FUTURE CONSIDERATIONS

Influenza activity in the southern hemisphere can be informative regarding the impact of 2009 H1N1 in the months ahead. Reports from Peru indicate that 8381 cases were confirmed between May 9, 2009, and September 27, 2009, with 137 confirmed influenza-related deaths. This translated to an estimated case fatality rate of 1.71% based on confirmed cases. Because the number of confirmed cases is undoubtedly lower than actual, this estimated case fatality rate is likely higher than actual. By comparison, the crude case fatality rate of the 1918 influenza pandemic is estimated to have been greater than 2.5%. The basic reproduction number (R0), used to define the average number of secondary cases generated in a susceptible population from 1 primary case, was estimated to be between 1.2 and 1.7, consistent with other reports. If the R0 is greater than 1, a pandemic can occur; however, when R0 is less than 1, a pandemic will not occur. By comparison, the R0 of the 1918 virus was estimated to have exceeded 1.3 and may have approached 3.1.

On the basis of historical interpretations of the waves of impact during the 1918 pandemic, some have speculated that this current 2009 H1N1 virus has potential to become more virulent. The first wave in 1918 was mild. The second was more virulent and within weeks had spread to most of the world’s cities. The first wave seemed to provide seroprotection for the second; however, neither the first nor the second wave provided seroprotection for the third. Current data do not show increasing influenza virulence over time with this virus; however, different countries, regions, and populations have experienced differing degrees of epidemic severity depending on multiple host and environmental factors. No evidence of the evolution of the 2009 H1N1 virus toward a more transmissible or pathogenic phenotype has been reported. Experience in the southern hemisphere has been similar to observations in the northern hemisphere between April and June 2009.

Despite efficient human transmission, the 2009 H1N1 virus lacks the molecular determinants usually associated with transmission. For example, 2009 H1N1 contains a glutamate at position 627 in the PB2 protein, characteristic of avian influenza viruses; human influenza viruses traditionally have a lysine at that position. Such findings suggest that this virus could enhance our knowledge of molecular determinants for transmissibility.

Although it has maintained susceptibility to NA inhibitors, multiple cases of oseltamivir-resistant 2009 H1N1 have been reported. Two immunocompromised patients infected with 2009 H1N1 in the state of Washington with no epidemiological link developed oseltamivir resistance during treatment. Isolates from both patients were initially susceptible to oseltamivir; however, during treatment with the drug, a mutation involving the substitution of a histidine for tyrosine at position 275 (H275Y) of the NA gene occurred, rendering the virus resistant. Zanamivir remains active against isolates with the H275Y mutation. Subsequently, the first epidemiologically linked cases of oseltamivir-resistant 2009 H1N1 infection were reported in 2 adolescent girls in North Carolina who had stayed in the same cabin during a summer camp. These isolated viruses contained the H275Y mutation in addition to a second previously unreported 2009 H1N1 mutation (I223V). If oseltamivir resistance is suspected, physicians may choose to treat with zanamivir or a combination of oseltamivir and amantadine or rimantadine.

CONCLUSION

The 2009 H1N1 virus has created the first influenza pandemic in more than 4 decades. Unlike previous pandemics, some of the population has had prior infection experience with this subtype. Thus far, in contrast to seasonal influenza viruses, the 2009 H1N1virus has disproportionately affected younger populations. Its virulence is similar to that of seasonal influenza viruses. The 2009 H1N1 virus is resistant to adamantanes but has remained susceptible to the NA inhibitors with few exceptions. Vaccine trials confirm that only 1 dose is required for persons older than 9 years and 2 doses for children aged 6 months to 9 years. Larger vaccine trials are in progress. Whether this virus will displace or cocirculate with the current seasonal strains is unknown. Clinicians are advised to stay up to date regarding H1N1 by frequently checking Web sites authored by the CDC and state health departments. An effective response to this pandemic and the amelioration of the associated morbidity and mortality must be predicated on a vaccinated, working, and informed health care population.
Seth J. Sullivan, MD, Robert M. Jacobson, MD, Walter R. Dowdle, PhD and Gregory A. Poland, MD
Published December 10, 2009, doi: 10.4065/mcp.2009.0588   Mayo Clinic Proceedings January 2010   vol. 85 no. 1 64-76

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