The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): III. Detection of IgA antibodies in human milk that bind to bacterial toxins implicated in SIDS

Two toxin-producing bacteria implicated in sudden infant death syndrome (SIDS) are Staphylococcus aureus and Clostridium perfringens. Epidemiological studies have shown that breast feeding reduces an infant's risk of SIDS. This protective effect could be due partly to IgA antibodies to these toxins in human milk. The aim of this work was to use a quantitative ELISA to determine levels of IgA antibodies that bound to toxic shock syndrome toxin (TSST-1), staphylococcal enterotoxin C (SEC) and C. perfringens enterotoxin A (CEA) in individual samples of human milk. All samples of milk tested contained IgA antibodies that bound to the bacterial toxins. For individual samples, IgA bound to TSST-1, SEC and CEA were in the range of 900-3100 ng ml(-1), 1000-3600 ng ml(-1) and 1000-4300 ng ml(-1) respectively. Isolation of S. aureus from mothers donating breast milk samples was used to determine if the presence of bacteria affected IgA levels which bound TSST-1 and SEC. For 3/5 samples with levels above the upper limit of the standard deviation (2375 ng ml(-1)) for IgA bound to TSST-1, S. aureus was isolated from the mother whilst 4/5 samples found to contain levels above the upper limit of the standard deviation (2627 ng ml(-1)) for IgA bound to SEC, had S. aureus isolated from the mother. In conclusion, if bacterial toxins do play a role in precipitating a SIDS death, the presence of IgA antibodies to toxins in breast milk, but not in infant formula, might contribute to the protective effect of breast feeding in relation to SIDS.     

The effect of Staphylococcus aureus carriage in late pregnancy on antibody levels to staphylococcal toxins in cord blood and breast milk

We investigated the effect of carriage of Staphylococcus aureus in the later stages of pregnancy on levels of antibody specific to the S. aureus toxins, staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin C (SEC) and toxic shock syndrome toxin-1 (TSST-1), in cord blood and breast milk and also explored the relationship between levels of antibody in antenatal serum and cord blood. Nasopharyngeal swabs and stool samples were collected on two occasions, from 96 women, during the last 6 weeks of pregnancy. Samples were cultured and S. aureus isolates were identified. Antenatal and cord blood samples from the same women and their infants were analysed for IgG antibody to SEB, SEC and TSST-1 by enzyme-linked immunosorbent assay. Breast milk samples were analysed for IgA antibody to the same toxins. We found that S. aureus carriage in pregnancy is common and exposure to a toxin-producing isolate boosts immunity. Over 89% of women and infants have some protective antibody to the toxins, and antitoxin IgG levels are higher in cord blood samples compared with antenatal samples. Levels of cord blood IgG and breast milk IgA specific for the staphylococcal toxins vary. Some infants lack protection and could be at risk of toxin-induced disease.     

The protective effect of immunisation against diphtheria, pertussis and tetanus (DPT) in relation to sudden infant death syndrome

Epidemiological evidence indicates infants immunised against diphtheria, pertussis and tetanus (DPT) are at decreased risk of sudden infant death syndrome (SIDS). Asymptomatic whooping cough and pyrogenic toxins of Staphylococcus aureus have been implicated in the aetiology of SIDS. The objectives of the present study were: (1) to determine if the DPT vaccine induced antibodies cross-reactive with the staphylococcal toxins; (2) to determine if antibodies to the pertussis toxin (PT) and the staphylococcal toxins were present in the sera of women during late pregnancy; (3) to examine the effects of infant immunisation on levels of antibodies to PT and the staphylococcal toxins; (4) to assess the effects of changes in immunisation schedules in the UK on the incidence and age distribution of SIDS. Enzyme-linked immunosorbent assays (ELISA) were used to measure binding of rabbit or human IgG to the DPT vaccine, PT, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins A (SEA), B (SEB) and C (SEC). Neutralisation activity of anti-DPT serum was assessed by a bioassay for induction of nitric oxide from human monocytes by the staphylococcal toxins. Anti-DPT serum bound to the DPT vaccine, PT and each of the staphylococcal toxins. It also reduced the ability of the four toxins to induce nitric oxide from monocytes. In pregnant women, levels of IgG to PT, SEC and TSST-1 decreased significantly in relation to increasing weeks of gestation while antibodies to SEA and SEB increased. In infants' sera there were significant correlations between levels of IgG bound to DPT and IgG bound to PT, TSST-1 and SEC but not SEA or SEB. Antibody levels to the toxins in infants declined with age; sera from infants < or = 2 months of age had higher levels of IgG bound to the toxins than those older than 2 months. This pattern was observed for infants whose immunisation schedules began at 2 months of age or 3 months of age. The decrease in IgG bound to the toxins was, however, less for those immunised at 2 months. The decrease in SIDS deaths after the change in immunisation schedules was greatest in the 4-6-month age range. While DPT immunisation might prevent some unexplained infant deaths due to asymptomatic whooping cough, these data indicate that immunisation with DPT also induces antibodies cross-reactive with pyrogenic staphylococcal toxins implicated in many cases of SIDS. Passive immunisation of infants who have low levels of these antibodies might reduce further the numbers of these infant deaths.     

