Introducing seasonal influenza vaccine in low‐income countries: an adverse events following immunization survey in the Lao People's Democratic Republic

Objective

In 2012, Lao PDR introduced seasonal influenza vaccine in pregnant women, persons aged ≥50 years, persons with chronic diseases, and healthcare personnel. We assessed adverse events following immunization (AEFI).

Methods

We used a multistage randomized cluster sample design to interview vaccine recipients.

Findings

Between April and May 2012, 355 902 were vaccinated. Of 2089 persons interviewed, 261 (12·5%) reported one or more AEFI. The most commonly reported AEFIs were local reactions. No hospitalizations or deaths were reported; 16% sought medical care. Acceptance and awareness of vaccination were high.

Conclusions

Following the introduction of seasonal influenza vaccine in Lao PDR, self-reported adverse events were mild.     

Influenza immunization practices and policies for health care students in Canada

BACKGROUND:

Influenza vaccine is recommended for all health care providers including health care students. Little is known about how health care student programs provide information about influenza vaccination to their students, deliver vaccines and document their vaccination status.

METHODS:

A mixed-methods approach was used and included key informant interviews of program coordinators for health care student programs in Halifax (Nova Scotia) and a national survey of program coordinators of health care student programs across Canada.

RESULTS:

All 21 coordinators of programs that had students placed at the IWK Health Centre (Halifax, Nova Scotia) during the influenza season were interviewed. Surveys were completed by 93 (36.3%) of 256 eligible coordinators representing 134 different programs (response rate 52.3%). Most programs encouraged seasonal influenza vaccination but only 28 (20.9%) required it. None of the Halifax programs delivered influenza vaccine and most preferred a coordinated, centrally administered program. In contrast, many programs across Canada delivered influenza vaccine and did not desire a centralized process.

CONCLUSION:

There is considerable variability in the delivery of influenza vaccine to health care students across Canada. Coordinated programs may be desirable where delivery programs do not already exist.     

Outcomes Associated with Influenza Vaccination in the First Year after Kidney Transplantation

Summary

Background and objectives

Influenza vaccination is recommended in all renal transplant recipients. However, immunosuppression in the early period post-transplant may attenuate the immunologic response to the vaccine. Additionally, it has been theorized that vaccination can induce an immune response that could trigger rejection episodes.

Design, setting, participants, & measurements

In a retrospective cohort of 51,730 adult Medicare primary patients who were first transplanted from January 2000 to July 2006 and followed through October 2006, we assessed Medicare claims for influenza vaccination and influenza infections, respectively. Outcomes included allograft loss and death.

Results

There were 9678 (18.7%) patients with claims for influenza vaccination in the first year post-transplant. Factors associated with vaccination included older age, diabetes, later year of transplant, and tacrolimus or mycophenolate at discharge. Vaccinations were less frequent among men, African Americans, highly sensitized patients, or those receiving induction immunosuppression or expanded criteria donor kidneys. Vaccination in the first year after transplant was associated with lower risk of subsequent allograft loss and death. Claims for influenza infection were reported in 310 (0.6%) patients and were not significantly associated with graft loss, although there was a trend toward death.

Conclusions

In the first year after renal transplantation, influenza vaccination was associated with a lower risk of subsequent allograft loss and death. Although this study cannot comment on formation of protective antibodies after vaccination, these data do not support withholding vaccination on the basis of concerns of adversely affecting allograft function.     

Effectiveness and knowledge,attitudes and practices of seasonal influenza vaccine in primary healthcare settings in South Africa, 2010–2013

Objectives

Influenza vaccine effectiveness (VE) and coverage data for sub-Saharan Africa are scarce. Using a test-negative case–control design, we estimated influenza VE annually among individuals with influenza-like illness presenting to an outpatient sentinel surveillance programme in South Africa from 2010 to 2013. A knowledge, attitudes and practices (KAP) influenza vaccine survey of programme clinicians was conducted in 2013.

Sample

In total, 9420 patients were enrolled in surveillance of whom 5344 (56.7%) were included in the VE analysis: 2678 (50.1%) were classified as controls (influenza test-negative) and 2666 (49.9%) as cases (influenza test-positive).

Results

Mean annual influenza vaccine coverage among controls was 4.5% for the four years. Annual VE estimates adjusted for age, underlying medical conditions and seasonality for 2010-2013 were 54.2% (95% confidence interval (CI): 2.4–78.6%), 57.1% (95% CI: 15.5–78.2%), 38.4% (95% CI: −71.7–78.1%) and 87.2% (95% CI: 67.2–95.0%), respectively. The KAP survey showed that >90% of clinicians were familiar with the indications for and the benefits of influenza vaccination.

