Development and validation of magnetic bead pentaplex immunoassay for simultaneous quantification of murine serum IgG antibodies to acellular pertussis, diphtheria and tetanus antigens used in combination vaccines.

We describe here a magnetic bead-based multiplex (pentaplex) immunoassay (MIA) platform developed as an alternative to enzyme-linked immunosorbent assays (ELISA) used in immunogenicity testing of DTaP/TdaP vaccine in animals. MIA simultaneously measures the concentration of serum (IgG) antibodies against B. Pertussis antigens; pertussis toxin, filamentous hemagglutinin (FHA), pertactin (PRN) and tetanus (T) and diphtheria (D) toxoid in the Tdap vaccine immunized animals. Assay validation experiments were done using a panel of serum samples. The results are expressed in IU/ml using WHO reference mice serum. The standard curve was linear with 4PL logistic fit over an eight 2-fold dilution range with LOQ of 0.003, 0.022, 0.005 IU/ml for PT, FHA and PRN and 0.016 U/ml for T and D antigens indicating sensitivity. No interference was observed in monoplex versus multiplex measurements. Specificity was demonstrated by ≥90% homologous and ≤15% heterologous inhibition for all the antigens. The assay was reproducible, with a mean coefficient of variation (CV) of ≤10% for intra-assay duplicates and ≤25% for interassays using different lots of beads and analyst. Accuracy was demonstrated wherein the ratio of observed vs. assigned unitages were within 80-120%. The study suggests that the Pentaplex (MIA) platform meets all the criteria for the serological assay combination vaccines with additional advantages of high throughput, reduced sample volumes, faster analysis with reduced manpower in contrast to conventional monoplex ELISA.

Validation of monoplex assays detecting antibodies against Corynebacterium diphtheriae and Clostridium tetani toxins, rubella virus and parvovirus B19 for incorporation into Multiplex Serology.

Serological assays detecting antibodies in serum or plasma samples are useful and versatile instruments to investigate an individual's infection and vaccination history, e.g. for clinical diagnosis, personal risk evaluation, and seroepidemiological studies. Multiplex Serology is a suspension bead array-based high-throughput methodology for simultaneous measurement of antibodies against multiple pathogens in a single reaction vessel, thus economizing sample volume, measurement time, and costs. We developed and validated bead-based pathogen-specific Monoplex Serology assays, i.e. assays including only antigens for the respective pathogen, to detect antibodies against Corynebacterium diphtheriae and Clostridium tetani toxins, rubella virus and parvovirus B19. The developed assays expand the portfolio of existing pathogen-specific bead-based serology assays and can be efficiently incorporated into larger Multiplex Serology panels. The newly developed Monoplex Serology assays consist of only one antigen per infectious agent, expressed as Glutathione S-transferase-fusion proteins in E. coli. Specificity, sensitivity and Cohen's kappa statistics in comparison with routine clinical diagnostic assays were calculated for serum dilutions 1:100 and 1:1000. All pathogen-specific assays were successfully validated at both serum dilutions with the exception of rubella Monoplex Serology which showed impaired sensitivity (57.6%) at dilution 1:1000. Specificities of successfully validated Monoplex Serology assays ranged from 85.6% to 100.0% (median: 91.7%), and sensitivities from 81.3% to 95.8% (median: 90.9%); agreement with the reference assays ranged from substantial to almost perfect (kappa: 0.66-0.86, median: 0.78). Statistical performance and slim assay design enable efficient incorporation of the developed assays into Multiplex Serology.

Dot immunoassay for the simultaneous determination of postvaccination immunity against pertussis, diphtheria, and tetanus.

