Wednesday, July 11, 2012

Life-changing-cause-and-effect-finding science

We write a lot here on MT about how difficult it is to sort out causes -- causes of many things, from the global economic crisis to a winning streak in baseball to genetic or any other risk factors for most complex diseases.  In part, as we repeat every time a new GWAS result is being tooted, that's because such complex effects generally have many causes and it's hard to sort the real from the spurious when the effect of each one is slight.  A new paper (astonishingly, it's open access, rare for a medical journal!) in the Journal of Neurosurgery by a colleague of Ken's, Steve Schiff and co-authors, reminds us that science is very good at finding causation when it's strong enough.  And it also reminds us that there's a lot of important, life changing science going on, and much of it's not in genetics.

Steve is an MD, PhD, a pediatric neurosurgeon here at Penn State and director of the Penn State Center for Neuroengineering. He has a long standing interest, in his own words, "in understanding the physics of dynamical disease of the nervous system and developing smart prosthetics." He has done pioneering work in treating epilepsy and cerebral palsy, and has fairly recently become interested in treating neurological disorders in East Africa. This work is described in a 2010 issue of Engineering Penn State Magazine.

In the new J of Neurosurgery paper, "Rainfall drives hydrocephalus in East Africa." Schiff and co-authors describe their work over 6 years treating hydrocephalus. They have previously reported that the disorder appears to have an infectious cause, but they now demonstrate its association with rainfall, with which the populations of infectious agents ebb and flow.
Hydrocephalus is the most common neurosurgical disorder in children, with rates of 3-5 per 1000 live births in developed countries and estimates in sub-Saharan Africa of more than 100,000 cases per year. The majority of infant hydrocephalus cases in East Africa appear to be post infectious, related to preceding neonatal infections, and are thus preventable if the microbial origins and routes of infection can be better understood.  Here we show that climate is an important factor in driving the infections that lead to PIH [post infection hydrocephalus].
Almost all cases of hydrocephalus are treated in a single hospital in Uganda. Schiff et al. made a spatiotemporal map of the cases and rainfall over 6 years. Most cases of PIH seem to have followed a febrile illness, often with seizures, sometime in the first month of life, and most often during a rainy season of which there are two every year. The average age of treatment, however, was 9.1 months and the median was 4 months, which means that most infants are brought to hospital with advanced hydrocephalus. The disorder can cause severe damage to the brain, so prevention is much preferable to treatment. Thus, understanding when infections are most likely to occur, and which microbes are prevalent when, is an important step.

Prior to this study, hydrocephalus was not known to vary with climate and environmental conditions. Importantly, it is now known that preventive measures must focus on infectious agents and treatment of neonatal infections.
A large-scale study of the bacterial and viral components associated with neonatal sepsis in this neonatal population is underway.  A simultaneous strategy of both improving the anti microbial agents and engineering rational environmental health strategies to prevent these infections will be required. 
As Schiff et al. point out, while expensive and complex, the cost-effectiveness of surgical intervention is readily demonstrable, although prevention is preferable in order to avoid the damaging sequelae of the disorder. PIH is a consequence of poverty, yes, but also of environmental conditions that could be remedied.

As this paper shows, alert scientists know that causation can suddenly be discovered, so to speak, out of the clear blue sky -- or in this case, can drop out of the clouds.

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