Genetic Shifts in Bordetella May Explain Surge in Pertussis

Nicola M. Parry, DVM

March 13, 2019

Genetic changes in circulating Bordetella pertussis may help explain the resurgence of whooping cough and reduced vaccine effectiveness in recent decades, a study published online today in Emerging Infectious Diseases suggests.

"We have developed a representative dataset of complete genome sequence assemblies derived from B. pertussis clinical isolates recovered in the United States that captures shifting population genetics concurrent with disease resurgence," write Michael R. Weigand, PhD, from the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.

In the United States, cases of whooping cough have been on the rise since the late 1980s."This resurgence has included >48,000 cases reported in 2012 and notable recent statewide epidemics," the authors say.

Among the potential causes of this increase is the possibility that circulating B. pertussis undergoes genetic variation, resulting in divergence between vaccine and clinical strains of the bacterium. However, until recently, detailed genetic information was available only for vaccine and laboratory reference strains of the bacterium. 

Therefore, Weigand and colleagues analzyed genotypes of 170 circulating B. pertussis isolates. The samples had been collected by state public health laboratories from ill patients between 2000 and 2013 and forwarded to CDC.

The completed genome assemblies from the isolates show that the genetic composition of clinical B. pertussis isolates has shifted away from that of vaccine strains during the current whooping cough surge.

This shift included a circulating mixture of gene sequence (single-nucleotide polymorphisms) and chromosome structure variants, as well as increased pertactin deficiency. Pertactin (Prn), a B. pertussis virulence factor, is a key component of the pertussis vaccine.

Weigand and colleagues found 10 Prn-deficient alleles among 57 of the clinical isolates in their study, with the proportion of these alleles rising rapidly from 2010. Mutations associated with Prn deficiency included missense substitutions, deletions, promoter disruption, and IS481 insertions.

Although the current pertussis vaccines remain effective, these findings "provide a foundation for needed research to direct future public health control strategies," the authors conclude.

This study was supported by the Advanced Molecular Detection program at the US Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

Emerg Infect Dis. Published online March 13, 2019. Full text

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