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Background: Pertussis vaccination in young mothers aims to protect neonates through cocooning. We estimated pertussis vaccination coverage (VC) in women at two months postpartum in France in 2021, and the proportion of women who got vaccinated in the first two months postpartum; associated determinants were studied., Methods: We used data from the 2021 National Perinatal Surveys conducted in metropolitan France (ENP 2021) and French overseas territories (ENP-DROM 2021). Multivariate poisson regressions were employed to study the following determinants: age, educational level, monthly household income, socio-professional situation, birth country, parity, health professional who monitored pregnancy, influenza vaccination during pregnancy, region of residence, prenatal care consultations, having health insurance, having a partner, and having a chronic pathology. Results were weighted., Results: The study sample comprised 7999 women. Estimated pertussis VC at two months postpartum was 66.8 % (95 %CI [65.5-68.0]). VC was significantly lower in i) unemployed women (vs. executives/managers, intermediate and higher intellectual professionals), ii) those on low income (vs. high), and iii) those with two or more children (vs. primiparous). It was significantly higher in i) women born in France, ii) those vaccinated against influenza during pregnancy, iii) those who received pre-natal care from a private midwife, and iv) those with more prenatal consultations. The proportion of women vaccinated against pertussis in the two-month postpartum period (33.4 % [31.7-35.9]) was significantly lower in i) women on low incomes, ii) unemployed women, iii) women with health insurance, and iv) multiparous women. It was significantly higher in those vaccinated against influenza during pregnancy., Discussion - Conclusion: Pertussis VC in women at two months postpartum in 2021 was insufficient and was marked by social and territorial inequalities in health. Vaccination for pregnant women has been recommended in France since 2022. A study monitoring the impact of this new recommendation is essential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pertussis (whooping cough) is a vaccine-preventable but re-emerging, highly infectious respiratory disease caused by Bordetella pertussis. There are currently no effective treatments for pertussis, complicating care for non-vaccinated individuals, especially newborns. Disease manifestations are predominantly caused by pertussis toxin (PT), a pivotal virulence factor classified as an ADP-ribosylating AB-type protein toxin. In this work, an unbiased approach using peptide libraries, bioassay-guided fractionation and mass spectrometry revealed α 1 -antitrypsin (α 1 AT) as a potent PT inhibitor. Biochemistry-, cell culture- and molecular modeling-based in vitro experimentation demonstrated that the α 1 AT mode of action is based on blocking PT-binding to the host target cell surface. In the infant mouse model of severe pertussis, α 1 AT expression was reduced upon infection. Further, systemic administration of α 1 AT significantly reduced B. pertussis-induced leukocytosis, which is a hallmark of infant infection and major risk factor for fatal pertussis. Taken together our data demonstrates that α 1 AT is a novel PT inhibitor and that further evaluation and development of α 1 AT as a therapeutic agent for pertussis is warranted. Importantly, purified α 1 AT is already in use clinically as an intravenous augmentation therapy for those with genetic α 1 AT deficiency and could be repurposed to clinical management of pertussis., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited., Design: Population-based linkage data were collected during 2001-2016., Setting: New South Wales, Australia., Population or Sample: A total of 1 453 037 singleton births., Methods: Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates., Main Outcome Measures: Adverse birth outcomes (preterm birth and low birth weight)., Results: Among 1 453 037 singleton births over 16 years, we identified pertussis in 925 (49; 5.3% hospitalised) and influenza in 2850 (1092; 38.3% hospitalised) women during pregnancy. Cases of pertussis were similarly distributed by trimester (32% 3rd) whereas 46% of influenza cases were in the 3rd trimester. Younger age, previous birth, and being overseas-born were associated with both pertussis and influenza, whereas identifying as Aboriginal or Torres Strait Islander, hypertension or diabetes before and during pregnancy, and a number of other factors were only associated with influenza. Both pertussis and influenza in pregnancy were associated with increased risk of preterm birth (pertussis: aHR = 1.30, 95% CI 1.01-1.68; influenza: aHR = 1.56, 95% CI 1.36-1.79) and these increased risks were greater when infections in the period within 2 weeks of birth were considered (pertussis: aHR = 2.36, 95% CI 1.26-4.41; influenza: aHR = 2.29, 95% CI 1.78-2.96)., Conclusions: Maternal pertussis and influenza infections close to the time of birth were associated with adverse birth outcomes. These findings highlight the benefits of vaccination during pregnancy., (© 2024 John Wiley & Sons Ltd.)

Introduction: A resurgence of pertussis has been reported in numerous countries. This study aimed to determine the incidence, clinical characteristics, and outcome of pertussis among infants in Sarawak, Malaysia., Methodology: We conducted a descriptive retrospective study of infants aged < 12 months with laboratory-confirmed pertussis admitted to Bintulu Hospital in Sarawak, Malaysian Borneo, from 2015 until 2021. Pertussis was confirmed in all patients using a polymerase chain reaction of nasopharyngeal aspirates., Results: Of 588 infants who had a nasopharyngeal aspirate, 108 (18%) had laboratory-confirmed pertussis. The average annual incidence was 482 per 100,000 infants aged < 12 months between 2015 and 2019, with a marked decline in 2020 and 2021. Eighty-two (76%) were < 3 months of age. Seventy-eight (72%) were unvaccinated for pertussis, including 75 (96%) who were too young to receive the first dose. A third of the cases had atypical presentations. Severe disease characterized by hypoxemia, pulmonary hypertension, recurrent apnea, encephalopathy, or cardiovascular dysfunction occurred in 32%. Forty-eight percent required humidified high-flow nasal cannula oxygen therapy and 22% required invasive ventilation. Twenty-four percent overall needed intensive care. One (1%) infant had a fatal outcome. Nearly all cases of severe disease or those that required invasive ventilation or intensive care had received ≤ 1 dose of pertussis vaccination., Conclusions: A high incidence of pertussis with a high rate of severe disease was observed in Sarawak, Malaysia, predominantly among infants too young to be vaccinated. Additional vaccination strategies such as maternal vaccination or cocooning should be considered., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Anand Mohan, Yee-Yen Tan, Rohaidah Hashim, David Chun-Ern Ng, Veronica Huey-Shin Wong, Da-Wei Liew, Su-Lin Chien, Lee-See Tan, Peter Sie-Teck Lau, Thilagam Rajandran, Yuwana Podin, Mong-How Ooi.)

Traditionally, eosinophils have been linked to parasitic infections and pathological disease states. However, emerging literature has unveiled a more nuanced and intricate role for these cells, demonstrating their key functions in maintaining mucosal homeostasis. Eosinophils exhibit diverse phenotypes and exert multifaceted effects during infections, ranging from promoting pathogen persistence to triggering allergic reactions. Our investigations primarily focus on Bordetella spp., with particular emphasis on Bordetella bronchiseptica , a natural murine pathogen that induces diseases in mice akin to pertussis in humans. Recent findings from our published work have unveiled a striking interaction between B. bronchiseptica and eosinophils, facilitated by the btrS -mediated mechanism. This interaction serves to enhance pathogen persistence while concurrently delaying adaptive immune responses. Notably, this role of eosinophils is only noted in the absence of a functional btrS signaling pathway, indicating that wild-type B. bronchiseptica , and possibly other Bordetella spp., possess such adeptness in manipulating eosinophils that the true function of these cells remains obscured during infection. In this review, we present the mounting evidence pointing toward eosinophils as targets of bacterial exploitation, facilitating pathogen persistence and fostering chronic infections in diverse mucosal sites, including the lungs, gut, and skin. We underscore the pivotal role of the master regulator of Bordetella pathogenesis, the sigma factor BtrS, in orchestrating eosinophil-dependent immunomodulation within the context of pulmonary infection. These putative convergent strategies of targeting eosinophils offer promising avenues for the development of novel therapeutics targeting respiratory and other mucosal pathogens., Competing Interests: The authors declare no conflict of interest.

In the last twelve months, a significant global increase in pertussis cases has been observed, particularly among infants under three months of age. This age group is at the highest risk for severe disease, hospitalization, and death. Maternal immunization with the Tdap vaccine during pregnancy has been recommended to protect newborns by transferring maternal antibodies transplacentally. This review examines the current epidemiology of pertussis, the importance of preventing it in young children, and the effectiveness of maternal immunization. Despite the proven benefits of maternal vaccination, which has been found effective in pertussis prevention in up to 90% of cases, coverage remains suboptimal in many countries. Factors contributing to low vaccination rates include vaccine hesitancy due to low trust in health authority assessments, safety concerns, practical barriers to vaccine access, and the impact of the COVID-19 pandemic, which disrupted routine vaccination services. The recent increase in pertussis cases may also be influenced by the natural cyclic nature of the disease, increased Bordetella pertussis ( Bp ) activity in older children and adults, and the genetic divergence of circulating Bp strains from vaccine antigens. Given the high efficacy of maternal vaccination in preventing pertussis in infants, increasing coverage rates is crucial. Efforts to improve vaccine uptake should address barriers to access and vaccine hesitancy, ensuring consistent immune protection for the youngest and most vulnerable populations. Enhanced maternal vaccination could significantly reduce the incidence of whooping cough in infants, decreasing related hospitalizations and deaths.

Recent months have seen an increase in pertussis cases in several countries across the Northern and Southern hemispheres. The lack of immune stimulation during the COVID-19 pandemic due to the reduced circulation of Bordetella pertussis, the pathogen responsible for pertussis, is likely to have led to increased population susceptibility which has been magnified the typical three to five yearly cyclical peaks in activity. Maternal immunization for pertussis proves highly effective in protecting infants under three months of age. It's also critical for immunizers and parents to maintain high and timely immunization uptake to ensure infants receive maximum early protection when they are most at risk of severe disease., Competing Interests: Declarations of competing interest AK is the Vice President for academia and strategy of the RCOG. All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pertussis toxin (PT) is a virulent factor produced by Bordetella pertussis, the causative agent of whooping cough. PT exerts its pathogenic effects by ADP-ribosylating heterotrimeric G proteins, disrupting cellular signaling pathways. Here, we investigate the potential of two antiarrhythmic drugs, amiodarone and dronedarone, in mitigating PT-induced cellular intoxication. After binding to cells, PT is endocytosed, transported from the Golgi to the endoplasmic reticulum where the enzyme subunit PTS1 is released from the transport subunit of PT. PTS1 is translocated into the cytosol where it ADP-ribosylates inhibitory α-subunit of G-protein coupled receptors (Gαi). We showed that amiodarone and dronedarone protected CHO cells and human A549 cells from PT-intoxication by analyzing the ADP-ribosylation status of Gαi. Amiodarone had no effect on PT binding to cells or in vitro enzyme activity of PTS1 but reduced the signal of PTS1 in the cell suggesting that amiodarone interferes with intracellular transport of PTS1. Moreover, dronedarone mitigated the PT-mediated effect on cAMP signaling in a cell-based bioassay. Taken together, our findings underscore the inhibitory effects of amiodarone and dronedarone on PT-induced cellular intoxication, providing valuable insights into drug repurposing for infectious disease management., Competing Interests: Declarations. Ethics approval: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Pertussis (Whooping Cough) is a respiratory infection caused by Bordetella pertussis . Pertussis usually occurs in childhood; severe infections are most common in infants. It can be fatal with severe complications such as pulmonary hypertension, heart failure, and encephalitis., Objectives: We sought to synthesize the existing literature on severe pertussis in infants and inform further study., Methods: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in Pubmed and Embase databases, with no restrictions on the language and date of publication., Results: Of the 1299 articles retrieved, 64 were finally included. The selected articles were published between 1979 and 2022, with 90.6% (58/64) of the studies in the last two decades. The studies covered epidemiology, pathology, clinical characteristics, risk factors, treatments, and burden of disease., Conclusion: The literature reviewed suggests that studies on severe pertussis in infants covered a variety of clinical concerns. However, these studies were observational, and experimental studies are needed to provide high-quality evidence.

Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo . We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats., Competing Interests: The authors declare no conflict of interest.

Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA's mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens., Competing Interests: The authors declare no conflict of interest.

Between March and October 2022, a peak of detection of Bordetella parapertussis by qPCR, real-time PCR was observed in France. Hypothesis/Gap Statement. Whether this peak was due to resurgence from previous circulating lineages or reintroduction into the country was unknown. Objective. The objective of this study is to understand B. parapertussis- transient increase observed in France in 2022 whereas it had virtually stopped being reported since the start of the COVID-19 pandemic in 2020. Methods. We analysed real-time PCR (qPCR) data from the two largest French outpatient laboratories performing whooping cough diagnosis and characterized all B. parapertussis isolates collected in the 2016-2022 period by the French National Reference Centre for Whooping Cough. Results. Microbiological analyses reveal that 13 of 18 bacterial isolates collected in 2022 produce the vaccine antigen pertactin, whereas none of the 22 isolates collected in the 2016-2021 period did. Conclusion. We hypothesize a re-introduction of B. parapertussis from regions of the world where whole-cell vaccines are still in use.

Bordetella pertussis is the causative pathogen of whooping cough or pertussis, a contagious respiratory disease. Aside from serodiagnosis, laboratory confirmation of pertussis is done through PCR, as B. pertussis is difficult to culture. The ELITe InGenius instrument (ELITechGroup, France) with accompanying Bordetella ELITe MGB Kit was evaluated against a laboratory-developed assay. Both assays combine two screening (IS481, IS1001) and two confirmation targets (recA, ptxA-Pr or IS1002) for optimal sensitivity and specificity. The company's stated claims on sensitivity and reproducibility were confirmed. Accuracy testing showed full concordance between both assays for the screening targets. Minor discrepancies were seen for the B. pertussis confirmation target. Some cross-reactivity with other Bordetella species was observed for the IS481-target, however, none of these were confirmed in the ptxA-Pr target. These results show the suitability of the Bordetella ELITe MGB Kit for the detection and differentiation of B. pertussis, B. parapertussis and B. holmesii., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helena Martini reports equipment, drugs, or supplies was provided by ELITechGroup BV. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Introduction: Cyclical pertussis epidemics primarily affect young infants. This study aims to estimate pertussis prevalence during the ongoing 2023 outbreak at our institution, focusing on affected age groups and clinical presentations., Materiel and Methods: This retrospective study includes patients admitted to Rabat University Hospital Center from 1st January 2021 to 30th June 2023. Symptomatic patients underwent Multiplex Respiratory Panel PCR testing for respiratory infections. The analysis included cases where RT-PCR identified Bordetella spp., with data analysed using SPSS 15.0., Results: Pertussis cases sharply increased from December 2022, constituting 85.4 % of positive samples. Most cases (78.2 %) occurred in infants under 3 months, presenting symptoms such as coughing (94.5 %) and dyspnoea (94.5 %). Pertussis was suspected in 60 % of RT-PCR confirmed cases. B. pertussis DNA was identified in 81.8 % of cases and B. parapertussis DNA in 18.2 % of cases., Conclusion: The study exposes a significant pertussis outbreak affecting predominantly young infants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Bordetella pertussis is a bacterial pathogen responsible for pertussis, which is a highly contagious respiratory disease. Despite the relatively high vaccination coverage, pertussis is considered a reemerging disease that necessitates enhanced strategies for identification, prevention, and control. The diagnosis of pertussis typically involves a combination of clinical evaluation, laboratory tests, and a thorough medical history. The current technologies for pertussis diagnosis have their own limitations, prompting the exploration of alternative diagnostic approaches that offer enhanced sensitivity, specificity, and speed. Microfluidic technology is considered a very promising tool for the diagnosis of infectious diseases, as it offers more rapid and accurate outputs. It allows point-of-care testing (POCT) at or near the patient site, which can be critical, especially for an outbreak or pandemic. In this paper, current pertussis diagnostic tools with their limitations were discussed, and microfluidic approaches for the diagnosis of pertussis were highlighted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis , which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

Rapid, sensitive and specific methods are crucial for nucleic acid detection. CRISPR/Cas12b has recently been widely used in nucleic acid detection. However, due to its thermophagic property, DNA isothermal recombinase-aided amplification (RAA) and subsequent CRISPR/Cas12b detection require two separate reactions, which is cumbersome and inconvenient and may cause aerosol pollution. In this study, we propose an RAA-CRISPR/Cas12b one-pot detection assay (Rcod) for Bordetella pertussis detection without additional amplification product transfer steps. The time from sample processing to response time was less than 30 min using nucleic acid extraction-free method, and the sensitivity reached 0.2 copies/μL. In this system, Alicyclobacillus acidoterrestris Cas12b protein (AacCas12b) exhibited strong and specific trans-cleavage activity at a constant temperature of 37 °C, while the cis-cleavage activity was weak. This characteristic reduces the interference of AacCas12b with nucleic acids in the system. Compared with real-time PCR, our Rcod system detected B. pertussis in 221 clinical samples with a sensitivity and specificity of 97.96 % and 99.19 %, respectively, with nucleic acid extraction-free method. The rapid, sensitive and specific Rcod system provides ideas for the establishment of CRISPR-based one-step nucleic acid detection and may aid the development of reliable point-of-care nucleic acid tests. IMPORTANCE: Pertussis is an acute respiratory infection caused by B. pertussis that is highly contagious and potentially fatal, and early diagnosis is essential for the treatment of whooping cough. In this study, we found that AacCas12b has high and strongly specific trans-cleavage activity at lower temperatures. A RAA-CRISPR/Cas12b one-step detection platform (Rcod) without interference with amplification was developed. In addition, the combination of Rcod and nucleic acid extraction-free method can quickly and accurately detect the qualitative detection of B. pertussis, and the detection results are visualized, which makes the pathogen nucleic acid detection and analysis process simpler, and provides a new method for the rapid clinical diagnosis of B. pertussis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Maternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination., Methods: We performed a time-trend analysis of infant pertussis hospitalizations during 2005-2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3-11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005-2014) and after vaccination introduction (2015-2019), using segmented Poisson regression., Results: During the pre-vaccination period, infants aged 0-2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0-2 months than in infants aged 3-11 months: annual reduction of 34 % (95 % CI: 31-38) versus 26 % (95 % CI: 21-31) in the hospitalization rate and 13 % (95 % CI: 11-15) versus 6 % (95 % CI: 2-9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups., Conclusions: Maternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest No conflict of interest to declare except for Elmira Flem who has been employed since April 2019 by Merck & Co., Inc., North Wales, PA, USA. The work for the current study was conducted by Dr. Flem under the previous affiliation at the Norwegian Institute of Public Health., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019., Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines., Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction)., Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes., ((c) 2024 The authors; licensee World Health Organization.)

