Comparative acceptance of pertussis and influenza immunization among health-care personnel

BackgroundPertussis and influenza immunization in health-care professionals (HCP) has been shown to lead to significant reduction of nosocomial infections. Parallel campaigns of pertussis and seasonal influenza immunization gave us a unique opportunity to compare attitudes towards influenza and pertussis immunization among HCP and to determine acceptance rates for both or either one of the two immunizations or refusal of both.MethodsA questionnaire was sent to HCP to anonymously obtain demographic data, profession, numbers of previous influenza immunizations, acceptance of influenza immunization in the current 2012/13 season, pertussis immunization currently or within the last 10 years, and reasons for acceptance or decline of pertussis and influenza vaccination.ResultsOf 638 HCP with patient contact, 314 (49%) responded and 303 (47%) were included in the analysis. Immunization acceptance rates were 33% for influenza, 57% for pertussis; 24% accepted both immunizations and 34% none of both. Acceptance of influenza immunization was significantly higher in those with one or more previous influenza vaccinations (p < 0.005). Among 130 HCP who declined pertussis immunization, missed opportunity (28%) was the dominant reason. Of 204 HCP who declined influenza immunization, the most frequently stated reason was “lack of influenza immunization is not considered an issue” (36%).ConclusionsMisconceptions about the efficacy and necessity of pertussis and especially influenza immunization continue to prevail among HCP. Active promotion, personal encouragement, providing more immunization opportunities and other incentives are measures that should be considered to increase the rate of immunization among HCP.     

Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women

Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012–2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus.Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine is transient and impaired during pregnancy.     

Effectiveness of acellular pertussis vaccine in a routine immunization program: A multicenter,case-control study in Japan

In 2008, the number of pertussis cases increased substantially among Japanese adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This study examined the effectiveness of DTaP vaccine in the routine immunization program in Japan. Between April 2009 and October 2012, we conducted a multicenter, case-control study, and compared the history of DTaP vaccination between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls. DTaP vaccine history was obtained by a self-administered questionnaire completed by their parents or guardians. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis.DTaP vaccination of ≥1 dose revealed a significantly lower OR for pertussis (OR = 0.20, 95%CI, 0.04–0.97), and the OR of complete vaccination (4 doses) was 0.22 (0.04–1.05). Even after limiting subjects to those whose vaccination status could be confirmed by the immunization records, the negative associations were observed. The decreasing ORs of 4-dose vaccinees remained, even among subjects who had received the fourth dose ≥9.2 years earlier (OR = 0.11, 95%CI, 0.01–1.02).In conclusion, DTaP vaccination had a preventive effect for pertussis. Effectiveness was observed even 9 or more years after the final dose.     

The impact of parental postpartum pertussis vaccination on infection in infants: A population-based study of cocooning in Western Australia

During a pertussis epidemic in 2011–2012 the Western Australian (WA) Department of Health implemented a ‘cocooning’ programme, offering free pertussis-containing vaccine (dTpa) to new parents. We assessed the impact of vaccinating parents with dTpa on the incidence of pertussis infection in newborns.Births in WA during 2011–2012 were linked to a register of parental pertussis vaccinations and to notified reports of laboratory-proven pertussis in children <6 months of age. Parents who received dTpa during the four weeks after their child's birth were defined as ‘vaccinated postpartum.’ Cox proportional-hazards methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of pertussis infection among infants born to parents vaccinated postpartum vs. unvaccinated parents, adjusted for maternal age, geographic region, timing of birth, and number of siblings.Of 64,364 live-births, 43,480 (68%) infants had at least one vaccinated parent (60% of mothers and 36% of fathers). After excluding records where parent(s) were either vaccinated prior to the birth, vaccinated >28 days after the birth, the vaccination date was uncertain, or the child died at birth (n = 42), the final cohort contained 53,149 children, 118 of whom developed pertussis. There was no difference in the incidence of pertussis among infants whose parents were both vaccinated postpartum compared to those with unvaccinated parents (1.9 vs 2.2 infections per 1000 infants; adjusted HR 0.91; 95%CI 0.55–1.53). Similarly, when assessed independently, maternal postpartum vaccination was not protective (adjusted HR 1.19; 95%CI 0.82–1.72). Supplemental sensitivity analyses which varied the time period for parental vaccination and accounted for under-reporting of vaccination status did not significantly alter these findings.In our setting, vaccinating parents with dTpa during the four weeks following delivery did not reduce pertussis diagnoses in infants. WA now provides dTpa vaccine to pregnant women during the third trimester.     

Defining long-term drivers of pertussis resurgence,and optimal vaccine control strategies

Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation.Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules.Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18–47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses.Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections.     

Immunogenicity of the pentavalent DTwP-HB-Hib vaccine (Shan-5) used in the Thai Expanded Program on Immunization compared to the hexavalent DTaP-HB-Hib-IPV and DTwP-HB-Hib (Quinvaxem) vaccines administered to infants at 2, 4, 6 months of age

BackgroundThe pentavalent DTwP-HB-Hib (Shan-5) vaccine was first introduced into the Thailand Expanded Program on Immunization (EPI) in 2019. The Shan-5 vaccine is administered to infants at 2, 4, and 6 months of age, after initial vaccination with monovalent hepatitis B (HepB) and Bacillus Calmette-Guérin (BCG) vaccines at birth. This study compared the immunogenicity of the HepB, diphtheria, tetanus, and Bordetella pertussis antigens incorporated in the EPI Shan-5 vaccine versus the optional pentavalent (DTwP-HB-Hib) Quinvaxem and hexavalent (DTaP-HB-Hib-IPV) Infanrix-hexa vaccine.MethodsThree-dose Shan-5-vaccinated children were prospectively enrolled at the Regional Health Promotion Centre 5, Ratchaburi province, Thailand, between May 2020 and May 2021. Blood sampling was performed at months 7 and 18. The levels of HepB surface antibody (anti-HBs), anti-diphtheria toxoid (DT) IgG, anti-tetanus toxoid (TT) IgG, and anti-pertussis toxin (PT) IgG were evaluated using commercially available enzyme-linked immunoassays.ResultsAnti-HBs levels of ≥10 mIU/mL were achieved in 100 %, 99.2 %, and 99.2 % of infants in the Shan-5 EPI group, hexavalent group and Quinvaxem group one month after four dose immunization (at 0, 2, 4, 6 months of age), respectively. The geometric mean concentrations of the EPI Shan-5 and hexavalent groups were comparable but were higher than those of the Quinvaxem group. At one month after primary vaccination (month 7), infants in the Shan-5 EPI group had significantly higher levels of anti-DT IgG, anti-TT IgG, and anti-PT IgG than infants in the hexavalent and Quinvaxem groups.ConclusionsThe immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization.     

全球百日咳防控面临的挑战

百日咳是由百日咳鲍特菌引起的急性高传染性呼吸道疾病, 是全球婴幼儿疾病和死亡的重要原因之一。自1974年全球逐步将百日咳疫苗纳入扩大免疫规划并维持着较高的疫苗覆盖率。近年来, 越来越多的国家或地区百日咳发病率在保持多年低水平后呈上升趋势甚至出现暴发疫情, 百日咳疾病负担被严重低估, 防控面临诸多挑战。本文综述了全球百日咳的流行现状、百日咳再现的影响因素, 以及防控面临的挑战, 为百日咳的防控策略提供参考依据。     

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis.After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR = 0.11, 95% CI, 0.01–0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR = 0.07, 95%CI, 0.01–0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR = 5.67) and those with a recent contact with a lasting cough (OR = 4.12).When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique.     

Tetanus,diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36 weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2 months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2 months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2 months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36 weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36 weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36 weeks of pregnancy was consistently protective against infant ARI in the first 2 months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.     

Inhibitory guanine nucleotide binding protein in pig epidermis: regulation of epidermal adenylate cyclase

Summary Islet-activating protein (IAP), one of the pertussis toxins, serving [-³²P]nicotinamide adenine dinucleotide (NAD) as a substrate for ADP ribosylation, radiolabelled a specific pig epidermal membrane protein. The IAP-specific substrate was detectable by sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a single band corresponding to a molecular weight of 40 kDa. The ADP ribosylation catalysed by IAP was inhibited by the addition of Mg²⁺ to the reaction mixture. IAP is known to work on intact cell systems resulting in the ADP ribosylation using intracellular NAD as the ADP ribose donor. Following IAP pretreatment of intact pig epidermis, the epidermal receptor adenylate cyclase responses were markedly increased; all the stimulatory receptor adenylate cyclase reponses (beta-adrenergic, prostaglandin E, adenosine and histamine responses) were significantly increased. Cholera toxin-induced cyclic AMP accumulation was also significantly increased. Forskolin-induced cyclic AMP accumulation was slightly increased after IAP pretreatment, but this was not statistically significant. The IAP-dependent ADP ribosylation of the epidermal 40 kDa membrane protein, which was prepared from the IAP pretreated epidermis, was significantly decreased. It is known that the tumour promoter, phorbol 12-myristate,13-acetate (PMA), decreases stimulatory receptor adenylate cyclase responses of the epidermis. Following the PMA pretreatment, IAP-dependent ADP ribosylation of the epidermal membrane protein was unaffected. Furthermore, following the PMA pretreatment, the IAP-induced increase in the epidermal receptor adenylate cyclase responses still remained. Our results indicate that pig epidermis contains 40 kDa membrane substrate for IAP-dependent ADP ribosylation, which has an inhibitory tonus on the epidermal adenylate cyclase until its ADP ribosylation by IAP. The results are consistent with the view that the epidermis contains an IAP-sensitive inhibitory guanine nucleotide binding protein (Gi) of the adenylate cyclase system. Although PMA decreases epidermal stimulatory receptor adenylate cyclase responses, it is unlikely that PMA reveals its effect through the modulation of Gi.