The transforming Streptococcus pneumoniae in the 21st century

Streptococcus pneumoniae, an important pathogen causing sepsis, sinusitis, otitis media, bacterial meningitis and bacterial pneumonia, results in global morbidity and mortality each year. The burden of pneumococcal disease is highest in children and the elderly. Treatment of pneumococcal infection has been hampered by the complexity of the host immune response. In recent decades, the increase of S. pneumoniae strains' resistance to beta-lactam antibiotics and other classes of antimicrobials has made treatment even more complicated. Fortunately, the advent of heptavalent conjugate vaccine confers a high degree of protection against pneumococcal disease and colonization caused by vaccine serotype strains. After the introduction of conjugate pneumococcal vaccine, invasive pneumococcal disease caused by vaccine serotypes and antibiotic-resistant isolates has been reduced. However, naturally transformable pneumococci may escape vaccine-induced immunity by switching their capsular genes to non-vaccine serotypes. Development of cheaper, serotype-independent vaccines based on a combination of protein antigens should be pursued.     

Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995-1998: Opportunities for prevention in the conjugate vaccine era

CONTEXT: Pneumococcal polysaccharide vaccine is recommended for elderly persons and adults with certain chronic illnesses. Additionally, a recently licensed pneumococcal 7-valent conjugate vaccine has been recommended for use in young children and could dramatically change the epidemiology of pneumococcal disease. OBJECTIVES: To assess pneumococcal disease burden in the United States, estimate the potential impact of new vaccines, and identify gaps in vaccine recommendations. DESIGN AND SETTING: Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based system in 9 states. PATIENTS: A total of 15 860 cases of invasive pneumococcal disease occurring between January 1, 1995, and December 31, 1998. MAIN OUTCOME MEASURES: Age- and race-specific pneumoccocal disease incidence rates per 100 000 persons, case-fatality rates, and vaccine preventability. RESULTS: In 1998, overall incidence was 23.2 cases per 100 000, corresponding to an estimated 62 840 cases in the United States. Incidence was highest among children younger than 2 years (166.9) and adults aged 65 years or older (59.7). Incidence among blacks was 2.6 times higher than among whites (95% confidence interval [CI], 2.4-2.8). Overall, 28.6% of case-patients were at least 65 years old and 85.9% of cases in this age group were due to serotypes included in the 23-valent polysaccharide vaccine; 19.3% of case-patients were younger than 2 years and 82.2% of cases in this age group were due to serotypes included in the 7-valent conjugate vaccine. Among patients aged 2 to 64 years, 50.6% had a vaccine indication as defined by the Advisory Committee on Immunization Practices (ACIP). The case-fatality rate among patients aged 18 to 64 years with an ACIP indication was 12.1% compared with 5.4% for those without an indication (relative risk, 2.2; 95% CI, 1.7-2.9). CONCLUSIONS: Young children, elderly persons, and black persons of all ages are disproportionately affected by invasive pneumococcal disease. Current ACIP recommendations do not address a subset of persons aged 18 to 64 years but do include those at highest risk for death from invasive pneumococcal disease.     

Pneumococcal vaccines

Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases in children and adolescents. The 23-valent pneumococcal polysaccharide vaccine could prevent invasive pneumococcal infection with broader serotype coverage but still has some limitations. On the other hand, 7-valent pneumococcal conjugate vaccine has been shown to decrease cases of nasopharyngeal acquired S. pneumoniae vaccine serotypes and proved herd immunity. The safety and efficacy against vaccine serotype pneumococcal diseases have been documented. However, the potential risk of increasing non-vaccine serotype pneumococcal diseases should be considered. This article reviews the current status of pneumococcal disease and pneumococcal vaccines. We also review the current situation of pneumococcal infections and vaccines in Taiwan. Surveillance of disease burden and clinical isolates should be continued.     

Invasive pneumococcal disease in children in Ireland—the anticipated benefit of conjugate pneumococcal vaccination

Background   Streptococcus pneumoniae is an important cause of childhood illness. Recently a safe and effective 7-valent conjugate pneumococcal vaccine for children has been licensed in the EU. Aims  To calculate the incidence of invasive pneumococcal disease (IPD) in children in Ireland, to estimate the burden of disease and to anticipate the protective effect of the conjugate vaccine. Methods  Retrospective review of data from children with IPD. Results  Ninety-six cases of IPD in 95 children including two related deaths were identified. All childhood IPD incidence was estimated at 10.6/100,000. We anticipate that the 7-valent conjugate vaccine could prevent up to 90% of sepsis and up to 82.5% of meningitis cases. Conclusions  IPD is an important cause of mortality and morbidity in children in Ireland. Routine use of conjugate pneumococcal vaccine would have a significant impact on pneumococcal disease, especially in vaccinated children but also in unvaccinated children and older adults. Prior to publication, data from this study was made available to the Health Protection Surveillance Centre (HSPC) in Ireland. These data contributed to the decision by the National Immunisation Advisory Committee to recommend the introduction of an universal childhood pneumococcal vaccination programme. This is currently expected to commence in September 2008.     

Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage

Rosalyn J. Singleton, MD, MPH; Thomas W. Hennessy, MD, MPH; Lisa R. Bulkow, MS; Laura L. Hammitt, MD; Tammy Zulz, BS; Debby A. Hurlburt, RN; Jay C. Butler, MD; Karen Rudolph, PhD; Alan Parkinson, PhD

JAMA. 2007;297:1784-1792.

Context  With routine childhood vaccination using heptavalent pneumococcal conjugate vaccine, one concern has been the potential for emergence and expansion of replacement disease caused by serotypes not contained in the heptavalent conjugate vaccine.

Objective  To determine whether replacement disease is associated with the overall decline in invasive pneumococcal disease among Alaska Native children.

Design, Setting, and Patients  Alaska statewide longitudinal population-based laboratory surveillance of invasive Streptococcus pneumoniae infections from January 1, 1995, through December 31, 2006.

Main Outcome Measures  Incidence and types of pneumococcal disease in children younger than 2 years.

Results  In the first 3 years after introduction of routine vaccination with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal disease decreased 67% in Alaska Native children younger than 2 years (from 403.2 per 100 000 in 1995-2000 to 134.3 per 100 000 per year in 2001-2003, P<.001). However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive disease in Alaska Native children younger than 2 years to 244.6/100 000 (P = .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine serotypes has increased 140% compared with the prevaccine period (from 95.1 per 100 000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period, there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A accounted for 28.3% of invasive pneumococcal disease among Alaska children younger than 2 years during 2004-2006. There was no significant increase in nonvaccine disease in non–Native Alaska children younger than 2 years.

Conclusions  Alaska Native children are experiencing replacement invasive pneumococcal disease with serotypes not covered by heptavalent pneumococcal conjugate vaccine. The demonstration of replacement invasive pneumococcal disease emphasizes the importance of ongoing surveillance and development of expanded valency vaccines.

     

Invasive Streptococcus pneumoniae infections: serotype distribution and antimicrobial resistance in Canada, 1992-1995.

OBJECTIVE: To report current information about invasive pneumococcal infections, capsular types and antimicrobial resistance in Canada. DESIGN: Retrospective analysis. SETTING: Canada. PATIENTS: A total of 976 patients from whom Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid between Jan. 1, 1992, and Dec. 31, 1995. OUTCOME MEASURES: Capsular type and antimicrobial susceptibility. RESULTS: Twenty types accounted for 90.8% of the isolates from patients over 5 years of age; all but type 15A are covered by the currently available 23-valent vaccine. Nine types accounted for 92% of the isolates recovered from children 5 years and less. Reduced susceptibility to penicillin was found in 7.8% of the collection and was associated with types 6B, 9V and 19A. Full resistance to penicillin was observed most frequently during 1995 and was associated with type 9V. Rates of reduced susceptibility over one 12-month period were 19.5% for trimethoprim-sulfamethoxazole and 4.5% or less for each of cefotaxime, ceftriaxone, chloramphenicol, erythromycin, ofloxacin and tetracycline. CONCLUSIONS: Over 90% of invasive pneumococcal infections are covered by the currently available vaccines (for people over 2 years of age) and the pneumococcal protein-polysaccharide conjugate vaccines under development for young children. The high frequency of antimicrobial resistance observed requires more complete investigation and confirmation; however, taken from a global perspective, it supports the need to develop better control strategies, including greater use of new and existing vaccines.     

