Leucocyte migration inhibition in diphtheria toxoid hypersensitivity

A donor who was highly reactive to diphtheria toxoid (DT) in delayed hypersensitivity and in lymphocyte transformation showed scant evidence of antigen-induced inhibition in the direct leucocyte migration agarose test. Other donors, weak or negative to DT in skin test and transformation, did show evidence of inhibition. Although the migration test is useful in assessing cellular reactivity to tubercular antigen, these results question its suitability for DT.     

Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults

It is important to monitor the long-term persistence of antibodies induced by vaccination. Four cohorts were followed for their long-term immunity after vaccination with a combined hepatitis A and B vaccine (Twinrix; SmithKline Beecham Biologicals, Rixsenart, Belgium). Two cohorts of adults (ages 17-60 years), one of 1-6-year-olds, and one of 6-15-year-olds were vaccinated following a 0, 1, and 6-month schedule. Follow-up data until month 72 (adults) and month 60 (children) are available. At month 72, antibody to hepatitis A virus (anti-HAV) seropositivity (S+) was 100% for both adult cohorts (n = 40 and n = 47) and 95% and 89% of the vaccinees were seroprotected against hepatitis B virus (HBV), respectively. The geometric mean titres (GMTs; mIU/ml) for anti-HAV were 977 and 542 and the GMTs for the antibody to hepatitis B surface antigen (anti-HBs) were 322 and 90. For 1-6-year-olds at month 60 (n = 39), anti-HAV S+ was 100% with a GMT of 479 and 97% were protected against HBV with a GMT of 195. At month 60 for the 6-15-year-olds (n = 42), anti-HAV S+ was 100% with a GMT of 990 and 95% were protected against HBV with a GMT of 263. There have been no safety issues during the follow-up. In the past 5 years, a postmarketing surveillance system was available. Using this system, all spontaneous adverse events are collected and archived. Although infrequent, the most commonly reported adverse events after more than 13 million doses were allergic-type reactions followed by fever and injection site reactions. The combined hepatitis A and B vaccine is safe and is well tolerated. Immunity provided by the vaccine remains high in adults and children with comparable results to those obtained with monovalent vaccines.     

Lower antibody response to tetanus toxoid associated with higher auto-anti-idiotypic antibody in old compared with young humans.

The production of anti-tetanus toxoid (TT) antibody and anti-anti-TT (auto-anti-Id) antibody has been measured in three young and three old persons. Both antibodies were measured using ELISA. We found that: (i) the anti-TT response of old subjects was lower than that of young subjects, (ii) serum auto-anti-Id antibody concentration was higher in old compared with young humans before boosting with TT, and (iii) anti-TT antibodies from different humans shared Id cross-reactivity when tested with a rabbit anti-Id antibody. Thus, the serum anti-TT antibody response to boosting was inversely correlated with the serum level of auto-anti-Id. This conclusion is consistent with the view that the higher level of auto-anti-antibody in older subjects contributes to their impaired antibody response to TT.     

Reduction of human anti-tetanus toxoid antibody in hu-PBL-SCID mice by immunodominant peptides of tetanus toxoid

Immunotherapy of murine autoimmune and allergic diseases by administration of peptides corresponding to the dominant T cell epitope is a reality. However, problems remain in applying this therapy to reduce antibody responses in humans. To overcome these difficulties, a preclinical system was developed to test the effect of immunodominant peptides from a common antigen, tetanus toxoid (TT), on the long-term human anti-TT response. Individuals whose T cells proliferated against dominant TT peptides were identified. Peripheral blood leucocytes (PBL) from these donors were injected intraperitoneally (i.p.) into mice with severe combined immunodeficiency (SCID) that had been depleted of murine natural killer (NK) cells (hu-PBL-SCID mice). Peptides or PBS were injected i.p. before a further injection of PBL and immunization with TT. The concentration of human IgG and anti-TT in murine plasma was followed for 10 weeks. The total IgG was similar in both groups. By contrast, there was a statistically significant reduction in IgG anti-TT from eight weeks onwards. It is considered that the hu-PBL-SCID model system may provide a means by which the efficacy of peptide immunotherapy for reduction of pathological antibodies in humans can be examined.     

Long-term follow-up of children born to women immunized with tetanus toxoid during pregnancy

Ten years after transplacental immunization with tetanus toxoid, the antibody responses of the immunized children to a booster immunization with 5 Lf tetanus toxoid did not differ from those of the control children. The tetanus toxoid-stimulated lymphocyte proliferative responses showed that there was no tolerance to tetanus toxoid induced by transplacental immunization, and the stimulation indices suggested that there may be some long-term memory for tetanus toxoid among the T lymphocytes in children who had been transplacentally immunized by maternal immunization with a standard dose of tetanus toxoid.     

Intraperitoneal immunization of human subjects with tetanus toxoid induces specific antibody-secreting cells in the peritoneal cavity and in the circulation, but fails to elicit a secretory IgA response.

Five patients on continuous ambulatory peritoneal dialysis (CAPD) were immunized intraperitoneally with tetanus toxoid (TT) through an indwelling catheter. Four control patients on CAPD received the same dose of TT intramuscularly. Before immunization, virtually no anti-TT antibody-secreting cells (AbSC) were detected by the enzyme-linked immunospot (ELISPOT) assay in peripheral blood or peritoneal fluid from patients of either group. One to 2 weeks after immunization, high frequencies of TT-specific AbSC were detected in the circulation and peritoneal cavity. More than 80% of those cells were of the IgG isotype, with IgA accounting for most of the remainder. Patients receiving TT by the i.p. route showed significantly higher frequencies of specific IgG and IgA AbSC in the peritoneal cavity than patients immunized intramuscularly. Frequencies of AbSC in peripheral blood did not significantly differ between the two groups. Immunization with TT by both routes resulted in a significant increase of IgG anti-TT antibodies in serum, saliva and peritoneal fluid. A significant IgA antibody response was seen only in serum and peritoneal effluents. Therefore, i.p. immunization of human subjects with TT elicited both a localized response in the peritoneal cavity as well as a systemic response in serum, but did not induce a salivary IgA response.     

Herd immunity to Newcastle disease virus in broiler flocks in Israel

Due to the ongoing need to protect poultry from virulent Newcastle disease virus, all commercial poultry flocks in Israel are vaccinated according to a defined programme using a combination of live and inactivated vaccines. The vaccination protocol for broilers during the years of the study comprised a live vaccine administered by spray on the day of hatching, inactivated vaccine by subcutaneous injection at 10–12 days of age, and another live vaccine given by aerosol at 17–21 days of age. A cross-sectional study was designed in order to examine the influence of herd immunity on the risk of Newcastle disease outbreak in broiler flocks. The study was based on the extensive field data kept in the Poultry Health Laboratories database. The results of serology tests employing haemagglutination inhibition for Newcastle disease virus were analysed and crossed with the list of flocks that had been diagnosed with ND in the years 2007–2014. At the peak of induced immunization (fifth week of growth), 87.5% of the tested flocks had achieved herd immunity (≥85% of birds in the flock with an HI titre ≥4). Based on a logistic regression model, the odds ratio for ND in flocks without herd immunity was 3.7 (95% CI 1.8–7.3, P-value?相似文献   

Prevalence and correlates of snoring among adults in Nigeria

Introduction

Snoring is a common sleep problem with significant public health concerns. Studies have characterized this in most developed countries. Hitherto there have been no published studies on this subject in Nigeria.

Objectives

To determine the prevalence and correlates of snoring in addition to morbidity in an adult population in Nigeria.

Design

A cross — sectional survey of 370 young adult and adult living in Abuja, Nigeria.. Data were collected on socio- demographic characteristics, sleep pattern as well as occurrence of snoring, apneas and excessive day time sleepiness was determined using Epworth Sleepiness Scale (ESS). Body Mass Index (BMI) and blood pressure were measured.

Results

Of the 370 respondents, 218 (59%) were females. The overall prevalence of snoring was 31.6%; habitual snoring (14%) and moderate snoring (17%). Apnea was reported in about 2% of the respondents while the prevalence of Clinically Suspected Obstructive Sleep Apneas (CSOSA) was 1%, (1.9% in males, 0.5% in females). Snoring was significantly associated with male sex, old age, increased BMI and cigarette consumption . The severity of snoring was also associated with a higher ESS score, day time symptoms and other morbidities.

Conclusions

Snoring among Nigerians is associated with multiple factors. There is a need for more awareness about this condition in order to control measures of factors associated with snoring.     

