

NOT Indicated

  • Amantadine and other M2 viral proton channel blockers are no longer indicated for influenza treatment due to nearly 100% resistance

Disposition

Complications

  • Pneumonia
    • Primary influenza pneumonia
      • Most severe and least common type of pneumonia
      • Rare in otherwise healthy adults
      • Consider in patients with persistent and worsening symptoms (esp high fever, shortness of breath, cyanosis)
      • CXR shows bilateral opacities with or with out superimposed consolidation
    • Secondary bacterial pneumonia
      • Exacerbation of fever and respiratory symptoms after initial improvement
        • Higher fever, productive cough, radiographic evidence of infiltrates
      • Microbiology
        • Pneumococcus and S. aureus (including MRSA) most common (35% and 28%, respectively)[9]
          • MRSA associated with necrotizing cavitary infections with high mortality rate in previously healthy young people[10][11]
  • Otitis Media
    • More common in children
  • Myositis and rhabdomyolysis
    • More common in children
    • Extreme tenderness of affected muscles (most commonly in the legs)
  • Pericarditis/myocarditis
    • Rare complication

See Also

References

  1. ↑ SURGICAL MASK VS. N95 RESPIRATOR FOR PREVENTING INFLUENZA AMONG HEALTH CARE WORKERS Loeb, M., et al, JAMA 302(17):1865, November 4, 2009
  2. ↑ CDC Clinical Flu
  3. ↑ Fiore AE, et al. Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). CDC. Recommendations and Reports. January 21, 2011. 60(RR01);1-24.
  4. ↑ Jefferson T, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348:g2545.
  5. ↑ CDC Guidelines. 2015-2016. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
  6. ↑ Heneghan CJ, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports. BMJ. 2014; 348:g2547.
  7. ↑ https://www.cdc.gov/flu/treatment/baloxavir-marboxil.htm
  8. ↑ https://www.gene.com/download/pdf/xofluza_prescribing.pdf
  9. ↑ Klein EY, Monteforte B, Gupta A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394-403. doi:10.1111/irv.12398
  10. ↑ Centers for Disease Control and Prevention (CDC). Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza--Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep. 2007;56(14):325-329.
  11. ↑ Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006;12(6):894-899. doi:10.3201/eid1206.051141
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