A very tricky business: the importance of accurately predicting the severity of swine flu

Abstract

Each year, inf luenza viruses cause substantial morbidity and mortality worldwide. Occasionally, a new strain arises against which there is no immunity in the population, and that can therefore spread rapidly around the world, causing a pandemic. This strain usually replaces the previous seasonal strain and continues to circulate in the interpandemic periods, causing seasonal epidemics that are generally less severe than in pandemic years due to the build-up of immunity in the population. There is historical evidence of influenza pandemics since the Middle ages [1]; in the past century, there were three flu pandemics of very different severity. The 1918 pandemic caused an estimated 20–40 million deaths worldwide, whereas the 1957 and 1968 pandemics were less severe, responsible for around 1–4 million deaths each [1]. The case–fatality ratio, defined as the proportion of people exhibiting clinical symptoms who will die as the result of the disease, is an important indicator of the severity of a disease. Good estimates of the case–fatality ratio are particularly important very early on in the pandemic, in order to shape the appropriate public health response. If indeed the current pandemic had been caused by a strain similar to the avian strain H5N1 with an estimated case–fatality ratio of over 50% in humans [2], much more aggressive strategies for control would be needed than in the current H1N1 (2009) pandemic. Flu viruses mutate rapidly, and selective pressure on a newly arisen strain would be expected to be even higher than the pressure on a seasonal strain as it still adapts to the human host. Indeed, in past pandemics different pandemic waves with different severity have been observed – for instance, a mild spring wave followed by a more severe autumn wave in the 1918 pandemic [3]. In order to pick up any changes in severity in a timely manner so that the public health response can be adapted, it is therefore important to have estimates of the case–fatality ratio that are consistent over time. While the 1918 pandemic was very severe, with an estimated case–fatality ratio of around 2% [4], the other two pandemics in the last century were milder, with case–fatality ratios similar to those seen in seasonal flu. This also appears to be the case for the current influenza A H1N1 2009 pandemic strain. However, with a new pandemic flu strain, there is no pre-existing immunity in the population, and therefore the attack rates, that is the proportion of the population getting infected during the pandemic, are expected to be much higher than those seen in the interpandemic periods. Furthermore, the age groups that carry the largest burden of morbidity and mortality differ between pandemic and seasonal flu, with much of the mortality of seasonal flu restricted to the elderly, whereas in pandemics, and to a lesser extent also the first post-pandemic years, this tends to be shifted to younger age groups [5].