Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

Effectiveness of Influenza Vaccination and Early Antiviral Treatment in Reducing Pneumonia Risk in Severe Influenza Cases.

INTRODUCTION: Influenza vaccination may be effective in preventing influenza infection and may reduce the risk of influenza-associated pneumonia. The study aim was to evaluate the effect of influenza vaccination in preventing pneumonia when it failed to prevent influenza hospitalization. METHODS: This was a case-control study comparing hospitalized cases of influenza with and without pneumonia in patients aged ≥18 years in 16 hospitals in Catalonia over 10 influenza seasons (2010-11 to 2019-20). Data on sociodemographic, virological characteristics, comorbidities, vaccination history, and antiviral treatment were collected and analysed. The crude odds ratio (OR) and adjusted OR (aOR) with the corresponding 95% confidence interval (CI) values were calculated. RESULTS: In total, 5080 patients hospitalized for severe influenza were included, 63.5% (3224/5080) of whom had pneumonia-mostly men (56.8%; 1830/3224) and mostly in the ≥75 age group (39.3%; 1267/3224)-and of whom 14.0% died (451/3224). Virus A and virus B accounted for 78.1% (2518/3224) and 21.9% (705/3224) of influenza types, respectively. Starting antiviral treatment ≤48 h after symptom onset (aOR = 0.69; 95%CI: 0.53-0.90) and a history of seasonal influenza vaccination (aOR = 0.85; 95%CI: 0.72-0.98) were protective factors in developing pneumonia. CONCLUSIONS: Adherence to seasonal influenza vaccination and starting antiviral treatment within 48 h of symptom onset can reduce pneumonia risk in severe influenza cases.

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months.

BACKGROUND: PERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2-11 months, VE of vaccination in pregnancy and of primary vaccination (PV). METHODS: From December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants' age group. RESULTS: Of 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35-91%] and 88% [95%CI: 57-96%]. Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33-90] and 95% [95%CI: 69-99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27-86] and 94% [95%CI: 59-99]. CONCLUSION: Our findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2-11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.

Influenza Vaccine Effectiveness in Preventing Severe Outcomes in Patients Hospitalized with Laboratory-Confirmed Influenza during the 2017-2018 Season. A Retrospective Cohort Study in Catalonia (Spain).

Seasonal influenza is a common cause of hospital admission, especially in older people and those with comorbidities. The objective of this study was to determine influenza vaccine effectiveness (VE) in preventing intensive care admissions and shortening the length of stay (LOS) in hospitalized laboratory-confirmed influenza cases (HLCI) in Catalonia (Spain). A retrospective cohort study was carried out during the 2017-2018 season in HLCI aged ≥18 years from 14 public hospitals. Differences in means and proportions were assessed using a t-test or a chi-square test as necessary and the differences were quantified using standardized effect measures: Cohen's d for quantitative and Cohen's w for categorical variables. Adjusted influenza vaccine effectiveness in preventing severity was estimated by multivariate logistic regression where the adjusted VE = (1 - adjusted odds ratio) · 100%; adjustment was also made using the propensity score. We analyzed 1414 HLCI aged ≥18 years; 465 (33%) were vaccinated, of whom 437 (94%) were aged ≥60 years, 269 (57.8%) were male and 295 (63.4%) were positive for influenza type B. ICU admission was required in 214 (15.1%) cases. There were 141/1118 (12.6%) ICU admissions in patients aged ≥60 years and 73/296 (24.7%) in those aged <60 years (p < 0.001). The mean LOS and ICU LOS did not differ significantly between vaccinated and unvaccinated patients. There were 52/465 (11.2%) ICU admissions in vaccinated cases vs. 162/949 (17.1%) in unvaccinated cases. Patients admitted to the ICU had a longer hospital LOS (mean: 22.4 [SD 20.3] days) than those who were not (mean: 11.1 [SD 14.4] days); p < 0.001. Overall, vaccination was associated with a lower risk of ICU admission. Taking virus types A and B together, the estimated adjusted VE in preventing ICU admission was 31% (95% CI 1-52; p = 0.04). When stratified by viral type, the aVE was 40% for type A (95% CI -11-68; p = 0.09) and 25% for type B (95% CI -18-52; p = 0.21). Annual influenza vaccination may prevent ICU admission in cases of HLCI. A non-significantly shorter mean hospital stay was observed in vaccinated cases. Our results support the need to increase vaccination uptake and public perception of the benefits of influenza vaccination in groups at a higher risk of hospitalization and severe outcomes.

Behavior of hospitalized severe influenza cases according to the outcome variable in Catalonia, Spain, during the 2017-2018 season.

Influenza is an important cause of severe illness and death among patients with underlying medical conditions and in the elderly. The aim of this study was to investigate factors associated with ICU admission and death in patients hospitalized with severe laboratory-confirmed influenza during the 2017-2018 season in Catalonia. An observational epidemiological case-to-case study was carried out. Reported cases of severe laboratory-confirmed influenza requiring hospitalization in 2017-2018 influenza season were included. Mixed-effects regression analysis was used to estimate the factors associated with ICU admission and death. A total of 1306 cases of hospitalized severe influenza cases were included, of whom 175 (13.4%) died and 217 (16.6%) were ICU admitted. Age 65-74 years and ≥ 75 years and having ≥ 2 comorbidities were positively associated with death (aOR 3.19; 95%CI 1.19-8.50, aOR 6.95, 95%CI 2.76-1.80 and aOR 1.99; 95%CI 1.12-3.52, respectively). Neuraminidase inhibitor treatment and pneumonia were negatively associated with death. The 65-74 years and ≥ 75 years age groups were negatively associated with ICU admission (aOR 0.41; 95%CI 0.23-0.74 and aOR 0.30; 95%CI 0.17-0.53, respectively). A factor positively associated with ICU admission was neuraminidase inhibitor treatment. Our results support the need to investigate the worst outcomes of hospitalized severe cases, distinguishing between death and ICU admission.

Validation and Implementation of a Diagnostic Algorithm for DNA Detection of Bordetella pertussis, B. parapertussis, and B. holmesii in a Pediatric Referral Hospital in Barcelona, Spain.

This study aimed to validate a comprehensive diagnostic protocol based on real-time PCR for the rapid detection and identification of Bordetella pertussis, Bordetella parapertussis, and Bordetella holmesii, as well as its implementation in the diagnostic routine of a reference children's hospital. The new algorithm included a triplex quantitative PCR (qPCR) targeting IS481 gene (in B. pertussis, B. holmesii, and some Bordetella bronchiseptica strains), pIS1001 (B. parapertussis-specific) and rnase P as the human internal control. Two confirmatory singleplex tests for B. pertussis (ptxA-Pr) and B. holmesii (hIS1001) were performed if IS481 was positive. Analytical validation included determination of linear range, linearity, efficiency, precision, sensitivity, and a reference panel with clinical samples. Once validated, the new algorithm was prospectively implemented in children with clinical suspicion of whooping cough presenting to Hospital Sant Joan de Deu (Barcelona, Spain) over 12 months. Lower limits of detection obtained were 4.4, 13.9, and 27.3 genomic equivalents/ml of sample for IS481 (on B. pertussis), pIS1001 and hIS1001, and 777.9 for ptxA-Pr. qPCR efficiencies ranged from 86.0% to 96.9%. Intra- and interassay variabilities were <3% and <5%, respectively. Among 566 samples analyzed, B. pertussis, B. holmesii, and B. parapertussis were detected in 11.1%, 0.9% (only in females >4 years old), and 0.2% of samples, respectively. The new algorithm proved to be a useful microbiological diagnostic tool for whooping cough, demonstrating a low rate of other non-pertussisBordetella species in our surveilled area.

Influenza vaccine coverage, influenza-associated morbidity and all-cause mortality in Catalonia (Spain).

The objective of this work was to study the behaviour of influenza with respect to morbidity and all-cause mortality in Catalonia, and their association with influenza vaccination coverage. The study was carried out over 13 influenza seasons, from epidemiological week 40 of 1994 to week 20 of 2007, and included confirmed cases of influenza and all-cause mortality. Two generalized linear models were fitted: influenza-associated morbidity was modelled by Poisson regression and all-cause mortality by negative binomial regression. The seasonal component was modelled with the periodic function formed by the sum of the sinus and cosines. Expected influenza mortality during periods of influenza virus circulation was estimated by Poisson regression and its confidence intervals using the Bootstrap approach. Vaccination coverage was associated with a reduction in influenza-associated morbidity (p<0.001), but not with a reduction in all-cause mortality (p=0.149). In the case of influenza-associated morbidity, an increase of 5% in vaccination coverage represented a reduction of 3% in the incidence rate of influenza. There was a positive association between influenza-associated morbidity and all-cause mortality. Excess mortality attributable to influenza epidemics was estimated as 34.4 (95% CI: 28.4-40.8) weekly deaths. In conclusion, all-cause mortality is a good indicator of influenza surveillance and vaccination coverage is associated with a reduction in influenza-associated morbidity but not with all-cause mortality.

Early HCV dynamics on Peg-interferon and ribavirin in HIV/HCV co-infection: indications for the investigation of new treatment approaches.

OBJECTIVES: To describe the 28-day hepatitis C virus (HCV) kinetics under Pegylated-interferon (Peg-IFN) + ribavirin (RBV) therapy in HIV/HCV co-infected patients. To evaluate the predictive value of early virological response (EVR) of achieving a sustained virological response (SVR). To investigate the baseline mutations in the interferon sensitivity determining region (ISDR)2209-2248 in the non-structural 5A protein of HCV according to genotype. METHODS: Open, prospective trial including 28 co-infected patients with directly observed treatment with Peg-IFN + RBV. We assessed the predictive values of EVR (> or = 2 log10 of HCV decay or a negative qualitative test) at days 1, 7, 28 and in week 12 of the SVR. RESULTS: The SVR in an intention-to-treat analysis was 28.6% (genotype 1, 1/13; genotype 3, 6/10; genotype 4, 1/5). Patients who reached SVR presented a significantly faster HCV plasma viral load reduction compared to non-responders from the first 24 h [-1.06 log10 (interquartile range, -1.7 to -0.4) versus -0.05 log10 (interquartile range, -0.4 to +0.14) respectively; P = 0.002]. The median HCV viral load at week 12 was significantly different from that at baseline in responder and transient responders but not in non-responder patients. The positive predictive value was 100% within the first month and the best negative predictive value was 92% and 88.8% at weeks 4 and 12 respectively. The only genotype 1 responder patient had eight mutations in ISDR2209-2248. CONCLUSIONS: A very early HCV viral decay is observed in responder patients. An early virological response assessment at week 4 and 12 might be a useful tool in the clinical management of the co-infected population.