A dot immunoassay for simultaneous semiquantitative detection of IgG against tetanus toxoid (Ttx) and diphtheria toxoid (Dtx) and qualitative detection of anti-Bordetella pertussis IgGs in human blood serum using carbon nanoparticles functionalized with streptococcal protein G was developed. Inactivated B. pertussis cells in suspension form were used as an antigen in the immunoassay. Pertussis, tetanus, and diphtheria antigens were separately spotted onto nitrocellulose strips, and then the immunostrips were successively incubated with blood sera and a suspension of carbon nanoparticles. The immunostrips were then scanned with a flatbed scanner, and the images obtained were processed with ImageJ. One hundred fifty-five venous blood serum samples from children vaccinated with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine were tested in comparison with a conventional ELISA and agglutination test. The total time required for analysis of 32 serum samples was less than 3 h. Comparison between the results of the dot immunoassay and the corresponding ELISA/agglutination test revealed a high level of agreement (Cohen's kappa between 0.765 and 0.813). The lower limit of quantification was 0.06 IU/ml for anti-Ttx and anti-Dtx. The intra-assay coefficients of variation were less than 15% for anti-Ttx and anti-Dtx and less than 10% for anti-pertussis. The diagnostic sensitivity of detection of the antibody protection level was 93.5% for anti-Ttx [95% confidence interval (CI) 83.5-97.9%], 92.4% for anti-Dtx (95% CI 80.9297.5%), and 90.2% for anti-pertussis (95% CI 75.9-96.8%). The diagnostic specificity was 90.9% for anti-Ttx (95% CI 57.1-99.5%), 85% for anti-Dtx (95% CI 61.1-96.0%), and 89.3% for anti-pertussis (95%CI 80.8-94.5%). The dot immunoassay developed does not require expensive reading equipment, and allows detection of antibodies against three antigens in a single analysis. The immunostrips can be stored for a long time without changes in the coloration of the spots. Graphical Abstract The assay procedure. BC Bordetella pertussis cell suspension, CNP carbon nanoparticle, Dtx diphtheria toxoid, Ttx tetanus toxoid.

Seroepidemiology of tetanus in Korean adults and adolescents in 2012.

This seroepidemiologic study was performed to evaluate the immune status against tetanus in Korean adolescents and adults and to provide evidence to develop strategies for tetanus prevention. Between July 2012 and December 2012, serum samples were collected from adults and adolescents 11 years of age and older, and serum anti-tetanus IgG titers were determined using a commercial ELISA kit. Subjects were divided into six age groups: 11-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, and ≥61 years. The mean anti-tetanus IgG titers and tetanus seroprevalence of the age groups were compared. A total of 1193 adults and adolescents were enrolled. Mean anti-tetanus IgG titer and tetanus seroprevalence of all subjects were 1.20 ± 3.58 IU/mL and 56.4%, respectively. The mean anti-tetanus IgG titer decreased with an increase in age (p < 0.001). Tetanus seroprevalence increased from 92.0% in the 11-20 year age group to 95.7% in the 21-30 year age group, and then decreased with a further increase in age (p < 0.001). These results reflected an appropriate Td booster vaccine coverage at 11-12 years of age. However, the tetanus seroprevalence of adults older than 41 years was as low as the levels in previous studies: therefore, adults should be more encouraged to acquire decennial Td booster vaccinations recommended by the National Immunization Program.

Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

[State of immunity to diphtheria and tetanus in women in early postpartum period].

AIM: Study of anti-diphtheria and anti-tetanus immunity in women in early postpartum period depending on age. MATERIALS AND METHODS: Women in early postpartum period (n =139) with unknown vaccine anamnesis aged 17 to 44 years and under the supervision of Rostov-on-Don maternity hospital No. 2 were examined for the evaluation of the anti-diphtheria and anti-tetanus immunity state. RESULTS: All the women had high level of protection form these infections. The level of anti-tetanus immunity intensity in the examined was higher than anti-diphtheria. CONCLUSION: Monitoring of anti-diphtheria and anti-tetanus immunity in women of childbearing age is necessary to resolve the issue of vaccine administration in this group. High level of maternal immunity intensity will allow to form a sufficient protection from infectious agents in neonates.

Novel neutralizing human monoclonal antibodies against tetanus neurotoxin.

Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)-reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix-reactive antibodies provided enhanced protection compared to the use of each antibody alone.

Tetanus as a cause of rhabdomyolysis and acute renal failure.

Acute renal failure developed in an elderly woman with a rapidly progressive illness characterized by nuchal rigidity, limb spasm, repetitive grunting vocalizations without intelligible speech, and risus sardonicus. Eventually she developed characteristic findings of increased tone in her masseter muscles (trismus) and rigid upper and lower extremities, consistent with generalized tetanus. Increasing serum creatinine was temporally associated with rising creatine phosphokinase (CPK) and striking elevations of plasma myoglobin. The patient had marked lability of blood pressure and pulse. She improved briefly after tetanus toxoid and broad-spectrum antibiotics, but died of heart failure after 9 days of hospitalization. A necrotic pelvic tumor was believed to be the source of infection. Tetanus is a preventable disease, which has not been eradicated, even in Western populations. Full-blown tetanus has a high fatality rate, and should be considered in the differential diagnosis of acute renal failure in the setting of rising CPK and continued release of muscle myoglobin.

Seroprevalence of antibodies against diphtheria, tetanus, and pertussis among healthy Thai adolescents.

OBJECTIVE: To determine the seroprevalence of antibodies against of diphtheria, tetanus, and pertussis among Thai adolescents. METHODS: A cross-sectional study was conducted among Thai adolescents aged 11-20 years who had completed five doses of diphtheria, tetanus, and pertussis (DTP)-containing vaccine during childhood, either diphtheria toxoid, tetanus toxoid, whole-cell pertussis (DTwP) or diphtheria toxoid, tetanus toxoid, acellular pertussis (DTaP) vaccine. Protective antibodies against diphtheria, tetanus, and pertussis were defined as anti-diphtheria toxoid IgG ≥0.1 IU/ml, anti-tetanus toxoid IgG ≥0.1 IU/ml, and anti-Bordetella pertussis toxin IgG ≥5 IU/ml, respectively. RESULTS: Of 220 adolescents (median age 16 years), 45% had received a tetanus toxoid, reduced diphtheria toxoid (Td) booster vaccine during adolescence, and none (0%) had received a tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) booster vaccine. Overall, 50%, 99%, and 57% of adolescents demonstrated protective antibodies against diphtheria, tetanus, and pertussis, respectively. The geometric mean concentrations (GMCs) of antibodies against diphtheria (p = 0.06) and tetanus (p < 0.001) were higher among adolescents who had received Td vaccine. Nevertheless, the antibody levels against both diseases waned over time, regardless of Td booster vaccination. Likewise, pertussis antibody levels gradually declined after the fifth childhood dose of DTwP/DTaP vaccine. CONCLUSIONS: Approximately half of these healthy Thai adolescents had not maintained protective antibodies against diphtheria and pertussis. A booster vaccination with diphtheria toxoid and/or acellular pertussis-containing vaccines is a crucial strategy to prevent such diseases in this population.

Tetanus Immunoglobulin G Assessment in Adults Trauma Patients.

BACKGROUND: Clostridium tetani is an anaerobic, gram-positive bacillus that causes tetanus infection. It usually enters the body through injury with contaminated objects. Tetanus differs from other diseases that can be prevented by vaccination in that it is not contagious and does not spread from person to person. The aim of this study is to evaluate the levels of Tetanus IgG in trauma patients admitted to the emergency department (ED). METHODS: The study was planned as cross-sectional, prospective, and single-center. The study was conducted from January to July 2018 in the Kahramanmaras Sütçü Imam University Hospital. Totally, 178 patients aged ≥18 years were included. For measurement of the level of Tetanus IgG, Clostridium tetani toxin 5S IgG kit (NovaLisa, NOVATEC) was used to quantitatively detect IgG type antibodies by micro-ELISA method in accordance with the manufacturer's recommendation. RESULTS: In total, 143 cases were male and 35 were female. The mean age of the cases was 40 ± 16 years. Tetanus IgG levels were found to be 0.29 ± 0.6 IU/mL in cases from rural areas and 2.14 ± 1.64 IU/mL in cases from urban areas (P < 0.001). There was a negative correlation between age and Tetanus IgG level (r: (-) 0.479; P < 0.001). The protective level of Tetanus IgG was observed to be even lower, especially in patients aged ≥40 years (n = 43, 78.9%). CONCLUSION: Measurements of Tetanus IgG levels should be performed as far as possible in the ED. In this way, unnecessary vaccination can be avoided.

Serologic Status of Routine Childhood Vaccines, Cytomegalovirus, and Epstein-Barr Virus in Children With Inflammatory Bowel Disease.

BACKGROUND: Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD. METHODS: In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD. We evaluated potential factors associated with serologic status. RESULTS: Of 156 subjects, vaccine coverage was up to date for age in 93.5% for measles, mumps, rubella, 95.6% for diphtheria, tetanus, pertussis, polio, hemophilus influenza B, 75.8% for HBV, and 93.5% for varicella, including past infection and vaccination. Seroprotection was present in 65.8% for measles, 60.5% for mumps, 79.1% for rubella, 79.5% for diphtheria, 80.8% for tetanus, 70.5% for varicella, and 62.8% for HBV of subjects. Older age at diagnosis was associated with seroprotection among subjects with complete HBV (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.03-1.39) and rubella series (OR, 1.18; 95% CI, 1.02-1.37). Older age at serum collection was associated with seroprotection among subjects with prior varicella vaccination or infection (OR, 1.69; 95% CI, 1.33-2.15). Only 25.2% and 37.8% demonstrated seropositivity to CMV and EBV, respectively. Among subjects on immunosuppressive medications, 75.3% and 62.4% were seronegative for CMV and EBV, respectively. CONCLUSIONS: Children with IBD have low serologic protection to childhood vaccines in spite of high vaccine coverage and universal vaccinations. Children with IBD, including a large proportion on immunosuppressive medications, have low seropositivity to CMV and EBV.

Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus.

Severe tetanus is characterised by muscle spasms and autonomic dysfunction. We recently reported the results of a randomised placebo controlled trial of magnesium sulphate infusions for the treatment of severe tetanus which showed magnesium was associated with improved muscle spasm and cardiovascular control. We hypothesised that magnesium controlled autonomic dysfunction by reducing catecholamine release and thus urinary excretion. Urinary adrenaline and noradrenaline concentrations were measured during the first 24 h of therapy in 180 adults with severe tetanus randomised to treatment with magnesium (n = 92) or placebo (n = 88). Magnesium therapy was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion. High urinary adrenaline concentrations were associated with documented autonomic dysfunction. Patients given magnesium had significantly less autonomic dysfunction, required less cardiovascular stabilising drugs, and had lower urinary concentrations of adrenaline. These findings suggest adrenaline is important in the pathophysiology of severe tetanus and magnesium controls autonomic dysfunction by reducing adrenaline release.

[Serological study carried out in Cambodia during a tetanus vaccination in adults]. / Résultats d'une enquê te sérologique réalisée au Cambodge lors d'une vaccination antit ténique des adultes.

In 1997, the Ministry of Health tested the feasibility and serological activity of a two-dose vaccine at one year interval within a catch-up tetanus immunization programme in a rural population. In the district of Angkor Thom in the Siem Reap province (15,000 inhabitants), a team of nurses and administrative clerks travelling by motorcycle, conducted between February 1998 and February 1999 an EPI and tetanus immunization of the whole population gathered in meeting points. In 132 childbearing age female volunteers, 49 following a two-dose schedule at one year interval, and 70 following a WHO three-dose schedule, with two doses at one month interval and a booster dose one year later tetanus antibodies have been measured before vaccination, one year after the first dose or the two first doses, and six months after the second or third dose of vaccine. 129 male volunteers of the same age were also recruited in the serological study following only the two-dose schedule. The titration was done first with monoantigen ELISA, then with mouse seroneutralisation, the reference method for measuring tetanus seroprotection. Only 148 (57%) volunteers completely attended the serological study Compared to seroneutralisation, sensitivity for seroprotection with ELISA was 89% (CI95%: 85%-94%) and specificity 84% (CI95%: 81%-89%). The coverage of the general population vaccinated with two doses, in both sexes and in all age-groups, increased on average from 5% to 70%. The three-dose schedule gave significantly more protection than the two-dose schedule in women tested with seroneutralisation. On a first sample in those with no protective antibodies and testifying they had not been vaccinated before, 51% of these volunteers after one dose and 93% after two doses acquired protective antibodies. On first sample, 52% of female volunteers had protective antibodies in seroneutralisation, against 11.7% in men. 14% of subjects tested in ELISA and 6.8% tested in seroneutralisation showed in a second sample a decrease in titres, although they had received a tetanus vaccine. For unprotected volunteers on first sample and testifying they had not been vaccinated before, neither age nor past chronic cutaneous lesions or cows living around their houses, two possible sources of contact with CI. tetani, increased significantly seroconversion. Only female volunteers were significantly more seroconverting (81%) compared to men of same age (51%) (RR: 1.60, CI95%: I. 17-2.18) suggesting a memory bias in women supposed to be vaccinated by EPI. 30% of volunteers in ELISA and 14% in seroneutralisation showed spontaneous protecting antibodies in the first sample without having any document or memory of a past tetanus vaccination. Tested by seroneutralisation, no relation was to be found for having spontaneous antibodies with past chronic cutaneous lesions and cows living around their houses. Only the eldest (35-45 y.o.) female volunteers showed significantly more spontaneous antibodies (RR: 3.83, CIs%: 1.74-8.2) than men in the same age-group. A memory bias may be found also in this female age-group. Good serological response should encourage implementation of a catch-up tetanus vaccination in this country considering the large number of unprotected adults, mainly male adults. Due to problems with notification and recalling past vaccinations, only a prospective study in an unimmunized large cohort, studying all possible factors of tetanus toxin neutralisation, could confirm the existence and cause of spontaneous antibodies. Excluding vaccination in at-risk population for such a study would be however ethically unacceptable.

