Conjoint Professor Caroline Blackwell

Carriage of non-serogroupable Neisseria meningitidis or Neisseria lactamica induces antibodies protective against meningococcal disease. Antibodies directed against outer membrane proteins are bactericidal and the serotype and subtype outer membrane protein antigens are being examined for their value as vaccine candidates for serogroup B disease. The aim of this study was to examine the effect of carriage of these two Neisseria species among children and young adults on induction of antibodies to outer membrane components from strains causing disease in Greece. Among 53 patients with meningococcal disease, IgG or IgM antibodies were detected by ELISA in 9 of 13 (69%) from whom the bacteria were isolated and 27 of 40 (67%) who were culture-negative. For military recruits (n=604), the proportion of carriers of meningococci with IgM or IgG to outer membrane proteins was higher than non-carriers, P<0.05 and P=0.000000, respectively. Among school children (n=319), the proportion with IgM or IgG to outer membrane proteins for carriers of meningococci was higher compared with non-carriers, P=0.000000 and P=0000043, respectively. Carriage of N. lactamica was not associated with the presence of either IgM or IgG to the outer membrane proteins in the children. The higher proportion of children (50%) with IgM to outer membrane proteins compared with recruits (10%) might reflect more recent exposure and primary immune responses to the bacteria. The lack of association between antibodies to outer membrane proteins and carriage of N. lactamica could reflect observations that the majority of N. lactamica isolates from Greece and other countries do not react with monoclonal typing reagents. Bactericidal antibodies to meningococci associated with high levels of IgG to N. lactamica were found in a previous study; these are thought to be directed to antigens other than outer membrane proteins or capsules and imply antigens such as lipo-oligosaccharide are involved in induction of antibodies cross-reactive with meningococci. Copyright (C) 1999 Federation of European Microbiological Societies.

It has been suggested that pyrogenic toxins of Staphylococcus aureus are involved in the series of events leading to some cases of sudden infant death syndrome (SIDS). The objectives of the study were to screen tissues from SIDS infants for pyrogenic toxins and to compare incidence of identification of these toxins among these infants from different countries. An enzyme-linked immunosorbent assay (ELISA) and a flow cytometry method were used to screen body fluids and frozen or formalin-fixed tissues for pyrogenic toxins of S. aureus, toxic shock syndrome toxin 1 (TSST), staphylococcal enterotoxins A (SEA), B (SEB), and C1 (SEC). Toxins were identified in tissues of 33/62 (53%) SIDS infants from three different countries: Scotland (10/19, 56%); France (7/13, 55%); Australia (16/30, 53%). In the Australian series, toxins were identified in only 3/19 (16%) non-SIDS deaths (¿2=5.42, P<0.02). The flow cytometry method was useful for toxin detection in both frozen and fixed tissues, but ELISA was suitable only for frozen tissues or those fixed for less than 12 months. Identification of pyrogenic toxins in >50% of SIDS infants from three different countries indicated further investigation into the role the toxins play in cot deaths might result in development of additional measures to reduce further the incidence of these infant deaths. Copyright (C) 1999 Federation of European Microbiological Societies.

The number of cases of meningococcal disease reported to the Meningitis Reference Laboratory in Athens rose dramatically in 1996-1997. The aims were (1) to determine if the increase was due to introduction of new strains, (2) to assess the geographic and age distribution of the cases, (3) to compare antibiotic sensitivity patterns of the current isolates with strains from the early 1990s. In 1993-1994, 15/19 (74%) of the cases for which information on age was available were in children =5 years; in 1995-1997, 80/179 (45%) of cases were in children =5 years and 99 (55%) in the older age range (P<0.02). From 593 cases in 1993-1997, 214 (36%) isolates were available for characterisation. Serogroup B was predominant in the early 1990s, but by 1997, serogroup C accounted for 46/72 (64%) of isolates and serogroup B for 25/72 (35%). Serogroup B was predominant in children =5 years (44/78, 56%) but only 19/99 (18%) of older children and adults (P=0.0000005). Sulfonamide resistance decreased from 10/22 (45%) in 1993-1994 to 27/192 (14%) in 1995-1997 (P<0.01). Multilocus enzyme electrophoresis of 70 strains obtained during this period identified the epidemic ET-15 clone in 24 (34.3)%. The profiles of the Greek ET-15 isolates were identical to C:2a:P1.2(P1.5) strains responsible for the epidemic in the Czech Republic which began in 1993. This genotype was not found in Greek strains isolated prior to 1993. We conclude that the increase in meningococcal disease is due to introduction of the epidemic serogroup C:2a:P1.2(P1.5) strain responsible for disease in the Czech Republic and Canada. Copyright (C) 1999 Federation of European Microbiological Societies.

Epidemiological studies indicate that breast-fed infants are at a decreased risk of sudden infant death syndrome (SIDS) compared to formula-fed infants. Increasing evidence suggests that infectious agents might be involved in some of these deaths, in particular bacteria which colonise mucosal surfaces and produce superantigenic toxins. One species implicated in recent studies of SIDS infants is Staphylococcus aureus. We tested the hypothesis that in comparison to infant formula, human milk might be a better inhibitor of binding of S. aureus to epithelial cells. In this study, two protocols were used for the binding assays which were assessed by flow cytometry: the in vitro method in which bacteria were treated with milk or formula, washed and added to epithelial cells; and a method more closely reflecting the competitive interactions in vivo in which cells, bacteria, and milk or infant formula were added at the same time. With the in vivo method, breast milk caused enhancement of bacterial binding to cells whilst infant formula caused inhibition; however, for the in vitro method, both human milk and infant formula caused consistent enhancement of binding. Flow cytometry and light microscopy studies indicated that the enhancement was due to the formation of bacterial aggregates. Human milk and infant formula preparations were also compared for components (antibodies or oligosaccharides) that could inhibit binding of S. aureus using the in vitro method. Human milk contained both IgA and IgG. Neither human milk nor infant formula contained oligosaccharides reactive with the Ulex europaeus lectin but both contained components that bound monoclonal antibodies to Lewisa and Lewisb antigens which can act as receptors for S. aureus. With both methods, synthetic Lewisa and Lewisb inhibited S. aureus binding in a dose-dependent manner. With human milk, however, the only component which showed a significant correlation with inhibition of binding was the IgA specific for the staphylococcal surface component that binds Lewisa. Both human milk and infant formula contain components which could potentially inhibit bacterial binding but only breast milk contains the IgA specific for the bacterial adhesin that binds Lewisa. Studies using the in vivo method suggest that protection associated with breast feeding in relation to SIDS could be due mainly to the formation of bacterial aggregates. The studies have implications for further research into constituents of infant formula. Copyright (C) 1999 Federation of European Microbiological Societies.

Recent studies on the aetiology of the Sudden Infant Death Syndrome (SIDS) have suggested that some of these deaths are the consequence of an overwhelming inflammatory response to the production of pyrogenic toxins from bacteria colonizing the upper respiratory tract, particularly the nasopharynx. The pyrogenic toxins of Staphlococcus aureus, one of the likelier bacterial candidates, are only produced in temperatures of over 37°C. This study examined nasopharyngeal temperatures in children. It is a preliminary study to develop an accurate means to measure how close to 37°C the nasopharyngeal temperature lies in infants at the age when SIDS deaths occur. Following a pilot study and power calculation, measurements of nasopharyngeal temperature were made on 30 apyrexial children aged 4-10 years and 30 adults with no nasal pathology, undergoing surgery under general anaesthesia, using an accurately sited thermocouple probe. The mean temperature in children (35.64°C) was significantly higher than in adults (34.01°C). Comparable measurements attempted with the same subjects awake gave similar results.

There is no convincing epidemiological or pathological evidence that particular infectious events cause sudden infant death syndrome (SIDS); therefore, we have explored the concept that ergy between bacterial endotoxins, exotoxins or viruses might elicit inflammatory responses during a period when the infant's do ine system is less able to 'damp down' cts of powerful mediators such as is factor or to maintain lu which is affected by these mediato his hypothesis is discussed with reference to the recent decline in the number of cot deaths. © 1995 Elsevier Science Ltd.

