Part 1 of 3
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Persistence of a vaccine-preventable disease
Faculty Reviewers Tina Q. Tan, MD Professor of Pediatrics Feinberg School of Medicine Northwestern University Chicago, Illinois
Audrey Stevenson, PhD, MPH, FNP-BC Director, Family Health Services Division Salt Lake Valley Health Department Salt Lake City, Utah
© Ariel Skelley/Corbis
or many people, health-care providers and the public alike, pertussis is old news—a once-feared disease long controlled by vaccination. The perception that pertussis is something we don’t have to worry about obscures the fact that, despite effective vaccines and generally high coverage, pertussis remains a stubborn public health threat to people of all ages, more prevalent and severe than is commonly recognized. Over the last 2 decades in the United States, deaths have actually increased among infants too young to have been fully immunized. In the prevaccine era, pertussis was a very common childhood disease and a major cause of death in the US.1 During the 1920s and 1930s, an average of more than 160,000 cases and 5000 deaths per year were reported.2 The average annual incidence of disease was 157 cases per 100,000 people.3 A whole-cell pertussis vaccine consisting of formalin-inactivated Bordetella pertussis cells was developed in the 1930s and widely administered by the mid-1940s.1 Within 3 short decades, routine childhood vaccination had reduced reported pertussis cases in the US to 0.5 per 100,000.4 By the 1990s, acellular pertussis vaccines— subunit formulations containing purified, inactivated components of B pertussis cells that cause fewer adverse reactions than whole-cell vaccine1—had been developed. These vaccines—diphtheria and tetanus toxoids with acellular pertussis (DTaP)—were licensed for the fourth and fifth doses of the childhood pertussis immunization series in 1991 and for the full primary immunization series in 1996.5 The whole-cell vaccine hasn’t been available in the US since 2002. A widespread misconception holds that childhood vaccination or infection with B pertussis confers lifelong immunity. In fact, immunity wanes within approximately 5 to 10 years after vaccination and anywhere from 7 to 20 years after natural infection.6,7 Many health-care providers are unaware of the phenomenon of waning immunity, contributing to an erroneous assumption that adolescents and adults don’t contract pertussis. In fact, not only do they contract pertussis, they are conduits of infection, transmitting pertussis most notably to infants, the group most likely to succumb to this vaccine-preventable disease.
Success, then a rising tide of cases After reaching a low point of 1016 reported cases in 1976, pertussis in the US began to rise in the 1980s.2,4 It has continued to increase steadily over most of the past 3 decades, usually peaking every 3 or 4 years, in keeping with the cyclical nature of pertussis.7 In 2004, 25,827 cases were reported, the highest number since 1959.1 Possible contributing factors for the increase include waning of vaccine-acquired immunity, decreased natural boosting of immunity because of reduced circulating levels of B pertussis during the years of declining disease, and increased detection and reporting of cases, especially among adolescents and adults.5,6 Reported cases of pertussis have declined since 2005, falling to 13,278 in 2008,8 comparable to the provisional number of cases reported for 2009.9 The decrease in reports may be attributable to better vaccine coverage, variations in reporting, or the cyclical pattern of pertussis. Notably, after rising for years, pertussis rates during 2004-2008 for adolescents 11 through 18 years of age declined more rapidly than rates for all other age groups combined.10 Possible reasons include a natural boosting of immunity among adolescents as a result of increased circulation of pertussis disease during 2004-2005, fluctuations in testing and reporting patterns, and the cyclical nature of pertussis.10 The decrease could also reflect some early benefit of tetanus, diphtheria, and acellular pertussis (Tdap) vaccines, which were licensed in 2005 as a singledose booster for adolescents and adults.10 From 2006-2008, Tdap vaccine coverage among adolescents 13-17 years of age increased from 11% to 41%.11,12 Even with recent declines in rates of pertussis, adolescents 10-19 years of age and adults 20 years of age and older still account for
5000 4000 3000 2000 1000 0
Age Group a Data for 2009 are provisional. Sources: CDC, 9,14,15,24,29 Güris D, et al.30
Figure 1. Pertussis cases by time period and age group, 1990-2009.
the preponderance of reported cases (Figure 1). From 2006-2008, 58% of cases occurred in people 10 years of age and older.13-15 While the number of cases remains highest among adolescents and adults, the incidence of pertussis is highest among infants, especially those in the first months of life. In 2008, the incidence was 79 per 100,000 people in infants younger than 6 months of age, compared with just 4 per 100,000 in the population at large.15 The number of reported cases of pertussis belies the true prevalence of disease, which appears to be much higher, because pertussis often goes unrecognized, especially among adolescents and adults. Experts believe an estimated 800,000 to 3.3 million cases of pertussis per year occur among adolescents and adults in the US.16 Worldwide, the annual estimate of pertussis cases is 50 million, with a quarter of a million deaths, mostly among infants who either are unimmunized or have not completed the primary immunization series.17,18 In spite of high immunization rates, pertussis remains endemic in the US and other industrialized countries due to the continuing circulation of B pertussis among susceptible adolescents and adults. It persists, in part, because the classic symptoms of pertussis, such as whoop and post-tussive emesis, are absent in many adolescents and adults; mild cough may be the only manifestation. Even when classic symptoms are present, health-care providers often fail to consider pertussis in the differential diagnosis.19 Studies indicate that pertussis is the cause of prolonged coughing in 13% to 17% of adolescents and adults, but most times goes undetected as the source of the cough.16 Pertussis is highly contagious, and undiagnosed disease permits transmission to close contacts and keeps B pertussis circulating in the general population, even though the reported incidence of disease has declined.16 By contrast, with other infectious diseases, such as measles, immunization has reduced both the incidence and circulation of the organism.16 As B pertussis circulation persists, so do outbreaks of disease in schools, health-care facilities, and community settings throughout the US. Many outbreaks have been traced back to adolescents (such as high school students) and adults (notably, health-care providers). Underimmunization of young children has also played a role. Outbreaks underscore the continued importance of immunizing with age-appropriate vaccines according to the US recommended schedule. For a discussion of several recent outbreaks, see “Pertussis outbreaks just keep rolling along,” on the next page.
How pertussis spreads Pertussis is a highly communicable disease exclusive to humans. The secondary attack rate is approximately 80%-90% among vulnerable household contacts.7 Pertussis is most often transmitted by the respiratory route through aerosolized droplets from a cough or sneeze or direct contact with respiratory secretions from an infected person.20 Less often, transmission results from direct contact with articles recently contaminated by an infected person.1 Pertussis disease has 3 stages. Patients are most infectious during the initial, or catarrhal, stage of disease—runny nose, sneezing, lowgrade fever, and mild, occasional cough lasting 1 to 2 weeks—and during the first 2 weeks after the onset of the second stage, marked by paroxysmal cough. The average period of high communicability thus lasts about 21 days.1 A person with pertussis gradually recovers during the third, or convalescent, stage of disease; a full recovery may take several months. Adolescents and adults, even those with mild disease, can transmit pertussis to susceptible contacts. They are often the initial source of infection in their household and an important source of infection in infants.1 Researchers from the Centers for Disease Control and Prevention (CDC) examined infant pertussis cases in Georgia, Illinois, Massachusetts, and Minnesota and identified 264 cases with a known or suspected source of infection.21 Seventy-five percent of those infants contracted pertussis from a family member. Mothers were the most frequent source (32%), followed by siblings (20%), fathers (15%), and grandparents (8%) (Figure 2). The most common sources of infection by age, when age was known, were adults and adolescents. Adults 30 years of age and older were responsible for 35% of infections; adults between 20 and 29 years of age, 21%; and adolescents between 10 and 19 years of age, 20%.21 In a multicenter study conducted in France, Germany, Canada, and the US, Wendelboe and colleagues examined the cases of 95 infants with pertussis who were 6 months of age or younger and 404 household or close nonhousehold contacts.22 Among the 44 infants for whom a source of pertussis could be identified, a household member was responsible for transmission in up to 82% of cases. Mothers were, again, the most frequent source of infection (37%), followed by fathers (18%), siblings (16%), and other relatives.22
Mom 32% Sibling 20%
Source: Bisgard KM, et al.21
Figure 2. Where do infants get pertussis? In most cases, from a parent.21,22
Corbis (Mom); Getty (Grandparent); Shutterstock (Dad, Sibling)
Average Cases Per Year
Pertussis outbreaks just keep rolling along
everal recent outbreaks of pertussis illustrate the breadth of infection in the US—affecting schools, health-care facilities, and entire communities, highly vaccinated as well as undervaccinated. In May 2008, an outbreak among the 300 students in kindergarten through 12th grade at the East Bay Waldorf School in Contra Costa County, California, resulted in a 1-day closing of the school.1 At least 16 students were affected, more than half of them kindergarteners. An unusually high number of students hadn’t been immunized against pertussis. (California law, like that in many states, permits parents to forgo having their children vaccinated for religious or philosophical reasons.) Underimmunization was also a factor in a 2004-2005 outbreak in an Amish community in Kent County, Delaware.2 Of a total of 345 cases, 41% were children between 1 and 5 years of age. The age distribution of pertussis cases was similar to that of the prevaccine era. In 45% of the 96 households interviewed that had a case of pertussis, none of the children had been vaccinated, often because parents feared side effects or “didn’t think about it.”2 In contrast to the Contra Costa and Kent County outbreaks, a 2003-2004 outbreak in Fond du Lac, Wisconsin, occurred in a highly vaccinated population and caused significant morbidity in adolescents and adults; in addition, 2 infants were hospitalized. Of the 261 people who contracted pertussis, 86% were 10 years of age or older.3 Pertussis spread among adolescents using a high school weight room and from there into the community, causing disease countywide. Notably, adults had more severe symptoms than adolescents. An aggressive response—5000 county residents received antimicrobial treatment or prophylaxis—may have helped to sharply decrease the number of cases. The outbreak highlights the potential benefits of vaccinating adolescents and adults with a booster dose of Tdap.3 Numerous pertussis outbreaks in hospitals, many arising from While effective vaccination of adolescents and adults in close contact with infants has the potential to significantly reduce the occurrence of infant pertussis,22 so does immunization of the wider community. Data from a follow-up to the multicenter study by Wendelboe and colleagues suggest that transmission of pertussis to infants by casual contacts in the community may be significant— accounting for approximately one third of cases.23 If that is so, maximum protection of young infants will depend on high rates of vaccination in the adolescent and adult populations as a whole.22 Infants are at highest risk Pertussis is most severe in infants, and deaths in this age group are increasing. During the 1980s, 61 pertussis-related infant deaths were reported in the US, 49 of them in babies younger than 4 months of age.2 In the 1990s, the number of deaths rose to 93, with 84 of these infants younger than 4 months of age.2 From 2000 through 2008, the number of deaths reported among infants younger than 4 months of age jumped to 164.7,14,24-26 During 2000-2004, among 12,174 infants younger than 12 months of age with pertussis for whom information on complications was available, nearly 2 out of 3 were hospitalized (Table).7 One in 10 of the infected infants had radiographically confirmed pneumonia. Apnea occurred in more than half the patients.
infected health-care workers, illustrate the importance of vaccinating this key population to protect staff and patients and avoid the substantial costs associated with outbreaks. Some recent examples: • Pertussis in a 2-month-old infant in a neonatal intermediate care nursery was traced to a health-care worker in the unit, one of 4 staff found to have the disease.4 • An outbreak of 122 cases at the Mayo Clinic in Rochester, Minnesota, involved transmission among health-care workers and from patients to workers. Aggressive management brought the outbreak under control. No transmission of disease from health-care workers to patients was documented.5 • Ten cases of pertussis among health-care workers and communi- ty contacts at 2 hospitals in Washington state were traced to an emergency physician and a respiratory therapist. One hospital incurred direct costs of $195,342 and indirect costs of $68,015 from the outbreak; direct and indirect costs to the other hospital were $71,130 and $50,000, respectively.6 REFERENCES
1. Contra Costa Health Services. Health officials close Contra Costa school to control whooping cough outbreak (press release). May 9, 2008. 2. CDC. Pertussis outbreak in an Amish community—Kent County, Delaware, September 2004February 2005. MMWR. 2006;55(30):817-821. 3. Sotir MJ, Cappozzo DL, Warshauer DM, et al. A countywide outbreak of pertussis. Initial transmission in a high school weight room with subsequent substantial impact on adolescents and adults. Arch Pediatr Adolesc Med. 2008;162(1):79-85. 4. Bryant KA, Humbaugh K, Brothers K, et al. Measures to control an outbreak of pertussis in a neonatal intermediate care nursery after exposure to a healthcare worker. Infect Control Hosp Epidemiol. 2006;27(6):541-545. 5. Leekha S, Thompson RL, Sampathkumar P. Epidemiology and control of pertussis outbreaks in a tertiary care center and the resource consumption associated with these outbreaks. Infect Control Hosp Epidemiol. 2009;30(5):467-473. 6. Baggett HC, Duchin JS, Shelton W, et al. Two nosocomial pertussis outbreaks and their associated costs—King County, Washington, 2004. Infect Control Hosp Epidemiol. 2007;28(5):537-543.
In infants younger than 6 months of age, bacterial pneumonia is the most common complication of pertussis and the leading cause of death.1 Pneumonia is also a frequent complication in children 6 months to 4 years of age. Neurologic complications (seizures and encephalopathy resulting from hypoxia) also occur more often in infants than in older children. Paroxysmal coughing may lead to pneumothorax, epistaxis, subdural hematomas, hernias, and rectal prolapse. Other possible complications include otitis media, anorexia, and dehydration.1 Pertussis-related hospitalization rates increase with decreasing age.7 Young infants who haven’t completed the primary vaccine series at 2, 4, and 6 months of age are especially vulnerable to complications, hospitalization, and death from pertussis,22 a fact that highlights the importance of timely immunization in compliance with the recommendations. The younger the infant, the higher the risk of a fatal outcome. During 2000-2008, 96% of reported deaths from pertussis occurred in infants younger than 4 months of age.7,14,24-26 In addition to young age, prematurity (gestational age less than 37 weeks) and Hispanic ethnicity appear to be risk factors for pertussisrelated deaths. The higher mortality among Hispanic infants hasn’t been explained and may reflect a disproportionate number of cases of pertussis in this group.2 Maternal antibody confers to newborns limited protection at
Table. COMPLICATIONS OF PERTUSSIS IN 12,174 INFANTS <12 Months of Age, 2000-20047 Complication
For 20% of infant cases, no information was available on hospitalization, seizure, or apnea; for 30%, no information was available on pneumonia.
best. Levels of pertussis-specific immunoglobulin G decline rapidly after birth and are negligible by 2 months of age.27 A recent study found that only 25% of infants had potentially protective pertussis antibody levels at birth. The investigators predicted that by 6 weeks of age, only about 10% would have protective titers, leaving the remaining 90% of babies vulnerable to pertussis infection.28 Prevention is the best defense Preventing pertussis through immunization is the first line of defense. Early treatment with antibiotics can reduce the likelihood of transmission by decreasing the period of communicability and eradicating B pertussis from the nasopharynx. Treatment usually doesn’t change the course of illness once the cough has started, however.7 Moreover, many cases of pertussis are never recognized and treated, meaning that opportunities to break the cycle of transmission are lost. Parts 2 and 3 of this newsletter series will discuss pertussis diagnosis, treatment, and prevention in detail. REFERENCES 1. Centers for Disease Control and Prevention (CDC). Pertussis. In: Atkinson W, Wolfe S, Hamborsky J, et al (eds): Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 11th ed: 199-216. Washington, DC: Public Health Foundation, 2009. 2. Vitek CR, Pascual FB, Baughman AL, et al. Increase in deaths from pertussis among young infants in the United States in the 1990s. Pediatr Infect Dis J. 2003;22(7):628-634. 3. Forsyth KD. Pertussis, still a formidable foe. Clin Infect Dis. 2007;45(11):1487-1491. 4. Brown K, Cassiday P, Tondella ML, et al. Pertussis. In: Manual for the Surveillance of Vaccine-Preventable Diseases. 4th ed. 2008. http://www.cdc.gov/vaccines/Pubs/surv-manual/ chpt10-pertussis.htm. Accessed April 7, 2010. 5. CDC. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines. Recommendations of the
Advisory Committee on Immunization Practices. MMWR. 2006;55(RR-3):1-45. 6. Wendleboe AM, Van Rie A, Salmaso S, et al. Duration of immunity against pertussis after natural infection or vaccination. Pediatr Infect Dis J. 2005;24(5 suppl):S58-S61. 7. CDC. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among healthcare personnel. MMWR. 2006;55(RR-17):1-37. 8. CDC. Notice to readers: Final 2008 reports of nationally notifiable infectious diseases. MMWR. 2009;58(31):856-884. 9. CDC. Data on file (Pertussis Surveillance Report, Weeks 1-52, 2009 [Provisional data]). MKT19431. 10. Skoff TH, Brown K, Cohn A, et al (CDC). Where has all the pertussis gone? Pertussis trends from 1990-2008 and the potential early impact of Tdap vaccination. Presented at: 43rd National Immunization Conference, Dallas, Texas, April 1, 2009. 11. CDC. National vaccination coverage among adolescents aged 13-17 years—United States, 2006. MMWR. 2007;56(34):885-888. 12. CDC. National, state, and local area vaccination coverage among adolescents aged 13-17 years— United States, 2008. MMWR. 2009;58(36):997-1001. 13. CDC. Data on file (Pertussis Surveillance Report, Weeks 1-52, 2006 [Final data]). MKT17595. 14. CDC. Data on file (Pertussis Surveillance Report, Weeks 1-52, 2007 [Final data]). MKT18596. 15. CDC. Data on file (Pertussis Surveillance Report, Weeks 1-52, 2008 [Final data]). MKT18761. 16. Cherry JD. The epidemiology of pertussis: a comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection. Pediatrics. 2005;115(5): 1422-1427. 17. Forsyth KD, Campins-Marti M, Caro J, et al. New pertussis vaccination strategies beyond infancy: recommendations by the Global Pertussis Initiative. Clin Infect Dis. 2004;39(12): 1802-1809. 18. World Health Organization. Immunization surveillance, assessment, and monitoring. Pertussis. http://www.who.int/immunization_monitoring/diseases/pertussis/en/index.html. Accessed April 14, 2010. 19. Wirsing von König CH, Halperin S, Riffelmann M, et al. Pertussis of adults and infants. Lancet Infect Dis. 2002;2(12):744-750. 20. CDC. Recommended antimicrobial agents for treatment and postexposure prophylaxis of pertussis: 2005 CDC Guidelines. MMWR. 2005;54(RR-14):1-16. 21. Bisgard KM, Pascual FB, Ehresmann KR, et al. Infant pertussis: who was the source? Pediatr Infect Dis J. 2004;23(11):985-989. 22. Wendelboe AM, Njamkepo E, Bourillon A, et al. Transmission of Bordetella pertussis to young infants. Pediatr Infect Dis J. 2007;26(4):293-299. 23. Wendelboe AM, Hudgens MG, Poole C, et al. Estimating the role of casual contact from the community in transmission of Bordetella pertussis to young infants. Emerg Themes Epidemiol. 2007;4:15. 24. CDC. Data on file (Pertussis Surveillance Reports, 2001-2006, Weeks 1-52 [Final data]). MKT17595. 25. CDC. Data on file (2006 Pertussis Surveillance Report, Pamela Srivastava e-mail), March 2008. MKT15248. 26. CDC. Data on file (2008 Pertussis Surveillance Report, Amanda Faulkner e-mail), February 2010. MKT19489. 27. Healy CM, Munoz FM, Rench MA, et al. Prevalence of pertussis antibodies in maternal delivery, cord, and infant serum. J Infect Dis. 2004;190(2):335-340. 28. Shakib JH, Ralston S, Raissy HH, et al. Pertussis antibodies in postpartum women and their newborns. J Perinatol. 2010;30(2):93-97. 29. CDC. Pertussis—United States, 1997-2000. MMWR. 2002;51(4):73-76. 30. Güris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the US: increasing reported incidence among adolescents and adults, 1990-1996. Clin Infect Dis. 1999;28(6):1230-1237.
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