Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2-5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept.

BACKGROUND: Patients with polyarticular-course juvenile idiopathic arthritis (pJIA), receiving disease-modifying anti-rheumatic drugs with immunosuppressive effects, may be at increased risk of vaccine-preventable infections. This substudy assessed protective antibody responses to diphtheria and tetanus vaccination given prior to study enrolment in patients with pJIA. FINDINGS: This was a substudy of a 24-month, single-arm, open-label, multicenter, Phase III trial (NCT01844518) of subcutaneous abatacept in children with active pJIA (N = 219). Patients aged 2-5 years, with ≥2 continuous months of weekly weight-tiered (10-< 25 kg [50 mg], 25-< 50 kg [87.5 mg]) subcutaneous abatacept treatment (with/without methotrexate and/or low-dose corticosteroids), who received diphtheria/tetanus vaccine prior to enrolment, were eligible. Protective antibody levels to diphtheria/tetanus (> 0.1 IU/mL), and safety, were assessed. Overall, 29 patients were analyzed: 19 (65.5%), 1 (3.4%) and 9 (31.0%) patients had > 12, 6-12 and 2-< 6 months of abatacept exposure, respectively. All patients had protective antibody levels to tetanus and 26 (89.7%) patients had protective antibody levels to diphtheria. Of the 3 patients without protective antibody levels to diphtheria, each had an antibody level of 0.1 IU/mL, bordering the lower threshold of protection. Concomitant use of methotrexate and/or low-dose corticosteroids had no evident effect on antibody levels. No unexpected adverse events, including cases of diphtheria or tetanus, were reported during the 24-month period. CONCLUSIONS: Patients aged 2-5 years with pJIA who received 2-24 months of weekly subcutaneous abatacept, with or without concomitant methotrexate and/or low-dose corticosteroids, maintained effective diphtheria and tetanus vaccination protection without new safety signals. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01844518); registered May 1, 2013; https://clinicaltrials.gov/ct2/show/NCT01844518?term=NCT01844518&rank=1.

Seroprotection rate in adults after 1-dose, 2-dose, and 3-dose series of a reduced-diphtheria-tetanus toxoid vaccine (Td) during a diphtheria outbreak in Thailand.

To evaluate seroprotection of different dosing strategies of reduced-diphtheria-tetanus-toxoid vaccine (Td) for adults during a diphtheria outbreak in Thailand, we enrolled 160 healthcare workers and 161 adults aged 20-60 years old and measured diphtheria antitoxin (DAT) level before administration of a Td vaccine. We scheduled a second Td at 4-8 weeks and a third Td at 6-12 months interval. DAT was measured 4 weeks after each dose. DAT levels of ≥0.1 and ≥1 IU/mL were considered as seroprotective and long-term seroprotective. Persons achieving long-term seroprotection were not given a further dose. The baseline seroprotection rate was 32.6%, which increased to 87.1% (95% confidence interval, 83.4-90.8%) after one dose. The seroprotection rate increased slightly with additional doses. The immune response was lowest among persons 30-49 years of age. We suggest 1-dose Td for adults during a diphtheria outbreak, and a 2-dose series being considered for those born before 1980.

Vaccination in Chronic Kidney Disease.

Infections after cardiovascular disease are the second most common cause of death in the chronic kidney disease population. Vaccination is an important component of maintaining health and wellness in patients with kidney disease. There is a changing epidemiologic landscape for several vaccine-preventable illnesses from childhood to adulthood and unfounded public perception of safety concerns. Several mechanisms have been proposed to cause inadequate vaccine protection in this high-risk group with chronic kidney disease. These have led to recent advances in new designs for vaccination strategies in kidney disease. In this article, we discuss the current evidence and recommendations for vaccination in those with kidney disease and needing renal replacement therapy (dialysis and transplant).

Tetanus-diphtheria vaccination in adults: the long-term persistence of antibodies is not dependent on polyclonal B-cell activation and the defective response to diphtheria toxoid re-vaccination is associated to HLADRB1∗01.

