A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. METHODS: A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post-first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. RESULTS: Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2-14.9; P = .02). CONCLUSIONS: High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.

Viral Respiratory Tract Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients in the Era of Molecular Testing.

Viral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015. Symptomatic patients were tested using respiratory multiplex polymerase chain reaction (PCR). Logistic regression and Kaplan-Meier analysis were used to identify risk factors for vRTI and the risk of death or intensive care unit (ICU) admission, respectively. A total of 382 patients were reviewed, and 65 episodes of vRTI were identified in 56 patients (14.7%). Rhinovirus accounted for the majority of infections (69.2%). The majority of episodes presented initially with upper respiratory tract infection (58.5%), with 28.9% of them progressing to lower respiratory tract infection. Eleven episodes (16.9%) were associated with ICU admission. There were no deaths directly due to vRTI. Previous autologous HSCT was associated with an increased risk of vRTI (odds ratio, 2.1; 95% confidence interval, 1.0 to 4.1). The risks of death (P = .47) or ICU admission (P = .65) were not significantly different by vRTI status. vRTI is common in the first 100 days after allo-HSCT and is associated with ICU admission.

Daily COVID-19 employee attestations at a large quaternary hospital in Melbourne, Australia - Limitations and lessons learnt.

BACKGROUND: As one of the many measures to limit the potentially infectious persons entering healthcare settings, the Victorian Department of Health (DH) introduced a daily attestation between 2020 and 2022. Upon entry to a health service, employees were required to confirm they were free from symptoms related to COVID-19 and did not have contact with a confirmed COVID-19 case in the previous 7-14 days. METHODS: We performed a retrospective analysis of employee attestations and SARS-CoV-2 tests performed between 1/6/2021 and 14/2/2022 at the main campus of the Royal Melbourne Hospital. RESULTS: We found the proportion of SARS-CoV-2 positive employees identified through workplace attestation was low (1.3%). Most SARS-CoV-2 positive employees analysed in this study (94%) were asymptomatic. DISCUSSION: Although the proportion of SARS-CoV-2 positive employees identified was low, attestations may have deterred unwell employees from presenting to work. Proactively monitoring employee attestations, such as measuring and reporting the number of symptomatic attestations, may make this a more useful tool.

Excess respiratory mortality and hospitalizations associated with influenza in Australia, 2007-2015.

BACKGROUND: Influenza is the most common vaccine-preventable disease in Australia, causing significant morbidity and mortality. We assessed the burden of influenza across all ages in terms of influenza-associated mortality and hospitalizations using national mortality, hospital-discharge and influenza surveillance data. METHODS: Influenza-associated excess respiratory mortality and hospitalization rates from 2007 to 2015 were estimated using generalized additive models with a proxy of influenza activity based on syndromic and laboratory surveillance data. Estimates were made for each age group and year. RESULTS: The estimated mean annual influenza-associated excess respiratory mortality was 2.6 per 100 000 population [95% confidence interval (CI): 1.8, 3.4 per 100 000 population]. The excess annual respiratory hospitalization rate was 57.4 per 100 000 population (95% CI: 32.5, 82.2 per 100 000 population). The highest mortality rates were observed among those aged ≥75 years (35.11 per 100 000 population; 95% CI: 19.93, 50.29 per 100 000 population) and hospitalization rates were also highest among older adults aged ≥75 years (302.95 per 100 000 population; 95% CI: 144.71, 461.19 per 100 000 population), as well as children aged <6 months (164.02 per 100 000 population; 95% CI: -34.84, 362.88 per 100 000 population). Annual variation was apparent, ranging from 1.0 to 3.9 per 100 000 population for mortality and 24.2 to 94.28 per 100 000 population for hospitalizations. Influenza A contributed to almost 80% of the average excess respiratory hospitalizations and 60% of the average excess respiratory deaths. CONCLUSIONS: Influenza causes considerable burden to all Australians. Expected variation was observed among age groups, years and influenza type, with the greatest burden falling to older adults and young children. Understanding the current burden is useful for understanding the potential impact of mitigation strategies, such as vaccination.

A second external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region highlights improved performance by participating laboratories.

Influenza viruses must be amplified in cell culture for detailed antigenic analysis and for phenotypic assays assessing susceptibility to antiviral drugs or for other assays. Following on from the first external quality assessment (EQA) for isolation and identification of influenza viruses using cell culture techniques in 2016, a follow up EQA was performed in 2019 for National Influenza Centres (NICs) in the World Health Organization (WHO) South East Asia and Western Pacific Regions. Nineteen WHO NICs performed influenza virus isolation and identification techniques on an EQA panel comprising 16 samples, containing influenza A or B viruses and negative control samples. One sample was used exclusively to assess capacity to measure a hemagglutination titer and the other 15 samples were used for virus isolation and subsequent identification. Virus isolation from EQA samples was generally detected by assessment of cytopathic effect and/or hemagglutination assay while virus identification was determined by real time RT-PCR, hemagglutination inhibition and/or immunofluorescence assays. For virus isolation from EQA samples, 6/19 participating laboratories obtained 15/15 correct results in the first EQA (2016) compared to 11/19 in the follow up (2019). For virus identification in isolates derived from EQA samples, 6/19 laboratories obtained 15/15 correct results in 2016 compared to 13/19 in 2019. Overall, NIC laboratories in the Asia Pacific Region showed a significant improvement between 2016 and 2019 in terms of the correct results reported for isolation from EQA samples and identification of virus in isolates derived from EQA samples (p=0.01 and p=0.02, respectively).

Impact of prior vaccination on antibody response and influenza-like illness among Australian healthcare workers after influenza vaccination in 2016.

BACKGROUND: Epidemiological studies suggest that influenza vaccine effectiveness decreases with repeated administration. We examined antibody responses to influenza vaccination among healthcare workers (HCWs) by prior vaccination history and determined the incidence of influenza infection. METHODS: HCWs were vaccinated with the 2016 Southern Hemisphere quadrivalent influenza vaccine. Serum samples were collected pre-vaccination, 21-28 days and 7 months post-vaccination. Influenza antibody titres were measured at each time-point using the haemagglutination inhibition (HI) assay. Immunogenicity was compared by prior vaccination history. RESULTS: A total of 157 HCWs completed the study. The majority were frequently vaccinated, with only 5 reporting no prior vaccinations since 2011. Rises in titres for all vaccine strains among vaccine-naïve HCWs were significantly greater than rises observed for HCWs who received between 1 and 5 prior vaccinations (p < 0.001, respectively). Post-vaccination GMTs against influenza A but not B strains decreased as the number of prior vaccinations increased from 1 to 5. There was a significant decline in GMTs post-season for both B lineages. Sixty five (41%) HCWs reported at least one influenza-like illness episode, with 6 (4%) identified as influenza positive. CONCLUSIONS: Varying serological responses to influenza vaccination were observed among HCWs by prior vaccination history, with vaccine-naïve HCWs demonstrating greater post-vaccination responses against A(H3N2).

Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers.

OBJECTIVE: To compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group). DESIGN: Prospective serosurvey. SETTING: Tertiary referral hospital. PARTICIPANTS: Healthcare workers. METHODS: Healthcare workers were vaccinated with the 2015 southern hemisphere trivalent influenza vaccine. Influenza antibody titres were measured pre-vaccination, 21-28days post-vaccination and 6months post-vaccination. Antibody titres were measured using the haemagglutination inhibition assay. Levels of seropositivity and estimated geometric mean titres were calculated. RESULTS: Of the 202 HCWs enrolled, 182 completed the study (143 high vaccination and 39 low vaccination). Both vaccination groups demonstrated increases in post-vaccination geometric mean titres, with greater gains in the low vaccination group. Seropositivity remained high in both high and low vaccination groups post-vaccination. The highest fold rise was observed among HCWs in the low vaccination group against the H3N2 component of the vaccine. CONCLUSIONS: Both high and low vaccination groups in our study demonstrated protective antibody titres post-vaccination. The findings from the current study are suggestive of decreased serological response among highly vaccinated HCWs. More studies with larger sample sizes and a greater number of people in the vaccine-naïve and once-vaccinated groups are required to confirm or refute these findings before making any policy changes.