Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

BackgroundThere is increasing recognition of the role of B cell dysfunction in HIV pathogenesis, but little is known about how these perturbations may influence responses to vaccinations.MethodsHealthy controls (n = 16) and antiretroviral therapy (ART)-treated aviremic HIV-infected subjects (n = 26) receiving standard-of-care annual influenza vaccinations were enrolled in the present study. Total bacterial 16 S rDNA levels were assessed by quantitative polymerase chain reactions in plasma. Serologic responses were characterized by ELISA, hemagglutination inhibition assay (HI), and microneutralization, and cell-mediated responses were assessed by ELISPOT (antigen-specific IgG+ antibody-secreting cells (ASCs)) and flow cytometry at pre-vaccination (D0), day 7–10 (D7) and day 14–21 (D14) post-vaccination.ResultsDecreased peripheral CD4+ T cell absolute counts and increased frequencies of cycling and apoptotic B cells were found at baseline in HIV-infected subjects relative to healthy controls. In healthy controls, post-vaccination neutralizing activities were related to the frequencies of vaccine-mediated apoptosis and cycling of B cells, but not to CD4+ T cell counts. In patients, both baseline and post-vaccination neutralizing activities were directly correlated with plasma level of bacterial 16S rDNA. However, overall vaccine responses including antibody titers and fold changes were comparable or greater in HIV-infected subjects relative to healthy controls.ConclusionB cell function correlates with measures of recall humoral immunity in response to seasonal influenza vaccination in healthy controls but not in ART-treated patients.     

Hepatitis B vaccination uptake and correlates of serologic response among HIV-infected and uninfected men who have sex with men (MSM) in Bangkok,Thailand

BackgroundVaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM.MethodologyHBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses.Results511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p < 0.0001). Median pre-vaccination IgG was higher among non-responders than responders overall (1238.9.0 vs. 1057.0 mg/dL, p = 0.003) and among HIV-infected participants (1534.0 vs. 1244.5 mg/dL, p = 0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3 mg/dL, p = 0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV-negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1 mg/dL, respectively, p < 0.0001). Among HIV-infected participants, median CD4 count in non-responders was 378 cells/μL vs. 431 cells/μL in responders (p = 0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p = 0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p < 0.01).ConclusionsHIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure.     

Effects of prior influenza virus vaccination on maternal antibody responses: Implications for achieving protection in the newborns

BackgroundIn the US, influenza vaccination is recommended annually to everyone ≥6 months. Prior receipt of influenza vaccine can dampen antibody responses to subsequent vaccination. This may have implications for pregnant women and their newborns, groups at high risk for complications from influenza infection.ObjectiveThis study examined effects of prior vaccination on maternal and cord blood antibody levels in a cohort of pregnant women in the US.Study designInfluenza antibody titers were measured in 141 pregnant women via the hemagglutination inhibition (HAI) assay prior to receipt of quadrivalent influenza vaccine, 30 days post-vaccination, and at delivery (maternal and cord blood). Logistic regression analyses adjusting for age, BMI, parity, gestational age at vaccination, and year of vaccination compared HAI titers, seroprotection, and seroconversion in women with versus without vaccination in the prior year.ResultsCompared to those without vaccination in the previous year (n = 50), women with prior vaccination (n = 91) exhibited higher baseline antibody titers and/or seroprotection rates against all four strains after controlling for covariates. Prior vaccination also predicted lower antibody responses and seroconversion rates at one month post-vaccination. However, at delivery, there were no significant differences in antibody titers or seroprotection rates in women or newborns, and no meaningful differences in the efficiency of antibody transfer, as indicated by the ratio of cord blood to maternal antibody titers at the time of delivery.ConclusionIn this cohort of pregnant women, receipt of influenza vaccine the previous year predicted higher baseline antibody titers and decreased antibody responses at one month post-vaccination against all influenza strains. However, prior maternal vaccination did not significantly affect either maternal antibody levels at delivery or antibody levels transferred to the neonate. This study is registered with the NIH as a clinical trial (NCT02148874).     

Safety,immunogenicity and shedding of LAIV4 in HIV-infected and uninfected children

ObjectivesHIV-infected children have poor responses to inactivated influenza vaccines. Live vaccines (LAIVs) are highly efficacious in children, but they are not used in HIV-infected children du e to limited information. We investigated the safety, immunogenicity and viral shedding of LAIV4 in HIV-infected compared with uninfected children.DesignForty-six HIV-infected and 56 uninfected children 2 to 25 years old, who had been previously vaccinated against influenza, consented to receive a single dose of LAIV4. All grade adverse events (AEs) were recorded in the first month post-vaccination and serious AEs (SAEs) throughout the influenza season. Nasopharyngeal swabs for influenza PCR and IgA ELISA and blood for hemagglutination inhibition antibody (HAI) measurements were collected at entry, 2–5, 7–10 and 21–28 days post-vaccination.ResultsThe HIV-infected subjects had median CD4+ cells of 649 cells/μL and plasma HIV RNA of 20 copies/mL. AEs were similar in the two groups. There were no vaccine-related SAEs. Shedding of ≥1 vaccine virus was detected in 67% HIV-infected and 50% uninfected participants (p = 0.14). HAI titers did not appreciably change, but mucosal IgA antibodies significantly increased post-vaccination in both groups. High baseline HAI and IgA antibody concentrations were associated with decreased viral shedding in controls, but not in HIV-infected subjects. Similar proportions of HIV-infected vaccinees and controls reported influenza-like illnesses (12% and 6%) throughout the season.ConclusionsLAIV4 was equally safe and immunogenic and caused similar viral shedding in HIV-infected and uninfected children. A correlate of protection against vaccine viral shedding was not identified in HIV-infected participants, although both circulating and mucosal antibodies correlated with protection in controls.     

Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines facilitates their uptake by older adults; however, data on immunogenicity and safety of concomitant administration of adjuvanted trivalent inactivated influenza vaccine (aIIV3) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) have not been reported.MethodsSubjects aged ≥65 years (N = 224) were randomized 1:1:1:1 to receive MF59-aIIV3 alone, MF59-aIIV3 + PPSV23 in contralateral arms, MF59-aIIV3 + PPSV23 in the same arm or PPSV23 alone (Clinical Trial Number – NCT02225327). Hemagglutination inhibition assay and multiplex opsonophagocytic killing assay were used to compare immunogenicity after single or concomitant vaccination.ResultsAll groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroconversion rates and geometric mean fold-increases, irrespective of concomitant vaccinations and injection site. For each pneumococcal serotype, opsonic index (OI) increased markedly after the PPSV23 vaccination, irrespective of the concomitant influenza vaccine. All subjects showed an OI ≥ 8 for serotypes 6B, 18C and 19A post-vaccination, with a suggestion that the ipsilateral concomitant vaccination might be associated with higher OIs for some antigens. Local and systemic adverse events were more common in subjects receiving PPSV23 compared to those receiving aIIV3 alone.ConclusionsNo interference was observed with antibody responses to influenza or pneumococcal antigens when aIIV3 and PPSV23 were administered concomitantly.     

Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial

ObjectivesOlder adults are less able to produce a protective antibody response to vaccinations. One factor that contributes to this is immune ageing. Here we examined whether diurnal variations in immune responses might extend to the antibody response to vaccination.DesignWe utilised a cluster-randomised trial design.Setting24 General Practices (GPs) across the West Midlands, UK who were assigned to morning (9–11 am; 15 surgeries) or afternoon (3–5 pm; 9 surgeries) vaccination times for the annual UK influenza vaccination programme.Participants276 adults (aged 65+ years and without a current infection or immune disorder or taking immunosuppressant medication).InterventionsParticipants were vaccinated in the morning or afternoon between 2011 and 2013.Main outcome measuresThe primary outcome was the change in antibody titres to the three vaccine influenza strains from pre-vaccination to one month post-vaccination. Secondary outcomes of serum cytokines and steroid hormone concentrations were analysed at baseline to identify relationships with antibody responses.ResultsThe increase in antibody levels due to vaccination differed between morning and afternoon administration; mean difference (95% CI) for H1N1 A-strain, 293.3 (30.97–555.66) p = .03, B-strain, 15.89 (3.42–28.36) p = .01, but not H3N2 A-strain, 47.0 (−52.43 to 146.46) p = .35; those vaccinated in the morning had a greater antibody response. Cytokines and steroid hormones were not related to antibody responses. No adverse events were reported.ConclusionsThis simple manipulation in the timing of vaccine administration to favour morning vaccination may be beneficial for the influenza antibody response in older adults, with potential implications for vaccination strategies generally.Trial registrationThis trial is registered with the ISRCTN (ISRCTN70898162).     

Vitamine D chez la personne âgée : pourquoi ? Quand ? Comment ?

Vitamin D deficiency is reported in young and older adults. However, elderly persons represent an important target for supplementation. First, aging of the skin reduces vitamin D synthesis. Second, lifestyle or dependency results in low sun exposure. More importantly, the effect of vitamin D deficiency may become more rapidly apparent in aging subjects with poorer bone and muscle reserve. Interventional studies that have shown positive clinical results of vitamin D supplementation have been conducted in aging subjects. Vitamin D supplementation reduces the risk of fracture and falls in the elderly, costs little, and this could have a major impact on public health. It is recommended to systematically supplement all elderly persons with vitamin D, with doses ranging from 800 to 1000 UI/day, either daily or 80,000 to 100,000 UI every 2–3 months.     

Elevated systolic blood pressure of children in the United States is associated with low serum 25-hydroxyvitamin D concentrations related to body mass index: National Health and Examination Survey 2007-2010

A negative association between serum 25-hydroxyvitamn D (25[OH]D) concentrations and blood pressure has been found in adults; whether a similar relationship exists in children remains unclear. We hypothesized that serum 25(OH)D concentrations of children would negatively correlate with blood pressure. Using a nationally representative sample of children aged 8 to 18 years from the National Health and Nutrition Examination Survey 2007-2010 (n = 2908), we compared serum 25(OH)D levels with diastolic and systolic blood pressure by vitamin D nutritional status categories. A high percentage of children were either vitamin D deficient (28.8%) or vitamin D insufficient (48.8%). Prehypertension was defined as blood pressure as ≥90th to <95th percentile and hypertension as ≥95th percentile by age, height, and sex national blood pressure percentile norms for children. Vitamin D–deficient children aged 8 to 13 years had higher systolic blood pressure (104.8 ± 0.7 mm Hg) than did vitamin D–sufficient children (102.3 ± 0.6 mmHg; P < .05). Controlling for age, sex, race/ethnicity, and income, systolic blood pressure was inversely associated with serum 25(OH)D concentrations (P < .03), but not when also controlling for body mass index (P = .63). A higher percentage of vitamin D–deficient and vitamin D–insufficient children (1.7%) vs vitamin D–sufficient children (0.6%) had prehypertension or hypertension. In conclusion, the association of low serum 25(OH)D concentrations with elevated systolic blood pressure in children is likely related to body weight and markers of adiposity.     

Knowledge of influenza vaccination recommendation and early vaccination uptake during the 2015–16 season among adults aged ≥18 years – United States

BackgroundSince 2010, the Advisory Committee on Immunization Practices (ACIP) has recommended that all persons aged ≥6 months receive annual influenza vaccination.MethodsWe analyzed data from the 2015 National Internet Flu Survey (NIFS), to assess knowledge and awareness of the influenza vaccination recommendation and early influenza vaccination coverage during the 2015–16 season among adults. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with adults’ knowledge and awareness of the vaccination recommendation and early vaccine uptake during the 2015–16 influenza season.ResultsAmong the 3301 respondents aged ≥18 years, 19.6% indicated knowing that influenza vaccination is recommended for all persons aged ≥6 months. Of respondents, 62.3% indicated awareness that there was a recommendation for influenza vaccination, but did not indicate correct knowledge of the recommended age group. Overall, 39.9% of adults aged ≥18 years reported having an influenza vaccination. Age 65 years and older, being female, having a college or higher education, not being in work force, having annual household income ≥$75,000, reporting having received an influenza vaccination early in the 2015–16 season, having children aged ≤17 years in the household, and having high-risk conditions were independently associated with a higher correct knowledge of the influenza vaccination recommendation.ConclusionsApproximately 1 in 5 had correct knowledge of the recommendation that all persons aged ≥6 months should receive an influenza vaccination annually, with some socio-economic groups being even less aware. Clinic based education in combination with strategies known to increase uptake of recommended vaccines, such as patient reminder/recall systems and other healthcare system-based interventions are needed to improve vaccination, which could also improve awareness.     

Humoral immune response following the inactivated quadrivalent influenza vaccination among HIV-infected and HIV-uninfected adults

BackgroundA limited amount of information is available about the immunogenicity of the quadrivalent inactivated influenza vaccine among human immunodeficiency virus (HIV)-infected individuals, especially in low and middle-income countries (LMICs).MethodsHIV-infected adults and HIV-uninfected adults received a dose of quadrivalent inactivated influenza vaccine including strains of H1N1, H3N2, BV and BY. Enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition assay (HAI) were used to determine IgA, IgG antibody concentration and geometric mean titers (GMT) at day 0 and day 28, respectively. Associated factors contributing to seroconversion or GMT changes were analyzed using simple logistic regression model.ResultsA total of 131 HIV-infected and 55 HIV-uninfected subjects were included in the study. In both HIV-infected and uninfected arms, IgG and IgA against influenza A and B all increased significantly at day 28 after receiving QIV (P < 0.001). GMTs of post-vaccination at day 28 showed that HIV-infected persons with CD4 + T cell counts ≤ 350 cells/mm³ were statistically less immunogenic to all strains of QIV than HIV-uninfected ones (P < 0.05). HIV-infected participants with CD4 + T cell counts ≤ 350 cells/mm³ were less likely to achieve seroconversion to QIV (H1N1, BY and BV) than HIV-uninfected individuals at day 28 after vaccination (P < 0.05). Compared with HIV-infected patients with baseline CD4 + T cell counts ≤ 350 cells/mm³, individuals with baseline CD4 + T cell counts > 350 cell/mm³ seemed more likely to generate antibody responses to H1N1 (OR:2.65, 95 %CI: 1.07–6.56) and BY (OR: 3.43, 95 %CI: 1.37–8.63), and showed a higher probability of seroconversion to BY (OR: 3.59, 95 %CI: 1.03–12.48). Compared with nadir CD4 + T cell count ≤ 350 cell/mm³, individuals with nadir CD4 + T cell count > 350 cell/mm³ showed a higher probability of seroconversion to H1N1(OR: 3.15, 95 %CI: 1.14–8.73).ConclusionInfluenza vaccination of HIV-infected adults might be effective despite variable antibody responses. HIV-positive populations with CD4 + T cell counts ≤ 350 are less likely to achieve seroconversion. Further vaccination strategies could be developed for those with low CD4 T cell counts.     

High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses

High-dose (HD) influenza vaccine shows improved relative efficacy against influenza disease compared to standard-dose (SD) vaccine in individuals ⩾65 years. This has been partially credited to superior serological responses, but a comprehensive understanding of cell-mediated immunity (CMI) of HD vaccine remains lacking. In the current study, a total of 105 participants were randomly administered HD or SD vaccine and were evaluated for serological responses. Subsets of the group (n = 12–26 per group) were evaluated for B and T cell responses at days 0, 7, 14 and 28 post-vaccination by flow cytometry or ELISPOT assay. HD vaccine elicited significantly higher hemagglutination inhibition (HI) titers than SD vaccine at d28, but comparable titers at d365 post-vaccination. HD vaccine also elicited higher vaccine-specific plasmablast responses at d7 post-vaccination than SD vaccine. However, long-lived memory B cell induction, cytokine-secreting T cell responses and persistence of serological memory were comparable regardless of vaccine dose. More strategies other than increased Ag amount may be needed to improve CMI in older adults.Trial Registration: ClinicalTrials.gov NCT 01189123     

Tetanus Toxoid carrier protein induced T-helper cell responses upon vaccination of middle-aged adults

IntroductionVaccines frequently induce suboptimal immune responses in the elderly, due to immunological ageing. Timely vaccination may be a strategy to overcome this problem, which classifies middle-aged adults as an interesting target group for future vaccine interventions. However, the immunological fitness of the middle-aged population is ill-defined. It is currently unknown whether effective T-cell help towards B-cells is initiated by conjugate-carrier vaccines at middle-age.AimWe characterized systemic Tetanus Toxoid (TT) specific T-helper cell responses in the circulation of middle-aged adults (50–65 years of age, n = 31) having received the MenACWY-TT vaccination.MethodsBlood samples were taken pre- as well as 7 days, 28 days, and 1 year post-vaccination. TT-specific T-cell responses were determined by IFNγ Elispot and by the secretion of IFNγ, IL13, IL10, IL17, and IL21 in cell culture supernatants. Circulating CD4+CXCR5+ICOS+IL21+ cells were analyzed by flow cytometry, and meningococcal and TT-specific IgG responses by bead-based immunoassays. The correlation between the T-cell help and humoral responses was evaluated.ResultsVaccination with a TT-carrier protein induced a mixed TT-specific Th1 (IFNγ), Th2 (IL13, IL10), and Th17 (IL17) response in most participants. Additionally, circulating CD4+CXCR5+ICOS+IL21+ cells were significantly increased 7 days post-vaccination. Pre-vaccination TT-specific cytokine production and post-vaccination Th2 responses correlated positively with the increase of CD4+CXCR5+ICOS+IL21+ cells. No correlation between T-cell help and antibody responses was found.ConclusionThe characteristics of the T-cell response upon a TT-carrier vaccination suggests effective T-cell help towards B-cells in response to meningococcal polysaccharides, although the absence of a correlation with the antibody responses warrants further clarification. However, the robust T-helper cell response in middle-aged adults, decades after previous TT vaccinations, strengthens the classification of this age group for future vaccine interventions in the context of population ageing.     

Humoral,T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

BackgroundWe analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.Methods71 kidney and heart transplant recipients (basiliximab [n = 43] and ATG [n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.ResultsMedian time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10⁶ PBMC, p = 0.0007), but no differences between treatment groups were observed (p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy.ConclusionsAfter influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.     

Longitudinal study on Streptococcus pneumoniae,Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine

BackgroundStreptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are all potentially pathogenic, which frequently colonize the nasopharynx (NP) prior to causing disease.We studied bacterial NP-colonization in 321 HIV-infected and 243 HIV-uninfected children vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) at 6, 10 and 14 weeks of age.MethodsHIV-uninfected infants included those born to HIV-uninfected (HUU) and HIV-infected women (HEU); HIV-infected children with CD4+ lymphocyte ≥25% were randomized to initiate antiretroviral therapy immediately (ART-Immed) or when clinically indicated (ART-Def). Nasopharyngeal swabs for bacterial culture were taken prior to each PCV7 dose (Visits 1–3) and at 20, 39, 47 and 67 weeks of age (Visits 4–7). Swabs were cultured by standard methods and pneumococcal serotyping done by the Quellung method.ResultsColonization patterns for pneumococcus, H. influenzae and S. aureus did not differ between HUU and HEU children; and were also generally similar between ART-Def and ART-Immed children. Prevalence of PCV7-serotype colonization was similar between HIV-infected and HIV-uninfected children, however, overall pneumococcal and specifically non-vaccine serotype colonization tended to be lower in HIV-infected children. HIV-infected children also had a 44% lower prevalence of S. aureus colonization at Visit-1 (p = 0.010); and H. influenzae colonization was also lower among HIV-infected than HIV-uninfected children at Visit-2, Visit-3, Visit-6 and Visit-7.ConclusionVaccine-serotype colonization is similar in PCV-immunized HIV-infected and HIV-uninfected children. We, however, identified a lower prevalence of overall-pneumococcal and H. influenzae colonization in HIV-infected children post-PCV vaccination, the clinical-relevance of which warrants further study.     

Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines

BackgroundA recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection.MethodsThe original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6–8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1 − Rate Ratio) × 100.Results31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6–27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3–55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5–12.8%).ConclusionsCompared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults.     

Reasons for low influenza vaccination coverage among adults in Puerto Rico,influenza season 2013–2014

BackgroundInfluenza vaccination is recommended annually for all persons 6 months and older. Reports of increased influenza-related morbidity and mortality during the 2013–2014 influenza season raised concerns about low adult influenza immunization rates in Puerto Rico. In order to inform public health actions to increase vaccination rates, we surveyed adults in Puerto Rico regarding influenza vaccination-related attitudes and barriers.MethodsA random-digit-dialing telephone survey (50% landline: 50% cellphone) regarding influenza vaccination, attitudes, practices and barriers was conducted November 19–25, 2013 among adults in Puerto Rico. Survey results were weighted to reflect sampling design and adjustments for non-response.ResultsAmong 439 surveyed, 229 completed the survey with a 52% response rate. Respondents’ median age was 55 years; 18% reported receiving 2013–2014 influenza vaccination. Among 180 unvaccinated respondents, 38% reported barriers associated with limited access to vaccination, 24% reported they did not want or need influenza vaccination, and 20% reported safety concerns. Vaccinated respondents were more likely to know if they were recommended for influenza vaccination, to report greater perceived risk of influenza illness, and to report being less concerned about influenza vaccine safety (p-value < 0.05). Of the 175 respondents who saw a healthcare provider (HCP) since July 1, 2013, 38% reported their HCP recommended influenza vaccination and 17% were offered vaccination. Vaccination rates were higher among adults who received a recommendation and/or offer of influenza vaccination (43% vs. 14%; p-value < 0.01).ConclusionsFailure of HCP to recommend and/or offer influenza vaccination and patient attitudes (low perceived risk of influenza virus infection) may have contributed to low vaccination rates during the 2013–2014 season. HCP and public health practitioners should strongly recommend influenza vaccination and provide vaccinations during clinical encounters or refer patients for vaccination.     

Valeurs de référence de la vitamine D chez la Femme du Sud Tunisien

IntroductionTotal 25 Hydroxyvitamin D (25OHD) is currently considered as the most representative metabolite of vitamine D status. Low levels of Vitamin D have been reported in many countries even in sunnier regions especially in Tunisia. We aimed to establish a Vitamin D reference range in healthy South Tunisian women, using electrochimiluminesence assay.MethodsCross-sectional study has been conducted in the south of Tunisia including Tunisian healthy women. Each participant underwent a questionnaire, clinical examination, food survey and biological exploration. 25OHD reference range was determined according to the recommendations of the Clinical and Laboratory Standards Institute.Results279 women accepted to participate in the study, 21 were excluded for hypocalcemia with/without hyperparathyroidism. 258 women were included with a mean age of 41,29 ± 17,06 years. 72% of participants were dark-skinned vs. 28% with a light phototype. No participants reached the recommended daily intakes of vitamin D and calcium. The average of 25OHD was 7,88 ± 6,08 ng/mL (IC 95%: 7,06 et 8,7). 25OHD levels were lower in dark skinned (P = 0,06) and veiled women compared to others subgroups (P = 0,03).ConclusionThere are a multitude of challenges that still deserve to be addressed. Despite recent technologies advances, 25OHD assessment and standardization remains complicated and needs to be discussed with clinicians when establishing practical guidelines and diagnosis cutoffs.     

Vitamin D,cardio-inflammation,and endothelial dysfunction in older adults after orthopedic surgery: Results from an open-label trial to ameliorate cardiac function

ObjectivesAfter orthopedic surgery, clinical outcomes are affected by comorbid cardiovascular diseases (CVDs) and low 25-hydroxy-vitamin D (25-(OH)D). Myocardial function was suggested to be influenced by both the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) and the marker of endothelial dysfunction asymmetric dimethylarginine (ADMA).Material and methodsWe investigated TNFα and ADMA changes in association with serum levels of vitamin D and cardiac function in 47 older adults after major orthopedic surgery. Subjects were characterized for biochemical profiles and transthoracic echocardiographic measures. Assessments were done before and after the correction of hypovitaminosis D through a 6-month supplementation with calcifediol started at post-operative rehabilitation.ResultsThe means serum levels of both TNFα and ADMA reduced from 1.39 ± 0.47 pg/mL to 1.30 ± 0.37 pg/mL (P < 0.05) and from 0.69 ± 0.05 μmol/L to 0.68 ± 0.04 μmol/L (P < 0.05), respectively. Significant treatment effects were observed for systolic blood pressure (P < 0.05), left ventricular ejection function (P < 0.01), global longitudinal strain (P < 0.0001), 25-(OH)D (P < 0.001), and calcemia (P < 0.001).ConclusionAfter the normalization of low levels of vitamin D, we were able to observe a reduction of circulating TNFα and ADMA together with the amelioration of cardiac function. Even if our results suggest that vitamin D might exert cardiac effects indirectly through the decrease in cardio-inflammation and endothelial dysfunction, a better understanding of the precise molecular regulations should be better investigated.     

Predictors of reported influenza vaccination in HIV-infected women in the United States, 2006–2007 and 2007–2008 seasons

ObjectiveTo estimate the cumulative incidence of self-reported influenza vaccination (“vaccination coverage”) and investigate predictors in HIV-infected women.MethodsIn an ongoing cohort study of HIV-infected women in five US cities, data from two influenza seasons (2006–2007 n = 1209 and 2007–2008 n = 1161) were used to estimate crude and adjusted prevalence ratios (aPR) and 95% confidence intervals ([,]) from Poisson regression with robust variance models using generalized estimating equations (GEE).ResultsIn our study, 55% and 57% of HIV-infected women reported vaccination during the 2006–2007 and 2007–2008 seasons, respectively. Using data from both seasons, older age, non-smoking status, CD4 T-lymphocyte (CD4) count ≥ 200 cells/mm³, and reporting at least one recent healthcare visit was associated with increased vaccination coverage. In the 2007–2008 season, a belief in the protection of the vaccine (aPR = 1.38 [1.18, 1.61]) and influenza vaccination in the previous season (aPR = 1.66 [1.44, 1.91]) most strongly predicted vaccination status.ConclusionInterventions to reach unvaccinated HIV-infected women should focus on changing beliefs about the effectiveness of influenza vaccination and target younger women, current smokers, those without recent healthcare visits, or a CD4 count < 200 cells/mm³.