Managed Care - October 2008 - (Page IS3) severe illness (CDC 2008a). Three influenza pandemics have been studied in an effort to gain a better understanding of the genetic diversity of the virus: the 1918 Spanish influenza (H1N1); the 1957 Asian influenza (H2N2); and the 1968 Hong Kong influenza (H3N2). Both the 1957 and 1968 pandemics were caused by viruses that clearly resulted from genetic reassortment events of the prevailing strain. The 1957 pandemic was caused by a hybrid virus resulting from a dual infection with the avian H2N2 and human H1N1 influenza strains. The resultant species contained a hemagglutinin, a neuraminidase, and a gene for a polymerase protein from the avian virus and five genetic segments from the human virus (Figure 1). In the 1968 variant, the hemagglutinin and polymerase genes of this virus were further replaced with alternative avian genes to form H3N2. This viral form continues to be the major source of influenza infections in humans today. Interestingly, however, Taubenberger (2005) found that the 1918 pandemic was caused not by a virus formed by reassortment, but by the mutation of a purely avian strain into an excessively virulent species that adapted to humans. Researchers worked with two preserved virus specimens from the 1918 pandemic — one, a soldier’s lung sample that had been stored at Walter Reed Medical Center, in Washington, and the other from an Eskimo who died in the pandemic and had been buried frozen in permafrost in Alaska — and were able to sequence the genes of the viral isolate. They found that all eight genes of the viral strain were derived from a duck virus that had adapted or mutated over time to permit human-tohuman transmission. This finding may have alarming implications for the future. A current avian virus, H5N1 influenza A, is extremely pathogenic and is decimating the fowl population in at least eight Asian countries. The strain has been spreading to new avian and nonavian species. The virus has infected 379 humans, causing 239 deaths (WHO 2008). If it were to adapt for widespread human transmission, there is fear of a pandemic of unusually high morbidity and mortality. Influenza epidemics The “flu” is perhaps the most widely disseminated respiratory infection in the world. There are approximately 1918 “Spanish influenza” H1N1 influenza virus 1957 “Asian influenza” H2N2 influenza virus 1968 “Hong Kong influenza” H3N2 influenza virus Next pandemic influenza H2N2 avian virus H1N1 human virus H3 avian virus H2N2 human virus Avian virus or Bird-to-human transmission of H1N1 virus avian virus H3N2 human virus Reassortment Hemagglutinin Neuraminidase Reassortment ? All 8 genetic segments thought to have originated from avian influenza virus 3 new genetic segments from avian influenza virus introduced (HA, NA, PB1); contained 5 RNA segments from 1918 2 new genetic segments from avian influenza virus introduced (HA, PB1); contained 5 RNA segments from 1918 All 8 genes new or further derivative of 1918 virus FIGURE 1 Mechanism of genetic reassortment in influenza virus: origin of the 1957 and 1968 strains Source: Belshe 2005 Copyright© 2005 Massachusetts Medical Society. All rights reserved. IMMUNIZATION STRATEGIES / MANAGED CARE 3
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