The post-exposure therapeutic efficacy of injectable peramivir against highly pathogenic avian influenza type A H5N1 was evaluated in mice and in ferrets. Seventy to eighty percent of the H5N1-infected peramivir-treated mice, and 70% in the oseltamivir treated mice survived the 15-day study period, as compared to 36% in control (vehicle) group. Ferrets were infected intranasally with H5N1 followed by treatment with multiple doses of peramivir. In two of three trials, a statistically significant increase in survival over a 16-18 day period resulted from peramivir treatment, with improved survival of 40-64% in comparison to mock-treated or untreated animals. Injected peramivir mitigates virus-induced disease, reduces infectious virus titers in the lungs and brains and promotes survival in ferrets infected intranasally with this highly neurovirulent isolate. A single intramuscular peramivir injection protected mice against severe disease outcomes following infection with highly pathogenic avian influenza and multi-dose treatment was efficacious in ferrets.
The replication efficiency and multi-organ dissemination of some influenza A (H5N1) viruses requires a rapid (re)evaluation of the available antiviral strategies. We assessed five regimens of the neuraminidase (NA) inhibitor peramivir in mice inoculated with H5N1 virus. The regimens differed by: (1) frequency of administration on first day (once vs twice); (2) duration of administration (1 day vs 8 days); (3) route of administration (intramuscular [IM] injection alone or followed by oral administration). In all regimens, BALB/c mice were administered 30 mg/kg peramivir IM one hour after lethal challenge with 5 MLD 50 of A/Vietnam/1203/04 (H5N1) influenza virus. When given only on the day of inoculation, a single IM injection produced a 33% survival rate, which increased to 55% with two injections. Eight-day regimens significantly increased survival; two IM injections followed by 7 daily IM injections was the most effective regimen (100% survival; inhibition of replication in lungs and brain). When this 8-day regimen began at 24 hours after inoculation, 78% of mice survived; 56% survived when treatment began at 48 after hours. Anti-HA antibody titer differed with the peramivir regimen and corresponded to the severity of disease. Overall, our results demonstrate that IM administration of peramivir is effective in promoting the survival of mice infected with systemically replicating H5N1 virus.
I n the pale predawn hours of Old San Juan last February, Neysha Burgos-Nieves and Hector Rosado loaded a battered black car with everything they might need for a few daysfrom bottled water and protein bars to flashlights and a change of clothes. Their first stop was more than two hours away, high in Puerto Rico's isolated central mountains. Although it had been more than four months since Hurricane Maria had slammed into the island in September 2017, much of the US territory remained without electricity, water or mobile-phone service. If Burgos-Nieves and Rosado ran into trouble once they left the relative safety of San Juan, the two research assistants would be on their own. Their goal was simple, if ambitious: calculate the excess mortality from Hurricane Maria. In other words, determine how many people perished in the months following the storm and subtract the number of people who, on average, probably would have died anyway. Burgos-Nieves, Rosado and their adviser Domingo Marqués, a clinical psychologist at Carlos Albizu University in San Juan, had no idea what that estimate might be. But anyone who had spent time in Puerto Rico knew that the excess deaths were much higher than the government's official count of 64. It was gruelling work. Many of the researchers in Marqués's team had lost electricity, water and, in some cases, their homes. Nearly all admit to breaking down in tears at least once. "Every day, you would hear more stories of suffering. It was exhausting, " Rosado says. But the project held a deeper meaning than simply counting those who had died. "We were giving light where there was a lot of darkness. We gave light to the truth, " Burgos-Nieves says. Throughout history, humanity has lurched from one disaster to the next. Some are born of nature's capriciousness; others arise from When scientists tallied how many people perished in Hurricane Maria and other crises, they battled statistical, political and physical hurdles. But new methods are in the works.
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