Toxigenic bacteria and sudden infant death syndrome (SIDS): nasopharyngeal flora during the first year of life

Many developmental and environmental risk factors for sudden infant death syndrome (SIDS) are similar to those for susceptibility to respiratory tract infection, and toxigenic bacteria have been implicated in some SIDS cases. We assessed nasopharyngeal flora of healthy infants in relation to risk factors to determine which species best lit the mathematical model proposed for the common bacterial toxin hypothesis and if these findings complemented results obtained from SIDS cases which occurred during the period of the survey. Longitudinal studies were carried out between April 1993 and March 1996 on 253 healthy infants and their mothers. 150 from a multiply deprived area, 103 from an affluent area. Concurrent SIDS infants (37) were screened for nasopharyngeal flora. Among healthy infants < or = 3 months of age, the predominant isolate was Staphylococcus aureus 57% compared with 86% for SIDS infants in that age range (P< 0.02). There were significant associations between isolation of different species from both mother and baby but no association between isolation of any species with: area of residence: parental smoking habits; breast or bottle feeding; symptoms of viral infection: seasonality. We conclude that S. aureus fits the mathematical model for SIDS. Both staphylococci and/or their toxins were identified in a significant proportion of SIDS cases. Isolation of staphylococci from healthy infants was associated with the 2-4-month age range, a risk factor consistently found in all epidemiological studies of SIDS. This might reflect the developmental stage in which 80-90% of infants express the Lewis(a) antigen which we have shown to be one of the receptors for S. aureus.     

Detection and toxin production of Staphylococcus aureus in sudden infant death cases in Hungary

The potential role of microbial agents was investigated in 13 cases of Sudden Infant Death Syndrome and in 9 non-SIDS cases in Budapest between September 1996 and May 1998. Autopsy, histological examination and microbiological tests were performed on samples of blood, cerebrospinal fluid, pharyngeal samples and lung tissue from infants under one year died suddenly, without previous diseases. The multifactorial pathomechanism of SIDS was suggested by the isolation of toxin producing Staphylococcus aureus-, Enterobacteriaceae and Candida albicans strains in large number and by the detection of Parainfluenza Type 2 virus antigen. S. aureus proved the predominant bacteria in the SIDS cases. Nasopharyngeal microbial flora and S. aureus carrier of 100 age matched healthy infants were tested during the same period. S. aureus was isolated from 54% of SIDS cases and 37% from healthy infants /OR = 1.986 (95% Confidence interval = 0.55-7.33), p = 0243/. The enterotoxin and TSST-1 toxin producing activity of S. aureus showed the characteristic difference. The toxigenic S. aureus was detected in 46% of SIDS cases and 16% of healthy infants /OR = 4.5 (95% CI = 1.15-17.72), p = 0.010/. The distribution of toxigenic and nontoxigenic isolates was 86% in SIDS cases and 43% in healthy infants /OR = 7.875 (CI = 0.78-191.89), p = 0.041/.     

Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome

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 (chi2 = 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.     

