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Jerry V. Pua MD 2nd year Resident

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1 Jerry V. Pua MD 2nd year Resident
It’s the simple things in life we forget You hear her talkin’ but don’t hear what she said Why do you make something so easy so complicated? Searching for what’s right in front of your face.. - Simple Things by Usher Approach to Cough Jerry V. Pua MD 2nd year Resident

2 Objectives To discuss etiology, differential diagnosis and work up for children presenting with cough To discuss approach, diagnosis, management, recommendations and prevention of B. pertussis infection

3 General Data A.E. 6 month old, Female Filipino, Catholic
Brgy. Batasan Hills, Quezon City Consulted at ER last June 15, 2013 Informant: Grandmother Reliability: 80%

4 Cough – 2 weeks duration Chief Complaint picture

5 History of Present Illness
2 weeks PTA Non productive cough No fever nor other associated symptoms No consult done 5 days PTA Persistence of recurring bouts of cough No other associated symptoms Consulted LHC – Carbocisteine and Amoxicillin (40mkday) animation

6 History of Present Illness
3 days PTA Persistence of continous non productive cough followed by facial cyanosis Difficulty breathing – alar flaring, tachypnea, ‘seesaw’ breathing Few hours PTA Persistence of symptoms prompted consult at Local Clinic A> Bronchopneumonia rule out Pertussis Advised consult at a tertiary institution animation

7 Review of Systems Decrease appetite
No failure to thrive, feeding interruption No skin lesions No diaphoresis, no fainting spells No vomiting, no diarrhea nor constipation No pallor No facial redness during bouts of cough No convulsion No limitation of movements No bleeding manifestations

8 No heredo-familial disease on both sides of the family
Family History (+) (+) cough (+) No heredo-familial disease on both sides of the family

9 Birth and Maternal History
Born to 39 year old G5P4 (4014) non smoker, non alcoholic beverage drinker mother No pre natal check up, denies maternal illness Multivitamins, Ferrous Sulfate intake Delivered Full term via NSD at home assisted by traditional birth attendant No feto-maternal complication during and after the delivery

10 Immunization History No immunization received

11 Nutritional History Milk Formula – since birth
No milk formula intolerance Complimentary feeding – 6 months old No interrupted feeding No feeding problems

12 Growth and Development
Motor Head control – 2 mos. rolls over – 4 mos. sits with support – 6 mos. Language Imitates sounds – 5mos Daily Living Put anything at the mouth – 4 mos. Social/Adaptive Social smile – 2 mos. plays with caregiver – 6 mos

13 Past Medical History No routine check up No previous hospitalization
No previous surgical intervention done. No allergies

14 Physical Examination Awake, irritable, in mild respiratory distress. Well hydrated. Weight: 6 kg (z score below 0 ) Height: 65 cm (z score 0 ) BP 80/50 HR 122 RR 38 T 37.1 Skin: Warm, Moist, No rashes or other dermatosis. No cyanosis.

15 Physical Examination HEENT: Normocephalic. Aniceteric sclera; pink palpebral conjunctivae; no eye discharge (+) intermittent alar flaring. No nasal discharge nor bleeding. No tragal tenderness, no aural discharge Non hyperemic posterior pharyngeal wall, no exudates, uvula midline (+) cervical lympadenopathy, bilateral Chest and Lungs: No chest deformity nor skin lesions at the chest. Symmetrical chest expansion, (+) subcostal and intercostals retractions (+) crackles on both lung fields

16 Physical Examination Heart: Adynamic precordium, Apex beat at 4th ICS LMCL, normal rate regular rhythm, no murmur Abdomen: Globular, No visible veins. Normoactive bowel sounds. Soft, non tender, no organomegaly. Genitalia: Grossly female Extremities: No preferential movement. Pulses on all extremities are full and equal. No clubbing, cyanosis of fingers or toes. CRT <2 seconds. No deformities.