Epidemiology of invasive pneumococcal infections in children in Finland.

OBJECTIVE--To study the epidemiologic characteristics of invasive infections in children caused by Streptococcus pneumoniae to provide background data for vaccination programs. DESIGN--A nationwide laboratory-based prospective surveillance of all invasive pneumococcal infections in children during 1985 through 1989. SETTING--A network of all microbiologic laboratories and pediatric wards in Finland. PATIENTS--Children aged 0 to 15 years who were admitted to a hospital with S pneumoniae isolated from blood, cerebrospinal fluid, or deep aspirate sample. RESULTS--Four hundred fifty-two invasive pneumococcal infections were diagnosed in 1985 through 1989. The annual incidence rate was 8.9 per 100,000 children less than 16 years of age (24.2 per 100,000 among children less than 5 years of age and 45.3 per 100,000 among those less than 2 years of age). The most common clinical entities were bacteremia without focus (310 cases), pneumonia (66 cases), and meningitis (51 cases), with other focal infections seen in 25 cases. The pneumococcal groups/types 14, 6, 19, 7, 18, and 23 comprised 78% of all invasive infections. CONCLUSIONS--Streptococcus pneumoniae is a common cause of invasive infections in children in Finland. A pneumococcal conjugate vaccine containing the six most common groups/types could prevent up to 70% of invasive pneumococcal infections of children in Finland if fully protective in infancy.     

Invasive pneumococcal disease in Indigenous people in north Queensland, 1999-2004

OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease (IPD), and the impact of pneumococcal vaccines on IPD, in Indigenous people in north Queensland. SETTING: North Queensland, 1999-2004; there are about 53 750 Indigenous people in the region, including nearly 6900 children < 5 years and nearly 5650 adults > or = 50 years. MAIN OUTCOME MEASURES: Incidences of IPD in Indigenous children and in Indigenous adults compared between the 3 years before and after the introduction of a 7-valent pneumococcal conjugate vaccine (7vPCV) (1999-2001 versus 2002-2004). RESULTS: Estimated annual incidence of IPD in Indigenous children < 5 years of age declined from 170 to 78 cases per 100 000 in the 3 years following the introduction of 7vPCV in 2001. The annual incidence of vaccine-preventable IPD in Indigenous adults had declined by 86% since a 23-valent pneumococcal polysaccharide vaccine (23vPPV) was introduced to the region in 1996, to 15 cases per 100 000 (95% CI, 8-25) in 2002-2004. CONCLUSION: Although there was a rapid decline in IPD in young Indigenous children, it is unlikely that the incidence will fall much further with the current 7-valent vaccine. There was a suggestion that vaccinating Indigenous children indirectly protected those aged 5-14 years and Indigenous adults > or =15 years of age. Incidence of IPD in Indigenous adults in 2002-2004 was the lowest on record in the region.     

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.      

