江苏省2018年健康人群百日咳毒素和丝状血凝素IgG抗体水平调查

目的了解江苏省2018年健康人群百日咳毒素(Pertussis toxin,PT)和丝状血凝素(Filamentous hemagglutinin,FHA)IgG抗体水平。方法采用分层抽样在江苏省两个市选择7个年龄组健康人群,采用间接酶联免疫吸附试验检测血清PT IgG抗体(IgG antibody against PT,Anti-PT IgG)和FHA IgG抗体(IgG antibody against FHA,Anti-FHA IgG),分析抗体阳性(抗体浓度≥20IU/mL)率和几何平均浓度(Geometricmeanconcentration,GMC)。结果共纳入受试者752名,Anti-PT IgG、Anti-FHA IgG阳性率分别为14.76%、28.72%,GMC分别为12.37IU/mL、17.13IU/mL。各年龄组Anti-PT IgG阳性率在8.62%(3-5岁)-23.15%(10-14岁)之间(χ^2=15.59,P<0.05),Anti-FHAIgG阳性率在10.38%(0-1.4岁)-53.27%(10-14岁)之间(χ^2=57.50,P<0.05)。在<3岁儿童中,无细胞百白破联合疫苗0-2剂次、3剂次、4剂次免疫儿童Anti-PT IgG阳性率分别为6.67%、10.75%、13.25%(χ^2=1.30,P>0.05),Anti-FHA IgG阳性率分别为6.67%、17.39%、30.12%(χ^2=6.74,P<0.05)。结论江苏省2018年健康人群Anti-PTIgG和Anti-FHAIgG水平较低;建议对特定人群进行百日咳组分疫苗选择性免疫或补充免疫。     

Age-related differences in antibody avidities to pertussis toxin and filamentous hemagglutinin in a healthy Japanese population

To gain insights into the current Japanese pertussis immunization schedule, we examined the distributions of antibody titers and avidities to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 460 Japanese healthy subjects (aged 1–60?years) based on age category. Our avidity enzyme-linked immunosorbent assays revealed that young children aged 1–2?years, which corresponded to ages after receiving primary and/or booster pertussis vaccinations, had relatively high-avidity anti-PT IgG (mean avidity index [AI], 40.5%) compared with other age groups (AI, 26.5–31.9%); however, they had relatively low-avidity anti-FHA IgG (AI, 41.8%). In contrast, children aged 3–6?years had both low-avidity anti-PT IgG (AI, 26.5%) and low-avidity anti-FHA IgG (AI, 40.4%). A significant age-related difference in anti-PT IgG avidity was observed between children aged 1–2?years and 3–6?years (P?<?0.05); however, the difference in anti-FHA IgG avidity was not significant. The anti-PT IgG avidity was positively correlated with the antibody titer, especially among children aged 1–15?years (r_s?=?0.508–0.685; P?<?0.01), indicating that the avidity of vaccine-induced anti-PT IgG decreases with decreasing IgG antibody titer to PT. Our findings strongly suggest that vaccine-induced anti-PT IgG avidity rapidly wanes after vaccination, but this is not observed for anti-FHA IgG avidity. Because children aged 3–6?years have both low-quantity and low-quality antibodies against PT, an additional booster vaccination with acellular pertussis vaccines is required for such children in Japan.     

Immunization of pregnant women against pertussis: The effect of timing on antibody avidity

