Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice

Background

Conflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy.

Methods

We randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams’ diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA.

Results

RBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (P < .0001). RRV vaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (P < .0001). Vaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (P < .05), however we detected no effects of undernutrition on viral clearance nor of infection on bodyweight. EDIM infection provoked higher anti-RV serum IgA levels in RBD vs. CD mice, regardless of vaccination (P < .0001). Last, RRV vaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (P < .0001).

Conclusions

Despite modulated IgA responses to vaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings.     

Evaluating the Brighton Collaboration case definitions,aseptic meningitis,encephalitis, myelitis,and acute disseminated encephalomyelitis,by systematic analysis of 255 clinical cases

Aims

Brighton Collaboration (BC) case definitions are independent from presumed causes or triggers, hence should be applicable in routine clinical settings.

Scope

255 cases with discharge diagnoses of aseptic meningitis (ASM; n = 164), encephalitis (ENC; n = 48), myelitis (MYE; n = 8), ADEM (n = 10), or bacterial meningitis (BM; n = 59; control group) were tested against the BC case definitions ASM, ENC, MYE, and ADEM. Overall rates of agreement between BC criteria and discharge diagnoses were 70%, 78%, 97%, and 97% for ASM, ENC, MYE and ADEM, respectively.

Conclusion

BC case definitions are easily applicable in retrospective chart reviews allowing causality assessments with minimal selection bias.     

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study

Background

In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected.

Methods

Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003–2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007–2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively.

Findings

The proportion of PCV7 serotypes among all IPD cases (n = 7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P < 0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P = 0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P = 0.008), 19A (P = 0.03) and 19F (P = 0.005), compared to serotype 1 and 7F.

Conclusion

There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.     

Duration of protection against hepatitis A for the current two-dose vaccine compared to a three-dose vaccine schedule in children

Background

Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown.

Methods

We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years.

Results

No significant differences were observed when comparing GMC between the two cohorts at 10 (P = 0.467), 12 (P = 0.496), and 14 (P = 0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years.

Conclusion

The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term.     

Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults

Background

Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.

Objective

To explore safety and immunogenicity of a recombinant protein vaccine candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine triad protein D (PhtD).

Methods

This phase I, exploratory, open-label, single-center clinical study enrolled adults (18–50 years). Participants in a pilot safety cohort received a single intramuscular injection of 6 μg. Following safety review, 3 dose cohorts were enrolled (6, 25, and 100 μg); participants received 2 injections administered approximately 30 days apart. Assignment of the second injection and successive dose cohorts were made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events, serious adverse events, and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD antibodies as measured by ELISA.

Results

Sixty-three participants were enrolled and received the pilot safety dose (n = 3) or at least 1 dose of PhtD vaccine candidate at 6 μg (n = 20), 25 μg (n = 20), or 100 μg (n = 20). No safety concerns were identified. No vaccine-related serious adverse event was reported. The most common solicited injection site reaction was pain and most common solicited systemic reactions were myalgia and headache; most reactions were mild and transient. Observed geometric mean concentrations (95% CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15 (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 μg dose cohorts, respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62 (1082.92, 2272.16) post-injection 2.

Conclusions

All dose levels were safe and immunogenic. The frequency of solicited reactions was highest at the 100 μg dose. Administration of a second injection significantly increased the levels of anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001).     

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage

Background

4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology.

Objective

To experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting.

Methods and results

We used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007–2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P = 0.022). MATS predicted coverage of 70% (95% CI, 55–85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72–95%). MATS had 78% accuracy and 96% positive predictive value against hSBA.

Conclusion

MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents.     

Impact of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on childhood pneumonia hospitalizations in Brazil two years after introduction

Introduction

Pneumococcal disease is a major public health problem worldwide. From March to September of 2010, 10-valent pneumococcal non-typeable Haemophilus influenzae protein conjugate vaccine (PHiD-CV) was introduced in the Brazilian childhood National Immunization Program (NIP) in all 27 Brazilian states. The aim of the present study is to report national time-trends in incidence of hospital admissions for childhood pneumonia in Brazil before and after two years of introduction of this new pneumococcal conjugate vaccine.

