In humans, pertussis (or “whooping cough”) disease is caused by Bordetella pertussis, a Gram-negative, aerobic coccobacillus.1 Pertussis was a common disease with an annual rate of reported cases of 157/100,000 population in the early twentieth century in the United States (US) before the availability of a vaccine.2 Two types of pertussis vaccines are currently broadly available. The whole-cell pertussis (wP) vaccines are composed of the whole inactivated organism. The acellular pertussis (aP) vaccines are composed of multiple purified bacterial proteins (such as pertussis toxin [PT], filamentous hemagglutinin [FHA], pertactin [PRN] and fimbriae [FIM2/3]). Immunization with the wP vaccine started in the 1940s in the US which led to a dramatic decrease in the incidence rate of the disease, and by the 1970s the reported yearly incidence rate was low at 1/100,000 population.2

Immunization with the wP vaccine was associated with significant local reactions and possible neurological symptoms (e.g. convulsions and hypotonic hyporesponsive episodes) in some small reports3, 4 while the aP vaccines were associated with fewer of these adverse events.5 Following demonstration of efficacy in several large phase III trials,6, 7 the aP vaccine replaced the wP vaccine in most high-income countries in the late 1990s and early 21st century and is currently used in these countries for all age groups, while the wP vaccine is still widely used in low and middle income countries. Multi-component aP vaccines exist in different formulations efficacy of which has been reported. A case controlled study from the UK showed that the 5-component aP vaccine was highly effective in preventing pertussis, not statistically significantly different than the wP vaccine, while the 3-component aP vaccine was associated with significantly lower protection compared with wP vaccines.8 In another study from the UK, the maternal vaccine effectivenss of both the 5-component and 3-component aP vaccines administered in pregnancy did not differ significantly and was high at 93% and 88% in prevention of pertussis in young infants, respectively.9

In the past two decades and despite high immunization coverage, there has been an increase in the incidence of pertussis in different world regions.10, 11, 12 Globally, it has been estimated that in 2014 there were 160,700 deaths caused by pertussis in children younger than 5 years of age,13 although these were estimated to occur mainly in Africa. The European Centre for Disease Prevention and Control (CDC) data showed that cases slightly dropped between 2014 and 2018 (from over 40,000 cases to over 35,000 cases, respectively).14 This trend had also been observed in the US, and according to US CDC reported incidence cases declined slightly from 10.3/100,000 in 2014 to 6.2/100,000 in 2019.15 Pertussis is still most severe in youngest infants leading to substantial morbidity and mortality16, 17, 18, 19, 20 as also evident in the pertussis outbreak in California in 2010.12

Several explanations have been provided to explain the resurgence of pertussis despite high immunization coverage. Specifically, waning immunity reflected by faster decline of anti-B. pertussis antibodies and limited prevention of transmission and colonization in individuals immunized with aP vaccines compared with wP vaccines.21 Indeed, a decrease in aP vaccine effectiveness with time since last dose was noted in several studies,22, 23, 24, 25 suggesting that waning immunity is an important contributor to the resurgence of pertussis. Furthermore, it is well-known that protection following either natural infection with B. pertussis or immunization against pertussis (wP or aP) is not lifelong.26, 27 Other explanations included loss of PRN on the bacterium due to immunization pressure,28, 29 and a change in the immune response from Th1 (following wP immunization) to Th2 (following aP immunization),30 and more awareness leading to increase testing and reporting of B. pertussis.