Mathematically Modeling Spillover Dynamics of Emerging Zoonoses with Intermediate Hosts

The World Health Organization describes zoonotic diseases as a major pandemic threat, and modeling the behavior of such diseases is a key component of their control. Many emerging zoonoses, such as SARS, Nipah, and Hendra, mutated from their wild type while circulating in an intermediate host population, usually a domestic species, to become more transmissible among humans, and moreover, this transmission route will only become more likely as agriculture and trade intensifies around the world. Passage through an intermediate host enables many otherwise rare diseases to become better adapted to humans, and so understanding this process with mathematical epidemiological models is necessary to prevent epidemics of emerging zoonoses, guide policy interventions in public health, and predict the behavior of an epidemic. In this paper, we account for spillovers of a zoonotic disease mutating in an intermediate host by means of modeling transmission dynamics within and between three host species, namely, wild reservoir, intermediate domestic animals, and humans. We calculate the basic reproductive number of the pathogen, present critical conditions for the emergence dynamics of zoonosis, and perform stability analysis of admissible disease equilibria. Our analytical results agree well with long-term simulations of the system. We find that in the presence of biologically realistic interspecies transmission parameters, a zoonotic disease can establish itself in humans even if it fails to persist in its reservoir and intermediate host species. Our model and results can be used to understand the dynamic behavior of any zoonosis with intermediate hosts and assist efforts to protect public health.Comment: Comments are welcom

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations