Pulmonary pathology of Rocky Mountain spotted fever (RMSF) in children.

Despite infrequent respiratory symptoms, histopathologic changes were identified in the lungs of 15 of 16 children dying of Rocky Mountain spotted fever (RMSF). Gross examination demonstrated increased lung weight, edema, congestion, focal hemorrhage, and bronchopneumonia in a few cases. Paraffin sections were stained with hematoxylin and eosin and phosphotungstic acid-hematoxylin, and available blocks were examined by direct immunofluoresence for Rickettsia rickettsii. Cases and controls matched for age and sex were randomized and examined blindly for pathologic changes. In addition, morphometric measurements of mean alveolar septal thickness were made in each case. The histopathologic findings include (1) diffuse interstitial mononuclear (lymphocyte and macrophage) inflammatory infiltrate in 15/16 cases of RMSF (5/10 controls), (2) pulmonary edema and intraalveolar hemorrhage in 11/16 cases of RMSF (2/10 controls), and (3) vasculitis of small pulmonary venules and arterioles in 5/16 RMSF cases (0/10 controls). Rickettsia rickettsii were identified in 4/8 RMSF cases by direct fluorescent antibody technique. Although pulmonary disease is not always clinically apparent in children with RMSF, involvement of the pulmonary microcirculation is a frequent event in fatal cases and may contribute to the development of non-cardiogenic pulmonary edema.

Infection cycle of Rickettsia rickettsii in chicken embryo and L-929 cells in culture.

The infection cycle of Rickettsia rickettsii, studied in slide chamber cultures of chicken embryo and L-929 cells, was found to be complex and did not conform to a one-step growth cycle. Initial uptake kinetics resembled those established for Rickettsia prowazekii, but subsequent events showed very marked differences. Intracytoplasmic growth commenced exponentially without measurable lag. However, very soon after infection, intracytoplasmic rickettsiae began to escape from the host cell into the medium in large numbers, resulting in (i) failure of large numbers of rickettsiae to accumulate in the cytoplasm, (ii) sustained rapid division of the organisms in the cytoplasm, (iii) substantial accumulation of extracellular rickettsiae, and (iv) rapidly spreading infection in the culture, with most cells infected in 48 to 72 h. In the occasional cell, rickettsiae were found in the nucleus, where they multiplied to form compact masses. Thus, analysis of the growth characteristics of R. rickettsii must consider the entire culture as a unit in which the rickettsiae are distributed among three compartments in which they behave in different ways: (i) intranuclear, (ii) intracytoplasmic, and (iii) extracellular. The rickettsial traffic is bidirectional across the host cell plasma membrane and dominantly monodirectional across the nuclear membranes. The implications of this behavior with respect to location and range of receptors and substrates involved in membrane penetration are discussed. In older cultures, unique intracytoplasmic ring or doughnut colonies were common, indicating a change in the intracytoplasmic environment. The possible significance of the growth characteristics in cell culture to the characteristics of infection in humans and animals is discussed.