1. DONE BY: HAMAD ALKHALAF F2- ACADEMIC GENERAL PAEDIATRICS FELLOW DECEMBER 13, 2013 Tele health rounds Pertussis In children

2. Objectives Understanding the pathophysiology of pertussis. Know the clinical presentation and potential complications of pertussis. Review the Epidemiology of pertussis. Master the laboratory diagnosis and management of pertussis in children. Describe the vaccination strategies for the prevention of pertussis infection.

3. Pertussis Latin term = intense cough Chinese term for pertussis = 100 –day cough. Commonly known as “whooping cough”. Highly contagious upper respiratory illness caused by the bacterium Bordetella Pertussis.

4. Pathophysiology B Pertussis is an aerobic gram –ve coccobacillus that infect only humans. Difficult to grow on the laboratory media commonly used for other respiratory pathogens. Inflamed ciliated respiratory epithelium  macrophage influx  reactive lymphoid hyperplasia of peri bronchial & tracheobronchial lymph nodes.

5. Pathophysiology Many virulence toxins (e.g. pertussis toxins, pertactin, adenylate cyclase) responsible for : * Suppressing the immune system’s signals. * Lymphocytosis. * Encephalopathy. *Hyperinsulinemia. Intracellular invasion in the alveolar macrophage is responsible for the prolonged cough.

6. Pertussis Epidemiology 50 million cases and 300,000 deaths /year. In Canada (2011): 676 cases per 100,000 /year. Since 1970, the rate of Pertussis incidence is increased !! Periodic epidemic outbreaks occur every 3-5 years.

8. Reported incidence (per 100,000 population) of pertussis in Canada by year and age group, 1980 to 2011*. Retrieved from: Public Health Agency of Canada: http://www.phac- aspc.gc.ca/im/vpd-mev/pertussis-eng.php

9. Pertussis Epidemiology Morbidity and mortality is highest on infants less than 3 months (86 % of the cases). Higher risk in preterm or unimmunized infants. Pertussis cases are more in :  children older than 10 years ( waning of the vaccine’s immunity).  young infants (weaning of the maternal antibodies).

10. Pertussis hospitalizations by age

11. Why Pertussis incidence increased??  clinicians awareness.  public health reporting. More sensitive diagnostic tests. Waning vaccine induced immunity in adolescent. Decrease compliance to Pertussis boosters. Decrease the efficacy of the current vaccine. Genetic changes in the pertussis strains. True increase in the incidence.

12. Pertussis Epidemiology According to CDC 2012 report:  50 % infected infants will require hospitalization.  Half of them will developed secondary pneumonia.  1% mortality.  Worldwide, Pertussis is one of the top 10 causes of death in infants < 1 year. Higher morbidities and mortalities and developing countries. Varying case definitions make comparison of true pertussis incidences between countries difficult.

13. Clinical presentation Spread by aerosol droplets from coughing or sneezing (22-45 % parents are the source). Infants are infected by older siblings or caregivers who may have only mild symptoms. Incubation periods (7 - 14 days ). relatively predictable clinical course although not always the case. Disease severity and prognosis is quite variable.

14. Clinical presentation Clinical course is classified into 3 stages : 1. Catarrhal stage (1-2 weeks). 2. Paroxysmal stage (2-6 weeks). 3. Convalescence stage (weeks to months).

15. Catarrhal stage Non specific symptoms that mimics most of the other URTIs. Clues : excessive lacrimation and conjunctival injection !! Delay in the diagnosis. Worsening of the cough mistaken as secondary bacterial pneumonia.

16. Parxosiaml stage Paroxysms of coughs (Rapid fire or staccato cough). 5 to 10 uninterrupted coughs followed by a whoop ( the patient rapidly draws in a breath). Several cough attacks/hr that results in cyanosis, salivation, lacrimation, and post tussive emesis and syncope. Exhaustion, lack of sleep and feeding.

17. Paroxysmal stage Despite the sever spells, the child appear relatively well between the episodes. Whooping cough is less heard less commonly in adolescents and adults. In infants less than 6 months: # whooping cough is often absent. # gasping, gagging, apnea.

18. Convalescent stage Less severity and frequency of the cough episodes. Duration of the cough is highly variable and unpredictable. Unnecessary medical workup in the missed cases.

19. complications Subclinical or milder in immunized children. Apnea, pneumonia (22 %), hypoglycemia, seizures (2 %), encephalopathy (0.5 % ). and death. Mortality is estimated to be : 1 %  infants less than 2 months. 0.5 %  2 months – 1 year.

