Seminal Mycobacterium Tuberculosis in vivo Transmission Studies: Reanalysis Using Probabilistic Modelling

Our current knowledge of the nature of Mycobacterium tuberculosis (MTB) transmission owes much to the in vivo guinea pig model of infection. In 1882 Koch, identified the causative agent responsible for consumption and demonstrated tuberculosis (TB) transmission to guinea pigs exposed to dried sputum from infected patients. Consequently, emphasis was placed on avoidance of desiccated secretions in dust and fomites, which was then considered the principal mode of transmission. In the 1930’s Wells, expanding on the earlier work of Flugge, proposed that TB transmission was the result of inhalation of infected droplet nuclei exhaled or coughed by a TB case.

Probabilistic Modelling
Probabilistic Modelling

In the 1950’s, Riley and colleagues performed seminal experiments, which confirmed airborne transmission from TB cases to guinea pigs, supporting Wells theory. Riley observed that guinea pig infections in his model occurred only as rare singleton lesions. He postulated that guinea pig TB infection was quantal, lesions followed a Poisson distribution (1 – e-λ) and that TB case quanta production was as low as 1 – 2 per day. A Poisson distribution following a quantum exposure (expected value λ=1) would result in 36.8% with no lesions and 63.2% with lesions (36.8% with a single lesion and 26.4% with multiple lesions). However, the Poisson distribution of lesions remained theoretical, as multiple lesions were not observed.

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