Pertussis resurgence: epidemiological trends, pathogenic mechanisms, and preventive strategies

Abstract

Pertussis, also known as whooping cough, is a highly contagious acute respiratory infection primarily caused by Bordetella pertussis. Although this disease can occur at any age, infants and young children remain the most vulnerable to severe illness and mortality. Moreover, epidemiological trends indicate a notable shift in the incidence of pertussis over time, with an increasing number of reported cases in adolescents and adults. During the 1950s, the widespread implementation of whole-cell pertussis (wP) vaccines significantly reduced the incidence and mortality associated with pertussis. Despite their effectiveness, the frequent adverse reactions linked to wP vaccines prompted a shift towards the utilization of acellular pertussis (aP) vaccines, which have a lower reactogenicity. However, over the past two decades, several countries with a high coverage of aP vaccines have experienced a notable rise in the incidence of pertussis, a phenomenon called pertussis resurgence. The causes of this resurgence are multifactorial and highly complex. Notably, the peak incidence of pertussis has shifted from the infant population to adolescents and adults, who now serve as the primary sources of infection in infants. Such a shift raises critical concerns regarding the current and future control of pertussis. The lack of comprehensive understanding of its pathogenesis is a significant contributing factor to this public health challenge. Although extensive research on the pathogenesis of pertussis has been conducted, it remains an issue without appropriate animal models that effectively replicate the symptomatology commonly observed in human cases. This review provides an overview of B. pertussis epidemiology and recent pathogenesis advances. It further analyzes the potential causes and contributing elements responsible for the resurgence of pertussis. Lastly, the review proposes evidence-based strategies aimed at enhancing public awareness and implementing effective measures to prevent the risk of unexpected outbreaks.

Keywords: Bordetella pertussis; epidemiology; pathogenic mechanisms; pertussis resurgence; preventive strategies; vaccines; waning immunity.

Figure 1

(A) Diphtheria tetanus toxoid and pertussis (DTP3) immunization coverage among 1-year-old children from 2003 to 2023 across the 6 WHO regions and globally (%). The x-axis represents the year, and the y-axis represents the immunization coverage rate for DTP3 among 1-year-old children (%). (B) Reported cases of pertussis from 2003 to 2023 across the 6 WHO regions and globally. The x-axis represents the year, and the y-axis represents the reported number of pertussis cases. Data were collected from the WHO website.

Figure 2

Regulatory systems of virulence factors in B. pertussis. At a temperature of 37°C, the sensor kinase BvgS is activated and transfers the phosphate group to its cognate response regulator BvgA through autophosphorylation. Upon phosphorylation, BvgA is activated, leading to the induction of virulence-activated genes (vags). The protein BvgR, encoded by vag, is capable of hydrolyzing cyclic di-GMP (c-di-GMP) into GMP. The response regulator RisA, which is phosphorylated by the sensor kinase RisK, binds to c-di-GMP in its phosphorylated form, triggering the expression of virulence-repressed genes while simultaneously repressing the expression of vags. The sensor kinase PlrS responds to carbon dioxide by phosphorylating the response regulator PlrR, potentially regulating genes required for bacterial colonization in the lower respiratory tract. The precise interaction between the PlrSR system and the BvgAS system remains to be fully elucidated. Created in Biorender.com.

Figure 3

The main causes of pertussis resurgence, including waning immunity, the application of aP vaccines, the misdiagnoses of other Bordetella species, the improvement of diagnostic tools, and others. Created in Biorender.com.

Figure 4

Differential immune responses to natural infection and immunization with whole-cell and acellular vaccines. (A) Natural infection elicits a cellular immune response dominated by T helper (Th) 1 and Th17 cells, while also inducing a Th2 cell-mediated immune response. Upon reinfection, CD4⁺ tissue-resident memory cells are activated, secreting interleukin (IL)-17A, which recruits neutrophils to the nasal mucosa. (B) The cellular immune response triggered by the whole-cell vaccines closely resembles that induced by natural infection; however, it does not predominantly involve Th2 cells. (C) The acellular vaccines predominantly induce a Th2 cell-mediated immune response, which is significantly different from the immune responses elicited by whole-cell vaccines and natural infection. Created in Biorender.com.

Figure 5

The key strategies to combat pertussis resurgence. Created in Biorender.com.