Cellular and humoral immune responses to tetanus-diphtheria vaccine (Td) were assessed in human leukocyte antigen (HLA)-typed Italian military personnel who received multiple concomitant vaccines. Td-specific antibodies and T-lymphocytes were measured in individuals with one (group-1) and more than one (group-2) Td boosters. A third group (group-3), who received several vaccines, but not Td, was studied to verify the hypothesis of the polyclonal B-cell activation as mechanism for antibody persistence. The antibody response to Td toxoids was higher in group-1, who showed lower baseline antibody levels, than in group-2 subjects. The antibody response to tetanus was higher than to diphtheria toxoid in both groups. No correlation between antibody and cellular response, and no interference in the response to Td by co-administration of different vaccines were observed. HLA-DRB1∗01 allele was detected at significant higher frequency in subjects unable to double the baseline anti-diphtheria antibody levels after the vaccination. Anti-tetanus and diphtheria antibodies half-lives were assessed and the long-lasting persistence above the threshold for protection (0.1 IU/ml) was estimated in over 65 and 20 years, respectively. No significant increase of anti-diphtheria antibodies was observed in consequence of polyclonal B-cell activation. This study emphasizes the duration of Td vaccination-induced seroprotection, suggesting that re-vaccination should probably be performed at intervals longer than 10 years. No reciprocal interference by concomitantly administered vaccines has been observed. HLA-DRB1∗01 allele was significantly associated with anti-diphtheria defective response. Finally, this study does not confirm that anti-diphtheria antibody levels are maintained by polyclonal B-cell activation. Clinical trial registry: The study was registered with NCT01807780.

Immune response to a Tdap booster in vertically HIV-infected adolescents.

BACKGROUND: Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. OBJECTIVE: To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). METHODOLOGY: Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Mean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52-32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0-35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88-6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3-26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. CONCLUSIONS: Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Lack of evidence for post-vaccine onset of autoimmune/lymphoproliferative disorders, during a nine-month follow-up in multiply vaccinated Italian military personnel.

Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response to apoptotic self-epitopes, without observing significant difference between baseline and one month post-vaccine. Multiple vaccinations in young adults are safe and not associated to autoimmunity/lymphoproliferation onset during a nine-month-long follow-up.

Vaccines for women for preventing neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. OBJECTIVE: To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. METHODS: A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U.S. population. Aggregate and incremental costs and pertussis cases avoided were presented undiscounted (as recommended for budget-impact analyses) annually and cumulatively over a 3-year time horizon in 2012 U.S. dollars. Scenario analyses were conducted on key parameters, including wound incidence, pertussis incidence, vaccine efficacy and waning protection against pertussis, uptake rates for Tdap, and vaccine prices using alternative data sources or alternative clinically relevant assumptions. RESULTS: For a health plan with 1 million covered lives aged < 65 years, vaccination with Tdap instead of Td was estimated to cost an additional $132,364 ($0.01 PMPM) in the first year and an additional $368,640 ($0.01 PMPM) cumulatively over 3 years. For a health plan with 1 million covered lives aged 65+ years, vaccination with Tdap instead of Td was estimated to cost an additional $201,165 ($0.02 PMPM) in the first year and an additional $549,568 ($0.02 PMPM) cumulatively over 3 years. For the U.S. population aged 10+ years, vaccination with Tdap instead of Td was estimated to result in protection against pertussis for an additional 2.7 million patients with wounds annually and was estimated to cost an additional $121,101,671 to avoid 42,104 cases of pertussis over the 3-year time horizon. Results were sensitive to input parameter values, particularly parameters associated with the number of patients with wounds vaccinated with Tdap (range 2.7 to 5.1 million patients). However, for all of the alternative scenarios tested, the expected increase in PMPM costs ranged from < $0.01 to $0.03. CONCLUSIONS: Vaccination of adolescents and adults with Tdap for wound management may result in an increase in PMPM costs for health plans of < $0.01 to $0.03. Given the potential reduction in pertussis cases at the population level, vaccination with Tdap for routine wound management could be considered as another strategy to help address the pertussis public health concern in the United States.

Vaccination guidelines for female infertility patients.

Encounters for infertility care are opportunities to assess and update immunization status. Women of reproductive age are often unaware of their need for immunization, their own immunization status, and the potentially serious consequences of preventable disease on pregnancy outcome. The purpose of this ASRM Practice Committee document is to summarize current recommendations regarding vaccinations for women of reproductive age.

Common vaccine antigens inhibit allergen-induced sensitization and airway hyperresponsiveness in a murine model.

BACKGROUND: Co-vaccination with cellular pertussis vaccine down-regulates allergic sensitization to diphtheria and tetanus antigens. Using a murine model, we investigated whether vaccination with diphtheria/tetanus toxoids, administered separately or simultaneously with the whole cell vaccine of Bordetella pertussis, inhibits subsequent allergen-induced immune and inflammatory responses. METHODS: BALB/c-mice were vaccinated intracutaneously with a combination of diphtheria and tetanus toxoids or a combination of diphtheria and tetanus toxoids with a whole cell vaccine of B. pertussis (three times, days -21 to -7) prior to systemic sensitization (days 1-14) and repeated airway challenges (days 28-30) with ovalbumin. RESULTS: Compared with negative controls, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, airway inflammation and development of in vivo airway hyperreactivity. Vaccination with diphtheria and tetanus toxoids prior to sensitization suppressed IgE formation and development of eosinophilic airway inflammation. Co-vaccination with a whole cell pertussis vaccine inhibited allergen sensitization, airway inflammation and development of in vivo airway hyperreactivity. Prevention was due to an allergen-specific and general shift from a predominant Th2 towards a predominant Th1 immune response. CONCLUSION: Vaccination with diphtheria and tetanus toxoids alone or in combination with whole cell pertussis vaccine prior to allergen sensitization prevented allergen-induced Th2 immune responses. Vaccine antigens may down-regulate allergic responses to a range of common allergens.