BackgroundThe Centers for Disease Control and Prevention recommend tetanus–diphteria–acellular pertussis (Tdap) immunization during pregnancy, preferably at 27–36 weeks gestation.AimsFirst, to assess the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) for newborns of women immunized with Tdap during late pregnancy as compared to unimmunized women. Second, to assess whether there is a preferential period of gestational Tdap immunization that provides the highest RAI of umbilical cord IgG to PT.MethodsRAI of IgG to PT was assessed via an adapted ELISA using NH₄SCN as a dissociating agent.ResultsWe found that newborns of women immunized with Tdap during late pregnancy (n = 52) had higher mean RAI of umbilical cord IgG to PT than those of unimmunized women (n = 8), 73.77% ± 12.08 (95% CI, 70.41–77.13) vs. 50.23% ± 21.32 (95% CI, 32.41–68.06), p < 0.001. Further, the RAI of umbilical cord IgG to PT was significantly higher in newborns of women immunized at 27–30⁺⁶ weeks gestation (n = 20) when compared with newborns of women immunized at 31–36 weeks (n = 22) and >36 weeks (n = 7), 79.53% ± 5.61 (95% CI, 76.91–82.16) vs. 71.56% ± 12.58 (95% CI, 65.98–77.14) vs. 63.93% ± 17.98 (95% CI, 47.31–80.56), p < 0.03.ConclusionGestational Tdap immunization between 27 and 30⁺⁶ weeks resulted in the highest avidity of IgG to PT conveyed at delivery as compared with immunization beyond 31 weeks gestation. Future studies should be conducted to confirm our findings to optimize pertussis-controlling strategies.     

健康成人抗百日咳毒素和抗百日咳丝状血凝素抗体检测与分析

目的评估健康成人抗百日咳毒素(anti-PT)和抗百日咳丝状血凝素(anti-FHA)抗体水平。方法选择20-59岁健康成人,采用改良ELISA(mELISA)、改良硫氰酸铵-ELISA分别测定血清anti-PT和anti-FHA IgG抗体的浓度、亲和力,分析二者的相关性;采用CHO细胞簇集试验测定anti-PT中和抗体滴度,分析与anti-PT IgG抗体浓度的相关性。结果共纳入研究对象73名,anti-PT、anti-FHA IgG抗体几何平均浓度(GMC)分别为10.4 IU/mL、58.2 IU/mL,抗体亲和力中位数分别为34.8%、61.4%,anti-PT中和抗体几何平均滴度(GMT)为1:27.3。anti-PT、anti-FHA IgG抗体的浓度与亲和力均呈正相关(r=0.45,P<0.01;r=0.76,P<0.01);anti-PT中和抗体滴度与浓度呈正相关(r=0.77,P<0.01)。结论健康成人anti-PT抗体水平较低,建议制定成人百日咳疫苗免疫程序;mELISA可替代CHO细胞簇集试验用于百日咳血清学检测。     

Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice

Mice were intranasally immunised with a mixture of Bordetella pertussis filamentous haemagglutinin (FHA) and recombinant pertussis toxin, PT-9K/129G (rPT) in combination with chitosan. For both antigens, this formulation induced systemic responses as measured by serum IgG and also mucosal responses as measured by secretory IgA in lung lavage and nasal washes. Immunosorbant assays were used to measure these responses. Both the systemic and mucosal responses were considerably higher than those produced when a mixture of rPT and FHA was administered nasally without chitosan. In comparison, intraperitoneally administered rPT/FHA adsorbed to Alhydrogel elicited only a systemic response, and nasal chitosan solution produced neither systemic nor mucosal response. This study clearly demonstrated that chitosan potentiated the serum and mucosal immune responses to nasally administered FHA and rPT in mice. Hence, this nasal chitosan delivery system has potential as a new non-injectable vaccine for the prophylaxis of whooping cough.     

Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants

BackgroundBacille Calmette–Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants.MethodsInfants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens.ResultsDelaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p = 0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p = 0.032 and p = 0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age.ConclusionDelaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants.Clinical Trial Registry: NCT02062580.     

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.     

Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women

IntroductionPregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.Materials and methodsPregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).ResultsThere was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.ConclusionsThe reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.     