Prevalence of antibodies to human cytomegalovirus in urban, kibbutz, and Bedouin children in southern Israel

Prevalence of antibody to human cytomegalovirus (CMV) was determined in a sample of 860 healthy children aged 1-13 years in Beer Sheva, in the Negev region of Israel. Three groups of children were tested: (1) urban Jewish children of low, middle, and high socioeconomic levels; (2) 8 rural communes (kibbutz) in which children live in close contact with each other from the 6th week of life under good hygienic conditions and a high standard of living; (3) Bedouin, seminomadic Arabs living in relatively poor hygienic conditions in the desert. Kibbutz children showed a significantly higher rate of CMV seropositivity by the second year of life than urban Jewish and Bedouin children (76% versus 44% and 54% respectively) with a gradual increase to 94% in the 10-13-year age group. Among children living in urban populations a significantly higher prevalence of CMV seropositivity was associated with crowding, but not with other socioeconomic indicators (place of residence, country of origin, or education level of parents). A marked rise of CMV seropositivity with age was found in urban Jewish children in the 2-5-year age group during which time they attend nurseries (44% to 67%) and in the Bedouin children in the 6-9-year age group (59% to 86%) when they first attend school. The data suggest that close contact is of major importance in CMV infection in childhood. The clinical implications of early acquisition and high prevalence of CMV antibodies in the kibbutz setting are discussed.     

Prevalence and correlates of disturbed dreaming in children

Relatively little is known about nightmares and other forms of disturbed dreaming in children. This article reviews the literature on the prevalence and correlates of nightmares in children and highlights key methodological issues in the field. Results show that regardless of how they are defined and measured, nightmares affect a significant proportion of children of all ages and there is some evidence to suggest that nightmare frequency may peak around the age of 10. Gender differences in nightmare frequency, with girls reporting more nightmares than do boys, tend to appear between the ages of 10 and 15. Although nightmares are associated with a range of psychosocial difficulties (e.g., stress, behavioural problems), elevated anxiety and concomitant sleep-related disorders (e.g., sleepwalking) are among the most robust correlates of nightmares. Very few studies have examined nightmare treatment in children, but promising results have been obtained with imagery rehearsal therapy. Overall, research in the field has been hampered by inconsistent definitions for nightmares, by extensive variability in questionnaire items used to measure nightmare frequency, and by a lack of awareness of how using parents versus children as respondents may impact results. Longitudinal studies are needed to better understand how nightmares and their correlates evolve during childhood and adolescence, to delineate their clinical significance, and to develop effective and age-appropriate treatment strategies.     

Prevalence and correlates of hormonal therapy among Israeli women in the post-WHI era

OBJECTIVES: Following the results of recent randomized controlled trials on the risks and benefits of the long-term use of hormonal therapy (HT), practice guidelines regarding HT use have been revised. The aim of the study is to assess the prevalence and the correlates of HT use in Israel in 2003. METHODS: This is a cross-sectional study, conducted on a representative sample of the general population in Israel aged 21 years and over. The study questionnaire is based on the European Health Interview Survey (EUROHIS) project, aimed to develop uniform study tools, to enable international comparisons. The current module of the survey focused on women's health, and telephone interviews were conducted with 1396 women by trained interviewers in the year 2003. RESULTS: Out of a total of 1396 participants, 535 were defined as peri- or postmenopausal (38%). Of them, 9.9% were currently using HT (11.7% and 2.9% among the Jewish and Arab participants, respectively), and their mean age (S.D.) was 57.7 (6.5) years. Mean duration of HT use was 8.0 (5.5) years. Treatment of menopausal symptoms was the most common reason for HT use (69.2%). Significant correlates of HT use were age, being secular and having seen a gynecologist in the previous 12 months. CONCLUSIONS: Current HT use rates reported are lower than those reported 3 years ago for Israeli women. Awareness of both physicians and patients to the WHI results (2002), may have accounted for this trend, at least partially.     

The acquisition of anti-pneumococcal capsular polysaccharide Haemophilus influenzae type b and tetanus toxoid antibodies, with age, in the UK.