Objectives: To evaluate the incidence of laboratory-confirmed pertussis (LCP) among infants hospitalized with acute respiratory infections (ARIs) and meeting the Centers for Disease Control and Prevention (CDC)-recommended clinical case definition., Methods: An investigator-initiated active surveillance for clinically suspected cases (CSCs) of pertussis screened infants aged ≤6 mo hospitalized with ARIs during January 2020-April 2022 at seven centers across India. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect Bordetella pertussis in nasopharyngeal swabs. Infants were classified as having 'LCP' or 'probable pertussis' (PP)., Results: Among 1102 screened infants, 400 participants met the CDC-2020 clinical case definition for pertussis. Of these, 34/400 (8.5%) had LCP and 46/400 (11.5%) had PP. The proportion of participants with LCP and PP was similar among infants aged 0-3 and 4-6 mo [LCP: 0-3 mo, 21/248 (~9%); 4-6 mo, 13/152 (~9%); PP: 0-3 mo, 30/248 (~12%); 4-6 mo, 16/152 (~11%)]. Cough illness lasted ≥2 wk in 3/34 (~9%) and 34/46 (~74%) participants with LCP and PP, respectively. Notably, 80% CSCs had neither LCP nor PP, and a respiratory pathogen apart from B. pertussis was detected in ~32%. Ventilation was required in 12 participants with LCP/PP., Conclusions: In this first study from India based on revised CDC guidelines, the incidence of LCP was 8.5%; cough illness was not a predominant feature. Infants below the age appropriate for vaccination are prone to pertussis-related hospital admissions, ICU care, and ventilation. Maternal immunization may be evaluated for neonatal protection, in addition to other strategies, to decrease disease burden in this highly vulnerable group., Clinical Trial Registration Number: CTRI/2019/12/022449., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

We report a record high pertussis epidemic in Denmark since August 2023. Highest incidence was in adolescents, while peak incidence in infants was lower vs previous epidemics in 2019 and 2016. Among infants aged 0-2 months, over half (29/48) were hospitalised and one infant died, underlining the disease severity in the youngest. To protect infants, pertussis vaccination in pregnant women was introduced in January 2024 in the national vaccination programme. Improved vaccination surveillance in pregnant women is being implemented.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Competing interests: None declared.

We evaluated the genetic diversity of Bordetella pertussis, the causative agent of pertussis, within households by whole-genome sequencing. In pairwise comparisons of 23 isolates collected from 11 households, single-nucleotide polymorphism (SNP) analysis revealed extremely low SNP diversity (≤1 SNP) between isolate pairs: no SNPs were detected in 10 households and one SNP was obtained in the remaining household. This SNP was uncommon for B. pertussis and resulted in a nonsynonymous substitution (Ala303Thr) in nicotinate phosphoribosyltransferase. We demonstrated that the same strain is transmitted between household members and that B. pertussis is genomically stable during household transmission., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26-35) to 9.6% (3-5) in Nha Trang (2017) and from 7.2% (age 26-35) to 11.4% (6-15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.

