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Infections in children with sickle cell anemia. Special reference to pneumococcal and salmonella infections.

Pneumococcal sepsis and/or meningitis are major causes of morbidity and mortality in young children with sickle cell disease. Abnormal complement activity, poor splenic function and a lack of type-specific pneumococcal antibody are responsible for the severity and frequency of these infections. A program consisting of early institution of antibiotic therapy for febrile episodes, antimicrobial prophylaxis, and administration of pneumococcal vaccine may be effective in reducing the incidence of pneumococcal disease. Specific guidelines for infection prevention are presented. Other infections that are more frequent or more severe in children with sickle cell disease (e.g., Salmonella, Haemophilus and mycoplasma infections) are also discussed.

Anemia, Sickle Cell↗

Invasive multidrug-resistant non-typhoidal Salmonella infections in Africa: zoonotic or anthroponotic transmission?

In Africa, multidrug-resistant non-typhoidal salmonellae (NTS) are one of the leading causes of morbidity and high mortality in children under 5 years of age, second in importance only to pneumococcal disease. The authors studied NTS isolates from paediatric admissions at two hospitals in Nairobi, Kenya, and followed the index cases to their homes, where rectal swabs and stools from parents and siblings, and from animals in close contact, were obtained. The majority of NTS obtained from cases were Salmonella enterica serotype Typhimurium (106 out of 193; 54.9%) and Salmonella enterica serotype Enteritidis (64; 33.2%), a significant proportion (34.2%) of which were multiply resistant to three or more antibiotics, including ampicillin, tetracycline, cotrimoxazole and chloramphenicol. Only 23.4% of NTS were fully susceptible to all 10 antibiotics tested. Of the 32 NTS obtained from contacts (nine adults and 23 children) at the homes of index cases, 21 (65.6%) isolates were similar by antibiotic-susceptibility profiles and plasmid content, and their XbaI- and SpeI-digested chromosomal DNA patterns were indistinguishable from those of the corresponding index cases. Only three out of 180 (1.7%) samples from environmental sources, including animals, soil, sewers and food, contained NTS matching those from corresponding index cases. The carriage of NTS in an asymptomatic population was represented by 6.9% of human contacts from 27 out of 127 homes sampled. This population of carriers may represent an important reservoir of NTS that would play a significant role in the epidemiology of community-acquired NTS bacteraemia in children.

Anti-Bacterial Agents↗

Animal models of Salmonella infections: enteritis versus typhoid fever.

The most common disease syndromes caused by Salmonella serotypes in humans, typhoid fever and enteritis, can be modeled using Salmonella enterica serotype Typhimurium infections in mice and calves, respectively. This article reviews murine typhoid and bovine enteritis and discusses strengths, limitations and distinctive features of these animal models.

Animals↗

Immunoprophylaxis of Salmonella gallinarum infection by Salmonella enteritidis-immune lymphokines in broiler chicks.

Research on the control of intestinal and tissue colonization of breeder and table-egg producing flocks by invasive Salmonella enteritidis (SE) has focused on the advancement of anti-salmonella feed additives, microbiological strategies, and the development of vaccines. Recent investigations in our laboratories have concentrated on the development of immunoprophylactic measures to control Salmonella infections. We have found an increased resistance to Salmonella enteritidis (SE) organ infectivity in chickens conferred by the prophylactic administration of SE-immune lymphokines (SE-ILK). Fowl typhoid, caused by Salmonella gallinarum (SG), is a septicemic disease of domestic birds resulting in morbidity with moderate to very high mortality within the first 2 weeks of age. The objective of the present studies was to evaluate the effect of a prophylactic treatment of neonatal broiler chicks with lymphokines derived from S. enteritidis (SE)-immunized chickens (SE-ILK) on the birds' resistance to an experimental infection with S. gallinarum (SG). On the day-of- hatch, chicks were intraperitoneally administered either SE-ILK, control nonimmune lymphokines (NILK), or nothing. Thirty min later, all chicks were gavaged with either 10(4) cfu or 10(6) cfu SG. For 10 days after challenge, the chicks were observed twice daily for morbidity and mortality. Chicks that died during the experiment had their livers cultured for SG. Chicks that survived throughout the 10 day experimental period were killed and their livers, spleens, and cecal tonsils cultured for SG. The prophylactic treatment of chickens with SE-ILK induced significant protection against an extraintestinal SG infections when compared to NILK as evidenced by: 1) a significant reduction (P < 0.005) in the mortality of chicks challenged with either 10(4) and 10(6) cfu sg; 2) increased average weight gains of chicks challenged with either 10(4) and 10(6) efu SG; and 3) a significant (P < 0.001) reduction in the total number of SG-organ-culture positive chicks. The results suggest that the prophylactic administration of SE-ILK can non-specifically confer protection to chicks against a pathogenic salmonellae as seen by reduced morbidity, mortality, and organ infectivity of SG in broiler chicks while enhancing weight gain during the first ten days of life.

Animals↗

Effect of indomethacin on intestinal water transport in salmonella-infected rhesus monkeys.

Indomethacin, a nonsteroidal anti-inflammatory agent, will abolish salmonella-induced rabbit ileal secretion when given prior to the establishment of infection. In the present study, we assessed whether indomethacin can inhibit salmonella-induced intestinal secretion when administered after infection and net intestinal secretion are well established. A physiological model of salmonellosis, salmonella-infected rhesus monkeys, was used. This model also permitted an examination of the effects of indomethacin in both the small and large intestines. The effect of indomethacin in control monkeys was also studied. Indomethacin caused a striking enhancement of net intestinal water transport in the jejunum,, ileum, and colon of salmonella-infected monkeys. These effects occurred promptly and were of sufficient magnitude in the ileum and colon to cause a reversal in the direction of net transport from net secretion to net absorption. Indomethacin also enhanced net water transport in the jejunum ileum, and colon of normal animals. These data show that indomethacin markedly enhances net intestinal water transport in both the small and large intestines of salmonella-infected monkeys, even when administered after salmonella infection and intestinal secretion are well established. Similar enhancement also occurs in the normal intestine. The mechanism(s) by which indomethacin produces these effects is not known.

Animals↗

[The effect of salmonella infection on the functional activity of the polymorphonuclear leukocytes].

Experiments on noninbred white mice have revealed that in the animals infected with S. moscow secondary immunodeficiency develops, which is manifested by a significant decrease in the activity of the bactericidal system of peripheral blood granular leukocytes. Simultaneously, the content of myeloperoxidase in the blood neutrophils of infected mice decreases 1.4 times and the content of lysozyme in these neutrophils decreases 2 times. Such changes are the consequence of an increase in the secretory activity of cells, occurring in the process of the development of Salmonella infection.

Animals↗

Monitoring the efficacy of steam and formaldehyde treatment of naturally Salmonella-infected layer houses.

AIMS: To monitor if a temperature-humidity-time treatment found to be effective in eliminating Salmonella in laboratory trials (Gradel et al. 2003) was efficient against Salmonella in naturally infected layer houses. METHODS AND RESULTS: Six layer houses with natural Salmonella infections were steam treated in a download period, aiming at >or=60 degrees C and 100% relative humidity (RH) during a 24-h period, with or without the addition of 30 ppm formaldehyde. In addition, two control layer houses were disinfected chemically. Salmonella samples taken from predetermined sites before and after treatment were tested qualitatively for Salmonella and coliforms. Samples with indicator bacteria (feed inoculated with Escherichia coli or Enterococcus faecalis and faeces with naturally occurring E. coli and enterococci) were placed during steam-treatment at 12 sites in each house (where the temperature was logged at 5-min intervals) and tested for surviving bacteria. Generally, the field test results confirmed the results of laboratory tests, especially when 30 ppm formaldehyde was added to the steam. In well-sealed houses, the recommended temperature-humidity-time scheme was accomplished at a minimum of 10 cm above floor level within 1 h. CONCLUSIONS: A steam treatment of >or=60 degrees C and 100% RH during a 24-h period with the addition of 30 ppm formaldehyde at the beginning of the process is recommended for eliminating Salmonella from naturally infected poultry layer houses. SIGNIFICANCE AND IMPACT OF THE STUDY: A specific recommendation for the elimination of Salmonella in poultry houses can be given.

Animals↗

Comparison of peptides eluted from the groove of HLA-B27 from Salmonella infected and non-infected cells.

Reactive arthritis (ReA) is associated with the MHC class-I molecule HLA-B27 and caused by certain Gram-negative bacteria. The mechanism by which HLA-B27 confers a higher susceptibility for this disease compared to other MHC Class-I alleles is still not known. We investigated whether infection of human HLA-B27+ cells is able to change the peptide repertoire presented by these HLA-B27 molecules. To this end large quantities of a B-cell line (C1R-B27) transfected with HLA-B2705 were infected with S. typhimurium. Peptides were eluted from the B27 molecules and separated by Reversed Phase Chromatography (RPC). We then compared the peptide profiles obtained from S. typhimurium infected CIR B-cells with that obtained from non infected cells. Apart from a few additional peaks present in the profile derived from the infected batch the peptide profiles were almost identical. A few fractions were subjected to sequencing by Edman degradation. All peptides found were nonameres with arginine (Arg) at position 2 which is in agreement with the previously described HLA-B27 peptide binding motif. The majority of peaks expressed a mixture of at least four different peptides. The analysis of differences between HLA-B27 bound peptides from Salmonella infected and non infected cells might lead to the identification of T-cell epitopes shared by Salmonella and autoantigens.

Arthritis, Reactive↗

Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

Adult↗

[Lipopolysaccharide-induced apoptosis of peripheral granulocytes in patients with prior salmonella infection].

The in vitro induction of granulocytes in the presence of high and low concentrations of lipopolysaccharides (LPS) allowed the authors to study a dose-dependent apoptotic response in the population of intact cells and in that of primed cells in the period of convalescence in patients with Salmonella infection. An experimental system was used to study a respiratory burst and granulocytic apoptosis in the presence of hypothalamic neuropeptides. The clinical manifestations of the diseases were studied in 32 inpatients. It was shown that there was an increase in the sensitivity of granulocytes to the apoptotic action of low, suboptimal doses (100 ng) of S. enteritidis LPS in patients with salmonellosis at convalescence. This correlates with the severity of a clinical course of the experienced disease and with the suppressed sensitivity of apoptosis to the optimal doses (1000 ng) LPS.

Apoptosis↗

Effect of experimental zinc deficiency on immunological responses in Salmonella-infected guinea-pigs.

Cellular and humoral immune responses to Salmonella dublin infection were studied in guinea-pigs given zinc-deficient (ZnD) or zinc-adequate (ZnA) diet, containing 1.03 or 52.4 mg Zn/kg, respectively. On day 30, each animal of each dietary group was inoculated intraperitoneally with 10(6)viable cells of S. dublin strain 493. On the 15th day after infection, the immune responses were assessed by skin hypersensitivity (SH) tests and enzyme-linked immunosorbent assay (ELISA) for serum antibody with Salmonella -extract antigen. ZnD animals had significantly decreased ability to produce Salmonella -specific immediate and delayed type SH responses. These results were further substantiated by histological examination of skin sections. The ELISA indicated significantly lower Salmonella -specific serum antibody titres in ZnD animals than in ZnA animals. Mean viable counts of S. dublin in the liver and spleen of ZnD animals were significantly higher than those in ZnA animals.

Animals↗