Staphylococcal enterotoxin genes are common in Staphylococcus aureus intestinal flora in Sudden Infant Death Syndrome (SIDS) and live comparison infants

Pathological and epidemiological findings in sudden infant death syndrome (SIDS) suggest an infectious aetiology with indications of involvement of staphylococcal enterotoxins (SEs). While SEA, SEB and SEC have been found in the sera and tissues of SIDS cases, little is known about the role of intestinal Staphylococcus aureus or the roles of later-described toxins SEE, SEG, SEH, SEI and SEJ in SIDS. We used a molecular-based approach to define whether the intestinal tract could be a source of SEs to support the staphylococcal toxic shock hypothesis for SIDS. Intestinal contents from 57 SIDS infants and faeces from 79 age- and gender-matched live comparison infants were cultured and tested for S. aureus and sea-b-c-e-g-h-j and TSST using PCR. High proportions of infants in both groups carried toxigenic and nontoxigenic S. aureus . Significantly greater proportions of SIDS compared with comparison babies were positive for S. aureus (68.4% vs. 40.5%) and for SE genes (43.8% vs. 21.5%), suggesting a possible role in SIDS. The results indicate that colonization by S. aureus with SE genes is common in infants; however, their detection is unlikely to be a strong predictive tool for SIDS. Other factors (including immune response) may reveal a specific susceptibility to SEs in SIDS infants.     

The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position

The aim of the investigation was to determine the effect of age, gender, viral upper respiratory tract infection (URTI), season and sleeping position on the composition of the nasopharyngeal bacterial flora in infancy. Seventy-two babies, 38 male and 34 female, whose birthdates were evenly spread throughout the year were followed from birth to 18 months of age. From 0 to 6 months nasopharyngeal swabs were obtained once a month in periods without URTI and daily for 3 days during episodes of URTI. From 12 to 18 months of age nasopharyngeal swabs were obtained in the early morning alter an overnight sleep and later in the day after the baby had been up for over 2 h. Swabs were obtained in prone and supine sleepers with and without infection. In infants aged 0-6 months URTI had little effect on the nasopharyngeal bacterial flora, but there was a marked effect of age and less marked effect of season and gender. In particular Staphylococcus aureus carriage decreased with age, was most common in the winter months and the density of colonisation was greater in males than females. In infants aged 12-18 months the combination of prone sleeping with URTI and an early morning swab led to increased carriage of staphylococci, streptococci. Haemophilus influenzae and Gram-negative bacilli which are not normally part of the nasopharyngeal flora. These results are relevant to sudden infant death syndrome (SIDS). The combination of prone sleeping and URTI reproduces the nasopharyngeal flora seen in SIDS. Gram-negative bacilli isolated from SIDS cases should not be dismissed as post-mortem contaminants. The features of S. aureus make it a prime candidate for a pathogenic role in SIDS.     

Mucosal immune responses to infections in infants with acute life threatening events classified as 'near-miss' sudden infant death syndrome

This study examined the hypothesis that dysregulation of mucosal immune responses to respiratory infections is a critical event, which could be causal in respiratory arrest of some previously healthy infants. To examine this hypothesis, a prospective study was undertaken of infants presenting to the emergency department of a major teaching hospital with acute life threatening events (ALTE) of unknown cause and classified as "near-miss" SIDS. Salivary immunoglobulin concentrations were measured on admission and again after 14 days. The salivary immunoglobulins were compared with three control groups: infants with a mild upper respiratory tract infection (URTI); bronchiolitis; and healthy age-matched infants. The salivary IgA and IgM concentrations in the ALTE infants at presentation to hospital indicated a significant mucosal immune response had already occurred, with nearly 60% of the IgA concentrations significantly above the population-based reference ranges. The hyper-immune response was most evident in the ALTE infants with pathology evidence of an infection; 87% of these infants had salivary IgA concentrations on average 10 times higher that the age-related median concentration. The most prevalent pathogen identified in the ALTE infants was respiratory syncytial virus (RSV) (64%). RSV was also identified in all subjects with bronchiolitis. Risk factors for SIDS were assessed in each group. The data indicated that the ALTE infants diagnosed as 'near-miss' SIDS were a relatively homogeneous group, and most likely these ALTE infants and SIDS represent associated clinical outcomes. The study identified exposure to cigarette smoke and elevated salivary IgA concentrations as predictors of an ALTE. The study findings support the hypothesis of mucosal immune dysregulation in response to a respiratory infection in some infants with an ALTE. They provide a plausible explanation for certain SIDS risk factors. The underlying patho-physiological mechanism of proinflammatory responses to infections during a critical developmental period might be a critical factor in infants who have life-threatening apnoea or succumb to SIDS. The study raises the possibility of using salivary IgA to test infants who present with mild respiratory infections to identify a substantial number of infants at risk of developing an ALTE or SIDS, thus enabling intervention management to prevent such outcomes.     

