Institut National de Santé Publique du Québec

BACKGROUND: Access is central to the performance of health care systems around the world. However, access to health care remains a complex notion as exemplified in the variety of interpretations of the concept across authors. The aim of this paper is to suggest a conceptualisation of access to health care describing broad dimensions and determinants that integrate demand and supply-side-factors and enabling the operationalisation of access to health care all along the process of obtaining care and benefiting from the services. METHODS: A synthesis of the published literature on the conceptualisation of access has been performed. The most cited frameworks served as a basis to develop a revised conceptual framework. RESULTS: Here, we view access as the opportunity to identify healthcare needs, to seek healthcare services, to reach, to obtain or use health care services, and to actually have a need for services fulfilled. We conceptualise five dimensions of accessibility: 1) Approachability; 2) Acceptability; 3) Availability and accommodation; 4) Affordability; 5) Appropriateness. In this framework, five corresponding abilities of populations interact with the dimensions of accessibility to generate access. Five corollary dimensions of abilities include: 1) Ability to perceive; 2) Ability to seek; 3) Ability to reach; 4) Ability to pay; and 5) Ability to engage. CONCLUSIONS: This paper explains the comprehensiveness and dynamic nature of this conceptualisation of access to care and identifies relevant determinants that can have an impact on access from a multilevel perspective where factors related to health systems, institutions, organisations and providers are considered with factors at the individual, household, community, and population levels.

Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination.

BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. METHODS: In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. RESULTS: The women were followed for an average of 3 years after administration of the first dose. In the per-protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group. Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the coprimary end points. In an intention-to-treat analysis, including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to 49), and the rate of cervical lesions regardless of the causal HPV type by 20% (95% CI, 8 to 31). CONCLUSIONS: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).

International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name re-assignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment of new genotypes and subtypes in the future.

Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of parents. Anti-vaccination movements have been implicated in lowered vaccine acceptance rates and in the increase in vaccine-preventable disease outbreaks and epidemics. In this review, we will look at determinants of parental decision-making about vaccination and provide an overview of the history of anti-vaccination movements and its clinical impact.

In March 2012, the SAGE Working Group on Vaccine Hesitancy was convened to define the term "vaccine hesitancy", as well as to map the determinants of vaccine hesitancy and develop tools to measure and address the nature and scale of hesitancy in settings where it is becoming more evident. The definition of vaccine hesitancy and a matrix of determinants guided the development of a survey tool to assess the nature and scale of hesitancy issues. Additionally, vaccine hesitancy questions were piloted in the annual WHO-UNICEF joint reporting form, completed by National Immunization Managers globally. The objective of characterizing the nature and scale of vaccine hesitancy issues is to better inform the development of appropriate strategies and policies to address the concerns expressed, and to sustain confidence in vaccination. The Working Group developed a matrix of the determinants of vaccine hesitancy informed by a systematic review of peer reviewed and grey literature, and by the expertise of the working group. The matrix mapped the key factors influencing the decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine-specific. These categories framed the menu of survey questions presented in this paper to help diagnose and address vaccine hesitancy.

BACKGROUND: The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. FINDINGS: Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination. INTERPRETATION: Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on maternal and newborn health is unclear. We aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies with comparison data on SARS-CoV-2 infection and severity of COVID-19 during pregnancy. We searched for eligible studies in MEDLINE, Embase, ClinicalTrials.gov, medRxiv and Cochrane databases up to Jan. 29, 2021, using Medical Subject Headings terms and keywords for "severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19" AND "pregnancy." We evaluated the methodologic quality of all included studies using the Newcastle-Ottawa Scale. Our primary outcomes were preeclampsia and preterm birth. Secondary outcomes included stillbirth, gestational diabetes and other pregnancy outcomes. We calculated summary odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CI) using random-effects meta-analysis. RESULTS: We included 42 studies involving 438 548 people who were pregnant. Compared with no SARS-CoV-2 infection in pregnancy, COVID-19 was associated with preeclampsia (OR 1.33, 95% CI 1.03 to 1.73), preterm birth (OR 1.82, 95% CI 1.38 to 2.39) and stillbirth (OR 2.11, 95% CI 1.14 to 3.90). Compared with mild COVID-19, severe COVID-19 was strongly associated with preeclampsia (OR 4.16, 95% CI 1.55 to 11.15), preterm birth (OR 4.29, 95% CI 2.41 to 7.63), gestational diabetes (OR 1.99, 95% CI 1.09 to 3.64) and low birth weight (OR 1.89, 95% CI 1.14 to 3.12). INTERPRETATION: COVID-19 may be associated with increased risks of preeclampsia, preterm birth and other adverse pregnancy outcomes.

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.

BACKGROUND: Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. METHODS: We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. RESULTS: A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. CONCLUSIONS: In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).

Despite large gains in health over the past few decades, the distribution of health risks worldwide remains extremely and unacceptably uneven. Although the health sector has a crucial role in addressing health inequalities, its eff orts often come into confl ict with powerful global actors in pursuit of other interests such as protection of national security, safeguarding of sovereignty, or economic goals. This is the starting point of The Lancet-University of Oslo Commission on Global Governance for Health. With globalisation, health inequity increasingly results from transnational activities that involve actors with diff erent interests and degrees of power: states, transnational corporations, civil society, and others. The decisions, policies, and actions of such actors are, in turn, founded on global social norms. Their actions are not designed to harm health, but can have negative sideeff ects that create health inequities. The norms, policies, and practices that arise from global political interaction across all sectors that aff ect health are what we call global political determinants of health.

BACKGROUND: A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)-transmission dynamics in Quebec. METHODS: HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998-2005; n=215) and the provincial genotyping program (2001-2005; n=481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n=593) and infections from untreated (n=135) and treated (n=660) chronically infected (CI) potential transmitter populations (2001-2005). Clinical features, risk factors, and drug resistance for clustered and nonclustered transmission events were ascertained. RESULTS: Viruses from 49.4% (293/593) of PHIs cosegregated into 75 transmission chains with 2-17 transmissions/cluster. Half of the clusters included 2.7+/-0.8 (mean+/-SD) transmissions, whereas the remainder had 8.8+/-3.5 transmissions. Maximum periods for onward transmission in clusters were 15.2+/-9.5 months. Coclustering of untreated and treated CIs with PHIs were infrequent (6.2% and 4.8%, respectively). The ages, viremia, and risk factors were similar for clustered and nonclustered transmission events. Low prevalence of drug resistance in PHI supported amplified transmissions at early stages. CONCLUSIONS: Early infection accounts for approximately half of onward transmissions in this urban North American study. Therapy at early stages of disease may prevent onward HIV transmission.

When faced with vaccine hesitancy, public health authorities are looking for effective strategies to address this issue. In this paper, the findings of 15 published literature reviews or meta-analysis that have examined the effectiveness of different interventions to reduce vaccine hesitancy and/or to enhance vaccine acceptance are presented and discussed. From the literature, there is no strong evidence to recommend any specific intervention to address vaccine hesitancy/refusal. The reviewed studies included interventions with diverse content and approaches that were implemented in different settings and targeted various populations. Few interventions were directly targeted to vaccine hesitant individuals. Given the paucity of information on effective strategies to address vaccine hesitancy, when interventions are implemented, planning a rigorous evaluation of their impact on vaccine hesitancy/vaccine acceptance will be essential.

BACKGROUND: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). METHODS: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. RESULTS: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. CONCLUSIONS: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.

The term vaccine hesitancy refers to delay in acceptance or refusal of vaccines despite the availability of vaccination services. Different factors influence vaccine hesitancy and these are context-specific, varying across time and place and with different vaccines. Factors such as complacency, convenience and confidence are involved. Acceptance of vaccines may be decreasing and several explanations for this trend have been proposed. The WHO Strategic Advisory Group of Experts (SAGE) on Immunization has recognized the global importance of vaccine hesitancy and recommended an interview study with immunization managers (IMs) to better understand the range of vaccine hesitancy determinants that are encountered in different settings. Interviews with IMs in 13 selected countries were conducted between September and December 2013 and various factors that discourage vaccine acceptance were identified. Vaccine hesitancy was not defined consistently by the IMs and most interpreted the term as meaning vaccine refusal. Although vaccine hesitancy existed in all 13 countries, some IMs considered its impact on immunization programmes to be a minor problem. The causes of vaccine hesitancy varied in the different countries and were context-specific, indicating a need to strengthen the capacity of national programmes to identify the locally relevant causal factors and to develop adapted strategies to address them.

BACKGROUND: The placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW). METHODS: Women enrolled in the placebo arm (n = 8800) of 2 randomized trials of a quadrivalent vaccine were examined for the presence of GW for up to 9 visits over approximately 4 years. A comprehensive examination of the perianal area, vulva, and vagina prompted biopsy. Biopsy samples were analyzed by a blinded panel of up to 4 histopathologists and tested for 14 HPV genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) by use of a polymerase chain reaction-based assay. Risk factors for the development of GW were assessed. RESULTS: Women were followed up for an average of 3.6 years (range, 0-4.9 years). Overall, 298 (3.4%) of 8800 participants developed GW related to HPV-6 or HPV-11 (incidence rate, 0.87 cases per 100 person-years-at-risk). In total, 520 distinct lesions were diagnosed as GW. HPV DNA was detected in 472 (90.8%) lesions, with HPV-6 and HPV-11 detected in 447 (86.0%) of these lesions (94.7% of 472 HPV DNA-positive lesions). We found high-risk HPV types in 161 (31.0%) of 520 lesions. Risk factors for HPV-6- and HPV-11-related GW included infection at baseline, acquisition of new sex partners, a higher number of sex partners, and DNA positivity at baseline for a high-risk HPV type. CONCLUSIONS: We confirm the major role played by HPV-6 and HPV-11 in GW, as well as associated risk factors. A vaccine that includes these types of HPV could substantially reduce the overall burden of HPV disease.

An often-stated public health comment is that "vaccination is a victim of its own success." While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified "the reluctance or refusal to vaccinate despite availability of vaccines" as one of the 10 threats to global health in 2019. The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.

The Canadian Integrated Program for Antimicrobial Resistance Surveillance describes a strong correlation (r = 0.9, p<0.0001) between ceftiofur-resistant Salmonella enterica serovar Heidelberg isolated from retail chicken and incidence of ceftiofur-resistant Salmonella serovar Heidelberg infections in humans across Canada. In Quebec, changes of ceftiofur resistance in chicken Salmonella Heidelberg and Escherichia coli isolates appear related to changing levels of ceftiofur use in hatcheries during the study period, from highest to lowest levels before and after a voluntary withdrawal, to increasing levels after reintroduction of use (62% to 7% to 20%, and 34% to 6% to 19%, respectively). These events provide evidence that ceftiofur use in chickens results in extended-spectrum cephalosporin resistance in bacteria from chicken and humans. To ensure the continued effectiveness of extended-spectrum cephalosporins for treating serious infections in humans, multidisciplinary efforts are needed to scrutinize and, where appropriate, limit use of ceftiofur in chicken production in Canada.

BACKGROUND: Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses. METHODS/FINDINGS: Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses. CONCLUSIONS: These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.

The goal of this commentary is to highlight the ageism that has emerged during the COVID-19 pandemic. Over 20 international researchers in the field of ageing have contributed to this document. This commentary discusses how older people are misrepresented and undervalued in the current public discourse surrounding the pandemic. It points to issues in documenting the deaths of older adults, the lack of preparation for such a crisis in long-term care homes, how some 'protective' policies can be considered patronising and how the initial perception of the public was that the virus was really an older adult problem. This commentary also calls attention to important intergenerational solidarity that has occurred during this crisis to ensure support and social-inclusion of older adults, even at a distance. Our hope is that with this commentary we can contribute to the discourse on older adults during this pandemic and diminish the ageist attitudes that have circulated.