بسم الله الرحمن الرحیم

1. بسم الله الرحمن الرحیم

2. Bordetella pertussis http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm Roxana M.Ghanaie Ped Infectious Disease Subspecialist

3. Bordetella pertussis Basics • Aerobic, Gram negative coccobacillus • Alcaligenaceae Family • Specific to Humans • Colonizes the respiratory tract • Whooping Cough (Pertussis)

4. Bordetella pertussis is a bacterium identified in 1900 by Jules Bordet and Octave Gengou but isolated only in 1906 because of the development of a medium containing potatoes extract and rabbit blood Jules Bordet 1870-1961

5. Estimated annual childhood deaths, 2002 Meningococcal (< 1%) rotavirus (16%) pneumococcal (28%) measles (21%) 24% 76% Hib (15%) pertussis (11%) tetanus (8%) { yellow fever (1%) diphtheria (<1%) polio (< 1%) 10.5 million deaths under 5 years of age 1.4 million from diseases where vaccination is currently available 1.1 million from diseases where vaccines will be available by 2008 Source: WHO/IVB

6. Reported Pertussis Cases U.S., 1922-2003*

7. Number of cases 1-2 3-4 5-6 7-12 2 3 4 5 6 7 8-12 15-20 20-25 25-35 Month Year Pertussis in a vaccinated country vs a non vaccinated country Low vaccine coverage *High morbidity and mortality in infants *Regular asymptomatic contacts throughout life *Unknown epidemiology in adults High vaccine coverage *Low morbidity and mortality in infants *Few asymptomatic contacts throughout life *Increase in susceptible adolescents and adults

8. Why speaking about Pertussis? • Iran pertussis incidence 2010 : 0.5/ 100000 • DTP3 coverage more than 95%

9. روند ميزان بروز سياه سرفه محتمل و پوشش واكسن ثلاثنوبت سوم(جمهوري اسلامي ايران 1391-1370)

10. فراواني موارد محتمل سياه سرفه برحسب دانشگاه علوم پزشکی 1391

11. توزیع جغرافیایی موارد مثبت بیماری سیاه سرفه دركشور 1391

12. TCT BrkA, Tcf, Vag8 TCT Pertussis toxin (PT) Fimbriae (FIM) Adenylate cyclase hemolysin (AC-Hly) Filamentous hemagglutinin (FHA) Pertactin (PRN) Adhesins: adhesion => multiplication and colonisation of respiratory tract Toxins: local and systemic cytopathogenic effects Bordetella pertussis virulence determinants TCT

13. Classic Manifestation • The incubation period of pertussis is usually 7 to 10 days, with a range of 4 to 21 days. • The clinical course of illness is divided into three stages.( age, vaccination, waning) 1/ The catarrhal stage is characterized by the onset of runny nose, sneezing, low-grade fever, and a mild cough. Cough gradually becomes more severe (1-2 weeks)

14. Classic Manifestation • 2/ The paroxysmal stage is characterized by coughing fits (paroxysms), which may be followed by a high-pitched inspiratory whoop, vomiting, and/or apnea. (1-6 weeks), but may continue for 10 weeks

15. 3/The convalescent stage is characterized by fewer paroxysmal coughing episodes and usually disappears in 2-3 weeks, but may continue for months

16. Complications • Losing weight, pneumonia, otitis, seizure, encephalopathy, apnea • Epistaxia, melena, subdural hematoma, inguinal hernia, rectal prolapse,

17. Infants • The severity of pertussis and the rapidity of its progression in young infants is effected by a number of factors such as: • the presence of transplacentally acquired maternal antibodies to B. pertussis, • the infectious dose of bacteria that the infant receives, • co-infection with respiratory • viruses and perhaps genetic • factors related to the • pathogen or the infant.

18. Infants • Short catarrhal period, longer convalescence period • Cough,feeding abn, res distress,apnea,cyanosis, bradycardia, whoop uncommon, • paroxysms and this may lead to apnea, gasp, hypoxia and occasionally seizures • Initially the chest is clear on auscultation but in fatal cases B. pertussis pneumonia is always present. • Co-infection with respiratory viruses (particularly RSV and adenoviruses) can confuse the diagnoses because of a bronchiolitic picture (air trapping and expiratory distress).

19. Pertussis Among Adolescents and Adults • Accounts for up to 7-30% of cough illnesses per year • Disease often milder than in infants and children • Infection may be asymptomatic, or may present as classic pertussis • Cough may last 21 d, st. paroxysmal

20. Clinical manifestation in immunized • Mild , unrecognized cough • Prolonged cough • Persons with mild disease may transmit the infection • Older persons often source of infection for children • Adults: sleep disturbances syncope, incontinence, rib Fx, pneumonia

22. Transmission • Very Contagious, 80% secondary attack rate among susceptible persons( even immunized) • Transmission occurs via respiratory droplets, direct contact with respiratory secretions from infected individuals • Parents are a common source of B. pertussis infections for infants, • grandparents, uncles , Aunts also provide another potential source of infection

24. Transmission Pertussis Infectious Period: • Most infectious during the catarrhal (early) stage. • Infectious during the first 21 days of cough if not treated with appropriate antibiotic. • No longer infectious after 5 days of treatment with appropriate antibiotic • Length of communicability: age, immunization status, appropirate antibiotic therapy • Isolation: standard, droplet

25. B. parapertussis • B. parapertussis infection in humans can cause unrecognized infection, mild pertussis, or classic pertussis • B. bronchisepica

26. DD prolonged cough • Adenovirus • Para influenza • Influenza A,B • M.pneumonia • RSV • C.trachomatis • C. pneumonia

27. DD prolonged cough • spasmodic attacks of coughing may be observed in children with: • bronchiolitis, bacterial pneumonia, cystic fibrosis, or tuberculosis. Afebrile Pneumonia Syndrome • The cough associated with: sinusitis, airway foreign body

28. Laboratory confirmation of pertussis is difficult and delayed. Therefore, clinicians need to make the diagnosis of pertussis presumptively in patients with a history of intense paroxysmal or chronic coughing with or without whooping, color changes, posttussive vomiting, incomplete or absent pertussis vaccination, and finding of lymphocytosis on laboratory examination.

29. CXR Indications • 1/ <1y • 2/ toxic • 3/ progressive cough>3 w • 4/ res distress • 5/ probable underlying dis( CF, CHD,forign body, Hilar LAD)

30. Chest Xray • Most common : Normal • Shaggy heart( central airway not periph) • Hyperinflation, hyper lucent lung • Micro athelectasia • Secondary bac. Pneumonia • Bronchiolitis oblitrans( adeno, influ, measles, pertussis) • pneumothorax

32. Diagnosis • Isolation by culture , preferred method of diagnosis(100% specificity) • Although PCR more sensetive,culture may be necessary for further case analysis including evaluation for antibiotic resistance and molecular typing http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg

33. Neg culture: • Previously immunized • Antibiotic usage • More than 3 w after cough onset • Bad-handled specimen

34. Definition: Clinical Case Definition of Pertussis • A cough illness lasting at least 14 days with one of the following: • paroxysms of coughing, • inspiratory “whoop”, • or post-tussive vomiting, • and without other apparent cause (as reported by a health professional).

35. Definition: Laboratory Criteria for Pertussis Diagnosis • Isolation of Bordetella pertussis from a clinical specimen (culture positive), or • Positive polymerase chain reaction (PCR) assay for B. pertussis DNA. Note: Serological testing for B. pertussis is not standardized • Serology and DFA results should not be relied on as a criterion for laboratory confirmation of pertussis.

36. Pertussis Case Classification • Confirmed: a/ A positive culture for B. pertussis and cough illness of any duration, or b/ Meets the clinical case definition and is confirmed by PCR, or c/ Meets the clinical definition and is epidemiologically linked directly to a case confirmed by either culture or PCR. • Probable: A case that meets the clinical case definition, is not laboratory confirmed, and is not epidemiologically linked to a laboratory-confirmed case; also includes cases meeting the outbreak case definition

37. Outbreaks • Outbreak: Two or more cases involving two or more households clustered in time (e.g., occurring within 42 days of each other) and either epi-linked or sharing a common space (e.g., in one building) where transmission is suspected to have occurred (e.g. a school). • One case in an outbreak must be lab confirmed (PCR positive and meets case definition, or culture positive). In an outbreak setting, a case may be defined as an acute cough illness lasting ≥ 2 weeks without other symptoms.