Whooping cough is a disease caused by Bordetella pertussis, whose morbidity has increased, motivating the improvement of current vaccines. Reverse vaccinology is a strategy that helps identify proteins with good characteristics fast and with fewer resources. In this work, we applied reverse vaccinology to study the B. pertussis proteome and pangenome with several in-silico tools. We analyzed the B. pertussis Tohama I proteome with NERVE software and compared 234 proteins with B. parapertussis, B. bronchiseptica, and B. holmessi. VaxiJen was used to calculate an antigenicity value; our threshold was 0.6, selecting 84 proteins. The candidates were depurated and grouped in eight family proteins to select representative candidates, according to bibliographic information and their immunological response predicted with ABCpred, Bcepred, IgPred, and C-ImmSim. Additionally, a pangenome study was conducted with 603 B. pertussis strains and PanRV software, identifying 3421 core proteins that were analyzed to select the best candidates. Finally, we selected 15 proteins from the proteome study and seven proteins from the pangenome analysis as good vaccine candidates., (Copyright © 2023 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Introduction: Pertussis is a highly contagious respiratory infection. It affects people of all ages, yet evidence of the impact of pertussis in adults with underlying conditions (UCs) is scarce. This study investigated the incidence and complication rate of pertussis in adult patients with and without UC., Methods: A retrospective analysis was conducted using routinely collected German claims data between 2015 and 2019. Patients with and without different pneumological, cardiovascular, endocrinological, musculoskeletal, and psychological UCs were matched for incidence estimation. Logistic regression models were used to estimate the risk of pertussis depending on the presence of UCs. Negative binomial models were used to assess complication rates in patients with pertussis and with and without UC., Results: In total, 4383 patients were diagnosed with pertussis during the study period. Patients with any UC had an increased risk for pertussis compared to matched patients without UC (odds ratio [OR] 1.72; 95% confidence interval [CI]1.60-1.84, p < 0.0001). Underlying asthma had the highest risk of pertussis (OR 2.70; 95% CI 2.50-2.91, p < 0.0001), followed by chronic obstructive pulmonary disease (OR 2.35; 95% CI 2.10-2.60, p < 0.0001) and depression (OR 2.08; 95% CI 1.95-2.22, p < 0.0001). Severe complications occurred in 10.8% of the pertussis cohort (13.4% with UC vs. 9.5% without UC). The UC-attributable effect on the risk of severe pertussis-related complications was significantly increased for any UC (incidence rate ratio [IRR] 1.29, 95% CI 1.19-1.39). The severe complication risk was also increased for patients aged 60+ (IRR 1.59, 95% CI 1.46-1.72)., Conclusion: This study shows that adults with certain UCs have an increased risk for pertussis and are more likely to have complications. These results provide further evidence that pertussis is a relevant and impactful infectious disease in adults with and without certain UC, indicating that these patients need to be considered when developing vaccination recommendations to avoid pertussis and its associated complications. A graphical abstract is available with this article., (© 2024. The Author(s).)

Here, we report the complete genome of Bordetella parapertussis strain 400431-b isolated from a nasopharyngeal swab from a 4-year-old patient presenting with a protracted course of whooping cough, vaccinated with three doses of diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis- Haemophilus influenzae type b vaccine., Competing Interests: The authors declare no conflict of interest.

Importance: Pertussis, caused by Bordetella pertussis , can cause debilitating respiratory symptoms, so whole-cell pertussis vaccines (wPVs) were introduced in the 1940s. However, reactogenicity of wPV necessitated the development of acellular pertussis vaccines (aPVs) that were introduced in the 1990s. Since then, until the COVID-19 pandemic began, reported pertussis incidence was increasing, suggesting that aPVs do not induce long-lasting immunity and may not effectively prevent transmission. Additionally, aPVs do not provide protection against other Bordetella species that are observed during outbreaks. The significance of this work is in determining potential new vaccine antigens for multiple Bordetella species that are predicted to elicit long-term immune responses. Genome-based approaches have aided the development of novel vaccines; here, these methods identified Bordetella vaccine candidates that may be cross-protective and predicted to induce strong memory responses. These targets can lead to an improved vaccine with a strong safety profile while also strengthening the longevity of the immune response., Competing Interests: The authors declare no conflict of interest.

Introduction: Whooping cough, also known as pertussis, remains a significant challenge as a vaccine-preventable disease worldwide. Since the switch from the whole-cell Pertussis (wP) vaccine to the acellular Pertussis vaccine (aP), cases of whooping cough have increased in countries using the aP vaccine. Understanding the immune system's response to pertussis vaccines and infection is crucial for improving current vaccine efficacy., Areas Covered: This review of the literature using PubMed records offers an overview of the qualitative differences in antibody and T cell responses to B. pertussis (BP) in vaccination and infection, and their potential association with decreased efficacy of the aP vaccine in preventing infection and subclinical colonization. We further discuss how asymptomatic infections and carriage are widespread among vaccinated human populations, and explore methodologies that can be employed for their detection, to better understand their impact on adaptive immune responses and identify key features necessary for protection against the disease., Expert Opinion: An underappreciated human BP reservoir, stemming from the decreased capacity of the aP vaccine to prevent subclinical infection, offers an alternative explanation for the increased incidence of clinical disease and recurrent outbreaks.

The present article offers a historical overview on pertussis (whooping cough) by analysing the ancient epidemic manifestations of the disease and the path towards the discovery of an effective vaccine against it. The original mentions of pertussis are examined with reference to Mediaeval Afghanistan and the famous AD 1578 Paris epidemic described by the French physician Guillaume de Baillou. The historical data are then matched with information derived from analyses of phylogenetic trees of B. pertussis. Finally, this article also highlights some recent challenges posed to public health by this infectious disease., Competing Interests: The authors declare no conflict of interest., (©2024 Pacini Editore SRL, Pisa, Italy.)