17 Neurologic Examination
Mental Status: Awake, irritable. GCS 15 Cranial Nerves: Intact Motor: Good muscle tone, no fasciculation or atrophy, no involuntary movement. MMT 5/5 on all extremities. DTR’s 2++ Sensory: No deficit. No babinski or clonus. Cerebellar: No nystagmus Meningeal signs: No Kernig’s, No Brudzinski, No nuchal rigidity

18 Bronchopneumonia Rule out Pertussis No stunting no wasting
Admitting Impression

19 Symptoms, sign, or laboratory findings pathognomonic of a disease
Approach to Diagnosis

20 COUGH Most common symptom presenting to medical practitioners
Cough is a forced expulsive maneuver, usually against a closed glottis Sound of a cough is due to vibration of larger airways and laryngeal structures during turbulent flow in expiration and which is associated with a characteristic sound Cough quality in children: a comparison of subjective vs. bronchoscopic findings Anne Bernadette Chang, et. al Dept of Paediatrics & Child Health, University of Queensland Dept Respiratory Medicine, Royal Children's Hospital, Brisbane

21 COUGH Estimating the duration of cough is the first step in narrowing the list of possible diagnoses THE DIAGNOSIS AND TREATMENT OF COUGH RICHARDS. IRWIN, M.D.,AND J. MARK MADISON, M.D. The New England Journal of Medicine

22 Types of Cough (Duration)
Acute Cough -- a recent onset of cough lasting <3 weeks Subacute Cough (Prolonged acute cough) -- cough slowly resolving over a 3–8-week period Chronic Cough -- A cough lasting >8 weeks Recurrent Cough -- cough without a cold is taken as repeated (>2/year) cough episodes, apart from those associated with colds, that each last more than 7–14 days Recommendations for the assessment and management of cough in children M D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the British Thoracic Society Cough Guideline Group

23 ACUTE COUGH Cough lasting for a maximum of 3 weeks
Common caused: URTI, acute bronchitis or tracheobronchitis (bacterial or viral) Such infections is usually self limited and subsides within one to two weeks along the clearing of the infection No targets or reliable measures to predict the duration of cough at its onset, also to predict which will persist into sub acute or chronic cough A detailed history is key to the identification of the underlying cause and any subsequent decision if treatment for cough or its underlying condition is necessary. The onset of cough can provide initial clues as to its origin. Abrupt onset can be related to aspiration, especially in small children and elderly persons. Signs and symptoms of an upper respiratory tract infection point to the most common and usually benign reasons for acute or sub acute cough. However, they can precede severe pneumonia and therefore occasionally require close observation. COUGH MANAGEMENT: A Practical Approach F. De Blasio, et. al

24 COUGH MANAGEMENT: A Practical Approach
F. De Blasio, et. al

25 COUGH MANAGEMENT: A Practical Approach
F. De Blasio, et. al

26 Types of Cough (Causes)
Specific Cough -- one in which there is a clearly identifiable cause Non specific isolated Cough -- typically have a persistent dry cough, no other respiratory symptoms, well with no signs of chronic lung disease and have a normal chest radiograph Post viral Cough -- cough originally starting with an upper respiratory tract infection but lasting <3 weeks Recommendations for the assessment and management of cough in children M D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the British Thoracic Society Cough Guideline Group

27 Types of Cough (Quality)
Classic Recognizable Cough Certain cough characteristics classically taught to point to specific etiologies Dry Cough Wet Cough Cough in children: definitions and clinical evaluation Position statement of the Thoracic Society of Australia and New Zealand

28 Salient Features 6 months old In mild respiratory distress
2 weeks history of cough No fever Cyanosis at bouts of cough Difficulty of breathing Siblings with cough No immunization received In mild respiratory distress Intermittent alar flaring Intercostal and subcostal retractions Crackles on both lung fields

29 Course at the Ward Patient: A.E. 6 months old, Female
Working Impression: Bronchopneumonia Rule out Pertussis

30 1st Hospital Day Diagnostics Arterial Blood Gas pH 7.24 pCO2 26
pO O2sat HCO BE CBC w/ PC Hgb Hct WBC Seg Lympho Platelet

