Melioidosis: pathogenesis and immunity in mice and hamsters. I. Studies with virulent strains of Malleomyces pseudomallei.

Abstract

The pathogenesis of acute respiratory melioidosis mice and hamsters is described. Inhaled organisms giving rise to lesions seemed to be first engulfed by the mononuclear alveolar phagocytes, but in less than 1 day polymorphonuclear cells made their appearance. In spite of this defense reaction, the bacteria continued to multiply and their products caused focal necrosis. These foci enlarged and gave rise to septicemia, toxemia, and eventually death, which usually occurred in 3 to 10 days depending on the dose. Melioidosis, is, therefore, an acute septicotoxemic disease resembling plague and anthrax in this respect. In hamsters the disease process developed more rapidly than in mice and death occurred sooner. The course of the disease in hamsters was sometimes complicated by intraglomerular deposits resembling "fibrinoid," which were similar to those of the generalized Shwartzman phenomenon. This phenomenon may have been an indirect cause of both the perifocal hemorrhage and the extremely large number of bacteria in some of the hamster lesions. When low infecting doses of organisms were employed, mice, but not hamsters, developed a chronic type of disease, lasting 2 to 8 weeks. This was characterized by large abscesses in the spleen or lung, marked proliferation of mononuclear phagocytes and plasma cells, and increased immunity against reinfection (about 40-fold against respiratory challenge). When mice and hamsters inhaled high infecting doses of organisms, a peracute disease resulted with death in 1 to 3 days. Increased numbers of bacteria were observed in the lesions, and the histological changes in the spleen resembled those following the intravenous injection of Malleomyces pseudomallei toxin or the intramuscular injection of large doses of cortisone. These changes were characterized by a swelling of the phagocytes of the white pulp with nuclear debris. The peracute, the acute, and the chronic forms of melioidosis in mice are similar to analogous clinical forms found in man.