Acceptance of pregnant women's vaccination against pertussis among French women and health professionals: PREVACOQ-1 and -2 studies

ObjectivesProtection of French young infants against pertussis only relies on their relatives’ vaccination. The alternative is vaccination of pregnant women against pertussis (cocooning strategy), but this strategy is not yet recommended in France. We assessed the acceptance of this strategy among French postpartum women and health professionals.Patients and methodsWe performed a multicenter survey in 2016 among postpartum women and health professionals (family physicians, obstetricians-gynecologists, midwives, and medical students) to determine the acceptance of anti-pertussis vaccination. We evaluated knowledge, perception, and attitude towards vaccination to identify factors associated with acceptance.ResultsQuestionnaires were completed by 52% (1208/2337) of women and 40% (694/1754) of health professionals. Seventy-seven per cent of women (95% CI: 74–79) and 93% of health professionals (95% CI: 91–95) were favorable to anti-pertussis vaccination of pregnant women. Thirty-three per cent (227/687) of health professionals believed that pertussis induced life-long immunity and 20% (136/687) of them were not aware of the cocooning strategy. In multivariate analysis, factors associated with acceptance among women were younger age, higher knowledge, having received advice during pregnancy, being vaccinated against influenza, and having never refused any vaccine; among health professionals, factors associated with acceptance were belief that inactivated vaccines are obstetrically safe, regular practice of influenza vaccination in pregnant women, pertussis cocooning strategy, and never prescribing preventive homeopathy for influenza.ConclusionVaccination of pregnant women against pertussis should be well-accepted by informed mothers and health professionals. If this strategy were to be implemented in France, efforts should be made towards adequate information.     

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women.

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.     

Psychosocial determinants of pertussis and influenza vaccine uptake in pregnant women: A prospective study

ObjectiveTo identify the psychosocial factors influencing women’s uptake and willingness to receive pertussis and influenza vaccine during pregnancy.MethodsThe study population comprised 1364 healthy nulliparous pregnant women who participated in a prospective cohort study at two obstetric hospitals in South Australia between 2015 and 2017. Information on women's vaccination status, sociodemographic, lifestyle and psychological state were collected at 9–16 weeks’ gestation and medical case notes were checked post-delivery to verify the reported vaccination status. Poisson regression models were used to estimate the crude and adjusted prevalence ratios (aPRs) to identify psychosocial factors influencing uptake of vaccination during pregnancy.ResultsWillingness to receive the recommended maternal vaccines was high (90%). Overall, 79% and 48% received maternal pertussis and influenza vaccines respectively. There was no evidence to support the influence of psychosocial factors on women’s willingness to receive immunization during pregnancy. High levels of anxiety (aPR 0.98, 95% CI: 0.87–1.09) was not associated with uptake of maternal pertussis vaccine. However, elevated depressive symptoms (aPR 1.14, 95% CI: 1.00–1.30) and very high-perceived stress during pregnancy were significantly associated with receipt of pertussis vaccination (aPR 0.87; 95% CI 0.76–0.99). Women with mild depressive symptoms (aPR 1.21, 95% CI 1.00–1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99–1.48) were more likely to receive influenza vaccine during pregnancy (aPR 1.27, 95% CI: 1.08–1.49). A history of major depressive disorder was independently associated with receipt of pertussis (aPR 1.16, 95% CI 1.06–1.26) and influenza vaccination during pregnancy (aPR 1.32; 95% CI 1.14–1.58).ConclusionRegardless of psychosocial factors, most women reported a positive willingness to receive the recommended vaccinations during pregnancy. However, psychosocial factors influenced the uptake of pertussis and influenza vaccines during pregnancy. Psychosocial factors should be taken into consideration in designing interventions and implementation of maternal pertussis and influenza immunization programs.     

Towards replacement of the acellular pertussis vaccine safety test: Comparison of in vitro cytotoxic activity and in vivo activity in mice

