Quantitative support for a theory of West Nile virus transmission using spatio-temporal modeling

The West Nile virus is a mosquito borne agent that has infected hundreds of thousands of birds and mammals and thousands of humans since its arrival in the United States in 1999. While there have been numerous hypotheses concerning the transmission cycle of the West Nile Virus, to this day, there has been no comprehensive theory of transmission of the virus to humans nor any quantitative evidence to support it.;In this research a conceptual model of transmission is introduced and evidence is offered which shows that viral amplification peaks 15--16 days prior to onset of symptoms in humans and begins to subside significantly 8 days later. These results are consistent with extrinsic incubation in mosquitoes and intrinsic incubation in humans.;The quantitative analysis which modeled this transmission involved the design and implementation of a system that is based on a geographic model that uses a Knox test to capture the nonrandom space-time interaction of dead birds, as an indicator of an intense West Nile virus amplification cycle, within a 1.5-mile (2.41-km) buffer area and 21-day moving window. The Knox analysis is implemented as an interpolation function to create a surface of probabilities over a grid of 1,400 cells overlaying New York City. The model's parameters are calibrated using year 2000 data and information on the vector-host transmission cycle. The system is implemented in a geographic information system and used operationally in New York City and, the City of Chicago where it is modified with an unconditional extension of the Knox to address weaknesses inherent in the Knox methodology and significance testing. The results from the traditional Knox method and the unconditional extension of the Knox method were evaluated using a novel space-time implementation of the kappa index of agreement for the Chicago data. They kappa results were used to quantify the success of each method and offer evidence for the role of dead birds in human West Nile virus transmission. It is shown that the discriminatory power of the unconditionally extended Knox is greater and that the two tests produce significantly different results.