Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents

BackgroundChildren and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies.MethodsPubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models.ResultsAmong the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17).ConclusionsThe immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.     

Immunogenicity,safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children

Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3–14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p < 0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p < 0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p < 0.01 for GMT values and p < 0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.     

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p = 0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p = 0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV.     

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n = 52), lineage drift (n = 15) and lineage mismatch (n = 43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.     

Efficacy of 23-valent pneumococcal polysaccharide vaccine in preventing community-acquired pneumonia among immunocompetent adults: A systematic review and meta-analysis of randomized trials

BackgroundData on the efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing adult community-acquired pneumonia (CAP) among the target population of individuals aged over 65 years and high-risk individuals aged 19–64 years are conflicting. As the Advisory Committee on Immunization Practices (ACIP) has recently demonstrated PPV-23 is likely beneficial to immunocompromised adults by the Grading, Assessment, Development, and Evaluation (GRADE) framework, we conducted meta-analysis to examine its efficacy in an immunocompetent population.MethodsWe searched the PUBMED, EMBASE, and Cochrane Library databases for randomized trials. Overall relative risks (RRs) with 95% confidential intervals (CIs) were calculated, and the Cochrane Q test (p, I²) was performed. Outcomes were assessed by the GRADE framework.ResultsSeven randomized trials involving 156,010 participants were included in this meta-analysis. High-quality evidence revealed that PPV-23 was weakly associated with the prevention of all-cause pneumonia ([RR] 0.87, [95%CI] 0.76–0.98, p = 0.11, I² = 43%), especially among the target population ([RR] 0.72, [95%CI] 0.69–0.94, p = 0.58 I² = 0%), the elderly group aged over 40 years ([RR] 0.80, [95%CI] 0.69–0.94) and the Japanese population ([RR] 0.72, [95%CI] 0.59–0.88, p = 0.24, I² = 30%). The target population included adults aged over 65 years and patients at high risk of pneumonia due to chronic lung disease, chronic obstructive pulmonary disease or living in a nursing home. Protective trends of PPV-23 in the outcomes of pneumococcal pneumonia ([RR] 0.54, [95%CI] 0.18–1.65, p = 0.01, I² = 77%) and mortality due to pneumonia ([RR] 0.67, [95%CI] 0.43–1.04, p = 0.67, I² = 0%) were observed, although the results were statistically insignificant, possibly due to the small number of trials included. PPV-23 did not prevent all-cause mortality ([RR] 1.04, [95%CI] 0.87–1.24, p = 0.95, I² = 0%).ConclusionsPPV-23 provided weak protection against all-cause pneumonia in an immunocompetent population, especially among the target population. The additional benefit of PPV-23 in preventing CAP further supports its application in the target population.     

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection

BackgroundApproaches to improve the immune response of immunocompromised patients to influenza vaccination are needed.MethodsChildren and young adults (3–21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine.ResultsEighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p = 0.27 and 0.09 after dose 1 and 2, respectively).ConclusionHD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV.     

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial

BackgroundCytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development.MethodsCMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens.Results402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: −36; 76, p = 0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: −9; 72, p = 0.08.ConclusionThe vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

四价流感病毒灭活疫苗在18~64岁人群免疫原性和安全性的系统综述和Meta分析

目的 用Meta分析的方法评价四价流感病毒灭活疫苗在18~64岁人群的免疫原性（抗体保护率和抗体阳转率）。方法 检索Medline、Cochrane Library、Science Direct数据库,将近10年内发表的比较18~64岁人群接种四价流感病毒灭活疫苗和三价流感病毒灭活疫苗免疫原性的临床随机对照试验纳入分析。采用Revman 5.3软件对纳入文献数据进行Meta分析。结果 共纳入8篇文献,针对甲型流感株（A/H1N1、A/H3N2）的抗体保护率和抗体阳转率,两种疫苗的反应差异无统计学意义;针对不含乙型流感株B/Victoria的三价流感病毒灭活疫苗,四价流感病毒灭活疫苗抗体保护率的合并RR值为1.28（95% CI：1.08~1.51,P<0.05）,抗体阳转率的合并RR值为1.94（95% CI：1.50~2.50,P<0.05）;针对不含乙型流感株B/Yamagata的三价流感病毒灭活疫苗,四价流感病毒疫苗抗体保护率的合并RR值为1.10（95% CI：1.02~1.18,P<0.05）,抗体阳转率的合并RR值为1.99（95% CI：1.34~2.97,P<0.05）,差异有统计学意义。结论 18~64岁人群中,四价流感病毒灭活疫苗与三价流感病毒灭活疫苗对于相同的疫苗株产生的免疫原性无差异,对于三价流感病毒灭活疫苗中不含的乙型疫苗株能产生良好的免疫效果。     

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults

Purpose

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009–2010 TIV) or a Yamagata B-lineage strain (2008–2009 TIV).

