Standard-dose versus MF59-adjuvanted, high-dose or recombinant-hemagglutinin influenza vaccine immunogenicity in older adults: comparison of A(H3N2) antibody response by prior season's vaccine status.

BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017/18 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016/17) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from Day 0 to Day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017/18 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) vs. without (range, 4.3-14.3) prior 2016/17 vaccination. MFR was significantly reduced by about one half to four fifths for previously vaccinated recipients of standard-dose and all three enhanced vaccines (ß range, 0.21-0.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR vs. standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

The Effect of Influenza Vaccination History on Changes in Hemagglutination Inhibition Titers After Receipt of the 2015-2016 Influenza Vaccine in Older Adults in Hong Kong.

BACKGROUND: Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same. METHODS: An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015-2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160. RESULTS: Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160. CONCLUSIONS: Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial.

BACKGROUND: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. METHODS: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. RESULTS: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. CONCLUSIONS: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. CLINICAL TRIALS REGISTRATION: NCT03330132.

Immune Responses to Twice-Annual Influenza Vaccination in Older Adults in Hong Kong.

Background: Many health authorities recommend influenza vaccination of older adults to reduce disease burden. We hypothesized that in tropical and subtropical areas with more prolonged influenza seasons, twice-annual influenza vaccination might provide older adults with improved immunity against influenza. Methods: In 2014-2015, Hong Kong experienced a substantial A(H3N2) winter epidemic with a mismatched vaccine. Local authorities procured and administered to older adults the 2015 southern hemisphere influenza vaccine, which included an updated and matching A/Switzerland/9715293/2013(H3N2) strain. We compared immune parameters in pre- and postvaccination sera from older adults ≥75 years of age who received 1 vs 2 influenza vaccines per year. Results: We enrolled 978 older adults with 470 vaccinations for summer 2015 and 827 vaccinations for winter 2015-2016. Recipients of southern hemisphere vaccination had higher geometric mean titers (GMTs) by the hemagglutination inhibition assay against all 3 vaccine strains. When receiving influenza vaccination for the subsequent winter, the southern hemisphere vaccine recipients had higher prevaccination GMTs but lower postvaccination GMTs, compared to those who had not received the southern hemisphere vaccine. Furthermore, cellular immunity was impacted by biannual vaccination, with reduced influenza-specific CD4 T-cell responses in the second season of vaccination. Conclusions: We observed some reductions in immune responses in the twice-annual vaccination group compared with the once-annual vaccination group, in the context of unchanging vaccine strains, while protection was likely to have been improved during the summer and autumn for the twice-annual vaccination group due to the continued circulation of the A/Switzerland/9715293/2013(H3N2) virus.

Factors affecting patient-reported outcomes after red blood cell transfusion in medical patients.

BACKGROUND: Physical variables like mortality or cardiac events were used to evaluate the requirement of red blood cell (RBC) transfusion. However, patient-reported outcomes (PROs) of blood transfusion recipients were seldom assessed. The health-related quality of life (HRQoL) of patients before and after RBC transfusion was compared in this study. STUDY DESIGN AND METHODS: The study period was February to June 2016. Standardized generic and anemia symptom-specific HRQoL instruments were administered to patients receiving RBC transfusion in the medical unit of a single center. The primary outcome was the change in HRQoL scores on Days 1 and 7 posttransfusion from baseline values on the day of transfusion (Day 0). Multiple linear regression analysis was performed to study the effect of transfusion strategy and other factors on PRO. RESULTS: The analysis included 99 general medical patients. The median (interquartile range) pretransfusion hemoglobin level was 72 (66-78) g/L. Two or more units of RBCs were prescribed to 45 patients (45%) on Day 0. Functional Assessment of Cancer Therapy-Anemia Subscale improved significantly on Days 1 and 7 by effect sizes of 0.41 and 0.38, respectively (p < 0.001). Regression analysis showed that lower baseline HRQoL scores were associated with better PRO on both Day 1 and Day 7 (p < 0.001). Transfusion trigger and number of RBC units transfused did not affect the change in HRQoL. CONCLUSION: Worse pretransfusion HRQoL is a predictor of improvement in PRO after blood transfusion. There is no evidence that a restrictive transfusion or single-unit policy jeopardizes PRO.

Increases in absenteeism among health care workers in Hong Kong during influenza epidemics, 2004-2009.

BACKGROUND: Acute respiratory infections (ARI) are a major cause of sickness absenteeism among health care workers (HCWs) and contribute significantly to overall productivity loss particularly during influenza epidemics. The purpose of this study is to quantify the increases in absenteeism during epidemics including the 2009 influenza A(H1N1)pdm09 pandemic. METHODS: We analysed administrative data to determine patterns of sickness absence among HCWs in Hong Kong from January 2004 through December 2009, and used multivariable linear regression model to estimate the excess all-cause and ARI-related sickness absenteeism rates during influenza epidemics. RESULTS: We found that influenza epidemics prior to the 2009 pandemic and during the 2009 pandemic were associated with 8.4 % (95 % CI: 5.6-11.2 %) and 57.7 % (95 % CI: 54.6-60.9 %) increases in overall sickness absence, and 26.5 % (95 % CI: 21.4-31.5 %) and 90.9 % (95 % CI: 85.2-96.6 %) increases in ARI-related sickness absence among HCWs in Hong Kong, respectively. Comparing different staff types, increases in overall absenteeism were highest among medical staff, during seasonal influenza epidemic periods (51.3 %, 95 % CI: 38.9-63.7 %) and the pandemic mitigation period (142.1 %, 95 % CI: 128.0-156.1 %). CONCLUSIONS: Influenza epidemics were associated with a substantial increase in sickness absence and productivity loss among HCWs in Hong Kong, and there was a much higher rate of absenteeism during the 2009 pandemic. These findings could inform better a more proactive workforce redistribution plans to allow for sufficient surge capacity in annual epidemics, and for pandemic preparedness.

The effectiveness of influenza vaccination against medically-attended illnesses in Hong Kong across three years with different degrees of vaccine match, 2014-17.

BACKGROUND: Influenza vaccination is the most effective intervention to prevent influenza virus infections. Vaccine effectiveness (VE) can vary due to factors such as matching between vaccine strains and prevailing strains, age and other characteristics of the vaccine recipients. OBJECTIVE: To evaluate influenza VE against medically-attended illness in different age groups and against specific influenza types/subtypes in Hong Kong. METHODS: A test-negative study was conducted from December 2014 through August 2017 in 20 outpatient clinics. Patients at least 6 months of age presenting with at least two symptoms of acute respiratory illness, ARI (fever ≥37.8 °C, cough, sore throat, runny nose, headache, myalgia and phlegm) within 72 h of onset were tested for influenza virus by reverse transcription polymerase chain reaction (PCR). Vaccination history was assessed by self-report or medical records at the clinics. VE against medically-attended illness was estimated using conditional logistic regression for influenza PCR result versus vaccination history, matching by calendar time and adjusting for age, age-squared, sex, and chronic medical illness. Additional analyses examined VE by age group and by influenza type/subtype. RESULTS: We enrolled 2566 patients, of whom 1118 (43.6%) tested positive for influenza A or B virus by PCR. Test-positive subjects were generally older, more likely to present with one of the symptoms of ARI, and less likely to receive vaccination against influenza. VE estimates for influenza A(H1N1), A(H3N2), B/Yamagata and B/Victoria were 61.6% (95% confidence interval, CI: 21.8%, 81.1%), 26.4% (95% CI: -1.3%, 46.6%), 67.0% (95% CI: 25.9%, 85.3%), 60.4% (95% CI: 0.3%, 84.3%), respectively. Estimates of VE by age group were generally higher in adults aged 50-64 and lower among children and older adults. CONCLUSIONS: VE against medically-attended influenza was moderate in Hong Kong, confirming the impact of influenza vaccination in reducing disease burden. The reduced VE for influenza A(H3N2) is a continuing concern.

A Smart Card-Based Electronic School Absenteeism System for Influenza-Like Illness Surveillance in Hong Kong: Design, Implementation, and Feasibility Assessment.

BACKGROUND: School-aged children have the highest incidence of respiratory virus infections each year, and transmission of respiratory viruses such as influenza virus can be a major concern in school settings. School absenteeism data have been employed as a component of influenza surveillance systems in some locations. Data timeliness and system acceptance remain as key determinants affecting the usefulness of a prospective surveillance system. OBJECTIVE: The aim of this study was to assess the feasibility of implementing an electronic school absenteeism surveillance system using smart card-based technology for influenza-like illness (ILI) surveillance among a representative network of local primary and secondary schools in Hong Kong. METHODS: We designed and implemented a surveillance system according to the Protocol for a Standardized information infrastructure for Pandemic and Emerging infectious disease Response (PROSPER). We employed an existing smart card-based education and school administration platform for data capture, customized the user interface, and used additional back end systems built for other downstream surveillance steps. We invited local schools to participate and collected absenteeism data by the implemented system. We compared temporal trend of the absenteeism data with data from existing community sentinel and laboratory surveillance data. RESULTS: We designed and implemented an ILI surveillance system utilizing smart card-based attendance tracking approach for data capture. We implemented the surveillance system in a total of 107 schools (including 66 primary schools and 41 secondary schools), covering a total of 75,052 children. The system successfully captured information on absences for 2 consecutive academic years (2012-2013 and 2013-2014). The absenteeism data we collected from the system reflected ILI activity in the community, with an upsurge in disease activity detected up to 1 to 2 weeks preceding other existing surveillance systems. CONCLUSIONS: We designed and implemented a novel smart card technology-based school absenteeism surveillance system. Our study demonstrated the feasibility of building a large-scale surveillance system riding on a routinely adopted data collection approach and the use of simple system enhancement to minimize workload implication and enhance system acceptability. Data from this system have potential value in supplementing existing sentinel influenza surveillance for situational awareness of influenza activity in the community.

A Foodborne Outbreak of Gastroenteritis Caused by Vibrio parahaemolyticus and Norovirus through Non-Seafood Vehicle.

Foodborne outbreaks caused by a mixed infection of Vibrio parahaemolyticus and norovirus have rarely been described. We reported a mixed outbreak of Vibrio parahaemolyticus and norovirus causing acute gastroenteritis in 99 staff members of a company in Guangdong, China, in May 2013, following consumption of roasted duck, an uncommon non-seafood vehicle for such mixed infection, in one meal served in the company's catering service. Epidemiological and laboratory findings indicated that a single asymptomatic food handler was the source of both pathogens, and the high rate of infection of both pathogens was exacerbated by the setting's suboptimal food hygiene practice.