Methods

Analysis of hospitalization data of children aged 0–4 years in Brazilian public health system with an admission diagnosis of pneumonia from 2002 to 2012 was performed comparing pre (2002–2009) and post-vaccination periods (2011–2012). Hospital number of admission due to pneumonia and all non-respiratory diseases were obtained from DATASUS, the Brazilian government open-access public health database system. Incidence of pneumonia hospitalization was compared to incidence of all non-respiratory admissions.

Results

Admission rates for pneumonia decreased steadily from 2010 to 2012. In children aged less than four years, incidence of pneumonia hospitalizations decreased 12.65% when pre (2002–2009) and post-vaccination introduction periods (2011–2012) were compared and adjusted for seasonality and secular-trend (p < 0.001). On the other hand, non-respiratory admission rates remained stable comparing both periods (p = 0.39).

Conclusion

Childhood pneumonia hospitalization rates were fluctuating prior to 2010 and decreased significantly in the two years after PHiD-CV introduction. Conversely, rate of non-respiratory admissions has shown no decrease. These data are an evidence of the effectiveness and public health impact of this new pneumococcal vaccine.     

Well-woman visit of mothers and human papillomavirus vaccine intent and uptake among their 9–17 year old children

Objective

To examine the association between attending a well-woman clinic in the prior 2 years and obtaining the human papillomavirus (HPV) vaccine for their 9–17-year-old child.

Methods

Women (n = 1256) who attended reproductive health clinics during September 2011 to February 2013 and had ≥1 children 9–17 years of age were asked to complete a self-administered questionnaire containing questions on demographic characteristics, prior well-woman visits, HPV awareness, and HPV vaccine intent and uptake among their adolescent children.

Results

Nearly 78% of women reported having undergone a well-woman visit during the past 2 years. Bivariate analysis showed that the HPV vaccine initiation (23.9% vs. 14.0%, P = .004) and completion (13.6% vs. 6.7%, P = .011) among 9–17 daughters differed between mothers who did or did not have a well-woman visit during the past 2 years. However, intent to vaccinate them (47.2% vs. 53.3%, P = .173) did not differ between these two groups. With regard to 9–17 year old sons, vaccine initiation (10.1% vs. 9.6%, P = .871), completion (4.6% vs. 2.4%, P = .273) and intent to vaccinate (47.3% vs. 52.1%, P = .311) did not differ between these two groups. Multivariable logistic regression analyses confirmed the findings of these bivariate analyses after adjusting for confounder variables.

Conclusion

The well-woman visit may be a missed opportunity for physicians to educate their patients about the benefits of HPV vaccination for their adolescent children in general and sons in particular. Intervention studies are warranted to assess the benefits of using this setting to improve HPV vaccine uptake in the US.     

Cluster randomized trial of a toolkit and early vaccine delivery to improve childhood influenza vaccination rates in primary care

Purpose

To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial.

Methods

Twenty primary care practices treating children (range for n = 536–8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months–18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010–2011 and 2011–2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes.

Results

Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P < 0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms – 8/10 Intervention (all P < 0.001) and 7/10 Control sites (P-values = 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.23–1.34), having commercial insurance (OR = 1.30; 95%CI = 1.25–1.35), higher pre-intervention practice vaccination rate (OR = 1.25; 95%CI = 1.16–1.34), and being in the Intervention arm (OR = 1.23; 95%CI = 1.01–1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates.

Conclusions

Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates.Clinical trial registry name/number: From Innovation to Solutions: Childhood Influenza/NCT01664793.     

Phase II,dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age

Introduction

ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus (WNV) produced by insertion of the genes encoding the pre-membrane (prM) and envelope (E) proteins of WNV (strain NY99) into the yellow fever 7D vaccine virus. This Phase II, randomized, double-blind, placebo-controlled, multi-center study in the US assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine.

Methods

The study included adults in general good health. Subjects aged ≥50 years were randomized to one of four treatment groups: ChimeriVax-WN02 4 × 10³ plaque-forming units (pfu) (n = 122), 4 × 10⁴ pfu (n = 124), 4 × 10⁵ pfu (n = 113), or placebo (n = 120). A subset of subjects was randomized to assess viremia after vaccination at three different dose levels. Subjects were followed for safety up to 6 months after vaccination.

Results

A total of 121subjects for WN024 × 10³, 122 for WN02 4 × 10⁴, 110 for WN02 4 × 10⁵, and 120 for the placebo group completed the study up to the 6-month safety follow-up. Seroconversion, as measured by plaque reduction neutralization test (PRNT), was achieved at Day 28 by 92.1%, 93.2%, and 95.4% of subjects in the WN02 4 × 10³, the WN02 4 × 10⁴, and the WN02 4 × 10⁵ groups, respectively. Viremia was transient, detected between Days 2 and 14 but not at Day 28, and in most cases did not reach the quantification threshold. The percentage of subjects reporting at least one event of reactogenicity was similar in the placebo and active vaccine groups and showed no dose relationship.

Conclusions

The ChimeriVax-WN02 vaccine was highly immunogenic and well tolerated among subjects ≥50 years old at all dose levels.     

Rubella seroprevalence in the first birth cohort reaching fertility age after 20 years of two dose universal vaccination policy in Israel

Background

A national program of a 2-dose universal childhood MMR vaccination policy has been in effect in Israel since 1988. As the 1988 birth cohort reached fertility age, questions regarding immunity against rubella were raised.

Objective

To assess the seroprevalence of rubella IgG antibodies among young Israeli adults born after 1987 in comparison to previous birth cohorts, in order to determine evidence based policy for prevention of rubella and congenital rubella syndrome.

Methods

We conducted a seroprevalence study of rubella IgG antibodies among 416 Israeli adults (42.5% females) born in 1988–1989, based on a representative sample of sera collected at age 18–19 upon recruitment to mandatory military service in 2007.

Results

In total, 87.7% were seropositive (>15 IU/ml) as compared with 84.8% in the 1999 recruitment (P = 0.26) and 93.4% in 1987 (P = 0.004). Yet there was a difference by gender. The proportion of seropositives among female young adults (92.7%) was significantly lower as compared to those measured in the 1999 (99.2%, P = 0.001) and 1987 (99.0%, P = 0.006) recruitments. The proportion of seropositives among males (84.1%) was significantly higher as compared to those measured in 1999 (73.0%, P < 0.001) but similar to those of 1987 (88.8%, P = 0.13). Females born in the FSU were found to be high risk groups as 11.5% were seronegative.

Conclusions

Our findings indicate that despite a successful program of congenital rubella syndrome prevention in Israel, there is a decline in seroprevalence among female young adults, especially immigrants from the FSU. A proactive catch-up program for females, especially for those of higher risk for susceptibility should be considered in Israel and in other countries.     

Neighborhood walkable urban form and C-reactive protein

Background

Walkable urban form predicts physical activity and lower body mass index, which lower C-reactive protein (CRP). However, urban form is also related to pollution, noise, social and health behavior, crowding, and other stressors, which may complement or contravene walkability effects.

Purpose

This paper assesses within-neighborhood correlation of CRP, and whether three features of walkable urban form (residential density, street connectivity, and land use mix) are associated with CRP levels.

Methods

CRP measures (n = 610) and sociodemographic data come from the 2001–3 Chicago Community Adult Health Study, linked with objective built environment data.

Results

Within-neighborhood correlations of CRP are greater than those of related health measures. A one standard deviation increase in residential density predicts significantly higher log CRP (e.g. β = 0.11, p < .01) in Chicago, while a one standard deviation increase in land use mix predicts significantly lower CRP (e.g. β = − 0. 19, p < 0.01). Street connectivity is unrelated to CRP in this highly walkable city.

Discussion

Results suggest that residential density may be a risk factor for inflammation, while greater walkability of mixed land use areas may be protective. It may be that negative aspects of density overcome the inflammatory benefits of walking.     

DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Background

We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.

Methods

Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.

Results

Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = −1.5, 67.7) for ‘Any illness with or without fever’ and 53% for ‘Upper respiratory tract infection’ (95% CI = 8.0, 77.7).

Conclusion

It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.     