Methods

Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009–2010 TIV, 2008–2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination.

Results

One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009–2010 and 2008–2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT_QIV/GMT_TIV > 0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups.

Conclusion

QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages.     

Pooled-sera hSBA titres predict individual seroprotection in infants and toddlers vaccinated with 4CMenB

The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) disease, has been extensively assessed in hSBA using pooled sera, directly or through the Meningococcal Antigen Typing System (MATS). The extent to which pooled-sera hSBA titres reflect individual protection is not yet fully understood.We analysed more than 17000 individual hSBA titres from infants and toddlers vaccinated with 4CMenB, pooled-serum hSBA titres from subsets therein and MATS data from a 40 strain panel representative of invasive MenB disease in England and Wales.Individual hSBA titres segregated in two normal distributions, respectively from responding and non-responding subjects (fit_model-data: r = 0.996, p-values <0.05). No individual subject showed abnormally high titres compared to the distributions. Also, when sera from the same subjects were tested individually and in pool, pooled-sera titre and average of individual titres from the same group were substantially indistinguishable (r = 0.97, p-value <<0.001).We identified a robust mathematical relationship between the mean of individual hSBA titres and the proportion of subjects achieving a protective titre (seroprotection rate, r = 0.95, p-value <<0.001). Using this relation, the seroprotection rate in 15 groups of vaccinees tested against 11 diverse meningococcal isolates was accurately predicted by the hSBA titre of the respective pooled sera (average prediction error 9%).Finally, strains defined covered by MATS had on average 77% predicted seroprotection rate (interquartile range, IQR: 66–100%) and 39% for non-covered strains (IQR: 19–46%).We conclude that seroprotection rates in infants and toddlers vaccinated with 4CMenB can be accurately predicted by pooled-serum hSBA, and that strain coverage defined by MATS is associated with high seroprotection rates.SummaryThe Serum Bactericidal Antibody assay (SBA) from individual sera is a surrogate of protection for meningococcal vaccines. We show that SBA performed on pooled sera predicts individual protection.     

Effect of multiple,simultaneous vaccines on polio seroresponse and associated health outcomes

BackgroundAdministration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults.MethodWe retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent.ResultsThe >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p < 0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p > 0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p < 0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p > 0.1).ConclusionA combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations.     

Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population

AimsTo investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach.MethodsA total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48 weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48 weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1.ResultsThe end of virological response (EVR) rate was 45.8% (97/212) and the sustained virological response (SVR) rate was 45.7% (58/127). Meanwhile, 35.4% (75/212) achieved HBeAg seroconversion at the end of treatment. In a multivariate analysis, the rs2464 CC genotype was independently associated with EVR (OR 2.21, 95% CI 1.23–3.98, P = 0.008) and SVR (OR 2.34, 95% CI 1.05–5.20, P = 0.037) after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. Meanwhile, rs2464 CC genotype were also independently associated with decline of HBsAg levels below 1500 IU/mL at 12 weeks of treatment (OR 2.52, 95% CI 1.01–6.29, P = 0.047). Furthermore, three SNPs were found to be independently associated with HBeAg seroconversion at the end of treatment. (1) The rs2326369 CC genotype was independently associated with no HBeAg seroconversion (OR 0.52, 95% CI 0.29–0.95, P = 0.034); (2) The rs6515831 TT genotype was independently associated with HBeAg seroconversion (OR 2.11, 95% CI 1.14–3.90, P = 0.017); (3) The rs2464 CC genotype was independently associated with HBeAg seroconversion (OR 2.36, 95% CI 1.26–4.42, P = 0.007).ConclusionsPolymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.     

Response to active hepatitis B vaccination and mortality in incident dialysis patients

All patients with advanced chronic kidney disease or on renal replacement therapy should receive active hepatitis B vaccination. The aim of this retrospective cohort study was to investigate the association between the immune response to hepatitis B vaccination and all-cause, cardiovascular or infection-related mortality in incident dialysis patients starting dialysis between 2001 and 2008 (n = 426) in two Austrian dialysis centers. Vaccination response was defined as follows: absent anti-HBs antibody titer or a titer <10 IU/L was classified as non-response, seroconversion (SC) was defined as a titer ⩾10 IU/L, and seroprotection (SP) as a titer ⩾100 IU/L. Kaplan-Meier survival curves and multivariable adjusted Cox Proportional Hazards Models were used to determine the association between vaccination response and all-cause, cardiovascular and infection-related mortality. Of all patients 207 (48.6%) were non-responders, SC was observed in 219 (51.4%), SP in 118 (27.7%) patients. During a median follow-up of 51.2 months 228 (53.5%) patients died. Patients with SP and SC showed a significantly lower all-cause (p < 0.001 for both) and cardiovascular mortality (p = 0.006 for SP, p = 0.01 for SC). SP and SC were independently associated with a significant risk reduction for all-cause mortality (SP: HR 0.69, 95% CI 0.49–0.97, p = 0.03; SC: HR 0.72, 95% CI 0.55–0.95, p = 0.02). In conclusion, achieving seroconversion and seroprotection after active hepatitis B vaccination is associated with significantly reduced all-cause mortality in incident dialysis patients. This simple and readily available tool allows estimation of patient survival independently of other well-known key parameters such as age, gender, the presence of diabetes and markers of malnutrition and inflammation.     

Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis

BackgroundHuman papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes.MethodsWe performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes.ResultsOf 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78–91%) was higher than that for the quadrivalent vaccine (61%; 39–79%; p = 0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37–64%) was also higher than that for the quadrivalent vaccine (16%; 6–36%; p = 0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials.ConclusionsThese data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting.     

Risk of complications in patients who are obese following upper limb arthroplasty: A systematic review and meta-analysis

PurposeA systematic review was performed to investigate the impact of obesity on complications following total shoulder arthroplasty (TSA), reverse total shoulder arthroplasty (RTSA) and total elbow arthroplasty (TEA).MethodsElectronic databases and grey literature were searched for studies that evaluated the influence of obesity (Body Mass Index[BMI] ≥30 kg m²) on upper limb arthroplasty outcomes. Fifteen studies were identified, however only twelve reported predetermined outcomes. Unadjusted data was pooled in statistical meta-analysis where appropriate. Effect sizes were expressed as odds ratios (OR) for categorical data and weighted mean differences for continuous data.ResultsOdds of infection increased with increasing BMI, from 2.37 (95%CI [1.653.41]) times in patients who were obese, to greater than five times (OR = 5.04; 95%CI [4.705.39]) in patients who were morbidly obese. Furthermore, patients who were obese or morbidly obese had 3.92 (95%CI [3.594.28]) to 5.46 (95%CI [4.916.07]) times greater odds of venous thromboembolism (VTE) compared to their non-obese counterparts, respectively. Conversely, obesity had no influence on the odds of urinary tract infection (OR = 0.88; 95%CI [0.481.61], or mortality (OR = 1.79; 95%CI [0.794.03]). TSA/RTSA patients who were obese experienced operations 10.00 minutes longer (95%CI [6.3113.69]) than patients with a BMI in the normal range, which increased to 12.48 min utes (95%CI [8.4016.55]) in patients with a BMI ≥ 35.0. Evidence examining the influence of obesity on blood transfusion was inconclusive, while minimal evidence was available on pneumonia.ConclusionSurgeons should consider advising patients who are obese of the greater risk of VTE and infection when considering elective upper limb arthroplasty. However, noteworthy limitations surrounded the lack of information regarding prophylaxis regimes and BMI measurement tools used in included studies.     

Measles seroprevalence in Chiradzulu district,Malawi: Implications for evaluating vaccine coverage

IntroductionSelf-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies.MethodsAs part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012.ResultsA total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive.Older age (OR = 1.11 per year increase in age; 95%CI: 1.09–1.14) and being female (OR = 1.90; 95%CI: 1.26–2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR) = 0.44; 95% confidence interval (CI): 0.22–0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR = 1.31; 95%CI: 0.49–3.51).Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages.Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific.ConclusionReported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.     

Short and long-term immunogenicity and safety following the 23-valent polysaccharide pneumococcal vaccine in juvenile idiopathic arthritis patients under conventional DMARDs with or without anti-TNF therapy

