Pertactin-Negative Bordetella pertussis Strains: Evidence for a Possible Selective Advantage

Martin, Stacey W.; Pawloski, Lucia; Williams, Margaret M.; Weening, K.; DeBolt, Chas; Qin, Xuan; Reynolds, Laura; Kenyon, Cynthia; Giambrone, Gregory P.; Kudish, Kathy; Miller, Lisa; Selvage, David; Lee, Adria; Skoff, Tami H.; Kamiya, Hajime; Cassiday, Pamela K.; Tondella, M. Lucia; Clark, Thomas A.

doi:10.1093/cid/ciu788

Cited by 166 publications

(142 citation statements)

References 30 publications

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“…One current hypothesis centers on the idea that B. pertussis strains harboring prn mutations (i.e., escape mutants) possibly have a selective advantage in individuals vaccinated with acellular vaccines (40,41). As previously mentioned, the majority of strains circulating in the Washington State epidemic are divergent from the two current U.S. vaccine strains, which both express prn1.…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of the Pertussis Epidemic in Washington State in 2012

et al. 2014

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dAlthough pertussis disease is vaccine preventable, Washington State experienced a substantial rise in pertussis incidence beginning in 2011. By June 2012, the reported cases reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011. We assessed the molecular epidemiology of this statewide epidemic using 240 isolates collected from case patients reported from 19 of 39 Washington counties during 2012 to 2013. The typing methods included pulsed-field gel electrophoresis (PFGE), multilocus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), and pertactin gene (prn) mutational analysis. Using the scheme PFGE-MLVA-MLST-prn mutations-Prn deficiency, the 240 isolates comprised 65 distinct typing profiles. Thirty-one PFGE types were found, with the most common types, CDC013 (n ‫؍‬ 51), CDC237 (n ‫؍‬ 44), and CDC002 (n ‫؍‬ 42), accounting for 57% of them. Eleven MLVA types were observed, mainly comprising type 27 (n ‫؍‬ 183, 76%). Seven MLST types were identified, with the majority of the isolates typing as prn2-ptxP3-ptxA1-fim3-1 (n ‫؍‬ 157, 65%). Four different prn mutations accounted for the 76% of isolates exhibiting pertactin deficiency. PFGE provided the highest discriminatory power (D ‫؍‬ 0.87) and was found to be a more powerful typing method than MLVA and MLST combined (D ‫؍‬ 0.67). This study provides evidence for the continued predominance of MLVA 27 and prn2-ptxP3-ptxA1 alleles, along with the reemergence of the fim3-1 allele. Our results indicate that the Bordetella pertussis population causing this epidemic was diverse, with a few molecular types predominating. The PFGE, MLVA, and MLST profiles were consistent with the predominate types circulating in the United States and other countries. For prn, several mutations were present in multiple molecular types.

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Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of the Pertussis Epidemic in Washington State in 2012

et al. 2014

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“…The global emergence of Prn deficiency is well documented (16)(17)(18)(19), and deficiency may confer a fitness advantage during infection (20,21). While Prn deficiency appears to be more prevalent in isolates recovered from fully vaccinated patients, it does not appear to impact the effectiveness of acellular pertussis vaccines (22,23).…”

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confidence: 99%

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

et al. 2017

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Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although Bordetella pertussis is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 B. pertussis isolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with Ͼ240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in B. pertussis is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology.IMPORTANCE Whooping cough, primarily caused by Bordetella pertussis, has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of B. pertussis includes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology.

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“…Several studies have suggested reasons for the resurgence of pertussis in the United States, including waning immunity from the acellular pertussis vaccine that replaced whole cell vaccine (9)(10)(11)(12)(13)(14)(15)(16)(17)(18); medical advancements that have allowed more effective diagnosis and reporting of pertussis cases (19,20); asymptomatic transmission of B. pertussis from individuals vaccinated with the acellular pertussis vaccine (21,22); evolving variant strains of B. pertussis circulating that are less protected by the vaccine (23)(24)(25); and a decrease in vaccine coverage that has compromised herd/community immunity (1,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). It is clear that the rise in reported pertussis cases in the United States is a multifaceted problem not fully captured in national or state-level data.…”

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confidence: 99%

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States

Aloe

Kulldorff

Bloom

2017

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

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Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4, to analyze nonmedical vaccine exemptions of children entering kindergarten in 2011 and 2012 and reported pertussis cases in 2012 for children in age groups 5 years and younger and 10 to 14 years. Eight statistically significant clusters of nonmedical vaccine exemptions in kindergarteners and 11 statistically significant clusters of pertussis cases in children and adolescents were identified and geospatially linked. Forty-five percent of the counties in the study had high rates of nonmedical vaccine exemptions. The proportion of kindergarteners with nonmedical vaccine exemptions was 2.8 times larger in the identified exemption clusters. In addition, 31 counties had geographic clusters of high rates of pertussis in children ages 10 to 14 years old, consistent with waning immunity. Our findings are consistent with the view that geographic clusters of nonmedical vaccine exemptions and waning immunity may have been factors contributing to community-level pertussis outbreaks.

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Pertactin-Negative Bordetella pertussis Strains: Evidence for a Possible Selective Advantage

Cited by 166 publications

References 30 publications

Molecular Epidemiology of the Pertussis Epidemic in Washington State in 2012

Molecular Epidemiology of the Pertussis Epidemic in Washington State in 2012

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States

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