Because of the exquisite sensitivity of the murine histamine sensitization test (HIST) in detecting minute amounts of active pertussis toxin (PTx), this animal-based test has been used to assure the safety of acellular pertussis vaccines in the United States and other countries around the world. Prompted by humane considerations, efforts are underway to find a suitable in vitro replacement assay that has critical attributes comparable to that of the HIST. In this study, we compared the sensitivity of the in vivo HIST with an in vitro Chinese Hamster Ovary (CHO) cell-based assay. Using vaccine samples that had been spiked with PTx, we found that both assays were capable of detecting as little as 4–10 ng of active pertussis toxin per dose of vaccine; thus, the sensitivities of the two assays are comparable. Because the strength of adsorption of PTx to the vaccine adjuvant could change over time, we also used both assays to examine the bioavailability of PTx in spiked vaccine samples that had been stored at 25 °C for 9 weeks, mimicking long term vaccine storage conditions. We found that both assays detected similar amounts of active PTx in these samples, indicating that bioavailability of the toxin in stored samples was similar. Taken together, our results indicate that critical attributes of the HIST are met by the CHO cell assay used in this study and provide proof of concept that the CHO cell assay may be further considered as a replacement for the in vivo HIST.     

Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: Comparison of three different vaccines and effect of a booster dose

Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq^® (TC), the acellular vaccine Tetravac^® (TV), or the acellular vaccine Infanrix-hexa^® (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.     

Determinants of influenza and pertussis vaccine uptake in pregnant women in Ireland: A cross-sectional survey in 2017/18 influenza season

In Ireland seasonal influenza and pertussis vaccination during pregnancy is recommended and every year national campaigns are organised to raise awareness and improve uptake. We estimated influenza and pertussis vaccine uptake and identified factors associated with vaccination status in pregnant women in 2017/18.We conducted a face-to-face omnibus survey, with quota sampling, among women aged 18–55 years and collected socio-demographic characteristics, self-reported vaccination status, awareness of vaccine campaigns, and attitudes towards vaccination. Sample was weighted to ensure representativeness with the target population. We performed univariate and multivariable logistic regression analyses on survey data.Overall, 241 pregnant women were enrolled. Influenza and pertussis vaccine uptake was 61.7% and 49.9%, respectively. Awareness of vaccine campaign and socio-economic status (SES) were associated with both influenza and pertussis vaccine uptake. The association between SES and uptake of vaccines differed by awareness. Women aware of the influenza vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those with high SES (aOR = 0.46; 95%CI: 0.22–0.97; aOR = 0.27; 95%CI: 0.12–0.60, respectively); women not aware of the pertussis vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those aware and with high SES (aOR = 0.15; 95%CI: 0.04–0.48; aOR = 0.05; 95%CI: 0.01–0.24, respectively).General practitioner (GP) recommendation was the main reason for receiving influenza vaccine (39.2%), and 71.8% of women were recommended pertussis vaccination from their GPs.The survey reports moderate uptake of vaccines among pregnant women, inequalities in uptake by SES and identifies GPs as primary source for vaccine recommendation. We recommend multifaceted campaigns, by engaging GPs, to target all socio-economic groups.     

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months

BackgroundPERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2–11 months, VE of vaccination in pregnancy and of primary vaccination (PV).MethodsFrom December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants’ age group.ResultsOf 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35–91%] and 88% [95%CI: 57–96%].Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33–90] and 95% [95%CI: 69–99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27–86] and 94% [95%CI: 59–99].ConclusionOur findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2–11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.     

Vaccination against influenza,measles, pertussis and varicella in workers in healthcare facilities in France: A national cross-sectional study in 2019

