Pertussis makes a nasty comeback

March 1, 2015

Pertussis has recently made an unwelcome comeback. The resurgence of this disease, also known as "whooping cough," leaves pediatricians with a number of problems.

has recently made an unwelcome comeback. The resurgence leaves pediatricians with a number of problems such as:

•           Managing communication strategies to address parents who do not want their children immunized.

•           Managing communication strategies to address parents who want advice on how to deal with unimmunized children and the magnitude of the risk to their own child.

•           Trying to understand why pertussis is making a comeback after being largely controlled for so many years.

•           What to recommend to parents, especially those with higher-risk children such as newborns who cannot yet be immunized.

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A brief history of fading protection

More cases of pertussis were reported in 2010 (27,550) and 2012 (48,277) than since the 1950s. In the 1930s, there were more than a quarter million US cases with the numbers dropping below 1700 in 1970, and numbers slowly rising until the recent peaks.1 Pertussis’ comeback is largely attributed to waning immunity from the acellular pertussis vaccine in combination with undervaccination because of factors such as parental vaccine refusal or other barriers to healthcare.2,3

Patients now in their late teens and older likely received some version of a whole cell pertussis vaccine, which results in a good immune response upon exposure even years later. However, adverse effects such as high fevers, agitation, injection site pain, and the fear of encephalopathy caused a great deal of angst among parents and pediatricians, resulting in lower vaccination rates. All these pressures led to a push for an acellular pertussis vaccine. In the early 1990s, acellular vaccines were approved for the 4th and 5th doses of the pertussis vaccine series and for the entire series in 1997.3

After the 2010 and 2012 outbreaks, researchers looked closely and determined that the acellular vaccine was the culprit. A 2012 study in the New England Journal of Medicine found that the risk of pertussis increased 42% per year after the 5th diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccination.4 A study published in Clinical Infectious Diseases found rates of pertussis highest in children aged 8 to 12 years with the longest intervals since their last vaccination, despite being vaccinated per guideline at the time.5 Although the acellular vaccines appear to be less reactogenic, the immunity appears to dissipate more quickly compared with the whole cell vaccine.3

Many countries much poorer than the United States have managed to maintain very low pertussis rates because they did not switch to the acellular vaccine. Yet, it is unlikely that US pediatricians or parents will support a strategy that entails going back to a whole cell vaccine without a reduction in adverse effects.

NEXT: Who's at risk?

 

Who is at risk?

California highlights the at-risk populations and challenges related to this problem. In June 2014, the California Department of Public Health declared a pertussis epidemic. Between January and November last year, there were 9935 reported cases corresponding to a rate of 26 per 100,000. Infants (174.6 cases per 100,000) and adolescents aged older than 15 years (137.8 cases per 100,000) were hit hardest. Infants aged younger than 1 year accounted for 275 of 347 pertussis-related hospitalizations, and the majority of hospitalizations were in children aged younger than 4 months. Also, there were 3 deaths reported in this age group, although 2 of the cases were diagnosed in late 2013. Severe disease occurred in less than 1% of adolescents despite the high rates of disease.3

For unknown reasons, Hispanic infants have higher infection rates and pertussis deaths compared with other racial groups. Hypotheses include larger family sizes and cultural practices that increase the number of people in contact with infants.3

Undervaccination places infants and children at an increased risk of pertussis.6 Nearly half of young children diagnosed with pertussis in a 2013 JAMA Pediatrics study had not received the 4 recommended vaccine doses.6 Not receiving 3 or 4 doses increased the odds of a pertussis infection by 18 and 28 times, respectively. Undervaccination can occur for many reasons such as parental refusal; parental concerns over the number of shots needed at a particular visit; limited healthcare access; or missed opportunities during well-child or other health visits.

The Centers for Disease Control and Prevention’s Advisory Committee for Immunization Practices now recommends that pregnant women receive tetanus-diphtheria-acellular pertussis (Tdap) vaccine during the third trimester to provide infants protection until beginning immunization at 2 months of age. However, only 17% of mothers of infants diagnosed with pertussis during the 2014 California epidemic received a pertussis vaccination according to this recommendation.

Among adolescent pertussis cases in the 2014 California epidemic, 87% had received the Tdap booster 3 or more years since diagnosis with only 2.2% never having received a pertussis vaccine. The data indicate that the likely culprit is waning immunity.3

More: Red flags for chronic cough

Additionally, data from Kaiser Permanente and the 2010 California outbreak as well as other studies indicate that simply living in areas with high rates of undervaccination may increase risk.7-9

According to the Morbidity and Mortality Weekly Report, infants aged younger than 12 months should be the target of the greatest public health interventions because this group is at the greatest risk of contracting, being hospitalized, or dying from pertussis.3

What to do?

There are a number of strategies that might help decrease the risk of contracting pertussis. This is especially important among high-risk patients aged younger than 1 year. These strategies include:

Cocooning. This is one of the few practices available to the pediatrician. In this strategy, vaccination is encouraged for all contacts of infants so that pertussis is not transmitted to an infant. Risk reduction is achieved by decreasing transmission risk because of the lack of passive immunity in newborns. Not only is this strategy difficult to implement, but infants are still at risk of exposure from other infected contacts.3

A recent study indicates just how difficult this strategy is to implement.10 In a survey of households in Switzerland where the cocooning strategy was implemented in 2011, only 7% of infants were protected by a complete cocoon. Cocooning was incomplete in 93% of families, and less than 20% of infants had cocoons with greater than 50% of close contacts being immunized.

Although this strategy is low risk and inexpensive from the pediatrician’s standpoint, research has recently called into question the cost-effectiveness of cocooning from a public-health perspective.11 Despite this, it seems that the development of counseling strategies and incorporating cocooning strategies into regular prenatal and newborn counseling practice is reasonable.

Vaccinating pregnant mothers. Although the pregnant mother is unlikely to seek care from the pediatrician, these patients can be educated during visits to the pediatrician’s practice with other children, and as part of a prenatal pediatric visit.

There is sufficient transplacental transmission of antipertussis antibodies that may protect the infant from infection until receiving the first vaccine at 2 months of age. The Tdap vaccine is recommended at 27 to 36 weeks’ gestation because immune response peaks 2 weeks following administration. This allows for optimal antibody transfer and protection at birth. Preliminary evidence demonstrates that when mothers are vaccinated in the 3rd trimester, their babies are at lower risk of developing a pertussis infection before beginning primary vaccination series.3

If prenatal providers are unable to provide vaccination, then recommending vaccination, providing a prescription, and referring to a vaccination site are also potential solutions.

Accelerating the DTaP series. The first DTaP can be given as early as 6 weeks of age if pertussis is prevalent in the pediatrician’s local community. This may possibly prevent disease in at-risk infants, and 1 dose provides some amount of protection.3,12

For the development of herd immunity given the current outbreaks, it is likely we will need to vaccinate all age groups and possibly at more frequent intervals.2

NEXT: Why are the vaccines failing?

 

Why do pertussis vaccines fail?

So why is the acellular pertussis vaccine failing? Some researchers point to inadequate definitions of a pertussis case and problems with epidemiological studies such as observational bias overestimating vaccine efficacy. The World Health Organization definition required both laboratory confirmation and 21 days of paroxysmal cough in the initial trials of the acellular pertussis vaccine. There were concerns that this would lead to overconfidence in the acellular vaccine’s efficacy.2

Studies demonstrated that simply changing the case definition to a less severe form of cough decreases observed efficacy of the vaccine by more than 10%.2 Similarly, there have been concerns about observer bias in some national studies done in countries with pertussis epidemics comparing tetanus toxoid and DTaP vaccines. Children receiving DTaP were less likely to have typical pertussis symptoms. The concerns are that parents were hyperaware of pertussis symptoms and essentially self-selected for evaluation, decreasing the efficacy of the tetanus toxoid while inflating the efficacy of DTaP. It is felt parents of children getting DTaP were less likely to seek evaluation for pertussis because symptoms were atypical.2

Although lack of potency was previously an issue with some pertussis vaccines, it is not an issue with the current acellular vaccine. More commonly today, antibodies decrease over time and efficacy wanes. There are other concerns such as genetic changes in pertussis strains that may lead to decreased efficacy rates.2

Other concerns include a recent study demonstrating that the acellular vaccine prevented symptoms but not colonization and transmission of the pertussis infection in a primate model. The researchers offer this as 1 explanation that could increase infection rates utilizing the acellular vaccine.13

Read more: ACIP says nasal spray beats flu shots

Finally, large populations of unvaccinated, susceptible children increase the risk of developing a pertussis infection by factor of 2.5.13

New therapeutic strategies

Given the current resurgence of pertussis, a number of vaccine strategies are being considered:

Live vaccine. Current animal studies have demonstrated that live attenuated vaccines (ie, the current measles and rotavirus vaccines) can generate immune responses that are capable of providing immunity.14,15 Early phase 1 clinical trials found a live, attenuated vaccine was immunogenic and safe, and it is now undergoing further development.16

Changes to current vaccine. Changing vaccine components may improve antibody response and lead to a more efficacious vaccine. Possible targets include: 1) adding adjuvants that stimulate the duration and magnitude of an immune response; 2) adding additional virulence factors; and 3) increasing the quantities/dose of current antigens to increase immune response. Although all are theoretically possible, all would likely require large scale clinical trials to evaluate safety and efficacy, and there are questions as to whether or not Pharma is willing to embark on this path given the time and dollars that went into the acellular vaccine development.17 Further, not only will the studies be expensive, but also the research will take a long time because the vaccines in use today appear to be effective for at least 2 years following administration before immunity begins to wane. An additional option would be to change the alleles in the acellular pertussis vaccine to those specific strains that are circulating in a fashion similar to the development of the flu vaccine, but it is not believed that this will be a complete solution.18

Revert back to a whole cell vaccine. If a whole cell vaccine were developed with detoxified lipopolysaccharide, the component leading whole cell vaccines to be so reactogenic, the vaccine might be more efficacious without the same adverse-effect profile.2 However, without significant changes to the whole cell vaccine (and possibly even with them), it is unlikely that this will be an acceptable solution.

Change the immunization schedule. Boosters of the acellular pertussis vaccine could be given more frequently but at a more substantial cost. Additionally, the acellular pertussis vaccine is currently given in combination with vaccination for tetanus and diphtheria.18

NEXT: The role of the pediatrician

 

The role of the pediatrician

The best way for pediatricians to protect children at greatest risk is to increase herd immunity. Pediatricians can and should advocate for policies that encourage vaccination and discourage exemptions except for specific health-related reasons. However, the greatest majority of pediatricians will make the biggest impacts in their office practices. Multiple field studies demonstrate that children impacted in epidemics often are not vaccinated or undervaccinated.3,19-22 The following suggestions will help pediatricians develop their own pertussis strategy:

Educate yourself. Vaccine-related education is important. In 1 measles epidemic in California, incorrect assumptions and practices by physicians likely led to increased difficulties in controlling the outbreak. Not immunizing children with minor illnesses, not giving more than 1 shot at a visit, and referring underinsured patients to other providers were all associated with inadequate vaccination.23 Further, developing protocols and systems in your office practice can help increase immunization rates and avoid missed opportunities.

Educate parents. Pediatricians are a preferred source of health information for parents. A 2009 survey of more than 21,000 households by the National Center for Immunization and Respiratory Diseases found that more than 86% of parents usually follow their healthcare provider’s advice, and nearly 85% trust their provider’s advice.24 A 2011 study in Pediatrics found that 76% of parents trusted their child’s doctor in regard to vaccine safety, and only 2% did not trust their child’s doctor at all.17

Develop and plan your communications. Given the data about parents looking to and trusting their physician’s advice, it seems prudent to develop a communication strategy for parents who refuse vaccination. The unvaccinated child in your practice did not make the decision to refuse or remain unvaccinated and needs your care.25

Recommended: Emphasizing vaccine benefits could be key

         - Take time to listen. Restate the parent’s concerns, maintain good eye contact, and give parents your full attention. How well the pediatrician listens will impact the parent’s decision to choose vaccination or not.

         - Ask open-ended questions. If parents express concern or just seem reluctant about vaccination, open-ended questions such as “You seem worried about the vaccination” improve communication by letting the parent know you want to hear all their questions and concerns despite a full schedule.

         - Be mindful of nonverbal communication. If parents think that their questions are inappropriate and that the pediatrician is offended by their vaccine-related questions, or they simply imply this from the pediatrician’s reactions or facial expressions, they will shut down communication and trust may be eroded.

         - Be careful not to include too much science. Although this can be difficult to measure because every parent is different, some parents may just want to hear a story or the pediatrician’s thoughtful recommendation after listening to their parental concern.

         - Reduce stress during immunizations. Stressed-out parents lead to stressed-out children, so encouraging parents to remain calm can decrease their child’s anxiety. In younger infants and children, a favorite toy, lovie, or blanket can decrease a child’s anxiety. Parental eye contact, touch, and talking are strategies that can also help calm a child during immunization. After the shot, breast-feeding or cuddling are strategies for comfort. In older children, telling a story, deep breathing, and singing are all distraction options; praise and reassurance are good strategies when the shots are done.

After understanding the current pertussis resurgence and how it came to be, pediatricians can develop clinical strategies and advocate for policies that will help get the current epidemic under control.

 

REFERENCES

1. Centers for Disease Control and Prevention; National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases. Pertussis cases by year (1922-2013). Available at: http://www.cdc.gov/pertussis/surv-reporting/cases-by-year.html. Reviewed August 28, 2013. Accessed February 20, 2015.

2. Cherry JD. Why do pertussis vaccines fail? Pediatrics. 2012;129(5):968-970.

3. Winter K, Glaser C, Watt J, Harriman K; Centers for Disease Control and Prevention (CDC). Pertussis epidemic-California, 2014. MMWR Morb Mortal Wkly Rep. 2014;63(48):1129-1132.

4. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R. Waning protection after fifth dose of acellular pertussis vaccine in children. N Engl J Med. 2012;367(11):1012–1019.

5. Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clin Infect Dis. 2012;54(12):1730-1735.

6. Glanz JM, Narwaney KJ, Newcomer SR, et al. Association between undervaccination with diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine and risk of pertussis infection in children 3 to 36 months of age. JAMA Pediatr. 2013;167(11):1060-1064.

7. Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE. Individual and community risks of measles and pertussis associated with personal exemptions to immunization. JAMA. 2000;284(24):3145-3150.

8. Omer SB, Enger KS, Moulton LH, Halsey NA, Stokley S, Salmon DA. Geographic clustering of nonmedical exemptions to school immunization requirements and associations with geographic clustering of pertussis. Am J Epidemiol. 2008;168(12):1389-1396.

9. Atwell JE, Van Otterloo J, Zipprich J, et al. Nonmedical vaccine exemptions and pertussis in California, 2010. Pediatrics. 2013;132(4):624-630.

10. Urwyler P, Heininger U. Protecting newborns from pertussis-the challenge of complete cocooning. BMC Infect Dis. 2014;14:397.

11. Skowronski DM, Janjua NZ, Tsafack EP, Ouakki M, Hoang L, De Serres G. The number needed to vaccinate to prevent infant pertussis hospitalization and death through parent cocoon immunization. Clin Infect Dis. 2012;54(3):318–327.

12. Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy TV. Trends in pertussis among infants in the United States, 1980-1999. JAMA. 2003;290(22):2968-2975.

13. Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci U S A. 2014;111(2):787-792.

14. Skerry CM, Mahon BP. A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model. Clin Vaccine Immunol. 2011;18(2):187-193.

15. Fedele G, Bianco M, Debrie AS, Locht C, Ausiello CM. Attenuated Bordetella pertussis vaccine candidate BPZE1 promotes human dendritic cell CCL21-induced migration and drives a Th1/Th17 response. J Immunol. 2011;186(9):5388-5396.

16. Thorstensson R, Trollfors B, Al-Tawil N, et al. A phase I clinical study of a live attenuated Bordetella pertussis vaccine-BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers. van Boven M, ed. PLoS ONE. 2014;9(1):e83449.

17. Freed GL, Clark SJ, Butchart AT, Singer DC, Davis MM. Sources and perceived credibility of vaccine-safety information for parents. Pediatrics. 2011;127 suppl 1:S107-112.

18. Plotkin SA. The pertussis problem. Clin Infect Dis. 2014;58(6):830-833.

19. Centers for Disease Control and Prevention (CDC). Pertussis epidemic-Washington, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(28):517-522.

20. Matthias J, Dusek C, Pritchard SP, et al; Centers for Disease Control and Prevention. Notes from the field: Outbreak of pertussis in a school and religious community averse to health care and vaccinations--Columbia County, Florida, 2013. MMWR Morb Mortal Wkly Rep. 2014;63(30):655.

21. Centers for Disease Control and Prevention (CDC). Notes from the field: Measles outbreak--Hennepin County, Minnesota, February-March 2011. MMWR Morb Mortal Wkly Rep. 2011;60(13):421.

22. Muñoz-Alía MÁ, Fernández-Muñoz R, Casasnovas JM, et al. Measles virus genetic evolution throughout an imported epidemic outbreak in a highly vaccinated population. Virus Res. 2015;196:122-127.

23. Insel K. Treating children whose parents refuse to have them vaccinated. Virtual Mentor. 2012;14(1):17-22.

24. Kennedy A, Basket M, Sheedy K. Vaccine attitudes, concerns, and information sources reported by parents of young children: results from the 2009 HealthStyles survey. Pediatrics. 2011;127 suppl 1:S92–S99.

25. Centers for Disease Control and Prevention. Provider resources for vaccine conversations with parents. Available at: http://www.cdc.gov/vaccines/hcp/patient-ed/conversations/. Updated December 17, 2014. Accessed February 20, 2015.