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1.

Background

The CRM197-conjugated 7-valent pneumococcal vaccine (PCV7) is protective against vaccine serotype disease and nasopharyngeal carriage. Data on PCV7-induced mucosal antibodies in relation to systemic or natural anticapsular antibodies are scarce.

Methods

In a randomized controlled setting, children received PCV7 at age 2 and 4 months (2-dose group), at age 2, 4 and 11 months (2+1-dose group) or no PCV7 (control group). From 188 children paired saliva samples were collected at 12 and 24 months of age. From a subgroup of 15 immunized children also serum samples were collected. IgG and IgA antibody-levels were measured by multiplex immunoassay.

Results

At 12 months, both vaccine groups showed higher serum and saliva IgG-levels against vaccine serotypes compared with controls which sustained until 24 months for most serotypes. Salivary IgG-levels were 10–20-fold lower compared to serum IgG, however, serum and saliva IgG-levels were highly correlated. Serum and salivary IgA-levels were higher in both vaccine groups at 12 months compared with controls, except for serotype 19F. Higher salivary IgA levels remained present for most serotypes in the 2+1-dose group until 24 months, but not in the 2-dose group. Salivary IgA more than IgG, increased after documented carriage of serotypes 6B, 19F and 23F In contrast to IgG, salivary IgA-levels were comparable with serum, suggesting local IgA-production.

Conclusions

PCV7 vaccination results in significant increases in salivary IgG and IgA-levels, which are more pronounced for IgG when compared to controls. In contrast, salivary anticapsular IgA-levels seemed to respond more to natural boosting. Salivary IgG and IgA-levels correlate well with systemic antibodies, suggesting saliva might be useful as potential future surveillance tool.  相似文献   

2.

Background & Aims

Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV) are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster.

Methods

Dutch infants (n = 132) were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes.

Results

One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs) for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group.

Conclusion

Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA) and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are important for PCV evaluation. How differences between the two vaccines relate to long-term protection requires further investigation.

Trial Registration

www.trialregister.nl NTR3069  相似文献   

3.

Background

In mid 2010, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent conjugate vaccine (PCV13) for childhood immunization in Italy. Our objective in this study was to obtain a snapshot of pneumococcal carriage frequency, colonizing serotypes, and antibiotic resistance in healthy children in two Italian cities one year after PCV13 was introduced.

Methods

Nasopharyngeal swabs were obtained from 571 children aged 0-5 years from November 2011-April 2012. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Penicillin and/or erythromycin non-susceptible isolates were analyzed by Multi Locus Sequence Typing (MLST).

Results

Among the children examined, 81.2% had received at least one dose of PCV7 or PCV13 and 74.9% had completed the recommended vaccination schedule for their age. Among the latter, 57.3% of children had received PCV7, 27.1% PCV13, and 15.6% a combination of the two vaccines. The overall carriage rate was 32.9%, with children aged 6-35 months the most prone to pneumococcal colonization (6-23 months OR: 3.75; 95% CI: 2.19-6.43 and 24-35 months OR: 3.15, 95%CI: 2.36-4.22). A total of 184 pneumococcal isolates were serotyped and divided into PCV7 (5.4%), PCV13 (18.0%), and non-PCV13 (82.0%) serotypes. Serotypes 6C, 24F, and 19A were the most prevalent (10.3%, 8.6%, and 8.1%, respectively). The proportion of penicillin non-susceptible (MIC >0.6 mg/L) isolates was 30.9%, while 42.3% were erythromycin resistant. Non-PCV13 serotypes accounted for 75.4% and 70.8% of the penicillin and erythromycin non-susceptible isolates, respectively.

Conclusions

Our results revealed low rates of PCV7 and PCV13 serotypes in Italian children, potentially due to the effects of vaccination. As the use of PCV13 continues, its potential impact on vaccine serotypes such as 19A and cross-reactive serotypes such as 6C will be assessed, with this study providing a baseline for further analysis of surveillance isolates.  相似文献   

4.

Background

The high cost of pneumococcal conjugate vaccine (PCV) and local epidemiological factors contributed to evaluating different PCV dosing-schedules. This study evaluated the immunogenicity of seven-valent PCV (PCV7) administered at 6-weeks; 14-weeks and 9-months of age.

Methods

250 healthy, HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines. Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1st and 2nd PCV-doses, prior to and two-weeks following the 3rd dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes following the 2nd and 3rd PCV7-doses. Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14 weeks of age.

