The Conglutination Phenomenon: XII. Immuno-Conglutinin in Experimental Infections of Laboratory Animals

Immuno-conglutinin has been stimulated in rabbits after infection with Listeria monocytogenes, Salmonella typhi-murium and other bacterial species. Infection of rabbits with Western Equine Encephalomyelitis, Hammon Reeves, Murray Valley Encephalitis and Aedes trivittatus viruses also stimulated the production of this substance. The most marked immuno-conglutinin response followed infection of rabbits with Trypanosma brucei.

Rickettsia burneti infection in guinea pigs produced a biphasic immuno-conglutinin response, the first phase being coincident with the rise of antibodies to the Phase II antigen and the second phase with the retarded rise of antibodies to the Phase I antigen.

In mice also, the immuno-conglutinin level was raised following infection with Escherichia coli, Salmonella typhi-murium and other bacterial species.

     

The Conglutination Phenomenon: XIII. In vivo Interactions of Conglutinin and Experimental Bacterial Infection

Some interrelations between the conglutinating activity of the serum of an animal and experimental bacterial infection were investigated. The passive transfer of conglutinating activity was demonstrated. The level of this activity reaches a peak within 2 days after subcutaneous injection, then declines until no significant titres are demonstrable in 12 to 14 days. It is shown that infection of animals with Salmonella typhimurium causes a rapid reduction in the conglutinating activity of the serum immediately after challenge. Evidence is presented which indicates that the previous injection of conglutinin preparations enhances bactericidal activity of the mouse against Salm. typhimurium.     

The Alexination and Conglutination Reactions: The Reactions Between Sensitized Erythrocytes and Horse Complement and Between Alexinated Erythrocytes and Conglutinin

A method is described for the quantitative measurement of the reactions between sensitized cells and horse complement and between alexinated cells and conglutinin. The method is laborious but its application has allowed the determination of the optimal times of the reactions at various temperatures. The results obtained in these experiments indicate that the alexinated configuration with which conglutinin and immuno-conglutinin react is not one of the recognized intermediates formed during the process of immune haemolysis.     

Resistance to Bacterial and Parasitic Infections in the Nutritionally Compromised Host

Tuberculosis, a bacterial disease prevalent since ancient times, continues to cause the most deaths globally compared with all other diseases. The causative agent Mycobacterium tuberculosis is responsible for different types of tuberculosis in humans; however, pulmonary tuberculosis is the most common and causes the most deaths. Mycobacterium tuberculosis is an intracellular pathogenic bacterium, which has developed sophisticated mechanisms to survive inside host mononuclear phagocytes and thus evade the host immune system. This is attributed primarily to an inadequate immune response toward infecting bacteria, which results in temporary growth inhibition rather than death and subsequently allows the bacteria to multiply immensely, leading to full-blown disease in an individual. This disease has become a challenge due to poor diagnosis, a low-efficiency tuberculosis vaccine (Mycobacterium bovis Bacillus Calmette-Guèrin [BCG]), a long-term antibacterial chemotherapy regimen (approximately 6 months), and an emergence of multiple drug resistant strains of Mycobacterium tuberculosis especially in people with human immune deficiency virus (HIV) infection, for whom researchers worldwide must develop effective short-term chemotherapy and an effective vaccine. In this review different aspects of vaccines in tuberculosis are discussed, and these include the traditional BCG vaccine, the modern auxotrophic vaccine, the subunit or acellular vaccine; and a DNA vaccine. We discuss also the potential of mycobacterial lipids as a vaccine or as an adjuvant in the future. Since complete genome information of Mycobacterium tuberculosis H37Rv and bioinformatics tools are available, it is possible to develop new strategies for a better and effective tuberculosis vaccine, which can replace the traditional BCG vaccine.     

Pyelonephritis XIV. Effect of Immunization on Experimental Escherichia coli Pyelonephritis

Mice immunized subcutaneously with heat-killed Escherichia coli were protected from pyelonephritis produced by the intravenous route, but there was little or no protection from ascending infection. No significant protection from ascending or hematogenous pyelonephritis was demonstrated when immunization was accomplished by injecting heat-killed E. coli into the bladder. Heat-killed E. coli injected either subcutaneously or into the bladder protected mice from early endotoxic death after intravenous or bladder challenge.     

Infections in Live Donor Liver Transplant Recipients: A Study of Timeline,Aetiology and Antimicrobial Resistance of Bacterial and Fungal Infections from the Developing World

Infections are the leading cause of morbidity and mortality in liver transplant (LT) recipients. We studied timeline, spectrum of infection, system involved, and antimicrobial resistance in 64 patients undergoing live donor LT with 6-month follow-up. Of 64 patients, 38 (59.5%) patients had 103 infectious episodes, 10 patients had single infectious episode and 28 patients had two or more infectious episodes. 96 (93.2%) were bacterial and Candida infections were in 7 (6.8%). Early phase had 30 (29.1%) episodes; intermediate phase 25 (24.2%) and late phase 48 (46.6%). Mortality was 11/64 (17.1%). Knowledge of timeline, aetiological agent and antimicrobial resistance is useful to guide empirical therapy and infection prevention.     

Effect of Induced Interferon in Experimental Rhinovirus Infections in Volunteers

Nasal administration of an interferon inducer, CP-20,961 (N, N-dioctadecyl-N′, N′-bis(2-hydroxyethyl)propanediamine), was evaluated in a double-blind, placebo-controlled study of experimental rhinovirus infection in 29 volunteers. Detectable nasal interferon developed in 10 of 15 subjects treated with CP-20,961, and 2 of 14 in the group receiving placebo (P < 0.006). Titers of CP-20,961-induced interferon ranged from 10 to 250 international units, concentrations similar to those observed in rhinovirus infections. Ten in the CP-20,961 group and eight in the placebo group became ill (P > 0.05). However, mean total sign scores were significantly diminished among CP-20,961-treated subjects as compared with placebo-treated subjects (P < 0.025). No significant effect was noted on quantitative virus shedding patterns or neutralizing antibody responses. These findings suggest that such concentrations of induced interferon do not protect against rhinovirus infection, and that factors other than interferon may be important in recovery from rhinovirus infection.     

Proinflammatory Cytokines in the Treatment of Bacterial and Fungal Infections

Mortality due to severe bacterial infections has not been markedly effected by the introduction of new antimicrobial drugs over the last 30-40 years. This has emphasized the need for development of new therapeutic strategies to combat sepsis. The outcome of an infection depends on two factors: the growth of the microorganisms (including the effect of antibacterial drugs), and the host's defensive response to the invading organism. It is known that injection of bacterial products into experimental animals leads to enhanced nonspecific resistance to a variety of microorganisms. The discovery of the specific mediators responsible for modulation of host defense has created new possibilities for the development of alternative treatment strategies. Molecules such as interleukins, interferons, tumor necrosis factors and hematopoietic growth factors have become available in recombinant form, and their therapeutic potential in various infectious diseases has been tested in various experimental models of infections. Initial data in various patient groups indicate that adjunctive therapy with recombinant proinflammatory cytokines may have beneficial effects in the treatment of bacterial and fungal infections.     

Bloom''s syndrome. XIV. The disorder in Japan

Fourteen persons have been diagnosed Bloom's syndrome in Japan, with cytological verification in 11. Widely separated birthplaces throughout Honshu, Shikoku, and Kyushu and a parental consanguinity incidence greater than in the general population suggest that the Bloom's syndrome mutation, although very rare, is distributed widely throughout the Japanese population. The locus mutated is the same as in Jews and persons of Western European extraction. The phenotype differs somewhat from most cases recognized elsewhere, in that dolichocephaly is a less constant feature, the facial skin lesion is less prominent, and life-threatening infections are less common. The characteristic predisposition to neoplasia exists, however, as probably does that to diabetes mellitus.     

Experimental Bacterial Endocarditis: II. Survival of Bacteria in Endocardial Vegetations

A method has been developed for assessing metabolic activity of bacteria in the vegetations of bacterial endocarditis using a labelled metabolite and autoradiography. Evidence provided by this technique suggests that there are different degrees of activity between superficial and more deeply placed bacterial colonies, and that variations in activity also exist within a single group of organisms. The possible relevance of these findings to the antibiotic therapy of endocarditis is discussed.     

Experimental Bacterial Endocarditis: III. Production and Progress of the Disease in Rabbits

A simple and reliable model for endocarditis in rabbits has been studied and standardized. Non-bacterial thrombotic endocarditis was produced on either side of the heart by the presence of a polyethylene catheter. One day later, this was converted into bacterial endocarditis by single intravenous injections of streptococci, staphylococci, Proteus and Candida. No infection resulted from injection of L-forms or virus. Reduction of inoculum size or withdrawal of the catheter reduced the incidence of bacterial endocarditis, but the presence of a catheter in the heart for only a few minutes predisposed to infection. Left-sided Streptococcus viridans infection was uniformly fatal, with average survival of about two weeks. Right-sided infection was not always fatal; approximately 25% of infected vegetations healed spontaneously.The advantages of a standardized model for endocarditis which allows exact timing of infection are discussed.     

Experimental Bacterial Endocarditis: I. Colonization of a Sterile Vegetation

Quantitative cultures were made to determine the sites of lodgement and the early fate of streptococci injected intravenously into rabbits with pre-existing non-bacterial thrombotic endocarditis, produced by prior placement of a polythene catheter in the right side of the heart. Serial blood cultures in normal animals showed rapid clearance of injected bacteria, whereas in animals with a pre-existing vegetation a persisting bacteraemia ensued. In such animals substantial numbers of injected bacteria adhered to the vegetation, and in this site they multiplied rapidly in a manner resembling the growth curve associated with favourable conditions in vitro. Within 2 days the organisms attained a comparatively stationary phase in the vegetation; and this appeared to be the source of the continued bacteraemia. The morphology of the developing lesion was studied in sections taken at various intervals after inoculation. A notable feature was the abrupt appearance of a superficial layer of fibrin between 18 and 24 hr, which may offer protection to the growing colonies.     

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections.