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In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen.

Our laboratory has previously shown that after immunization with a strain of Salmonella typhimurium, SL3235, made avirulent by a blockage in the pathway of aromatic synthesis, murine splenocytes were profoundly suppressed in their capacity to mount an in vitro antibody plaque-forming cell (PFC) response to sheep erythrocytes. Evidence indicated that suppression was mediated by nitric oxide (NO), since the in vitro addition of NG-monomethyl-L-arginine blocked suppression. The present studies examined the effect of blocking NO production on Salmonella-induced immunosuppression by in vivo administration of aminoguanidine hemisulfate (AG). AG was administered to C3HeB/FeJ mice in their drinking water (2.5% solution) for 7 days prior to intraperitoneal inoculation with SL3235. AG treatment inhibited the increase in nitrate and nitrite levels in plasma and nitrite levels in the spleen seen in immunized mice. Importantly, AG treatment completely blocked suppression of the splenic PFC response and markedly attenuated the suppression of the response to concanavalin A in immunized mice, providing further evidence that Salmonella-induced immunosuppression is mediated by NO. AG treatment also alleviated the majority of the splenomegaly associated with SL3235 inoculation, which correlated with a blockage of influx of neutrophils and macrophages into spleens, as assessed by flow cytometry. AG treatment unexpectedly resulted in 90% mortality in mice injected with the highly attenuated vaccine strain of Salmonella, SL3235. Increased mortality in AG-treated mice correlated with inability to clear organisms from the spleen by day 15 postinoculation and with persistent bacteremia, compared with control mice. Collectively, these in vivo results underscore the dual biological consequences of NO production following Salmonella infection, with NO being necessary for host defense, but also having the potentially adverse effect of immunosuppression. A unifying hypothesis to explain how these seemingly paradoxical effects could both result from NO production is presented.

Animals↗

Extra-intestinal non-typhoidal Salmonella infections in children.

Extra-intestinal non-typhoidal Salmonella (NTS) infections are uncommon in developed countries but common in developing ones. The risk factors, clinical features and outcome of children admitted to the Department of Paediatrics, University of Malaya Medical Center, Kuala Lumpur from 1978 to 1998 with extra-intestinal NTS infections were reviewed. All positive cultures of NTS, blood, cerebrospinal fluid, urine, synovial, pericardial and other body secretions (except stools), were included. Of the 98 cases reviewed, 56 were boys and 42 girls. The mean age was 2.1 years (range: newborn to 14 years). Twenty-seven children were severely immunocompromised and 21 had underlying chronic medical disorders. Bacteraemia was the most commonly detected type of infection and meningitis the commonest focal infection. The overall mortality rate was 15%. An immunocompromised state or underlying chronic medical disorder was associated with increased mortality. The three serotypes most commonly isolated were S. enteritidis, S. paratyphi B and S. typhimurium. Most isolates were sensitive to antibiotics commonly used in salmonellosis.

Adolescent↗

[The morphometric characteristics of the immune system organs in dynamic experimental Salmonella infection].

Quantitative and morphological changes in the immune system (CBA x C57BL/6)F1 mice after their enteral (group 1) and intraperitoneal (group 2) inoculation with Salmonella typhimurium in a dose of 2 x (10)6 microbial cells per mouse were studied. The study revealed that on day 28 after inoculation the death rate of the animals was 12.5 +/- 6.75% in group 1 and 57.84 +/- 4.89% in group 2. The same type of changes in the organs of the immune system was observed in both groups of mice, but in the animals of group 2 these changes were more pronounced. This was manifested by leukocytosis, exhaustion of thymic cells, hyperplasia, hypertrophy of the spleen and an increase in the proliferative activity in its B-zone, a decrease in the number of myelokaryocytes. Such changes are indicative of their importance in the resistance of the body to Salmonella infection.

Animals↗

Outbreaks of salmonella infection in hospitals in England and Wales 1978-87.

A total of 248 outbreaks of salmonella infection in hospital affecting over 3000 patients and 110 associated deaths were ascertained in England and Wales in 1978-87, compared with 522 outbreaks of salmonella in 1968-77. The largest reduction was found in outbreaks from children's units and maternity units. Fifty seven (24%) outbreaks were considered to be due to foodborne salmonellosis, and 70 (30%) were reported as person to person spread of the infection. The psychiatric hospital was the type of hospital in which foodborne outbreaks most often occurred, but the risk of being affected in an outbreak not due to food seemed to be highest in maternity units. Better control of infection and better surveillance should lead to earlier investigation and control of outbreaks.

Cohort Studies↗

Lymphocyte transformation responses to gram negative bacteria after Yersinia and Salmonella infection: the importance of enterobacterial common antigen for the response.

Increased lymphocyte transformation (LT) responses have been observed in Yersinia infections both against the causative bacterium and against other enterobacteria. The responses of patients with reactive arthritis are lower than those of non-arthritic patients. We have now studied the LT responses against several gram negative bacteria and against a pair of enterobacterial common antigen (ECA) positive and ECA negative Salmonella typhimurium strains in patients after Yersinia or Salmonella infection. The haptenic ECA alone seemed not to be responsible for the increased LT responses. We conclude that some other common antigenic determinants present on the bacteria are responsible for the LT response.

Antigens, Bacterial↗

[Biological properties of salmonellae and local immunity in Salmonella infection].

The comparative study of the biological properties of S. enteritidis and S. typhimuruim, isolated from patients and convalescent carriers, was carried out. Factors inactivating the components of the local immunity of the intestine (lysozyme, complement, lactoferrin, IgG, IgM and IgA) were detected in the causative agents of Salmonella infections. The spread and expression degree of properties of a causative agent were serovar-depended: high penetration characteristics and the expression of anti-lactoferrin and anti-immunoglobulin activity were characteristic of S. typhimurium. S. enteritidis strains isolated from patients with carrier state formed in the convalescence period were found to have higher persistence level. In co-profiltrates obtained from carriers at the peak of the disease and during convalescence lower levels of IgM, IgG, sIgA, complement and lactoferrin were determined in comparison with those in coprofiltrates obtained from patients in whom no subsequent carrier state was formed. These results indicate that an increase in the persistence of salmonellae, occurring simultaneously with the local immunodeficiency, contributes to the prolonged survival of bacteria in the intestine.

Antibodies, Bacterial↗

Detection of Salmonella C1, D and V1 antigens, by coagglutination, in blood cultures from patients with Salmonella infections.

Protein A-containing Staphylococcus aureus was coupled to Salmonella C1, D and Vi monovalent antisera to produce C1-, D- and Vi-COAG reagents. The reagents were used to detect their homologous Salmonella antigens in blood cultures (BC). The D and Vi antigens were detected in 79 of 239 BC from patients with suspected typhoid fever and Salmonella typhi was later isolated from the same 79 BC. The C1 antigen was detected in 8 BC from which only S. oranienburg was later isolated. The COAG test was generally positive at the same time the BC became culture positive. However, because of subculture and biochemical identification requirements the COAG test could be interpreted 1-2 days before culture results were available. The COAG test can be used to presumptively identify Salmonella typhi and Salmonella group C1 in blood cultures before the culture results are available.

Agglutination Tests↗

The epidemiology of Salmonella infection of calves: the role of dealers.

Salmonellas were detected in the environment of 10 of the 12 calf dealers' premises studied. The cleaning and disinfection routines were often ineffective and salmonellas were isolated from 7.6% and 5.3% of the wall and floor samples before disinfection and 6.8% and 7.6% afterwards. Eight different salmonella serotypes were detected, of which the commonest were Salmonella typhimurium, predominantly phage type DT204C, and S. dublin. Plasmid profiles were used to fingerprint S. typhimurium DT204C and the results indicated that with the exception of one of the premises, prolonged salmonella-persistence in the environment was not occurring. Three separate epidemics of salmonellosis in calves were studied by use of plasmid profile analysis. The results illustrated the role of delers, and their subcontractors, in the dissemination of salmonellas. The study concludes with suggestions for methods to reduce the spread of salmonellas in the calf marketing chain.

Animals↗

The protective role of interleukin-18 in Salmonella infection.

Since its derivation, much has been learned about the proinflammatory inducing cytokine interleukin-18, and its role in resolving infectious diseases. Studies to date that examined interleukin-18 have shown that endogenously induced interleukin-18 plays an important protective role in some viral and bacterial infections. However, interleukin-18 has a limited role in protective immunity to Salmonella infections, and is secondary to the protective role of interleukin-12. This lack of sensitivity to interleukin-18 may be in part related to the dependence on interleukin-12 for interleukin-18 receptor expression and to the nanomolar concentrations that are required. Nonetheless, an understanding of how some pathogens have evolved to circumvent interleukin-18 and of how interleukin-18 can be effectively induced are essential to our ability to develop better vaccines against enteric pathogens.

Animals↗

[Comparison of the ELISA (lipopolysaccharide) and Widal reactions (O antigen) in the diagnosis of Salmonella infections].

At various times after the onset of disease 50 sera of patients with bacteriologically proven salmonella infections were investigated for O-antigen specific antibodies in ELISA and Widal-tests. 21 of these sera were derived from patients with typhoid fever, 10 from patients with gastroenteritis due to various species of salmonella group D and 19 from patients with group B salmonella-gastroenteritis. Additional 44 sera stemming from patients without such infection were included in the investigation as a control. With ELISA the sera were examined for antibodies of the IgM- and IgG-class separately. As antigens lipopolysaccharide W-preparations from S. typhi ("group D-antigen") and S. typhimurium ("group B-antigen") were used in the ELISA. High reciprocal titers (geometric means: 1404, 2560, and 1020) of IgM were demonstrable in sera drawn 11-30 days after onset of the disease with group D- and group B-antigen respectively (Fig. 1, Table 1 and Table 2). With increasing distance of time from the onset of the disease these titers decreased rapidly. The titers of agglutinating antibodies as measured in the Widal-test behaved similarly to those of IgM (Fig. 1, Table 1 and 2), and the correlation between both was high (r = +0.93, Fig. 2). In contrast, titers of IgG-antibodies reached their maximum later, namely 31-60 days after onset of the disease (Table 1), and the correlation to the agglutinin-titers (r = +0.33, Fig. 3) was much lower. In sera of patients with typhoid fever reciprocal titers of IgM against the homogeneous group antigen surmounted those of IgG at the average by about 5 log2-step (mean g: 1404 and 79 respectively) between the 11th and 30th day of disease. At this stage of the disease also sera from patients with gastroenteritis due to both salmonella D or B demonstrated clearly an IgM-dominated ratio. After a period of more than 2 month this ratio was about 1:1 in sera of patients with typhoid fever or with salmonella group D-gastroenteritis, but was clearly IgG-dominated in sera obtained from patients with group B-gastroenteritis. This might be due to the fact that most of the sera classified as "obtained greater than 2 months after onset" stemmed from excreters of salmonella B species.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Bacterial↗