关注肺炎链球菌结合疫苗应用后的血清型替换现象

肺炎链球菌是人类感染性疾病的重要病原,尤其对于儿童和老年人.目前针对儿童开发应用的是7价蛋白多糖结合疫苗(PCV7:4、6B、9V、14、18C、19F和23F).美国等推广PCV7应用后,肺炎链球菌侵袭性疾病显著减少;同时,非疫苗血清型定植、致病增多,在分离株中所占比例升高,该现象称为血清型替换(serotype replacement).某些单个非疫苗血清型导致的侵袭性疾病发病率已经呈现明显上升,如3、19A、22F和33F型,某些非疫苗血清型菌株的抗生素耐药性也增强.可以通过增加结合疫苗的血清型和研发对所有血清型均可提供保护的通用疫苗来应对血清型替换.     

中国儿童肺炎链球菌性疾病诊断、治疗和预防专家共识

肺炎链球菌感染至今仍是5岁以下儿童死亡的重要原因。我国肺炎链球菌性疾病(PDs)诊治水平及实验室检测水平在不同地区、医院、科室间差异较大,且临床医师对疫苗免疫关注不够。为了进一步规范PDs的防治,我们组织国内呼吸、感染、免疫和急救领域里在PDs和肺炎链球菌临床与科研方面有经验的儿科专家,制定出一个能代表临床医师观点的共识,以提高我国儿童PDs诊治及防控水平,保障儿童健康。     

肺炎链球菌的感染与免疫研究进展

肺炎链球菌是儿童侵袭性细菌感染的主要病原菌,可以引起肺炎、脑膜炎和脓毒症等危及生命的疾病。作为上呼吸道常见定植菌,了解其感染过程中机体的免疫反应对于疾病的治疗至关重要。该文综述肺炎链球菌抗原结构、肺炎链球菌结合疫苗及主要毒力因子,并重点描述肺炎链球菌感染后机体的免疫反应,包括固有免疫、巨噬细胞、中性粒细胞和T细胞的作用。     

肺炎链球菌疫苗和经济学研究

肺炎链球菌性疾病是全球严重的公共卫生问题之一,给全球儿童和成人带来了严重的健康威胁和沉重的经济负担。已在全球证明肺炎链球菌疫苗(PCV)是一种安全有效的干预措施,可预防侵袭性和非侵袭性肺炎链球菌性疾病。在世界范围内使用PCV在挽救生命、避免残疾及成本效益方面均有很大益处,特别是在非洲和亚洲。     

儿童肺炎链球菌非疫苗血清型致病性研究进展

肺炎链球菌感染为儿童常见的呼吸系统疾病, 其所引起的侵袭性肺炎链球菌性疾病(invasive pneumococcal disease, IPD)是全球儿童死亡的重要原因之一。肺炎链球菌疫苗的使用在一定程度上对儿童起到保护作用, 但致病力强、耐药性高的肺炎链球菌非疫苗血清型(non-vaccine type,NVT)的流行, 对儿童健康造成严重威胁。由于各地区疫苗接种及抗生素使用等情况的不同, 各地区NVT分布也存在一定的差异。该文对肺炎链球菌的致病过程、NVT的产生机制、各地区NVT的分布及致病情况进行综述, 以期充分认识NVT的致病性及危害, 为卫生策略调整提供数据支持, 为临床诊疗以及未来疫苗的研发和使用提供参考。     

儿童侵袭性肺炎链球菌疾病及其致病菌株研究进展

肺炎链球菌是儿童常见的感染性病原,可以引起侵袭性和非侵袭性疾病,而侵袭性疾病造成的负担和后果尤为严重。现阐述侵袭性肺炎链球菌疾病的流行病学、疾病分布及其菌株变化的最近进展,为疫苗设计、免疫策略的选择及临床诊治提供参考。     

住院肺炎患儿不同血清型肺炎链球菌对抗菌药物的耐药性分析

目的 了解当前从我国住院肺炎儿童分离的肺炎链球菌血清型分布和不同血清型菌株对抗菌药物的耐药状况,评估应用疫苗预防儿童肺炎链球菌感染和控制耐药菌传播的价值。方法 肺炎链球菌分离自4家儿童医院呼吸科年龄 ≤ 5岁的住院肺炎患儿,采用荚膜肿胀试验进行血清型分析,E试验法检测菌株对8种抗菌药物的敏感性。结果 279株肺炎链球菌中以19F型为最常见（占60.6%）,其次为19A（9.7%）。23F（9.3%）和6B（5.4%）,7价结合疫苗（PCV7）覆盖率为81.0%,PCV7在青霉素不敏感菌株和敏感菌株中的覆盖率分别为84.2%（202/240）和61.5%（24/39）。超过90%的19F和19A型菌株对青霉素不敏感,19F型以中介株为主（71.6%）,19A型以耐药株为主（55.6%）。结论 住院儿童肺炎病例分离的肺炎链球菌以19F。19A。23F和6B型常见;PCV7覆盖大多数肺炎链球菌和青霉素不敏感菌株,应用该疫苗可有效地预防国内儿童肺炎链球菌感染和阻止耐药菌株传播;非PCV7覆盖的19A型具有较强耐药性。     