Invasive pneumococcal disease in Indigenous people in north Queensland: an update, 2005-2007

OBJECTIVE: To examine trends in invasive pneumococcal disease (IPD) in Indigenous people in north Queensland following the introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV). DESIGN: Trends in IPD were compared over three 3-year periods: before the introduction of 7vPCV for Indigenous children (1999-2001), and two consecutive periods after its introduction (2002-2004 and 2005-2007). MAIN OUTCOME MEASURES: Incidences of IPD in Indigenous children and adults in 1999-2001 and 2005-2007; trends in IPD caused by 7vPCV and non-7vPCV serotypes; and trends in indirect protective effects and emergence of non-7vPCV serotype IPD. RESULTS: From 1999-2001 to 2005-2007, there was a 60% decline in IPD, with the virtual elimination of 7vPCV serotype IPD in young (< 5 years) Indigenous children. There is no evidence yet of an increase in non-7vPCV serotype IPD in these children. Although the annual incidence of IPD in Indigenous adults remained virtually unchanged, there was a 75% decline in 7vPCV serotype IPD in these adults (chi2(trend) = 11.65, P < 0.001). However, the incidence of IPD caused by non-7vPCV serotypes more than tripled in adults (chi2(trend) = 7.58, P = 0.006). Serotype 1 IPD has been prominent over the 9 years, but there is no evidence of a recent increase in serotype 19A IPD. CONCLUSIONS: Vaccinating Indigenous children with 7vPCV has protected Indigenous adults in north Queensland through an indirect "herd immunity" effect. However, this benefit has been offset by a recent increase in non-7vPCV IPD in Indigenous adults. Newer pneumococcal conjugate vaccines could prevent, both directly and indirectly, a considerable amount of the persisting IPD in Indigenous people in the region.     

侵袭性肺炎链球菌148株血清型、耐药性及分子分型研究

目的 研究临床分离的侵袭性肺炎链球菌血清型分布、耐药性及分子流行病学特点,为抗生素的应用和免疫预防提供参考依据.方法 收集2005年1月至2008年8月全国15个地区148株来自血液、脑脊液等侵袭性感染部位的肺炎链球菌.采用琼脂稀释法测定青霉素等抗生素对148株肺炎链球菌的最低抑菌浓度(MIC);采用简易棋盘式肺炎链球菌分型系统和荚膜肿胀实验进行血清分型;多位点序列分型(MIST)技术对53株19群菌株进行基因分型,了解其与国际流行株的关系.结果 血清分型共检出20个血清型/群,主要集中在19A、19F、3、23F、5、6、14和9血清型/群,共计105株,占70.9%,以19A(22.3%,33/148)、19F(16.9%,25/148)最常见,其次为3群(7.4%,11/148)和23F(6.8%,10/148).7价疫苗(PCV7)在2岁以下儿童中的覆盖率为33.3%(12/36).PCV7相关血清型肺炎链球菌对阿莫西林/克拉维酸、红霉素等耐药率均明显高于非疫苗相关血清型菌株(P<0.05).53株19群肺炎链球菌MIST分析共检出9种序列型(ST),其中以ST320(28/53,52.8%)和ST271(12/53,22.6%)为主.结论 我国侵袭性肺炎链球菌血清分型以19A、19F、3和23F血清型为主.侵袭性肺炎链球菌耐药情况严重.     

Nasal carriage of Streptococcus pneumoniae among children in Beijing

目的　了解北京地区儿童鼻部携带的肺炎链球菌对抗生素的敏感性以及血清型分布 ,分析鼻部携带青霉素非敏感肺炎链球菌的危险因素。方法　用纸片扩散法检测肺炎链球菌对红霉素 ,复方新诺明 ,氯霉素和四环素的敏感性 ;E -试验确定青霉素 ,头孢呋新 ,头孢噻肟 ,安灭菌和亚胺培南的最小抑菌浓度 ;Quellung反应确定肺炎链球菌的血清型。结果　未发现对青霉素和头孢呋新高度耐药的肺炎链球菌 ,但对青霉素和头孢呋新中度耐药的肺炎链球菌分别占 8 2 %和 2 1%。所有菌株均对头孢噻肟 ,安灭菌和亚胺培南敏感。对红霉素 ,复方新诺明和四环素耐药的肺炎链球菌特别多 ,分别占 72 % 70 %和 79%。所有肺炎链球菌中 ,有 5种血清型 (19,6 ,14 ,2 3,17)共占 5 4 7% ,不定型占 2 0 6 %。既往中耳炎病史是鼻部携带青霉素非敏感肺炎链球菌的危险因素。结论　连续监测肺炎链球菌对抗生素的敏感性具有重要意义。需要进行更大规模的研究以明确目前的 7价或 9价肺炎链球菌结合疫苗是否适合中国儿童     

