The relationship between Bordetella pertussis genotype and clinical severity in Australian children with pertussis

Clarke, Michelle; McIntyre, Peter; Blyth, Christopher C; Wood, Nick; Octavia, Sophie; Sintchenko, Vitali; Giles, Lynne C.; Quinn, Helen; Hill, Verity; Hanly, G; Lan, Ruiting; Marshall, Helen

doi:10.1016/j.jinf.2015.11.004

Cited by 32 publications

(21 citation statements)

References 25 publications

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“…However, conclusions from these and similar studies are tentative since such small numbers of strains are used (just one strain of each type in the Lan study). Other studies have found no difference in the severity of pertussis disease in human infants infected with either Prn-expressing or Prn-deficient strains [49 ▪ ,50], although it remains possible that compensatory mutations have occurred in Prn-deficient strains to account for the loss of Prn. Very few B. pertussis strains deficient in expression of Fha or pertussis toxin (Ptx) have been described [51,52,53 ▪ ].…”

Section: Emergence Of B Pertussis Strains With Increased Virulence?mentioning

confidence: 99%

“…Interestingly, Mooi’s group found that ptxP3 strains not only produce higher levels of several virulence factors than ptxP1 strains, but are less sensitive to sulfate-mediated modulation of virulence gene expression through the Bvg regulatory system, probably because of differential expression of sulfate utilization and transport genes [64 ▪ ]. It is still unclear whether ptxP3 strains are really more virulent than ptxP1 strains, especially since most of these analyses have included very few strains of each type, but one recent study of young children hospitalized with pertussis found a significant association between ptxP3 strains and severe disease [49 ▪ ]. Additional studies similar to this may reveal a true relationship between the ptxP3 strain genotype and increased virulence, and will spur the development of improved vaccines and therapeutics to account for this increase.…”

Section: Emergence Of B Pertussis Strains With Increased Virulence?mentioning

confidence: 99%

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Bordetella pertussis

Carbonetti

2016

Current Opinion in Infectious Diseases

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Purpose of review The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines. Recent findings Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions. Summary Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention.

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Section: Emergence Of B Pertussis Strains With Increased Virulence?mentioning

confidence: 99%

Section: Emergence Of B Pertussis Strains With Increased Virulence?mentioning

confidence: 99%

Bordetella pertussis

Carbonetti

2016

Current Opinion in Infectious Diseases

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“…A mutation that increases the production of pertussis toxin has also attracted considerable attention, the so-called ptxP3 allele (66). The ptxP3 allele has spread in vaccinated populations, and it is associated with increased hospitalizations, durations of stay, and deaths (66)(67)(68)(69)(70). These increases may be due to the immunosuppressive effects of the toxin (71)(72)(73).…”

Section: Vaccine Resistancementioning

confidence: 99%

“…2). Moreover, vaccination substantially reduces the risk of severe disease, even when infected with prn − /ptxP3 strains (70). Current research into improving the efficacy of pertussis vaccines has been quite diverse, ranging from using live bacteria or inactivated cells to altering antigens, adjuvants, doses, number of boosters, and timing of boosters (77).…”

Section: Vaccine Resistancementioning

confidence: 99%

Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance

Kennedy

Read

2018

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

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Vaccines and antimicrobial drugs both impose strong selection for resistance. Yet only drug resistance is a major challenge for 21st century medicine. Why is drug resistance ubiquitous and not vaccine resistance? Part of the answer is that vaccine resistance is far less likely to evolve than drug resistance. But what happens when vaccine resistance does evolve? We review six putative cases. We find that in contrast to drug resistance, vaccine resistance is harder to detect and harder to confirm and that the mechanistic basis is less well understood. Nevertheless, in the cases we examined, the pronounced health benefits associated with vaccination have largely been sustained. Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being. Studies of pathogen strains that evolve the capacity to replicate and transmit from vaccinated hosts will enhance our ability to develop next-generation vaccines that minimize the risk of harmful pathogen evolution.

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“…pertussis populations in many countries worldwide [9, 14]. These P3 strains have been associated with the resurgence and severity of pertussis [11, 15, 16]. …”

Section: Introductionmentioning

confidence: 99%

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

et al. 2017

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Vaccines against pertussis have been available for more than 60 years. Nonetheless, this highly contagious disease is reemerging even in countries with high vaccination coverage. Genetic changes of Bordetella pertussis over time have been suggested to contribute to the resurgence of pertussis, as these changes may favor escape from vaccine-induced immunity. Nonetheless, studies on the effects of these bacterial changes on the immune response are limited. Here, we characterize innate immune recognition and activation by a collection of genetically diverse B. pertussis strains isolated from Dutch pertussis patients before and after the introduction of the pertussis vaccines. For this purpose, we used HEK-Blue cells transfected with human pattern recognition receptors TLR2, TLR4, NOD2 and NOD1 as a high throughput system for screening innate immune recognition of more than 90 bacterial strains. Physiologically relevant human monocyte derived dendritic cells (moDC), purified from peripheral blood of healthy donors were also used. Findings indicate that, in addition to inducing TLR2 and TLR4 signaling, all B. pertussis strains activate the NOD-like receptor NOD2 but not NOD1. Furthermore, we observed a significant increase in TLR2 and NOD2, but not TLR4, activation by strains circulating after the introduction of pertussis vaccines. When using moDC, we observed that the recently circulating strains induced increased activation of these cells with a dominant IL-10 production. In addition, we observed an increased expression of surface markers including the regulatory molecule PD-L1. Expression of PD-L1 was decreased upon blocking TLR2. These in vitro findings suggest that emerging B. pertussis strains have evolved to dampen the vaccine-induced inflammatory response, which would benefit survival and transmission of this pathogen. Understanding how this disease has resurged in a highly vaccinated population is crucial for the design of improved vaccines against pertussis.

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The relationship between Bordetella pertussis genotype and clinical severity in Australian children with pertussis

Cited by 32 publications

References 25 publications

Bordetella pertussis

Bordetella pertussis

Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

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