31 Diagnostics: Radiographic findings
Chest radiographic : only mildly abnormal in the majority of hospitalized infants Showing perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis Pneumothorax, pneumomediastinum, and subcutaneous emphysema can be seen occasionally

32 Case Definitions: Pertussis (WHO)
Cough lasting at least 2 wk with at least 1 of the following symptoms: paroxysms of coughing inspiratory whooping posttussive vomiting (ie, vomiting immediately after coughing) Clinical case: a case that meets the clinical definition, but is not laboratoryconfirmed Laboratory-confirmed case: a case that meets the clinical case definition and is laboratory-confirmed Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

33 Clinical Definitions: Pertussis (CDC)
Cough illness lasting ≥ 2 weeks with 1 of the following without apparent cause: Paroxysms of coughing Inspiratory “whoop” Posttussive vomiting Probable case: symptoms, absence of laboratory confirmation and epidemiologic linkage to a laboratory-confirmed case of pertussis Confirmed case: symptoms + > 1 following – PCR positive for pertussis or contact with laboratory-confirmed case of pertussis Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

34 Diagnostics Common laboratory diagnostic methods:
Culture – gold standard Direct antigen detection PCR Direct fluorescent antibody (DFA) testing Serologic demonstration enzyme-linked immunosorbent assay (ELISA) or Western blot with various B. pertussis antigens and agglutination Measuring an increase in titers between acute and convalescence phase serum specimens or high single serum antibody values Defining Pertussis Epidemiology Clinical, Microbiologic and Serologic Perspectives James D. Cherry, MD, et al Pediatr Infect Dis J 2005

35 Diagnostics: Serologic Testing
Proper performance of culture, PCR and ELISA to measure increases or decreases in IgG and IgA antibody titers to Pertussis Toxin in paired serum samples, the sensitivity and specificity of the laboratory diagnosis of B. pertussis infection The greatest sensitivity is obtained when culture, PCR and serologic testing are all performed on individuals with cough illness Acute phase serum collected 3–4 weeks after onset of symptoms in previously vaccinated children and 5–6 weeks after onset of symptoms in previously unvaccinated children -- demonstration of decrease in titer between acute and convalescent phase specimens is also indicative of infection Defining Pertussis Epidemiology Clinical, Microbiologic and Serologic Perspectives James D. Cherry, MD, et al Pediatr Infect Dis J 2005

36 Pertussis PCR Key factors for the successful application of PCR in the diagnosis of infection by Bordetella spp.: Sample collection and processing DNA purification Primer selection Amplification conditions PCR as a diagnostic tool has the advantage of a much higher sensitivity compared with conventional culture Defining Pertussis Epidemiology Clinical, Microbiologic and Serologic Perspectives James D. Cherry, MD, et al Pediatr Infect Dis J 2005

37 Pertussis: PCR A 2.6-fold increase in detection of B. pertussis using PCR compared with culture PCR results were compared with serologic diagnosis; PCR had a sensitivity of 61% and a specificity of 88% Patients with symptoms meeting the CDC clinical case definition for pertussis and who had a specimen positive by PCR or DFA were considered to have true B. pertussis infections Defining Pertussis Epidemiology Clinical, Microbiologic and Serologic Perspectives James D. Cherry, MD, et al Pediatr Infect Dis J 2005

38 2nd Hospital Day Diagnostic Referred to Infection Control Committee
Blood CS Nasopharyngeal Pertussis PCR 2D Echo with PAP

39 Complete Blood Counts 06/15/13 06/16/13 06/17/13 06/18/13 06/20/13
Hemoglobin 137.7 125.1 126.2 131.4 140.3 Hematocrit 0.42 0.38 0.40 0.43 WBC Count 35.5 27.5 25.9 19.2 16.8 Diff. Count Segmenter Lymphocytes Monocytes 21 79 14 72 10 16 65 15 62 31 63 06 Platelet 647 523 537 539 465

40 Diagnotics: Complete Blood Count
A total count of ≥ 20,000 WBCs/mm3 with ≥ 10,000 lymphocytes/mm3 in a young infant with coryza, cough, apnea or other respiratory distress is indicative of B. pertussis infection A total count of ≥ 30,000 WBCs/mm3 is cause for concern and the rapidity of the WBC count rise is also an important indicator of worsening condition Pertussis in Young Infants – Guidance for Clinicians James D. Cherry MD, et. al. May 2010

41 Microbiology Blood Culture and Sensitivity: No growth for 5 days of incubation Nasopharyngeal Bordetella pertussis Polymerase Chain Reaction POSITIVE for Bordetella pertussis DNA

42 Pertussis Bronchopneumonia no stunting no wasting
Final Diagnosis

43 Pertussis Acute respiratory infection caused by Bordetella pertussis
‘intense cough’ Extremely contagious -- attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range

44 Bordetella pertussis Tiny, fastidious, gram-negative coccobacilli that colonize only ciliated epithelium Expresses pertussis toxin (PT), the major virulence protein After aerosol acquisition, pertussis organism attaches to ciliated respiratory epithelial cells Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms Responsible for the local epithelial damage filamentous hemagglutinin (FHA), some agglutinogens, and nonfimbrial surface protein called pertactin are important for

45 Epidemiology Worldwide, pertussis is a significant cause of infectious mortality 20 to 40 million cases 200,000 to 400,000 death per years Most of cases and deaths occur in infancy WHO. Pertussis vaccines. Wkly Epidemiol Rec. 1999;74:137–143

46 Epidemiology Philippine Pediatric Society Registry
99 out of cases Philippine Children’s Medical Center 32 cases: Total probable and confirmed pertussis cases admitted from JANUARY-JUNE 2013

47 Source of Infection Rate of subclinical infection is as high as 80%
Coughing adolescents and adults -- major reservoir for B. pertussis -- usual sources of infection for infants and children Household contact with infected adolescent and adults – major source of pertussis infection in not fully immunized infants (usually not recognized as having pertussis) Infant Pertussis and Household Transmission n Korea. The Korean Academy of Medical Sciences.

48 Mode of Transmission

49 Stages of Pertussis Infection
Catarrhal stage (1-2 wk) begins insidiously after an incubation period (3-12 days) Paroxysmal stage (2-6 wk) onset marks by coughing Cough begins as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms Post-tussive emesis is common, and exhaustion is universal. Convalescent stage (≥2 wk), the number, severity, and duration of cough episodes diminishes

50 Stages of Pertussis Infection

51

52 Pertussis in Young Infants
Catarrhal stage -- characterized by excessive sneezing or “throat clearing” -- adherence of organism in the ciliated epithelium throughout the respiratory tract – tissue necrosis, production of mucus, and inflammatory cell response Paroxysmal stage – atypical Acute life-threatening episode is common Spells of cough leading to cyanosis or bradycardia and limpness as well as apnea Post-tussive vomiting is common “whoop cough” is rarely present in very young infant Generated when deep inhalation causes air to rush past partially open glottis Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

53 1st - 2nd Hospital Day Management Isolation D5LR (mild) O2 at 10Lpm
Medications: Ampicillin (100) Erythromycin (40) ---- Azithromycin (10) Salbutamol nebulization every 4 hours NPO

54 Goals of hospitalization
Assess progression of disease and likelihood of life- threatening events at peak of disease Prevent or treat complications Educate parents in the natural history of the disease and in care that will be given at home

55 Goals of therapy Limit the number of paroxysms
Observe the severity of the cough Provide assistance when necessary Maximize nutrition, rest, and recovery without sequelae

