Emergence of amantadine-resistant H5N2 avian influenza virus during a simulated layer flock treatment program

An experiment was designed to simulate field conditions in which preventive treatment is not initiated until after some chickens in a flock are infected with avian influenza (AI). Twelve hens began to receive amantadine hydrochloride on the day they were inoculated (day 0) with highly pathogenic AI virus, A/chicken/Pa/1370/83. These hens remained clinically normal through 8 days postinoculation (PI), but five died after day 9; mean death time (MDT) was 18 days. Three of 12 hens given amantadine beginning 1 day PI died (MDT 5.4 days), seven of 12 hens given amantadine beginning 3 days PI died (MDT 3.7 days), and all 12 inoculated hens not given amantadine died (MDT 4.9 days). The delayed mortality in the day 0 treatment group was likely due not to the original inoculum but to the emergence of a drug-resistant virus population. Virus isolated from a dead hen from that group was resistant to the actions of amantadine in both in ovo and in vivo tests. The lack of late mortality due to the drug-resistant virus in the day 1 and day 3 treatment groups, which were in close contact with the day 0 treatment group, was attributed to their becoming infected before treatment with the drug and to the development of protective immunity.