住院肺炎患儿不同血清型肺炎链球茵对抗菌药物的耐药性分析

目的 了解当前从我国住院肺炎儿童分离的肺炎链球萧血清型分布和不同血清型菌株对抗菌药物的耐药状况,评估应用疫苗预防儿童肺炎链球菌感染和控制耐药菌传播的价值.方法 肺炎链球菌分离自4家儿童医院呼吸科年龄≤5岁的住院肺炎患儿,采用荚膜肿胀试验进行血清型分析,E试验法检测菌株对8种抗菌药物的敏感性.结果 279株肺炎链球菌中以19F型为最常见(占60.6%),其次为19A(9.7%)、23F(9.3%)和6B(5.4%),7价结合疫苗(PCV7)覆盖率为81.0%,PCV7在青霉素不敏感菌株和敏感菌株中的覆盖率分别为84.2%(202/240)和61.5%(24/39).超过90%的19F和19A型菌株对青霉素不敏感,19F型以中介株为主(71.6%),19A型以耐药株为主(55.6%).结论 住院儿童肺炎病例分离的肺炎链球菌以19F、19A、23F和6B型常见;PCV7覆盖大多数肺炎链球菌和青霉素不敏感菌株,应用该疫苗可有效地预防国内儿童肺炎链球菌感染和阻止耐药菌株传播;非PCV7覆盖的19A型具有较强耐药性.     

北京上海广州深圳4家儿童医院肺炎住院患儿肺炎链球菌分离株的血清型分布

目的了解目前从中国住院治疗肺炎患儿分离到的肺炎链球菌的血清型分布，及几种蛋白多糖结合疫苗的覆盖率，评估应用蛋白多糖结合疫苗预防肺炎链球菌感染的价值。方法选择2006年2月16日至2007年2月16日在首都医科大学附属北京儿童医院、复旦大学附属儿科医院、广州市儿童医院和深圳市儿童医院呼吸科住院治疗的肺炎患儿为研究对象，采用一次性吸痰管收集全部病例的呼吸道分泌物标本分离肺炎链球菌，部分患儿进行脑脊液、血液和胸腔积液中肺炎链球菌的分离。采用荚膜肿胀实验进行血清型分析。对4家儿童医院肺炎链球菌分离率和血清型进行分析，率的比较采用χ2检验或Fisher精确概率法。结果 研究期间共纳入2 865例肺炎患儿，2 865例呼吸道吸取物标本中分离到肺炎链球菌279株，其中有2株不同血清型菌株分离自同一病例，分离阳性率为9.7％（278/2 865）。3/8例胸腔积液中分离到肺炎链球菌，其中2例同时从呼吸道分泌物分离到肺炎链球菌，取其一进行血清分型，另1株从胸腔积液中分离的肺炎链球菌复苏失败，未进行血清分型。脑脊液和血液标本中未分离到肺炎链球菌。共有279株肺炎链球菌进行了血清型分析，以19F型最常见（60.6％，169/279），其次为19A（9.7％，27/279）、23F（9.3％，26/279）和6B（5.4％，15/279），上述4种血清型占全部菌株的84.9％（237/279）。肺炎链球菌7价结合疫苗（PCV7）覆盖率为81.0％，但在北京仅为46.0％，明显低于上海（80.0%）、广州(98.4%)和深圳（94.4%）。9价、10价和11价疫苗的覆盖率与PCV7相比并没有明显增加。13价疫苗的覆盖率（92.8％）较PCV7明显升高。结论4家儿童医院肺炎住院患儿分离的肺炎链球菌以19F、19A、23F和6B型常见。PCV7覆盖率为87％     

肺炎链球菌常见血清型国内分离株的耐药克隆变迁

肺炎链球菌是儿童社区获得性感染的首位致病病原,可引起侵袭性和非侵袭性疾病。近年来由于抗菌药物的广泛使用,国内肺炎链球菌耐药克隆的替代使耐药问题日趋严重。推广疫苗及合理使用抗生素对控制肺炎链球菌耐药克隆的播散具有重要作用。     

Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children

OBJECTIVE: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. METHODS: This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. RESULTS: 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated individuals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. CONCLUSION: The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.     