56 Medications Age Primary Agents Alternate Agents Azithromycin
Erythromycin Clarithro TMP-SMZ <1 mo 10 mg/kg/day in a single dose for 5 days (Infantile hypertrophic pyloric stenosis) 40-50 mg/kg/day in 4 divided doses for 14 days Not recommended (safety data unavailable) Contraindicated for infants aged <2 mo (risk for kernicterus) 1-5 mo 40-50 mg/kg/day in 4 divided doses for 14 days 15 mg/kg/d in 2 divided doses for 7 days Contraindicated at age <2 mo For infants aged ≥2 mo: TMP 8mg/kg/day plus SMZ 40 mg/kg/day in 2 divided doses for 14 days Infants aged ≥6 mo and child 10 mg/kg in a single dose on day 1 (maximum 500 mg), then 5 mg/kg/day (maximum 250 mg) on days 2-5 40-50 mg/kg/day (maximum 2 g/day) in 4 divided doses for 14 days 15 mg/kg/d in 2 divided doses (maximum 1 g/day) for 7 days TMP 8 mg/kg/day plus SMZ 40 mg/kg/day in 2 divided doses for 14 days

57 Pertussis Complications in Young Infants
Life-threatening complications are most common in infants younger than 3 months Respiratory tract complications: apnea, bacterial pneumonia, and pulmonary hypertension Secondary bacterial pneumonia – leading identified cause of pertussis-related infection Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

58 Pertussis Complications in Young Infants
Respiratory Failure with Pertussis may stem from complications of Pneumonia, Pulmonary Hypertension, and Apnea Apnea – due to failure of self-rescue breathing at the end of a paroxysm of coughing or profound vagal stimulation Infants intubated due to respiratory failure secondary to apnea have better prognosis than those intubated due to pneumonia or pulmonary hypertension Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

59 Pertussis Complications in Young Infants
Severe Bordetella pertussis consist of constellation of bronchopneumonia, extreme leukocytosis, refractory hypoxemia, and pulmonary hypertension White blood cell counts > in the setting of B. pertussis pneumonia associated with increase mortality Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange Transfusion Michael J. Romano, et. al. Pediatrics 2004

60 Pertussis: Proposed Pathologic Course
Infection of tracheal epithelium with Bordetella pertussis Ciliostasis, epithelial damage and compromised mucociliary clearance Pulmonary Infection Toxin mediated leukocytosis apnea Necrotizing bronchopneumonia hypoxemia Increase whole blood mass ARDS Pulmonary vasoconstriction Increase vascular resistance PULMONARY HYPERTENSION Pathology and Pathogenesis of Fatal Bordetella pertussis Infection in Infants Christopher D. Paddock, et. al. Cardiac Failure and Shock

61 3rd -5th Hospital Day The rest of hospital stay patient completed her antibiotics. O2 supplementation was titrated down and eventually discontinued. Patient discharged well and stable.

62 Indications for ICU referral
Infants less than or equal 3 months old with clinical deterioration White Cell Count more than or equal to 30, 000 or rapidly rising in count (>10,000 in 6 hours) Respiratory failure or frequent apnea Progressive pneumonic changes in CXR Persistent tachycardia/ cardiovascular instability Neurological symptoms including seizure South Thames Retrieval Service Guideline

63 ICU care Apnea, pneumonia, and seizures are the most common presenting symptoms requiring ICU care Leukocytes aggregate within the pulmonary circulation and form a mechanical obstruction to transpulmonary blood flow with the result being severe hypoxemia and pulmonary hypertension Cardiac failure associated with critical pertussis is likely right sided heart failure secondary to the pulmonary hypertension

64 Double Volume Exchange Transfusion
Multiple authors have reported double volume exchange transfusion as an effective therapy for the pulmonary hypertension, and secondarily the hypoxemia and cardiac failure Technique of double volume exchange utilized is the same as performed for the newborn with hyperbilirubinemia Hypomagnesemia and especially hypocalcemia may occur thus recommended routine calcium supplementation from binding to the citrate in the transfused blood Chen H, Lee M, Tsao L. Exchange Transfusion Using Peripheral Vessels Is Safe and Effective in Newborn Infants. Pediatrics 2008

65 Indications for DVET White cell count more than or equal to 30,000 and rapidly rising count White cell count more than or equal to 30, 000 with pneumonia or hemodynamic instability White cell count more than or equal 50,000 South Thames Retrieval Service Guideline

66 Studies shows… Appearance of respiratory symptoms paralleled the rise in leukocyte count Temporal relationship between the initiation of exchange transfusion and improvement in oxygenation Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange Transfusion Michael J. Romano, et. al. Pediatrics 2004

67 Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension: Improvement in Oxygenation After a Double Volume Exchange Transfusion Michael J. Romano, et. al. Pediatrics 2004

68 Criteria for Hospital Discharge
Over a 48-hr period disease severity is unchanged or diminished No intervention is required during paroxysms Nutrition is adequate No complication has occurred Parents are adequately prepared for care at home

69 Prevention: Vaccination
Efficacy of the vaccine in reducing disease severity was 48% among children vaccinated with 3 doses of whole-cell (67%) or acellular (32%) Pertussis vaccination substantially decrease the severity of breakthrough disease in vaccinated children (3 doses) compared to unvaccinated children Unvaccinated children twice likely to have severe disease than vaccinated children Effects of Pertussis vaccination on Disease: Vaccine Efficacy in Reducing Clinical Severity Preziosi, Marie-Pierre, et.al. Clinical Infectious Disease 2003

70 Prevention: Vaccination
DTaP (Diphtheria, tetenus toxoid and acellular Pertussis) contain inactivated PT and 2 or more other bacterial components (FHA, Pn, and Fim 2 and 3) 4 doses during the 1st 2 years of life 2,4,6 and months 5th dose of DTaP recommended for children at 4-6 yr of age ; a 5th dose is not necessary if the 4th dose in the series is administered on or after the 4th birthday

71 Prevention: Vaccination
Tdap (Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed) Preferred age for Tdap vaccination is 11-12 yr Pregnant adolescents who are in their 2nd or 3rd trimester All adolescents 11-18 yr of age who received Td, but not Tdap, should receive a single dose of Tdap to provide protection against pertussis

72 Vaccination of women during pregnancy and newborns
Timing of maternal Tdap immunization is important – administered during the third trimester to have maternal pertussis antigen-specific IgG levels at their peak Immunization with DTaP or aP vaccines is not recommended in newborns -- controversial Pertussis re-emergence in the post-vaccination era Chiappini et al. BioMedCentral Infectious Disease 2013

73 Cocooning strategy Providing indirect protection to infants who are too young to be immunized or protected by vaccine through immunization of their parents and other family members, caregivers and close contacts Maximum response to Tdap achieved until 14 days after vaccination --- infants risk for infection Pertussis re-emergence in the post-vaccination era Chiappini et al. BioMedCentral Infectious Disease 2013

74 Vaccination of preschool and adolescent
Contributes to increase herd immunity Reduce transmission of pertussis to susceptible population Reduce reservoir of pertussis within population and indirectly prevent pertussis case in infants and young children Pertussis re-emergence in the post-vaccination era Chiappini et al. BioMedCentral Infectious Disease 2013

75 Immunization of health-care workers
Pertussis among health-care personnel has been reported to be 1.7 times higher than the general population Health-care personnel who have direct contact with patients should receive single dose of TdaP as soon as feasible, if they have not previously received TdaP Pertussis re-emergence in the post-vaccination era Chiappini et al. BioMedCentral Infectious Disease 2013

76 Updates Patient follow up at OPD – well, active
Received her first dose of DPT, OPV, and Hepatitis B Relatives were educated regarding the importance of immunization as well as proper hygiene to stop the vicious cycle of transmission

77 Summary A case of 6 month old unimmunized infant who presented with subacute cough with paroxysms, who after a nasopharyngeal swab PCR was confirmed with Bordetella pertussis Started on Azithromycin per orem and eventually discharged well and stable Recommendations for management of pertussis Emphasized the importance of immunization on preventing vicious transmission cycle

78 Thank You!!!


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