Effect of oseltamivir, zanamivir or oseltamivir-zanamivir combination treatments on transmission of influenza in households.
BACKGROUND
The effectiveness of neuraminidase inhibitors to reduce transmission when used as treatment in influenza-infected patients remains debated.


METHODS
In a prespecified analysis of a blinded randomized controlled trial on the efficacy of oseltamivir-zanamivir combination therapy versus oseltamivir and zanamivir monotherapy conducted during the 2008-2009 seasonal influenza epidemic, we compared the rate of secondary illness in household contacts of influenza-positive index patients between arms. Secondary illness was defined as occurrence in contacts of fever plus cough within 7 days from randomization of index patients. Analyses were conducted according to the delay between patients' onset of symptoms and intervention.


RESULTS
A total of 543 household contacts of 267 index patients were included, of which 466 had follow-up assessment. A secondary illness was reported in 58 (12.5%) contacts with no significant difference between arms overall (P=0.07). When the analysis was limited to the 232 contacts of 136 index patients with first treatment intake within 24 h of onset of symptoms, a lower rate of secondary illness was reported in the combination therapy arm (2 of 56 [4%]) than in the oseltamivir arm (14 of 81 [17%]; P=0.014) and the zanamivir arm (14 of 95 [15%]; P=0.031). Multivariate analysis accounting for intra-household correlation confirmed these findings.


CONCLUSIONS
Our analysis suggests a greater effectiveness of the combination therapy to reduce transmissibility when given to the index patient within 24 h of onset of symptoms. As the finding was obtained from a subgroup analysis, it should be interpreted with caution.
APHP, Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France. carrat@u707.jussieu.fr
Fabrice
F
Carrat
Xavier
X
Duval
Florence
F
Tubach
Anne
A
Mosnier
Sylvie
S
Van der Werf
Annick
A
Tibi
Thierry
T
Blanchon
Catherine
C
Leport
Antoine
A
Flahault
France
F
Mentré
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003371:Cough / Q000188:drug therapy / Q000821:virology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005191:Family Characteristics; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000821:virology; D005500:Follow-Up Studies; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000472:pathogenicity; D007251:Influenza, Human / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D053139:Oseltamivir / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult; D053243:Zanamivir / Q000627:therapeutic use*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir