Guinea pigs have been used as a model for
Mycobacterium tuberculosis infection for many years and have been more recently adopted as a model for testing new
tuberculosis (TB)
vaccines. From the time of Robert Koch, who used guinea pigs to test theories about the newly discovered pathogen, the guinea pig has modeled active human
infections, as it is susceptible to
infection with low numbers of organisms. This article describes the modern use of the guinea pig to examine the pathology of the disease and the protocols used to examine specific outcomes associated with
aerosol infection with virulent M.
tuberculosis. The guinea pig is used extensively to investigate the ability of new TB
vaccines to reduce TB disease, and two models have been employed. The first is the long-term disease model, in which vaccinated guinea pigs are monitored for disease after
infection, and the second is the short-term assessment of mycobacterial burden model, which can determine the ability of a
vaccine to reduce organism burden. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation of virulent Mycobacterium tuberculosis seed stocks for animal
infections Basic Protocol 2: Preparation of virulent Mycobacterium tuberculosis working stocks for animal
infections Basic Protocol 3: Preparation of M.
tuberculosis for
aerosol infection of guinea pigs Basic Protocol 4: Injection of guinea pigs Basic Protocol 5: Blood collection from live guinea pigs Basic Protocol 6: Guinea pig
euthanasia.