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How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

ABSTRACT Objective Design Setting Population or Sample Methods Main Outcome Measures Results Conclusions Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited.Population‐based linkage data were collected during 2001–2016.New South Wales, Australia.A total of 1 453 037 singleton births.Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates.Adverse birth outcomes (preterm birth and low birth weight).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).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. [ABSTRACT FROM AUTHOR]

Background: Dried blood spots (DBSs) enable the study of serological markers of various pathogens without the need to obtain serum/plasma through venipuncture. Methods: Sixty-four blood samples were prepared on Whatman™ 903 cards using specimens obtained by venipuncture to study the detection of serological markers of diphtheria, tetanus, and pertussis in DBSs, and their stability 4 months post-collection. An automated chemiluminescent immunoassay was used to investigate diphtheria, tetanus, and pertussis IgG levels from both DBSs and plasma samples. Results: An optimal cut-off value for DBSs was calculated to improve the performance of diphtheria and tetanus serological markers in DBSs, achieving high sensitivity (95% and 98%, respectively) and specificity (91.7% and 92.3%, respectively). No protection against pertussis was found in the population studied. The correlation observed between the plasma and the DBSs processed after sample collection was high (0.967–0.970) for all antibodies studied except pertussis (0.753), both considering hematocrit before sample elution or not. The correlation between DBSs and plasma for diphtheria and tetanus remained strong following a 4-month delay in DBS processing at 4 °C (0.925–0.964) and −20 °C (0.924–0.966), with only a minor decrease observed for diphtheria at room temperature (0.889), while maintaining a strong correlation for tetanus (0.960). For pertussis, the correlation between DBSs and plasma was drastically reduced after delaying its processing for 4 months at any temperature. Conclusions: To summarize, hematocrit levels within the normal range do not affect the processing of DBSs in the study of serological markers of diphtheria, tetanus, and pertussis. The DBS stability for serological diagnosis of diphtheria and tetanus is adequate when samples are stored at −20 °C for a period of 4 months. The pertussis serological marker does not appear to remain stable after 4 months, even when the DBS is stored frozen at −20 °C. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics of pulmonary function changes in older children with pertussis. Methods Clinical data and pulmonary function date of older children diagnosed with pertussis in outpatient clinics from April 2021 to December 2023 were collected. The clinical data of the case group were collected. A group of healthy older children were included as the control group. Pulmonary function parameters included peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, expiratory flow at 50% of vital capacity (FEF50), maximum mid-expiratory flow (MMEF) and expiratory flow rate with 75% vigorous exhalation (FEF75). Results Seventy children (36 boys and 34 girls) with pertussis were recruited in the case group, including 54 children with pertussis only and 16 children with pertussis and asthma together. The incidence of paroxysmal cough was 40.0% (28/70) and inspiratory croup 8.5% (6/70) in the case group. Sixty healthy children (28 boys and 32 girls) were included in the control group. There were no significant differences in gender, age, height and body weight between children with pertussis alone group and the control group (P＞0.05). The pulmonary function parameters were significantly lower in the children with pertussis alone group than those in the control group, and PEF had the most obvious decline: PEF%pred [80.5 (62.6, 85.9) vs. 109.8 (103.2, 118.7)]. Compared with the pertussis alone group, pulmonary function was not decrease further in the pertussis combined with asthma group. After the improvement of clinical symptoms of children in the pertussis alone group, the level of pulmonary function (PEF and FEF50) increased significantly, but they were still lower than those of the control group. Conclusion The pulmonary function declines slightly in loder children with pertussis. The decreased PEF is most significant. [ABSTRACT FROM AUTHOR]

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Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1–14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1–14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5–14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1–4 years and 5–14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592–2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299–2.550 in Riskesdas 2018). In the adjusted analysis for respondents' characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670–3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5–14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control. [ABSTRACT FROM AUTHOR]

Background: Bordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines. Results: This work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs). Conclusion: These findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis. [ABSTRACT FROM AUTHOR]

