Human Mortality From H5N1 - Predicting Pandemic Mortality Rate

Predicting Pandemic Mortality Rate

Although the actual rate of mortality during a pandemic is unknowable in advance, it is pressing to predict the possible ranges for that lethality responsibly in advance. The pre-pandemic case fatality ratio of over 50% provides a grim backdrop for the fact that the currently circulating H5N1 strains have certain genetic similarities with the Spanish Influenza pandemic virus. In that pandemic, 50 million to 100 million people worldwide were killed during about a year in 1918 and 1919. The highly lethal second and third waves of the 1918 Spanish flu evolved through time into a less virulent and more transmissible human form. Although the overall fatality rate for the Spanish Flu was at most 1% to 2% of the population, the lethal waves of the Spanish Flu are not reported to have emerged with anything like the over-50% case fatality ratio observed to date in human H5N1 infection. Studies indicating that an H5N1 pandemic may be more pathogenic than was the Spanish Flu include a mouse study in which the H5N1 virus elicited significantly higher levels of pro-inflammatory cytokines in the lungs.

Unfortunately, a human H5N1 pandemic might emerge with initial lethality resembling that over-50% case fatality now observed in pre-pandemic H5N1 human cases, rather than with the still-high 1-2% seen with the Spanish Flu or with the lower rates seen in the two more recent influenza pandemics. As a WHO working group noted,

Determinants of virulence and transmissibility.

... One especially important question is whether the H5N1 virus is likely to retain its present high lethality should it acquire an ability to spread easily from person to person, and thus start a pandemic. Should the virus improve its transmissibility by acquiring, through a reassortment event, internal human genes, then the lethality of the virus would most likely be reduced. However, should the virus improve its transmissibility through adaptation as a wholly avian virus, then the present high lethality could be maintained during a pandemic.

The U.S. CDC presents a similarly sobering conclusion authored by Robert G. Webster et al.:

... We cannot afford simply to hope that human-to-human spread of H5N1 will not happen and that, if it does, the pathogenicity of the virus will attenuate. Notably, the precursor of the severe acute respiratory syndrome (SARS)–associated coronavirus (31) repeatedly crossed species barriers, probably for many years, before it finally acquired the capacity for human-to-human transmission, and its pathogenicity to humans was not attenuated. We cannot wait and allow nature to take its course. SARS was interrupted by early case detection and isolation, but influenza is transmissible early in the course of the disease and cannot be controlled by similar means.

Although some mammalian adaptations have been noted, H5N1 remains better adapted for infecting birds than mammallian hosts, which is why the disease it causes is called a bird flu. No pandemic strain of H5N1 has yet been found. The precise nature and extent of the genetic alterations that might change one of the currently circulating avian influenza strains into a human flu strain cannot be known in advance.

While many of the current H5N1 strains circulating in birds can generate a dangerous cytokine storm in healthy adult humans, the ultimate pandemic strain might arise from a less-lethal strain, or its current level of lethality might be lost in the adaptation to a human host.

If H5N1 mutates so that it can jump from human to human, while maintaining a relatively high level of mortality, how many people could die? Risk communication analysts Peter M. Sandman and Jody Lanard give a round-up of the various estimates:

Worldwide mortality estimates range all the way from 2-7.4 million deaths (the “conservatively low” pandemic influenza calculation of a flu modeling expert at the U.S. Centers for Disease Control and Prevention) to 1000 million deaths (the bird flu pandemic prediction of one Russian virologist). The estimates of most H5N1 experts range less widely but still widely. In an H5N1 pandemic, the experts guess that somewhere between a quarter of us and half of us would get sick, and somewhere between one percent and five percent of those who got sick would die — the young and hale as well as the old and frail. If it's a quarter and one percent, that's 16 million dead; if it's a half and five percent, it's 160 million dead. Either way it's a big number.

The renowned virus expert Robert G. Webster provided perhaps the most extreme estimate when he acknowledged in March 2003 that H5N1 has the theoretical capacity to mutate into a form that could kill one half of the human population, stating, "Society just can't accept the idea that 50 percent of the population could die. And I think we have to face that possibility".