Search Results (145)

Background/Objectives: Following the COVID-19 pandemic, pertussis resurged sharply across Europe, with 209,674 cases reported in the EU/EEA in 2024. This study characterises the epidemiology of the 2024 pertussis resurgence across five counties of southeastern Romania, with emphasis on vaccination status, clinical severity, and regional surveillance performance. Methods: A retrospective, population-based analysis was conducted on 452 cases notified between February 2024 and January 2025, extracted from the national surveillance database. A pre-specified reclassification of PCR-positive cases yielded 326 confirmed cases. Categorical, non-parametric, correlation, and multivariate logistic regression analyses were performed. Results: The epidemic peaked in September 2024, with 56.0% of cases occurring between August and October. Children under five years accounted for 63.2% of confirmed cases, and 72.1% were not vaccinated according to age-appropriate schedule, predominantly due to parental refusal (43.0%) and non-attendance (36.6%). Pneumonia affected 36.8% of confirmed cases, ranging from 81.0% in infants under two months to 0% in adolescents. Age-appropriate vaccination was independently protective against pneumonia (adjusted OR = 0.53, 95% CI 0.29 to 0.96, p = 0.035; population attributable risk 37.3%). Significant inter-county heterogeneity was identified in PCR implementation (72 to 100%) and reporting delays. Conclusions: Vaccination gaps were the principal modifiable driver of the resurgence, supporting targeted coverage improvement and the introduction of a national maternal Tdap programme. Full article

Background/Objectives: Pertussis, caused by Bordetella pertussis, remains a global health problem, despite high vaccine coverage. In countries with high acellular pertussis vaccine (aPV) coverage, pertactin-negative B. pertussis strains emerged due to vaccine pressure on the sole bactericidal target of aPVs. In contrast, the live attenuated intranasal vaccine BPZE1 induces bactericidal antibodies to multiple antigenic targets that kill pertactin-positive and pertactin-negative B. pertussis strains. Here, we developed two high-throughput human complement-mediated serum bactericidal assays (SBA) using clinical samples to demonstrate bactericidal activity against B. pertussis. Methods: Assay accuracy, precision, linearity, range and robustness of the SBAs against pertactin-positive and pertactin-negative B. pertussis strain B1917 were determined using a panel of commercial and clinical trial samples. The assay was used to analyze a cohort of BPZE1 and tetanus–diphtheria–acellular pertussis (Tdap) vaccinee samples at baseline and 28 days post-vaccination from a phase 2b clinical trial. Results: Inter- and intra-assay variability of both assays had coefficients of variation for repeatability < 20% and for intermediate precision of <30%. The assays measured titers ranging from ~8 to ~20,000 and showed high linearity (R² > 0.98) between bactericidal titers and serum dilutions. On clinical samples, BPZE1 induced similar bactericidal activity as Tdap against pertactin-positive B. pertussis, despite inducing lower anti-aP antigen IgG concentrations than Tdap. Additionally, BPZE1 induced serum bactericidal activity against pertactin-negative B. pertussis, while Tdap did not. Conclusions: High-throughput SBAs were developed and qualified against pertactin-positive and pertactin-negative B. pertussis, enabling measurement of 120 samples per day per analyst. These assays will support clinical development of next-generation pertussis vaccines, including BPZE1. Full article

Background: Pertussis toxin (Ptx) is a major virulence factor and protective antigen of Bordetella pertussis. Understanding its antigenic landscape is essential for improving vaccine design. This study aimed to compare the linear epitope profiles of Ptx recognized by antibodies from vaccinated children and mice, identifying conserved and species-specific immune targets across subunits S1–S5. Methods: Two libraries of overlapping 14-mer peptides spanning the full-length Ptx sequence were synthesized. Sera from children and mice immunized with the whole-cell pertussis vaccine were analyzed to map antibody-binding regions. Comparative and structural analyses were performed to evaluate epitope distribution and recognition patterns. Results: Murine sera recognized 12 major epitopes, whereas children’s sera identified 24. Eleven epitopes were shared between species, mainly in subunits S1 (Ep3–5, 7, 9, 10), S3 (Ep20, 21, 25, 26), and S5 (Ep32), although minor positional shifts were observed. Eight epitopes were unique to children’s sera, located in S1 (Ep1, 6, 8), S3 (Ep22–24), and S4 (Ep27, 29–30). In the S2 subunit, four distinct epitopes were identified for each species, while only one mouse-specific epitope was detected in S4 (Ep28). Structural analysis revealed non-uniform antibody recognition, with dominant targeting of S3 and conserved antigenic hotspots, as well as selective recognition of the catalytic S1 subunit. Fourteen novel epitopes were identified. Conclusions: These findings highlight both shared and species-specific Ptx epitopes, revealing differences between murine and human immune responses. The identified conserved regions and novel epitopes provide a basis for improved pertussis vaccine design. Full article

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α₁-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

Background: Molecular diagnostics may detect several respiratory pathogens simultaneously with rapid turnaround times. The aim of this study was to determine the frequency and distribution of respiratory pathogens among symptomatic outpatients. Methods: All outpatients presented for testing due to suspected acute respiratory infection between 1 January and 31 December 2024 to the Teaching Institute for Public Health of Split-Dalmatia County, Croatia, and multiplex real-time PCRs for 13 respiratory pathogens were included. Results: Out of 15,437 analyzed panels, 8878 (57.5%) were positive. Single-pathogen infections dominated (82.6%), while co-infections were recorded in 17.4% of panels; therefore, a total of 10,546 individual pathogens were detected, which were mostly viruses (87.0%). The following distribution of pathogens was observed: rhinovirus/enterovirus in 38.9% of positive results, influenza A virus in 14.5%, SARS-CoV-2 in 9.5%, parainfluenza virus in 7.9%, respiratory syncytial virus in 7.3%, Mycoplasma pneumoniae in 4.9%, Bordetella pertussis in 4.6%, human metapneumovirus in 4.2%, adenovirus in 3.4%, Chlamydia pneumoniae in 3.4%, influenza B virus in 1.3%, Bordetella parapertussis in 0.1% and Legionella pneumophila had one positive result. The first trimester of the year had the highest number of positive test panels (47.0%). Conclusions: Our study demonstrates a predominance of viral pathogens across all age groups and seasons, further supporting guideline-based practice and highlighting the importance of confirming bacterial infection before initiating antibiotic therapy. This insight into the post-pandemic circulation of respiratory pathogens may help inform public health strategies, including improved surveillance, anticipation of seasonal outbreaks, and targeted interventions, thereby supporting future pandemic preparedness and mitigation efforts. Full article

Pertussis, caused by Bordetella pertussis, remains a public health concern despite long-standing vaccination programs. After a marked decline during the COVID-19 pandemic, a resurgence was observed in Europe and Italy, with a sharp increase in 2024. This study describes pertussis epidemiological trends in the Tuscany Region (Italy) from 2019 to 2024 to identify high-risk groups and inform prevention strategies. A retrospective population-based analysis was conducted using cases reported to the national surveillance system (PREMAL). Incidence rates were calculated using ISTAT population data, and demographic, temporal, and clinical characteristics were analyzed. Overall, 669 cases were reported (mean annual incidence rate: 3.03/100,000 (IC 95% 2.47–3.59; period incidence rate: 18.2/100,000 (IC 95% 16.81–19.56)), with 89% occurring in 2024 (16.34/100,000 (IC 95% 15.03–17.65)). No sex differences were observed, and most cases were reported in Central Tuscany (64%). Children under 15 years accounted for 87% of cases. The highest incidence was observed among 10–14-year-olds, while infants < 1 year, particularly those under 4 months, showed the highest burden in narrower age strata. Hospitalizations occurred in 12.6% of cases, decreasing substantially in 2024. The 2024 resurgence likely reflects waning immunity, disruptions to routine vaccinations during the pandemic, and reduced pathogen circulation in previous years due to containment and isolation measures related to the pandemic. Strengthening surveillance and improving booster and maternal vaccination coverage are essential to protect vulnerable populations. Full article

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its G_i protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive G_i signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis. Full article

Objective: To investigate how the high-altitude environment modifies severe pertussis in young infants and analyze its pathophysiological mechanisms and clinical management implications. Methods: Clinical data of two young infants with severe pertussis residing at 3650 m were retrospectively analyzed, including presentation, laboratory findings, pathogen detection, treatment, and outcomes. A literature review explored synergistic interactions between high-altitude factors and pertussis pathophysiology. Results: Case 1 had macrolide-resistant Bordetella pertussis (MRBP, 23S rRNA A2047G) with peak WBC 52.25 × 10⁹/L, and received cefoperazone-sulbactam, piperacillin-tazobactam and azithromycin, and was successfully treated with trimethoprim-sulfamethoxazole combined with exchange transfusion. Case 2 had Bordetella pertussis confirmed by PCR with peak WBC 36.55 × 10⁹/L, receiving cefoperazone-sulbactam and azithromycin, and recovered. Both developed respiratory failure requiring non-invasive ventilation and survived without pulmonary hypertension. High-altitude stressors—hypoxia, enhanced pulmonary vascular reactivity, and hypercoagulability—synergize with pertussis-induced hyperleukocytosis as a “dual hit,” accelerating cardiopulmonary deterioration and elevating thrombotic risks. Conclusions: High altitude is an independent risk modifier in infantile pertussis, demanding heightened vigilance and proactive interventions: early non-invasive ventilation, prophylactic anticoagulation, and timely exchange transfusion before pulmonary hypertension develops. This is the first high-altitude case series that provides essential insights for clinicians in similar environments globally, guiding early recognition and proactive management strategies to improve outcomes in this vulnerable population. Full article

Background: In 2019, pneumonia caused 740,180 deaths in children under five years of age, representing 22% of global mortality in this age group. During the COVID-19 pandemic, public health interventions markedly reduced the circulation of most respiratory viruses other than SARS-CoV-2, leading to significant post-pandemic shifts in respiratory pathogen epidemiology. This study aimed to characterize the epidemiology, clinical features, and risk factors associated with respiratory viruses and bacteria causing pneumonia in Mexican children during the late pandemic and post pandemic periods. Methods: Children younger than 14 years with pneumonia were recruited from seven hospitals in Mexico. Demographic and clinical data were collected, and nasopharyngeal swabs were analyzed using a multiplex PCR panel detecting 19 viruses and 7 bacteria. Univariate, bivariate, and logistic regression analyses were performed (SPSS v25). Results: A total of 1715 children were included: 704 during the pandemic (2021–2023) and 1011 post-pandemic (2023–2025). Co-infections (72% vs. 65%, p < 0.001), virus–virus co-infections (25% vs. 11%, p < 0.001), and single viral infections (20% vs. 15%, p = 0.007) were more frequent during the pandemic. Pathogen detection was high in both periods, though negative samples increased post-pandemic (5.4% vs. 15%, p < 0.001). During the pandemic, the 5 most frequently detected pathogens were rhinovirus (66%), RSV A and B (38%), Streptococcus pneumoniae (30%), Haemophilus influenzae (28%), human metapneumovirus (13%). In the post-pandemic period, the 5 most frequently detected pathogens were rhinovirus (52%), Haemophilus influenzae (36%), Streptococcus pneumoniae (35%), RSV A and B (28%), metapneumovirus (11%). Rhinovirus and RSV predominated during the pandemic, whereas Haemophilus influenzae, Streptococcus pneumoniae, parainfluenza viruses, Bordetella pertussis, and Mycoplasma pneumoniae significantly increased post-pandemic. Conclusions: Pediatric pneumonia epidemiology shifted from a predominantly viral profile during the pandemic to increased bacterial detections and virus–bacteria co-infections post-pandemic, alongside re-emergence of typical RSV and influenza seasonality. Higher mean age and rhinovirus as the most frequent pathogen persist after the pandemic. Sustained molecular surveillance and reinforced vaccination programs remain essential in the post-pandemic era. Full article

Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly significant role. These infections not only reduce life expectancy but can also delay cancer therapy, negatively affect treatment outcomes, and increase healthcare costs. In recent years, the burden of respiratory infections in this population has been driven by influenza virus, SARS-CoV-2, respiratory syncytial virus, Streptococcus pneumoniae, and Bordetella pertussis. Effective vaccines are available for all these pathogens and are recommended for adults with cancer, yet vaccination uptake remains suboptimal despite their heightened vulnerability. This review provides practical guidance for healthcare professionals on vaccinating adults with cancer against respiratory infections, summarizing key information to help clinicians address vaccination-related complacency, confidence, and convenience. Evidence from studies in both the general population and cancer patients consistently shows that vaccination benefits outweigh potential risks, with adverse event rates comparable to those seen in individuals without cancer. Early vaccination is encouraged, as there is limited justification for delaying immunization even when immune responses may be reduced. Vaccine dosing aligns with recommendations for the general population, with important exceptions. Live attenuated vaccines should be avoided because of the risk of replication and disease in immunocompromised patients, and selected groups may require booster doses to achieve adequate protection. Notably, cancer immunotherapy does not appear to impair vaccine-induced immune responses. Full article

Background: Bordetella pertussis causes pertussis, a respiratory infection with whooping cough. Despite a high vaccine coverage, pertussis resurged post-COVID-19 pandemic. Meanwhile, isolates resistant to macrolides—the first-line therapy—have increased in several countries, including Japan. Culturing B. pertussis and detecting resistance are difficult; reports remain limited in Japan. Methods: From March to August 2025, we collected nasopharyngeal samples from children aged 0–15 years with suspected pertussis at six Japanese clinics. Pediatricians obtained swabs and tested them using gene-amplification kits (e.g., BioFire^® SpotFire^® in four clinics, LAMP Pertussis Detection^® in two clinics). B. pertussis was confirmed by PCR; isolates were sequenced to identify macrolide-resistant mutations. Results: Samples were taken from 54 children, the number of boys and girls was 34 and 20, and their median age was 12 years old. Among 54 B. pertussis isolates, 43/52 (82.7%) sequenced strains harbored the A2047G mutation associated with macrolide resistance. Resistance rates at each clinic varied from 40% to 96%. Conclusions: These findings indicate a post-pandemic rise in macrolide-resistant B. pertussis in Japan. Ongoing resistance surveillance is essential, and repurposing residual clinical samples after routine testing is useful given culture and detection challenges. Full article

Background: Whooping cough caused by Bordetella pertussis is re-emerging despite high vaccination coverage, with rising incidence in adolescents and adults in the acellular vaccine (aP) era. This narrative review synthesizes evidence on the drivers of this paradox and their implications for pertussis control. Methods: We conducted a structured (but not fully systematic) literature search and narrative synthesis of PubMed, Web of Science, and Embase for publications from January 2000 to February 2025 using terms related to “Bordetella pertussis,” “pertussis resurgence,” “acellular vaccine,” “waning immunity,” “ptxP3,” “pertactin-deficient,” “macrolide resistance,” and “whole-genome sequencing.” English-language, peer-reviewed studies, surveillance reports, genomic analyses, and immunological investigations were included. About 1900 records met broad eligibility criteria and were screened, and key studies were selected for narrative synthesis. Results: The resurgence appears to result from three convergent factors: (1) waning and non-sterilizing aP-induced immunity, which allows bacterial colonization and transmission; (2) vaccine-driven genomic evolution of B. pertussis, marked by global dominance of the ptxP3 lineage and widespread pertactin-deficient (PRN−) strains; and (3) emergence of macrolide-resistant clones, exemplified by the MT28-Shanghai strain. Whole-genome sequencing (WGS) has been central for defining these processes and clonal sweeps under combined vaccine and antibiotic pressure, supporting a three-driver framework of waning aP immunity, vaccine-driven evolution, and macrolide resistance. Conclusions: Pertussis resurgence illustrates pathogen adaptation to human interventions. Effective mitigation requires WGS-integrated global surveillance, re-evaluation of vaccine formulations to keep pace with antigenic change, and strengthened antibiotic stewardship, alongside development of next-generation vaccines that induce durable mucosal immunity and block transmission. Full article

Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a particular problem for the pediatric population among whom the highest mortality from the disease is recorded. Several reasons for this phenomenon can be mentioned, but what is particularly important from the microbiological point of view is the correlation of the increased number of pertussis cases with the introduction of a new form of vaccine—the acellular vaccine in place of the whole-cell vaccine. In this review, we summarized the current state of knowledge on potential factors that may contribute to the decline in immunization efficacy against the pathogen. The post-vaccination response profile, symptomatic of vaccination with vaccination-acellular, is characterized by recruitment of Th₂ and Th₁₇ lymphocytes; it has been reported that in the long term, this results in insufficient activation of B cells and low titers of antibodies to key bacterial antigens (hemagglutinin, pertactin). Moreover, the immune response proceeds by bypassing the recruitment of tissue-resident memory T cells, resulting in a lack of protection against colonization of the nasal cavity by the bacterium despite vaccination. The decline in vaccination efficacy should also be attributed to the phenotypic variability of Bordetella. The popularization of the PtxP3 strain, characterized by its ability to incompletely activate immune mechanisms, poses a real threat to public health. The growing resistance of B. pertussis to standardly used antibiotics including macrolides also remains a problem. This makes it difficult to eradicate pathogens from the nasal cavity area and increases the pool of bacterial carriers in the population area. The increasing prevalence of the disease prompts reflection on more effective methods of prevention. Particularly promising in this field seem to be new vaccines, especially mucosally implemented, e.g., intranasal, or developed on the basis of B. pertussis antigens other than those used so far. Full article

Pertussis, a highly contagious disease, contributes to a great number of hospitalizations among children, with an increased risk of morbidity and mortality. The aim of the study was to investigate the epidemiological and clinical features of B. pertussis infections among hospitalized children and to compare the clinical course according to vaccination status and the presence of co-infections. We performed a retrospective study, which included patients positive for B. pertussis detected by multiplex RT-PCR panels, from September 2022 to May 2025. Out of 2493 samples, 84 tested positive for B. pertussis (3.37%). Age-appropriate immunization was achieved in 19.1% (16/84) cases, 10.7% (9/84) were incompletely vaccinated, 9.5% (8/84) did not meet the age criteria and 60.7% (51/84) were not vaccinated. Infants ≤ 3 months were more susceptible to mixed co-infections (52%), had a more severe course, with transfers to the ICU (32%) and a prolonged average length of stay (9.2 days). Co-infections were found in 39.3% cases, rhinovirus being the most common agent (17.9%). B. pertussis and rhinovirus co-infection was associated with a decreased SpO₂ level (<92%) and increased CRP and Ferritin levels. Full article