Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group.
BACKGROUND
As prophylaxis against influenza in families, amantadine and rimantadine have had inconsistent effectiveness, partly because of the transmission of drug-resistant variants from treated index patients. We performed a double-blind, placebo-controlled study of inhaled zanamivir for the treatment and prevention of influenza in families.


METHODS
We enrolled families (with two to five members and at least one child who was five years of age or older) before the 1998-1999 influenza season. If an influenza-like illness developed in one member, the family was randomly assigned to receive either inhaled zanamivir or placebo. The family member with the index illness was treated with either 10 mg of inhaled zanamivir (163 subjects) or placebo (158) twice a day for 5 days, and the other family members received either 10 mg of zanamivir (414 subjects) or placebo (423) once a day as prophylaxis for 10 days. The primary end point was the proportion of families in which at least one household contact had symptomatic, laboratory-confirmed influenza.


RESULTS
The proportion of families with at least one initially healthy household contact in whom influenza developed was smaller in the zanamivir group than in the placebo group (4 percent vs. 19 percent, P<0.001); the difference represented a 79 percent reduction in the proportion of families with at least one affected contact. Zanamivir provided protection against both influenza A and influenza B. A neuraminidase-inhibition assay and sequencing of the neuraminidase and hemagglutinin genes revealed no zanamivir-resistant variants. Among the subjects with index cases of laboratory-confirmed influenza, the median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivir was well tolerated.


CONCLUSIONS
When combined with the treatment of index cases, prophylactic treatment of family members with once-daily inhaled zanamivir is well tolerated and prevents the development of influenza. In this study there was no evidence of the emergence of resistant influenza variants.
Hayden
F G
FG
University of Virginia, Charlottesville, USA.
Gubareva
L V
LV
Monto
A S
AS
Klein
T C
TC
Elliot
M J
MJ
Hammond
J M
JM
Sharp
S J
SJ
Ossi
M J
MJ
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D005192:Family Health; D005260:Female; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000302:isolation & purification; D009981:Influenza B virus / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D011714:Pyrans; D012367:RNA, Viral / Q000032:analysis; D017423:Sequence Analysis, RNA; D012794:Sialic Acids / Q000627:therapeutic use*; D053243:Zanamivir
D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012367:RNA, Viral; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir