Bordetella pertussis (Pertussis) Heather L. Daniels, DO,* Camille Sabella, MD* *Center for Pediatric Infectious Diseases, Cleveland Clinic Children’s, Cleveland, OH Education Gaps 1. Clinicians must understand the changing epidemiology of pertussis and the reasons for the endemic and epidemic nature of infection despite widespread vaccination. 2. Clinicians must understand the strategies developed to prevent pertussis in those who are at high risk for complications. Objectives After completing this article, readers should be able to: 1. Recognize the antigenic components of pertussis. 2. Understand the changing epidemiology of the disease and the major factors contributing to this change. 3. Describe the clinical features during the natural progression of pertussis and the complications of infection. 4. List the options for laboratory testing of pertussis and their respective limitations. 5. List the recommended agents for antimicrobial treatment and postexposure chemoprophylaxis of pertussis. 6. Understand the rationale for the current pertussis vaccine recommendations. AUTHOR DISCLOSURE Drs Daniels and Sabella have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a INTRODUCTION commercial product/device. Bordetella pertussis is a fastidious gram-negative coccobacillus responsible for the ABBREVIATIONS respiratory infection commonly known as “whooping cough.” The organism is CDC Centers for Disease Control and spread by respiratory droplets and is highly contagious among close contacts. The Prevention typical incubation period is 7 to 10 days, but it may be as long as 21 days. Neither DTaP diphtheria, tetanus, and acellular natural infection nor pertussis vaccination results in long-lasting immunity, pertussis vaccine DTwP diphtheria, tetanus, and whole cell contributing to endemic infection and 3- to 5-year cycles of pertussis epidemics. pertussis vaccine IHPS infantile hypertrophic pyloric stenosis PATHOGENESIS PCR polymerase chain reaction Several active components, which play a role in immunity and are responsible for Tdap tetanus toxoid, reduced diphtheria ’ B pertussis toxoid, and acellular pertussis the organism s ability to cause disease, are produced by . (1) Pertussis vaccine toxin, filamentous hemagglutinin, pertactin, and agglutinogen allow the organism Th T-helper to adhere to ciliated epithelium of the respiratory tract, where it exerts its effects. Vol. 39 No. 5 MAY 2018 247 Pertussis toxin also induces cell cytoxicity, inhibits neutro- 1955. (3) Worldwide, pertussis is responsible for 16 million philic and monocytic responses, and delays induction of cases and approximately 195,000 deaths annually. (4) specific immune responses. Pertussis toxin is postulated to Historically, the incidence of pertussis peaked in children be responsible for the systemic manifestations of pertussis, 1 to 5 years of age and was less common in those younger including the leukocytosis and lymphocytosis evident in than 1 year and older than 10 years. There has been a shift in young infants. This virulence factor is also thought to sen- recent decades with an increase in the incidence among sitize b-islet cells in the pancreas, which may lead to hyper- infants younger than 1 year, adolescents, and adults (Fig 2). insulinism, which rarely manifests as hypoglycemia in young In 2015, 55% of reported pertussis cases in the United States infants. Other substances elaborated by the organism include were in individuals older than 10 years, and children youn- adenylate cyclase and tracheal cytotoxin, which allow the ger than 1 year accounted for 13% of cases. (5) bacteria to cause damage to the respiratory epithelium and There are multiple factors that seem to be responsible for evade the host immune system by altering leukocyte function. the change in epidemiology of pertussis: the switch from Pertussis vaccines contain these various antigenic compo- whole cell pertussis vaccine to acellular pertussis vaccine, nents. Central nervous system complications of pertussis are waning immunity, change in the organism, vaccine refusal, thought to be secondary to hypoxemia induced by coughing lack of natural disease to boost immune response, and un- and apnea associated with infection rather than to a direct diagnosed individuals serving as reservoirs. effect on the central nervous system by the organism. (2) Switch from Whole Cell Pertussis Vaccine to Acellular Pertussis Vaccine EPIDEMIOLOGY Concerns about the reactogenicity of the diphtheria and In the 1940s, before the introduction of pertussis vaccine in tetanus toxoids and whole cell pertussis vaccine (DTwP) lead the United States, there were 100,000 to 200,000 cases of to the development and introduction of the diphtheria and whooping cough and thousands of deaths annually. After the tetanus toxoids and acellular pertussis vaccine (DTaP). The introduction of pertussis vaccine, there was a 99% decrease DTaP was incrementally introduced into the US pediatric in the number of cases; the lowest number of cases was in immunization schedule starting in 1992, with all children 1976, with only 1,010 cases reported. Over the past few receiving only the DTaP by 1997. (6) Acellular pertussis decades there has been an increasing incidence of pertussis vaccines are significantly less reactogenic than whole cell (Fig 1). According to the Centers for Disease Control and vaccines. Prevention (CDC), there were 48,277 cases reported in the Recent studies during epidemic outbreaks in Australia United States in 2012, the highest number of cases since demonstrated that children who received the DTwP series Figure 1. Reported pertussis cases, 1922-2015. From the Centers for Disease Control and Prevention National Notifiable Diseases Surveillance System for 1950 through 2015 and from passive reports to the Public Health Service from 1922 through 1949. DTP¼diphtheria, tetanus toxoids, and pertussis vaccine, DTaP¼diphtheria, tetanus, and acellular pertussis vaccine, Tdap¼tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. 248 Pediatrics in Review Figure 2. Pertussis incidence by age group, 1990-2015. From the Centers for Diseases Control and Prevention National Notifiable Diseases Surveillance System. had lower rates of pertussis than those who received the DTaP, with only an estimated 10% of children retaining DTaP series. (7) This effect may be related to the different immunity 8.5 years after the last immunization. (18) responses elicited by the 2 types of vaccines: the whole cell pertussis vaccine activates T-helper (Th) type 1 cells, and the Change in the Organism acellular pertussis vaccine elicits a Th2 response. The Th1 Current vaccines contain various antigens to components of B pertussis, fi responses result in robust interferon-g production, which is such as pertussis toxin, mbriae, pertactin, and fi required for cell-mediated immunity and rapid clearance of lamentous hemagglutinin. Since the introduction of the the organism on repeated exposure, whereas Th2 responses whole cell and acellular vaccines there have been genetic B pertussis do not seem to have the same effect on interferon-g, changes of . Variants that are emerging include prn2 resulting in less effective clearing of the organism from allele changes to the genes that code for pertactin ( ), ptxP3 fi Fim3 the respiratory tract after infection. Thus, humoral immu- pertussis toxin promoter ( ), and mbriae ( ). (6) nity provided by acellular pertussis vaccines seems to be (19)(20)(21) Studies in Europe and Asia have demonstrated effective at preventing severe disease but may lack the that current pertussis strains are different from when the cellular responses needed to effectively eradicate the infec- vaccines were developed, which may be limiting the mem- tion from the respiratory tract. (7)(8)(9)(10)(11)(12)(13)(14) ory provided by vaccination. (20)(21) In addition, the adap- tation of these components may make the organism more Waning Immunity virulent and adept to evade the immune response. (19) Neither natural infection nor vaccination induces lifelong Vaccine Refusal immunity. Recent studies demonstrate that immunity There is concern that vaccine hesitancy or refusal has wanes 4 to 20 years after natural infection and 4 to 12 years contributed to the resurgence of preventable diseases, espe- after vaccination. (15) After pertussis outbreaks in California cially measles and pertussis. Phadke et al (22) reviewed the in 2010 and 2014, it was determined that patients who analysis of 32 pertussis outbreaks and found high percent- developed pertussis were more likely to have had a longer ages of unvaccinated individuals (24%–45%) in the states period of time since their last DTaP or tetanus toxoid, with the largest outbreaks, with a significant proportion of reduced diphtheria toxoid, and acellular pertussis vaccine individuals (59%–93%) unvaccinated by choice. (Tdap). (16)(17) More specifically, immunity began to wane 5 years after the last DTaP, with a 42% increase in the odds of Lack of Natural Disease to Boost Immune Response developing pertussis each year thereafter. (16) These studies Some have proposed that with decreased rates of pertussis also determined that immunity began to wane 2 to 3 years since vaccine development there are fewer cases of pertussis after Tdap vaccination. (17) Another study showed that the to which an individual is exposed during their life, thereby odds of pertussis increased 1.33 times per year after