Impact of adenovirus (Ad) vaccine on clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection (URI)

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Impact of adenovirus (Ad) vaccine on clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection (URI) Single-centre study (USA; ): N=2,711 Air Force trainees presenting for clinical care for URI → prospective collection of demographic, clinical and PCR data from respiratory specimens (throat swab + nasal swab) Live oral Ad vaccine including serotypes 4 + 7: introduced Oct-Nov % of data collected before vaccine introduction (pre-VI) 28% of data collected after vaccine introduction (post-VI) Symptoms: P<0.01 for all comparisons, except for sore throat (not significant) Young A. IDWeek 2014 abs of 3 Data from oral presentation Comparison

Impact of adenovirus (Ad) vaccine on clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection (URI) Median duration of URI symptoms: Pre-VI: 3 days vs Post-VI: 6 days (P<0.01) Vital signs: P<0.01 for all comparisons Young A. IDWeek 2014 abs of 3 Data from oral presentation

Impact of adenovirus (Ad) vaccine on clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection (URI) Frequency of pathogen detection: Ad vaccine seems to be highly effective in reducing febrile URI and Ad- specific illness. Ad was detected less frequently, while other respira- tory pathogens, especially rhinovirus, were detected more frequently Young A. IDWeek 2014 abs of 3 Data from oral presentation

Prevalence of influenza among afebrile and vaccinated healthcare workers (HCWs) Single-centre study (Jan-Feb 2014; USA): Temporary sick policy for HCWs with respiratory symptoms (cough, sore throat, runny nose, congestion): –HCWs with respiratory symtoms but no fever: influenza test: If +: refrain from work for 7 d or until symptom resolution (whichever longer) If -: continue work but wear mask until symptom resolution –HCWs with fever: optional influenza test: If + or not tested: refrain from work for 7 d or until symptom resolution If -: return to work when afebrile for >24h without use of antipyretics; wear mask until symptom resolution 449 HCWs underwent influenza testing: –Positive for any respiratory pathogen: 54% (N=243) –Positive for influenza A: 7.6% (N=34) Influenza A H1N1: 7.3% (N=33; 1 coinfected with influenza B) Influenza A H3: 0.2% (N=1) –Diagnosis of influenza A H1N1 by outside physicians: N=7 Ridgway JP. IDWeek 2014 abs of 2 Data from oral presentation

Prevalence of influenza among afebrile and vaccinated healthcare workers (HCWs) Nearly 50% of HCWs with influenza may be afebrile prior to diagnosis and may pose a risk of influenza transmission to pts and coworkers Ridgway JP. IDWeek 2014 abs of 2 Data from oral presentation Frequency of fever among influenza-pos. HCWs, according to prior influenza vaccination history

Multi-centre, phase IIIb-IV, double-blind RCT (USA, Canada; ): N=31,989 adults aged ≥65 yr, randomised to: –Standard-dose (SD) IIV3 (15 µg haemagglutinin/strain): N=15,998 –High-dose (HD) IIV3 (60 µg haemagglutinin/strain): N=15,991 Primary efficacy endpoint: Occurrence, ≥14 days after vaccination, of laboratory-confirmed influenza caused by any influenza viral (sub)types, in association with a protocol-defined influenza-like illness Safety: High dose (HD) vs standard dose (SD) trivalent inactivated influenza vaccine (IIV3) for older adults Diazgranados C et al. N Engl J Med 2014;371: Diazgranados C. IDWeek 2014 abs of 2

High dose (HD) vs standard dose (SD) trivalent inactivated influenza vaccine (IIV3) for older adults Expanded immunogeniticity (serum samples provided ±28 d after vaccination) : Full immunogenicity subset (study yr 2: influenza season ) : IIV-HD: N=2,879 / IIV-SD: N=2,872: Haemagglutinin inhibition (HAI) assay using egg-propagated H3N2 antigen: GMT ratio=1.82 (95% CI: ) Substudy using case-cohort design: N=675 representative serum samples (123 who developed PCR/culture-confirmed H3N2 influenza illness; 552 from random subset of 10% of non-cases) In adults ≥65 yr, IIV-HD may induce higher Ab responses and provide better protection against lab-confirmed influenza illness than IIV-SD Diazgranados C et al. N Engl J Med 2014;371: Diazgranados C. IDWeek 2014 abs of 2 Data from poster Expanded immunogenicity assayGMT ratio (95% CI) HAI using MDCK cell-propagated H3N2 Ag1.48 ( ) N2 Ab titres by ELLA1.42 ( ) NT titres by assay using egg-propagated H3N2 Ag1.53 ( ) NT titres by assay using cell-propagated H3N2 Ag1.75 ( ) Ab: antibody; ELLA: enzyme-linked lectin assay; GMT: geometric mean titre; H3N2 Ag: A/Victoria/361/2011 antigen; N2: anti-neuraminidase; NT: viral neutralisation

New criteria for ventilator-associated pneumonia (VAP) from NHSN definitions of ventilator-associated events (VAEs) 1 McMullen K. IDWeek 2014 abs Magill SS. IDWeek 2014 abs of 3 reviewed by: Klompas M. N Engl J Med 2013;368: CFU: colony-forming unit; LPF: low-power field; min.: minimum; pos.: positive

New criteria for ventilator-associated pneumonia (VAP) from NHSN definitions of ventilator-associated events (VAEs) Traditional definition of VAP (tVAP) vs new definition of VAE: comparison: Single-centre study ( ; USA) 1 : N=1,832 pts ventilated for >2 days in 6 ICUs; total ventilator (vent) days: 14,904; median days/pt: 5 (range: 2-80) Surveillance using VAP definition: done manually through routine surveillance processes of trained infection prevention specialists (IPS) Surveillance using new VAE definition: done retrospectively through combination of automated and manual surveillance (IPS blinded to results of existing VAP surveillance) tVAP vs new probable/possible VAP definition: poor agreement (κ=0.05) 1 McMullen K. IDWeek 2014 abs Magill SS. IDWeek 2014 abs of 3

New criteria for ventilator-associated pneumonia (VAP) from NHSN definitions of ventilator-associated events (VAEs) Retrospective study ( ; USA) 2 in 9 ≠ types of adult ICUs: ±79% of VAEs: in pts on MV for ≥5 d or in hospital for ≥5 d at time of VAE onset Compared with the tVAP definition, the new VAE definitions seem to result in higher event rates and different patient characteristics 1 McMullen K. IDWeek 2014 abs Magill SS. IDWeek 2014 abs of 3 *P≤0.003 for comparison all VAEs with tVAP; MV: mechanical ventilation