Monday, December 20, 2004

How long can you hold your breath?

A recent issue of Nature (16 December 2004) contains an important article by Mills, Robins and Lipsitch on the 1918 influenza pandemic (the "Spanish flu"). By fitting parameters in a mathematical model (technically called a SEIR deterministic model, a system of ordinary differential equations) by using mortality data from 45 cities they estimated a median reproductive number of less than four. The reproductive number ("R naught," usually written R0) is the average number of additional cases each infected case produces. If R0 drops below one, the disease dies out. The 1918 flu estimate of less than four is not large compared to other contagious diseases [cf. measles (13 - 14), pertussis (16 - 18) or polio (8 - 12) (data from Anderson and Mays, Infectious Diseases of Humans, Oxford U. Press, 1991)], there is reasonable expectation that vigorous control measures might quickly shorten a pandemic.

But two characteristics of the 1918 pandemic are not so encouraging. One is the extremely rapid spread, with a doubling time of only 3 days, attributable to the short serial interval, the average time between a primary case and the secondary cases it produces. The other is the high case fatality, roughly ten times that of previous influenza pandemics. The likely explanation for the latter is the absence of any effective population immunity to influenza A(H1N1) in 1918. We are faced with a similar situation if H5N1 were to get loose by mutating to a form where person-to-person transmission becomes possible. In this context, the rather low R0 of the 1918 flu sounds more ominous: it shows the virus does not have to mutate to a super-contagious form to have catastrophic effects.

Given the speed of transmission and the essential lack of enough antivirals or a vaccine against this virus, Mills et al. suggest the most effective control measures at the start of such an epidemic would be to limit person-to-person contact. This could be done through quarantine, cancellation of public meetings and gatherings and possibly shut-down of public transport. The economic costs, of course, would be enormous. But as they point out:
Increased passenger travel relative to 1918 will facilitate the spread of a new virus across the globe. It is imperative that real-time surveillance information be shared freely, and that preventive measures be taken very early in a new pandemic. Therefore, while the relatively modest reproductive number estimated for 1918 pandemic influenza suggests the feasibility of controlling a similar future pandemic, significant planning and investment will be required to facilitate a rapid and effective response.
So, once again, I ask what preparations are being made for an immediate response should surveillance data suggest that a match has lit the tinder? Do we have in place measures that would reduce person-to-person contact? Or are we going to make it up as we go along, too little, too late and "holding our breath" the while?