Bordetella Pertussis Research Articles

Structural Basis for Antibody Neutralization of Pertussis Toxin.

Antibodies neutralizing pertussis toxin (PT) prevent the severe clinical symptoms associated with infection by Bordetella pertussis . However, the molecular basis of effective PT-targeted immunity is poorly understood. To gain insight into PT-inhibitory mechanisms, we determined the cryo-electron microscopy structure of genetically detoxified PT (PTg) with two potently neutralizing antibodies to precisely define their epitopes. Carbohydrate-binding studies show that the hu11E6-binding surface on PT interacts with N-linked glycans and that blocking these interactions prevents PT's T cell mitogenic activities. Hu1B7 binds an epitope near the S1 active site that includes S5 contacts but these do not appear important for neutralization. This work identifies PT-neutralizing epitopes and supports inclusion of the hu1B7 and hu11E6 epitopes in next-generation vaccines and PT-based immunogens.

The Effect of Erythromycin in Macrolide-Resistant Bordetella pertussis: Inhibitory Effect on Growth, Toxin Expression, and Virulence.

The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear. The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin. This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR. The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin. The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.

Programming Bordetella pertussis lipid A to promote adjuvanticity

BackgroundBordetella 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.ResultsThis 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).ConclusionThese 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.

Association between real-time polymerase chain reaction cycle threshold value and clinical presentation in children with Bordetella pertussis

BackgroundThe cycle threshold (Ct) value is inversely proportional to the number of copies of the target region in a sample, suggesting that a low Ct value indicates a high pathogen load. The relationship between Ct value and clinical presentation in children with pertussis is not well-defined.MethodsWe investigated the relationships between the Ct value of nasopharyngeal samples positive for Bordetella pertussis deoxyribonucleic acid via real-time polymerase chain reaction (PCR), collected from children on admission and their adult family members between May 2022 and March 2024 at Hangzhou Children’s Hospital, China. The study focused on the correlation between Ct value and clinical presentation in children with pertussis.ResultsThe Ct value was positively correlated with age (r = 0.362, P = 0.001). The mean Ct value for children with pertussis was 28.0 (range: 22.0–32.0), which was lower than the 32.0 (range: 30.0–34.0) observed in adults. Ct value was inversely correlated with length of stay, an indicator of disease severity (r = -0.356, P = 0.001). Logistic regression analyses revealed that both Ct value (OR: 0.891, 95% CI: 0.799–0.993, P = 0.036) and white blood cell count (OR: 1.127, 95% CI: 1.005–1.263, P = 0.040) were independently associated with severity of pertussis.ConclusionsReal-time PCR Ct values at initial diagnosis for pertussis may potentially predict severe disease outcomes in children.

Alpha-1 antitrypsin inhibits Clostridium botulinum C2 toxin, Corynebacterium diphtheriae diphtheria toxin and B. anthracis fusion toxin

The bacterium Clostridium botulinum, well-known for producing botulinum neurotoxins, which cause the severe paralytic illness known as botulism, produces C2 toxin, a binary AB-toxin with ADP-ribosyltranferase activity. C2 toxin possesses two separate protein components, an enzymatically active A-component C2I and the binding and translocation B-component C2II. After proteolytic activation of C2II to C2IIa, the heptameric structure binds C2I and is taken up via receptor-mediated endocytosis into the target cells. Due to acidification of endosomes, the C2IIa/C2I complex undergoes conformational changes and consequently C2IIa forms a pore into the endosomal membrane and C2I can translocate into the cytoplasm, where it ADP-ribosylates G-actin, a key component of the cytoskeleton. This modification disrupts the actin cytoskeleton, resulting in the collapse of cytoskeleton and ultimately cell death. Here, we show that the serine-protease inhibitor α1-antitrypsin (α1AT) which we identified previously from a hemofiltrate library screen for PT from Bordetella pertussis is a multitoxin inhibitor. α1AT inhibits intoxication of cells with C2 toxin via inhibition of binding to cells and inhibition of enzyme activity of C2I. Moreover, diphtheria toxin and an anthrax fusion toxin are inhibited by α1AT. Since α1AT is commercially available as a drug for treatment of the α1AT deficiency, it could be repurposed for treatment of toxin-mediated diseases.

Vaccination of Adolescents as an Important Way to Preserve Demographic Nation's Potential

Relevance. Currently, adolescents are protected against 8 infections within the framework of the National Vaccination Schedule: tuberculosis, viral hepatitis B, diphtheria, tetanus, measles, rubella, mumps and influenza (annually). Post-vaccination immunity to whooping cough, acquired in the first years of life, begins to decline since 4–7 years. In recent decades, there has been an increase in the incidence, including among adolescents, of such pathogens as Neisseria meningitidis, Streptococcus pneumoniae, Bordetella pertussis, strains of the human papillomavirus (HPV) of high oncogenicity, the herpes zoster virus and etc., that affect the creation of the foundation of future health nation. Aim. To substantiate the vaccination strategy for adolescents as one of the most important factors for creating the demographic security of the nation. Results. The burden of infectious pathologies of meningococcal, pneumococcal etiology, pertussis, HPV and herpes Zoster, its impact on the development of the health of adolescents in Russia and the intended tactics for implementing vaccination of young people with the help of modern immunobiological drugs are shown. Conclusion. Vaccination of adolescents against infections such as meningococcal and pneumococcal infections, whooping cough, chicken pox, and HPV is a strategic task, since reducing the risk of contracting infectious diseases in this age group directly affects the preservation of the demographic potential of the nation

Pertussis Epidemiology in Children: The Role of Maternal Immunization.

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.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008–2019

ObjectivesVirulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. MethodsSymptomatic infants aged <6 months with a positive B. pertussis culture from 2008–2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. ResultsWe included 361 infants with pertussis (median age 63 days [interquartile range, 39–86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76–7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06–16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02–19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02–13.83). DiscussionPRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

International treatment outcomes of neonates on extracorporeal membrane oxygenation (ECMO) with persistent pulmonary hypertension of the newborn (PPHN): a systematic review

BackgroundPPHN is a common cause of neonatal respiratory failure and is still a serious condition and associated with high mortality.ObjectivesTo compare the demographic variables, clinical characteristics, and treatment outcomes in neonates with PHHN who underwent ECMO and survived compared to neonates with PHHN who underwent ECMO and died.MethodsWe adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of PPHN in neonates who underwent ECMO, published from January 1, 2010 to May 31, 2023, with English language restriction.ResultsOf the 5689 papers that were identified, 134 articles were included in the systematic review. Studies involving 1814 neonates with PPHN who were placed on ECMO were analyzed (1218 survived and 594 died). Neonates in the PPHN group who died had lower proportion of normal spontaneous vaginal delivery (6.4% vs 1.8%; p value > 0.05) and lower Apgar scores at 1 min and 5 min [i.e., low Apgar score: 1.5% vs 0.5%, moderately abnormal Apgar score: 10.3% vs 1.2% and reassuring Apgar score: 4% vs 2.3%; p value = 0.039] compared to those who survived. Neonates who had PPHN and died had higher proportion of medical comorbidities such as omphalocele (0.7% vs 4.7%), systemic hypotension (1% vs 2.5%), infection with Herpes simplex virus (0.4% vs 2.2%) or Bordetella pertussis (0.7% vs 2%); p = 0.042. Neonates with PPHN in the death group were more likely to present due to congenital diaphragmatic hernia (25.5% vs 47.3%), neonatal respiratory distress syndrome (4.2% vs 13.5%), meconium aspiration syndrome (8% vs 12.1%), pneumonia (1.6% vs 8.4%), sepsis (1.5% vs 8.2%) and alveolar capillary dysplasia with misalignment of pulmonary veins (0.1% vs 4.4%); p = 0.019. Neonates with PPHN who died needed a longer median time of mechanical ventilation (15 days, IQR 10 to 27 vs. 10 days, IQR 7 to 28; p = 0.024) and ECMO use (9.2 days, IQR 3.9 to 13.5 vs. 6 days, IQR 3 to 12.5; p = 0.033), and a shorter median duration of hospital stay (23 days, IQR 12.5 to 46 vs. 58.5 days, IQR 28.2 to 60.7; p = 0.000) compared to the neonates with PPHN who survived. ECMO-related complications such as chylothorax (1% vs 2.7%), intracranial bleeding (1.2% vs 1.7%) and catheter-related infections (0% vs 0.3%) were more frequent in the group of neonates with PPHN who died (p = 0.031).ConclusionECMO in the neonates with PPHN who failed supportive cardiorespiratory care and conventional therapies has been successfully utilized with a neonatal survival rate of 67.1%. Mortality in neonates with PPHN who underwent ECMO was highest in cases born via the caesarean delivery mode or neonates who had lower Apgar scores at birth. Fatality rate in neonates with PPHN who underwent ECMO was the highest in patients with higher rate of specific medical comorbidities (omphalocele, systemic hypotension and infection with Herpes simplex virus or Bordetella pertussis) or cases who had PPHN due to higher rate of specific etiologies (congenital diaphragmatic hernia, neonatal respiratory distress syndrome and meconium aspiration syndrome). Neonates with PPHN who died may need a longer time of mechanical ventilation and ECMO use and a shorter duration of hospital stay; and may experience higher frequency of ECMO-related complications (chylothorax, intracranial bleeding and catheter-related infections) in comparison with the neonates with PPHN who survived.

Virus-like particles displaying the mature C-terminal domain of filamentous hemagglutinin are immunogenic and protective against Bordetella pertussis respiratory infection in mice.

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.

ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.

The cGAS/STING sensor system drives innate immune responses to intracellular microbial double-stranded DNA (dsDNA) and bacterial cyclic nucleotide second messengers (e.g., c-di-AMP). STING-dependent cell-intrinsic responses can increase resistance to microbial infection and speed pathogen clearance. Correspondingly, STING activation and signaling are known to be targeted for suppression by effectors from several bacterial pathogens. Whether STING responses are also positively regulated through sensing of specific bacterial effectors is less clear. We find that STING activation through dsDNA, by its canonical ligand 2'-3' cGAMP, or the small molecule DMXAA is potentiated following intracellular delivery of the AB5 toxin family member pertussis toxin from Bordetella pertussis or the B subunit of cholera toxin from Vibrio cholerae. Entry of pertussis toxin or cholera toxin B into mouse macrophages triggers markers of endoplasmic reticulum (ER) stress and enhances ligand-dependent STING responses at the level of STING receptor activation in a manner that is independent of toxin enzymatic activity. Our results provide an example in which STING responses integrate information about the presence of relevant ER-transiting bacterial toxins into the innate inflammatory response and may help to explain the in vivo adjuvant effects of catalytically inactive toxins.

Biological impact of manual blood exchange in malignant Bordetella pertussis infection in infants.

Manual blood exchange (MBE) is a leukoreduction therapy for hyperleukocytosis in Bordetella spp. We describe the impact of BE on clinical and biological parameters in critically ill children with malignant pertussis. This is a monocentric retrospective review of patients with malignant pertussis infection treated with MBE. It describes the evolution of haemodynamic, ventilatory, haematologic and metabolic characteristics before and after MBE. Between January 2006 and December 2021, nine patients (median age 43 days, range: 13-80 days) had 16 MBE for malignant pertussis. All patients were mechanically ventilated, and 7/9 patients developed pulmonary hypertension during their paediatric intensive care unit (PICU) stay. Overall, 3/9 patients survived, and the mean PICU length of stay was 8.5 days (range: 1-52 days). We found a significant reduction of the leukocyte count (pre-MBE: 61.8 G/L [interquartile range (IQR): 55.8-74.8] vs. post-MBE: 19.4 G/L [IQR: 17.7-24.1]; p ≤ 0.001) and significant oxygenation improvement (pre-MBE SpO2/FiO2: 190 [IQR: 106-200] vs. post-MBE SpO2/FiO2: 242 [IQR: 149-250]; p = 0.03). The main side effects were a significant reduction of thrombocytes (pre-MBE: 411 G/L [IQR: 166.5-563.5] vs. post-MBE: 66 G/L [IQR: 46-82.5]; p = <0.001) and of ionized calcium (iCa) (pre-MBE iCa: 1.3 [IQR: 1.22-1.37] vs. post-MBE iCa: 1.25 [IQR: 1.85-2.24]; p = 0.03). MBE efficiently reduces leukocytes and improves oxygenation in severe Bordetella pertussis infection in infants. Careful monitoring of calcium and thrombocytes seems mandatory.

Severe course of whooping cough in a month-old child

Acute respiratory diseases are more and more being registered among the population. According to Rospotrebnadzor, the incidence of acute respiratory infections in the Russian Federation in 2023 amounted to 15911.94 per 100.000 of population. Whooping cough plays a special role in the structure of acute respiratory infections. The largest increase is noted in the last months of 2023. In total, 20.497 cases of whooping cough were registered in the Russian Federation for 9 months of 2023. Whooping cough is an acute anthroponotic infection caused by whooping cough bacteria (Bordetella pertussis), accompanied by catarrhal phenomena in the upper respiratory tract and paroxysmal spasmodic cough. In young children, severe forms of whooping cough are still the most common, leading to a fatal outcome. One of the severe complications in children of the first years of life is encephalopathy, with persistent organic brain damage. In adolescents and adults, whooping cough often occurs in atypical forms and is manifested by a prolonged cough, for which they receive, as a rule, ineffective therapy from a pediatrician, therapist, allergist and otorhinolaryngologist. Whooping cough refers to diseases controlled by specific prevention. However, for children of an earlier age, infection from older children in the family or from adults is typical. This article presents a clinical observation of a severe course of whooping cough in a child aged 1 month, the disease proceeded with a paroxysmal cough, mainly nocturnal, with long reprises and redness of the face, ending with apnea of varying severity and duration. Determination of the severity of the course of pertussis infection is based on a complex of clinical and laboratory data. An early and effective method of etiological verification of whooping cough in children of the first year of life is PCR (polymerase chain reaction) of nasal/oropharyngeal smears.

Periplasmic binding proteins Bug69 and Bug27 from Bordetella pertussis are in vitro high-affinity quinolinate binders with a potential role in NAD biosynthesis.

Bordetella's genome contains a large family of periplasmic binding proteins (PBPs) known as Bugs, whose functions are mainly unassigned. Two members, Bug27 and Bug69, have previously been considered potential candidates for the uptake of small pyridine precursors, possibly linked to NAD biosynthesis. Here, we show an in vitro affinity of Bug27 and Bug69 for quinolinate in the submicromolar range, with a marked preference over other NAD precursors. A combined sequence similarity network and genome context analysis identifies a cluster of Bug69/27 homologs that are genomically associated with the NAD transcriptional regulator NadQ and the enzyme quinolinate phosphoribosyltransferase (QaPRT, gene nadC), suggesting a functional linkage to NAD metabolism. Integrating molecular docking and structure-based multiple alignments confirms that quinolinate is the preferred ligand for Bug27 and Bug69.

Designing a Novel Temperature- and Noncanonical Amino Acid-Controlled Biological Logic Gate in Escherichia coli.

Genetic code expansion (GCE) is a powerful strategy that expands the genetic code of an organism for incorporating noncanonical amino acids into proteins using engineered tRNAs and aminoacyl-tRNA synthetases (aaRSs). While GCE has opened up new possibilities for synthetic biology, little is known about the potential side effects of exogenous aaRS/tRNA pairs. In this study, we investigated the impact of exogenous aaRS and amber suppressor tRNA on gene expression in Escherichia coli. We discovered that in DH10β ΔcyaA, transformed with the F1RP/F2P two-hybrid system, the high consumption rate of cellular adenosine triphosphate by exogenous aaRS/tRNA at elevated temperatures induces temperature sensitivity in the expression of genes regulated by the cyclic AMP receptor protein (CRP). We harnessed this temperature sensitivity to create a novel biological AND gate in E. coli, responsive to both p-benzoylphenylalanine (BzF) and low temperature, using a BzF-dependent variant of E. coli chorismate mutase and split subunits of Bordetella pertussis adenylate cyclase. Our study provides new insights into the unexpected effects of exogenous aaRS/tRNA pairs and offers a new approach for constructing a biological logic gate.

Rising pertussis cases and deaths in China: current trends and clinical solutions

ABSTRACT Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently experienced a dramatic increase in incidence and associated deaths in China, drawing significant clinical attention. This article retrospectively analyzes national data on pertussis incidence and mortality from 2010 to 2024, exploring potential factors contributing to this trend. It also discusses strategies for enhancing vaccination programs, improving early diagnosis and treatment, and optimizing the clinical management of high-risk infants, with the aim of addressing the challenges posed by the current pertussis epidemic.

Comparison of in-house enzyme-linked immunosorbent assay (ELISA) and six commercial ELISAs for Detection of antibodies to Bordetella pertussis

Enzyme-linked immunosorbent assays (ELISA) are currently the method of choice for the serodiagnosis of pertussis and play a key role in the diagnosis of pertussis in adolescents and adults, as well as in epidemiological studies. In the present study, the in-house developed indirect ELISA was comparatively evaluated with six commercial kits from various manufacturers. Antipertussis antibodies were measured in 40 serum samples from patients with clinical symptoms of respiratory tract infection, in two WHO standards, and in seven human ECDC control sera. IgA and IgG antibodies were detected at a diagnostically significant level by different ELISA kits of 5.0% to 27.0% and 12.0% to 70.0% of patients' sera, appropriately. The analysis of results carried out with six commercial kits showed only 17.5% consistent results in class IgG (either clearly positive or negative). The average percentage of errors in the level of antibodies determined in the control samples, reference serum samples, differed quite significantly and ranged from 9.5% to 35.4% depending on the kit. This poor correlation of the results obtained on various serological tests intended for the serodiagnosis of pertussis may cause very serious diagnostic problems, especially when examining a serum sample obtained once during the course of the disease.

Resurgence of Bordetella pertussis, including one macrolide-resistant isolate, France, 2024.

As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.

Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza

Bacterial-viral co-infections are frequent, but their reciprocal effects are not well understood. Here, we examined the effect Bordetella pertussis infection and the role of pertussis toxin (PT) on influenza A virus (IAV) infection and disease. In C57BL/6J mice, prior nasal administration of virulent B. pertussis BPSM and PT-deficient BPRA provided effective and sustained protection from IAV-induced mortality. However, BPSM or BPRA administered together with purified PT (BPRA + PT) had a stronger protective effect on weight loss compared to BPRA alone, reduced the viral load, and induced IL-17A in the lungs. In IL-17−/− mice, BPSM- and BPRA + PT-mediated protection against viral replication was abolished, while BPSM, BPRA and BPRA + PT provided similar levels of protection against IAV-induced mortality and weight loss. In conclusion, B. pertussis infection protects against influenza by two mechanisms: one reducing viral replication depending on PT and IL-17, and the other, independently of PT and IL-17, resulting in protection against influenza disease without reducing the viral load.

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China

ObjectivesChina 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. MethodsWe 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. ResultsFrom 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. Discussion: 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.