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and to tetanus toxoid (TT), were measured in serum samples of 750 age-stratified subjects from the UK. The study subjects comprised healthy adult volunteers and hospitalized children undergoing elective surgery, excluding those with a history of infection or under investigation for immunological or haematological disorders. These antibody levels were calibrated by comparison with serum pool obtained from healthy adult volunteers, who were immunized with Hib polyribose-phosphate vaccine (Merieux). The data are intended to provide reference ranges to assist in the interpretation of specific antibody measurements in the clinical setting. Maternal IgG pneumococcal capsular polysaccharide (PCP) specific antibody levels, geometric-mean titre (GMT) 1/22, were lost by 6 months of age (GMT of 1/9). They remained low until 3-5 years (GMT of 1/20), and consisted principally of IgG1. Thereafter, IgG anti-PCP antibody titres increased steadily to adult levels (GMT of 1/275), of which 80% was IgG2. Anti-PCP antibody titres of the IgM isotype rose steadily from a GMT 1/21 (0-6 months) to 1/420 (3-5 years), a level which was maintained until adulthood. Anti-Hib antibody concentrations, determined by RABA, again demonstrated the decline in maternal antibody, from 0.18 micrograms/ml in the 0-6 month age cohort, to 0.09 microgram/ml between 6 and 12 months. Geometric-mean antibody concentrations remained below 0.2 micrograms/ml until 3-5 years, then increased with age, attaining the mean adult level of 1.02 micrograms/ml. Anti-TT antibody concentrations were measured in the same sera, by ELISA. Two peaks in anti-TT antibody levels were seen in children of 0.059 IU/ml and 0.166 IU/ml corresponding to the schedule of routine childhood immunization in the first year and at 5 years of age.     

Susceptibility to diphtheria in adults: prevalence and relationship to gender and social variables

Recent outbreaks of diphtheria have drawn attention to the re-emergence of this disease. This study investigated susceptibility to diphtheria in north-east Germany and its relationship to gender and social factors. A study population of 4275 individuals recruited for the population-based Study of Health in Pomerania (SHIP) was available for analysis. IgG antibodies against diphtheria toxin were determined by ELISA and were used to define susceptibility to diphtheria (i.e., IgG titres < 0.1 IU/mL). The prevalence of susceptibility to diphtheria was 32.4%. Multivariate analysis revealed 45% increased odds of women being susceptible to diphtheria. Women who had not received diphtheria toxoid vaccination during the previous 10 years had four-fold increased odds of being susceptible to diphtheria toxin compared with unvaccinated men. None of the social factors investigated was associated with susceptibility status. It was concluded that a high proportion of middle-aged adults was susceptible to diphtheria. Women lacked seroprotection more often than men, which might be explained, in part, by gender-specific immune responses following vaccination. There is a need for information campaigns to improve public awareness of these problems.     

Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates.

Twenty residue peptides from the 185-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphteria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.     

Nasal immunization with diphtheria toxoid conjugated-CD52 core peptide induced specific antibody production in genital tract of female mice

PROBLEM: The common mucosal immune system (CMIS) has developed as a barrier for the numerous encounters between the host and various pathogens. It is possible to exploit this system to induce secretion of IgA antibody which inhibits sperm penetration in the female genital tract. In this study, the immunogenicity of a human sperm surface antigen (CD52) introduced by intranasal immunization was investigated with a view to developing a contraceptive vaccine. METHOD OF STUDY: A synthetic peptide corresponding to CD52 core peptide (GQNDTSQTSSPS) was prepared and conjugated with diphtheria toxoid (DT) as a carrier protein. The immunogen was given to mice with DOTAP:cholesterol liposome adjuvant intranasally, followed by determination of Ig and IgA class antibody levels in the sera and vaginal washes. RESULTS: The CD52 core peptide elicited IgA class as well as Ig antibodies both in the sera and vaginal secretions after intranasal immunization. An additional nasal inoculation after decrease of the antibody titer raised the antibody level to its highest level during the experiment. CONCLUSIONS: These results indicate that the CMIS could induce Ig and IgA class antibodies reactive to CD52 core peptide in the female genital tract. Intranasal immunization of a sperm-specific antigen would be a promising regimen for a safe and easy contraceptive vaccine.     

Macrophage T-cell interaction in man: Handling of tetanus toxoid antigen by human monocytes

An absolute requirement for monocytes was demonstrated in the T-cell proliferative response to tetanus toxoid (TT) antigen. Antigen-pulsed monocytes were shown to be effective in triggering T-cell proliferation. Using¹²⁵I-radiolabeled TT antigen, uptake by monocytes increased progressively over an 18-hr period, at which time 80–85% of the monocytes contained radiolabeled material. The ability of antigen-pulsed monocytes to trigger T-cell proliferation paralleled antigen uptake over an 18-hr period. Monocytes pulsed with antigen, then washed, lost their ability to trigger T-cell proliferation following a 24- to 48-hr culture period. Metabolic inhibitors blocked antigen uptake by monocytes and monocyte triggering of T-cell proliferation. Trypsin treatment of TT-pulsed monocytes did not affect the amount of antigen associated with monocytes or T-cell triggering by monocytes. Anti HLADR alloantibodies, which when added during antigen pulsing of monocytes inhibit the capacity of these monocytes to trigger T-cell proliferation, did not interfere with antigen uptake. These results indicate that human monocytes present antigen to T cells via an active process and in association with DR determinants, and that the immunogenic moiety of antigen does not remain indefinitely available to the T cell.     

