Some Thoughts on Deficiencies in our Understanding of Epidemics

I'm sitting here trying to think of good research ideas to focus on; the areas of interest to me are (1) Infectious Disease, but specifically areas of epidemiology related to those infections that cause massive morbidity and mortality over short periods of time. So, this covers what is typically called "Emerging" and "Re-Emerging" infections as well as agents typically considered agents of biowarfare/bioterrorism in addition to a few infections that we constantly risk the evolution of a repeated outbreak (such as pandemic influenza).

Given the areas of specific interest I have, I also like to consider the sorts of methodologies which I either (1) have some basic skill in, or (2) would very much like to learn much more about. Of course, as a physician, this includes the clinical acumen to some degree, but I find myself more drawn to an interest in information technology and computational technologies to solve old problems which we still struggle with.

So, then, what sorts of problems do we find that we still need to address? And what sorts of questions or problems could one solve that is likely to make a significant impact to the world at large?

Well, what I am feeling that I would like to learn much more about is the computational modeling and simulation of epidemics. For one, I wonder if our understanding of the basic modeling of epidemics is still insufficient. For this, I will need to learn much more about the current field and then try to identify areas which are still lacking.

In addition, I believe that in the past, we have not had sufficient technology to fully incorporate the multitude of factors (human, societal, environmental, microbiological, political, etc...) that come in to play. For this, of course I need to learn much more, but I think it is much safer to say that this is likely to be the case. There is much technology that is only in its infancy which is applicable to these problems, (i.e. better computational power, graphical information systems, etc.)

Well, just some thoughts; more of me putting "ink on paper" to form my thoughts.

More to come...

Technorati Tags: Epidemiology , GIS , Computational Biology

Researchers Find Mutation in Influenza A H5N1 Which May Increase Infectivity in Humans

I've discussed before a little about Influenza A H5N1 which is more commonly referred to in the media as "avian influenza". I may have to post some other time about what this nomenclature means, and how H5N1 comes about into a human population from the original avian source (or, even better, I might be able to directly link to a review article I recently wrote if it will be made available publicly by the publisher). So, I am sorry, but the following couple paragraphs will assume some background knowledge of influenza genetics and epidemiology:

However, suffice it to say that when H5N1 is referred to by the press as being seen in a human case; this is referring to a human case of disease where the human directly contracted this virus from an avian source. The classical case involves people who are in direct contact with poultry such as is seen in parts of Asia. This is important to point out because more evidence is pointing to this direct spread of H1N1 to humans prior to the 1918 pandemic.

This is surprising because until H5N1 became noticed in 2003 (and the more recent work on a recovered strain of 1918 H1N1); it had been conventional thinking that the appearance of entirely new strains of influenza occurred through other means. Specifically, this "Antigenic Shift" was thought to occur from the mixing of strains in animals such as pigs who are able to be infected by both avian and humanized strains of influenza A. This thinking mostly is based upon the study of the H2N2 and H3N2 pandemics which were less devastating than the H1N1 pandemic and are more likely to have been started by a partially humanized, yet new, virus. However, the implications of a fully avian pandemic are strikingly different.

One key point that is missing in the investigation of why and how do these avain viruses jump straight to humans lies in the specific interactions between the virus and it's host. This is fairly basic stuff; viruses are made up of DNA (or RNA in the case of influenza) just like humans are, and any changes to this genetic code has a direct impact on the structure and function of the virus. This is particularly explicit with viruses because they are such simple organisms that their genetic code is so much more analagous to a computer program. In a virus, a single base mutation can make the difference between infectivity in an entirely new host species or significant attenuation of virulence. In addition, because of the extremely rapid growth rates of many viruses, it is almost certain that in a population of virus, there exists (on average) at least one mutation per base position across the entire genome.

In the article cited below, the researchers discover a single change in amino acid to a Lysine at position 627 of the PB2 gene which confers a phenotype much more amenable to infection in a mouse model of human infection. Of course, the implications of this are significant in the study of how this gene, and it's related pathophysiology, is important to infection in humans. And, I have no doubt that there may exist other positions across the influenza genome which may also serve as 'switches' to turn on a more human-specific virus.

However, as I love to point out, this also serves as a target for genetic engineering of a pandemic strain of influenza which could be designed for dispersal into the human population. This reminds me of the report of mutations mousepox related to IL-2 regulation from Australia which profusely increased lethality (mousepox is related to smallpox, btw). So, thus is the consequencs of studying infectious agents for good cause, we need to be aware that this same information could be used for nefarious means.

• Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, et al. Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice. PLoS Pathogens Vol. 3, No. 10, e133 doi:10.1371/journal.ppat.0030133

2DTV - Saddam Hussain - Germ Warfare

That 'ol Saddam... he sure was a "pain in the neck"...