Evaluating the impact of pluridisciplinary training on proper glove use in hospital

Objective

The authors of this randomized study had for aim to evaluate the impact of training on proper glove use by comparing compliance to glove use recommendations between trained and untrained healthcare personnel according to healthcare professional groups.

Patients and methods

A random selection of trained and untrained nurses, nurse aids, and hospital housekeepers was performed in a French University hospital, using a listing of healthcare personnel. The audits were conducted by two infection control nurses, in series of 10 observations, with a maximum time limit of two hours. The evaluation criteria were compliance or non-compliance of glove-wearing practices with internal hospital recommendations, disclosed to professionals during training.

Results

Overall, 111 professionals were audited and 794 acts were observed. Hand hygiene was significantly better in trained vs. untrained healthcare professionals (P < 0.01). Proper glove use practices were similar between trained and untrained nurses (85% of compliance), whereas the difference was statistically significant in favor of trained healthcare personnel for the other categories (P < 0.001 for nurse aids and P = 0.02 for housekeepers).

Conclusion

We demonstrated the impact of pluridisciplinary training on proper glove use practices in hospital settings, but with different benefits found according to professional groups. The lower the initial training level, the greater the overall benefit appeared to be.     

Development and evaluation of the Motivation to Limit Screen-time Questionnaire (MLSQ) for adolescents

Objective

The aim of this study was to design and evaluate a brief scale to assess adolescents' motivation to limit their screen-time using a self-determination theory (SDT) framework.

Methods

The development and evaluation of the Motivation to Limit Screen-time Questionnaire (MLSQ) involved three phases. In Phase 1, experts in SDT were asked to review the content validity of the MLSQ items. In Phase 2, adolescent boys (N = 342, mean age = 12.7 ± .5 years) completed the MLSQ and the factorial validity of the model was explored. In Phase 3, adolescent boys (N = 48, mean age = 14.3 ± 1.3 years) completed the MLSQ on two occasions separated by 1-week. Phases 2 and 3 were conducted in New South Wales, Australia in 2012.

Results

Twenty four SDT experts reviewed the original scale items. Validity coefficients associated with six of the original eight items exceeded the threshold value (V > .68, p < .01). In Phase 2, the revised three-factor (9-items) model provided a good fit to the data (SRMR = .07, CFI = .96). The intraclass correlation (ICC) values were .67 for amotivation and .70 and .82 for controlled and autonomous motivation, respectively.

Conclusion

This study has provided preliminary evidence for the validity and reliability of the MLSQ in adolescent boys.     

Safety,reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults: A phase I/II randomized clinical study

Background

New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) are being developed to provide broader protection against pneumococcal disease. This study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults.

Methods

In a phase I double-blind study (www.clinicaltrials.gov: NCT00707798), healthy adults (18–40 years) were randomized (1:2:2:2:2:2:2) to receive two doses of one of six investigational vaccine formulations 2 months apart, or a single dose of the control 23-valent pneumococcal polysaccharide vaccine (23PPV; Pneumovax23™, Sanofi Pasteur MSD) followed by placebo. The investigational formulations contained dPly alone (10 or 30 μg), or both dPly and PhtD (10 or 30 μg each) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Vaccines). Two groups primed with a formulation containing dPly and PhtD (10 or 30 μg each) continued to the follow-up phase II study (NCT00896064), in which they received a booster dose at 5–9 months after primary vaccination.

Results

Of 156 enrolled and vaccinated adults, 146 completed the primary immunization and 43 adults received a booster dose. During primary and booster vaccination, for any formulation, ≤8.9% of doses were followed by grade 3 solicited local or general adverse events. No fever >39.5 °C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following ≤33.3% of investigational vaccine doses. No serious adverse events were reported for adults receiving investigational vaccine formulations. Formulations containing dPly with or without PhtD were immunogenic for these antigens; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides.

Conclusion

Investigational vaccine formulations containing dPly and PhtD were well tolerated and immunogenic when administered to healthy adults as standalone protein vaccine or combined with PHiD-CV conjugates.     

Surgical site infections and mortality in elderly patients

Objective

We present the characteristics and outcome of surgical site infections (SSI) in patients 65 years of age or more, and determine the factors influencing mortality.

