Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

<p>Abstract</p> <p>Background</p> <p>Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.</p> <p>Methods</p> <p>6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was ≥ 45%. Cases of influenza like illness (defined as fever (oral temperature ≥37.8°C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.</p> <p>Results</p> <p>TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).</p> <p>Conclusion</p> <p>Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.</p> <p>Trial Registration</p> <p>Clinical trial registery: NCT00197223.</p

Mycoplasma pneumoniae infections, 11 countries in Europe and Israel, 2011 to 2016

Background: Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia, with large epidemics previously described to occur every 4 to 7 years. Aim: To better understand the diagnostic methods used to detect M. pneumoniae; to better understand M. pneumoniae testing and surveillance in use; to identify epidemics; to determine detection number per age group, age demographics for positive detections, concurrence of epidemics and annual peaks across geographical areas; and to determine the effect of geographical location on the timing of epidemics. Methods: A questionnaire was sent in May 2016 to Mycoplasma experts with national or regional responsibility within the ESCMID Study Group for Mycoplasma and Chlamydia Infections in 17 countries across Europe and Israel, retrospectively requesting details on M. pneumoniae-positive samples from January 2011 to April 2016. The Moving Epidemic Method was used to determine epidemic periods and effect of country latitude across the countries for the five periods under investigation. Results: Representatives from 12 countries provided data on M. pneumoniae infections, accounting for 95,666 positive samples. Two laboratories initiated routine macrolide resistance testing since 2013. Between 2011 and 2016, three epidemics were identified: 2011/12, 2014/15 and 2015/16. The distribution of patient ages for M. pneumoniae-positive samples showed three patterns. During epidemic years, an association between country latitude and calendar week when epidemic periods began was noted. Conclusions: An association between epidemics and latitude was observed. Differences were noted in the age distribution of positive cases and detection methods used and practice. A lack of macrolide resistance monitoring was noted

Predominance of influenza virus A(H3N2) 3C.2a1b and A(H1N1)pdm09 6B.1A5A genetic subclades in the WHO European Region, 2018–2019

Network authors: Portugal - Raquel Guiomar, Pedro Pechirra, National Influenza Reference Laboratory, Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge, Lisbon, PortugalBackground: The 2018/2019 influenza season in the WHO European Region was dominated by influenza A (H1N1)pdm09 and (H3N2) viruses, with very few influenza B viruses detected. Methods: Countries in the European Region reported virus characterization data to The European Surveillance System for weeks 40/2018 to 20/2019. These virus antigenic and genetic characterization and haemagglutinin (HA) sequence data were analysed to describe and assess circulating viruses relative to the 2018/2019 vaccine virus components for the northern hemisphere. Results: Thirty countries reported 4776 viruses characterized genetically and 3311 viruses antigenically. All genetically characterized A(H1N1)pdm09 viruses fell in subclade 6B.1A, of which 90% carried the amino acid substitution S183P in the HA gene. Antigenic data indicated that circulating A(H1N1)pdm09 viruses were similar to the 2018/2019 vaccine virus. Genetic data showed that A(H3N2) viruses mostly fell in clade 3C.2a (75%) and 90% of which were subclade 3C.2a1b. A lower proportion fell in clade 3C.3a (23%) and were antigenically distinct from the vaccine virus. All B/Victoria viruses belonged to clade 1A; 30% carried a double amino acid deletion in HA and were genetically and antigenically similar to the vaccine virus component, while 55% carried a triple amino acid deletion or no deletion in HA; these were antigenically distinct from each other and from the vaccine component. All B/Yamagata viruses belonged to clade 3 and were antigenically similar to the virus component in the quadrivalent vaccine for 2018/2019. Conclusions: A simultaneous circulation of genetically and antigenically diverse A(H3N2) and B/Victoria viruses was observed and represented a challenge to vaccine strain selection.Highlights: Co-circulation of different clades/subclades of influenza A viruses in 2018/2019 in the Region; Most circulating A(H1N1)pdm09 viruses (6B.1A) carried S183P in hemagglutinin; Genetically heterogeneous A(H3N2) viruses, with co-circulation of clades 3C.2a and 3C.3a; Antigenically distinct A(H3N2) clade 3C.3a viruses were increasingly detected until 02/2019 and then decreased; Co-circulation of genetically and antigenically diverse A(H3N2) strains challenges vaccine strain selection.info:eu-repo/semantics/publishedVersio