38. Suspect: a clinical syndrome compatible with pertussis; an illness consistent with pertussis and without other apparent cause, such as: • a. cough of ≥ 7 days, or • b. paroxysmal cough of any duration, or • c. cough with inspiratory whoop, or • d. cough associated with apnea in an infant, or • e. cough in a close contact of a confirmed or probable case. Summary of Pertussis Investigation and Control Guidelines Colorado Department of Public Health and Environment Communicable Disease Epidemiology Program

39. مراقبت بيماري سياه سرفه سياه سرفه از دسته بيماري هاي مشمول گزارشدهي فوري مي باشد. مراقبت بيماري بر اساس مبناي مورد بيماري انجام مي شود. هر مورد محتمل لازم است قبل از شروع درمان جهت نمونه برداري به آزمايشگاه مركز بهداشت ارجاع شود در تمامي سطوح مراقبت گزارشدهي انجام مي گيرد، در مواردي كه مورد بيماري وجود ندارد ارسال گزارش صفر بيماري الزامي است.

40. Management: • The desired outcomes are: 1/ observing the severity of cough 2/ limiting the number of paroxysms, 3/ providing assistance when necessary, 4/ maximizing nutrition, rest, and recovery, 5/ follow the course of disease 6/ prevent/treat complications

41. Admitt: 1- all infants<3 m despite severity & all 3-6 m except the attacks are mild as observed by physician 2- with complications(intractable nausea and vomiting, failure to thrive,seizures, encephalopathy, or for patients with sustained hypoxemia during coughing paroxysms who require supplemental oxygen,) hx of prematurity in infant, with underlying cardiac, pul, neuromuscular dis

42. Management • For the hospitalized patient, in addition to standard precautions, droplet precautions are recommended • Monitor heart rate, respiratory rate, and oxygen saturation of hospitalized patients continuously,especially in relation to coughing paroxysms. Coughing, feeding, vomiting, and weight changes should be recorded.

43. Management: • Oxygen,suction,hydration, nutrition • Patients who are severely ill may require treatment in an ICU. • Investigate all probable, pertussis reports. • Recommend antibiotics for the index case (first case reported to public health authorities), all household and close contacts. Antibiotic inspite of age, immunization Hx

44. Report & find contacts • Only confirmed and probable cases are reported. • Recommend DTaP/Tdap vaccination according to appropriate age for exposed children, adolescents and adults. • Exposed children < 7 years of age whose last DTP ( 4th dose) was more than 3 years ago should be vaccinated.( more than 6m after 3rd dose)

45. Report & find contacts • Evaluate close contacts for pertussis symptoms, and when possible collect specimens for lab testing from symptomatic persons • Satisfactory documentation of disease: recovery of B. pertussis on culture, OR typical symptoms and clinical course when epidemiologically linked to a culture- proven case

46. Treatment (cont) • During catarrhal stage ameliorate disease • After cough establishment, does not generally lessen duration; protect others • Limited benefit if begun >21 days after onset/exposure • Exception: high risk cases/contacts - treat up to 6 weeks

47. Treatment • Antibiotic therapy • Erythromycin • Azithromycin • Clarithromycin http://www.aboutthatbug.com/AboutThatBug/files/CCLIBRARYFILES/ FILENAME/0000000032/033_lg.jpg http://www.vet.purdue.edu/bms/courses/lcme510/chmrx/macrohd.htm

48. Treatment Erythromycin For children: 40-50 mg/kg/d in 4 divided doses;10-14 days • For adults: 1 to 2 g/day given every 6 h

49. Treatment Azithromycin • for children: at 10 mg/kg on day 1 and 5 mg/kg on days 2 to 5 as a single dose for 5 days • 10-12 mg/kg/d PO in 1 dose for a total of 5 days. ( < 6m) • for adults: 500 mg on day 1 and 250 mg on days2 to 5

50. Treatment Clarithromycin • for children: at 15 to 20 mg/kg/day in two divided doses for 7 days • for adults: 1 g/day in two doses for 7 days