Results

The proportion of infants with serotype-specific antibody ≥0.35 µg/ml following the 2nd PCV7-dose ranged from 84% for 6B to ≥89% for other serotypes. Robust antibody responses were observed following the 3rd dose. The proportion of children with OPA ≥8 for serotypes 9V, 19F and 23F increased significantly following the 3rd PCV7-dose to 93.6%; 86.0% and 89.7% respectively. The quantitative antibody concentrations following the 2nd PCV7-dose were comparable to that after the 3rd -dose in the 6-10-14 week schedule. Geometric mean concentrations (GMCs) following the 3rd PCV7-dose were higher for all serotypes in this study compared to the historical cohort.

Conclusions

The studied PCV7 dosing schedule induced good immune responses, including higher GMCs following the 3rd-dose at 9-months compared to when given at 14-weeks of age. This may confer longer persistence of antibodies and duration of protection against pneumococcal disease.  相似文献   

5.

Background

Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule.

Methods

We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.

Results

We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.

Conclusions

PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.

Trial Registration

ClinicalTrials.gov NCT00219401NCT00219401  相似文献   

6.

Background

The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.

Methods

600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.

Results

Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.

Conclusions

Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.

Trial Registration

ClinicalTrials.gov NCT01028326  相似文献   

7.

Background

Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13).

Method

Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients’ diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5–64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines.

Results

The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines’ coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals.

Conclusion

Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss.  相似文献   

8.

Background

Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies.

Methods

Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2–30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study.

Results

57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26–0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87–1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50–0.92], p = 0.013 in control villages and HR 0.31 [0.19–0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06–2.06], p = 0.022) and (HR 1.52 [1.11–2.10], p = 0.010 respectively) were significantly higher.

Conclusion

PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring.

Trial Registration

ISRCTN Register 51695599  相似文献   

9.

Background

In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance.

Methods

Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children <2 years and 2 to 4 years old, and patients ≥5 years old. Trends of frequency for each serotype were also analyzed.

Results

Comparison of pre-vaccination (2003–2007) and post-vaccination (2008–2012) periods showed a significant decrease in IPD incidence among children <2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p<0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33.

Conclusion

Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children <5 years of age in Uruguay.  相似文献   

10.

Background

We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines.

Methods and Findings

Nasopharyngeal swabs were taken from children <5 y old and family members (n = 400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case∶carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76–1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence.

Conclusion

Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors'' Summary  相似文献   

11.

Background

Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7).

Methodology

Nasopharyngeal swabs (n 1120) were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP) analysis. Serotypes were identified by agglutination, multiplex PCR and microarray.

Principal Findings

Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38). Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status.

Conclusions

Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.  相似文献   

12.

Background

Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs).

Methodology

In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction.

Principal Findings

S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively.

Conclusions

This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.  相似文献   

13.

Introduction

Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization’s routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries.

Methods

An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes.

Results

Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2ug/ml and 0.35ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality.

Discussion

PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to effectively implement extended age vaccinations, access to affordably-priced PCV is critical.  相似文献   

14.

Objective

Pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. Because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV).

Methods

Profiles of the nasopharyngeal microbiota of 60 children aged 12-59 months, who had been randomized to receive 2 doses of PHiD-CV (n=30) or Hepatitis A vaccine (n=30) 60 days apart, were constructed by 16S rRNA gene pyrosequencing of swab specimens collected before vaccination and 180 days after dose 1.

Results

Prior to vaccination, Moraxella catarrhalis (median of 12.3% of sequences/subject), Streptococcus pneumoniae (4.4%) and Corynebacterium spp. (5.6%) were the most abundant nasopharyngeal bacterial species. Vaccination with PHiD-CV did not significantly alter the species composition, abundance, or prevalence of known pathogens. Distinct microbiomes were identified based on the abundances of Streptococcus, Moraxella, and Haemophilus species. These microbiomes shifted in composition over the study period and were independent of age, sex, school attendance, antibiotic exposure, and vaccination.

Conclusions

Vaccination of children with two doses of PHiD-CV did not significantly alter the nasopharyngeal microbiome. This suggests limited replacement carriage with pathogens other than non-vaccine strains of S. pneumoniae.

Trial Registration

clinicaltrials.gov NCT01028326  相似文献   

15.

Background

Internet support groups (ISGs) are popular, particularly among people with depression, but there is little high quality evidence concerning their effectiveness.

Aim

The study aimed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program.

