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.

Evaluation of the Completeness and Timeliness of the Infant Pertussis Surveillance System in the Czech Republic in 2015, 2017 and 2019.

Introduction: The completeness and timeliness of the pertussis questionnaire-based enhanced surveillance system (ESS) among infants and reported pertussis data within the electronic nationwide notification system (NNS) in the years 2015, 2017 and 2019 were evaluated in a pilot study. Methods: The completeness of the variables for demographic characteristics, date of symptom onset, hospitalisation and vaccination status were assessed in both systems. Timeliness of reporting in the NNS was analysed as the interval between symptom onset and a) the date of first specimen collection (diagnostic delay), and b) the date of the Regional Public Health Authority receiving notification (notification delay). Results: A total of 121 confirmed pertussis cases were reported to the NNS in the study years, while in the ESS a total of 104 confirmed cases were reported in infants. In both systems most cases were in the age group of one completed month of life (20% versus 23%) and males (55% versus 55%). The majority of cases were hospitalised (81% versus 85%) and unvaccinated (77% versus 78%). Within the NNS, the first dose of vaccine was reported in 13 cases, the second dose in 11, and third dose in three cases. Within the NNS, 100% completeness of following variables was found: symptom onset, week and region of reporting, age, gender and place of isolation. Median diagnostic delay was nine days. Median notification delay was 18 days. Conclusions: Data completeness was high in the NNS, except for lack of vaccination data in those eligible by age. Efforts to improve the completeness of laboratory-related variables and timeliness are essential. Based on the study results, the project of improving the ESS for infants will continue with regular evaluation.

Vaccination against influenza in pregnant women in a maternity hospital in the Czech Republic in the season 2020-2021.

OBJECTIVES: Pregnant women are among the priority groups to receive influenza vaccines in the Czech Republic since 2011, data on vaccination coverage are not yet available. The aim of the study was to determine the influenza vaccination coverage (IVC) and provide source data for further activities. METHODS: A prospective observational study was performed in a large maternity hospital in Prague. The self-completed questionnaire was distributed to 5,475 pregnant women between September 1, 2020 and August 31, 2021. Questions included maternal sociodemographic characteristics, influenza vaccination status and sources of maternal vaccination recommendations during pregnancy. RESULTS: A total of 4,617 completed questionnaires have been analysed. The median age of study participants (N = 4,592) was 33 years (range: 18-51 years). The majority (69.7%) of women had completed their university education, most women were childless (58.5%) or had one child (32.5%) before the start of the study. Less than 2% of women reported being vaccinated against influenza during their pregnancy (1.5%; 95% CI, 1.1-1.9%). Only 21% of women knew that it's possible to get vaccinated against influenza during pregnancy. Participants considered influenza vaccination in pregnancy as important (3.3%), useful (41.1%) and useless (44.4%). Out of 959 pregnant women who had information about influenza vaccination during pregnancy, only 6.9% were vaccinated, while among those who did not have this information, 0.1% were vaccinated during pregnancy (p < 0.001). The most frequent source of information was Internet, then media and a general practitioner. CONCLUSIONS: The IVC during pregnancy in our study was extremely low. In order to improve IVC among pregnant women, it is necessary to increase awareness of recommendations and vaccination options among the public and professionals and incorporating vaccination recommendation in routine antenatal practice.

Monitoring the vaccination of pregnant women against pertussis - single-centre one-year study in the Czech Republic.

OBJECTIVES: This observational study aimed to analyse data from big maternity hospital, determine the vaccination coverage and provide source information for further activities. BACKGROUND: Although vaccination of pregnant women against pertussis is recommended in the Czech Republic, data on vaccination coverage are not available. METHODS: The self-completed questionnaire was distributed to 5,475 pregnant women in the maternity hospital between 2020 and 2021. Questionnaires collected mother's sociodemographic characteristics, pertussis vaccination status and sources of recommendations for vaccinations during pregnancy. RESULTS: A total of 4,617 completed questionnaires were analysed. Pertussis vaccination coverage during pregnancy was 1.6 % (95% confidence interval, 1.3-2.0 %). Only 12.5 % of women knew about the possibility of being vaccinated against pertussis during pregnancy. Women considered pertussis vaccination in pregnancy as important (12.9 %), useful (49.1 %) and useless (24.0 %). Of 579 pregnant women who had information about pertussis vaccination during pregnancy, only 12.1 % were vaccinated, while among those who did not have this information, 0.1% were vaccinated during pregnancy (p < 0.001). The most frequent source of information was Internet, then a general practitioner. CONCLUSION: It is necessary to raise awareness of recommendations for pregnancy vaccination among public and professionals, to emphasize the benefits of such vaccination in order to increase the vaccination coverage (Tab. 3, Ref. 31). Text in PDF www.elis.sk Keywords: pertussis, whooping cough, pregnancy, vaccination, health knowledge, prevention.

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.

Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis.

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Comparative Omics Analysis of Historic and Recent Isolates of Bordetella pertussis and Effects of Genome Rearrangements on Evolution.

Despite high vaccination coverage, pertussis is increasing in many industrialized countries, including the Czech Republic. To better understand Bordetella pertussis resurgence, we analyzed historic strains and recent clinical isolates by using a comparative omics approach. Whole-genome sequencing showed that historic and recent isolates of B. pertussis have substantial variation in genome organization and form separate phylogenetic clusters. Subsequent RNA sequence analysis and liquid chromatography with mass tandem spectrometry analyses showed that these variations translated into discretely separated transcriptomic and proteomic profiles. When compared with historic strains, recent isolates showed increased expression of flagellar genes and genes involved in lipopolysaccharide biosynthesis and decreased expression of polysaccharide capsule genes. Compared with reference strain Tohama I, all strains had increased expression and production of the type III secretion system apparatus. We detected the potential link between observed effects and insertion sequence element-induced changes in gene context only for a few genes.

Trends in the Minimum Inhibitory Concentrations of Erythromycin, Clarithromycin, Azithromycin, Ciprofloxacin, and Trimethoprim/Sulfamethoxazole for Strains of Bordetella pertussis isolated in the Czech Republic in 1967-2015.

OBJECTIVE: The aim of the study was to determine trends in the minimum inhibitory concentrations (MICs) of erythromycin used as first-line therapy and alternative antibiotics against Bordetella pertussis (B. pertussis) strains isolated from patients with whooping cough in the Czech Republic (CR) in three periods from 1967 to 2015. METHODS: In total, 135 isolates from the years 1967­2015 were analysed. The strains were divided into three groups by the year of isolation: 1967­1999 (42 strains), 2004­2010 (43 strains), and 2011­2015 (50 strains). MIC of selected antibiotics (erythromycin, clarithromycin, azithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole) were obtained by the reference agar dilution method on Bordet Gengou Agar with 15% defibrinated sheep blood. RESULTS: The study set included 70 strains previously tested for MICs of erythromycin and four other antibiotics. In the three study periods, the MICs of the tested antibiotics for B. pertussis were nearly identical. All but a single strain, inhibited by erythromycin at a concentration of 0.03 mg/l, were inhibited by two concentrations of erythromycin and azithromycin (0.06 and 0.125 mg/l). Clarithromycin inhibited the strains from all three study periods at the following concentrations: 0.03, 0.06, and 0.125 mg/l. Any of the 135 strains was inhibited by ciprofloxacin at a single concentration of 0.06 mg/l and by trimethoprim/sulfamethoxazole at three concentrations (0.125, 0.25, and 0.5 mg/l). CONCLUSION: The study set of 135 Czech strains of B. pertussis isolated in 1967­2015 appears to be homogeneous in terms of the MICs for five antimicrobials. The MICs remained in a narrow range of two to three low concentrations; the unimodal distribution of the MICs suggests the absence of resistance mechanisms. The highest MICs of erythromycin, clarithromycin, and azithromycin were equally 0.125 mg/l, that of ciprofloxacin was 0.06 mg/l, and that of trimethoprim/sulfamethoxazole was 0.5 mg/l. Over the study period of 55 years, the MICs of the study antibiotics remained in the same ranges.