Experimental aspects of intraabdominal abscess.

Two animal models were used to examine the bacteriologic aspects and antibiotic treatment of intraabdominal abscess. The first model was designed to simulate the septic complications of colonic perforation using an inoculum of stool implanted intraperitoneally in rats. The results showed that coliforms were responsible for early lethality, Bacteroides fragilis appeared to play a particularly important role in abscess formation, and optimal treatment required antimicrobial regimens directed against both coliforms and anaerobes. The second model was designed to examine the pharmacokinetic properties of antibiotics and therapeutic efficacy of various antimicrobials in a subcutaneous abscess involving B. fragilis in mice. This work showed all drugs penetrated abscesses, although there was a diminishing antimicrobial effect with progressive delays in the time that treatment was initiated. It is suggested that bacteria within an abscess are in a stationary phase of growth so that early institution of treatment is critical for optimal in vivo activity, and bactericidal drugs may be preferred once an abscess has formed.

Origins of pathogenic anti-DNA idiotypes in the NZB X SWR model of lupus nephritis.

The investigations with the NZB X SWR model show that the development of systemic autoimmune disease is a multistep, multigene process. Severe lupus nephritis in the NZB X SWR hybrids results from the interaction of genes inherited from both the autoimmune NZB and the normal SWR parents. A similar genetic interaction occurs in the NZB X NZW hybrids, but in this model, both the parental strains are abnormal and the nature of the gene products or their mechanism of action is unknown. In the NZB X SWR model, we have been able to identify a restricted subpopulation of nephritogenic anti-DNA antibody idiotypes that are encoded by genes of the normal SWR parents. Thus, these are one set of genes that determine the development of severe lupus nephritis in the F1 hybrids. In addition, another set of genes allows for the expansion of B cells that produce such pathogenic anti-DNA idiotypes in the F1 hybrids since such B-cell clones remain dormant in the normal SWR parents. The latter category of genes, presumably specifying defects in immunoregulation, are probably inherited from the NZB parents or may be the result of complementation of genes inherited from both parents. Further investigations with the NZB X SWR model will help us define the immunoregulatory defects in SLE that are specific for the T and B cells involved in pathogenic autoantibody production.

Experimental meningococcal meningitis in the infant rat.

Experimental infection of the infant rat could be established with intraperitoneal challenge with strains of all three meningococcal groups A, B, and C tested. 5-day-old rats were challenged with 3 different doses (10(2), 10(4), and 10(6) bacteria/animal) and the development of peritonitis, bacteraemia and meningitis detected as a function of time at 3, 6, and 9 h. Mortality was followed up to 24 h. Group B strains caused a rapidly developing and sustained high level bacteraemia and meningitis with all challenge doses. Bacteraemia and meningitis following challenge with MenA and MenC were of somewhat shorter duration and reached lower peak levels. Repeated 'rat passages' of meningococcal strains that had been kept stored for long periods markedly increased their virulence. This study shows that the infant rat model can be applied for studying pathogenesis of meningococcal bacteraemia and meningitis. Previous work from this laboratory has shown it to be suited also for studying antibody-mediated protection from this disease.

Establishment of a mouse model for human rhinovirus infection.

We describe here a mouse model for rhinovirus infection using a variant of human rhinovirus type 2 (HRV2/H) which replicated 50- to 300-fold in the lungs of BALB/c mice. The variant virus differed only marginally from HRV2/H according to various biochemical parameters. Use of a photosensitive inoculum and pretreatment of the animals with actinomycin D were necessary for detection of reproducible and significant levels of virus replication. This mouse model of rhinovirus infection is the first example of human rhinovirus replication in a non-primate mammal, and provides an important link for the development of rhinovirus therapy or prophylaxis.

Pathogenicity of Dermatophilus and Geodermatophilus.

Cutaneous infection in laboratory animals could not be induced with any of several strains of Geodermatophilus. A model for consistent production of streptotrichosis in rabbits, with cultures of Dermatophilus congolensis, is presented.

Campylobacter diarrhea in an adult mouse model.

An adult mouse (18-20 g) model was developed for studying the pathogenesis of Campylobacter isolates. Iron-loaded BALB/c mice given 10(8)-10(9) Campylobacter colony forming units by intraperitoneal injection developed a severe mucoid diarrhea within 4 h. Severe diarrhea, consisting of unformed stools containing blood, mucus, and fecal leukocytes, persisted for 24 h. Diarrheal symptoms in surviving mice resolved gradually; no diarrhea was observed 5 days after inoculation. Mice not pretreated with iron developed no diarrheal symptoms, and no severe diarrhea was produced in mice inoculated orally. A transient (less than 24 h) bacteremia occurred in mice inoculated either orally or intraperitoneally. Liver, spleen, and kidney were positive for Campylobacter for 48 h; intestinal contents were positive for 5-7 days. Mice given greater than or equal to 10(10) colony forming units showed symptoms of endotoxemia (ruffled fur, inactivity, shaking, tearing, and hypothermia) and died without diarrheal symptoms. Mice given nonpathogenic Escherichia coli strain HB101, heat-killed C. jejuni cells (greater than 10(10)), C. jejuni lipopolysaccharide extract, or purified lipopolysaccharide from either Vibrio cholerae 569B or Salmonella typhimurium showed no diarrheal symptoms.

Infection of rabbits with human immunodeficiency virus.

An important requirement for the development of a vaccine against the human immunodeficiency virus (HIV-1), the causative agent of AIDS, is a readily available animal model that would allow possible immunogens to be evaluated. The only species to have been infected with HIV-1 so far is the chimpanzee. However, the scarcity of this animal and its designation as an endangered species place severe restrictions on its use as an animal model. Attempts to infect mice, rats, hamsters, guinea-pigs, musk shrews, and rabbits with HIV-1 or infected cells have all been unsuccessful. We now report that the intraperitoneal inoculation of rabbits with HIV-1 or chronically infected H9 cells consistently induces a persistent infection.

Legionnaires' pneumonia after intratracheal inoculation of guinea pigs and rats.

We have developed a model of legionnaires' pneumonia in guinea pigs and rats. A reproducible population of Legionella pneumophila was obtained in late exponential growth phase and inoculated into the trachea of young animals. Either immunologic or microbiologic evidence of infection was demonstrated in 27 or 28 guinea pigs and 19 of 20 rats that had been inoculated with 10(5) to 10(7) colony-forming units. An acute pneumonia that resembled human legionnaires' disease was produced in both species, and Legionella antigen was closely related to inflammation in the distal air spaces. A fatal illness was produced in guinea pigs, and pneumonia was more extensive than in rats. Extrapulmonary inflammatory lesions, particularly splenic necrosis, were more frequent in guinea pigs than in rats. Each rodent species has potential advantages for testing specific questions and both should be useful for future investigations.