See also "Influenza Vaccine"

I. Clinical diagnosis of influenxa

  1. "Classic" clinical features include abrupt onset of dry cough, fever, and myalgias.  Presence of all three, when local influenza activity exists, has a positive predictive value of > 50% for influenza infection
  2. GI symptoms are not typical but may occur
  3. The following were ass'd with influenza in a retrospective analysis of 3744 pts presenting with febrile illnesses, 2/3 of whom had eventual laboratory confirmation of influenza (Arch. Int. Med. 160:3243, 2000--JW):
    1. Confirmed fever (80% of pts with temp > 38'C had influenza)
    2. Fever + cough (positive predictive value 79%, negative predictive value 49%)
    3. Cough
    4. Absence of sore throat
  4. In a meta-analysis of 6 studies of clinical diagnosis of influenza, absence of fever, cough, or nasal congestion were ass'd with likelihood ratios of 0.4, 0.42, and 0.49 (all sig.) for influenza; in pts > 60yo, absnece of sneezing was ass'd with LR of 0.47 for influenza (JAMA 293:987, 2005--abst)
  5. Clinical decision rule rule for influenza diagnosis (from J. Am. B. Fam Med. 25:55, 2012)
Clinical featurePoints
Acute onset within prior 48h1
Chills or sweats1
Fever AND cough2

Predicted probability of influenza in setting of influenza activity in the community, based on total score:

II. Laboratory diagnosis of influenza-Note that false-positive results can occur with rapid tests if influenza vaccine administered in prior 7d

  1. Directigen Flu A (only detects influenza A)
  2. Flu OIA--Detects A or B in nasopharyngeal swabs, throat swabs, sputum, and nasal aspirates. Takes 15-20min. Sens/Spec 77%/93%
  3. Quickvue--Detects A or B in nasal swab or aspirate. Takes 10min. Sens/Spec 73-81%/95-99%
  4. ZStatflu--Detects A or B in throat swabs. Takes 20min. Sens/Spec 57-65%/95-100%

III. Antivirals for prophylaxis/tx of influenza:

  1. 70-90% effective for pre-exposure prophylaxis
  2. Both cause GI side f/x in about 3%
  3. Tx for the shortest duration possible (3-5d or till 24-48h after sx disappear) to avoid inducing resistance
  4. May not be effective if started > 48h after onset of symptoms, though commonly used beyond that time window in hospitalized patients
  5. Pts should avoid contact w/uninfected persons even if receiving tx
  6. CDC advises antivirals for influenza if:
    1. < 2yo or high-risk and < 5yo
    2. > 65yo
    3. Chronic pulmonary, cardiovascular, renal, hepatic, hematologic, metabolic, or neurologic disorders
    4. Immunosuppression
    5. Pregnancy or < 2wks postpartum
    6. < 19yo and on long-term aspirin therapy
    7. Native Americans
    8. Morbid obesity
    9. Resident of a chronic care facility
  7. Specific drugs
  1. Neuraminidase inhibitors
    1. Zanamivir (Relenza; inhaled also intranasal) 10mg BID x 5d (for prophylaxis, 10mg QD)
  1. Active against Influenza A & B
  2. Inhibits influenza neuraminidase
  3. Effective at tx of acute influenza
    1. Ass'd with more rapid relief of sx w/o sig. diff. in side f/x in a randomized trial of 455 pts (mean age 37) with sx of influenza for < 36h ("MIST" trial, Lancet 352:1877, 1998--JW)
    2. 1256 teenagers and adults with flu-like sx randomized to zanamivir vs. placebo; resolution of sx occurred 1d sooner on average in zamanivir group (J. Inf. Dis. 180:254, 1999--JW)
  4. Effective at prevention of influenza in healthy adults
    1. 1107 adults 18-69yo randomized to Zamanivir 10mg inhaled QD x 4wks during flu season; RR of laboratory-confirmed clinical influenza was 33%--sig.; JAMA 282:31, 1999--abst)
  5. Post-exposure prophylaxis
    1. In a randomized study in 837 family members of pts with influenza > 5yo randomized to Zamanavir 10mg inhaled BID x 5d vs. placebo to start within 36h of onset of sx in the index case; over 2wk f/u, incidence of clinical influenxa was 8% in Zamanavir group vs. 29% in placebo group (NEJM 343:1282, 2000--AFP)
  6. Can cause cough, nasal & throat discomfort, and, in pts with asthma, bronchospasm (Med. Lett. 45:78, 2003)
  1. Oseltamivir (Tamiflu) 75mg PO BID x 5d (for prophylaxis, 75mg QD)
    1. Reduces severity & duration of influenza (A and B) sx c/w placebo BUT causes nausea and/or vomiting in 20% of pts (JAMA 283:1016, 2000--JW)
    2. 695 kids 1-12yo wit influenza randomized to Oseltamivir 2mg/kg BID vs. placebo x 5d; active tx group had sig. more rapid resolution of sx (median duration 101 vs. 137h) (Ped. Inf. Dis. J. 20:127, 2001--JW)
    3. Less effective against influenza B than influenza A in one observational study (Clin. Inf. Dis. 44:197, 2007--JW)
    4. Case reports exist of neuropsychiatric adverse effects, e.g. delirium.
  1. Adamantanes, a.k.a. "M2 ion blockers" (Amantadine, Rimantadine)-No longer used for treatment of influenza due to resistance
(Sources include MMWR 48 [RR-6]:1, 1998-AFP; Core Content Review of Family Medicine, 2012)