Protection against Tetanus and Diphtheria in Europe: The impact of age, gender and country of origin based on data from the MARK-AGE Study.

Due to the successful implementation of vaccination strategies early-life morbidity and mortality due to infectious disease has been reduced dramatically. Vaccines against tetanus and diphtheria are among the most frequently used vaccines worldwide, but various studies in different European countries have shown that protection against tetanus and particularly against diphtheria is unsatisfactory in adults and older persons. In this study we analyzed tetanus- and diphtheria-specific antibody concentrations in 2100 adults of different age from 6 selected European countries (Austria, Belgium, Germany, Greece, Italy, Poland) in order to investigate differences in the level of protection against tetanus and diphtheria across Europe. Our data reveal that tetanus- and diphtheria-specific antibody concentrations vary greatly between countries, which is also reflected in the percentage of persons with antibody concentrations below the protective level (0.1IU/ml), which ranged from 2 to 31% percent for tetanus and 28-63% for diphtheria. In most countries, tetanus- and diphtheria-specific antibody concentrations decrease with age. This phenomenon is more pronounced in countries with generally low antibody levels, such as Italy, Poland and Greece. Interestingly, tetanus-specific antibody concentrations are generally higher in males than in females, which is probably due to vaccination during their military service or more frequent booster vaccinations after injuries, whereas no gender-related differences were found for diphtheria-specific antibodies. In conclusion, our study demonstrates that the European population is not fully protected against tetanus and diphtheria. Measures to improve protection should include a life-long perspective on vaccination, more education to increase awareness of and compliance with vaccination guidelines, and a harmonization of recommendations and incentives across Europe.

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

Seroprevalence of tetanus antibody in the Thai population: a national survey.

Tetanus is a disease with high mortality and the most important measure for effective prevention is vaccination. Tetanus immunization has been introduced to Thailand's national immunization program for 30 years. Yet, the coverage and seroprevalence of tetanus antibody in vast parts of the population has not been assessed. This study has been performed on 1,277 subjects aged between 6 months and 60 years or above from four geographically distinct provinces of Thailand. Tetanus antibody levels were measured using a commercially available ELISA kit. Most of the Thai population had immunity against tetanus. The level of antibodies to tetanus, as demonstrated by the geometric mean titer of antibody (GMT) (and 95% confidence interval) was 2.62 (2.34-2.91) IU/ml. The highest and lowest GMT was found in subjects aged between 5 and 9 years, and above 60 years of age with GMT (and 95% confidence intervals) of 3.64 (3.34-3.96) and 1.24 (0.67-2.29) IU/ml respectively. The minimum protective level of antitoxin (>0.01 IU/ml) was detected in 99.7 % of subjects. More than 90% of subjects displayed durable antibody protection levels (DAPL) (> or = 1.0 IU/ml), except for subjects above the age of 60 years (82%). According to this study, the majority of the population expresses tetanus antibody levels that can confer long term protection. Yet, considering the lowest GMT and the highest incidence of tetanus cases found in subjects aged above 60 years, re-immunization should be targeted at this age group especially if they had sustained any tetanus-prone injury.

Seroprotection against diphtheria and tetanus among Russian and Norwegian teenagers.

Russian children between 7 and 10 years of age have been shown to have significantly higher seroprotection against diphtheria compared to Norwegian children. That was due to a reinforcing dose given on entering school to Russian but not to Norwegian children. The next booster was given at the age of 11-12 years in both countries. We have compared diphtheria and tetanus antitoxin levels among 13- to 14- and 15- to 16-year-old teenagers to see if the difference was maintained among the older age group. Serum samples obtained from 106 Russian and 117 Norwegian teenagers were tested by enzyme immunoassay. The Russian and Norwegian adolescents exhibited adequate rates of protection against diphtheria with similar geometric mean antitoxin concentrations of 1.26 and 1.15 IU/ml, respectively, at 13-14 years, and 0.33 and 0.29 IU/ml at 15-16 years. Differences within the age groups were not significant. However, at 13-14 years the Norwegians were much better protected 2 years after a reinforcing dose of tetanus toxoid than the Russians who had not been boosted for 7 years. At the age of 15-16 the difference diminished and became statistically not significant.

Duration of tetanus immunoglobulin G titres following basic immunisation of horses.