Problem: Effective interventions are needed to promote informed decision making about vaccination., Background: We developed a group-antenatal care (CP; Centering Pregnancy) intervention, i.e., a session about MPV within existing group-care settings, to promote informed decision making about Maternal Pertussis Vaccination in the Netherlands., Aim: This study aimed to assess (1) to what extent the intervention was implemented as intended, (2) to what extent the intervention met the needs and wishes of pregnant individuals and midwives facilitating CP., Methods: We conducted exploratory interviews with 6 CP facilitators and 10 CP participants to assess the implementation of the intervention, and how the intervention and its different components were perceived. Interviews were analysed using thematic analysis. In addition, we conducted a pre- and post-intervention survey amongst 35 participants, measuring knowledge about MPV, and MPV attitude and intention., Results: The CP intervention was implemented as intended in 6 out of 7 groups. Participants were positive about the interactive CP-methods used to discuss MPV. Participants and facilitators evaluated the intervention as positive and relevant, although the intervention was time-consuming, and some participants had already made the de decision about MPV. Those who had not yet decided indicated that the session was helpful for their decision., Discussion and Conclusion: Discussing MPV in CP care settings is a feasible strategy to support decision making about MPV during pregnancy. The intervention could be improved by discussing the MPV sooner than 16-18 weeks of pregnancy. A larger-scale study is needed to assess effects on MPV uptake and informed decision making., Competing Interests: Declaration of Competing Interest The authors declare that they do not have competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015-2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50-64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.

Background: Pertussis and influenza cause significant morbidity and mortality in pregnancy and the neonatal period. Maternal vaccination in pregnancy would reduce harm, but low vaccine uptake is a concern. This scoping review aimed to understand the reasons for, and approaches, to non-uptake of pertussis and influenza vaccinations in pregnant women in the UK and Ireland., Methods: The inclusion criteria of this scoping review consist of pregnant women who avail of pertussis and influenza vaccines in the UK and Ireland. MEDLINE, EMBASE, Web of Science and CINAHL databases were searched in June 2021 and updated in October 2022. Searches were limited to English language reports published after 2011. We followed the Joanna Briggs Institute guidance on scoping reviews. Data were extracted and charted., Results: Five themes emerged from the literature. Acceptability, as well as organisational and awareness issues, were overarching themes regarding reasons for and approaches to non-uptake of the vaccines respectively. Other themes included healthcare professional factors, information interpretation and pregnancy-related factors., Conclusions: Women need clear, comprehensible information, ideally provided by their healthcare professionals, in a way that is meaningful and addresses their circumstances and risk perceptions. This research will serve as a base for future work that aims behaviour science interventions at the wider pregnant population as well as the target groups that have been identified in this review., (© 2023. The Author(s).)

Previously developed whole-cell vaccines against Bordetella pertussis , the causative agent of whooping cough, appeared to be too reactogenic due to their endotoxin content. Reduction in endotoxicity can generally be achieved through structural modifications in the lipid A moiety of lipopolysaccharides (LPS). In this study, we found that dephosphorylation of lipid A in B. pertussis through the heterologous production of the phosphatase LpxE from Francisella novicida did, unexpectedly, not affect Toll-like receptor 4 (TLR4)-stimulating activity. We then focused on the inner core of LPS, whose synthesis has so far not been studied in B. pertussis . The kdtA and kdkA genes, responsible for the incorporation of a single 3-deoxy-D- manno -oct-2-ulosonic acid (Kdo) residue in the inner core and its phosphorylation, respectively, appeared to be essential. However, the Kdo-bound phosphate could be replaced by a second Kdo after the heterologous production of Escherichia coli kdtA . This structural change in the inner core affected outer-core and lipid A structures and also bacterial physiology, as reflected in cell filamentation and a switch in virulence phase. Furthermore, the eptB gene responsible for the non-stoichiometric substitution of Kdo-bound phosphate with phosphoethanolamine was identified and inactivated. Interestingly, the constructed inner-core modifications affected TLR4-stimulating activity. Whereas endotoxicity studies generally focus on the lipid A moiety, our data demonstrate that structural changes in the inner core can also affect TLR4-stimulating activity., Competing Interests: Authors M.P., D.I., N.D. and S.S. are employed by the GSK group of companies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Bordetella pertussis , the causative agent of whooping cough, is an extracellular, strictly human pathogen. However, it has been shown that B. pertussis cells can escape phagocytic killing and survive in macrophages upon internalization. Our time-resolved RNA-seq data suggest that B. pertussis efficiently adapts to the intramacrophage environment and responds to host bactericidal activities. We show that this adaptive response is multifaceted and, surprisingly, related to the BvgAS two-component system, a master regulator of virulence. Our results show that the expression of this regulatory circuit is downregulated upon internalization. Moreover, we demonstrate that the switch to the avirulent Bvg - phase augments a very complex process based on the adjustment of central and energy metabolism, cell wall reinforcement, maintenance of appropriate redox and metal homeostasis, and repair of damaged macromolecules. Nevertheless, not all observed effects could be simply attributed to the transition to Bvg - phase, suggesting that additional regulators are involved in the adaptation to the intramacrophage environment. Interestingly, a large number of genes required for the metabolism of sulphur were strongly modulated within macrophages. In particular, the mutant lacking two genes encoding cysteine dioxygenases displayed strongly attenuated cytotoxicity toward THP-1 cells. Collectively, our results suggest that intracellular B. pertussis cells have adopted the Bvg - mode to acclimate to the intramacrophage environment and respond to antimicrobial activities elicited by THP-1 cells. Therefore, we hypothesize that the avirulent phase represents an authentic phenotype of internalized B. pertussis cells.

