Saturday, May 13, 2006
Proof That Viruses Cooperate with Bacteria in Producing Disease
In many experiments using animal models, bacterial infections have been superimposed at various times after inoculation of viruses. Enhancement of bacterial infection was demonstrated by comparisons of the bacterial contents of appropriate tissues with those of animals receiving bacteria alone. Exacerbation of disease was shown by more-severe lesions or higher death rates than for animals receiving either the bacteria or viruses alone.
The classical investigation using an animal model was that of Shope in 1931 (94) using influenza virus and H. influenzae in pigs. However, mice have been the experimental animals used for most investigations. Examples are as follows. Influenza virus enhanced respiratory infections with pneumococci (36,59,97), staphylococci (43), Listeria monocytogenes (28), group B streptococci (49), and Bacillus thuringiensis (39). Sendai virus enhanced respiratory infections with Mycoplasma pulmonis (41). Reovirus enhanced staphylococcal infection (53), and cytomegalovirus enhanced P. aeruginosa infection (33). Observations for other animal models included increased infection with H. influenzae in RSV-infected cotton rats (71), the effect of influenza virus on colonization of the nasopharynx of chinchillas by different phenotypes of S. pneumoniae (102), and enhanced streptococcal infection following influenza virus infection of ferrets (10, 29).
Neonatal ferrets infected with influenza virus provided an animal model for SIDS. An intranasally administered virulent strain (clone 7a) killed the neonates, and the pathology of some was akin to that seen in SIDS. In contrast to the virulent strain, killing of the neonates by a less virulent strain (PR8) could be prevented by antibiotic treatment, indicating that it was due to virus exacerbation of naturally acquired bacterial infection (42).
For obvious reasons, humans have not been deliberately infected with respiratory viruses followed by bacterial pathogens to study the progress of subsequent bacterial infection as described above for animal models. However, the effect of experimental influenza A virus infection of volunteers on selection of pathogens from the natural nasopharyngeal flora has been studied; S. pneumoniae was not isolated from any subject prior to virus challenge but was isolated in substantial numbers from 15% of the subjects on the sixth day following challenge (105).
Also, cells and fluids have been harvested, either from patients with natural infections or volunteers experimentally infected with viruses, and interacted with pathogenic bacteria in vitro in biological tests related to infection. For example, S. aureus, H. influenzae, and S. pneumoniae showed enhanced adherence to pharyngeal cells obtained from volunteers infected with influenza virus compared with cells from uninfected controls (23). Other examples are given below.
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