Immunization status of children under 7 years in the Vikas Nagar area, North India.

BACKGROUND: Immunization has played a major part in reducing childhood morbidity and mortality worldwide. Knowledge of vaccine coverage and reasons for poor uptake are essential for the achievement of herd immunity. METHOD: An observational study was carried out in September 2003, in 10 villages in the Vikas Nagar area around Herbertpur Christian Hospital in Uttaranchal, North India. We aimed to assess vaccination rates and potential socio-cultural, economic and religious influences on vaccine uptake. A total of 470 families were visited and details of immunization status of the oldest child under 7 years in each household were taken. Age range of children included was 9 months to 6 years. RESULTS: The overall primary immunization rate was 77.2%, children receiving the first booster was 73.1% and children receiving the second booster was 58.4%. The most common vaccinations to be missed were the diphtheria, pertussis, tetanus at 18 months and diphtheria, tetanus at 5 years. Measles was the most frequently omitted vaccination in the primary course (19.4%). Poor education was the most frequent reason given by parents for failure to vaccinate. Immunization rates did not differ according to gender of the child. A lower immunization rate was found in Muslim families (65.4% primary) compared with Hindu (85.2%). Parental literacy had a beneficial effect such that up to 20% more children were immunized. CONCLUSION: These results highlight the potential importance of literacy, and religious or cultural influences on the success of the Expanded Programme of Immunization, and will have important implications for areas with similar cultural demographics.

A model for immunological correlates of protection.

Immunological assays measure characteristics of the immune system, such as antibody levels, specific to certain diseases. High assay values are often associated with protection from disease. A question of interest is how the relationship between assay values and subsequent development of disease should be quantitatively modelled. Existing approaches successfully model the relationship for high assay values, where the probability of developing disease is low. However at low assay values, the probability of developing disease is more closely associated with factors such as disease prevalence rates and an individual's chance of exposure to infection; these are less well captured by existing models. This paper presents a model that accommodates both assay values and factors independent of assay values, enabling protection from disease to be modelled over the whole range of assay values and proposing a method for predicting the efficacy of a vaccine from the assays of vaccinees and non-vaccinees.

Immunizations for HIV-infected adults: indications, timing, and response.

Vaccines routinely recommended for HIV-infected adults include those for influenza, hepatitis A virus, hepatitis B virus, pneumococcal infection, and tetanus. Responses to vaccination may be affected by CD4+ cell count and viral load. A number of live vaccines are contraindicated in the HIV-infected population. This article summarizes a presentation on immunization in HIV-infected adults made by David H. Spach, MD, at the 9th Annual Ryan White CARE Act Clinical Update in Washington, DC, in August 2006. The original presentation is available as a Webcast at www.iasusa.org.

The impact of a school entry law on adolescent immunization rates.

PURPOSE: Middle school entry laws increase coverage with recommended vaccines, but their effect on vaccines that are not required is unknown. We compared vaccination coverage for hepatitis B, tetanus and diphtheria (Td), and measles, mumps and rubella (MMR) in areas of states with discordant middle school, hepatitis B school entry laws, and evaluated the relationship between demographic characteristics and adolescent immunization rates. METHODS: Retrospective design with purposive school sampling, using location of residence to determine study group. In each school, immunization records from a random sample of up to 75 students in ninth grade (affected by a new hepatitis B law) and 12th grade (not affected by the law) from 11 schools in two areas discordant for the law were analyzed. All areas had long standing two-dose MMR and Td requirements. RESULTS: Ninth graders in schools with the law had hepatitis B rates higher (72.8%) than those without the law (18.6%) (U = 2.0, p < .01). There were no significant differences between grades or schools for MMR and Td. However, even in the presence of the law, rates were significantly lower in schools with lower socioeconomic indicators. CONCLUSIONS: Middle school immunization laws are effective at raising adolescent hepatitis B, but in this study there wasn't enough power to discern the effect on rates for other vaccines or the influence of demographic variables on rates. Results suggested that laws did not appear to completely overcome disparities. For school mandates to be more effective, additional efforts, presumably on enforcement, especially in areas with lower socioeconomic indicators, are needed.