Conclusions

Our study showed that the vaccine was significantly protective in 2010, 2011 and 2013, but not in 2012 when the circulating A(H3N2) strain showed genetic drift. Vaccine coverage was low despite good clinician knowledge of vaccination indications. Further studies are needed to investigate the reason for the low uptake of influenza vaccine.     

Effectiveness of the 2010 and 2011 Southern Hemisphere trivalent inactivated influenza vaccines against hospitalization with influenza‐associated acute respiratory infection among Thai adults aged ≥50 years

Background

Inactivated influenza vaccine (IIV) effectiveness has been evaluated among older adults in high-income countries, but data on IIV effectiveness in low- and middle-income countries remain sparse. We conducted a test-negative case–control analysis to estimate 2010 and 2011 trivalent IIV effectiveness against hospitalization with influenza-associated acute respiratory infection (ARI) among persons aged ≥50 years in rural Thailand.

Methods

During 2010–2011, active surveillance for ARI hospitalization was conducted in two provinces; patients were tested for influenza viruses by real-time RT-PCR. Vaccination status was obtained from vaccine registries. Case and control patients were patients with nasopharyngeal swabs positive and negative for influenza viruses, respectively. Vaccine effectiveness (VE) was estimated for the 6 months after vaccination began. Logistic regression was used to evaluate the association between case status and vaccination while adjusting for age, province, medical conditions, and time.

Results

During 2010–2011, there were 1545 patients with ARI, of whom 279 (18%) were influenza-positive case patients and 1266 (82%) were influenza-negative control patients. Of the 279 case patients, 247 (89%) had influenza A and 32 (11%) had influenza B. Fourteen of 279 (5%) case patients and 108 of 1266 (9%) control patients were vaccinated against influenza. The unadjusted IIV effectiveness against hospitalization with influenza-associated ARI was 43% (95% CI: 0–68%); adjusted VE was 47% (95% CI: 5–71%).

Conclusion

The 2010 and 2011 IIVs were moderately effective against hospitalization with influenza-associated ARI among Thais aged ≥50 years, but IIV coverage was low. Additional efforts are warranted in Thailand to improve IIV uptake in this target group.     

Pandemic influenza is a strong motivator for participation in vaccine clinical trials among HIV-positive Canadian adults

BACKGROUND:

HIV-positive patients represent an immunosuppressed population at risk for severe influenza. In the event of a pandemic, such as 2009 H1N1, rapid implementation of vaccine clinical trials in target populations will be critical. In the present paper, knowledge and attitudes of HIV-positive adults regarding seasonal/pandemic influenza vaccination were evaluated, and facilitators and barriers to participation in vaccine clinical trials were explored.

METHODS:

A validated, 70-item, self-administered questionnaire was distributed to all HIV patients presenting for routine follow-up at eight Canadian Institutes of Health Research Canadian HIV Trials Network (CTN) sites from October 2008 to February 2009, as well as all participants in CTN trial 237. This study has representation from all Canadian provinces.

RESULTS:

In total, 610 HIV-positive adults responded (298 CTN 237 participants; 312 non-CTN 237 participants). Most reported receiving influenza vaccine last season (83% of CTN 237 participants versus 83% non-CTN 237 participants; P not significant) and most would receive a pandemic influenza vaccine if offered (76% versus 73%; P not significant). A majority believed that it was important to include HIV patients in vaccine clinical trials (65% versus 53%; P<0.001) and would agree to participate in trials of a pandemic vaccine if invited (86% versus 51%; P≤0.0001). Predictors of willingness to participate in a pandemic vaccine trial were ‘desire to be protected from pandemic flu’, OR 4.5 (95% CI 2 to 8) and ‘desire to help others’, OR 2.3 (95% CI 1.3 to 4.5). ‘Fear of needles’, OR 0.49 (95% CI 0.1 to 1.5) and ‘need for extra blood tests’, OR 0.49 (95% CI 0.2 to 1.4) were key barriers to participation.

CONCLUSION:

Most HIV-positive Canadian adults surveyed receive influenza vaccination. Protection from pandemic influenza is considered important and is a motivator for receiving influenza vaccine and future trial participation. Modifiable barriers to these objectives identified in the present study should be the focus of efforts to increase influenza immunization in this population.     

An audit of influenza vaccination status in adults with inflammatory bowel disease

BACKGROUND

Several guidelines recommend influenza vaccination for high-risk patients, including those on immune-suppressing medications (IS).

OBJECTIVE:

To assess the vaccination status and immunization history of an outpatient inflammatory bowel disease (IBD) population for H1N1 and seasonal influenza.

RESULTS:

Among 250 patients, 104 (41.6%) had been immunized against H1N1 and 62 (24.8%) against seasonal influenza, and 158 (63.2%) were taking IS (azathioprine, 6-mercaptopurine, infliximab, adalimumab, methotrexate, cyclosporine or prednisone). Among subjects on IS, the presence of comorbidities warranting vaccination was associated with higher likelihood of H1N1 immunization (62.5% versus 35.8%; P=0.022) but not of seasonal influenza vaccination (25.0% versus 17.2%; P=0.392). Among patients without comorbidities warranting vaccination, IS was associated with a decreased likelihood of vaccination against seasonal influenza (17.2% versus 30.7%; P=0.036) but not H1N1 (35.8% versus 41.3%; P=0.46). The frequency of H1N1 vaccination was significantly higher among patients who visited a general practitioner at least once yearly (45.7% versus 20%; P=0.0027), with a similar trend for seasonal influenza vaccination (27.1% versus 12.5%; P=0.073). Among 91 patients on IS who declined vaccination, 39.6% reported fear of immediate side effects, 29.7% reported concerns about developing serious medical complications, 15.4% reported concerns about activating IBD and 15.4% were not aware that vaccination was indicated.

CONCLUSIONS:

Current strategies for vaccinating IBD patients on IS are inadequate. Primary care provider education, incentive programs and regular primary care contact may improve immunization uptake.     

Efficacy of Influenza A H1N1/2009 Vaccine in Hemodialysis and Kidney Transplant Patients

Summary

Background and objectives

Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients.

Design, setting, participants, & measurements

We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer.

Results

We excluded 19 individuals seroprotected (≥1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P = 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012) patients. For the transplant subgroup, longer time after transplantation (P = 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 ± 20.8 versus 71.6 ± 10.1 years, P = 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable.

Conclusion

The novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients.     

Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies

Background

We previously showed that vaccination with one dose of PR1 and WT1 peptides induces transient anti-leukemia immunity. We hypothesized that maintenance of a sustained anti-leukemia response may require frequent boost injections.

Design and Methods

Eight patients with myeloid malignancies were enrolled in this phase II study, and 6 completed 6 injections of PR1 and WT1 peptides in Montanide-adjuvant with GM-CSF, every two weeks.

Results

Both high- and low-avidity PR1 or WT1-specific CD8⁺ T cells were detected in all evaluable patients after the first vaccine dose. Repeated vaccination led to selective deletion of high avidity PR1- and WT1-specific CD8⁺ T cells and was not associated with significant reduction in WT1-expression. Additional boosting failed to increase vaccine-induced CD8⁺ T-cell frequencies further and in all patients the response was lost before the 6^th dose. PR1- or WT1-specific CD8⁺ T cells were not detected in bone marrow samples, excluding their preferential localization to this site. Following a booster injection three months after the 6^th vaccine dose, no high-avidity PR1 or WT1-specific CD8⁺ T cells could be detected, whereas low-avidity T cells were readily expanded.

Conclusions

These data support the immunogenicity of PR1 and WT1 peptide vaccines. However, repeated delivery of peptides with Montanide-adjuvant and GM-CSF leads to rapid loss of high-avidity peptide-specific CD8⁺ T cells. These results may offer an explanation for the lack of correlation between immune and clinical responses observed in a number of clinical trials of peptide vaccination. New approaches are needed to induce long-term high-avidity memory responses against leukemia antigens. (ClinicalTrials.gov Identifier: NCT00499772)     

The Seroconversion Rate of Hepatitis A Virus Vaccination among Patients with Hepatitis B Virus-Related Chronic Liver Disease in Korea

Background/Aims

The aim of this study was to evaluate the seroconversion rate of a hepatitis A virus (HAV) vaccination in patients with hepatitis B virus (HBV)-related chronic liver disease (CLD).

Methods

Analyses were conducted using clinical records from 94 patients with chronic HBV infection who were seronegative for IgG anti-HAV antibodies between September 2008 and June 2009. Two doses of an HAV vaccine were administered 24 weeks apart. A third vaccine dose was administered only for patients seronegative for anti-HAV antibodies at week 48.

Results

The seroconversion rate of anti-HAV following the two-dose vaccination was 86.17%. The seroconversion rate of anti-HAV was not significantly different according to age or status of liver disease. The rate was higher in female than in male patients. A third HAV vaccine dose was administered to 13 patients seronegative for anti-HAV after the two-dose regimen, and 84.62% of these patients showed seroconversion at week 72.

Conclusions

HAV vaccination is effective in most Korean patients with HBV-related CLD, and it might be necessary to evaluate three-dose vaccination approach for non-responders to the conventional regimen to maximize the success of an HAV vaccination program.     

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis: A Cohort Study

Summary

Background and objectives

In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients.

Design, setting, participants, & measurements

Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: ≥4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology.

Results

The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39).

Conclusions

The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.     

Seroprevalence of antibody to influenza A(H1N1)pdm09 attributed to vaccination or infection,before and after the second (2010) pandemic wave in Australia

Objectives

Historical records of influenza pandemics demonstrate variability in incidence and severity between waves. The influenza A(H1N1)pdm09 pandemic was the first in which many countries implemented strain-specific vaccination to mitigate subsequent seasons. Serosurveys provide opportunity to examine the constraining influence of antibody on population disease experience.

Design

Changes in the proportion of adults seropositive to influenza A(H1N1)pdm09over the 2009/10 (summer) interepidemic period and 2010 (winter) influenza season were measured to determine whether there was a temporal relationship with vaccine distribution and influenza activity, respectively.

Setting

Australia.

Sample

Plasma samples were collected from healthy blood donors from seven cities at the end of the first wave (November 2009), and before (March/April 2010) and after (November 2010) the subsequent influenza season.

Main outcome measures

Haemagglutination inhibition (HI) assays were performed to assess reactivity of plasma against A(H1N1)pdm09, and the proportion seropositive (HI titre ≥ 40) compared over time, by age group and location.

Results

Between the 2009 and 2010 influenza seasons, the seropositive proportion rose from 22% to 43%, an increase observed across all ages and sites. Brisbane alone recorded a significant rise in seropositivity over the 2010 influenza season – from a baseline of 35% to 53%. The seropositive proportion elsewhere was ≥40% pre-season, and did not rise over winter.

Conclusions

A vaccine-associated increase in seropositive proportion preceding the influenza season correlated with low levels of disease activity in winter 2010. These observations support the role of immunisation in mitigating the ‘second wave’ of A(H1N1)pdm09, with timing critical to ensure sustained herd protection.     

Effectiveness of seasonal influenza vaccinations against laboratory‐confirmed influenza‐associated infections among Singapore military personnel in 2010–2013

Background

Limited information is available about seasonal influenza vaccine effectiveness (VE) in tropical communities.

Objectives

Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore''s Armed Forces from 1 June 2009 to 30 June 2012.

Methods

Consenting servicemen underwent nasal washes, which were tested with RT-PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach.

Results

A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A(H1N1)pdm09 and influenza B were 84% (95% CI 78–88%, 79–86%, respectively). Vaccine efficacy against influenza A(H3N2) was markedly lower (VE 33%, 95% CI −4% to 57%). An estimated 70% (RR = 0·30; 95% CI 0·11–0·84), 39% (RR = 0·61;0·25–1·43) and 75% (RR = 0·25; 95% CI 0·11–0·50) reduction in the risk of influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed.

Conclusions

Overall, the blanket influenza vaccine programme in Singapore''s Armed Forces has had a moderate to high degree of protection against influenza A(H1N1)pdm09 and influenza B, but not against influenza A(H3N2). Blanket influenza vaccination is recommended for all military personnel.     

The utility of a 5th nap in multiple sleep latency test

Background

This is the first study that aimed to look specifically at the utility of the 5^th nap in the multiple sleep latency test (MSLT), a test used to assist in the diagnosis of narcolepsy.

Methods

Data was retrospectively collected from the Sleep Disorders Centre of a Tertiary Hospital on patients that had a 5^th nap during their MSLT from the 08^th November 2011 to 12^th November 2014.

Results

Fifty-three patients had a 5^th nap performed out of 378 MSLT studies. In 16% of cases a diagnosis of narcolepsy was given directly due to the inclusion of the 5^th nap on the MSLT. Here a 5^th nap allowed diagnostic criteria of mean sleep latency <8 minutes and >2 SOREMPS to be met. In 53% of cases the mean sleep latency increased due to 5^th nap inclusion; the mean sleep latency of the first four naps was 5.6 vs. 6.7 after inclusion of the 5^th nap.

Conclusions

The 5^th nap is not often performed within the MSLT studies. Our study shows that only a few patients may benefit from a 5^th nap opportunity which also led to increase of the mean sleep latency at the expense of extra time, cost, labour and increased patient anxiety.     

Granulocyte Colony Stimulating Factor Adjuvant Role on the Immunological Response to Hepatitis B Vaccine in Patients With Cirrhosis: A Double Blind Randomized Placebo Controlled Trial

Background:

Patients with liver cirrhosis have usually poor antibody response to hepatitis B virus (HBV) vaccination.

