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

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Exposing nonhuman primates to infectious pathogens (such as tuberculosis, malaria, or the simian equivalent of HIV) is an important model for testing vaccines or other interventions designed to prevent infection or disease. In fact, demonstrating efficacy in animals is often a requirement before clinical testing in humans can be started. A critical variable in such testing is the dose of the pathogen used: this dose should be similar to what humans would encounter. Using too-high a dose may overcome the intervention and mask a successful approach; using too-low a dose may not be relevant. Often, an optimal dose will lead to “successful” infections only a fraction of the times the animal is exposed. A successful intervention experiment therefore needs to use a precisely calibrated dose of the infectious agent; this calibration can only be done by exposing animals to a range of doses and measuring how often they become infected. Here I define the most parsimonious method for performing this calibration: one that uses the least number of animals and procedures. Given the large number of new pathogens being tested in animal models, adoption of such a parsimonious protocol is both economically and ethically warranted, and will thereby enable favorable review of proposed animal use numbers by Institutional Animal Care and Use Committees.

Vyšlo v časopise: Parsimonious Determination of the Optimal Infectious Dose of a Pathogen for Nonhuman Primate Models. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005100
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005100

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