Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.     

2010年白山市健康人群百日咳、白喉及破伤风IgG抗体水平监测

目的了解白山市健康人群百日咳、白喉、破伤风血清抗体水平。方法在全市6个县(市、区)采取随机抽样的方法抽取八道江区,对0～1岁、1～2岁、3～4岁、5～6岁、7～14岁、15～19岁、﹥20岁7个年龄组的健康人群进行抗体水平监测。结果百日咳IgG抗体阳性率为80.0%,白喉IgG抗体阳性率为68.10%,新生儿破伤风IgG抗体阳性率为49.52%。不同年龄组人群百日咳、白喉、破伤风抗体阳性率比较,差异有统计学意义(P﹤0.05)。结论在进一步提高常规免疫接种率的基础上,加强人群免疫水平监测,考虑对成人进行加强免疫[1]。     

吸附精制百白破混合制剂两针接种的血清学效果免疫持久性观察

预防百日咳、白喉、破伤风的方法是注射百白破混合制剂,共注射三针,吸附制剂注射两针,每针间隔一个月。于1978~1984年在江苏省东海县应用吸附精制百白破混合制剂进行两针注射观察。经血清学效果测定表明:白喉、破伤风、百日咳三种抗体均显著上升,且达到保护水平以上,百日咳抗体仅能维持六个月左右,一年后大多数低于保护水平,但经加强免疫后又能达到保护水平以上。基免三年至五年结果表明,两针免疫后白喉和破伤风可产生满意的血清学效果,百日咳抗体水平上升尚可。     

Immunogenicity and reactogenicity of acellular diphtheria/tetanus/pertussis vaccines given as a pre-school booster: effect of simultaneous administration of MMR.

Four acellular diphtheria/tetanus/pertussis (aDTP) vaccines were compared with two diphtheria/tetanus (DT) vaccines given as a pre-school booster to 1033 children aged 4 to < 6 years who had completed primary immunisation with DTP vaccine according to the UK 2, 3 and 4 month schedule; 71 children had received aDTP vaccine and the remaining 962 a whole cell DTP vaccine for primary immunisation. The effect of simultaneous administration of a second dose of MMR vaccine was evaluated in 374 (37%). Overall, there was little difference in the frequency of post-vaccination symptoms in DT and aDTP vaccinees, although local reactions occurred more quickly in the aDTP group. The concomitant administration of MMR had no effect on local reactions or fever within 10 days, or on the proportions requiring a doctor's visit in the 4--6 week post-vaccination period. Local reactions > or = 3 cm were higher on day 2 in children who had received aDTP for primary immunisation (erythema 32.4% vs. 17.4% for wDTP, P = 0.0012; swelling 28.2% vs. 15.5%, P = 0.0027). Pertussis antibody responses were consistent with the antigen content of the aDTP vaccines. All were more immunogenic with respect to PT -- the only pertussis antigen which by itself has been shown to be protective in clinical trials -- than a wDTP pre-school booster given in an earlier trial. MMR vaccine had no significant effect on antibody responses to either the pertussis or diphtheria and tetanus antigens. Diphtheria antibody responses in children who had received wDTP for primary immunisation were 2.8 times higher than in those who had received aDTP vaccine (P < 0.0001); they were also higher in children who had received a single dose of a Haemophilus influenzae type b vaccine containing CRM(197) conjugate after 12 months of age. For countries currently using DT vaccines as a pre-school booster, replacement with an aDTP vaccine is unlikely to have a perceptible effect on reactogenicity, at least in children given wDTP for primary immunisation, and would boost antibody levels to antigens known to be associated with protection.     

Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children.

The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.     

Controlled trial of Haemophilus influenzae type B diphtheria toxoid conjugate combined with diphtheria, tetanus and pertussis vaccines, in 18-month-old children, including comparison of arm versus thigh injection.

A randomized, controlled comparison was made in 175 healthy 18-month-old children given either diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) and haemophilus b diphtheria toxoid conjugate vaccine (PRP/D) concurrently at separate sites (66 children) or a new vaccine combining these products (109 children). Rates of local or systemic adverse effects postimmunization and antibody responses to each component did not differ significantly between groups. DTP-containing vaccines were better tolerated when given in the thigh than in the arm. The combination DTP-PRP/D vaccine performed satisfactorily at 18 months of age, avoiding the inconvenience of two injections.     

