Monday, June 22, 2009

Signature features of Influenza Pandemics – Implications for Policy

In a recent Perspective article in the New England Journal of Medicine (N Engl J Med 360; 25 June 18, 2009), Mark A. Miller et al. enumerate the signature features of influenza pandemics and discuss their implications for policy.

“Past pandemics were characterized by [I’ve numbered these for ease of reading]
1. a shift in virus subtype
2. shifts of the highest death rates to younger populations
3. successive pandemic waves
4. higher transmissibility than seasonal influenza
5. differences in impact in different geographic regions.”

The authors go on to outline how knowledge of the signature features of pandemics can be used to inform and prioritize national strategies and aid in addressing initial and successive pandemic waves:

1. “Although influenza pandemics are classically defined by the first of these features, the other four characteristics are frequently not considered in response plans.…
2. Advance knowledge of which subpopulations are most likely to be at increased risk for death can shape the optimization of control strategies.…
3. The occurrence of multiple waves potentially provides time for health authorities to implement control strategies for successive waves. …
4. Since models of containment and pandemic control assumed lower reproductive numbers for the current epidemic than those that have been historically observed, they are likely to be overly optimistic regarding the success of containment strategies.…
5. This variability is probably explained by the complex heterogeneity in the degree of immunity in local populations to the circulating influenza strains, as well as by transmission factors such as geographic conditions, social mixing, degree of viral infectiousness, and ‘seasonal forcing’ (small seasonal changes in the effective transmission rate). The benefits of sharing data on all these variables provide major incentives for international collaboration."

Of interest to those following our blog, the authors also provide their perspective on other subtypes which may pose a pandemic threat:

“Although the A/H5N1 influenza subtype has spread to avian populations in more than 30 countries and infected nearly 400 persons, with a case fatality rate above 50%, scientists disagree about its pandemic potential. Such a highly pathogenic virus does not usually adapt well to its host, since it tends to kill faster than it can be transmitted. Other avian subtypes are also considered to be pandemic threats. Although avian viruses have a different tropism for respiratory cellular receptors in birds than for those in humans, gradual viral mutations or gene-segment reassortments in a mammal “mixing vessel” could result in a novel viral clade or subtype that spreads rapidly in a population that has largely not previously been exposed to it. Such changes may have occurred in the current swine H1N1 circulating strain.

The death toll of a future pandemic depends not only on the virulence of the virus in question but also on the rapidity with which we are able to introduce effective preventive and therapeutic measures. Although A/H5N1 has been associated with a “cytokine-storm” phenomenon reminiscent of that observed in 1918 and 1919, new methods for the timely manufacture and administration of antiviral agents and influenza and pneumococcal vaccines could mitigate the effects of a pandemic.

The evidence of multiple waves in the 20th-century pandemics underlines the importance of active real-time viral surveillance on a global scale. Transnational collaborations are crucial for the effective exchange of genomic, clinical, and epidemiologic data that will make possible the development of vaccines and treatment protocols and the identification of the best population-based strategies….

Though the rapidity of transmission of influenza virus during pandemics necessitates immediate action, it can be hoped that close collaborations and lessons drawn from previous pandemics will contribute to reducing national and global mortality. The documented relevant signature features can help health authorities prioritize national strategies and aid international collaborators in addressing the initial and successive waves of illnesses and deaths.”

This article can be viewed in its entirety (be sure to scroll down to the second half of the first page that displays on the site) at:

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