Bordetella Parapertussis Infection Research Articles

Molecular epidemiology and genomic features of Bordetella parapertussis in Shanghai, China, 2017-2022.

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. 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. 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. 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.

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children-A Systematic Review and Meta-Analysis.

Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis.

Widespread Bordetella parapertussis Infections-Wisconsin, 2011-2012: Clinical and Epidemiologic Features and Antibiotic Use for Treatment and Prevention.

During October 2011-December 2012, concurrent with a statewide pertussis outbreak, 443 Bordetella parapertussis infections were reported among Wisconsin residents. We examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention. Patients with polymerase chain reaction results positive for B. parapertussis reported during October 2011-May 2012 were interviewed regarding presence and durations of pertussis-like symptoms and receipt of azithromycin treatment. Data regarding acute cough illnesses and receipt of azithromycin prophylaxis among parapertussis patient household members (HHMs) were also collected. Using multivariate repeated measures log-binomial regression analysis, we examined associations of treatment receipt by the HHM with the earliest illness onset and prophylaxis receipt among other HHMs with the presence of any secondary cough illnesses in the household. Among 218 patients with parapertussis, pertussis-like symptoms were frequently reported. Illness durations were significantly shorter among patients with treatment initiated 0-6 days after cough onset, compared with nonrecipients (median durations: 10 vs 19 days, P = .002). Among 361 HHMs from 120 households, compared with nonrecipients, prompt prophylaxis of HHMs was associated with no secondary cough illnesses (relative risk: 0.16; 95% confidence interval, .04-.69). Bordetella parapertussis infection causes pertussis-like illness that might be misclassified as pertussis if B. parapertussis testing is not performed. Prompt treatment might shorten illness duration, and prompt HHM prophylaxis might prevent secondary illnesses. Further study is needed to evaluate antibiotic effectiveness for preventing parapertussis and to determine risks and benefits of antibiotic use.

Prevalence of asymptomatic Bordetella pertussis and Bordetella parapertussis infections among school children in China as determined by pooled real-time PCR: A cross-sectional study

Studies have documented that older children and adolescents act as a reservoir of Bordetella pertussis infection for young infants who have not yet completed their primary immunization schedule. Asymptomatic pertussis infection has been reported during outbreaks. This cross-sectional study aimed to investigate whether B. pertussis and Bordetella parapertussis can colonize the nasopharynx of healthy school children, using culture and pooled real-time PCR with targets for insertion sequences IS481 and IS1001. Nasopharyngeal (NP) swabs were taken from 629 asymptomatic school children aged 7 to 15 y in 4 counties of China during the period July-September 2011. The number of subjects included in each county ranged from 153 to 165. The 4 counties selected are located in the north, south, east, and southwest regions of China. NP swabs were inoculated onto Regan-Lowe agar for isolation of suspected Bordetella organisms. Pooled real-time PCRs were used to detect B. pertussis and B. parapertussis based on the IS481 and IS1001 targets separately. Of the 629 subjects, 2 (0.3%) and 30 (4.8%) were confirmed to be culture-positive and PCR-positive, respectively, for B. pertussis, and 1 (0.2%) and 13 (2.1%) were confirmed to be culture-positive and PCR-positive, respectively, for B. parapertussis. All culture-positive samples were also PCR-positive. Furthermore, positive B. pertussis and B. parapertussis samples were found in all counties. Our results indicate that asymptomatic B. pertussis infections are common in school children in China, and asymptomatic B. parapertussis infections are more prevalent than previously documented.

Outer membrane vesicles derived from Bordetella parapertussis as an acellular vaccine against Bordetella parapertussis and Bordetella pertussis infection

Bordetella parapertussis, a close related species of B. pertussis, can also cause the disease named pertussis or whooping cough. The number of cases caused by this related pathogen has risen sustained in the last years. The widely used cellular (wP) or acellular (aP) pertussis vaccines have little or no efficacy against B. parapertussis. In an effort to devise an effective acellular vaccine against B. parapertussis infection, outer membrane vesicles (OMVs) were obtained from B. parapertussis. Proteomic analysis of the resulting OMVs, designated OMVsBpp, evidenced the presence of several surface immunogens including pertactin. The characterized OMVsBpp were used in murine B. parapertussis intranasal challenge model to examine their protective capacity when administered by systemic route. Immunized BALB/c mice were challenged with sublethal doses of B. parapertussis. Significant differences between immunized animals and the negative control group were observed (p<0.001). OMVsBpp protected against B. parapertussis infection, whereas current commercial aP vaccine showed little protection against such pathogen. More interestingly, protection induced by OMVsBpp against B. pertussis was comparable to our previously designed vaccine consisting in OMVs derived from B. pertussis (OMVsBp). For these experiments we used as a positive control the current commercial aP vaccine in high dose. As expected aP offered protection against B. pertussis in mice. Altogether the results presented here showed that the OMVs from B. parapertussis are an attractive vaccine candidate to protect against whooping cough induced by B. parapertussis but also by B. pertussis.

Pertussis epidemic

Winter et al1Winter K. Harriman K. Zipprich J. Schechter R. Talarico J. Watt J. et al.California Pertussis Epidemic, 2010.J Pediatr. 2012; 161: 1091-1096Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar describe the clinical and epidemiologic characteristics of the 2010 California pertussis epidemic. They illustrate high disease burden and mortality in Hispanic patients, especially among infants, despite comparable vaccination coverage. The authors speculate that the high burden of disease in Hispanic patients might be caused by having larger households and possibly more contacts. Because the inference of a causal relationship between household size and high pertussis burden among Hispanics was not supported by data in this study, it would be beneficial if the authors considered doing an ecologic analysis by geocoding cases to census tract, aggregating case count by census tract, then using the census tract economic and housing data to understand factors that could further explain the high burden of disease as demonstrated in a similar study in which the authors used county-wide coverage levels.2Duffy E, Shea K. Poster No 499: Effect of County-level Pertussis Vaccine Coverage on County-level Pertussis Incidence Rates in California During the 2010 Pertussis Epidemic. ID Week San Diego, California 2012. https://idsa.confex.com/idsa/2012/webprogram/Paper35961.html. Accessed February 12, 2013.Google Scholar Previous investigators have demonstrated that occupational exposures to pertussis occur frequently in pediatric health care settings3Kuncio D, Middleton M, Cooney M, Ramos M, Coffin S, Feemster K. Poster 458: Healthcare Worker Pertussis Exposure and Potential Transmission to Vulnerable Patients Missed Opportunities for Prevention. ID Week. San Diego, California 2012. https://idsa.confex.com/idsa/2012/webprogram/Paper37014.html. Accessed February 12, 2013.Google Scholar and that vaccination of health care personnel (HCP) is cost effective.4Greer A.L. Fisman D.N. Use of models to identify cost-effective interventions: pertussis vaccination for pediatric health care workers.Pediatrics. 2011; 128: e591-e599PubMed Google Scholar The authors did not discuss the role that HCP might have played in the epidemic because they usually are the first to come in contact with infants, and infected HCP may be a source of infection. Previous authors have demonstrated the presence of other Bordetella species in outbreaks5Rodgers L. Martin S.W. Cohn A. Budd J. Marcon M. Terranella A. et al.Epidemiologic and laboratory features of a large outbreak of pertussis-like illnesses associated with co-circulating Bordetella holmesii and Bordetella pertussis—Ohio, 2010–2011.Clin Infect Dis. 2012; 56: 322-331Crossref PubMed Scopus (112) Google Scholar and that Bordetella parapertussis infections may contribute to cases thought to be vaccine failures.6Cherry J.D. Seaton B.L. Patterns of Bordetella parapertussis respiratory illnesses: 2008–2010.Clin Infect Dis. 2012; 54: 534-537Crossref PubMed Scopus (56) Google Scholar Of the confirmed cases in this outbreak, 82% were laboratory-confirmed by polymerase chain reaction testing. Because this was a large outbreak with several thousands of cases, epidemiologic and clinical distribution of cases by species type would add to the growing body of literature and help readers understand whether there are changes in the spectrum of diseases caused by other Bordetella species. California Pertussis Epidemic, 2010The Journal of PediatricsVol. 161Issue 6PreviewIn 2010, California experienced the highest number of pertussis cases in >60 years, with >9000 cases, 809 hospitalizations, and 10 deaths. This report provides a descriptive epidemiologic analysis of this epidemic and describes public health mitigation strategies that were used, including expanded pertussis vaccine recommendations. Full-Text PDF

Prevalence of Bordetella pertussis and Bordetella parapertussis infections in Tunisian hospitalized infants: results of a 4-year prospective study

The prevalence of pertussis in Tunisia remains undetermined essentially because of the unavailability of a basic laboratory diagnostic service. Specific diagnostic tools were applied for the first time in a Tunisian prospective study in order to get a first estimation of the prevalence of Bordetella pertussis/parapertussis infections and to evaluate their use to determine the epidemiologic characteristics of these infections in Tunisian infants. Between 2007 and 2011, a total of 626 samples from 599 infants aged <1 year with and without pertussoid cough were investigated for the presence of B. pertussis/parapertussis using culture and real-time polymerase chain reaction (PCR). The real-time PCR (RT-PCR) targets include IS481 commonly found in B. pertussis, B. bronchiseptica, and B. holmesii; IS1001 specific of B. parapertussis, in combination with the pertussis toxin promoter region gene (ptx) of B. pertussis; and the recA gene specific of B. holmesii. When possible, patients' household contacts provided nasopharyngeal aspirates (NPAs) for RT-PCR detection of B. pertussis/parapertussis or single-serum samples for anti-PT IgG quantification. All except 1 NPAs were negative by conventional culture, whereas PCR gave positive signals for 126 specimens (21%): B. pertussis, B. parapertussis, and Bordetella spp. were detected in 82%, 6%, and 4% of the samples, respectively. The simultaneous presence of B. pertussis and B. parapertussis was noted in 8% of the cases. Pertussis was reported throughout the year with a peak during the summer of the year 2009. The prevalence of Bordetella infection was 20% between 2007 and 2011. Most of these cases corresponded to patients younger than 6 months who received <3 doses of pertussis vaccine. Among the household contacts enrolled in the study, mothers seemed to be the likely source of infection. This study showed that pertussis is still prevalent in Tunisia and that the disease remains a public health problem affecting not only infants but also adults. Given this situation, sensitive and specific laboratory tests are needed to improve the accuracy of pertussis diagnosis.

T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

BackgroundDespite the extensive use of efficacious vaccines, pertussis still ranks among the major causes of childhood mortality worldwide. Two types of pertussis vaccines are currently available, whole-cell, and the more recent acellular vaccines. Because of reduced reactogenicity and comparable efficacy acellular vaccines progressively replace whole-cell vaccines. However, both types require repeated administrations for optimal efficacy. We have recently developed a live attenuated vaccine candidate, named BPZE1, able to protect infant mice after a single nasal administration.Methodology/Principal FindingsWe determined the protective mechanism of BPZE1-mediated immunity by using passive transfer of T cells and antibodies from BPZE1-immunized mice to SCID mice. Clearance of Bordetella pertussis from the lungs was mediated by both BPZE1-induced antibodies and CD4+, but not by CD8+ T cells. The protective CD4+ T cells comprised IFN-γ-producing and IL-17-producing subsets, indicating that BPZE1 induces both Th1 and Th17 CD4+ T cells. In addition, and in contrast to acellular pertussis vaccines, BPZE1 also cross-protected against Bordetella parapertussis infection, but in this case only the transfer of CD4+ T cells conferred protection. Serum from BPZE1-immunized mice was not able to kill B. parapertussis and did not protect SCID mice against B. parapertussis infection.Conclusions/SignificanceThe novel live attenuated pertussis vaccine BPZE1 protects in a pre-clinical mouse model against B. pertussis challenge by both BPZE1-induced antibodies and CD4+ T cell responses. It also protects against B. parapertussis infection. However, in this case protection is only T cell mediated.

Acellular pertussis vaccination facilitatesBordetella parapertussisinfection in a rodent model of bordetellosis

Despite over 50 years of population-wide vaccination, whooping cough incidence is on the rise. Although Bordetella pertussis is considered the main causative agent of whooping cough in humans, Bordetella parapertussis infections are not uncommon. The widely used acellular whooping cough vaccines (aP) are comprised solely of B. pertussis antigens that hold little or no efficacy against B. parapertussis. Here, we ask how aP vaccination affects competitive interactions between Bordetella species within co-infected rodent hosts and thus the aP-driven strength and direction of in-host selection. We show that aP vaccination helped clear B. pertussis but resulted in an approximately 40-fold increase in B. parapertussis lung colony-forming units (CFUs). Such vaccine-mediated facilitation of B. parapertussis did not arise as a result of competitive release; B. parapertussis CFUs were higher in aP-relative to sham-vaccinated hosts regardless of whether infections were single or mixed. Further, we show that aP vaccination impedes host immunity against B. parapertussis-measured as reduced lung inflammatory and neutrophil responses. Thus, we conclude that aP vaccination interferes with the optimal clearance of B. parapertussis and enhances the performance of this pathogen. Our data raise the possibility that widespread aP vaccination can create hosts more susceptible to B. parapertussis infection.

Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza

Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR(+) inflammatory chemokine MIP-2 (CXCL2/GRO-beta) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza.

Evaluation of 5′-MGB hybridization probes for detection of Bordetella pertussis and Bordetella parapertussis using different real-time PCR instruments

Rapid and accurate tests capable of distinguishing Bordetella pertussis from milder Bordetella parapertussis infection can aid in treating patients. We evaluated a novel real-time polymerase chain reaction (PCR) method that allows rapid and accurate diagnosis and distinction between B. pertussis and B. parapertussis infections. The method is based on a fluorescent 5′-minor groove-binding molecule hybridization probe that can clearly distinguish between B. pertussis and B. parapertussis by post-PCR melt curve analysis. The reagents worked equally well in several different real-time PCR instruments. The Bordetella detection reagents are combined with internal control components to account for PCR inhibition without compromising assay sensitivity.

Bordetella holmesii DNA is not detected in nasopharyngeal swabs from Finnish and Dutch patients with suspected pertussis

Bordetella holmesii is a Gram-negative bacterium first identified in 1995. It can cause pertussis-like symptoms in humans. B. holmesii contains insertion sequences IS481 and IS1001, two frequently used targets in the PCR diagnosis of Bordetella pertussis and Bordetella parapertussis infections. To investigate the prevalence of B. holmesii in Finnish and Dutch patients with pertussis-like symptoms and whether B. holmesii has caused any false-positive results in diagnostic PCRs, B. holmesii-specific real-time PCRs were developed. The Finnish methods were conventional IS481 PCR and B. holmesii-specific real-time PCR (LightCycler, Roche) targeting the B. holmesii recA gene. The Dutch methods were IS481 and IS1001 PCRs with conventional or real-time formats and B. holmesii-specific real-time PCR targeting the homologue of IS1001. Of 11,319 nasopharyngeal swabs, 2804 were collected from Finnish patients from 2000 to 2003, and 8515 from Dutch patients from 1992 to 2003. B. holmesii DNA was not found in the samples analysed. The results suggest that B. holmesii is not among the causative agents of pertussis-like symptoms in Finnish and Dutch patients and thus does not in practice confound IS481 and IS1001 PCRs.

Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.

Epidemiology and characterization of Bordetella parapertussis strains isolated between 1995 and 2002 in and around Warsaw, Poland

The aim of the study presented here was to analyze parapertussis infections occurring in the region of Warsaw, Poland, between 1995 and 2002 and to characterize the Bordetella parapertussis isolates using macrorestriction digestion of genomic DNA. Fourteen of the 17 patients with confirmed Bordetella parapertussis infection were between the ages of 5 and 9 years, and 14 had documented vaccination with the diphtheria-tetanus-pertussis whole-cell vaccine; for the remaining three patients vaccination data was not available. DNA fingerprinting performed using recommended standard methodology revealed a close relationship between the examined strains and reference strain ATCC 9305, thus confirming the conservative nature of Bordetella parapertussis.

Immunologic and epidemiologic experience of vaccination with a monocomponent pertussis toxoid vaccine.

Pertussis re-emerged in Sweden with a cumulative incidence of about 60% during the first 10 years of life, when the locally produced cellular vaccine lost its efficacy around 1970 and general vaccination was discontinued in 1979. The epidemiology, clinical features, and immunology of pertussis and a monocomponent pertussis toxoid vaccine were studied in Göteborg, Sweden. After phase 1 and 2 studies, a randomized, double-blind, placebo-controlled trial of pertussis toxoid (PTox), compounded with diphtheria and tetanus toxoids, was administered to 3450 children according to the Swedish schedule at 3, 5, and 12 months of age. After a mean follow-up of 18 months, the efficacy was 71% overall and 75% in household contacts, respectively. A statistically significant correlation was found between the level of PTox-induced antibodies and protection against pertussis. As observed with cellular and with multicomponent acellular vaccines, PTox reduced the severity of disease and the percent of children with positive cultures. Furthermore, vaccination reduced the transmission of Bordetella pertussis to household contacts in the vaccinees compared with the controls who received only diphtheria and tetanus toxoids. Patients with culture-verified Bordetella parapertussis infection reacted with antibodies to pertactin and to filamentous hemagglutinin but not to pertussis toxin, and some subsequently developed pertussis. The antibody responses of patients with pertussis to the surface polysaccharides of B pertussis and to B parapertussis were cross-reactive serologically. Serosurveys showed that only antibodies to pertussis toxin were related to the occurrence of pertussis in the general population: antibodies to filamentous hemagglutinin and pertactin were probably stimulated by antigens of other bacteria as well as Bordetellae. Mass vaccination of Göteborg children born in the 1990s was started in 1995. In February 1999, about 55% had been vaccinated and both B pertussis and pertussis decreased significantly in individuals of all ages (herd immunity). Similar to diphtheria, PTox-induced immunity to pertussis occurs both on an individual and community basis. The apparent greater efficacy of multicomponent acellular pertussis vaccines compared with monocomponent PTox was proposed to be an artifact created when the diagnosis of pertussis was made by the serologic criteria of the World Health Organization only. Our conclusion is that PTox is both an essential and alone sufficient antigen in acellular pertussis vaccines.

Whooping cough caused by Bordetella pertussis and Bordetella parapertussis in an immunized population.

The prevalence of Bordetella pertussis and Bordetella parapertussis infections among outpatients in an immunized population is not known. To study the prevalence of these infections in outpatients with paroxysmal cough in Finland, where the pertussis vaccine coverage of 4 doses is 98%. Prospective cohort study. Thirty-two health centers in southwestern Finland. A total of 584 patients with paroxysmal cough seen at local health centers from October 1994 through March 1997 from whom nasopharyngeal swabs were collected. Prevalence of positive cultures for B pertussis or B parapertussis and/or positive polymerase chain reaction (PCR) results and frequency of symptoms in those with pertussis and parapertussis. A total of 153 subjects (26.2%) had Bordetella infection by culture or PCR: 93 (60.8%) had B pertussis infection, 49 (32.0%) had B parapertussis infection, and 1 1 (7.2%) had both. Of these cases, 39 (25.5%) had positive cultures and 95 (62.1%) had positive PCR results for B pertussis, and 19 (12.4%) had positive cultures and 55 (35.9%) had positive PCR results for B parapertussis. At the time of diagnosis, no difference was found in the frequency of symptoms between patients with B parapertussis infection and those with B pertussis infection. Bordetella parapertussis infection was as common as B pertussis infection in children before school entry, whereas in schoolchildren and adults, B pertussis infection was more common than B parapertussis infection (P<.001). Bordetella infections are common in an immunized population, and B parapertussis infections apparently are more prevalent than previously documented.

The efficacy of a whole cell pertussis vaccine and fimbriae against Bordetella pertussis and Bordetella parapertussis infections in a respiratory mouse model

Due to local and systemic side-effects, the currently used, highly effective, whole-cell pertussis vaccines (WCVs) will be replaced by acellular vaccines (ACVs) in some countries. These ACVs contain detoxified pertussis toxin, either alone or in combination with the filamentous haemagglutinin, pertactin and fimbriae. Ongoing clinical trials show that ACVs are clearly less reactogenic than WCVs, and that ACVs comprised of three to five proteins are highly efficacious in inducing protection against Bordetella pertussis infections. An important unresolved question is, what the effect will be of the switch from WCVs to ACVs on the incidence of Bordetella parapertussis infections, the second causative agent of pertussis. A comparison of the efficacy of WCVs and ACVs against B. parapertussis infection is required to answer this question. We show that the Dutch WCV, although prepared from B. pertussis strains, protects against B. parapertussis infection in a murine respiratory model, although less efficiently than against B. pertussis infection. It was shown previously that the ACV components pertussis toxin, FHA and pertactin did not protect against B. parapertussis infection in a murine respiratory model. We have investigated the efficacy of two other ACV components, B. pertussis serotype-2 and -3 fimbriae against B. parapertussis infection in the murine model. The B. pertussis fimbriae protected mice against B. parapertussis infection although less efficiently than against B. pertussis infection. This result indicates that B. pertussis and B. parapertussis fimbriae are antigenically distinct. B. pertussis fimbriae were found to be as efficacious as the WCV against B. pertussis infection. Our results are discussed in the light of the switch from WCVs to ACVs.

Protective role of immunoglobulin G antibodies to filamentous hemagglutinin and pertactin of Bordetella pertussis in Bordetella parapertussis infection.

An outbreak of parapertussis was studied prospectively in 38 first and second grade pupils of an elementary school. Eleven (29%) children were confirmed to be culture positive for Bordetella parapertussis. Serum samples were collected from 31 children for assay of antibodies to filamentous hemagglutinin (FHA), pertactin (PRN), and pertussis toxin of Bordetella pertussis. At the first sampling, ten children were found to have a cough and 21 were asymptomatic. Of the latter, 12 remained asymptomatic and eight developed cough within 11 to 53 days (mean +/- standard deviation, 31 +/- 12 days) after sampling. One child was identified as culture positive for Bordetella pertussis and, thus, not included in the analysis of Bordetella parapertussis infection. The mean levels of IgC antibodies to FHA and PRN were significantly higher in the 12 asymptomatic children than in the eight children who later developed cough or in 20 healthy control children of the same age (for FHA, p = 0.009 and < 0.001, respectively; for PRN, p = 0.002 and 0.002, respectively). These preliminary data suggest that Bordetella parapertussis infection is more prevalent than documented, and that children with high levels of IgG antibodies to FHA and PRN can remain asymptomatic.

Respiratory infections of sheep

Sheep respiratory infections appear as differing clinical syndromes. Mild, acute infections are usually due to parainfluenza 3 (PI3) virus. A mild but chronic respiratory problem in lambs under 1 year old is thought to be caused by Mycoplasma ovipneumoniae probably in association with Pasteurella and PI3. Acute bacterial pneumonia usually results from infection with Pasteurella of biotype A. Infection with PI3 can initiate invasion by Pasteurella. Bordetella parapertussis infection has also been implicated. Serotypes of biotype T P. haemolytica cause an acute septicaemia. Stressful management practices may be a predisposing factor. Chronic proliferative pneumonia results from infection by retroviruses of pulmonary adenomatosis or maedi-visna. Both infections have incubation periods extending into years. The former produces fatal tumorous masses in the lungs. Diagnostic tests are being actively sought. Maedi-visna can present as several clinical problems, frequently as an insidious but fatal proliferative pneumonia.

A causal relationship between Bordetella pertussis and Bordetella parapertussis infections.

Bordetella parapertussis is isolated during the late stages of pertussis outbreaks and occasionally from patients infected with pertussis. The relationship between Bordetella pertussis and B. parapertussis was investigated in mice with monoinfections and mixed infections. Four groups of 10 2-week-old suckling mice were studied: mice born to mice vaccinated against pertussis during pregnancy and unvaccinated controls consequently did and did not receive antipertussis toxin (PT) antibody transcolostrally. The mice were infected transnasally with B. parapertussis strain 422 and 2 identical groups were infected transnasally with B. parapertussis strain 422 and B. pertussis strain 18-323. Bacterial colonization of the lungs and trachea was studied at 1, 2, and 3 weeks after challenge. No persistent colonization by B. parapertussis of the lungs or trachea of monoinfected suckling mice were observed. Persistent colonization by B. parapertussis was observed when suckling mice that received anti-PT antibody transcolostrally were infected with both species. These findings are consistent with the clinical characteristics of B. parapertussis. The results of this study demonstrate that B. pertussis infection facilitates B. parapertussis infection.