ScienceWeek

EPIDEMIOLOGY: ON PREDICTION IN INFLUENZA CONTROL

The following points are made by Derek J. Smith (Science 2006 312:392):

1) Few would be surprised if there were an influenza H5 (bird flu) pandemic in humans. The source and basic mechanisms of the threat are clear, yet there is much we cannot predict: how severe such a pandemic would be, how fast it would spread, where it would start, whether it would become resistant to existing drugs, what strain to use in a vaccine, or whether a vaccine would be available in time to protect a large proportion of the population. Most important, we do not know how close the virus is to sustained human-to-human transmission, and thus to initiating a pandemic.

2) How can there be this much uncertainty when many of the best virologists, molecular biologists, epidemiologists, and public health scientists work or have worked on the influenza virus, when so much is already known, and when the global surveillance system is better than the system for any other pathogen? The answer lies in the inherent variability of influenza viruses, in their seemingly endless capacity to continue to change, and, in the case of type A viruses, in their rich and diverse ecology in many species and their ability to cross species barriers and adapt to new hosts [1,2].

3) An influenza H5 virus capable of causing a pandemic in humans is likely to differ from the avian H5 viruses that have caused a pandemic in birds and have occasionally caused highly pathogenic infections in humans. A human-adapted H5 virus, by definition, should be able to transmit effectively among humans; it might have antigenic differences compared with avian strains and would possibly be less pathogenic in humans. Adaptation to the human host may occur as a result of either mutation or a combination of mutation and reassortment with an existing human virus. A key event would probably be a change in the binding specificity of the virus from a receptor in the lower respiratory tract to one in the upper respiratory tract. This may result in a decrease in at least the initial pathogenicity, as the infection would be more likely to start with a tracheal bronchitis rather than pneumonia [3,4]. In addition, if human adaptation resulted from reassortment with a human virus, pathogenicity factors on gene segments not in the resulting reassortment would be lost, and there may be a degree of prior immunity in the population to the human virus derived gene segments, both further reducing pathogenicity in humans.

4) In summary: The threat of pandemic human influenza looms as we survey the ongoing avian influenza pandemic and wonder if and when it will jump species. What are the risks and how can we plan? The nub of the problem lies in the inherent variability of the virus, which makes prediction difficult. However, it is not impossible; mathematical models can help determine and quantify critical parameters and thresholds in the relationships of those parameters, even if the relationships are nonlinear and obscure to simple reasoning. Mathematical models can derive estimates for the levels of drug stockpiles needed to buy time, how and when to modify vaccines, whom to target with vaccines and drugs, and when to enforce quarantine measures. Regardless, the models used for pandemic planning must be tested, and for this we must continue to gather data, not just for exceptional scenarios but also for seasonal influenza.[1-5]

References (abridged):

1. R. G. Webster, W. J. Bean, O. T. Gorman, T. M. Chambers, Y. Kawaoka, Microbiol. Rev. 56, 152 (1992)

2. T. Kuiken et al., Science 312, 394 (2006)

3. K. Shinya et al., Nature 440, 435 (2006)

4. D. van Riel et al., Science 312, 399 (2006)

5. N. M. Ferguson et al., Nature 437, 209 (2005)

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