Comparison of the efficacies of amantadine treatment of swine-origin influenza virus A H1N1 and seasonal influenza H1N1 and H3N2 in Japan (2008-2009)

Amantadine is not thought to be effective for the treatment of swine-origin influenza virus (S-OIV) based on an analysis of genetic sequences of the M2 protein. However, the actual clinical efficacy of amantadine has not been well documented. Here, we were able to compare the efficacies of amantadine and neuraminidase inhibitors. Subjects consisted of 428 patients, including 144 with seasonal influenza (flu) identified between 2008 and 2009, and 284 with S-OIV identified between July 1 and November 30, 2009. Diagnosis of flu was established using a rapid diagnostic kit obtained commercially in Japan. Body temperature sheets were obtained from 95% of the S-OIV patients. Times required to recover normal body temperature were compared among subjects using different antiviral drugs. Genetic abnormalities in the M2 protein were also investigated in 66 randomly selected subjects from within the patient pool. Overall, the average hours required to recover normal body temperature in S-OIV patients treated with amantadine (160 cases), with oseltamivir (59 cases), or with zanamivir (65 cases) were 33.9 ± 20.7, 31.7 ± 16.0, or 36.3 ± 21.6, respectively. These differences were not statistically significant. The N31S abnormality was found in all 14 samples taken from the H3N2 patients and in all of the 23 samples taken from in S-OIV patients. However, this abnormality was not found in any of the 30 samples taken from seasonal H1N1 patients. Amantadine was found to be equally effective in treating S-OIV patients as neuraminidase inhibitors. The genetic abnormality resulting in S31N amino acid conversion identified in some of the H3N2 and S-OIV patients is thought to alter the function of M2 protein only mildly.