Parsimonious Determination of the Optimal Infectious Dose of a Pathogen for Nonhuman Primate Models

Abstract

The nonhuman primate (NHP) model is often the best experimental model for testing interventions designed to block infection by human pathogens, such as HIV, tuberculosis, and malaria. A physiological model may require the use of a limiting dose of the infectious agent, where only a fraction of animals become infected upon any given challenge. Determining the challenge dose of the pathogen in such experiments is critical to the success of the experiment: using too-high or too-low a challenge dose may lead to false negative results and an excessive use of animals. Here I define an optimized protocol for defining the dose of pathogen that infects 50% of the time (AID50); other challenge doses, e.g. AID80, can be easily calculated from the same data. This protocol minimizes the number of animals, as well as resources and procedures, while providing an estimate of the AID50 within 1.5-fold of the true value.