Airborne Transmission of Bordetella pertussis

Warfel, Jason M.; Beren, Joel; Merkel, Tod J.

doi:10.1093/infdis/jis443

Cited by 127 publications

(120 citation statements)

References 11 publications

(30 reference statements)

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“…Previously infected animals were clear of B. pertussis infection for 1 to 2 mo before reinfection. Direct challenge and transmission studies were performed as described previously (17,18). The inoculum for each direct challenge was between 10 9 -10 10 cfu as determined by measurement of optical density and confirmed by serial dilution and plating to determine the number of cfu per mL of inoculum.…”

Section: Discussionmentioning

confidence: 99%

“…The coughing fits last on average >2 wk in the baboon, although this is less than some severely infected children, where the cough can last up to 12 wk (1,17). We also characterized airborne transmission of B. pertussis from infected to naïve animals, which is the route of transmission postulated to occur between humans (18). Because this is the only model of pertussis to reproduce the cough illness and transmission of the human disease, we believe it provides the unique opportunity to test our hypothesis that aP vaccines fail to prevent B. pertussis colonization, thus enabling transmission among vaccinated individuals.…”

mentioning

confidence: 99%

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Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Warfel

Zimmerman

Merkel

2013

Proc. Natl. Acad. Sci. U.S.A.

525

531

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Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.whooping cough | T-cell memory | animal models | adaptive immunity |

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Warfel

Zimmerman

Merkel

2013

Proc. Natl. Acad. Sci. U.S.A.

525

531

View full text Add to dashboard Cite

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“…Baboons were obtained from the Oklahoma Baboon Research Resource at the University of Oklahoma Health Sciences Center. The housing and biocontainment unit was designed for study of airborne transmission of pertussis, with unidirectional airflow from directly inoculated (index) subjects to naïve subjects, as previously described (33,34). The walls of cages of naïve subjects were mesh on the ends facing index cases in order to allow free airflow.…”

Section: Methodsmentioning

confidence: 99%

“…The recently characterized baboon model mimics human per-tussis, with prolonged paroxysmal cough and transmission, and allows serial sample acquisition for following the course of infection (33,34). We hypothesized that infected baboons could be used in conjunction with in vitro studies and human specimens to estimate the concentration of ACT present in the airway and at the bacterium-epithelial cell interface during pertussis.…”

mentioning

confidence: 99%

Quantification of the Adenylate Cyclase Toxin of Bordetella pertussisIn Vitroand during Respiratory Infection

et al. 2013

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dWhooping cough results from infection of the respiratory tract with Bordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro, ACT has not been observed or quantified in vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and in vitro data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to ϳ10 8 CFU/ml B. pertussis and 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When ϳ10 8 CFU/ml of a laboratory strain of B. pertussis was cultured in vitro, ACT production was detected in 60 min and reached a plateau of ϳ60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis.

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“…Warfel et al (427)(428)(429) argue that current acellular pertussis vaccines fail to prevent nasopharyngeal colonization and transmission of B. pertussis. To test this hypothesis, they vaccinated nonhuman primates (infant baboons) at 2, 4, and 6 months of age with acellular pertussis or whole-cell pertussis vaccine and challenged them with B. pertussis at 7 months of age.…”

Section: Vaccine-induced Immunitymentioning

confidence: 99%

Pertussis: Microbiology, Disease, Treatment, and Prevention

et al. 2016

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SUMMARYPertussis is a severe respiratory infection caused byBordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution ofB. pertussisstrains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmitB. pertussisto younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding ofB. pertussispathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines.

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Airborne Transmission of Bordetella pertussis

Cited by 127 publications

References 11 publications

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Quantification of the Adenylate Cyclase Toxin of Bordetella pertussisIn Vitroand during Respiratory Infection

Pertussis: Microbiology, Disease, Treatment, and Prevention

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