M. W. Raza

Association between secretor status and respiratory viral illness.

OBJECTIVE--To determine whether non-secretion of blood group antigens is associated with respiratory virus diseases. DESIGN--Study of secretor status in patients with respiratory virus diseases determined by an enzyme linked immunosorbent assay (ELISA) developed to identify Lewis (Le) blood group antigen phenotypes (Le(a) non-secretor; Le(b) secretor). SUBJECTS--Patients aged 1 month to 90 years in hospital with respiratory virus diseases (584 nasal specimens). MAIN OUTCOME MEASURES--Criteria for validation of ELISA (congruence between results on ELISA testing of 1155 saliva samples from a previous study and previously established results on haemagglutination inhibition (HAI) testing, proportions of Le(a), Le(b), and Le- phenotypes in 872 samples of nasal washings from a previous study compared with the normal population). Secretor status of patients determined by ELISA and viruses isolated. RESULTS--Agreement between HAI and ELISA for 1155 saliva samples was 97%. Lewis antigens were detected by ELISA in 854 (97.9%) of nasal washings (Le(a) 233 (26.7%), Le(b) 621 (71.2%), and Le- 18 (2.1%)) in proportions predicted for a northern European population. Secretors were significantly overrepresented among patients from whom influenza viruses A and B (55/64, 86%; p less than 0.025), rhinoviruses (63/72, 88%; p less than 0.01), respiratory syncytial virus (97/109, 89%; p less than 0.0005), and echoviruses (44/44, p less than 0.0005) had been isolated compared with the distribution of secretors in the local population. CONCLUSION--Secretion of blood group antigens is associated with respiratory virus diseases.

Factors enhancing adherence of toxigenic Staphylococcus aureus to epithelial cells and their possible role in sudden infant death syndrome

Toxigenic strains of Staphylococcus aureus have been suggested to play a role in sudden infant death syndrome (SIDS). In this study we examined two factors that might enhance binding of toxigenic staphylococci to epithelial cells of infants in the age range in which cot deaths are prevalent: expression of the Lewis(a) antigen and infection with respiratory syncytial virus (RSV). By flow cytometry we demonstrated that binding of three toxigenic strains of S. aureus to cells from nonsecretors was significantly greater than to cells of secretors. Pre-treatment of epithelial cells with monoclonal anti-Lewis(a) or anti-type-1 precursor significantly reduced bacterial binding (P < 0.01); however, attachment of the bacteria correlated only with the amount of Lewis(a) antigen detected on the cells (P < 0.01). HEp-2 cells infected with RSV bound significantly more bacteria than uninfected cells. These findings are discussed in context of factors previously associated with SIDS (mothers smoking, bottle feeding and the prone sleeping position) and a hypothesis proposed to explain some cases of SIDS.

Effect of respiratory syncytial virus infection on binding of Neisseria meningitidis and Haemophilus influenzae type b to a human epithelial cell line (HEp-2)

It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virus-infected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0.001) and Hib (P < 0.01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.

The potential role of bacterial toxins in Sudden Infant Death Syndrome (SIDS)

SummaryToxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence thatClostridia spp. are associated with SIDS in Britain, strains ofStaphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy. The pyrogenic toxins, produced by some strains of group AStreptococcus pyogenes as well as staphylococci, are powerful “superantigens” that have significant physiological effects including induction of fever > 38°C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infants expression of Lewisa antigen which acts as a receptor for some microorganisms; viral infections; the effect of mothers smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths.ZusammenfassungIn einigen Fällen des Sudden Infant Death Syndrom (SIDS) wurde die Rolle Toxin bildender Bakterien diskutiert. Obwohl es keinen Beweis gibt, daß Clostridia spp. mit SIDS in Großbritanien assoziiert sind, sind von signifikanter Anzahl dieser Kinder bei der Autopsie Stämme von Stapylokkokus aureus isoliert worden, welche Fieber erzeugende Toxine produzieren. Die Fieber erzeugenden Toxine, welche von einigen Stämmen der Gruppe A Streptokkokus pyogenes produziert werden, wie auch von Staphylokkoken, sind mächtige „Superantigene”, welche signifikante physiologische Effekte haben unter Einbeziehung der Induktion von Fieber mit mehr als 38°C. In diesem Artikel werden Interaktionen zwischen genetischen und Umgebungsfaktoren erörtert, welche die Kolonisierung epithelialer Oberflächen durch Toxin bildende Staphylokkoken steigern könnten: die Expression des Lewisa Antigens des Kindes, welches als Rezeptor für einige Mikroorganismen wirksam ist; virale Infektionen; die Auswirkung des mütterlichen Rauchens auf die Empfänglichkeit für Atemwegsinfektionen. Basierend auf epidemiologischen Befunden und Laboratoriumsuntersuchungen wird eine Hypothese vorgeschlagen, wie Bakterien; welche pyrogene Toxine produzieren, zu einigen plötzlichen Kindstodesfällen beitragen könnten.

The Effect of Respiratory Virus Infection on Expression of Cell Surface Antigens Associated with Binding of Potentially Pathogenic Bacteria

Serious secondary bacterial infection can occur following illness due to respiratory viruses and viral infections have also been suggested to be predisposing factors for bacterial meningitis [Moore et al., 1990; Cartwright et al., 1991]. Respiratory virus infection can compromise host defences against bacterial infection in a number of ways: immune suppression; diminished phagocytosis by polymorphonuclear leucocytes; local tissue injury; loss of mucociliary function and decreased bacterial clearance; formation of exudates that enhance bacterial growth; and increased bacterial binding to virus infected cells. Most investigators have studied associations of influenza virus and respiratory pathogens such as Streptococcus pneumoniae [Plotkowski et al., 1986], Staphylococcus aureus [Musher and Fainstein, 1981] and Haemophilus influenzae [Bakeletz et al., 1988; Fainstein et al.,1980].

Bactericidal activity of a monocytic cell line (THP-1) against common respiratory tract bacterial pathogens is depressed after infection with respiratory syncytial virus

Non-typable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and respiratory syncytial virus (RSV) are commonly isolated from patients during the course of chronic obstructive pulmonary disease (COPD). Earlier studies found that virus infection enhanced binding of bacterial respiratory pathogens to epithelial cells in vitro. The objective of the present study was to assess the effect of RSV infection of a human monocytic cell line on bactericidal activity and cytokine production in response to these bacterial respiratory pathogens. The effect of RSV infection on binding, uptake and intracellular killing of bacteria by a human monocytic leukaemia cell line, THP-1, was assessed. Cell culture supernates were examined with a mouse fibroblast cell assay for tumour necrosis factor-alpha (TNF-alpha) bioactivity. Expression of CD14, CD11a, CD18, CD15 and CD29 on uninfected and RSV-infected THP-1 cells was assessed by flow cytometry in relation to differences in bacterial binding. RSV infection of THP-1 cells significantly decreased their ability to bind and kill bacteria. Compared with uninfected cells, fewer bacteria bound to RSV-infected THP-1 cells and the surface antigens that have been reported to bind bacteria were expressed at lower levels on RSV-infected cells. RSV-infected cells incubated with bacteria exhibited less TNF-alpha bioactivity than uninfected cell incubated with bacteria. The results elucidate some of the mechanisms involved in the increased susceptibility of virus-infected patients to secondary bacterial infection. Reduced bacterial killing by virus-infected monocytes might contribute to reduced clearance of bacteria from the respiratory tract and damage elicited by the bacteria or cytokine response in COPD patients.

Adhesins Of Staphylococcus Aureus that Bind Lewisa Antigen

Sudden Infant Death Syndrome (SIDS) is defined as “the sudden death of any infant or young child which is unexpected by history, and in which a thorough postmortem examination fails to demonstrate an adequate cause of death” [Beckwith, 1969]. Since 1990, there has been a steady reduction in the numbers of SIDS in Britain [Court, 1995; Scottish Cot Death Trust, personal communication]; however, SIDS is still the major cause of post perinatal mortality during the first year of life. Petechiae in the lungs and thymus, liquid heart blood and empty bladder are common findings at autopsy [Berry, 1992]. While there is little evidence that could explain why the infant died, there are common findings that suggest immune or inflammatory reactions have been elicited before death(Table 1).