2011年湖北省麻城市健康人群百日咳、白喉、破伤风抗体水平调查

目的调查评估麻城市2011年健康人群中百日咳、白喉和破伤风抗体水平。方法随机抽取健康人群血清480人份,分为六个年龄组,采用ELISA法检测百日咳IgG、白喉IgC和破伤风IgG。结果百日咳IgG、白喉IgG和破伤风IgG保护率分别为21．04％、73．33％和67．71％。3-6岁与7-14岁白喉抗体保护率分别为90％和76．67％,两年龄段抗体保护率差异有统计学意义（X^2=29．73,P〈0．01）;3-6岁与7-14岁破伤风抗体保护率分别为93．33％和66．67％,两年龄段抗体保护率差异有统计学意义（X^2=40．52,P〈0．01）。结论麻城市人群中百日咳抗体水平较低,6岁以后人群中白破抗体水平下降明显。     

2015年新建县948例入园儿童计划免疫效果评价

目的 了解入园儿童接种乙型肝炎(乙肝)、脊髓灰质炎(脊灰)、百日咳、白喉、破伤风疫苗(以下简称“五防”疫苗)后抗体阳性率与疫苗“首针及时接种率、全程接种率、全程及时接种率”的吻合程度,评价儿童预防接种效果和免疫状况。方法 选取2015年新建县长堎地区新近入园的948例儿童作为研究对象,利用间接ELISA法检测血清标本中抗体阳性水平,通过查验儿童预防接种证收集预防接种信息,并进行比较分析。结果 948例入园儿童中,脊灰、百日咳、白喉、破伤风抗体阳性率均超过90%,乙肝抗体阳性率低于65%。除城镇儿童白喉、破伤风抗体阳性率显著高于农村(P<0.05)外,性别、户籍、居住地对“五防”疫苗的抗体阳性率影响不大(P>0.05)。全程接种乙肝、百白破三联疫苗的入园儿童乙肝、白喉、破伤风IgG抗体阳性率显著高于未全程接种者(P<0.05)。首针、全程是否及时接种“五防”疫苗对入园儿童这5种IgG抗体阳性率的影响不大(P>0.05)。结论 948例入园儿童脊灰、百日咳、白喉、破伤风免疫效果较好,而乙肝抗体阳性率相比较低。全程接种率相比首针及时接种率和全程及时接种率对评价儿童乙肝、白喉、破伤风疫苗免疫效果更有意义,值得关注并推广。     

Immunity of children aged 6-8 against pertussis,tetanus and diphtheria

Vaccination against pertussis has been performed since 1960. Whole cell pertussis vaccine produced by Plant of Sera and Vaccines Biomed S.A. in Kraków, has been used. After vaccination has been introduced, epidemiological situation of pertussis in Poland improved, but in 90's the decrease of immunity was observed. The aim of this work was to determine pertussis immunity of children after several years from the last dose of pertussis vaccine. For comparison purposes immunity against tetanus and diphtheria was tested. Protective antibody levels were detected in 70%, 58%, and 45% children aged 6, 7, and 8, respectively. It shows that decrease of immunity may cause increasing number of pertussis in children above 5. Taking into consideration our results, it seems necessary to introduce additional dose of pertussis vaccine among children aged 5 years. The level of tetanus and diphtheria antibodies was high in all tested groups.     

2008年费县部分健康人群百日咳、白喉、破伤风抗体水平调查

[目的]了解费县健康人群百日咳、白喉、破伤风抗体水平,评价百白破三联制剂免疫效果,为制定免疫策略提供科学依据。[方法]2008年随机抽取费县446名健康人群进行血清百日咳、白喉、破伤风抗体水平检测。[结果]检测446人,百日咳抗体保护率为68．39％,抗体几何平均滴度为1：306．56;白喉抗毒索均值为0．11IU／ml,保护率为77．13％;破伤风抗毒素均值为0．12IU／ml,保护率为76．01％。百日咳、白喉、破伤风抗体保护率,〈15岁组分别为76．53％、84．24％、83．42％。[结论]费县15岁以下健康人群对百日咳、白喉、破伤风均有较高的免疫水平,但15岁以上人群的抗体水平明显降低。     