Three fatal pneumococcal polysaccharide vaccine failures

Three Indigenous Australian adults died of invasive pneumococcal disease, despite vaccination with the pneumococcal polysaccharide vaccine an average of 18 months previously. Pneumococcal isolates from the patients had serotypes that are included in the vaccine. Two of the adults were alcoholics and the other had heavy recent alcohol intake. The public health implications, and possible optimal vaccination schedules to minimise vaccine failures, are discussed.     

Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections

Context  Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites. Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown. Objective  To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States. Design, Setting, and Patients  Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states. Patients were 15 923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002. Main Outcome Measures  Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences. Results  Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks. Due to these declines, 14 730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999. Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval [CI], 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4). Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002. By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses. Conclusion  Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease.      

Clinical outcome of invasive infections in children caused by highly penicillin-resistant Streptococcus pneumoniae compared with infections caused by penicillin-susceptible strains

BACKGROUND: In this report based on data from the Institutional Surveillance System during 1994-1998, we document the continuing emergence of drug-resistant Streptococcus pneumoniae strains at the Hospital Infantil de Mexico Federico Gómez in Mexico City. METHODS: We evaluate the clinical course of 49 invasive pneumococcal infection outside the central nervous system (CNS) by a number of factors including the site, severity, and place where the infection was acquired, the underlying health of the patient, and the adequacy of antimicrobial therapy. RESULTS: An underlying illness was present in 21 of 49 (43%) patients, 37 (75%) patients had taken previous antimicrobial therapy, and 25% of the infections were nosocomially acquired. Overall, 25 of 49 (51%) of the pneumococcal strains tested were pencillin-resistant; strains with the highest resistance to penicillin were also resistant to cephalosporins. Twenty-two percent of all strains were considered to be multidrug-resistant. Eleven of 25 penicillin-resistant strains were identified as multidrug-resistant, i.e., to erythromycin, TMP/SMX, and chloramphenicol. Ten serotypes accounted for 88% of the isolates, the most frequent serotypes being 23F, 14, 19V, 6A, and 6B. The overall case-fatality rate was 37% (18 of 49), with most deaths occurring within 3-5 days after antibiotic therapy was initiated. There was no difference in the case fatality rate between children with penicillin-nonsusceptible and penicillin-susceptible pneumococcal infections; instead; case-fatality rate correlated with severity of illness on admission and presence of underlying disease. CONCLUSIONS: Characterizing groups at risk for invasive pneumococcal disease could aid in the development of preventive programs and increase the benefits from wide use of future conjugated vaccines.     

北京儿童医院2013—2017年住院儿童肺炎链球菌分离株的血清型分析

目的 分析分离自住院患儿的肺炎链球菌的血清型分布,评估肺炎链球菌结合疫苗(PCV)预防感染的价值。 方法 以2013年3月-2017年12月从北京儿童医院住院的751例患儿临床标本分离出的肺炎链球菌菌株为研究对象,采用荚膜肿胀试验对菌株进行血清分型。 结果 5年共收集非重复病例肺炎链球菌751株,其中非侵袭性菌株684株,侵袭性菌株67株。非侵袭性菌株主要分离自呼吸道分泌物(52.3%)和支气管灌洗液(44.4%),侵袭性菌株主要来自血液(50.7%)、胸腔积液(25.4%)和脑脊液(23.9%)。751株菌株中常见血清型为19F(37.0%)、19A(14.2%)、23F(9.5%)、14(7.9%)、6A(7.7%)和6B型(5.2%),共占总血清型的81.5%。PCV10、PCV13和PPV23的覆盖率分别为61.5%、84.3%和82.6%。非侵袭性菌株常见血清型为19F(37.3%)、19A(13.5%)、23F(9.5%)、6A(8.0%)、14(7.0%)和6B(5.6%),PCV10和PCV13的覆盖率分别为60.8%和83.0%。侵袭性菌株常见血清型为19F(34.3%)、19A(22.4%)、14(16.4%)、23F(9.0%)、6A(4.5%)、9V(3.0%)和1型(3.0%),PCV10和PCV13的覆盖率分别为68.7%和95.5%。 结论 北京儿童医院住院患儿分离的肺炎链球菌以19F、19A、23F、14、6A和6B型常见,PCV13覆盖率超过80%,在侵袭性感染株中更高,推广接种PCV13能够预防绝大多数肺炎链球菌感染。      

Bacterial vaccines and antibiotic resistance

Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to generate a vaccine that covers all possible genetic lineages prone to develop resistance unless the vaccine target(s) is absolutely necessary for spread and/or disease development. Targeting the resistance mechanism itself by a vaccine is an interesting but hitherto unexplored approach.     

Prevention of pneumococcal infection in children with homozygous sickle cell disease

The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1. No pneumococcal isolations occurred in the penicillin group while receiving penicillin, although four isolations occurred within one year of stopping penicillin. Probably the most effective prophylaxis against pneumococcal infection requires penicillin beyond the age of 3. The age at which pneumococcal vaccine should be given must await further data on antibody response and clinical efficacy in these patients.     

广西玉林市住院患者肺炎链球菌的血清型分布及耐药性分析

目的 分析住院患者肺炎链球菌分离株的血清型分布、耐药率及耐药基因携带,评估疫苗对本地区肺炎链球菌血清型的覆盖率,为临床合理使用抗菌药物提供参考。方法 收集2015年1月—2019年12月广西玉林市第一人民医院住院患者送检标本分离的非重复肺炎链球菌150株,进行血清分型及抗菌药物敏感性试验。用PCR方法检测pbp2b、ermB、tetM三种耐药基因的携带率。结果 150株肺炎链球菌经PCR技术分型率为93.1%,经荚膜肿胀试验分型率为100%,共分出19种血清型,以19F和6B为主。儿童血清型以19F、6B和15A为主;成人血清型以19F、14和23F为主。PCV7、PCV10、PCV13和PPV23疫苗的覆盖率依次分别为36.8%、42.1%、57.9%和68.4%。血清型为19F、6B、3和23F的菌株对抗菌药物的耐药率较高。肺炎链球菌对青霉素的敏感率大于96.0%。侵袭性与非侵袭性菌株中耐药率有显著差异的抗菌药物为青霉素、莫西沙星和左氧氟沙星。菌株同时携带ermB和tetM两种耐药基因占96.0%,pbp2b、ermB、tetM三种耐药基因与耐药表型的一致率>98.0%。共检...     

Epidemiology of invasive childhood pneumococcal infections in Israel. The Israeli Pediatric Bacteremia and Meningitis Group.

OBJECTIVE--To study the epidemiology of childhood pneumococcal invasive infections in Israel as a background for immunization programs. DESIGN--A 2-year (October 1988 through September 1990) prospective, nationwide surveillance of all invasive pediatric pneumococcal infections. SETTING--All 25 medical centers hospitalizing children in Israel, including all laboratories performing blood cultures from pediatric patients. PATIENTS--Infants and children aged 0 to 12 years visiting the pediatric emergency department or hospitalized in pediatric departments were included if Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid. RESULTS--Four hundred sixty-nine invasive infections were diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual incidence was 42 per 100,000 for children younger than 5 years of age (104 per 100,000 for those < 12 months old). The two most common serotypes were 1 and 5, which are rare in Western Europe and North America. Eight groups comprised 82% of all invasive infections. Extrapolated to a population in which 100,000 live births occur yearly, the total annual hospitalizations for pneumococci infections was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it was 30% during the first month of life. CONCLUSIONS--Pneumococcal invasive infections are common in children in Israel and carry considerable morbidity.