Development and characterization of a new swine model of invasive pneumococcal pneumonia.

Streptococcus pneumoniae is the most common microbial cause of community-acquired pneumonia. Currently, there are no available models of severe pneumococcal pneumonia in mechanically ventilated animals to mimic clinical conditions of critically ill patients. We studied endogenous pulmonary flora in 4 healthy pigs and in an additional 10 pigs in which we intra-bronchially instilled S. pneumoniae serotype 19 A, characterized by its resistance to penicillin, macrolides and tetracyclines. The pigs underwent ventilation for 72 h. All pigs that were not challenged with S. pneumoniae completed the 72-h study, whereas 30% of infected pigs did not. At 24 h, we clinically confirmed pneumonia in the infected pigs; upon necropsy, we sampled lung tissue for microbiological/histological confirmation of pneumococcal pneumonia. In control pigs, Streptococcus suis and Staphylococcus aureus were the most commonly encountered pathogens, and their lung tissue mean ± s.e.m. concentration was 7.94 ± 20 c.f.u./g. In infected pigs, S. pneumoniae was found in the lungs of all pigs (mean ± s.e.m. pulmonary concentration of 1.26 × 105 ± 2 × 102 c.f.u./g). Bacteremia was found in 50% of infected pigs. Pneumococcal pneumonia was confirmed in all infected pigs at 24 h. Pneumonia was associated with thrombocytopenia, an increase in prothrombin time, cardiac output and vasopressor dependency index and a decrease in systemic vascular resistance. Upon necropsy, microbiological/histological pneumococcal pneumonia was confirmed in 8 of 10 pigs. We have therefore developed a novel model of penicillin- and macrolide-resistant pneumococcal pneumonia in mechanically ventilated pigs with bacteremia and severe hemodynamic compromise. The model could prove valuable for appraising the pathogenesis of pneumococcal pneumonia, the effects associated with macrolide resistance and the outcomes related to the use of new diagnostic strategies and antibiotic or complementary therapies.

Amelioration of pneumonia with Streptococcus pneumoniae infection by inoculation with a vaccine against highly pathogenic avian influenza virus in a non-human primate mixed infection model.

BACKGROUND: Highly pathogenic avian influenza virus (HPAIV) infection has a high mortality rate in humans. Secondary bacterial pneumonia with HPAIV infection has not been reported in human patients, whereas seasonal influenza viruses sometimes enhance bacterial pneumonia, resulting in substantial morbidity and mortality. Therefore, if HPAIV infection were accompanied by bacterial infection, an increase in mortality would be expected. We examined whether a vaccine against HPAIV prevents severe morbidity caused by mixed infection with HPAIV and bacteria. METHODS: H7N7 subtype of HPAIV and Streptococcus pneumoniae were inoculated into cynomolgus macaques with or without vaccination of inactivated whole virus particles. RESULTS: Vaccination against H7N7 HPAIV decreased morbidity caused by HPAIV and pneumonia caused by S. pneumoniae. Bacterial replication in lungs was decreased by vaccination against HPAIV, although the reduction in bacterial colonies was not significant. CONCLUSIONS: Vaccination against HPAIV reduces pneumonia caused by bacterial superinfection and may improve prognosis of HPAIV-infected patients.

Lethal pneumonia in a captive juvenile chimpanzee (Pan troglodytes) due to human-transmitted human respiratory syncytial virus (HRSV) and infection with Streptococcus pneumoniae.

BACKGROUND: During an outbreak of respiratory disease in captive chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), Bornean orangutans (Pongo pygmaeus), and red-capped mangabeys (Cercocebus torquatus) also staff members showed non-specific upper respiratory signs. One infant female chimpanzee with severe respiratory symptoms died despite immediate medical treatment and was submitted for necropsy. METHODS: Routine post mortem, histological and bacteriological examinations were conducted. Additionally lung tissue samples form the chimpanzee and swab samples from the staff members and the other primates were examined by PCR. RESULTS: A severe catarrhal to purulent bronchopneumonia and an interstitial pneumonia were found and human respiratory syncytial virus (HRSV) as well as Streptococcus pneumoniae was detected in lung samples by PCR. Swab samples from one animal keeper revealed the same HRSV sequence as of the chimpanzee. CONCLUSIONS: Therefore, it is suggested that the outbreak of respiratory disease within a zoological institution was due to transmission of HRSV between both human and primates.

Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment.

BACKGROUND: We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung. METHODS: Our primary objective was to determine whether an intra-bronchial inoculum of at least 10(6)S. pneumoniae colony-forming units, or one as high as 10(8)-10(9) organisms, could detectably survive in rhesus macaques for a period longer than 1-2 weeks. If so, we hypothesized, it would be possible to observe signs of pneumonia commonly observed in humans, and discriminate between vaccinated/protected animals and controls. Infection was detectable in bronchoalveolar lavage fluids 3-5 weeks post-inoculation. RESULTS: The clinical course of disease mimicked aspects of that of human pneumococcal pneumonia. Signs of inflammation typical of the disease in humans, such as elevated concentrations of neutrophils and of pro-inflammatory cytokines in bronchoalveolar lavage fluids were also observed. CONCLUSIONS: These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.