The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): I. The effect of human milk and infant formula preparations on binding of toxigenic Staphylococcus aureus to epithelial cells

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 Lewis(a) and Lewis(b) antigens which can act as receptors for S. aureus. With both methods, synthetic Lewis(a) and Lewis(b) 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 Lewis(a). 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 Lewis(a). 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.     

Cortisol levels and control of inflammatory responses to toxic shock syndrome toxin-1 (TSST-1): the prevalence of night-time deaths in sudden infant death syndrome (SIDS)

There is evidence that inflammatory responses have been induced in the tissues and body fluids of many SIDS infants. We suggested that some of these deaths are due to uncontrolled inflammatory responses to infectious agents and possibly cigarette smoke. The majority of SIDS deaths occur during the 2-4 month age range when infants have decreasing levels of maternal antibodies to infectious agents. Most deaths occur during the early hours of the morning. Adults are more susceptible to inflammatory responses at night due to lower levels of cortisol associated with circadian rhythm patterns. Infants develop these patterns between the ages of 7 weeks and 4 months, at which time their night-time cortisol levels drop dramatically. The objective of this study was to use an in vitro model system to assess the effects of different cortisol levels on proinflammatory cytokine production in response to the staphylococcal toxic shock syndrome toxin-1 (TSST-1) which has been identified in a significant number of SIDS infants. Levels of cortisol present in infants at night and during the day before and after the development of the circadian rhythm pattern were examined. Human buffy coats (n = 9) were stimulated with TSST-1 and responses assessed over 72 hours by a bioassay for tumour necrosis factor-alpha (TNF-alpha) and an enzyme linked immunosorbent assay (ELISA) for interleukin-6 (IL-6). Cortisol levels present in an infant at night after development of circadian rhythm (< or = 5 microg dl(-1)), did not significantly increase or decrease production of either TNF-alpha or IL-6. Concentrations of cortisol greater than 5 microg dl(-1) usually found in infants during the day or at night prior to the physiological change significantly decreased production of TNF-alpha at 12 hours and of IL-6 at 12 and 16 hours. Only cortisol levels greater than 5 microg dl(-1) significantly decreased production of the pro-inflammatory cytokines by human buffy coats stimulated with TSST-1. If the switch to the circadian rhythm pattern occurs in an infant when maternal antibodies are still present or after they have developed their own active immunity, the infant could neutralise common viruses, toxins or bacteria: however, if this switch occurs in an infant when antibody levels are low, this could be a window of vulnerability during which infants are at an increased risk of death if uncontrolled inflammatory responses are induced by infectious agents or their products.     

新生儿巨细胞病毒感染的检测

建立了用ELISA检测巨细胞病毒(HCMV)IgA抗体的方法,並用于检测北京地区100对母婴的HCMV抗体,母血、脐带血、母乳中HCMV-IgG抗体的阳性率分别为83％,75％和38％,HCMV-IgA抗体的阳性率分别为19％,15％和58％,对其中的16名婴儿半年后追踪观察,5名出生时母、脐血全为阴性的,有2名抗体阳转。8名出生时母、脐血均阳性的,有1名IgA仍阳性並检查发现肝大肋下二指。另1名IgG持续阳性,其他6名婴儿抗体转阴。3名出生时母血HCMV-IgG阳性者中,1名婴儿IgA和‘gG转阳,此时母亲IgA也阳转。随访的16名婴儿中有3名可能是生后半年内受HCMV感染。     

