Diptheria, Pertussis, and Tetanus: Evidence-Based Management of Pediatric Patients in the Emergency Department (Pharmacology CME)

Table of Contents

 

1. Abstract
2. Case Presentations
3. Critical Appraisal of the Literature
4. Introduction
5. Etiology And Pathophysiology
   1. Etiology And Pathophysiology Of Diphtheria
   2. Etiology And Pathophysiology Of Pertussis
   3. Etiology And Pathophysiology Of Tetanus
6. Epidemiology And Prevalence
   1. Epidemiology And Prevalence Of Diphtheria
   2. Epidemiology And Prevalence Of Pertussis
   3. Epidemiology And Prevalence Of Tetanus
   4. Vaccines For Diphtheria, Pertussis, And Tetanus
7. Clinical Features
   1. Clinical Features Of Diphtheria
   2. Clinical Features Of Pertussis
   3. Clinical Features Of Tetanus
8. Differential Diagnosis
9. Prehospital Care
10. Emergency Department Evaluation
    1. History
    2. Physical Examination
11. Diagnostic Studies
    1. Diagnostic Studies For Diphtheria
12. Treatment
    1. Treatment For Diphtheria
    2. Treatment For Pertussis
    3. Treatment For Tetanus
       1. Reducing Circulating Toxin And Eradicating The Organism
       2. Controlling Muscle Spasms
          • Benzodiazepines
          • Magnesium Sulfate
          • Other Drugs
       3. Maintaining Autonomic Stability
       4. Wound Care
    4. Treatment Of Vaccine Side Effects And Adverse Events
    5. Reporting Cases Of Diphtheria, Pertussis, And Tetanus
13. Special Circumstances
    1. Managing Close Contacts Of Patients With Diphtheria
    2. Managing Close Contacts Of Patients With Pertussis
14. Controversies And Cutting Edge
    1. Vaccine Refusal
    2. Acellular Pertussis Efficacy
15. Disposition
16. Summary
17. Risk Management Pitfalls In Patients with Diphtheria, Pertussis, Or Tetanus
18. Time- And Cost-Effective Strategies
19. Case Conclusions
20. Clinical Pathway For The Management Of Patients With Suspected Diphtheria, Pertussis, Or Tetanus
21. Tables and Figures
    1. Figure 1. A Strongly Adherent Pseudomembrane Of Diphtheria
    2. Figure 2. The “Bull Neck” Appearance Of Diphtheria
    3. Figure 3. Facial Grimacing In An Infant With Neonatal Tetanus
    4. Table 1. Possible Causes Of Membranous Pharyngitis
    5. Table 2. Illnesses Causing Sporadic Prolonged Cough
    6. Table 3. Conditions Presenting With Muscular Contractions
    7. Table 4. Post–Wound Tetanus Vaccination Guidelines
22. References

Abstract

Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted.

Case Presentations

A panicked mother rushes into the emergency department, screaming that her baby is not breathing. Taking the apneic infant from her, you hurry to the resuscitation bay. Within seconds, the infant begins to breathe spontaneously. You provide supplemental oxygen by face mask as the team attaches leads and obtains vital signs. The monitor shows a respiratory rate of 30 breaths/min, heart rate of 140 beats/min, and oxygen saturation of 98% on room air. As you note a rather unremarkable physical examination, apart from occasional gagging, his school-age sibling begins coughing. Does this sibling’s apparent upper respiratory illness have anything to do with your patient’s condition? You consider the infectious processes that could present with apnea and the key historical questions you should ask the mother, and you begin to plan your next step in the assessment and management of this baby.

Leaving a resident to begin appropriate investigations on the baby, you enter an examination room to find a 5-year-old boy holding a bandage to his foot. His parents report that he stepped on a nail while playing at a farm earlier that day. On examination, you note a small puncture wound that does not appear grossly soiled and is not actively bleeding. He is otherwise both engaging and well-appearing. As you review the triage notes, your eye falls to a red circle around the words, “No Imm!” You quickly realize this child is unimmunized and at risk for tetanus. You sigh, hesitant to broach the topic. It seems unlikely you alone can change the parents’ minds about vaccines. Should you bother discussing the topic? Should you call the primary care doctor and see if he can convince them? Could an antibiotic prevent tetanus infection?

As you consider your options, the ambulance bay doors open and a local EMS crew comes rushing in with a toxic-appearing young girl on the gurney in obvious respiratory distress. The child has a fever of 38ºC, respiratory rate of 35 breaths/min, heart rate of 150 beats/min, and a blood pressure of 75/45 mm Hg. On examination, there is inspiratory stridor, significant cervical lymphadenopathy, and a thick, grayish membrane that seems to be coating the posterior pharynx. Chest examination reveals bilateral rales and tachycardia with frequent ectopic beats. Having now decided that this patient is your top priority, you ask the charge nurse to notify the PICU and cardiology, and you begin to form a differential diagnosis in your mind. Could this child have a viral myocarditis associated with a simple pharyngitis? Or is there is a more sinister etiology at play? You turn to your senior resident and ask him to page the on-call pediatric infectious disease specialist. You ask the nurse to institute strict isolation precautions. As the phone rings, you grow increasingly confident of your patient’s diagnosis.

Critical Appraisal Of The Literature

A PubMed search for the terms diphtheria, pertussis, and tetanus was performed, along with terms such as diagnosis, treatment, and case report. A search of the Cochrane Database of Systematic Reviews was also performed for each of the 3 diseases. The United States Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), the World Health Organization (WHO), and the National Guideline Clearinghouse websites were searched for related articles or web pages. The vast majority of recent literature on these illnesses focuses on the vaccines themselves rather than the management of the diseases. Pediatric-specific literature is extremely limited. Most of the relevant literature for this issue is in the form of expert consensus, review articles, and case reports.

Introduction

At the beginning of the 20^th century, 10% of all babies born in the United States died before their first birth day, often from infectious diseases.¹ Current estimates are that childhood vaccination will save over 700,000 American lives for those born in the United States in the last 20 years.² The Advisory Committee on Immunization Practice (ACIP) annually reviews the recommended routine childhood (age 0-18 years) vaccination schedule.³ Despite this carefully considered schedule that is designed to be both maximally safe and effective, there has been an increase in certain vaccine-preventable diseases in the United States. This is due, in part, to geographical pockets of low vaccination coverage despite overall high vaccination coverage nationally.⁴ Because of this, emergency clinicians should not only advocate for vaccination, but also be able to recognize and manage these illnesses when they do occur. This issue of Pediatric Emergency Medicine Practice reviews 3 vaccine-preventable illnesses—diphtheria, pertussis, and tetanus—and describes the role of the emergency clinician in managing these illnesses, identifying and managing close contacts, and involving local health officials.

Risk Management Pitfalls In Patients with Diphtheria, Pertussis, Or Tetanus

1. “The nurse marked ‘immunizations up to date,’ so there was no need to ask.”
   It is essential for the emergency clinician to have an accurate vaccination history on each patient. Not only does this information have a significant effect on clinical decision making, it provides an opportunity to stress the importance of vaccines to all families.
    
2. “That baby with an episode of apnea had a completely normal examination. There was no need for labs. I’ll just admit her for observation.”
   While true for many infants presenting with apneic spells, further testing (eg, a complete blood count) to look for hyperleukocytosis should be considered based upon the clinical history and examination. A lack of maternal immunization, ill family members or close contacts, or a high local prevalence of B pertussis should lead, at least, to consideration of pertussis infection as the cause of apnea in an otherwise well-appearing baby.
    
3. “Everyone in the waiting room is coughing! Why worry about isolation?”
   While many conditions may cause cough in children, a severe spasmodic cough, posttussive emesis, and family members with similar symptoms should heighten the suspicion for pertussis infection. Respiratory isolation of patients suspected of infection with B pertussis is essential to control further spread, particularly among the more vulnerable patients in the pediatric emergency department.
    
4. “The siblings of the patient with known pertussis all had their vaccinations, so I did not give them antibiotics.”
   Current recommendations are for postexposure antibiotics for all close contacts of patients diagnosed with pertussis, regardless of their vaccination history. Because the vaccine is not 100% effective, immunity wanes rapidly with time, and given the high infectivity of B pertussis, even fully immunized siblings should be treated with azithromycin unless it is contraindicated.
    
5. “That cough is pretty nasty. I think we should try some albuterol.”
   Multiple medications have been studied for symptomatic treatment of pertussis and, based on current evidence, cannot be routinely recommended. Cough medicine in children should be avoided due to a lack of efficacy and a high risk of side effects.
    
6. “It can’t be diphtheria, the child lives just down the street. I doubt he’s ever left the state.”
   A travel history is not essential for the diagnosis of diphtheria. Both toxigenic and nontoxigenic strains exist in the United States. Toxigenicity can be induced via phage conversion, and severe illness can occur with nontoxigenic strains. Therefore, awareness of the early signs and symptoms of diphtheria is crucial to identifying patients who need early and life-saving treatment.
    
7. “We need to wait for laboratory confirmation of diphtheria before calling the CDC.”
   The expedient administration of DAT is critical to prevent progression and to lessen the severity of diphtheria. Because DAT is only available through the CDC’s Emergency Operations Center, a suspicion of toxigenic C diphtheriae infection warrants a phone call to discuss whether DAT is indicated. Information on the process for requesting DAT can be found on the CDC’s website at: http://www.cdc.gov/diphtheria/dat.html.
    
8. “The wound is not that dirty, I think we can skip the TIG.”
   Current recommendations for wound management emphasize the need for TIG for patients with tetanus-prone wounds and either an uncertain or incomplete immunization schedule. Young children who have received < 3 primary boosters meet CDC criteria for TIG administration. However, it is important to remember than seemingly clean wounds and even surgical incisions are potential entry points for C tetani.
    
9. “Paralyze and sedate. That’s really all we can do for tetanus.”
   The successful management of tetanus requires treatment of the muscle spasms and autonomic dysfunction, as well as any secondary morbidity. Therefore, a variety of medications may be necessary to maintain cardiorespiratory function while minimizing the risks associated with long-term sedation, paralysis, and mechanical ventilation. This should be done after administration of antibiotics and TIG to prevent further toxin effects.
    
10. “That pregnant woman is afraid of shots. She probably doesn’t need one as long as the father and grandmother of the fetus have a booster shot.”
    While immunizing adults who have contact with an infant provides indirect protection, this should be considered a secondary strategy. Immunizing pregnant women between 27 and 36 weeks of each pregnancy directly confers maximal antibody protection to babies too young to receive the vaccine. Thus, a key strategy to protect the most vulnerable patients is by maternal vaccination.

Tables And Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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