Pneumonia in weanlings.

Lower respiratory tract infection is common in weanling- and suckling-aged animals. Increased susceptibility to disease in this age group can result from a delay in the establishment of a competent immune system and environmental factors, such as overcrowding, shipping, and sales. S zooepidemicus and R equi are the two most common bacterial isolates. S equi is primarily a disease of the lymph nodes and upper respiratory tract. Viral agents can compromise the natural defense mechanisms of the respiratory tract, resulting in secondary bacterial infections. The acute respiratory distress syndrome is one of unknown etiology and high mortality.

Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence.

Streptococcus suis is an economically important pathogen of pigs responsible for a variety of diseases including meningitis, septicemia, arthritis, and pneumonia, although little is known about the mechanisms of pathogenesis or virulence factors associated with this organism. Here, we report on the distribution and genetic diversity of the putative virulence factor suilysin, a member of the thiol-activated toxin family of gram-positive bacteria. On the basis of PCR analysis of over 300 isolates of S. suis, the suilysin-encoding gene, sly, was detected in 69.4% of isolates. However, sly was present in a considerably higher proportion of isolates obtained from cases of meningitis, septicemia, and arthritis (>80%) and isolates obtained from asymptomatic tonsillar carriage (>90%) than lung isolates associated with pneumonia (44%). With the exception of serotypes 1, 14, and 1/14, there was no strong correlation between the presence of suilysin and serotype. Analysis of the genetic diversity of suilysin by restriction fragment length polymorphism and sequence analysis found that the suilysin gene, where present, is highly conserved with a maximum of 1.79% diversity at the nucleotide level seen between sly alleles. Assays of hemolytic activity and hybridization analysis provided no evidence for a second member of the thiol-activated toxin family in S. suis. Inverse PCR was used to characterize regions flanking sly, which in turn allowed the first characterization of the equivalent region in a strain lacking sly. Sequence comparison of these regions from sly-positive (P1/7) and sly-negative (DH5) strains indicated that two alternative arrangements are both flanked by genes with highest similarity to haloacid dehalogenase-like hydrolases (5' end) and putative N-acetylmannosamine-6-phosphate epimerases (3' end). However, sly appears to be completely absent from the alternative arrangement, and a gene of unknown function is located in the equivalent position. Finally, PCR analysis of multiple sly-positive and -negative strains indicated that these two alternative genetic arrangements are conserved among many S. suis isolates.

Lentivirus infection in an African lion: a clinical, pathologic and virologic study.

In May 1991, clinical, pathologic, and virologic investigations were carried out on an 8-yr-old male lion (Panthera leo), with recurrent infections, in captivity with two lionesses in the Zoological Garden of Pistoia, Tuscany, Italy. The lion had severe pneumonia, neutropenia, thrombocytopenia, and an increase in blood urea nitrogen and creatininemia; in spite of therapy, it died within 3 months. At necropsy, the animal had a lymphoma and other lesions similar to those described in feline immunodeficiency virus-infected cats. We identified FIV gag-sequence using PCR amplification of lymph node tissues.

Susceptibility of ponies to infection with Streptococcus pneumoniae (capsular type 3)

Welsh Mountain ponies were inoculated with an isolate of Streptococcus pneumoniae, SPE 1618 (capsular type 3) recovered from the equine respiratory tract: 10 ml of a suspension of 10(8) or 10(9) cfu/ml were instilled intratracheally. Fever was observed after either dose but the greater concentration also produced coughing, ocular and nasal discharge, depression and enlargement of submandibular lymph nodes. Cytological evidence of infection was also observed in tracheal washings during the first week after inoculation and corresponded with isolation of S. pneumoniae from the washes. Morbid anatomical and histopathological examinations of selected animals revealed focal pneumonia affecting the ventral lung, especially the cardiac area and accessory lobe, with a propensity to affect the right lung. S. pneumoniae was isolated directly in pure culture from these lesions or was demonstrable by immunostaining of macrophages bearing specific capsular type 3 antigen. By 10 days after inoculation, the ponies were healthy and had developed antibodies to S. pneumoniae. S. pneumoniae was therefore a primary pathogen in the horse under the conditions of the challenge.

Mortality causes of owl monkeys (Aotus nancymae and Aotus vociferans) in captivity.

To determine the main causes of death in "owl monkeys" (Aotus nancymae and A. vociferans) in captivity, 115 necropsies were performed. According to the macroscopic findings and clinical data, results are as follow: acute lobular pneumonia (25.2%), chronic nephropathy (10.4%), acute catarrhal enteritis (8.7%), acute hemorrhagic enteritis (7%), acute toxic hepatitis (5.2%), trauma (5.2%), and others.

Hypertrophic osteopathy associated with a bronchial foreign body and lobar pneumonia in a dog.

Hypertrophic osteopathy was diagnosed in a dog with a bronchial foreign body and lobar pneumonia. Hypertrophic osteopathy is generally associated with primary or secondary neoplasms of the lungs and rarely associated with nonneoplastic thoracic lesions. The foreign body and affected lung lobe were removed by pneumonectomy, resulting in recovery of the dog and resolution of the hypertrophic osteopathy lesions.