Methods

We conducted a prospective observational cohort study, comparing patients who survived with those who died, to identify risk factors associated with mortality among elderly patients presenting with SSI. The diagnosis of SSI was made for each patient, according to the CDC's standardized criteria.

Results

Seventy-five patients presenting with SSI were included in the study. The mean age of patients was 75 ± 6 (65–92), 68% were male patients. The most frequently isolated pathogen was Acinetobacter baumannii (n = 24). The overall in-hospital mortality rate was 25.3%. The statistical analysis revealed that gastrointestinal surgery, organ/space infections, polymicrobial infections, and higher SOFA scores were significantly associated with hospital mortality (P = 0.005, P = 0.0001, P = 0.047, P = 0.0001). According to laboratory tests, higher white blood cell (WBC) and neutrophil count, higher total bilirubin level, and lower thrombocyte count and albumin levels were significantly associated with hospital mortality (P = 0.040, P = 0.014, P = 0.001, P = 0.019, P = 0.002). Multivariate analyses revealed that serum albumin (P = 0.004, OR = 11.3, CI 95% 2.16–59.07), organ/space SSI (P = 0.0001, OR = 11.65, CI 95% 3.003–45.21), and SOFA score (P = 0.030, OR = 2.742, 1.100–6.84) were independent risk factors associated with mortality.

Conclusions

Serum albumin levels, organ/space infections, and higher SOFA scores were independently significantly associated with hospital mortality in older patients with SSI. Serum albumin levels should be closely monitored, and if necessary, early surgery should be performed.     

Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)

Background

Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence.

Methods

A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficile infection (CDI). Twenty-nine subjects received a single intravenous infusion of 10 mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion.

Findings

CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p = NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20 μg/ml, respectively; p = 0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p = 0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p = 0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p < 0.001), anti-toxin A at day 28 (p < 0.001) and infection with the BI/NAP1/027 strain at enrollment (p = 0.002) were all predictive of CDI recurrence.

Interpretation

In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.     

Liver stiffness values in HIV-infected patients with isolated anti-hepatitis B core antibodies

Background

Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population.

Methods

We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values.

Results

Fifty-one out of 69 patients (74%) had low LSV (≤ 7.1 kPa). In univariate analysis, high LSV (> 7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0–62.9; P = 0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1–20.7; P = 0.031) remained associated with high liver stiffness values.

Conclusions

Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients.     

Parental and community acceptance of the benefits and risks associated with meningococcal B vaccines

Objective

A new meningococcal serogroup B (Men B) vaccine has been licensed in the European Union (EU) and Australia. This study aimed to assess community and parental attitudes to introduction of new Men B vaccines and identify facilitators and barriers to vaccine implementation.

Methods

Cross-sectional survey including face-to-face interviews with adolescents, parents and adults from randomly selected households in South Australia in 2012. Survey data were weighted to the age, gender and geographical area profile of the population.

Results

3055 interviews were conducted with individuals aged 15–97 years, including 966 parents. Participation rate was 66.4%. 82.5% (95% CI 79.7–85.4) of parents (797/966) wanted their child to receive the Men B vaccine, with 12.2% (9.7–14.7) (118/966) unsure. Main parental concerns included potential side effects (41.3% (26.7–46.0)) and adequate vaccine testing (11.7% (9.4–14.1)). Potential for an extra injection at an immunisation visit resulted in 15.7% (12.8–18.5) of parents (n = 152/966) less likely to have their child immunised. Potential redness/swelling at the injection site or mild/moderate fever resulted in only 8.5% (6.3–10.7) and 10.8% (8.5–13.2) of parents, respectively, less likely to have their child immunised. Children being up to date with vaccinations and recommendation from family physician were the strongest independent predictors of parents agreeing their children should be immunised with Men B vaccine (OR = 6.58; p = 0.006 and OR = 4.15; p < 0.001, respectively). Only 16.4% (14.9–17.9) of adults (501/3055) stated that they would not want to receive a Men B vaccine, with family physician recommendation the strongest independent predictor of acceptance (OR = 3.81; p < 0.001).

Conclusions

There is strong community support for introduction of Men B vaccines, with parental willingness to have children immunised, impacted more by number of injections than potential for adverse events such as local reactions or fever.