2008年邻水县健康人群抗体水平监测结果分析

目的了解2008年广安市邻水县健康人群麻疹、白喉、百日咳、破伤风和乙型肝炎免疫水平状况,及时为免疫决策提供科学依据。方法在邻水县随机抽取7个年龄组304名健康人群作为监测对象,进行麻疹IgG抗体、白喉和破伤风抗毒素、乙肝表面抗体和百日咳凝集抗体水平检测。结果麻疹IgG抗体阳性（〉200mIU/ml）有289人,阳性率为95.07%;白喉抗毒素达到保护水平的有290人,阳性率为95.39%,抗毒素平均值为0.28IU/ml;百日咳抗体阳性（≥1∶20）有295人,阳性率为97.04%,保护性抗体阳性率为66.78%;破伤风抗毒素达到保护水平的有247人,阳性率为81.25%;乙肝表面抗体阳性的有164人,阳性率为53.95%;结论广安市邻水县健康人群麻疹、白喉和百日咳抗体达到标准水平;破伤风抗毒素和乙肝表面抗体未达到标准水平,需加强免疫接种工作,提高人群免疫水平。     

Vaccination coverage among children entering school--United States, 2005-06 school year

One of the national health objectives for 2010 is to achieve and sustain > or =95% vaccination coverage among children in kindergarten through first grade for the following vaccines: hepatitis B vaccine; diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine, or diphtheria and tetanus toxoids vaccine (DTP/DTaP/DT); poliovirus (polio) vaccine; measles, mumps, and rubella vaccines; and varicella vaccine. To determine vaccination coverage among children entering kindergarten, data were analyzed from reports submitted to CDC by states and the District of Columbia (DC) for the 2005-06 school year. This report summarizes the results of that analysis, which indicated that coverage for each vaccine was reported to have exceeded 95% in more than half of the states.     

Quadruple vaccines containing pertussis and poliomyelitis vaccines

Quadruple vaccines (DTP-P), prepared by mixing crude adsorbed Salk poliomyelitis vaccines, heat-killed pertussis vaccines and adsorbed purified diphtheria and tetanus toxoids were found to be toxic for mice. However, by using purified poliomyelitis and heat-killed formalinized pertussis components, vaccines were prepared that were non-toxic. The pertussis component of these vaccines retained potency over extended periods of storage. Stable, potent DTP-P vaccines offer an excellent alternative to DTP and live poliomyelitis vaccine in the basic immunization of infants and children.     

连云港市赣榆区1～10岁健康儿童流行性脑脊髓膜炎A、C群、百日咳、白喉、破伤风抗体水平的监测

目的 了解江苏省连云港市赣榆区1～10岁健康儿童流行性脑脊髓膜炎A、C群（分别简称A群流脑和C群流脑）、百日咳、白喉、破伤风特异性抗体水平,从而为免疫规划工作提供参考依据。方法 通过儿童计划免疫管理系统,从本地25个接种点接种数据库中随机抽取1～10岁全程免疫健康儿童,采集末梢血样18 747份,采用酶联免疫吸附试验法检测上述5 种传染病特异性IgG抗体水平,并对结果进行统计学分析。结果 调查的18 747份末梢血样中,A群流脑、C群流脑、百日咳、白喉、破伤风IgG 抗体阳性率分别为97.9%、98.0 %、 99.1%、 98.5%、99.0%,各个年龄组的5种抗体阳性率均在94.9%以上。城镇儿童和农村儿童间5种抗体阳性率差异均有统计学意义,城镇儿童5种抗体阳性率均低于农村儿童。 结论 赣榆区1～10岁儿童上述5类传染病特异性抗体均维持在较高水平,城镇儿童5种抗体阳性率均低于农村儿童,应加强流动人口的免疫规划疫苗接种工作。     

Immunogenicity and safety of one dose of diphtheria,tetanus, acellular pertussis and poliomyelitis vaccine (Repevax) followed by two doses of diphtheria,tetanus and poliomyelitis vaccine (Revaxis) in adults aged ≥40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years

Introduction

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years.

Methods

This open-label, multicentre study was conducted in adults aged ≥40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥0.1 IU/mL by seroneutralization assay [SNA]); tetanus (≥0.1 IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥5 EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥0.01 IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose.

Results

Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5–96.8); tetanus and poliomyelitis, 100% (CI: 98.8–100). Percentage of participants with an antibody titre ≥5 EU/mL against pertussis antigens was ≥95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8–100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%).

Conclusions

This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an adult population to achieve maximal protection against diphtheria, tetanus, poliomyelitis and pertussis simultaneously.     

Immunogenicity of a low-dose diphtheria,tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria,tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap–IPV, Repevax^®; Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis^®; Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap–IPV, Tetravac^®; Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection.All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01 IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap–IPV, Tdap + OPV and DTap–IPV, respectively, had protective antitoxin levels greater than 0.1 IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV.Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.     

