Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).     

Serum antibody response to three non-typeable Haemophilus influenzae outer membrane proteins during acute otitis media and nasopharyngeal colonization in otitis prone and non-otitis prone children

Non-typeable Haemophilus influenzae (NTHi) is the most common bacteria responsible for episodic acute otitis media (AOM; non-otitis prone), recurrent AOM (rAOM; otitis prone) and AOM treatment failure (AOMTF) in children. In this 3.5 years of prospective study, we measured the serum antibody response to outer membrane proteins D, P6 and OMP26 of NTHi in children with AOM (n = 26), rAOM (n = 32), AOMTF (n = 27). The geometric mean titers (GMTs) of IgG at their acute AOM visit against Protein D in otitis prone children were significantly lower compared to AOMTF (p value < 0.01) and non-otitis prone (p value < 0.03) children; otitis prone children had significantly lower IgG levels to P6 compared to AOMTF children (p value < 0.02); otitis prone children had significantly lower IgG levels to OMP26 compared to AOMTF children (p value < 0.04). Comparing acute to convalescent titers after AOM, otitis prone and AOMTF children had no significant change in total IgG against all the three proteins, while non-otitis prone children had significant increases to Protein D. Anti-protein D, P6 and OMP26 antibody levels measured longitudinally during NP colonization between age 6 and 24 months in 10 otitis prone children and 150 non-otitis prone children showed <2-fold increases over time in otitis prone children compared to >4 fold increases in the non-otitis prone children (p value < 0.001). We conclude that otitis prone children mount less of an IgG serum antibody response toward Protein D, P6 and OMP26 after AOM which may account for recurrent infections. The data on acute sera of otitis prone vs non-otitis prone children and the acute-to-convalescence response in non-otitis prone children point to a possible link of anti-PD to protection. Moreover, the data suggest that otitis prone children should be evaluated for their responses to Protein D, P6 and OMP26 vaccine antigens of NTHi.     

Pertussis vaccines: WHO position paper--recommendations

This article presents the WHO recommendations on the use of pertussis vaccines excerpted from the recently published Pertussis vaccines: WHO position paper. This document replaces the WHO position paper entitled Pertussis vaccines: WHO position paper published in the Weekly Epidemiological Record in January 2005. Footnotes to this paper provide a limited number of core references; their abstracts as well as a more comprehensive list of references may be found at http://www.who.int/immunization/documents/positionpapers/en/index.html. Grading tables which assess the quality of scientific evidence for key conclusions are also available through this link and are referenced in the position paper.In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This updated paper reflects the recent recommendations of WHO's Strategic Advisory Group of Experts on immunization, or SAGE.     

Vaccine administration error rates at a large academic medical center and its affiliated clinics – Familiarity matters

ObjectiveThe purpose of this study was to track and describe the absolute number of vaccine administration errors and corresponding error rates over time and by patient age and vaccine type.MethodsTotal vaccines administered to patients aged 0 through 19 years 364 days from 1/1/2006 through 12/31/2017 at a large academic health system in the Midwest United States with primary, specialty and school-based clinics, and a pediatric hospital were obtained from an electronic medical record. Vaccine administration errors over the same time period for the same patient criteria were analyzed from the health system’s incident reporting system and further compared to the frequency of all incidents reported. Vaccine administration error rates were calculated. Data were analyzed by patient age, vaccine type and year administered.ResultsOf the 1,431,206 vaccine doses given, 552 vaccine administration errors were identified (0.04%). The highest error rates occurred in children aged 2, 3, and 19 years. Vaccine types with the highest error rate were Td, rabies and pneumococcal polysaccharide vaccines. Overall vaccine doses given and errors reported increased over the study period. However, the increase was disproportionate, resulting in an increase in the error rate initially followed by a stabilization at the end of the study period.ConclusionsVaccine administration errors are uncommon. The error rate appears to be stabilizing. Errors are more likely at ages when vaccines are not commonly given, with vaccines that have age-specific dosing and with vaccines that are given less often. This suggests more safety checks are needed for vaccines that are rarely used or given off-schedule, and manufacturers should avoid vaccines with age-specific dosing.     

Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: A phase 2 clinical trial

Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/severe COPD and prior exacerbations.In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40–80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care.Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PilA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4⁺ T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval −24.2 to 39.5; p = 0.44).The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD.     