Endotoxin in blood and tissue in the sudden infant death syndrome

Although the explanation for sudden infant death syndrome (SIDS) remains unknown, an increasing body of evidence now exists to suggest a possible role for bacterial toxins in the aetiology, and a number of investigators have considered that endotoxaemia could explain some of the associated features. Following the development of an animal model which confirmed that endotoxaemia could be detected after death, we studied endotoxin levels in blood and tissue samples taken at autopsy from SIDS infants, child controls and adult controls. There were significant correlations between endotoxin levels in blood and the various organs sampled particularly in SIDS cases and child controls, and blood endotoxin levels in SIDS cases were higher in those infants where there was histological evidence of mild to moderate inflammation. However, overall no significant differences were found between endotoxin levels in blood or tissue in the three study groups. Further studies into possible actions or interactions of endotoxin in SIDS are required.     

Interleukin-10 and sudden infant death syndrome

Uncontrolled pro-inflammatory responses to infections or bacterial toxins have been suggested to play a role in triggering the physiological events leading to sudden infant death syndrome (SIDS). We tested the hypothesis that these uncontrolled responses might be due to interactions between the gene polymorphisms inducing low levels of IL-10 and exposure to cigarette smoke. In vitro, the IL-10 (G-1082A) polymorphism was associated with low IL-10 levels and the -1082G allele was associated with high levels. The first objective was to assess the distribution of this polymorphism among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess effects of human recombinant IL-10 on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) responses of human leukocytes to staphylococcal toxins implicated in SIDS. The third objective was to assess IL-10 responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non-smokers in relation to the IL-10 (G-1082A) polymorphism. There were major differences in the distributions of these polymorphisms between Europeans and Bangladeshis (p=0.00) and between Europeans and Aboriginal Australians (p=0.00); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. There were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants compared to control groups. IL-10 significantly reduced IL-6 and TNF-alpha responses to TSST and staphylococcal enterotoxins A and C. At 50 ng ml(-1), IL-10 significantly increased TNF-alpha but not IL-6 responses to TSST and enterotoxin A. Although IL-10 responses to endotoxin were lower from leukocytes of smokers who were homozygous for the G allele, the differences were not significant; however, significantly lower IL-10 responses were found for smokers who were homozygous for the A allele (p=0.01) and heterozygotes (p=0.04). The pooled data found smokers had significantly lower levels of IL-10 responses to TSST, but there were no significant differences for smokers compared with non-smokers for the three genotypes. The high incidence of SIDS and serious respiratory infections among Aboriginal Australian infants and the low incidence of these conditions among Bangladeshi infants might be explained in part by our findings of differences in IL-10 responses between smokers and non-smokers. The lowest levels of IL-10 responses were observed among smokers who were homozygous for the A allele which is most prevalent among the Aboriginal Australians (83%) and Bangladeshis (84%). The major difference between the risk factors for SIDS in these two groups is the level of exposure of infants to cigarette smoke associated with maternal smoking.     

Production of enterotoxins and toxic shock syndrome toxin by Staphylococcus aureus isolated from bovine mastitis in Brazil

The production of toxic shock syndrome toxin 1 (TSST-1) and enterotoxins (SE) A, B, C and D by bovine mastitis isolates of Staphylococcus aureus was evaluated by immunodiffusion using the Optimum-Sensitivity Plate method. S. aureus strains were isolated from bovine mastitis in 23 dairy herds in the state of Minas Gerais, Brazil, during 1994-9. Of 127 isolates, 83 (65.04%) produced one or several toxins, and among them production of SE was found in 54 (43.0%) isolates, of which 1138 (29.09%) secreted enterotoxin identified as type D. TSST-1 was found in 5829 (45.723.0%) isolates.     

Bindings of toxic shock syndrome toxin-1 and staphylococcal enterotoxins A, B, and C to rabbit spleen cells

Toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SE) A, B, and C were studied on binding to rabbit spleen cells. The toxins showed remarkable mitogenic effects on the cells. Among them, SEA and TSST-1 had much stronger mitogenic activities than SEB and SEC. Binding study showed that labeled TSST-1 and SEA bound considerably to cells, but that labeled SEB or SEC was not observed to bind at a detectable level under the same conditions as TSST-1 and SEA. Competitive binding analysis between toxins to cells proved that TSST-1 and SEA clearly competed with each other in binding. Scatchard plots for TSST-1 and SEA in binding were linear at the doses used. The Scatchard analysis for TSST-1 and SEA gave a dissociation constant of 2.5 X 10(-9) M and 7.6 X 10(-8) M and the number of binding sites per cell of 5.3 X 10(3) and 1.0 X 10(5), respectively.     