Objectives:

This study aimed to investigate the effect of granulocyte colony stimulating factor (G-CSF) on increasing antibody titers, after HBV vaccination, in patients with liver cirrhosis waiting for transplantation.

Patients and Methods:

From 56 patients with cirrhosis, 28 patients were allocated to receive double dose HBV vaccine (40 μgr) plus G-CSF and 28 patients were allocated to receive double dose HBV vaccine (40 μgr) plus placebo. Injections were performed on weeks 0, 4 and 8 and the blood samples were obtained one month after each vaccination session.

Results:

There was no statistically significant difference between anti-HBV antibody titers in patients receiving double dose HBV vaccination plus G-CSF and patients receiving double dose HBV vaccination plus placebo, after first, second or third vaccination rounds (P > 0.05). Although the adjuvant G-CSF injection did not cause significant increased antibody titers in our patients compared to the placebo group, the increase in antibody titers following vaccination, happened faster in this group, compared to the placebo group.

Conclusions:

The present study showed that G-CSF is not superior to placebo in production of protective antibody titers after HBV vaccination but could result in a more rapid antibody response, compared to the placebo.     

Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host

Background

In 2009 the declaration by the World Health Organization of a global pandemic of influenza-H1N1 virus led to a vaccination campaign to ensure protection for immunocompromised patients. The goal of this study was to determine the efficacy of the 2009 H1N1 vaccine in patients with hematologic malignancies.

Design and Methods

We evaluated humoral and cellular immune responses to 2009 H1N1 vaccine in 97 adults with hematologic malignancies and compared these responses with those in 25 adult controls. Patients received two injections of vaccine 21 days apart and the controls received one dose. Antibody titers were measured using a hemagglutination-inhibition assay on days 0, 21 and 49 after injection of the first dose. Cellular immune responses to H1N1 were determined on days 0 and 49.

Results

By day 21 post-vaccination, protective antibody titers of 1:32 or more were seen in 100% of controls compared to 39% of patients with B-cell malignancies (P<0.001), 46% of allogeneic stem cell transplant recipients (P<0.001) and 85% of patients with chronic myeloid leukemia (P=0.086). After a second dose, seroprotection rates increased to 68%, (P=0.008), 73%, (P=0.031), and 95% (P=0.5) in patients with B-cell malignancies, after allogeneic stem cell transplantation and with chronic myeloid leukemia, respectively. On the other hand, T-cell responses to H1N1 vaccine were not significantly different between patients and controls.

Conclusions

These data demonstrate the efficacy of H1N1 vaccine in most patients with hematologic malignancies and support the recommendation for the administration of two doses of vaccine in immunocompromised patients. These results may contribute towards the development of evidence-based guidelines for influenza vaccination in such patients in the future.     

Adverse reactions during voluntary donation of blood and/or blood components. A statistical-epidemiological study

Background

Voluntary donors normally tolerate blood donation very well, but, occasionally, adverse reactions of variable severity may occur during or at the end of the collection. Aim of this study was to estimate and possibly avoid the cause of unwanted reactions.

Materials and methods

The study was conducted over a period of 6 months, from 24^th October, 2005 to 24^th April 2006. The donor population analysed consisted of 4,906 donors (3,716 male and 1,190 female). In total, 3,983 (81%) voluntaries have donated whole blood, 851 (17%) plasma from apheresis, 64 (1.3%) experienced multicomponent donation, and 8 (0.1%) were donors of plasma-platelet apheresis.

Results

Only 63 donors (1.2% of all the volunteers) suffered some kind of adverse reaction: 59 (1.08% of the subjects) had mild reactions (agitation, sweating, pallor, cold feeling, sense of weakness, nausea), and only 4 (3 males and 1 female, 0.2%) had more severe disorders, including vomiting, loss of consciousness, and convulsive syncope.

Conclusions

Although the number of donors who developed disturbances during or at the end of blood donations was very low, it is nevertheless desirable to reduce risks to a minimum. A set of advices is provided for preventing problems.     

Phase II,randomized, open,controlled study of AS03‐adjuvanted H5N1 pre‐pandemic influenza vaccine in children aged 3 to 9 years: follow‐up of safety and immunogenicity persistence at 24 months post‐vaccination

Background

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years.

Methods

In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3–9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03_A or AS03_B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. ({"type":"clinical-trial","attrs":{"text":"NCT00502593","term_id":"NCT00502593"}}NCT00502593).

Results

The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4⁺ T cells with a T_H1 profile were observed.

Conclusions

Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.