Neuraminidase inhibitors for preventing and treating influenza in healthy adults.
BACKGROUND
Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in interpandemic years and in a pandemic.


OBJECTIVE
To assess the effects of NIs in preventing or ameliorating influenza, its transmission and its complications in healthy adults and to estimate the frequency of adverse effects.


METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2004 to September, Week 4 2005), EMBASE (2003 to June 2005) and contacted manufacturers, researchers in the field, and authors of studies evaluated in the review.


METHODS
Randomised or quasi-randomised placebo-controlled studies of NIs in healthy adults exposed to naturally occurring influenza.


METHODS
Two authors applied inclusion criteria, assessed trial quality and extracted data. We structured the comparisons into prophylaxis, treatment and adverse events with further subdivision by outcome and dose.


RESULTS
We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza.


CONCLUSIONS
Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.
Jefferson
T O
TO
Demicheli
V
V
Di Pietrantonj
C
C
Jones
M
M
Rivetti
D
D
D000081:Acetamides / Q000627:therapeutic use; D000588:Amines / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir; D011714:Pyrans / Q000627:therapeutic use; D012794:Sialic Acids / Q000627:therapeutic use; D053243:Zanamivir
D000081:Acetamides; D000588:Amines; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir