[Chronic fistulating wound infection after Lichtenstein repair of inguinal hernia, caused by a small colony variant of Staphylococcus aureus]. / Chronisch fistelnde Wundinfektion nach Lichtensteinreparation einer Leistenhernie, verursacht durch eine Small-colony-Variante von Staphylococcus aureus.

We report a case of chronic wound infection (abscess, fistula) after a Lichtenstein repair of inguinal hernia. After surgical treatment (mesh explantation), a small-colony variant (SCV) of Staphylococcus aureus was cultured microbiologically. SCV represent subpopulations of Staphylococcus aureus which are associated with chronic infections and which respond poorly to usual treatment regimes. In this case surgery and specific antibiotic treatment with flucloxacillin and rifampicin were successful.

Stimulation of cell-mediated resistance in mice to infection with Listeria monocytogenes by vitamin A.

Vitamin A given as retinol-acetate, retinol-palmitate as well as the derivates retinoic acid and a retinoid, strongly fortified the resistance of mice to infection with virulent cells of Listeria monocytogenes. However, strong enhancement of resistance was only achieved when high toxic doses of vitamin A were given. Apparently, this effect was due to a stimulation of the function of the mononuclear phagocytic system rather than of the T lymphocyte.

Murine model for therapy of listeriosis in the compromised host. III. The effect of rifampicin.

10 different strains of Listeria monocytogenes tested in vitro were found to be susceptible to rifampicin showing minimal inhibitory concentrations between 0.0075 and 0.06 microgram/ml. Mice infected with a virulent strain of L. monocytogenes were treated with this antibiotic. Bacterial counts rapidly declined. In dextran sulfate-treated animals, deprived of their macrophage system and consequently highly susceptible to Listeria infection, rifampicin was able to protect the animals. Furthermore, nude athymic mice, chronically infected with L. monocytogenes, were also nearly cured. A few remaining bacteria, however, started to multiply after cessation of therapy, so that a relapse was noted. Development of resistance of L. monocytogenes to rifampicin during treatment was not observed.

[Immunosuppression mediated by antibodies (author's transl)]. / Immunsuppression durch Antiköper

Until quite recently, it was generally believed that antibody-mediated immunosuppression is purely effected by virtue of covering up antigenic determinants in the periphery of the immune system, thus preventing any contact of the antigen with immunologically competent cells within the central parts of the immune system. But this conception was not able to give a plausible explanation of experimental data obtained during the last years. It was therefore repeatedly postulated that the passively administered 7S antibody may have a "central" effect, whereby both B- and T-cells were considered as target cells. The experimental data available are discussed in connection with the possible consequences for the administration of antibodies in man.

[Resistance to infection with Listeria monocytogenes in normal and thymusless mice treated with ampicillin (author's transl)]. / Infektabwehr von Listeria monocytogenes bei normalen und immundefekten Mäusen unter Ampicillintherapie.

NMRI mice were infected intravenously with a sublethal dose of Listeria monocytogenes and divided into four groups. One group served as the control and the other three were treated with ampicillin beginning 4, 8 or 24 hours after infection. The animals were injected in the morning and in the evening each time with 4 mg ampicillin subcutaneously until a total dose of 48 mg was reached. As demonstrated by counting of the bacteria in the spleen, Listeria could multiply in the ampicillin treated mice in comparison to the control group at best delayed but the infection continued to persist for some days at a level of 10(3)-10(4) Listeriae per spleen independent from the starting point of the treatment. Eight days after the first infection all animals received a challenge dose of 10(4) Listeriae. Compared with the control animals the ampicillin treated mice had a clearly reduced immunity, even in the group in which ampicillin application had been started 24 hours after the primary infection. If the challenge infection was given at first after an intervall of six weeks between primary and secondary infection, only a reduced immunity was found. Furthermore, whereas spleen cells of mice 7 days after infection were able to transfer immunity to untreated recipients, spleen cells of ampicillin treated mice were unable to do so. Finally, an attempt was made to cure chronic listeric infection in thymusless nude mice by the application of high doses of ampicillin. The observation of a continuous infection in these animals showed that the T-cells played a primary importance in the elimination of the bacteria.

Age-related defense against infection with intracellular pathogens.

Young adult (6--12 weeks old) and aged (20--24 months old) NMRI mice were infected with various intracellular parasites. The following results were obtained: (1) After a sublethal infection with Listeria monocytogenes, aged mice were found to show a resistance similar to that of young adults. A challenge infection with this pathogen was followed by specific immunity of long duration in both age-groups. (2) On the other hand, young animals were significantly more resistant to Salmonella typhimurium than aged mice. It was concluded that this was due to the LD50 which was 14 times greater for 2-month-old than for 20-month-old mice. Furthermore, during 7 weeks after infection there were more S. typhimurium in the spleens of senescent mice than in those of young adult controls. (3) Aged mice showed highly increased susceptibility to the weakly virulent DX strain of Toxoplasma gondii. Almost all aged animals died whereas the control mice survived. When death of the aged mice was prevented by treatment with sulfadiazine after infection with the DX strain, the aged mice were found to be as well protected against subsequent infection with the strongly virulent BK strains as the young adult mice. These results suggest that the susceptibility of the aged animal to infectious agents may considerably vary from one pathogen to another.

[Endocarditis from Erysipelothrix rhusiopathiae]. / Endokarditis durch Erysipelothrix rhusiopathiae.

Erysipelothrix rhusiopathiae only seldom causes cases of endocarditis. Contact with infectious animals leads to endocarditis of the left heart with high lethality. Vancomycin and aminoglycosides, which are often used in gram-positive endocarditis, show no effect.

Listeria monocytogenes infection in nude mice.

As compared to phenotypically normal (nu/+)NMRI mice showing the typical course of an experimental listeric infection, that of congenitally hypothymic (nude, nu/nu)NMRI mice was found to be characterized from the outset bya chronic trend. During the early phase of the infection, significantly reduced numbers of Listeria monocytogenes were observed in the spleens of nude mice.

Variable Adjuvant Activity of Bordetella pertussis with Respect to the Primary and Secondary Immunization of Mice.

We carried out a study on the adjuvant effect of Bordetella pertussis vaccine on the primary and secondary immune responses of the mouse to sheep erythrocytes, quantitating antibody-producing spleen cells and serum antibody. The simultaneous injection of sheep erythrocytes and B. pertussis, when compared to immunization with sheep red blood cells alone, resulted in an increased and prolonged multiplication of antibody-forming spleen cells. The adjuvant effect was also documented by increased production of serum hemolysins and agglutinins. Further, B. pertussis enhanced the priming effect of the antigen for the secondary response. However, when the bacterial adjuvant was given together with a second antigenic stimulus 41 days after the primary immunization, the peak values of direct and indirect plaque-forming spleen cells did not differ from the corresponding control animals further inoculated with sheep erythrocytes alone. Nonetheless, the influence of the bacterial adjuvant was still expressed by the delayed decrease of the numbers of plaque-forming spleen cells. On the basis of the X-Y-Z scheme it is suggested that B. pertussis cells as adjuvant enhance the multiplication of antigen-sensitive X cells or affect the initial stages of differentiation of these cells. This effect of the pertussis vaccine can be distinguished from a general proliferative action on other cells.

Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus.

The adjuvant activity of Bordetella pertussis was investigated, both at the cellular and humoral levels, when the bacterial adjuvant was administered at various times before the primary antigenic stimulus of both 8 x 10(6) and 4 x 10(8) sheep erythrocytes. In all experiments, both adjuvant and erythrocyte antigen were given intraperitoneally. Adjuvant activity was measured on the basis of the primary immune response and on the degree of priming for the secondary immune reaction. A maximal effect on the primary immune response was found in mice which had received B. pertussis vaccine simultaneously with the erythrocyte antigen. A significant degree of adjuvancy was also demonstrable when B. pertussis vaccine was administered within a period of 48 hr before antigen. Adjuvant effectiveness was less as the time interval between the injection of antigen and adjuvant increased. The process of priming for the secondary response, however, was found to be equally affected when the adjuvant was given either simultaneously with the antigen or 12, 24, and 48 hr before sheep erythrocytes. On the basis of these and previous findings, it is suggested that adjuvancy of B. pertussis is caused chiefly by additional recruitment of responding cells. It is also suggested that memory-cell production may develop concurrently with, but independently of, the cellular proliferative events which lead to antibody formation during the primary immune response.

[Studies on the mechanism and duration of antibody-mediated immunosuppression (author's transl)]. / Experimentelle Untersuchungen über Wirkungsweise und Dauer der Antikörper-bedingten Immunsuppression

The simultaneous injection of either 10(8) or 5 X 10(5) sheep erythrocytes (SE) and an allogeneic anti-SE serum into mice produced not only a suppression of the primary immune response, but, moreover, the secondary immune reaction elicited, either 4, 8, 12, 16 or 30 weeks after the primary antigenic stimulation, was found to be impaired. This was mainly demonstrated by the significantly reduced numbers of 7 S antibody-synthesizing spleen cells. The suppression of the secondary immune responses is hardly compatible with the conception that the antibody-mediated immunosuppression is solely due to an inactivation of the antigenic determinants by the passively administered specific antibody in the periphery of the immune system. This objection against the so-called "peripheric theory" is supported by a further finding. When mice primarily immunized by a simultaneous injection of 10(8) SE and anti-SE-serum were treated with 2 X 10(7) SE 24 hours before boostering with 10(8) SE, in order to eliminate a possibly existing residual activity of the passively administered specific antibodies given together with the primary antigenic stimulus, the secondary 7 S response was likewise found to be significantly suppressed. On the basis of these findings it is suggested that besides the "peripheric mechanism" a "central" effect plays a significant role in the phenomenon of antibody-mediated immunosuppression, this being due to the reversible or irreversible inactivation of immunocompetent precursor cells by the attachment of antigen-antibody-complexes which results in an inhibition of their differentiation into antibody-producing cells.

Cell-mediated resistance to infection with Listeria monocytogenes in nude mice.

Congenitally dysthymic nude (nu/nu) NMRI mice showed increased resistance to viable Listeria monocytogenes cells during the initial phase of infection as compared with euthymic control mice. The intravenous mean lethal dose (LD50), as determined for euthymic mice after an observation time of 7 and 14 days, amounted consistently to 6 X 10(4) Listeria. The corresponding values determined in nude mice were found to be increased by either 20-fold (1.2 X 10(6) Listeria after an observation time of 7 days) or 4-fold (2.4 X 10(5) Listeria after an observation time of 14 days). The transfer of spleen cells from immune euthymic donor mice into chronically infected nude mice caused almost complete elimination of Listeria within 1 week. The injection of dextran sulfate 24 h before a secondary infection with L. monocytogenes caused loss of antibacterial resistance in both chronically infected nude mice and Listeria-immune euthymic mice, this being expressed by a rapid increase in the numbers of bacteria in the spleens as well as the occurrence of serious signs of illness.

Time relationships between injection of antigen and adjuvant. 3. Adjuvancy of Bordetella pertussis given at various times after the primary antigenic stimulus.

The adjuvant activity of Bordetella pertussis was investigated, both at the cellular and humoral levels, when the bacterial adjuvant was given at various times after the primary antigenic stimulus of both 2 x 10(7) (suboptimal dose) and 4 x 10(8) (optimal dose) of sheep erythrocytes. In all experiments, both adjuvant and sheep erythrocytes were administered by the intraperitoneal route. Adjuvant activity was measured on the basis of the early and late phases of the primary response and on the degree of priming for the secondary immune reaction. A maximal adjuvant activity was found in mice which had received B. pertussis vaccine simultaneously with the antigen. Adjuvant effectiveness became less as the time interval between the injection of antigen and adjuvant increased. Adjuvancy also depended on the amount of antigen used as the primary antigenic stimulus. With 4 x 10(8) sheep erythrocytes, significantly increased priming for the secondary response was produced only when B. pertussis cells were administered within a period of 24 hr. When the bacterial adjuvant was administered either 48 or 72 hr after the primary antigenic stimulus, adjuvancy was found to be limited to the late phase of the primary response and to the prolonged development of antibody-forming cells during the secondary immune reaction. In contrast, significantly enhanced priming for the secondary response was detectable when the adjuvant was administered as late as 48 hr after primary immunization with 2 x 10(7) sheep erythrocytes. When the bacterial adjuvant was administered either 6, 24, 48, or 72 hr after the primary immunization with 2 x 10(7) sheep erythrocytes, the early phase of the primary 19S and 7S hemolysin response was found to be suppressed, and adjuvancy became detectable only thereafter.

[Influence of killed Bordetella pertussis cells on the resistance against infection with Listeria monocytogenes (author's transl)]. / Einfluss von abgetöteten Zellen von Bordetella pertussis auf die Infektabwehr gegen Listeria monocytogenes.

The influence of killed Bordetella pertussis cells (B.p.) on the cell-mediated resistance of mice against infection with virulent germs of Listeria monocytogenes has been studied. Resistance of mice was decreased, when 3 X 10(9) B.p. were injected 1 day before, simultaneously with or 1 day after infection, resulting in augmented amounts of viable Listeriae recovered from the spleens 3 days after infection (figure 1). The LD50 was strongly reduced (Table 1). Transfer of immune spleen cells to recipient mice, which had been treated 1 day previously with 3 X 10(9)B.p., did not support resistance definitely (Table 2). Therefore, it can be concluded that probably the macrophage system was impaired just after B.p. injection. When, however, B.p. were given several days before infection, resistance was increased. A maximum of resistance enhancement was seen 7-14 days after B.p. treatment. Thereafter, this beneficial effect gradually decreased but persisted for at least 67 days (figure 1). This resistance enhancing effect of B.p. was surely not due to adjuvant effect of B.p. on the T-lymphocyte-mediated immune reaction to Listeriae, since in B.p.-pretreated mice the development of immunity during the primary infection to a secondary listeric infection has even been lacking (Table 3). It is more likely that the macrophage system was stimulated at this time by B.p. In mice treated 7 days prior to infection the elimination of Listeriae from the spleens was supported from the very beginning of the infection (figure 2).

Murine model for therapy of listeriosis in the compromised host. I. Effect of ampicillin.

Therapy of listeriosis with ampicillin was examined in two murine models with compromised defense mechanisms. In mice treated with dextran sulfate paralysing the function of the macrophage system, ampicillin was less able to reduce death rates as well as bacterial counts in the spleens than after infection of normal mice. In nude mice with chronic listeriosis, treatment with ampicillin was started 8 days after infection. The numbers of viable listeria cells decreased under therapy, but a bacteriologic cure was not achieved in a 6-day schedule. Relapse followed cessation of therapy.

[Evaluation of a new latex agglutination test for identification of staphylococcus aureus]. / Beurteilung eines neuen Latex-Agglutinations-Tests zur Identifizierung von Staphylococcus aureus.

286 clinical isolates of staphylococci and 19 Micrococcus spp. were tested in a new latex agglutinating test to detect bound coagulase and protein A simultaneously. Coagulase-positive strains of staphylococci (n = 119) were all found to be latex-positive. Negative latex agglutination test results were obtained with 154 out of 167 coagulase-negative strains, the other 13 (7.8%) strains gave positive latex tests. Furthermore 3 out of 19 Micrococcus strains yielded positive agglutinating results. According to the results presented a negative latex test allows a rapid exclusion of S. aureus. A positive latex test requires the determination of further typical characteristics to differentiate among the staphylococcal isolates.

Lemierre's syndrome with spondylitis and pulmonary and gluteal abscesses associated with Mycoplasma pneumoniae pneumonia.

Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular veins, sepsis, and multiple metastatic infections. It commonly leads to pulmonary parenchymal abscesses and occasionally to septic arthritis, osteomyelitis, or liver or spleen abscesses. Reported here is a case of spondylitis and pulmonary and gluteal abscesses that occurred as part of a classic presentation of Lemierre's syndrome. Treatment with imipenem and clindamycin was successful.

The role of macrophages in primary and secondary infection of mice with Salmonella typhimurium.

Elimination of macrophages with high-molecular dextran sulphate (DS) markedly impairs resistance of mice to primary infection with smooth, virulent strains of Salmonella typhimurium, whereas stimulation of this system by killed Bordetella pertussis organisms increases resistance. In infection with rough, avirulent strains of S. typhimurium the elimination of macrophages was not followed by an essential loss of resistance, and it appears that other non-specific defence mechanisms, for example the complement system, may have compensated for the lack of macrophages. Macrophages, therefore, play an important role in defence during primary infection with virulent strains. In immunity to challenge infection with S. typhimurium, macrophages play an even more significant role. Treatment with DS completely removes immunity, and both humoral and cell-mediated immune mechanisms seem to require the participation of macrophages.

Morphology and time course of experimental listeriosis in nude mice.

Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, listeric infection in congenitally dysthymic nude (nu/nu) mice does not proceed in clear-cut phases, develops more slowly, displays a chronic tendency from the beginning, and shows a considerably different morphology. The inability of nude mice to effectively control and terminate infection by Listeria monocytogenes obviously results from the lack of T lymphocytes.

Infection of congenitally athymic (nude) mice with Toxoplasma gondii.

Nude mice, congenitally lacking most thymus-derived lymphocytes, are neither more susceptible nor more resistant against primary infection with virulent T. gondii cells than normal control mice. Both mouse groups died at the same time after intraperitoneal infection. Treatment with sulfadiazine protected both mouse groups against acute fatal disease. After termination of treatment with sulfadiazine the Nude mice gradually died, whereas the normal hairy mice survived. The latter had developed high amounts of antibodies and protective immunity to an otherwise lethal challenge infection. In the serum of Nude mice no antibodies could be detected. Pathologic alterations existed in the livers of Nude mice at the time of death.