BackgroundInfluenza 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/FindingsComponent-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.ConclusionsThese 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.

In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu.

Prostate cancer screening may detect nonprogressive cancers, leading to overdiagnosis and overtreatment. The potential for overdiagnosis can be assessed from the reservoir of prostate cancer in autopsy studies that report incidental prostate cancer rates in men who died of other causes. We aimed to estimate the age-specific incidental cancer prevalence from all published autopsy studies. We identified eligible studies by searches of Medline and Embase, forward and backward citation searches and contacting authors. We screened the titles and abstracts of all articles; checked the full-text articles for eligibility and extracted clinical and pathology data using standardized forms. We extracted mean cancer prevalence, age-specific cancer prevalence and validity measures and then pooled data from all studies using logistic regression models with random effects. The 29 studies included in the review dated from 1948 to 2013. Incidental cancer was detected in all populations, with no obvious time trends in prevalence. Prostate cancer prevalence increased with each decade of age, OR = 1.7 (1.6–1.8), and was higher in studies that used the Gleason score, OR = 2.0 (1.1–3.7). No other factors were significantly predictive. The estimated mean cancer prevalence increased in a nonlinear fashion from 5% (95% CI: 3–8%) at age <30 years to 59% (95% CI: 48–71%) by age >79 years. There was substantial variation between populations in estimated cancer prevalence. There is a substantial reservoir of incidental prostate cancer which increases with age. The high risk of overdiagnosis limits the usefulness of prostate cancer screening.What’s new?Before symptoms of prostate cancer manifest clinically, many men die of other causes. Yet, prostate screening, particularly in older men, frequently turns out positive, resulting in overdiagnosis and overtreatment. This meta-analysis of published autopsy studies shows that incidental prostate cancer increases with age and with the use of sensitive screening strategies, especially in older men. Among men whose prostate cancers are designated “favorable-risk,” active surveillance and subsequent biopsy can result in reclassification with higher-grade cancer, purely by chance. The potential for the detection of clinically irrelevant, incidental prostate cancer is high, indicating a need for improved screening strategies.

Using an integrated surveillance platform, we incorporated genetic, antigenic, and epidemiologic indicators to evaluate agent–host factors that contributed to low vaccine effectiveness during the 2014–2015 influenza season, including variation in the viral genome and negative effects of serial vaccination.

Objective To assess whether screening for abdominal aortic aneurysms in men reduces mortality. Design Population based randomised controlled trial of ultrasound screening, with intention to treat analysis of age standardised mortality. Setting Community based screening programme in Western Australia. Participants 41 000 men aged 65-83 years randomised to intervention and control groups. Intervention Invitation to ultrasound screening. Main outcome measure Deaths from abdominal aortic aneurysm in the five years after the start of screening. Results The corrected response to invitation to screening was 70%. The crude prevalence was 7.2% for aortic diameter ≥ 30 mm and 0.5% for diameter ≥ 55 mm. Twice as many men in the intervention group than in the control group underwent elective surgery for abdominal aortic aneurysm (107 v 54, P = 0.002, 2 test). Between scheduled screening and the end of follow up 18 men in the intervention group and 25 in the control group died from abdominal aortic aneurysm, yielding a mortality ratio of 0.61 (95% confidence interval 0.33 to 1.11). Any benefit was almost entirely in men aged between 65 and 75 years, where the ratio was reduced to 0.19 (0.04 to 0.89). Conclusions At a whole population level screening for abdominal aortic aneurysms was not effective in men aged 65-83 years and did not reduce overall death rates. The success of screening depends on choice of target age group and the exclusion of ineligible men. It is also important to assess the current rate of elective surgery for abdominal aortic aneurysm as in some communities this may already approach a level that reduces the potential benefit of population based screening.