Photo Credit – CDC PHIL
# 5912
There is a belief, at least among some researchers, that there exists some – as yet unidentified - genetic propensity for contracting the H5N1 virus.
This idea is based primarily on the observation that - despite ample opportunities for exposure – relatively few humans have been infected, and that the few clusters of human-to-human transmissions we've seen appear to happen primarily among blood relatives.
While this idea has been around for a number of years, it hasn’t exactly been universally embraced.
In 2007 the CDC’s Emerging Infectious Diseases Journal published a study suggested that mere chance could account for family clustering.
Little Evidence for Genetic Susceptibility to Influenza A (H5N1) from Family Clustering Data
Virginia E. Pitzer , Sonja J. Olsen†, Carl T. Bergstrom‡, Scott F. Dowell†, and Marc Lipsitch
Abstract
The apparent clustering of human cases of influenza A (H5N1) among blood relatives has been considered as evidence of genetic variation in susceptibility. We show that, by chance alone, a high proportion of clusters are expected to be limited to blood relatives when infection is a rare event.
While this article proposed a plausible alternative theory for family clustering, it didn’t disprove that host genetics played a role in transmission.
In 2008, in the Journal of Infectious Diseases, we saw a study that suggested there might be a heritable susceptibility to death from the influenza virus.
Evidence for a heritable predisposition to death due to influenza.
Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA.
Abstract (extract)
Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza.
Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.
While interesting, this study doesn’t provide us with a smoking gene. However, the following year a PLoS ONE research article (doi:10.1371/journal.pone.0004857) came a bit closer.
Entitled Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections by Srivastava B, Błażejewska P, Heßmann M, Bruder D, Geffers R, et al., it reports on the results of experiments utilizing seven inbred strains of lab mice that were exposed to influenza A viruses.
From the abstract:
The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism.
While mouse models are often useful, what happens in mice doesn’t always correspond to what happens with human physiology.
Another (as far as I can tell, unpublished) study, conducted in Thailand, Singapore, and Indonesia by the South East Asia Infectious Disease Clinical Research Network, looks at whether:
“. . . host genetic factors may shed light on key pathogenic interactions between H5N1 and human cells . . . ”
The overview of the study is available on clinicaltrials.gov at:
Host Genetic Susceptibility to Avian Influenza A/H5N1
Hopefully this will provide us with more clues as to why some people appear susceptible to the H5N1 virus, while others less so.
All of which serves as prelude for a study that appeared yesterday in the journal Clinical Infectious Diseases, which provides more evidence supporting the notion that host genetics influences acquisition and transmission of the H5N1 virus.
This study looked at 113 sporadic and 26 cluster outbreaks of the H5N1 virus in Indonesia through July 30th, 2009 and found human transmission of bird flu to be heavily influenced by host genetic susceptibility.
Below you’ll find a link to the abstract, and an excerpt (slightly reformatted for readability) of the results. Go read it, and when you return I’ll have a little more.
Risk Factors for Cluster Outbreaks of Avian Influenza A H5N1 Infection, Indonesia
Tjandra Y. Aditama, Gina Samaan, Rita Kusriastuti1, Wilfried H. Purba, Misriyah, Hari Santoso, Arie Bratasena, Anas Maruf, Elvieda Sariwati, Vivi Setiawaty, Alex R. Cook, Mark S. Clements, Kamalini Lokuge, Paul M. Kelly, and I. Nyoman Kandun
(EXCERPT)
Risk factors for cluster outbreaks were the number of first-degree blood-relatives to the index case (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI]: 1.20–1.86) and index cases having direct exposure to sources of AI H5N1 virus (aOR, 3.20; 95% CI: 1.15–8.90).
Risk factors for secondary case infection were being aged between 5 and 17 years (aOR, 8.32; 95% CI: 1.72–40.25), or 18 and 30 years (aOR, 6.04; 95% CI: 1.21–30.08), having direct exposure to sources of AI H5N1 virus (aOR, 3.48; 95% CI: 1.28–9.46), and being a first-degree relative to an index case (aOR, 11.0; 95% CI: 1.43–84.66).
Siblings to index cases were 5 times more likely to become secondary cases (OR, 4.72; 95% CI: 1.67–13.35).
In Indonesia, young age (under 30) and being a blood relative to the index case in a cluster, were both found to significantly increase the odds of catching the virus.
While it is more than a little tempting to hope that some unidentified human genetic quirk limits the ability of the H5N1 virus to ever become a pandemic, the whole point of viral evolution is to figure out a host’s defenses.
What may have served as a limiting factor in the past, doesn’t provide a guarantee for the future.
Determining what (if any) genetic factors influence transmission could provide vital clues of just how big of a pandemic threat the H5N1 virus really presents, and might even lead to more effective treatments and prevention.
The difficulty, of course, is that studies like this take time to mount and to interpret, and the virus never sleeps.
