Infections in the Immunocompromised Host

By Paul Actor

Subjects: Immunology, Communicable diseases, Congresses, Complications, Infection, Maladies infectieuses, Immunological deficiency syndromes, Immunologic Deficiency Syndromes, Congrès, Infections, Complications et séquelles, Syndromes de déficit immunitaire

Description: The subject matter of this volume, the basis for which was a conference held in Philadelphia which focused on the subject of infections, including their diagnosis and treatment, in immunocompromised individuals. The material is of the rapid spread of acquired immunodeficiency syndrome (AIDS). The first section dealt with the general subject of the immunocompromised host. Here, reviewed in detail, were the epidemiological and clinical aspects of opportunistic infections in patients with defective immune responses. It is widely acknowledged that infections are a major complication of the neoplastic process. Cancer-bearing patients are more prone to certain kinds of infectious and cancer chemotherapy almost always increases susceptibility to such infections. Depending upon the basic disease process of the cancer, a specific array of infectious diseases can predicted. Patients altered in thymus-derived lymphocyte populations or mononuclear phagocyte capabilities resulting in defects in cell mediated immunity or delayed hypersensitivity become highly susceptible to certain groups of organisms, whereas, profoundly neutropenic patients usually become infected with different organisms. The types of infection noted are relatively predictable for the type of immune defect, with some variations according to epidemiological factors. Major advances have been made in the early diagnosis and treatment of infectious complications with increasing knowledge of their use. The application of so-called preventive procedures has had limited value to date, including immunotherapy, which appears to hold much promise. Covered also was the immunodulatory effects of microorganisms and their products. Infectious agents including bacteria, viruses, fungi and parasites can stimulate the nonspecific proliferation and activation of the immune system or specifically stimulate the antimicrobial immune response resulting in humoral antibody or specific sensitized cells. Various microorganisms and their products, especially those derived from mycobacteria, and other intracellular bacteria, can stimulate nonspecific responses and activate macrophages. The perturbation of the immune response observed during experimental and human infections is well-documented. For the most part, this is brought about by either generalized anergy or a selective derequlation of immune responses. Additionally, bacterial, viral and fungal functions. Parasites can alter the immune response by enchancing polyclonal antibody responses or inducing excessive number of suppressor cells, which inhibit both specific and non-specific immune responses. Viral infections, in man and animals are known to depress existing immune responses including delayed hypersensitivity. Onchogenic viruses, in particular, have been widely studied in regards to their effects on immune parameter. These latter studies have direct relevance to AIDS with the demonstration that a human T-cell virus is the etiological agent. A wide variety of immunomodulatory agents have been studied experimentally in terms of their ability to reverse immunodeficiency induced by tumor viruses. The immunomodulatory properties of products derived from bacteria, including endotoxins, lipoteichoic acids and exotoxins have been shown to be due to selective effects on certain classes of immunocompetent cells. The interaction of bacteria of their products with macrophages results in the release of immunomodulatory mediators. Induction of small molecular weight substances such as prostaglandins also may occur in response to microorganisms or their products on immune response mechanisms. Subsequent session of the Symposium dealt with laboratory aspects of diagnosis of infectious diseases in compromised patients, as well as the description of various opportunistic infections in such patients. Non-tuberculous mycobacterial species are found in increasing numbers in compromised patients. Among these are Mycobacterium marinum and M. intracellulari. Various aspects of herpesvirus infections in immunocompromised hosts were covered in detail as were laboratory diagnosis and treatment. Fungal infections continue to be an important pathogen in immunocompromised patients. The role of Pneumocystis carinii and other parasitic infections in compromised hosts was discussed as was Cryptosporidium, another protozoan parasite. The effects of various biologically-active agents and immunostimulants on host immune response were covered in the concluding session. Liposomes and other particulate drug carriers can serve as models for localizing drugs predominantly in the mononculear phagocytic cells of the reticuloendothelian system. Liposomes containing natural and synthetic immunomodulatory or anti-infective drugs (e.g. amphotericin B) have been shown effective in both animal and human infections as well as in animal tumor systems. The potential utility of this approach is compromised by toxicity problems encountered during extended treatment with liposomes with and without immunomodulators. Impairment of RES function and significant bone marrow pathology has been observed in animals treated i.v. with liposomes. These problems are a serious potential limiting factor in the future development of liposomes as a drug delivery system. The use of lymphokines and other biological response modifiers in the treatment of cancer was reviewed. Attempts to stimulate immune responses with a variety of non-specific immunomodulators in the form of bacterial extracts, viruses and chemicals have been largely unsuccessful in man. The rapid advances with genetically engineered biological products such as lymphokines and ctyokines and monclonal antibodies may prove useful for cancer treatment, but here again, early results have not been highly successful. Such agents may act directly on tumor cells and/or stimulate the patient to produce an anti-tumor response. The topics of infectious disease and malignancy in immunocompromised hosts and the immunological defects underlying such conditions are being examined with greater frequency by many scientists, tumor biologists and clinicians in exploring the nature and mechanism of immunodeficiency in various disease states and the types and frequency of infectious diseases in such patients should provide valuable new knowledge in the future for treating and, perhaps, even preventing such diseases.