南通市流动儿童免疫规划相关疾病免疫水平监测结果分析

目的评价南通市外来从事规模种植业农民、砖窑厂工人及渔船民0～7岁子女免疫规划相关疾病免疫水平,为制订流动儿童预防接种管理措施提供依据。方法采用分层整群抽样调查法,对南通市9个县(市、区)外来人口集聚地流动儿童抗体水平进行检测并作统计学分析。结果乙肝抗-HbsAg阳性率76.17%;脊髓灰质炎Ⅰ、Ⅱ、Ⅲ型抗体阳性率和抗体几何平均滴度(GMT)分别为96.11%、97.28%、94.94%和1∶439.43、1∶295.34、1∶93.613;白喉抗体阳性率和抗体GMT分别为76.71%、1∶10.836;百日咳抗体阳性率和抗体水平分别为22.41%、15.976IU/ml;破伤风抗体阳性率和抗体GMT分别为67.87%、1∶33.644;麻疹抗体阳性率和抗体水平分别为94.74%、1 105.1mIU/ml;A群流脑抗体阳性率和抗体GMT分别为64.78%、1∶11.522;乙脑抗体阳性率和抗体GMT分别为62.89%、1∶11.704。结论脊灰、麻疹阳性率和抗体水平均较高,对这部分人群的保护较好。而乙肝、白喉、百日咳、破伤风、A群流脑、乙脑阳性率偏低,显示本市上述行业流动儿童免疫覆盖水平不足,易受到相关传染病的侵袭,预防接种工作有待于进一步加强。     

Antikörper gegen impfpräventable Erkrankungen bei Schwangeren und deren Neugeborenen

In the eastern part of Germany, the age of primigravid women has increased from the end of the 2nd decade to the second half of the 3rd decade since 1990. This might influence the vaccine-induced immunity in pregnant women as well as their newborns. The objective of the present study was to examine the influence of the higher age of pregnant women on antibody protection. Maternal and cord blood samples of 290 women in the eastern part of Germany with a mean age of 28 years were analyzed for antibodies against the vaccine-preventable diseases diphtheria, pertussis, and tetanus. Compared with the data on vaccination history, the seroprevalence rate of tetanus was significantly enhanced and the seroprevalence rate of diphtheria and pertussis was significantly reduced. Detectable levels of antibodies against tetanus toxin were found in 93% of the mothers, against diphtheria toxin in 70%, and against Bordetella pertussis in 37%. Cord blood samples had a significantly higher prevalence of antibodies against pertussis and diphtheria in comparison to maternal probes. In addition,there were significantly enhanced antibody concentrations against diphtheria toxin in the newborns. In conclusion, the prevalence of antibodies determined suggests they are insufficient for protecting the newborns efficiently against pertussis and diphtheria in spite of the evidence for an active placental antibody transfer.     

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination

IntroductionDuration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations.MethodsBlood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays.ResultsAt 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children.ConclusionsThe pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis.ISRCTN65428640; ISRCTN64117538; NTR4089.     

Global routine vaccination coverage, 2010

The Expanded Program on Immunization was established by the World Health Organization (WHO) in 1974 to ensure universal access to routinely recommended childhood vaccines. Six vaccine-preventable diseases initially were targeted: tuberculosis, poliomyelitis, diphtheria, tetanus, pertussis, and measles. In 1974, fewer than 5% of the world's infants were fully immunized; by 2005, global coverage with the third dose of diphtheria-tetanus-pertussis (DTP) vaccine (DTP3) was 79%, but many children, especially those living in poorer countries, still were not being reached. That year, WHO and the United Nations Children's Fund (UNICEF) developed the Global Immunization Vision and Strategy (GIVS), with the aim of decreasing vaccine-preventable disease--related morbidity and mortality by improving national immunization programs. One goal of GIVS was for all countries to achieve 90% national DTP3 coverage by 2010. This report summarizes the status of vaccination coverage globally and regionally in 2010 and progress toward meeting the GIVS goal. In 2010, 130 (67%) countries had achieved 90% DTP3 coverage, and an estimated 85% of infants worldwide had received at least 3 doses of DTP vaccine. However, 19.3 million children were not fully vaccinated and remained at risk for diphtheria, tetanus, and pertussis and other vaccine-preventable causes of morbidity and mortality; approximately 50% of these children live in India, Nigeria, and the Democratic Republic of Congo. Despite the overall improvement in vaccination coverage during the past 37 years, routine vaccination programs need to be strengthened globally, especially in countries with the greatest numbers of unvaccinated children.