Previous studies suggested that the most frequent means of transmission of Lassa virus was by either direct or indirect contact with infectious material. Aerosol stability and respiratory infectivity of the Josiah strain of Lassa virus were assessed to determine the effect of environmental factors on aerosol-induced infection. The stability of the virus in aerosol, particularly at low relative humidity (30% RH), plus the ability of the virus to infect guinea pigs and monkeys via the respiratory route emphasize the potential for aerosol transmission of Lassa virus. Biological half-lives at both 24 and 32 degrees C ranged from 10.1 to 54.6 min, and were sufficient for aerosol dispersion of virus to considerable distances in natural situations. Infectivity of Lassa virus in small particle aerosol was demonstrated in outbred guinea pigs and cynomolgus monkeys using dynamic aerosol equipment. Monkeys exposed to inhaled doses to 465 PFU were infected and died. The median infectious dose (ID50) for guinea pigs was 15 PFU, yet a definitive median lethal aerosol dose (LD50) could not be established. Organ tropism of aerosol-induced Lassa virus infections in outbred guinea pigs was similar to that previously reported for inbred guinea pigs infected by subcutaneous inoculation.
Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study to obtain evidence of a retrovirus in BAC.A panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line expressing a human endogenous retrovirus protein was examined immunohistochemically using a rabbit antiserum directed against the JSRV capsid protein.Specific staining was detected only in the cytoplasm of recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs, 17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The remaining samples were negative.These results support the hypothesis that some human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus-related retrovirus, warranting further studies. Eur Respir J 2000; 15: 330±332.
Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.
A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.
Transmission and scanning electron microscopy were used to study the phagocytosis of virulent and avirulent strains of Legionella pneumophila. The interaction between L. pneumophila and peritoneal macrophages from normal guinea pigs or from animals that had survived infection was studied. The virulent strains survived and proliferated within the phagocyte after ingestion by either type of macrophage, whereas the avirulent strain of bacteria was killed by normal macrophages. Although the addition of immune serum enhanced phagocytosis, the outcome was the same as with normal serum.
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