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an observation that illustrates the difficulties of using animal
models to represent human disease.
Older mice are relatively resistant to respiratory infection;
infant or suckling mice have reproducible symptoms and mortality
from pertussis pneumonia, and the disease resembles the disease in
humans (Pittman et al., 1980; Sato and Sato, 1988; Sato et al.,
1981). Infection induced by intranasal inoculation (Pittman et al.,
1980) has been reported to be less reproducible than that induced
by aerosol inhalation (Sato and Sato, 1988). The strain of mice
used can affect the results (Pittman et al., 1980). Survivors
of a sublethal dose of organisms can develop a chronic infection
that lasts for weeks or months (Dolby et al., 1961; Sato et al.,
1981; Weiss et al., 1984).
Using intranasal inoculation of infant mice, Weiss and
colleagues (1983, 1984) showed that mutant strains of B.
pertussis lacking pertussis toxin (PT) or extracytoplasmic
adenylate cyclase were much less virulent than the wild-type
(naturally occurring) organism. A mutant deficient in filamentous
hemagglutinin was nearly as virulent as the wild-type strain. The
results obtained with these carefully engineered strains raise a
question about the contribution of filamentous hemagglutinin to
virulence. Such a contribution had been suggested by data from
other models. These and other considerations warrant reservations
about the general applicability of the results obtained with this
or the other models to the disease in humans.
Mice infected intracerebrally have been the most widely used
animal model for pertussis. To achieve this model, anesthetized
mice are injected with various numbers of organisms, in some cases
after immunization with bacteria or bacterial products (usually
given intraperitoneally). Only one strain of B. pertussis,
strain 18-323, works well in the model, which raises further
questions regarding the applicability of this model to the natural
disease in humans. In fact, analysis of isoenzyme patterns suggests
that this bacterial strain is genetically more closely related to
Bordetella bronchiseptica than it is to other strains of
B. pertussis (Musser et al., 1986). In mice, the bacteria
attach to the ciliated cells of the ependymal lining of the
ventricles (Berenbaum et al., 1960), which simulates attachment to
the respiratory cilia in humans with whooping cough. However, this
infection within the skull otherwise deviates rather markedly from
the presentation of the disease in humans. Despite these obvious
differences from the infection in humans, protection in this model
has correlated with vaccine efficacy in humans (Medical Research
Council, 1959; Standfast, 1958).
STANDARDIZED ANIMAL TESTS OF VACCINE
The intracerebral mouse protection test (Kendrick et al., 1947,
1949) has served importantly in the progress in vaccine development
that has been made to date. The test uses a standardized strain of
bacteria (strain 18-323)