ISPH Investigators Hongbin Zhang and Elizabeth Kelvin awarded NIH R03 grant

For immediate release.

Assistant Professor Hongbin Zhang and Associate Professor Elizabeth Kelvin, investigators with the CUNY Institute for Implementation Science in Public Health at CUNY SPH, were awarded an R03 grant from the National Institutes of Health to work with collaborators from Columbia University and University of Cuenca, Ecuador, to tackle the difficult disease of neurocysticercosis (NC).

Despite accumulating evidence that NC cyst evolution varies within the brain, the life course of the encysted parasite remains relatively understudied. Cyst evolution differs between parenchymal and extraparenchymal brain locations and possibly by patient age and sex, but little is known about the timing of the transitions through the stages of evolution overall or by cyst and patient characteristics, nor how cyst and patient characteristics impact the effect of anthelminthic (anti-parasitic) treatment such as albendazole (ALB). In this field, the understanding of cyst evolution is hindered by the fact that most studies examine only patient-level aggregate measures of NC cyst burden within the brain. However, individual NC cysts in the same patient can evolve differently, and ALB may kill some parasites but have little effect on others within the same patient; only by following individual cysts can we understand these differences.

Zhang, Kelvin and team will add cyst-level data from patients with multiple cysts in the same brain location to the data they have already disaggregated from the patient level to the cyst level. These additional cyst phase transitions will substantially increase the sample size to ensure sufficient power. They will then use a modeling approach known as a multi-state model (MSM) to characterize the NC cyst evolution. MSM allows a longitudinal trajectory and a survival event to be combined within a single framework and enables the impact of receiving treatment to be modeled at all stages of disease progression. They will further develop statistical methods that address the complex nature of this data and apply those methods to the cyst-level dataset to look at the average time cysts spend in each phase and whether cysts transition faster between phases depending on ALB treatment and finally, they will also look at whether the impact of ALB is modified by patient and cyst characteristics or cyst burden.

“The funding is timely,” Zhang says of the opportunity. “There are quite a number of methodological challenges with the data. The methods developed in this proposed study can be used to evaluate these alternate treatment strategies and for research on other diseases, such as cancer, that evolve through a predefined clinical states and impact multiple body regions when assessed in longitudinal studies with intermittent data collection and various forms of censoring. ”

“The award is terrific,” Kelvin says. “Neurocysticercosis is a neglected disease, according to the World Health Organization (WHO), and current treatment fails a high proportion of patients. A better understanding of the disease and reasons for its heterogeneity are essential in order to develop more precise treatment options.”