2015 - 2017年无锡市含无细胞百白破成分疫苗预防接种安全性评价

目的 评价无锡市无细胞百白破疫苗（DTaP）和无细胞百白破-灭活脊髓灰质炎- b型流感嗜血杆菌联合疫苗（DTaP - IPV - Hib）的预防接种安全性。方法 分别通过中国AEFI监测信息管理系统和无锡市免疫规划信息管理系统收集AEFI监测数据和疫苗接种数据，采用描述性流行病学方法对2015 - 2017年无锡市的DTaP和DTaP - IPV - Hib接种后的不良反应进行分析。结果 2015 - 2017年无锡市接种DTaP 、DTaP - IPV - Hib一般反应报告发生率分别为327.67/10万、268.23/10万，异常反应报告发生率分别为19.79/10万、15.58/10万。DTaP和DTaP - IPV - Hib 的一般反应和异常反应均以加强免疫为主，集中在接种后0～1 d。一般反应均主要表现为红肿（80.73%，65.31%）、硬结（45.14%，33.33%）和发热（22.69%，44.22%），异常反应主要表现均以过敏性皮疹为主（58.11%，50%）。结论 DTaP和DTaP - IPV - Hib的不良反应报告发生率无差别，均主要发生在加强免疫期间，具有良好的预防接种安全性。     

2016—2018年河南省儿童医院细菌分布及耐药性分析

目的 了解河南省儿童医院2016—2018年临床分离菌株的分布及常用抗菌药物的耐药情况,为儿科临床合理用药提供依据。方法 选择2016—2018年所有临床分离菌株,采用Phoenix 100微生物分析仪和纸片扩散法进行药敏实验,按照历年CLSI标准判读药敏结果,用WHONET5.6软件进行耐药性分析。 结果 2016—2018年共收集临床非重复分离株21404株,其中革兰阳性菌7772株,占36.3%,革兰阴性菌13632株,占63.7%。无菌体液标本共分离出致病菌2312株,排在前三位的细菌为凝固酶阴性葡萄球菌、大肠埃希菌和肺炎克雷伯菌。 3105株非脑脊液分离的肺炎链球菌中青霉素不敏感率为0.5%。耐甲氧西林金黄色葡萄球菌(MRSA)和凝固酶阴性葡萄球菌(MRCNS)平均检出率分别为34.2%和72.0%;MRSA和MRCNS对绝大多数测试抗菌药物的耐药率均显著高于甲氧西林敏感株金黄色葡萄球菌(MSSA)和凝固酶阴性葡萄球菌(MSCNS)。对万古霉素和利奈唑胺不敏感的葡萄球菌未检出。检出耐万古霉素屎肠球菌1株,未发现对万古霉素不敏感的粪肠球菌。流感嗜血菌β-内酰胺酶阳性率为53.7%,除了对复方磺胺甲噁唑的耐药率高于80.0%外,对大多数抗菌药物比较敏感。 2016—2018年大肠埃希菌产超广谱β-内酰胺酶(ESBL)的检出率依次为70.4%、72.1%和66.6%,大肠埃希菌对碳青霉烯仍高度敏感,3年来其对碳青霉烯类药物的耐药率都低于10.0%。2016—2018年肺炎克雷伯菌产ESBL检出率依次为61.3%、75.6%和72.0%,对亚胺培南的耐药率为39.3%、32.7%和43.1%,对美罗培南的历年耐药率为40.4%、30.8%和43.2%。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为22.8%和19.6%。鲍曼不动杆菌对美罗培南和亚胺培南的耐药率均为60.5%。结论     

Simultaneous single-tube PCR assay for the detection of Neisseria meningitidis, Haemophilus influenzae type b and Streptococcus pneumoniae

Rapid, accurate and inexpensive diagnosis of bacterial meningitis is critical for patient management. This study describes the development and evaluation of a multiplex PCR assay for the detection of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b, which globally account for 90% of cases of bacterial meningitis. The single-tube assay, based on the ctrA, ply and bex targets, respectively, enabled detection of 5-10 pg DNA. When the assay was tested with clinical samples (n = 425), its sensitivity for the three targets was 93.9%, 92.3% and 88%, respectively, while the overall specificity and positive predictive value of the assay was 100%. The negative predictive value was 99.1-99.5%. The methodology permits rapid and accurate detection of the three main pathogens that cause bacterial meningitis.     

Immunogenicity,safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2–17-year-old children with asplenia or splenic dysfunction: A phase 3 study

BackgroundImmunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population.MethodsThis phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2–4, 5–10 and 11–17 years), was conducted in Poland and the Russian Federation. For the 2–4 years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2 months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31 days post-vaccination, respectively, and serious AEs (SAEs) throughout the study.ResultsOf 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2 µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child.ConclusionPHiD-CV was immunogenic and well tolerated in 2–17-year-old children with asplenia or splenic dysfunction.Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.