Low prevalence of diphtheria antitoxin in children and adults in northern Germany

Recent outbreaks of diphtheria in neighbouring eastern European countries and in the Russian Federation prompted us to evaluate immunity to diphtheria in a sample of 400 healthy individuals (210 male, 190 female) from northern Germany. An age-stratified study population was chosen, including newborns, children, adults and elderly persons over 60 years divided into 8 subgroups of 50 persons each. Diphtheria antitoxin was tested by enzyme immunoassay. The median antitoxin titre was 0.39 IU/ml. There was no difference in the median antitoxin titres of men and women. Inadequate immunity to diphtheria was detected in more than 90 % of the 400 individuals tested, including 4 % who completely lacked immunity (titre<0.01 IU/ml), a further 20 % with minimal protection (titre 0.01–0.1 IU/ml) and the majority of 69 % who showed relative protection for less than one year (titre 0.1–1.0 IU/ml). Only 7 % exhibited lasting protection for more than five years (titre>1.1). Newborns and persons over 50 years of age constituted the least protected groups, with significantly lower median antitoxoid titres than the other age groups (p<0.001). The absence of protective immunity in 7 of the 50 newborns examined (14 %) reflects the inadequate protection of women of reproductive age. Children aged 1 to 10 years were the best immunized and protected group. The results suggest that routine booster immunizations of the majority of the adult population would be advisable in view of the ongoing migration from and the visits to high-risk areas.     

Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group.

Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8-66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P < 0.0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells.     

IgG1 is the predominant subclass ofin vivo- andin vitro-produced anti-tetanus toxoid antibodies and also serves as the membrane IgG molecule for delivering inhibitory signals to anti-tetanus toxoid antibody-producing B cells

Peripheral blood leukocytes from individuals immunized with tetanus toxoid can be stimulated by pokeweed mitogen to produce IgG anti-tetanus toxoid antibody (IgG-Tet)in vitro. Previous studies have shown that treatment of these cells with tetanus toxoid or anti-human IgG reagents can inhibit thisin vitro antibody synthesis. We have examined the four IgG subclasses on the surface of B cells for their relative contributions in the anti-IgG antibody-induced inhibition of IgG-Tet production. With all donors, the inclusion of anti-IgG₁, but not anti-IgG₂,-IgG₃, or -IgG₄, antiserum resulted in thein vitro inhibition of IgG-Tet synthesis. The magnitude of this inhibition was similar to that induced by treatment of the B cells with tetanus toxoid antigen. When the supernatants from normalin vitro cultures were assayed for IgG-Tet of the various IgG subclasses, it was observed that the IgG-Tet were almost exclusively IgG₁. Similar results were obtained when serum IgG-Tet were measured. Thus, IgG₁ appears to be the major subclass for (1) thein vivo-produced IgG-Tet, (2) thein vitro-produced IgG-Tet, and (3) the membrane receptor which can selectively convey an inhibitory signal to the IgG-Tet B cell.     

Levels of antibodies specific to tetanus toxoid,Haemophilus influenzae type b,and pneumococcal capsular polysaccharide in healthy children and adults

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and for tetanus toxoid were measured in serum samples of 386 age-stratified subjects. The study group consists of healthy adult blood donors and hospitalized children undergoing elective surgery, excluding individuals with a history of infection. In children, anti-tetanus toxoid antibody levels displayed two peaks of 1.20 IU/ml (20.4 mg/liter) and 1.65 IU/ml (28.1 mg/liter) related to the schedule of routine childhood immunization in the first year and at 8 years of age. Eighty percent of the antibodies are of the immunoglobulin G1 (IgG1) isotype. For pneumococcal capsular polysaccharide (PCP), the specific antibody levels represent the acquisition of natural immunity. The initial concentration of 9.2 mg/liter was low in infancy (0.5 to 1 years of age) and remained low until 3 to 4 years of age (14.6 mg/liter). During this period PCP antibodies were almost 100% of the IgG2 subclass. Thereafter, IgG anti-PCP antibody titers increased steadily to adult levels (59.5 mg/liter). The data are intended to provide reference ranges to aid in the interpretation of specific antibody determinations in the clinical setting.