Objective To clarify the epidemiological and spatiotemporal clustering characteristics of pertussis in Ningxia Hui Autonomous Region from 2012 to 2023, providing reference for pertussis prevention and control. Methods Case information was obtained from the Infectious Disease Surveillance System of the Chinese Center for Disease Control and Prevention, and immunization history information was obtained from the Immunization Planning Information System of Ningxia. Descriptive epidemiological methods and spatiotemporal scan analysis were used for analysis. Results From 2012 to 2023, totally 1 394 pertussis cases were reported in Ningxia, with an average annual incidence rate of 1.66/100 000. The overall incidence showed a fluctuating upward trend, with the highest annual incidence rates in 2022 (16.78/100 000), 2019 (1.02/100 000), and 2021 (0.70/100 000). No cases were reported in 2013. The incidence showed a unimodal distribution, with a peak in July-August. Spatiotemporal scan analysis identified 9 spatiotemporal clusters in 2022, with a relative risk ranging from 5.81 to 113.92. These clusters covered 4 municipalities and 14 counties, with the primary cluster located in Jinfeng District of Yinchuan city, with a clustering period from April to September 2022. The high-risk population was concentrated in the age groups of 0 years, 1 to 4 years, and 5 to 9 years, with significantly higher incidence rates in 2022 compared to 2019, increasing by 5.53 times, 11.29 times, and 581.52 times, respectively. The proportions of cases with immunization history and complete four-dose immunization history were 75.47% and 60.40%, respectively. Conclusion From 2012 to 2023, pertussis incidence in Ningxia showed a fluctuating upward trend with spatiotemporal clustering. The disease mainly affected infants with incomplete basic immunization and school-age children (5 to 9 years) without complete immunization. It is necessary to improve the pertussis surveillance system, optimize pertussis immunization strategies, and enhance timely vaccination. [ABSTRACT FROM AUTHOR]

Maternal vaccines during pregnancy offer crucial protection against infections for both the pregnant person and their newborn. Vaccines against influenza, pertussis, coronavirus disease 2019, and respiratory syncytial virus are routinely recommended by the Centers for Disease Control and Prevention to safeguard pregnant women and their infants from potentially severe complications. Administering these vaccines during pregnancy helps transfer protective antibodies from the mother to the baby, enhancing immunity during the vulnerable early months of life. Extensive research supports the safety and efficacy of maternal vaccines, with numerous studies demonstrating their protective benefits for both pregnant people and newborns. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article provides a summary of Stefania Pandolfo's book "Knot of the Soul: Madness, Psychoanalysis, Islam," which explores the experiences of individuals with psychosis and their understanding of interiority. The author of the article shares their own experiences with mental illness and finds resonance in Pandolfo's work, particularly in the discussions of Islamic theology and the vocabulary used to understand the inner landscape. The article emphasizes the importance of witnessing and storytelling in the context of mental health and delves into themes of imagination and divine contact in relation to psychosis. It also examines the concept of the soul in Islamic theology and the role of healers in treating mental illness. The author concludes by discussing the potential of anthropology to comprehend and uncover the inner experiences of individuals. [Extracted from the article]

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Background: Previous studies have compared the incidence of pertussis before and during the COVID-19 pandemic, finding that public health measures related to COVID-19 contributed to a temporary decline in reported pertussis cases during the pandemic. However, the post-pandemic period has seen a resurgence in respiratory infections, influenced by relaxed health measures and decreased public vigilance. This study investigates the epidemiological dynamics of pertussis among patients with acute respiratory tract infections (ARTI) in Zhejiang Province, China, providing essential reference information for ongoing public health strategies. Methods: This study analyzed multicenter data from January 2023 to May 2024, involving 8,560 patients with ARTI from three hospitals in Zhejiang Province. Inclusion criteria included patients who presented with cough symptoms and were clinically diagnosed with either acute upper respiratory tract infections (URTI) or acute lower respiratory tract infections (LRTI), and who had undergone at least one Bordetella pertussis DNA test. The study analyzed the epidemiological changes of pertussis positivity rates and their associations with time, age, gender, and diagnosis types (URTI and LRTI). Results: From January 2023 to May 2024, the positivity rate and testing number for pertussis among patients with ARTI generally showed a gradual increasing pattern. In March 2024, the positivity rate reached its peak at 31.58%, followed by a weekly decline. The overall positivity rate was 23.59%, with no significant differences observed between genders. Pertussis incidence was higher in patients with LRTI (24.49%) compared to those with URTI (18.63%, OR= 1.40, 95% CI: 1.20-1.63, p < 0.001) and in outpatients (25.32%) compared to inpatients (6.09%, OR= 4.17, 95% CI: 3.07-5.64, p < 0.001). According to a generalized additive model analysis, there was a wave-shaped, non-linear relationship between age and pertussis incidence, with a relatively high rate observed in the 5 to 17 age group, peaking at age 10 (33.85%). Additionally, the impact of age, patient type, and diagnosis type on the pertussis infection rate varied across different age groups. Conclusion: After the COVID-19 pandemic, the positivity rate of pertussis in Zhejiang Province peaked in early 2024 and then showed a declining pattern. Children and adolescents were particularly affected, emphasizing the need for enhanced vaccination and public health interventions in this population. [ABSTRACT FROM AUTHOR]

Copyright of Remedia is the property of Medical Tribune CZ, s.r.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. We performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3 -lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. : We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3 -MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance. [ABSTRACT FROM AUTHOR]

Relevance. Antibacterial drugs are widely used to treat and prevent infections of the upper and lower respiratory tract. The large-scale and unjustified use of antimicrobials to treat these infections has led to the emergence of resistance in most pathogens. The aim. To study antimicrobial susceptibility testing to erythromycin and azithromycin of strains of B. pertussis isolated in Russia. Materials & Methods. The research included 165 strains of B. pertussis isolated in January 2014 to June 2020. Antimicrobial susceptibility to erythromycin and azithromycin was determined by disk diffusion method and MIC test (HiMedia Laboratories Pvt. Limited, India). The A2047G mutation in the 23S rRNA gene was detected by PCR and subsequent sequencing. Results. Disk diffusion zone diameters for erythromycin in the studied strains ranged from 25 to 62 mm (median 44 mm) and disk diffusion zone diameters for azithromycin ranged from 22 to 80 mm (median 50 mm). Isolates with growth inhibition of more than 42 mm in diameter after 7 days of incubation were considered as susceptible. Among the studied strains, 57 (34.5%) were resistant to erythromycin and 23 (13.9%) to azithromycin. Then, MIC of erythromycin and MIC of azithromycin, respectively, were determined for these 57 and 23 strains using the MIC test. The comparison group included 79 isolates that were classified as sensitive to erythromycin (n = 31) and azithromycin (n=48) according to the results of the previous study. A MIC value of 0.12 μg/ml was considered as the cut-off for susceptible strains. All isolates were fully susceptible to erythromycin (MIC ≤ 0.01 μg/ml, median MIC 0.001 μg/ml) and azithromycin (MIC ≤ 0.01 μg/ml, median MIC 0.0001 μg/ml). An A-to-G mutation was not found at position 2047 in the 23S rRNA gene in 80 isolates that had a diameter of growth inhibition zone less than 42 mm. Conclusion. This study demonstrates no significant decrease in the susceptibility to erythromycin and azithromycin among B. pertussis strains isolated in Russia in 2014–2020. The studied B. pertussis strains exhibit a homozygous phenotype for macrolide resistance.

To develop and validate a diagnostic prediction model based on blood parameters for predicting the pertussis in children. A retrospective study of 477 children with suspected pertussis at Zigong First People's Hospital was performed between January 2020 and December 2021. The patients were randomly divided into training cohort and validation cohort. Stepwise regression and R software was performed to develop and validate the model. Stepwise regression analysis showed that white blood cell (WBC), hematocrit (HCT), lymphocyte (LYMPH), C-reactive protein (CRP) and platelet distribution width to mean platelet volume ratio (PDW-MPV-R) were found to be independent factors associated with pertussis. The model containing WBC, CRP and PDW-MPV-R had the best performance. The area under curve (ROC, 0.77 for the training cohort and 0.80 for the validation cohort) of the model indicated satisfactory discriminative ability. The sensitivity and specificity of the model were 72.1% and 72.6% in training cohort and 74% and 72.1%, respectively, in validation cohort. Based on the ROC analysis, calibration plots, and decision curve analysis, we concluded that the model exhibited excellent performance. A model based on blood parameters is sufficiently accurate to predict the probability of pertussis in children, and may provide some reference for clinical decisions. [ABSTRACT FROM AUTHOR]

Nandina domestica: Thunb. is a traditional Chinese herbal drug that has long been used in China and Japan for the treatment of colds, fevers, asthma, chronic bronchitis, conjunctivitis, whooping cough, pharyngeal tumors, etc. Published data have reported at least 366 constituents from N. domestica, including alkaloids, flavonoids, lignans, terpenoids, phenolic acids and their derivatives, fatty acids, and others. Of these, the isoquinoline alkaloids are considered characteristic markers for N. domestica. These alkaloids also showed the most promising bioactivities. The crude extracts or semi-purified constituents of N. domestica exhibit a variety of activities, including antitumor, dermatological, antiinflammatory, antioxidant, antimicrobial, and detoxification activities, as well as effects on respiratory system, etc. The fruit is considered poisonous when eaten raw, with nausea, vomiting, diarrhea, and abdominal pain as side effects after ingestion. Most traditional uses are supported by biological activities demonstrated in modern experimental studies, suggesting a potential medicinal value of N. domestica. However, more information is needed on its mechanisms of activity, pharmacokinetic profile of the constituents, and its safety and efficacy profile in humans. [ABSTRACT FROM AUTHOR]

Background: Pertussis is a highly contagious respiratory illness mainly caused by Bordetella pertussis (BP). Bordetella parapertussis (BPP) can induce symptoms compatible with pertussis, but has been underdiagnosed and underreported. The current pertussis vaccines offer low protection against BPP. Herein, we aim to reveal the epidemiology and genomic evolution of BPP in Shanghai, China. Methods: Children diagnosed with BPP infection from January 2017 to December 2022 in Shanghai, China were enrolled. We performed antimicrobial susceptibility testing (AST), multiple locus variable-number tandem repeat analysis (MLVA), and whole genome sequencing (WGS) analysis. A total of 260 international BPP genomes were chosen for comparison to investigate the genomic diversity and phylogenetic characteristics of Chinese strains within a global context. Results: Sixty patients were diagnosed with BPP infection by culture, with the positive ratio of 3.5‰ (60/17337) for BPP in nasopharyngeal swap samples. The average age of patients was 4.5 ± 0.3 years. BPPs contained four MLVA types including MT6 (65.0%), MT4 (26.7%), untype-1 (6.7%) and MT5 (1.7%), and none of strains showed resistance to macrolides. All strains carried virulence genotype of ptxP37/ptxA13/ptxB3/ptxC3/ptxD3/ptxE3/fim2-2/fim3-10. MT4 and MT5 strains carried prn54, whereas MT6 and untype-1 BPPs expressed prn101. We identified two outbreaks after 2020 caused by MT4 and MT6 strains, each corresponding to distinct WGS-based phylogenetic lineages. The MT4-lineage is estimated to have originated around 1991 and has since spread globally, being introduced to China between 2005 and 2010. In contrast, the MT6-lineage was exclusively identified in China and is inferred to have originated around 2002. Conclusion: We revealed the genomic diversity of BPPs circulating in Shanghai, China, and reported the outbreaks of MT6 and MT4 BPPs after 2020. This is the first report on the emergence and regional outbreak of MT6 BPPs in the world, indicating that continuous surveillance on BPPs are thus required. [ABSTRACT FROM AUTHOR]

Little is known about oxygen utilization during infection by bacterial respiratory pathogens. The classical Bordetella species, including B. pertussis, the causal agent of human whooping cough, and B. bronchiseptica, which infects nearly all mammals, are obligate aerobes that use only oxygen as the terminal electron acceptor for electron transport-coupled oxidative phosphorylation. B. bronchiseptica, which occupies many niches, has eight distinct cytochrome oxidase-encoding loci, while B. pertussis, which evolved from a B. bronchiseptica-like ancestor but now survives exclusively in and between human respiratory tracts, has only three functional cytochrome oxidase-encoding loci: cydAB1, ctaCDFGE1, and cyoABCD1. To test the hypothesis that the three cytochrome oxidases encoded within the B. pertussis genome represent the minimum number and class of cytochrome oxidase required for respiratory infection, we compared B. bronchiseptica strains lacking one or more of the eight possible cytochrome oxidases in vitro and in vivo. No individual cytochrome oxidase was required for growth in ambient air, and all three of the cytochrome oxidases conserved in B. pertussis were sufficient for growth in ambient air and low oxygen. Using a high-dose, large-volume persistence model and a low-dose, small-volume establishment of infection model, we found that B. bronchiseptica producing only the three B. pertussis-conserved cytochrome oxidases was indistinguishable from the wild-type strain for infection. We also determined that CyoABCD1 is sufficient to cause the same level of bacterial burden in mice as the wild-type strain and is thus the primary cytochrome oxidase required for murine infection, and that CydAB1 and CtaCDFGE1 fulfill auxiliary roles or are important for aspects of infection we have not assessed, such as transmission. Our results shed light on the environment at the surface of the ciliated epithelium, respiration requirements for bacteria that colonize the respiratory tract, and the evolution of virulence in bacterial pathogens. Author summary: Cytochrome oxidases, critical components for aerobic respiration, have been shown to be vital for pathogenesis and tissue tropism in several bacterial species. However, the majority of the research has focused on facultative anaerobes and infections of microoxic to anaerobic host environments, like the gut. We sought to understand the role of cytochrome oxidases during respiratory infection by Bordetella bronchiseptica, an obligate aerobe, performing the first analysis of cytochrome oxidases in an extracellular respiratory pathogen that we know of. By comparing B. bronchiseptica to the closely related B. pertussis, a strictly human-specific pathogen and the causative agent of whooping cough, we found three cytochrome oxidases that are important for growth and survival within the mammalian respiratory tract. We also found that a bo3-type cytochrome oxidase, predicted to have a low affinity for oxygen and therefore best suited to ambient air levels of oxygen, was sufficient for both the establishment of infection and persistence in the respiratory tract in mice. Our findings reveal the importance of low affinity cytochrome oxidases in respiratory pathogens, and emphasize the need to study the physiology of diverse classes of pathogens. [ABSTRACT FROM AUTHOR]

Continued circulation of the whooping cough pathogen, even in countries with high vaccine coverage, can be related to persistence of Bordetella pertussis biofilms in the respiratory tract. The films differ from planktonic cells by increased resistance to the host immune system and antibacterial drugs. The available acellular pertussis vaccines (aPV) containing antigens isolated from planktonic cultures of B. pertussis protect from severe forms of whooping cough, but do not effectively influence circulation of virulent strains in the subclinical forms of the disease and asymptomatic carriage. It is promising to create new generation aPV based on antigens isolated from biofilm cultures of B. pertussis capable of more effectively controlling the entire infectious cycle of whooping cough, including colonization, persistence, and transmission of the pathogen. From antigenic complexes isolated from the culture medium of biofilm and planktonic cultures of the strain B. pertussis No. 317 (serotype 1.2.3), experimental aPV were made: aPV-B and aPV-P, respectively. In intracerebral infection of mice with a virulent strain of B. pertussis, aPV-B demonstrated 2.5-fold higher protective activity than aPV-P and also more effectively reduced colonization of the lungs by B. pertussis cells in mice after intranasal infection with a virulent strain. Both vaccine preparations were safe and did not cause death in mice after administration of histamine. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the serum antibody levels against pertussis toxin (PT) in children experiencing an acute asthma attack and to explore the potential association between these levels and asthma. Methods: A prospective investigation was conducted, which involved 107 children with acute asthma attacks and 77 children diagnosed with bronchitis. The serum immunoglobulin G (IgG) antibody levels specific to PT were measured by using an in-house enzyme-linked immunosorbent assay. Based on the serum PT-IgG antibody levels, the children with asthma were categorized into three groups: non-pertussis infected, suspected pertussis infected, and recent pertussis infected. The clinical manifestations and pulmonary function of pediatric patients diagnosed with asthma were assessed and compared across various groups. Results: Of the total asthma group, 25 patients tested positive for PT-IgG, whereas only six patients in the bronchitis group were PT-IgG positive. The prevalence of recent pertussis infection was observed to be higher in the asthma group compared with the bronchitis group. Within the asthma group, those with recent pertussis infection exhibited a higher likelihood of experiencing wheezing and impaired lung function in comparison with the non-pertussis infection group. Conclusion: Pertussis infection is relatively common in children with asthma and correlates with the severity of asthma. [ABSTRACT FROM AUTHOR]

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Background In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying polymerase chain reaction (PCR)-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in 7 sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. Methods We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. Results Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. Conclusions Despite a substantial decrease in reported pertussis cases in the setting of coronavirus disease 2019 (COVID-19), our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts. [ABSTRACT FROM AUTHOR]

Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic cough (CC) is a prevalent yet underexplored medical condition, with limited real-world data regarding its healthcare burden. This study investigates the epidemiology, associated comorbidities, and healthcare service utilization among patients with CC. Methods: In this retrospective cohort study, adult patients with at least 3 physician diagnoses of cough over a period spanning a minimum of 8 weeks and a maximum of 12 months anytime between 2009 and 2018, were defined as patients with CC (PwCC). The reference group were adults without cough matched in a 1:1 ratio for age, sex, and place of residence. Results: The study included 91,757 PwCC, reflecting a prevalence of 5.5%. Of those, 59,296 patients (mean [SD] age, 53.9 [16.8] years; 59.6% females) were first diagnosed with CC during the study period, representing a 10-year incidence rate of 3.26% (95%CI: 3.24–3.29%). Diseases associated with the highest OR for CC included lung cancer (OR = 3.32; 95%CI: 2.90–4.25), whooping cough (OR = 3.04; 95%CI: 2.70–3.60), and respiratory infections (OR = 2.81; 95%CI: 2.74–2.88). Furthermore, PwCC demonstrated increased healthcare service utilization, leading to a higher adjusted annual estimated mean cost (USD 4038 vs. USD 1833, p < 0.001). Conclusions: Chronic cough emerges as a relatively prevalent complaint within community care, exerting a considerable economic burden. This study underscores the need for heightened awareness, comprehensive management strategies, and resource allocation to address the multifaceted challenges associated with chronic cough. [ABSTRACT FROM AUTHOR]

Individuals with chronic respiratory illnesses may be at higher risk of pertussis infection and severe pertussis than those without. What is the incidence of pertussis and pertussis complications in cohorts with preexisting asthma or COPD vs age- and sex-matched control patients from the general population in the United States? This observational, retrospective study included individuals aged ≥ 10 years from an administrative health claims system between 2007 and 2019. Individuals with preexisting asthma or COPD were matched with control patients from the general population. The incidence of pertussis infections and pertussis-related complications were assessed overall and by age. The incidence of asthma or COPD exacerbations was also assessed before and after diagnosis of pertussis. In the general population, incidence per 100,000 person-years of pertussis infection ranged from 5.33 in 2007 to 13.04 in 2012, with highest (all years) in those aged 10 to 17 years. The risk of pertussis was higher for the asthma (rate ratio, 3.57; 95% CI, 3.25-3.92) and COPD cohorts (rate ratio, 1.83; 95% CI, 1.57-2.12) than the general population. Those with asthma or COPD had a 4.12-fold (95% CI, 3.16-5.38) and 2.82-fold (95% CI, 2.14-3.27) increased risk of pertussis with complications than the general population, respectively. Exacerbations were most frequent 30 days before pertussis diagnosis (incidence rate [IR], 25%) in the asthma cohort and 30 days before (IR, 26%) and after (IR, 22%) pertussis diagnosis, remaining elevated for 180 days after diagnosis, in the COPD cohort. Among these insured individuals, asthma or COPD increased the risk for pertussis disease and complications vs the general population. COPD and asthma exacerbations were observed most frequently within 30 days of receiving a pertussis diagnosis and remained elevated, suggesting a long-term effect of pertussis in the COPD cohort. [ABSTRACT FROM AUTHOR]

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers. Synopsis: Newborns/infants remain at high risk for severe morbidity/mortality from pertussis infection. Vaccination in pregnancy has become a key strategy to reduce this serious and potentially fatal disease. Herein, we focus on vaccination challenges and strategies for obstetric and gynecologic health care providers. [ABSTRACT FROM AUTHOR]

Pertactin (PRN), a non-fimbrial outer membrane protein of Bordetella pertussis, is the limiting component of the acellular pertussis vaccine because of its low concentration. This study aimed to develop a large-scale urea-based process for PRN extraction from B. pertussis. Cell pellet processing conditions, including freezing and thawing, were found to substantially affect PRN yield. A single cycle of rapid freezing of the cell pellet at − 30 °C with slow thawing at 5 ± 3 °C resulted in up to fivefold higher PRN yield than condition without freezing and thawing. The search for urea treatment conditions was also conducted, and 5 M urea treatment for 2 h was the optimal condition. The developed urea-based process was applied to 50 L culture scale, and residual impurities were removed by sequential anion exchange, hydrophobic interaction and gel filtration chromatography and resulted in PRN with a purity of over 95% at a yield of 33.2%. From 50 L culture broth, the final yield of PRN per cell pellet was 0.23 mg/g (wet weight). Thus, a large-scale production process for high-quality PRN from B. pertussis was developed based on urea extraction process. The results may serve as a reference for production of other membrane proteins. [ABSTRACT FROM AUTHOR]