BackgroundVaccine recommendations for healthcare workers (HCW) aim to protect them and reduce transmission to susceptible patients. We conducted a national randomised survey in 2019 whose main objectives were to estimate national vaccination coverage (VC) for measles, pertussis, varicella, and influenza in HCW working in healthcare facilities (HCF) in France, and to identify determinants associated with higher VC.MethodsWe performed a cross-sectional survey of physicians, nurses, midwives and nursing assistants in HCF using a random stratified three-stage sampling design. Data were collected during face-to-face interviews using a tablet computer and complemented with information from the individual HCW vaccination records. We investigated possible determinants of higher VC using univariate and multivariate Poisson regressions and estimated the prevalence ratio (PR).ResultsWe included 8594 HCW working in 167 HCF. Self-declared VC was 73.3% (CI95%: 71.0–75.5) for measles in HCW with no history of measles (at least one dose), 53.5% (49.9–57.0) for pertussis (booster dose during adulthood), 26.4% (23.0–30.2) for varicella in HCW with no history of varicella (at least one dose) and 34.8% (32.8–37.4) for influenza. Taking into account the history of each disease and related VC, 14.6% and 10.1 % of HCW were susceptible to measles and varicella. VC varied by profession, age group, ward and sex. Higher influenza VC was observed in HCW working in wards where i) there was a staff vaccination contact person (PRa: 1.2, CI95% 1.1–1.4), ii) staff vaccination was organized in the ward (1.4: 1.2–1.6), iii) information on influenza vaccines was provided (1.2: 1.1–1.4), and iv) the ward manager supported the HCW vaccination campaign (1.3: 1.1–1.6).DiscussionOver a 10-year period, VC for HCW working in HCF improved in France. However, vaccination objectives were not achieved for measles (95%) or influenza (80%). Vaccination efforts should be continued, especially in wards with at-risk patients.     

Acellular pertussis vaccine use in risk groups (adolescents, pregnant women, newborns and health care workers): a review of evidences and recommendations

Background

Pertussis is an acute infectious illness, caused by the bacteria Bordetella pertussis and commonly known as “whooping cough”. Waning immunity after vaccination or after natural infection contributes significantly to the increasing incidence rates in adolescents and adults. Prevention of pertussis in industrialized countries is mainly based on immunization with acellular vaccines in combination with other antigens. A booster dose with an adult-formulation tetanus-diphtheria toxoid and acellular pertussis vaccine (Tdap) is now recommended for all adolescents by several countries, and replacement of the decennial Td dose with a single or more doses of Tdap is recommended for adults.

Objective

Our review aims at describing the current knowledge on the impact of acellular pertussis vaccination in adolescents and adults, with particular focus on specific risk groups: adolescents, pregnant women and their newborns, and health care workers (HCWs), and secondly at suggesting possible immunization strategies.

Methods

Data were retrieved by searches of Pubmed, references, from relevant articles and open-access websites.

Results

In countries where an adolescent booster dose was adopted, a certain decrease of incidence rates was observed. No serologic correlate of protection after immunization exists, but subjects with high antibody levels against pertussis antigens are less likely to develop the disease. Tdap vaccine was demonstrated to induce antibodies to pertussis antigens exceeding those associated with efficacy in infants, in both adolescents and adults. Tdap use in pregnant women seems to be safe and might represent a useful tool in order to prevent pertussis cases in the first months of life. Neonatal immunization with monovalent acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune responses. Cocooning strategies involving all those surrounding newborns have started to be implemented. Their impact on infant pertussis cases will be evaluated in the coming years. Coverage in HCWs should be increased, given their important role in pertussis transmission in health care settings.

Conclusions

Despite the more recent position paper of WHO gives priority to infant and childhood vaccination against pertussis and leaves adolescent, adult and risk group immunization as an option for the future, data are quickly accumulating to support the need to consider pertussis vaccination as a crucial preventative intervention even in adolescents and special risk groups.     

An observational study of antibody responses to a primary or subsequent pertussis booster vaccination in Australian healthcare workers

