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A résumé is presented of recent developments in the field of infectious diseases of particular interest of practising physicians. Examples are given to illustrate recent discoveries concerning the frequent misuse of antibiotics, the problem of infections developing in hospitalized patients, the biology of microbial infection, the etiology of well-known illnesses, new infectious diseases, and the development of vaccines. It is evident that the rate at which new and important information is evident that the rate at which new and important information is being reported demands particular effort in medical school teaching to ensure that students learn how to acquire and evaluate new information as well as how to discard ideas which are no longer valid.

In the period August 10-29, 1986, 29 confirmed cases of Legionnaires' disease occurred in Sheboygan, Wisconsin; two cases were fatal. No common source of indoor exposure was identified. Water specimens were obtained from all known cooling tower units in Sheboygan; Legionella pneumophila serogroup 1 was isolated at 1 x 10(6) colony-forming units per liter from a specimen obtained August 27 at plant A. This isolate was identical to the only clinical isolate by monoclonal antibody and isoenzyme subgrouping. Of 29 persons with Legionnaires' disease, 21 lived or worked within one mile (1.6 km) of plant A; seven of the remaining eight visited within one to two miles (1.6 to 3.2 km) of plant A from three to seven days before onset of illness. Attack rates were highest for persons living within 0.5 mile (0.8 km) of plant A. These findings associate a cooling tower with community-acquired Legionnaires' disease and suggest that dissemination of Legionella may occur over longer than previously recognized distances.

Despite the introduction of many effective antibiotics and an increased understanding of appropriate infection control measures, new pathogens continue to emerge as nosocomial opportunities. Some of these bacteria have developed increased antibiotic resistance; others have acquired the ability to survive in antiseptics, in intravenous infusion solutions, or on intravascular catheters; and still others are ubiquitous in the hospital and readily colonize compromised patients. Because some of these organisms are fastidious, they have not always been readily cultured and identified. Other species have not been fully appreciated as nosocomial pathogens because of taxonomic uncertainties. The changing spectrum of hospital-acquired infection continues to pose new challenges that necessitate the development of highly active agents such as imipenem for effective treatment.

Of 67 hospitalized AIDS patients, 39 had pulmonary pathology. More than half of these patients died of pulmonary disease. Pneumocystis carinii, cytomegalovirus, Cryptococcus neoformans and Mycobacterium avium-intracellulare were the most common pulmonary pathogens, and Kaposi's sarcoma was the most common neoplasm. Infections and neoplasms frequently coexist in the thorax of an AIDS patient. The chest radiograph may be normal in an AIDS patient with active Pneumocystis pneumonia.

Over a 10-month period, 24 cases of Legionnaires' disease pneumonia occurred among patients admitted to an Iowa hospital, most of whom were immunosuppressed. Eleven patients died. Twenty-one patients were admitted to a recently completed hospital addition, 16 of these to a new hematology-oncology unit. Legionella pneumophila serogroup 1 was isolated from the patients, water outlets, and hot water in the new addition. Water quality variables in the hospital addition were adequate. Shock chlorination, temporary elevation of the hot water temperature, and continuous chlorination of hospital water decreased the frequency of isolation of Legionella. Water use by patients in the hematology-oncology unit was restricted until the water was free of Legionella. The incidence of Legionnaires' disease decreased. Indirect evidence supports an hypothesis of water-borne disease in this cluster of cases. Current variables of acceptable water potability may not guarantee water free of L. pneumophila.

Four cases of legionnaires' disease were diagnosed by specific serologic tests in a group of 33 immunocompromised patients admitted to the same hematologic department for acute febrile pneumonitis. The underlying disease of these four patients was hairy-cell leukemia (HCL) in three cases and allogeneic bone marrow transplantation in the other. This article stresses the enhanced susceptibility of patients with HCL to Legionella pneumophila and discusses its possible causes, especially monocyte deficiency. We propose the use of erythromycin as part of the initial empiric antibiotic therapy in immunocompromised hosts with acute pneumonitis until the results of specific serologic tests or isolation of L pneumophila is obtained.