20. Complications The paroxysms attacks can cause pressure related complications :  Pneumothorax, pneumomediastinum, subcutaneous emphysema.  Rectal prolapse, rib fractures, hernia, lumbar strain.  Petechial, subconjunctival or intracranial hemorrhages. Co-infection with RSV or influenza can lead to more severe clinical course.

21. Diagnosis of Pertussis High index of suspicion. CBC :  WBC with absolute lymphocytosis. Lymphocytosis is a good marker for the disease severity especially in young infants. Virology studies to role out other respiratory infections or confirm the co-infection may be necessary.

22. Laboratory diagnosis of Pertussis Nasopharyngeal swab or special cultures used to be the gold standard for detecting Pertussis. NP swabs have low sensitivity & specificity where as the culture is 100% specific. In the paroxysmal stage, pertussis culture is +ve in only 1-3 %. i.e. culture time is only 2 weeks.

23. Laboratory diagnosis of Pertussis PCR is beginning to replace the culture in many clinical sitting (higher sensitivity but lower specificity). +ve PCR cases need to be confirmed by culture to avoid the high false +ve results.

24. Laboratory diagnosis of Pertussis + ve PCR for pertussis in the absence of the symptoms could be :  False +ve ( DNA cross – contamination).  Atypical pertussis  Transient colonization

25. Laboratory diagnosis of Pertussis Serological testing for pertussis is available in some areas and useful to diagnose Pertussis at late stages. Serological testing are non standardized and shouldn’t be used as a confirmatory tests. In preexisting immunity, need to have significant titer differences in 2 specimens 2-3 weeks apart to prove the diagnosis.

26. Laboratory methods for detecting Pertussis

27. Retrieved from: Centers of Diseases Control and Prevention: http://www.cdc.gov/pertussis/clinical/diagnostic-testing/diagnosis-confirmation.html

28. DDxs for Pertussis Respiratory viral pathogens. Chlamydia Trachomatis. Atypical pneumonia. Others : GERD, asthma, postnasal drip, ACE inhibitors.

29. Treatment of Pertussis Hydration and oxygenation. If left untreated, most individuals will clear the pertussis from the nasopharynx within 2 to 4 weeks of infection. However, untreated individuals can be contagious for 6 weeks from the cough onset. In the catarrhal stage, antibiotics can shorten the clinical course

30. Treatment of Pertussis In the paroxysmal stage, antibiotics will only shorten the period of the contagiousness. Antibiotics options include :  macrolides ( erythromycin, azithromycin ).  TMP-SMX (septra )

31. Antibiotics options for Pertussis Erythromycin: * The old standard therapy. * Risk for pyloric stenosis. * More GI symptoms. * Frequent doses ( compliance ) * Cytochrome P450 inhibitor.

32. Antibiotics options for Pertussis Azithromycin( the drug of choice in very young infants ): * Less risk for pyloric stenosis. * Fewer GI side effects and better taste. * Available in once daily dosage. * Do not inhibit the cytochrome P450 system.

33. Antibiotics options for Pertussis TMP-SMX : * Contraindicated in children < 2 months. * Acceptable taste. * 7 days course is adequate.

34. Antimicrobial agents for pertussis

35. Adjunctive Treatments for Pertussis Bronchodilators: In two small trials ( total 34 patients)  No improvement. Corticosteroids: * retrospective small trials show possible benefits. * there are no prospective well-controlled trials to support this.

36. Adjunctive Treatments for Pertussis Antitussives: *should be avoided. Immunoglobulin: * Unlikely to be beneficial based on small retrospective studies. * B pertussis immunoglobulin used in blinded prospective multicenter studies.  improved the frequency of whoops compared to the controls.

37. Adjunctive Treatments for Pertussis ECMO and leukodepletion: * Based on case reports and a single series  greater than expected survival rates. * Still investigational.

38. Prophylaxis for Pertussis Antibiotics may prevent infection with B pertussis in exposed individuals if given with 21 days of symptom onset of the index case. The CDC & AAP currently recommend prophylaxis of high –risk close contacts, as well as close contacts who may have contact with high risk individuals. Antibiotics choices and dosage are the same as for treatment.

39. Pertussis Prophylaxis : Definition of Close Contact and High Risk

40. Prophylaxis for Pertussis The vaccination status should not be considered to determine the need of prophylaxis. Confirmed or highly suspected cases should be kept from school or daycare sittings pending the evaluation and after completing 5 days of antimicrobial therapy. If not appropriately treated: the isolation period should be 21 days from the symptom onset.

41. Pertussis Vaccines 80 to 85 % efficacy to prevent Pertussis infections if all doses completed. Pertussis Vaccines can lower the severity of the illness in fully immunized children. Partially immunized children should complete the schedule doses even if they had been infected with Pertussis.

42. Pertussis Vaccines All currently available Pertussis vaccines are combined with tetanus ( T ) and diphtheria ( D ) toxoids as: DTaP (primary doses) followed by Tdap (booster doses). The primary series of 3 DTaP doses to be given at age 2, 4, 6 months, followed by boosters at 18 months,4-6 years, and 14 – 16 years of age.

43. Pertussis Vaccines For booster doses : Tdap is preferable to minimize the local reactions. Tdap in adults is the best proven strategy to break the infection cycles (vaccine rate is only 6% ) Neonatal immunization is a promising strategy but still under research (AAP ground rounds 2012). In pregnant women, Tdap is safe and recommended by CDC.

44. Pertussis -containing vaccines

45. Safety of the pertussis Vaccine DTP vaccine (whole cell pertussis vaccine) introduced in mid 1940s was associated with non life threatening hypotonic hypo responsive reactions. This vaccine was falsely linked to brain insults cases happened to some of the immunized population. DTP vaccine production was stopped at 1980’s

46. Safety of the DTaP Vaccine Multiple well-designed studies have repeatedly failed to link the vaccine to the brain insults. In 1990, Purified acellular pertussis vaccine DTaP was introduced with much less incidence of adverse effects but with less efficacy compared to DTP vaccines.

47. Safety of the DTaP Vaccine Local reactions : *Pain, redness, mild swelling ( 20-40 %). * swelling of entire limb (2 to 3 % ). Systemic reactions : * High grade fever > 40.5 °c ( 0.3 %). * Anaphylaxis ( 2 per 100,000 injections ) or urticaria. * Seizure ( 1 per 1750 doses ). * Hypotonic- hypo responsive episodes ( 1 in 1750 doses ). * prolonged crying ( 1 % ). Both reactions common after the the 4 th or 5 th dose, and typically self resolved.

48. Safety of the DTaP Vaccine DTaP is contraindicated in : * History of immediate anaphylactic reaction to latex or any other components of the vaccine. * Encephalopathy -not due to an identifiable cause- occurring within 7 days after the vaccine.

49. Safety of the DTaP Vaccine DTaP vaccine need to be delayed or reassessed in : * Uncontrolled epilepsy, infantile spasms. * Seizures that has not been evaluated yet. * Progressive encephalopathy.

50. Safety of the DTaP Vaccine DTaP vaccines is not contraindicated in : * Well controlled epilepsy. * Cerebral palsy. * Minor reactions to latex. * Breast feeding. * Immunosuppressive disease or therapy. * High fever, convulsions, brachial neuritis or even shock-like state following a previous dose.

51. Home Message High index of suspicion is needed to early diagnose pertussis. Pertussis need to be considered in any young infant with apneas. Pertussis is an important DDx in any chronic cough. The choice of diagnostic test depend on the duration of the cough ( 1 -4 weeks  PCR +culture ) (> 4weeks  serology )

52. Home Message Supportive care is the mainstay of treatment. Macrolides are indicated for both treatment and prophylaxis. DTaP is a safe vaccine with few reactions and contraindications.

53. Thank you

54. References Cody, M. What do you know about pertussis-containing vaccines? 2013;34(12). Cornia, P. & Lipsky, B. Clinical manifestations and diagnosis of Bordetella pertussis infections in adolescents and adults. 2012. Retrieved from: www.uptodate.com Cornia, P. & Lipsky, B. Microbiology, epidemiology, and pathogenesis of Bordetella pertussis infection. 2013. Retrieved from: www.uptodate.com Hay W. Et al. Current Diagnosis and treatment Pediatrics. McGraw-Hill: 2012. Kliegman RM, et al. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa.: Elsevier Saunders; 2011. Misegades, LK., Winter, K., Harriman, K., et al. Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine, California, 2010. JAMA. 2012;308(20):2126-2132. Pickering L. et al. Red Book 2012 Report of the Committee on Infectious Diseases 29th edition. AAP: 2012. Skoff, TH, Cohn AC, Clark TA, et al. Early impact of the US Tdap vaccination program on pertussis trends. Arch Pediatr Adolesc Med. 2012;155(4):344-349. Snyder, J. & Fisher, D. Pertussis in Childhood. pediatrics In Review 2012; 33; 412. Yeh, S. Treatment and prevention of Bordetella pertussis infection in infants and children. 2012. Retrieved from: www.uptodate.com