Evaluation of BioFire Respiratory Panel 2 plus for Detection of Bordetella pertussis in Nasopharyngeal Swab Specimens from Children with Clinically Suspected Pertussis.

The objective of this study was to compare the performances of BioFire Respiratory Panel 2 (RP2) plus, quantitative real-time PCR (qPCR), and culture for the detection of Bordetella pertussis in nasopharyngeal swab (NPS) specimens. Consecutive NPS specimens were collected from patients with clinically suspected pertussis from 1 March 1 to 31 July 2018 in Shenzhen Children's Hospital. All the specimens were tested in parallel by RP2 plus, qPCR, and culture methods. A total of 464 children were enrolled in this study. The positive pertussis rates of culture, RP2 plus, and qPCR were 23.1%, 39.0%, and 38.4%, respectively. Compared to the combined reference standard, the sensitivity, specificity, positive predictive value, and negative predictive values were, respectively, 56.6% (95% confidence interval [CI], 49.2 to 63.7%), 100% (98.3 to 100%), 100% (95.7 to 100%), and 77.0% (72.2 to 81.2%) for culture, 89.9% (84.5 to 93.7%), 96.0% (92.8 to 97.9%), 93.9% (89.1 to 96.8%), and 93.3% (89.5 to 95.8%) for RP2 plus, and 86.8% (80.9 to 91.1%), 94.9% (91.4 to 97.1%), 92.1% (86.9 to 95.5%), and 91.3% (87.2 to 94.2%) for qPCR. The most prevalent codetected pathogen was human rhinovirus/enterovirus (n = 99, 52.4%), followed by parainfluenza virus (n =32, 16.9%) and respiratory syncytial virus (n = 29, 15.3%), in children with B. pertussis present, which was consistent with the top three pathogens previously found in children with B. pertussis absent. Turnaround times for RP2 plus, qPCR, and culture were 2 h, 8 h, and 120 h, respectively. RP2 plus quickly and accurately detected B. pertussis, providing valuable information for an early clinical diagnosis and optimal choice of therapy. IMPORTANCE In recent years, there have been some epidemic or local outbreaks of pertussis in countries with high vaccination rates. One of the crucial factors in controlling pertussis is early diagnosis, which is based on specific laboratory measurements, including culture, serological tests, and PCR assays. Compared to culture and serological tests, PCR is more suitable for clinical application, with a fast detection speed of several hours independent of the disease stage and individual vaccination status. BioFire Respiratory Panel 2 plus, a multiplex PCR assay for simultaneously detecting 22 respiratory pathogens, facilitates the quick detection of Bordetella pertussis and coinfecting respiratory pathogens. It also provides valuable information for an early clinical diagnosis and optimal choice of therapy for children with clinically suspected pertussis.

Decay of anti-Bordetella pertussis antibodies in women of childbearing age following COVID-19 non-pharmaceutical measures.

BACKGROUND: Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. METHODS: Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction. RESULTS: Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2-10.9) vs. 8.4 IU/ml (5.1-13.9; p = 0.004); 18.8 IU/ml (10.9-32.2) vs. 23.6 IU/ml (13.2-42.1; p < 0.001); and 37.1 IU/ml (18.1-75.9) vs. 47.2 IU/ml (24.8-89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018-2019, 8.4 IU/ml (95% CI, 5.1-13.9) vs. 5.4 IU/ml (95% CI, 3.8-7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2-42.1) vs. 20.1 IU/ml (95% CI, 13.4-30.2; p = 0.656), and 47.2 IU/ml (24.8-89.9) vs. 17.3 IU/ml (95% CI, 10.5-28.7; p = 0.021), respectively. DISCUSSION: B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.

Impact of the COVID-19 pandemic on Bordetella pertussis infections in England.

BACKGROUND: In March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases. We assess the impact of the COVID-19 pandemic on pertussis incidence and on the immunisation programme in England. METHODS: We assessed trends in pertussis cases from 2012 to 2020 by age group and month. Incidence from the time that England eased its initial lockdown measures in July 2020 through to summer 2021 was calculated and the incidence rate ratios of pertussis cases from five years prior to the pandemic (July 2014 - June 2019) compared to the same time period during the pandemic (July 2020 - June 2021). Vaccine coverage estimates for pertussis containing vaccines were reviewed for the maternal and childhood programmes. RESULTS: A substantial decline in pertussis cases was observed from April 2020 onwards, marking the lowest number of cases in the last decade. Pertussis incidence dropped in all age groups, particularly among infants less than one year old (0.50 / 100,000 during July 2020 to June 2021 compared to 24.49/ 100,000 from July 2014 to June 2019). The incidence rate ratio was 0.02 (95% CI 0.01 to 0.02) for July 2014 to June 2019 (pre-pandemic) compared to the pandemic period of July 2020 to June 2021. None of the cases had a co-infection with SARS-CoV-2. Vaccine coverage for infants born between January to March 2020 with three doses of pertussis vaccine by 12 months of age decreased by 1.1% points compared to infants born between January to March 2019 (91.6% and 92.7%, respectively). Prenatal pertussis coverage for the 2020 to 2021 financial year was 2.7% points lower than the year prior to the pandemic (70.5% and 76.8%, respectively). CONCLUSIONS: Lockdown measures due to the COVID-19 pandemic have had a significant impact on pertussis transmission. With the easing of restrictions it is important to continue monitoring pertussis cases in England alongside coverage of the maternal and childhood immunisation programmes.

Molecular Basis for Bordetella pertussis Interference with Complement, Coagulation, Fibrinolytic, and Contact Activation Systems: the Cryo-EM Structure of the Vag8-C1 Inhibitor Complex.

Complement, contact activation, coagulation, and fibrinolysis are serum protein cascades that need strict regulation to maintain human health. Serum glycoprotein, a C1 inhibitor (C1-INH), is a key regulator (inhibitor) of serine proteases of all the above-mentioned pathways. Recently, an autotransporter protein, virulence-associated gene 8 (Vag8), produced by the whooping cough pathogen, Bordetella pertussis, was shown to bind to C1-INH and interfere with its function. Here, we present the structure of the Vag8-C1-INH complex determined using cryo-electron microscopy at a 3.6-Å resolution. The structure shows a unique mechanism of C1-INH inhibition not employed by other pathogens, where Vag8 sequesters the reactive center loop of C1-INH, preventing its interaction with the target proteases.IMPORTANCE The structure of a 10-kDa protein complex is one of the smallest to be determined using cryo-electron microscopy at high resolution. The structure reveals that C1-INH is sequestered in an inactivated state by burial of the reactive center loop in Vag8. By so doing, the bacterium is able to simultaneously perturb the many pathways regulated by C1-INH. Virulence mechanisms such as the one described here assume more importance given the emerging evidence about dysregulation of contact activation, coagulation, and fibrinolysis leading to COVID-19 pneumonia.

Bordetella pertussis is a common pathogen in infants hospitalized for acute lower respiratory tract infection during the winter season.

INTRODUCTION: There is some evidence that Bordetella pertussis (B. pertussis) can co-infect with viral respiratory infections in young infants. METHODS: B. pertussis infection was studied by culture, polymerase chain reaction (PCR), and loop-mediated isothermal amplification (LAMP) from nasopharyngeal swabs (NPSs) in 49 infants < 12 months of age, who were admitted for lower respiratory tract infections during the winter season. Seven other possible viral pathogens were documented by antigen detection or PCR in NPSs. The clinical feature of infants with mixed infection of B. pertussis and respiratory viruses were examined. RESULTS: Overall, B. pertussis infection was found in 10 (20.4%) cases, nine were less than 6 months of age and seven were unvaccinated. Viral etiology was found in 41 (84%) cases and pertussis-viral co-infection was present in eight patients, five of whom had mixed infection with respiratory syncytial virus. Only the presence of staccato coughing, cyanosis, and lymphocytosis were significantly different in B. pertussis-positive cases compared with B. pertussis-negative cases. Of the 10 pertussis cases, only the culture-positive cases showed the typical symptoms and laboratory findings of pertussis in addition to virus-associated respiratory symptoms with severe hospital course, whereas cases identified as DNA-positive lacked the characteristics of pertussis and their clinical severities were the same as B. pertussis-negative cases. CONCLUSION: In the absence of typical paroxysmal cough and lymphocytosis, we should carefully consider diagnosis of pertussis in young children hospitalized for presumed viral respiratory illness according to local epidemiological surveillance.

The incidence and clinical effects of Bordetella pertussis in children hospitalized with acute bronchiolitis.

BACKGROUND: Pertussis is a disease leading to high morbidity and mortality in neonates and infants. Bronchiolitis is the most common cause of hospitalization especially in children < 2 year-old. Although the clinical findings are different in these two diseases, it is sometimes difficult to make this distinction in partially or fully vaccinated children. This study aimed to identify the incidence, clinical and laboratory effects of B. pertussis as a causative agent in hospitalized children with acute bronchiolitis. METHODS: The study included patients diagnosed with acute bronchiolitis and admitted to the Division of Pediatric Infectious Diseases from January 2012 to December 2015, aged 24 months or younger, evaluated for viruses and bacteria with polymerase chain reaction in respiratory tract secretions. RESULTS: The study included 380 patients hospitalized with acute bronchiolitis. Of these patients, 85.8% were identified to be positive for at least one respiratory pathogen. The most commonly identified pathogens were respiratory syncytial virus (RSV) A/B, rhinovirus, parainfluenza virus, adenovirus, bocavirus and metapneumovirus A/B. B. pertussis was only detected in 5 patients (1.5%). In the patients with B. pertussis identified, coinfection with another virus was observed including rhinovirus (n= 2), influenza A virus (n= 1), coronavirus OC43 (n= 1) and RSV A/B (n= 1). The presence of B. pertussis did not appear to cause any significant clinical or laboratory differences in patients. CONCLUSIONS: B. pertussis is a rare pathogen in patients admitted to hospital for acute bronchiolitis. However, in patients who do not respond to standard bronchiolitis treatment, B. pertussis should be considered as a causative agent. Early identification of this pathogen is important in terms of quarantining the patient, administering appropriate antimicrobial treatment, and prophylactic treatment to household and other close contacts.

COVID-19 in children: Could pertussis vaccine play the protective role?

While COVID-19 continues to spread across the globe, diligent efforts are made to understand its attributes and dynamics to help develop treatment and prevention measures. The paradox pertaining to children being the least affected by severe illness poses exciting opportunities to investigate potential protective factors. In this paper, we propose that childhood vaccination against pertussis (whooping cough) might play a non-specific protective role against COVID-19 through heterologous adaptive responses in this young population. Pertussis is a vaccine-preventable infectious disease of the respiratory tract and it shares many similarities with COVID-19 including transmission and clinical features. Although pertussis is caused by a bacterium (Bordetella pertussis) while COVID-19 is a viral infection (SARS-CoV-2), previous data showed that cross-reactivity and heterologous adaptive responses can be seen with unrelated agents of highly divergent groups, such as between bacteria and viruses. While we build the arguments of this hypothesis on theoretical and previous empirical evidence, we also outline suggested lines of research from different fields to test its credibility. Besides, we highlight some concerns that may arise when attempting to consider such an approach as a potential public health preventive intervention against COVID-19.

Respiratory bacterial pathogen spectrum among COVID-19 infected and non-COVID-19 virus infected pneumonia patients.

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients.

Could Bordetella pertussis vaccine protect against coronavirus COVID-19?

According to the World Health Organization (WHO), as of today, there are 2.165.500 confirmed cases of the novel coronavirus disease (COVID-19) and 145.705 deaths in over 185 countries. Unfortunately, despite the tremendous efforts to develop a vaccine initiated by various leading health institutions all over the world, it may be 18 months before a vaccine against the coronavirus is publicly available. We are proposing a theory about testing the use of the Bordetella pertussis vaccine to protect against COVID-19. We deliver this theory to the scientific community, aiming to raise the concern about it, and to provide us with support by realistic and experimental evidence.

Early Leukapheresis Depletion in an Ex-Premature with Severe Acute Respiratory Distress Syndrome Due to Bordetella Pertussis and Coronavirus Infection.

We describe a 2 weeks corrected gestational age infant admitted in pediatric intensive care unit (PICU) for severe acute respiratory distress syndrome (ARDS) associated to Bordetella pertussis and Coronavirus infection. He developed leukocytosis as soon as ARDS required intubation and aggressive mechanical ventilation: hence he underwent 3 early therapeutic leukapheresis treatments in order to avoid the worsening of related cardiopulmonary complications, according to recent literature on pertussis infection in infants. The infant was discharged from PICU healthy.