Pneumococcal disease in western Europe: burden of disease, antibiotic resistance and management

Streptococcus pneumoniae- the pneumococcus- affects children and adults worldwide. Invasive pneumococcal disease, including pneumonia, meningitis and bacteraemia, has been linked annually to the deaths of millions of children. The pneumococcus is also a significant contributor to mucosal infections such as acute otitis media and sinusitis. Though pneumococcal infections can occur at any age, persons at greatest risk include children younger than 2 years of age and adults aged 65 years or more. Rates of pneumococcal disease and the prevalence of pneumococcal serotypes vary by geographic location and patient age. Accurate ascertainment and sound epidemiological data are essential for the rational development of effective programmes for prevention and treatment. Pneumococcal resistance to penicillin and other antibiotics has emerged rapidly in recent years, highlighting the importance of vaccine development. Newer pneumococcal vaccines, such as those conjugated to protein carriers, can now overcome the limitations of older polysaccharide vaccines. Such conjugated vaccines induce excellent immune responses even in infants and young children and they may also reduce asymptomatic nasopharyngeal carriage of pneumococci. Pneumococcal 7-valent conjugated vaccine PNCRM7 contains common prevalent serotypes coupled to a nontoxic diphtheria variant (CRM197). This vaccine has demonstrated high efficacy against invasive pneumococcal disease in clinical trials in infants and young children and is currently licensed for use in the United States and selected countries in Europe and Latin America. CONCLUSION: across Europe, pneumococcal infection is responsible for considerable morbidity and mortality, particularly in the very young and the elderly, groups whose members respond poorly to non-conjugated vaccines. The advent of new conjugated pneumococcal vaccines now offers an exciting opportunity in developed countries to reduce both the current burden of disease and the threat of rising antibiotic resistance. Rolling out the use of such vaccines across Europe must be accompanied by detailed ongoing surveillance in order to detect any changes that might occur in the pattern of pneumococcal serotypes.     

Surveillance for invasive pneumococcal disease during 2000-2005 in a population of children who received 7-valent pneumococcal conjugate vaccine

OBJECTIVES: To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000-2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. RESULTS: For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (10(5) p-y) compared with 62.5 cases/10(5) p-y in the prelicensure years of 1996-2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/10(5) p-y during the prelicensure years to 4.9 cases/10(5) p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/10(5) p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/10(5) p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. CONCLUSION: The incidence of IPD has significantly decreased in a large population of children after the introduction of PCV7. Vaccine-type IPD was rare in patients who received full 4-dose immunization with PCV7. There is no clear evidence of a significant increase in nonvaccine-serotype IPD. Introduction of a 4-dose infant schedule of PCV7 into this population has resulted in a marked and sustained reduction of IPD in children.     

Program Szczepień Ochronnych w 2017 roku − powszechne szczepienia przeciwko pneumokokom u dzieci

In Poland, starting from 2017, mandatory vaccination against pneumococcus in children will be financed. There are two conjugate vaccines: PCV10 and PCV13 for children from 2 months of age. PCV10 vaccine was purchased for mandatory vaccination programme. In 2011?2015, PCV13 vaccine in children provided more than 20% broader serotypes coverage than the PCV10 vaccine (www.koroun.edu.pl). PCV13 is the only vaccine that demonstrated protection against invasive and non-invasive diseases caused by serotype 19A, which is the most common multi-drug resistant serotype in the population (approximately 80% of the isolates of 19A are MDR). Serotype 19A was the third most common serotype after 6B and 14, responsible for invasive pneumococcal disease (IPD) in children up to 2 years of age. The vaccine PCV10 does not include antigen of serotype 19A.In Kielce, over the last 10 years of the universal immunization programme, PCV7 / PCV13 in children showed reduction in carriage of penicillin-resistant serotypes of Streptococcus pneumoniae. Indirect effect as a decrease in pneumonia in non-vaccinated elderly population has been observed.Pediatric Group of Experts on the Immunization Programme by the Ministry of Health, based on the Polish data KOROUN, recommended vaccine PCV13 for the implementation as universal immunization for children. The arguments for the recommendation take into account the broadest serotype coverage, reducing the carriage of antibiotic-resistant serotypes and the impact of PCV13 vaccine to reduce pneumonia in non-vaccinated population.Vaccination in high-risk groups, including preterm newborns, remains unchanged. For this group, PCV13 is recommended.In the assessment of the effective prevention of pneumococcal disease, serotype coverage, real-world effectiveness of vaccines and health benefits for the entire population should be taken into account.     

Impact of pneumococcal conjugate vaccine and the severity of winter influenza-like illnesses on invasive pneumococcal infections in children and adults

BACKGROUND: Pneumococcal conjugate vaccine (PCV7), recommended in July 2000 for routine use in infants, has resulted in a reduction in the rate of invasive pneumococcal disease (IPD) in young children. We studied the impact of PCV7 and the possible contribution of the severity of influenza-like respiratory infection season on the rate of IPD on children and adults. METHODS: In 7 hospitals of a health system, episodes of IPD were identified by the microbiology laboratories during the 2-year period before July 2000 and the 4-year period after July 2000 during routine use of PCV7, and patient records were reviewed. Episodes of influenza-like illnesses during each winter in a local county were prospectively measured by reports from all acute care hospitals and episodes of absenteeism resulting from influenza-like illnesses from all schools. RESULTS: There were 720 patients with blood and/or cerebrospinal fluid isolates of Streptococcus pneumoniae. There were significant reductions in cases of IPD in children younger than 2 years, 68% reduction; children 2-4 years of age, 70%; adults 18-49 years of age, 42%; and adults older than 64 years, 30%. Annually, during the PCV7 period, there were significantly fewer episodes of influenza-like illnesses than during the pre-PCV7 years. CONCLUSIONS: PCV7 efficacy and resultant herd-type immunity resulted in a reduction in the rate of IPD not only in young children but also in young and elderly adults. Milder winter respiratory viral seasons may possibly have contributed to the observed reduction in the rate of IPD.     

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007.
Methods: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996–2007, were retrospectively reviewed.
Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children <16 years, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known risk factors. The Streptococcus pneumoniae serotype was available for 81 cases. Seventy-five percent of the IPD cases in children aged <2 years were caused by one of the serotypes contained within PCV7, compared to only 24% in children ≥2 years.
Conclusion: Our data indicate that an estimated 75% of all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination.     

Eradication of Invasive Pneumococcal Disease due to the Seven-valent Pneumococcal Conjugate Vaccine Serotypes in Calgary, Alberta

BACKGROUND:: The seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in Canada in 2001. Routine infant vaccination programs in Alberta began in 2002. Several years after PCV7 introduction, the routine use of PCV7 in infants and high-risk children has led to near elimination of invasive pneumococcal disease (IPD) caused by vaccine serotypes. METHODS:: Prospective, population-based surveillance of all IPD cases was conducted from January 1998 to December 2010. Demographic, clinical and microbiologic data were collected. RESULTS:: There were 1462 IPD cases over 13 years. Comparing PCV7 serotype IPD incidence in the prevaccine period (1998-2001) to the late postvaccine period (2007-2010), there were declines in children 0-5 months (100%), 6-23 months (98%), 2-4 years (97%), 5-15 years (100%) as well as in adults 16-64 years (73%), 65-84 years (90%) and ≥85 years of age (100%). From 2008 to 2010, there were no cases of PCV7 serotype IPD in children under 2 years of age. There have been increases in non-PCV7 serotype IPD; notably, serotypes 5 and 19A have increased significantly in adults and 19A in children. CONCLUSIONS:: PCV7 serotype IPD has been eliminated in vaccine-eligible young children and nearly eliminated in all other age groups. Serotype 19A increased significantly at all ages before the introduction of an expanded valency pneumococcal conjugate vaccine.     

Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine

BACKGROUND: Heptavalent pneumococcal conjugate vaccine was licensed in the United States in February 2000 and, following national guidelines, universally distributed in Massachusetts starting in July 2000 to children younger than 2 years of age and selected children 2-5 years of age. We performed statewide surveillance for all cases of invasive pneumococcal disease (IPD) in children younger than 18 years of age to determine risk features and contribution of vaccine failure to ongoing pneumococcal invasive disease. METHODS: Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children younger than 18 years for 2 years starting in October 2001. Serotyping was performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Case demographic and clinical data (including dates of prior doses of PCV7) were collected via follow-up telephone interviews with case primary care providers and/or parents. RESULTS: Between October 1, 2001 and September 30, 2003, 191 cases of IPD were identified statewide (138 in children younger than 5 years). Annual incidence rate for IPD was 17.4 per 100,000 children younger than 5 years, representing a decline of 69% when compared with annual incidence rate of 56.9 per 100,000 from Massachusetts statewide active surveillance performed 1990-1991. In 2001-2003, 30% of cases occurred in the first year of life (36.5 per 100,000), representing a 7.8-fold increased risk compared with children older than 1 year of age. Race-specific annual incidence rates in blacks and Hispanics were 2.3-fold (95% confidence interval, 1.21-4.42) and 1.9-fold (95% confidence interval, 1.06-3.37), greater than in whites. Fifty-nine cases were reported to have underlying comorbid conditions. Serotyping was available for 136 of 191 (71%) cases younger than 18 years; of isolates available for serotyping, 40 (29%) were vaccine serotype (ST), 31 (23%) vaccine-related ST and 65 (48%) nonvaccine ST. Seven of 40 cases with IPD caused by vaccine ST received at least 3 doses of PCV7 vaccine before IPD. CONCLUSIONS: Universal administration of PCV7 to children younger than 2 years of age and selective administration to children 2-5 years of age has resulted in a significant decline in IPD in Massachusetts. Children younger than 1 year of age, African American and Hispanic children and those with recognized comorbid illnesses (malignancy, human immunodeficiency virus, immune deficiency, nephrotic syndrome, etc.) continue to remain at risk for IPD. These risk features should be considered when evaluating febrile infants and children.     

Invasive pneumococcal disease in England and Wales: what is the true burden and what is the potential for prevention using 7 valent pneumococcal conjugate vaccine?

BACKGROUND: The annual reported incidence rates for laboratory confirmed invasive pneumococcal disease (IPD) underestimate the true burden of invasive disease attributable to pneumococcal infection. AIMS: To estimate the proportion of "unspecified" mortality of infectious cause in infants and young children aged 1 month to 4 years reported by the Office for National Statistics (ONS) in England and Wales that could reasonably be attributed to IPD, thereby revising the total number of deaths per year potentially attributable to IPD, and producing a more accurate figure for the number of deaths that may be prevented by a programme of pneumococcal conjugate vaccination. METHODS: Polymerase chain reaction, latex agglutination, and other alternate methodologies to microbiological culture have been applied in various studies to the detection of Streptococcus pneumoniae. Some of these tests have been shown to be more sensitive indicators of pneumococcal infection. In our analysis the implications of these tests were applied theoretically to the "unspecified" clinical deaths caused by septicaemia, meningitis, and pneumonia reported by the ONS, with a 20% correction/reduction factor for nasopharyngeal carriage which these sensitive tests may coincidentally detect. RESULTS: The ONS reported an average of 13 deaths per year (1989-99) in infants and children aged 1 month to 4 years caused by pneumococcal septicaemia, meningitis, or pneumonia. By applying the rates for the more sensitive tests to the most recent ONS "unspecified" mortality data available (1999), the actual annual number of deaths caused by IPD in the age group 1 month to 4 years is shown to be at least as high as 43. CONCLUSIONS: The mortality as a result of IPD in infants and young children may be at least three times the reported rate. The 7 valent pneumococcal conjugate vaccine may have the potential to prevent up to 26 (61%) of the IPD deaths per year in infants and young children in England and Wales alone.     

Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects

BACKGROUND: Pneumococcal conjugate vaccine (PCV) has been in routine use in the United States for 5 years. Prior U.S. cost-effectiveness analyses have not taken into account the effect of the vaccine on nonvaccinated persons. METHODS: We revised a previously published model to simulate the effects of PCV on children vaccinated between 2000 and 2004, and to incorporate the effect of the vaccine in reducing invasive pneumococcal disease (IPD) in nonvaccinated persons during those years. Data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention (2000-2004) were used to estimate changes in the burden of IPD in nonvaccinated adults since the introduction of PCV (compared with the baseline years 1997-1999). Results combined the simulated effects of the vaccine on the vaccinated and nonvaccinated populations. RESULTS: Before incorporating herd effects in the model, the PCV was estimated to have averted 38,000 cases of IPD during its first 5 years of use at a cost of dollar 112,000 per life-year saved. After incorporating the reductions in IPD for nonvaccinated individuals, the vaccine averted 109,000 cases of IPD at a cost of dollar 7500 per life-year saved. When the herd effect was assumed to be half that of the base case, the cost per life-year saved was dollar 18,000. CONCLUSIONS: IPD herd effects in the nonvaccinated population substantially reduce the cost, and substantially improve the cost-effectiveness, of PCV. The cost-effectiveness of PCV in actual use has been more favorable than predicted by estimates created before the vaccine was licensed.