INFLUENZA

See also "Influenza Vaccine"

I. Clinical diagnosis of influenxa

  1. 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
  2. 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)

II. Laboratory diagnosis of influenza (Source: Med. Lett. 41:121, 1999)

  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. Pts should avoid contact w/uninfected persons even if receiving tx
  5. Specific drugs
  1. Adamantanes, a.k.a. "M2 ion blockers"--Note that increasing resistance in the U.S. has been seen among influenza A isolates as of the 2005-2006 influenza season.
    1. Amantadine 100mg BID x 5d (for prophylaxis, 100mg BID or 200mg QD)
  1. Can reduce severity & duration of influenza (A only) in adults if given < 48h after onset of sx
  2. Can give to pts > 1y old
  3. Has anticholinergic properties
  4. Higher incidence of CNS side f/x than rimantadine (behavioral changes, delirium, hallucinations; mostly in elderly and pts with renal insufficiency)
  1. Rimantadine 100mg BID or 200mg QD x 5d (same dose for prophylaxis)
  1. Can reduce severity & duration of influenza (A only) in adults if given < 48h after onset of sx
  2. Can give to kids only for prophylaxis; to adults for tx or prophylaxis
    1. However, one meta-analysis found no benefit of Rimantadine vs. placebo for post-exposure prophylaxis for influenza A (Lancet 367:303, 2006--AFP)
  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.

(Sources include MMWR 48 [RR-6]:1, 1998--AFP)