Method

Volunteers with elevated psychological distress were identified using a community-based screening postal survey. Participants were randomised to one of four 12-week conditions: depression Internet Support Group (ISG), automated depression Internet Training Program (ITP), combination of the two (ITP+ISG), or a control website with delayed access to e-couch at 6 months. Assessments were conducted at baseline, post-intervention, 6 and 12 months.

Results

There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG. However, both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group. The ITP program was effective relative to control at post-intervention but not at 6 months.

Conclusions

ISGs for depression are promising and warrant further empirical investigation.

Trial Registration

Controlled-Trials.com ISRCTN65657330  相似文献   

16.

Background

Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era.

Methods

A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region.

Results

Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6–70.8) in children less than 5 years, 42.6% (95% CI: 29.9–55.4) in children 5–15 years and 28.0% (95% CI: 19.0–37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9–24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes.

Conclusion

Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination.  相似文献   

17.

Background

Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).

Objective

To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.

Design

One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.

Results

Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1∶40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1∶40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1∶32.

Conclusion

This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.

Trials Registration

ClinicalTrials.gov NCT00546585  相似文献   

18.

Objective

To provide guidance for clinical disease prevention and treatment, this study examined the epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae (S. pneumoniae) associated with invasive pneumococcal diseases (IPDs) among children less than 14 years of age in Shenzhen, China.

Materials and Methods

All the clinical strains were isolated from children less than 14 years old from January 2009 to August 2012. The serotypes and antibiotic resistance of strains of S. pneumoniae were determined using the capsular swelling method and the E-test.

Results

A total of 89 strains were isolated and 87 isolates were included. The five prevailing serotypes were 19F (28.7%), 14 (16.1%), 23F (11.5%), 19A (9.2%) and 6B (6.9%). The most common sequence types (ST) were ST271 (21.8%), ST876 (18.4%), ST320 (8.0%) and ST81 (6.9%) which were mainly related to 19F, 14, 19A and 23F, respectively. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccine were 77.0%, 77.0%, and 89.7%, respectively. Among the 87 isolates investigated, 11.5% were resistant to penicillin, and for meningitis isolates, the resistance rate was 100%. Multi-drug resistance (MDR) was exhibited by 49 (56.3%) isolates. Eighty-four isolates were resistance to erythromycin, among which, 56 (66.7%) carried the ermB gene alone and 28 (33.3%) expressed both the ermB and mefA/E genes.

Conclusions

The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 19A and 6A in Shenzhen. The clinical treatment of IPD needs a higher drug concentration of antibiotics. Continued surveillance of the antimicrobial susceptibility and serotypes distribution of IPD isolates may be necessary.  相似文献   

19.

Background

Streptococcus pneumoniae is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, that has since become a major public health concern. In this study, the serotypes distribution of pneumococcal isolates was investigated to predict the efficacy of the 7-valent pneumococcal conjugate vaccine (PCV7) among the Malaysian populations.

Methodology/Principal Findings

A total of 151 clinical isolates were serotyped using multiplex PCR assays. Out of them, there were 21.2% penicillin-resistant, 29.1% penicillin-intermediate, and 49.7% penicillin-susceptible S.pneumoniae strains. Serotypes detected among the Malaysian isolates were 1, 3, 10A, 11A/11D, 12F/12A, 14, 15A, 15B/15C, 16F, 18C/18B/18A/18F, 19A, 19F, 23F, 35B, 35F/47F, 6A/6B, 7C/7B/40, 7F/7A, 9V/9A, and 34. Serotype 19F and 23F were the two most prevalent serotypes detected. Serotypes are highly associated with invasiveness of isolates (p = 0.001) and penicillin susceptibility (p<0.001). Serotype 19F was observed to have increased resistance against penicillin while serotype 19A has high invasive tendency. Age of patients was an important factor underlying the pneumococcal serotypes (p = 0.03) and clinical sites of infections (p<0.001). High prevalence of pneumococcal isolates were detected among children <5 years old at nasopharyngeal sites while elderly adults ≥60 years old were at increased risk for pneumococcal bacteremia.

Conclusion/Significance

Current study revealed that a number of serotypes, especially those associated with high penicillin resistance, have been formulated in the PCV7. Therefore, the protections expected from the routine use of PCV7 would be encouraging for the Malaysian. However, it is not possible to predict serotypes that might become predominant in the future and hence continued surveillance of circulating serotypes will be needed.  相似文献   

20.

Background

The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).

Methods & Principal Findings

In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.

Conclusions

RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.

Trial Registration

ClinicalTrials.gov. NCT00307021  相似文献   

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