Adult pertussis vaccination is increasingly recommended to control pertussis in the community. However, there is little data on the duration and kinetics of immunity to pertussis boosters in adults. We compared IgG responses to vaccination with a tetanus, low-dose diphtheria, low-dose acellular pertussis (Tdap) booster at 1 week, 1 month and 1 year post-vaccination in whole-cell (wP)-primed Australian paediatric healthcare workers who had received an adult Tdap booster 5–12 years previously, to those who received their first Tdap booster.Tdap vaccination was well tolerated in both groups. Previously boosted adults had significantly higher pre-vaccination IgG concentrations for all vaccine-antigens, and more were seropositive for pertussis toxin (PT)-specific IgG (≥ 5 IU/mL) (69.5%; 95% confidence interval (CI) 59.5–79.5) than adults in the naïve group (45.2%; 95% CI 32.8-57.5). Tdap vaccination significantly increased IgG responses 1 month post-vaccination in both groups. This increase was more rapid in previously boosted than in naïve adults, with geometric mean fold-increases in PT-IgG at 1 week post vaccination of 3.6 (95% CI 2.9–4.3) and 2.6 (95% CI 2.2–3.2), respectively. Antibody waning between 1 month and 1 year post-vaccination was similar between groups for IgG specific to PT and filamentous haemagglutinin (FHA), but was faster for IgG against pertactin (PRN) in the naïve group (GMC ratio 0.36; 95% CI 0.31–0.42) than the previously boosted group (GMC ratio 0.45; 95% CI 0.39–0.50). At baseline, all but one adult had protective IgG titres against tetanus toxin (TT) (≥ 0.1 IU/mL), and 75.6% in the previously boosted and 61.3% in the naïve group had protective IgG titres against diphtheria toxoid (DT) of ≥ 0.1 IU/mL.This study shows that pertussis immune memory is maintained up to 12 years after Tdap vaccination in wP-primed Australian adults. There was no evidence that pertussis immune responses waned faster after a booster dose. These findings support current recommendations of repeating Tdap booster vaccination in paediatric healthcare workers at least every 10 years. Clinical trials registry: ACTRN12615001262594.     

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants

BackgroundPreterm (PT) infants are at greater risk for severe influenza infection and experience decrements in long-term antibody responses to vaccines. This may related to defects in antibody secreting cell (ASC) generation.ObjectiveTo investigate the relationships among the frequencies of influenza-specific antibody secreting cells, ASC numbers and subsets, and antibody responses to influenza vaccines (IV) among PT and full-term (FT) infants.Design/methodsWe enrolled 11 former PT (≤32 weeks′ gestation, ≤1500 g′ birth weight) and 11 FT infants, 6–17 months of age, receiving their first influenza immunizations. Infants received two doses of inactivated trivalent (T)IV or quadrivalent (Q)IV during the 2012–2013 and 2013–2014 influenza seasons, respectively, at 0 and 28 days, and blood was drawn at 0, 10, 35, and 56 days and 9 months. Vaccine-specific antibody was measured by hemagglutination inhibition (HAI) at 0 and 56 days and 9 months, vaccine-specific ASC numbers by enzyme linked immunospot (ELISPOT) at 10 and 35 days, and ASC subsets by flow cytometry at 0, 10 and 35 days.ResultsPT infants had post-vaccine HAI titers to all 4 vaccine strains at least equal to FT infants at 56 days and 9 months after beginning immunization. Influenza-specific ASC ELISPOT responses at 35 days were higher among PT than FT infants (median 100 v. 30 per 10⁶ PBMC, p = 0.04). ASC numbers at 35 days were positively correlated with serum HAI titers at 56 days (ρ = 0.50–0.80). There were no statistical differences between PT and FT infants in the frequency of five ASC subsets and no specific ASC subset correlated with durability of serum antibody titers.ConclusionsInfluenza-specific ASC numbers in both FT and PT infants correlated with peak antibody titers, but ASC subsets did not correlate with durability of antibody response.     

The financial impact of a state adopting a personal/philosophical belief exemption policy: Modeling the cost of pertussis disease in infants, children and adolescents

State school immunization exemption policies help reduce the risk of individual and community disease. Assessing the costs of vaccine preventable disease associated with a state adding a philosophical/personal belief school exemption policy is useful for making future policy decisions. Two formulas were developed to estimate the infant, child and adolescent hospitalization and non-medical costs of pertussis disease that are associated with adding a philosophical/personal belief school exemption policy. The parameter estimates were obtained from peer reviewed literature and the Centers for Disease Control and Prevention. The state of Iowa was used as an example in order to demonstrate how the formulas can be applied. The annual projected impact of pertussis disease in Iowa is $273,365 without a philosophical/personal belief exemption policy and an average of $410,047 (range of $281,566-$582,267) with adding a personal belief exemption policy. We project that adding a philosophical/personal belief exemption will cost 50% more dollars annually.