Introduction: This case report presents a unique acute dystonic reaction (ADR) induced by metoclopramide in a 6-year-old male patient with pertussis-associated vomiting. The rarity of such a reaction in pediatric patients underscores the significance of this case in contributing to the scientific literature. This report highlights the need for heightened awareness of the potential adverse effects of medications commonly used in pediatrics and emphasizes the importance of tailored interventions for this population., Main Symptoms and Important Clinical Findings: Following the administration of metoclopramide for vomiting associated with pertussis cough, the patient exhibited distressing symptoms, including torticollis, facial grimacing, and tongue protrusion. These involuntary movements were promptly recognized, leading to the suspicion of an ADR. The clinical findings underscore the importance of vigilant monitoring for extrapyramidal symptoms following medication administration, especially in children., The Main Diagnoses, Therapeutic Interventions, and Outcomes: The primary diagnosis of ADR induced by metoclopramide was confirmed, prompting the cessation of the medication and the initiation of anticholinergic therapy with benztropine. This intervention rapidly resolved the patient's symptoms, highlighting the importance of tailored and swift therapeutic strategies. The outcome demonstrated the efficacy of timely intervention in managing ADR in pediatric patients., Conclusion: The main takeaway lesson from this case lies in the critical need for healthcare practitioners to remain vigilant for potential adverse reactions in pediatric patients, even when prescribing commonly used medications. The successful management of this case underscores the importance of prompt recognition, appropriate interventions, and continuous monitoring. Ultimately, this case contributes to the scientific literature by highlighting the unique manifestation of ADR in a pediatric patient, reinforcing the significance of individualized patient care and medication safety., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-‍6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.

Bordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the Bordetella type III chaperone of BtrA.In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node.

Objective: COVID-19 vaccination is a key approach to reduce morbidity and mortality in pregnant patients and their newborns. Anti-vaccine sentiment has recently increased with unclear impact on pregnant patients. We examined the association between acceptance of tetanus-diphtheria-acellular pertussis (Tdap) and influenza vaccines, considered to be routine pregnancy vaccines, and COVID-19 vaccine acceptance. Secondarily, we identified other predictors of COVID-19 vaccine uptake and described pregnancy outcomes in patients who were and were not vaccinated during pregnancy., Methods: A retrospective cohort study of all patients who delivered at a single site from December 2020 - March 2022. Demographic, pregnancy, neonatal, and vaccination data were abstracted from the electronic medical record, which imports vaccine history from the California Immunization Registry. The relationship between influenza and Tdap vaccine acceptance, other baseline characteristics, and COVID-19 vaccine uptake was assessed using univariable and multivariable regression analysis., Results: Of the 7857 patients who delivered during the study period, 4410 (56.1%) accepted the COVID-19 vaccine. Of those who received the COVID-19 vaccine, 3363 (97.6%) and 3049 (88.5%) received influenza and Tdap vaccines, respectively. Patients were more likely to receive the COVID-19 vaccine if they had advanced maternal age, obesity, Asian race, and private insurance. After adjustment for baseline differences, COVID vaccine acceptance was associated with receipt of Tdap (aOR 2.10, 95% CI 1.90-2.33) and influenza vaccines (aOR 2.83, 95% CI 2.55-3.14). There were no differences in preterm birth, low birthweight, and NICU admission between patients who received and did not receive the COVID-19 vaccine., Conclusion: Patients were more likely to accept COVID-19 vaccination if they received Tdap or influenza vaccinations. Older age, obesity, Asian race, and private insurance were independent predictors of vaccine uptake. Disparities in COVID-19 vaccination uptake bear further exploration to guide efforts in equitable and widespread vaccine distribution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)