Legionnaires' disease outbreak investigation toolbox

Experimental studies in animals exposed to aerosolised Legionella

Whilst Legionella infections have been induced experimentally in many animals [1; 2], it is the guinea pig that is considered to respond to Legionella in a way that is most similar to humans. Twisk-Mijssen et al. [3] found that symptoms present in guinea pigs within 2 - 3 days of infection, almost regardless of the amount of Legionella retained in the lung after initial exposure. Over 90% of the animals developed symptoms within the above time frame following exposure despite wide differences in retained dose; ranging between 10⁵ and 10⁸ Legionella bacteria. Furthermore, over 60% of animals became symptomatic within a very similar time frame when exposed to even lower doses (e.g. 10⁴). Baskerville et al. [1; 4] found similar results with exposures of 10³- 10⁴ bacteria; the animals again showing symptoms within 2 - 3 days of exposure, and with only slightly shorter incubation periods (1-2 days) with exposures to 10⁵ bacteria. They also noted that the group of guinea pigs exposed to lower doses (2 x 10²) showed no signs of subsequent infection. Breiman & Horowitz [2] also observed symptoms beginning at 2 -5 days following exposures in the range of 10⁷- 10⁸ bacteria, with a 100% fatality rate at doses equal to or greater than 10⁸. Muller, Edwards & Smith [5] similarly found an equivalent 3-day incubation period for guinea pigs even with the low dose exposures that they employed (10³ and below). It should be noted that all authors except Twisk-Mijssen et al. [3] used Hartley strain guinea pigs with weights in the range of 250 - 500g.

In summary, from examination of the available data, it appears that some of the otherwise rather limited variation in the duration of the incubation period between studies, may be more likely due to experimental (exposure) methodology than to any potential differences in the intrinsic biological susceptibility of the different strains of guinea pig used. Similar, relatively limited and consistent, dose-dependent trends are seen which overall suggest only a relatively small increasing risk of infection and death with increasing dose, once a particular threshold has been passed.

Reference List

1. BASKERVILLE A., FITZGEORGE R., BROSTER M. G., HAMBLETON P. & DENNIS P. J. (1981) Experimental transmission of Legionnaires' disease by exposure to aerosols of Legionella pneumophila The Lancet 19, 1389 http
2. BREIMAN R. F. & HORWITZ M. A. (1987) Guinea pigs sublethally infected with aerosolised Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge Journal of Experimental Medicine 164, pp.799 - 811 http pdf
3. TWISK-MEIJSSEN M. J. M., MEENHORST P. L., VAN CRONENBURG B. J., MULDER J. D., SCHEFFER E. & VAN FURTH R. (1987) The course of Legionella pneumophila in guinea pigs after inhalation of various quantities of L. pneumophila Immunobiology 176(1-2), pp.108 - 124 http
4. BASKERVILLE A., FITZGEORGE R., BROSTER M. G. & HAMBLETON P. (1983) Histopathology of experimental Legionnaires' disease in guinea pigs, rhesus monkeys and marmosets Journal of Pathology 139, pp.349 - 362 http
5. MULLER D., EDWARDS M. L. & SMITH D. W. (1983) Changes in iron and transferrin levels and body temperature in experimental airborne legionellosis Journal of Infectious Diseases 147, pp.302 - 307 http