Novel therapies for the treatment of pertussis disease

Abstract

Whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. Previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. Early diagnosis is complicated by the non-diagnostic presentation of disease early in infection. This review focuses on previous attempts at developing novel host-directed therapies for the treatment of pertussis. In addition, two novel approaches from our group are discussed. Manipulation of the signaling pathway of sphingosine-1-phosphate, a lipid involved in many immune processes, has shown great promise, but is in its infancy. Pendrin, a host epithelial anion exchanger upregulated in the airways with B. pertussis infection, appears to drive mucus production and dysregulation of airway surface liquid pH and salinity. In addition to detailing these potential new therapeutic targets, the need for greater focus on the neonatal model of disease is highlighted.

Keywords: ECMO; acetazolamide; leucocytosis; pendrin; respiratory disease; sphingosine-1-phosphate.

Graphical Abstract Figure.

This review covers existing and potentially new treatments for the resurgent disease pertussis.

Figure 1.

Schematic of pertussis classical and severe disease and points of therapeutic intervention. Classical pertussis (A) is readily broken into three stages, each with specific clinical manifestations. Severe disease (B), most commonly observed in unvaccinated infants, presents with multiple complications. S1P, sphingosine-1-phosphate; ACTZ, acetazolamide; ECMO, extracorporeal membrane oxygenation.