In addition to providing a powerful approach for identifying bacterial factors required for full infectivity and disease production, genetic analysis of Legionella pathogenesis should also lend critical insight into the biology of the macrophage and into the pathogenesis of other intracellular parasites. The interaction between L. pneumophila and the macrophage exhibits many features found in a wide variety of prokaryotic and eukaryotic intracellular human pathogens. For example, binding to complement receptors has been shown to occur for Mycobacterium tuberculosis, M. leprae, Leishmania donovani, Leishmania major and Histoplasma capsulatum. Coiling phagocytosis has been observed during entry of L. donovani. Phagosomes that contain Toxoplasma gondii or M. tuberculosis fail to fuse with lysosomes and, in the case of T. gondii, have been shown to remain close to neutral pH. Although the molecular bases for these phenomena are unknown, their functional similarities to the L. pneumophila-macrophage interaction provide optimism that generally applicable principles are involved. The genetic techniques reviewed here will provide the molecular tools with which such questions of a general biologic nature can be framed and eventually answered. Together with more traditional methods in biochemistry, microbiology and cell biology, molecular genetics offers a robust means toward identifying and understanding the bacterial factors involved in the pathogenesis of Legionnaires' disease. Molecular studies of L. pneumophila can also help address questions concerning the epidemiology, diagnosis and prevention of disease. For example, the distribution of virulence factors might help explain and predict the attack rates of different L. pneumophila strains or Legionella species. Moreover, bacterial genes/factors that are shown to be conserved in Legionella strains could be used to develop such diagnostic tools as DNA probes. Novel types of vaccines consisting of genetically constructed, avirulent L. pneumophila strains or subunit vaccines based on the molecular characterization of virulence factors might be developed and tested as protective immunogens. In this way, the capacity to analyze and to manipulate L. pneumophila genetically may facilitate the use of Legionnaires' disease as a model infection for studying protective cell-mediated immunity. Apart from its clinical significance as the etiologic agent of Legionnaires' disease, L. pneumophila may be a key to broader understandings in microbial pathogenesis and human cell biology and immunology. Although the extremely complex processes of bacterial infection and virulence are best understood when a variety of experimental approaches are employed, we believe that the evolving molecular genetic techniques reviewed here will be critical elements in many important breakthroughs in the future.

The medicolegal medical toxicologist is described: What they do, what toxicology is, how the toxicologist moves in a world of regulations, chemicals, differential diagnosis, and treatment of poisoning; his or her knowledge as an expert witness in evaluation of serious adverse drug reactions, medical malpractice, and poisoning cases; and the toxicologist's awareness of the role of alcohol, the problem of causation of death, and the limitations of the laboratory are discussed.

Sixty-nine laboratory-documented cases of Legionnaires' disease occurred in Vermont between 1 May and 31 December 1977. Clinical manifestations were similar to those in the 1976 Philadelphia epidemic. Case-control studies suggested that Legionnaires' disease patients were more likely to present with headache or diarrhea than were patients with pneumonia of presumed nonbacterial cause. The case-fatality ratio for patients treated with erythromycin was 4%, compared with 17% in patients not treated with erythromycin. Thirteen patients had been hospitalized throughout the 10 days preceding onset of illness, equaling the maximal known incubation period. This suggests either acquisition or reactivation of infection in the hospital. However, even during the week of peak disease activity, cases occurred in patients with no recent hospital contact. The only community factor possibly associated with acquisition was home air conditioning. This prevalence of seroreactivity to the Legionnaires' disease bacterium in various community populations was as high as 26%, suggesting a possible endemic area.

Immunologic factors affecting viability of the Legionnaires' disease (LD) bacterium were studied in vitro and in vivo in mice and guinea pigs. In bactericidal tests, fresh human serum quickly killed LD cells. Heating fresh serum to 56 degrees C for 30 min destroyed bactericidal activity; absorbing it with bentonite had little effect. Fresh normal human serum was more effective than guinea pig serum. Adding LD cells to fresh normal human serum caused a greater than 50% depletion in functional complement activity, apparently by activating the classic C-142 pathway, because human serum deficient in C4 was not bactericidal. Antibodies to the Knoxville 1 LD strain in guinea pigs showed enhanced complement-mediated bactericidal activity. Without complement, immune guinea pig or human sera prolonged in-vitro LD cell survival. Antibodies to Knoxville 1 in mice depressed in-vitro bactericidal activity of human complement against Knoxville 1. In-vitro bactericidal tests support in-vivo studies in subcutaneous chambers. Complement-deficient mice immunized with Knoxville 1 were (P less than 0.01) less resistant to homologous challenge than nonimmunized mice. Immunized guinea pigs had a greater than 80-fold increase in resistance to subcutaneous-chamber infection.