REASONS FOR PERFORMING STUDY: Recommendations for prophylactic vaccination against tetanus in horses vary greatly between countries and have scarce scientific support in the peer-reviewed literature. In human medicine, recommended booster vaccination intervals are also very variable, but are considerably longer than for horses. More information is needed about the duration of immunity induced by modern vaccines. OBJECTIVES: To investigate if the duration of antibody titres previously determined to be protective against tetanus differ from what is indicated by recommended vaccination intervals for horses. STUDY DESIGN: Prospective seroconversion study. METHODS: Thirty-four horses were enrolled for basic immunisation with an ISCOM Matrix-combination vaccine (Equilis Prequenza Te). Horses received the first vaccination at age 5-11 months, and the second dose 4 weeks later. A third vaccine dose was given 15-17 months after the second dose. Serum tetanus antibody titres were analysed by toxin-binding enzyme-linked immunosorbent assay 2 weeks as well as 14-16 months after the second dose. After the third vaccine dose, titres were checked once yearly for 3 years. Results were described by age and level of antibody titre at first sampling. RESULTS: Two weeks after the second dose, all horses (34/34) had antibody levels that exceeded the limit of detection, 0.04 iu/ml. After 16 months the levels were above 0.04 iu/ml in 28/33 horses, the remaining 5 horses potentially had suboptimal protection against tetanus. After the third vaccine dose antibody levels remained above 0.04 iu/ml in 25/26 horses for 1 year, 16/16 horses for 2 years, and 8/8 horses for 3 years. CONCLUSIONS: Horses that undergo basic immunisation with 3 doses of vaccine after age 5 months are likely to have serum antibody titres consistent with protection against tetanus for more than 3 years. Current guidelines for tetanus prophylaxis should be revised.

Humoral immunity to tetanus, measles and rubella in children with acute lymphoblastic leukemia after chemotherapy. / Inmunidad humoral a tétanos, sarampión y rubéola en niños con leucemia linfoblástica aguda luego del tratamiento quimioterápico.

Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients.

Los regímenes de quimioterapia y los avances en el soporte clínico han mejorado la supervivencia de los niños con leucemia linfoblástica aguda. Son temas de preocupación las secuelas del tratamiento, entre ellas, el daño inmunológico inducido por la terapia inmunosupresora, que se refleja en la pérdida de niveles protectores de anticuerpos provistos por inmunizaciones previas. Nuestro objetivo fue evaluar la presencia de títulos protectores de anticuerpos para sarampión, rubéola y tétanos en pacientes con leucemia linfoblástica aguda luego de haber finalizado el tratamiento quimioterápico. Se incluyeron 61 niños con leucemia linfoblástica aguda asistidos en el Hospital Garrahan, que habían finalizado el tratamiento, como mínimo, 6 meses antes y con vacunación completa previa al diagnóstico. Las tasas de anticuerpos protectores fueron sarampión: 46% (IC 32-59); tétanos: 53% (IC 40-67); rubéola: 60% (IC 47-63). Estos resultados refuerzan la necesidad de reconsiderar la revacunación en este grupo de pacientes.

Seroprevalence of vaccine-preventable diseases among young children in the United Arab Emirates.

OBJECTIVES: In the United Arab Emirates (UAE), many vaccine-preventable diseases are notifiable and are often reported despite high estimated immunization coverage. The serological assessment of immunity against these infections (serosurveillance) complements disease surveillance (notification). This study aimed to assess the yet unmeasured serological immunities to nine vaccine-preventable infections among vaccinated Emirati children. METHODS: This cross-sectional study involved children who attended the Well-Child Care Programme of the Ambulatory Healthcare Services (Al-Ain, UAE) between July 2014 and September 2015. Serological testing was performed in 227 Emirati children (49% females); subjects were aged (mean±standard deviation) 45±14 months (median 43, range 23-71 months). RESULTS: The seroprevalence rates varied markedly among the studied vaccine-preventable diseases, ranging from 39.2% (pertussis) to 98.3% (rubella). Other high seroprevalence rates were noted for measles (98.2%) and poliovirus (92%). The seroprevalence rate for mumps was 82.8%, for varicella was 68.3%, for diphtheria was 86.4%, for tetanus was 89.9%, and for Haemophilus influenzae type B was 84.1%. CONCLUSIONS: A large number of the studied children had low seroprevalence rates against pertussis, varicella, and mumps. Studies are needed to explore whether modifying the national immunization programme could improve these low seroprevalence estimates.