Steven Schiff, professor of neurosurgery and Brush Chair Professor of Engineering in Engineering Science and Mechanics, has received a $4.1 million National Institutes of Health Director’s Pioneer Award. It will fund research aimed at reducing the number of infant deaths from neonatal sepsis in developing countries by identifying the roots of infection, from season of birth to home environment.
The Pioneer Award supports individual scientists of exceptional creativity who propose pioneering – and possibly transforming – approaches to major challenges in biomedical and behavioral research. The proposed research must reflect ideas substantially different from those already being pursued in the investigator’s laboratory or elsewhere. This is the first Pioneer Award that Penn State has received and the first received by a neurosurgeon. The award will be administered through Penn State College of Medicine.
“There are about 1 million newborns, almost all in the developing world, that die each year from infection in the first few weeks of life – neonatal sepsis,” said Schiff. “There are more infant infection deaths than malarial deaths of any age, and they are comparable to global deaths from tuberculosis.”
Because the vast majority of the causes of these serious infections are unknown, the researchers will first look for unknown bacterial and viral causes of sepsis. Survivors of neonatal sepsis often develop infant hydrocephalus – fluid build-up in the brain, which, untreated, leads to brain damage and frequently death.
“We will use new genomic approaches to DNA and RNA analysis of infants and their mothers in Uganda, seeking to characterize all of the bacteria, viruses and other microbial agents causing infection, as well as the interactions between groups of such organisms,” Schiff said. “We know that climate – specifically rainfall – is associated with the cases that go on to develop hydrocephalus, and we will combine microbial surveillance with satellite rainfall data to form predictive models that will enable us to predict, at any given week or location, the optimal antimicrobials to administer to newborns with sepsis.”
Much of the work will be conducted at Penn State College of Engineering, where Schiff is director of Penn State Center for Neural Engineering, as well as at the Center for Infectious Disease Dynamics of the Huck Institutes and at the Institute for Personalized Medicine at Penn State College of Medicine. Schiff will use an engineering control strategy to develop a model-based system to prevent infections.
Schiff will also look at the efficacy of current treatment because the organisms responsible for infant infection are different in sub-Saharan Africa than in the United States and Europe. Antibiotics typically recommended in the West may be less effective in the African context. Hoping to avoid the necessity of surgery, Schiff and his team will characterize the specific organisms that infect the brain in these settings.
“We are doing exhaustive patient follow-up following sepsis, traveling to remote villages to examine children for hydrocephalus and performing neurocognitive testing,” Schiff said. “Using such patient outcome feedback, we will apply modern engineering control principles – computational methods to represent a process to be controlled – to do model-based optimization of treatment.”
The researchers will attempt to develop a universal system that can be applied in any country to control infectious disease through engineering control principles.
“Engineering control theory and its implementations are the way we control things such as self-driving cars or airplane autolanders,” Schiff said. “We make a model of the system and use that in a computer to emulate the system, synchronize to it and optimally control it. The use of engineering control principles has had little role so far in the control of epidemic infections. Our methodology will also apply to other types of infectious processes we seek to gain better control of.” Schiff wrote the first book on Neural Control Engineering (MIT Press, 2012).
This project will incorporate work with partners, including colleagues at several African universities, Harvard University and an African pediatric neurosurgical hospital run by CURE International – based in Lemoyne, Pennsylvania. At Penn State, collaboration will occur between faculty across colleges of Medicine, Engineering, Science, and Agriculture at the University Park and Hershey campuses.
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