A "new pneumonia" is named legionnaires' disease after a gramnegative bacillus - Legionella pneumophila, unknown until 1977. Sofar it has been observed mostly in older male patients, rarely in children and never before in Germany. The legionnaires' disease in our patient, a five and half years old boy with cystic fibrosis caused a severe dyspnea and multilobular pulmonary densifications on the chest X-ray film. The diagnosis was verified by the rise of the titer in the indirect immune fluorescence test and the success of the therapy with erythromycin.

A 65-year-old woman presented with an autoimmune hemolytic anemia and was subsequently diagnosed as having malignant lymphoma. Cytotoxic chemotherapy was followed by the development of fatal Legionnaires' disease, confirmed by isolation of L. pneumophila serogroup 6 from pleural and lung aspirate specimens. This is believed to be the first reported isolation of serogroup 6 L. pneumophila in Australia.

In August and September 1977 a discrete cluster of 27 serologically or pathologically confirmed cases of Legionnaires' disease, plus six highly presumptive cases were identified in the area of Kingsport, Tennessee. Three patients died. Most patients manifested severe pneumonia and fever; no mild or asymptomatic disease forms were recognized despite intensive case-finding efforts. Illness was epidemiologically associated with residing, visiting, or working in one geographic area of Kingsport, residence there being the factor most strongly associated. Although the attack rate for area residents was 0.64%, the randomly determined prevalence of serologic reactors was 5.2%, which is not significantly different from that in a nonimplicated control neighborhood. The epidemic did not correlate temporally with any identified environmental or demographic event. No source of the bacterium was found either by a detailed case-control study of area associations or by bacterial isolation from sentinel guinea pigs or environmental specimens. There was no evidence of person-to-person spread.

Legionella pneumophila serogroup 1 was isolated from post mortem specimens from 13 out of 58 patients with pneumonia diagnosed at autopsy. The results of a study undertaken in the hospital environment showed that the water plumbing system was colonized with L. pneumophila serogroup 1 which could also be isolated from respiratory devices filled with tap water. Control measures instituted are described.

Pontiac fever affected ten men who had cleaned a steam turbine condenser with compressed air. Previous epidemics of Pontiac fever and Legionnaires' disease--both caused by Legionella Pneumophila (proposed sp. nov.)--involved "airborne spread" from air-conditioning cooling towers or evaporative condensers. Aerosols of contaminated water in heat-rejection systems appear to be important sources of epidemic legionellosis.

One hundred patients with sporadic, community-acquired, serologically confirmed Legionnaires' disease were matched with control subjects known by the patients (acquaintance controls) and control subjects chosen from among patients with negative serodiagnostic tests for Legionnaires' disease (clinical controls). Each clinical control subject was also matched with an acquaintance control of his own. Legionnaires' disease patients had smoked more cigarettes, consumed more alcohol, and were more likely to have resided near excavation sites than acquaintance or clinical control subjects. Parallel differences between clinical controls and their acquaintances were not seen. Legionnaires' disease patients had traveled away from home for more time during the 2 weeks before onset of illness than had their acquaintances. The difference was of greater magnitude than that between clinical control subjects and their acquaintances. Legionnaires' disease patients were more likely to have resided near construction sites than clinical controls, and there were more construction workers among patients than among clinical control subjects.

A prospective pneumonia study was conducted simultaneously on head-and-neck surgery wards at two hospitals over 2 years; one hospital had a water supply contaminated with Legionella pneumophila but no record of having had a case of legionella pneumonia, and the other had just decontaminated its water supply because of known endemic nosocomial legionellosis. Special laboratory tests for legionella were done on all cases of nosocomial pneumonia irrespective of clinical impression. Over the first 18 months, the rate of nosocomial legionellosis was 30% at the first hospital and 0% at the second. Patients who underwent laryngectomy did not acquire the disease. Hyperchlorination at the first hospital was followed by a fall (p less than 0.01) in legionella pneumonias. Thus legionella pneumonias can be overlooked if special laboratory tests are not applied routinely, and surgical patients with head-and-neck cancer may be at high risk of nosocomial legionellosis because of the potential for pulmonary aspiration of contaminated water or orophyaryngeal microflora and/or frequent manipulation of the respiratory tract. This study demonstrates the benefits of examining the environment for legionella despite the absence of documented disease.