Immunologic aspects of human colostrum and milk. III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn

A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich human colostrum 18 to 72 hr after birth. Subsequently, the presence of IgG, IgA, and IgM immunoglobulin and poliovirus antibody activity was determined in serial serum and fecal samples of the neonates. Absorption of IgA immunoglobulin from the colostrum to the circulation was observed in three infants who were fed with colostrum between 18 and 24 hr after birth. Another group of infants of tuberculin-positive mothers who were being breast fed by their own mothers were followed for the development of in vitro correlates of cell-mediated immunity against tuberculin after prolonged breast feeding. Tuberculin-specific proliferative response was observed in the peripheral blood lymphocytes of two neonates after 5 weeks of breast feeding. The responses were undetectable after 12 weeks, although the infants continued to breast feed. No tuberculin reactivity was observed in the cord lymphocytes. These observations suggest uptake of IgA immunoglobulin and components of cellular immunity in the intestine during the immediate neonatal period.     

Detection of enterotoxins and TSST-1 secreted by Staphylococcus aureus isolated from ruminant mastitis. Comparison of ELISA and immunoblot.

The production of staphylococcal enterotoxins (SE) and toxic shock syndrome toxin-1 (TSST-1) was studied in 81 strains of Staphylococcus aureus isolated from cases of mastitis in cattle, goats and sheep. SE and TSST-1 were detected by two techniques: ELISA double antibody sandwich, and an immunoblot technique combined with a semiautomated electrophoresis system. More Staph. aureus strains isolated from sheep produced enterotoxins than those from goats and cattle. SEC was the predominant type in all isolates from these animal species. The highest proportion of strains producing TSST-1 were obtained from sheep, twice as many as those from goats or cows. The two techniques gave similar results, as all the strains positive by immunoblot were also positive by ELISA, and only three were positive by ELISA but negative by immunoblot.     

Ethnicity, infection and sudden infant death syndrome

Epidemiological studies found the incidence of SIDS among Indigenous groups such as Aboriginal Australians, New Zealand Maoris and Native Americans were significantly higher than those for non-Indigenous groups within the same countries. Among other groups such as Asian families in Britain, the incidence of SIDS has been lower than among groups of European origin. Cultural and childrearing practices as well as socio-economic factors have been proposed to explain the greater risk of SIDS among Indigenous peoples; however, there are no definitive data to account for the differences observed. We addressed the differences among ethnic groups in relation to susceptibility to infection because there is evidence from studies of populations of European origin that infectious agents, particularly toxigenic bacteria might trigger the events leading to SIDS. The risk factors for SIDS parallel those for susceptibility to infections in infants, particularly respiratory tract infections which are also major health problems among Indigenous groups. Many of the risk factors identified in epidemiological studies of SIDS could affect three stages in the infectious process: (1) frequency or density of colonisation by the toxigenic species implicated in SIDS; (2) induction of temperature-sensitive toxins; (3) modulation of the inflammatory responses to infection or toxins. In this review we compare genetic, developmental and environmental risk factors for SIDS in ethnic groups with different incidences of SIDS: low (Asians in Britain); moderate (European/Caucasian); high (Aboriginal Australian). Our findings indicate: (1) the major difference was high levels of exposure to cigarette smoke among infants in the high risk groups; (2) cigarette smoke significantly reduced the anti-inflammatory cytokine interleukin-10 responses which control pro-inflammatory responses implicated in SIDS; (3) the most significant effect of cigarette smoke on reduction of IL-10 responses was observed for donors with a single nucleotide polymorphism for the IL-10 gene that is predominant among both Asian and Aboriginal populations. If genetic makeup were a major factor for susceptibility to SIDS, the incidence of these deaths should be similar for both populations. They are, however, significantly different and most likely reflect differences in maternal smoking which could affect frequency and density of colonisation of infants by potentially pathogenic bacteria and induction and control of inflammatory responses.