ObjectivesTo assess immunogenicity and safety of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in juvenile idiopathic arthritis (JIA) patients under conventional DMARDs with or without anti-TNF therapy. The influences of demographic data, disease activity and treatment on immune response and the potential deleterious effects of vaccine on disease itself were also evaluated.Methods17 JIA patients immediately pre-etanercept (Group 1) and 10 JIA patients on stable dose of methotrexate (Group 2) received one dose of PPV23. All patients were evaluated pre-vaccination, 2 months and 12 months post-vaccination for seven pneumoccocal serotypes. Serology was performed by enzyme immunoassay and the immunogenicity endpoints included seroprotection (SP), seroconversion (SP) and geometric mean concentration of antibodies(GMC). Clinical and laboratorial parameters of JIA were evaluated before and after vaccination.ResultsGroups 1 and 2 were comparable regarding age, gender, disease duration and other DMARDs use (p > 0.05). Pre-immunization SP and GMC were alike in patients with and without anti-TNF therapy (p > 0.05). The frequencies of patients achieving adequate vaccine response (seroconversion in ≥50% of all serotypes) at 2 months (53 vs. 30%, p = 0.424) and 12 months (36 vs. 40%, p = 1.0) were similar in JIA patients with and without anti-TNF therapy. Further comparison of patients with and without adequate response at 2 months revealed no influence of demographic, clinical and laboratorial JIA parameters (p > 0.05). Serious adverse events were not observed.ConclusionsAnti-TNF therapy in JIA patients does not seem to have an additional deleterious effect on short/long-term PPV23 immunogenicity compared to MTX alone and no influence on disease parameters was observed with this vaccine.     

Influenza during pregnancy: Incidence,vaccination coverage and attitudes toward vaccination in the French web-based cohort G-GrippeNet

IntroductionPregnancy is a risk factor for severe influenza. However, data on influenza incidence during pregnancy are scarce. Likewise, no data are available on influenza vaccine coverage in France since national recommendation in 2012. We aimed to assess these points using a novel nationwide web-based surveillance system, G-GrippeNet.MethodsDuring the 2014/2015 influenza season, pregnant women living in metropolitan France were enrolled through a web platform (https://www.grippenet.fr/). Throughout the season, participants were asked to report, on a weekly basis, if they had experienced symptoms of influenza-like-illness (ILI). ILI episodes reported were used to calculate incidence density rates based on period of participation from each participant. Vaccination coverage was estimated after weighing on age and education level from national data on pregnant women. Factors associated with higher vaccination coverage were obtained through a logistic regression with Odds Ratio (OR) corrected with the Zhang and Yu method.ResultsA total of 153 women were enrolled. ILI incidence density rate was 1.8 per 100 person-week (95%CI, 1.5–2.1). This rate was higher in women older than 40 years (RR = 3.0, 95%CI [1.1–8.3], p = 0.03) and during first/second trimesters compared to third trimester (RR = 4.0, 95%CI [1.4–12.0], p = 0.01). Crude vaccination coverage was 39% (95%CI, 31–47) and weighted vaccination coverage was estimated at 26% (95%CI, 20–34). Health care provider recommendation for vaccination (corrected OR = 7.8; 95%CI [3.0–17.1]) and non-smoking status (cOR = 2.1; 95%CI [1.2–6.9]) were associated with higher vaccine uptake.ConclusionThis original web based longitudinal surveillance study design proved feasible in pregnant women population. First results are of interest and underline that public health policies should emphasize the vaccination promotion through health care providers.     

Séroprévalence des marqueurs de l’infection chez les donneurs de sang à Niamey (Niger)

BackgroundThe study aimed to determine the seroprevalence of transfusion-transmitted infectious (TTI) markers for human immunodeficiency virus (HIV), hepatitis B and C viruses (HBV, HCV) and syphilis among blood donors in Niamey (Niger). The association between seroprevalence of ITT markers and sociodemographic characteristics of blood donors was investigated.MethodsA cross-sectional study was conducted in 2010 among 3213 blood donors. Data were collected from a pre-donation questionnaire and from laboratory tests results.ResultsThe male/female ratio was 4/1. Up to 18.1% of donations had at least one positive marker, in which 2.7% presented a positive test for two or more agents. A seroprevalence of 1.62% (95%CI: 1.21–2.12) was associated with HIV, 15.4% (13.9–16.7) with HBV, 1.18% (0.84–1.62) with HCV, and 0.47% (0.26–0.77) for blood samples reacted with RPR test for syphilis. The HIV seroprevalence was two-fold higher in family than in volunteer donors (OR = 2.15, 95%CI: 1.24–3.73). It was also higher in Rhesus D negative donors (OR = 2.40, 95%CI: 1.11–5.17). The hepatitis B surface antigen seroprevalence was significantly higher in males than females (OR = 1.85, 95%CI: 1.39–2.45) and in first time than in regular donors (P < 0.0001). The HCV seroprevalence was significantly higher in male donors (OR = 4.41, 95%CI: 1.06–18.4) and in donors from rural areas (OR = 4.09, 95%CI: 1.42–11.8). Syphilis marker was significantly associated with the marital status (higher seroprevalence in divorced donors, P = 0.0085).ConclusionPrevalence of TTI markers is high and national strategies for safe blood transfusion have to be strengthened. It is essential to recruit and maintain more volunteer donors, while females should be encouraged to donate blood.