Because there is little evidence that invasive bacterial diseases contribute to cot deaths, most studies on infectious causes of SIDS have focused on viruses or toxin producing bacteria. Although epidemiological studies found marginally significant associations between influenza virus and SIDS, respiratory syncytial virus (RSV) was isolated from 90% of older infants with SIDS. There are conflicting reports that some toxigenic bacteria (Clostridium botulinum, Clostridium difficile, enterotoxigenic Escherichia coli and Staphylococcus aureus) might be implicated in cot deaths. S aureus are common micro-organisms and their toxins are very powerful. As the pyrogenic toxic shock syndrome toxin of S aureus can kill a previously healthy adult, it might easily kill a small infant. Based on our studies on susceptibility of infants to other infections, we suggest the following might be factors leading to colonisation of infants by toxin producing S aureus: - The Lewisa blood group antigen appears to act as a receptor for some micro-organisms. Epithelial cells expressing high concentrations of Lewisa bound appreciably more toxin producing S aureus than cells expressing low concentrations of the antigen. - Lewisa is expressed in secretions of nearly 90% of infants aged 3 months, the peak age for SIDS. - RSV infects about 50% of infants by the first year of life and it is often isolated from infants with SIDS. Studies in our laboratory indicate that RSV infected HEp-2 cells bind more toxin producing S aureus than uninfected controls.

Epidemiological studies on the associations between ABO blood group antigens, secretor status and susceptibility to infectious agents are summarized. Evidence for association of non-secretion with some autoimmune diseases for which infectious aetiologies have been proposed is also given. Several hypothesis are proposed to explain the host-parasite interactions underlying the epidemiological observations, and evidence to support or refute them is presented. © 1989.

Strains of Escherichia coli isolated from urine of secretors (242) and non-secretors (121) were compared for their serotype and their ability to express mannose-sensitive (MS) haemagglutinins and mannose-resistant (MR) haemagglutinins and to produce haemolysin. The results of the survey refuted our hypothesis that strains with characteristics associated with virulence, those with MR haemagglutinins and/or haemolysins, would be isolated more frequently from non-secretors. MR haemagglutinins were detected among 36.4% of isolates from secretors and 27.3% of isolates from non-secretors. Haemolysin production was detected among 19.8% of isolates from secretors and 12.5% of isolates from non-secretors. Both MR haemagglutinins and haemolysin were detected only on 12.4% of strains from secretors and 6.7% of strains from non-secretors. © 1989.

This study tested the hypothesis that the Lewis a blood group antigen found predominantly on the cells of non-secretors might be one of the receptors for Candida species. Binding of strain 3118C to epithelial cells from either secretor or non-secretor donors was not inhibited by treating the cells with anti-Lewis a or anti-Lewis b antisera. Binding of strain 3091 to non-secretor cell was inhibited by pretreating the cells with anti-Lewis a, but this was not observed for secretor cells. The results suggest that Lewis a might be one of the receptors for some yeast strains. © 1989.

In a study of 718 women referred for specialist investigation for recurrent urinary tract infections, 250 (34.8%, P<0.01) were non-secretors. The proportion of non-secretors among the women with renal scars (42.6%) was higher than that found for women with no evidence of renal scars (36.6%). Among 29 patients in whom symptoms began in childhood or adolescence, 51.7% were non-secretors. The proportion of non-secretors among individuals with renal scars in this study (42.6%) and that reported in the accompanying paper for Swedish children (40%) suggests that non-secretion might influence the pathogenic sequelae of these infections. Possible host-parasite interactions underlaying the increased proportion of non-secretors among women with recurrent urinary tract infections and those leading to development of renal scars are discussed. © 1989.

Epidemiological evidence is summarized for associations of ABO blood group and secretor status with susceptibility to invasive disease due to capsulate organisms responsible for the majority of bacterial meningitis. Host-parasite interactions that might underly these findings are proposed and evidence to support or refute them provided. © 1989.

Recognition of bacteria, antigen presentation and regulation of the immune response by the class II antigens of the major histocompatibility complex (MHC) are among the many factors that influence a host's response to microbial infection. 'Lectin-like' receptors on the macrophage membrane recognize a variety of bacteria by interaction with their cell-wall sugars. These receptors are susceptible to environmental factors and appear to be associated with the I-A subregion of the mouse MHC. Possible effects of this recognition system on the pathogenesis of microbial infection and reactive arthritides are considered.