AEROSOL INFECTION OF MAN WITH PASTEURELLA TULARENSIS

Tularemia acquired by natural means is manifested by a variety of clinical syndromes in the human host. If one assumes that the existing literature reflects accurately the true state of affairs in this disease, tularemia in the United States is predominantly of the ulceroglandular, oculoglandular, and glandular varieties (3-5, 9). Thus, among the several large series of human cases reported in this country, only 5 to 10% of patients were afflicted with what is generally referred to as typhoidal tularemia. When there has been obvious contact with a potentially infected arthropod or warm-blooded animal, principally of the rodent group, the appearance of an eschar and enlargement of regional lymph nodes clearly establishes the source and pathogenesis of infection. Development of pneumonia during the course of ulceroglandular tularemia may reasonably be ascribed to the circulation of Pasteurella tularensis in the blood. This is properly referred to as secondary or embolic pneumonia. Twelve to fifteen per cent of patients with ulceroglandular disease exhibited this manifestation of tularemia prior to the advent of effective antimicrobial drugs (1, 3, 6). By contrast, approximately 50% of patients with tularemia, in whom a portal of entry of microorganisms was not discernible, developed some pleuropulmonary manifestation of the disease (12). This obvious difference in incidence of lung involvement strongly suggests that the portal of entry may be the respiratory tract. However, it should be recognized that the mechanism of infection in so-called typhoidal tularemia is still a matter of controversy, there being those who doubt the importance or even the existence of primary pneumonic tularemia. One of the objectives of this presentation will be to marshal evidence in support of the concept that primary respiratory tularemia occurs as a naturally acquired as well as induced disease. Information obtained from the study of induced disease may lead to a better understanding of pathogenetic mechanisms which are operative in typhoidal tularemia. The unique capacity of P. tularensis to adapt to various environments is reflected in the multiple epidemiological patterns observed throughout the world. For example, the maintenance of endemic foci among water rats in certain parts of the Soviet Union is associated with waterborne outbreaks of tularemia among human beings in that country (11). During World War II, hundreds of thousands of people contracted tularemia as a result of the breakdown in public health and sanitation. In the Rostov area alone, 14,000 cases were encountered in January 1942, and tularemia is alleged to have been a serious cause of disability in Russian troops. Although ulceroglandular and typhoidal tularemia are also frequently observed in the Soviet Union, the obvious relationship which exists between consumption of water contaminated with P. tularensis and the occurrence of anginoglandular as well as abdominal tularemia serves to delineate clearly the clinical syndromes and most likely portals of entry associated with various types of tularemia in the human host. The extreme rarity of pharyngeal or tonsillar as well as abdominal tularemia in the United States seems to be evidence enough that few people in this country acquire the disease via the alimentary tract. Conversely, it is unlikely that typhoidal tularemia is acquired in this manner in view of the paucity of patients manifesting signs of anginoglandular and abdominal disease. Pneumonic tularemia has been recognized as a serious disease for many years. Sixty-nine of ninety-five (73%) patients who had succumbed to tularemia and who were subjected to postmortem examination presented lesions of pneumonic tularemia (12). Prior to the advent of effective antibiotic therapy, 40 to 60% of patients who developed pleuropulmonary tularemia died of this disease. Of the 268 cases of tularemia pneumonia reviewed by Stuart and Pullen (12), 64% had ulceroglandular disease and 36% were said to have had typhoidal tularemia in the absence of a visible primary lesion. Among the 115 who were aware of contact with a potential source of infection, 92 had handled rabbits, 13