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PHM 456 Common Infectious Diseases of Childhood James Tjon, BSPhm, PharmD, RPh Department of Pharmacy The Hospital for Sick Children October 21, 2004 Objectives Review the epidemiology, etiology, pathophysiology, clinical presentation, treatment and prevention associated with the following pediatric infectious diseases: Croup Pertussis Bronchiolitis The Respiratory System Croup 4 different classifications of Croup Syndrome: Laryngotracheitis Spasmodic Bacterial tracheitis Epiglottitis Croup Definition Involves inflammation and edema of the larynx, subglottic tissues and trachea, causing airway obstruction and is due to an infectious agent Croup Epidemiology > 15% of respiratory tract disease in pediatric practice Age: 6 months to 3 years Peak age: 2 years More common in boys Late fall and winter Croup Microbiology Primarily viral Parainfluenza (types 1, 2 & 3) Influenza A & B Adenovirus, Respiratory Syncytial Virus (RSV), measles Bacterial Croup Pathophysiology Begins in nasopharynx Spreads to larynx and trachea Inflammation, erythema and edema in trachea Subglottic area is major site of airway obstruction Croup: Chest X-Ray Croup Clinical Presentation Gradual onset Duration normally 5 days Low grade fever Classic “barking” cough Hoarse voice Stridor Dyspnea Sore throat Croup Clinical Presentation Worsening of breathing difficulty Cyanosis Difficulty swallowing Possible hospital admission Croup Treatment Cold air Humidified air • cool mist vaporizer • steamy bathroom • humidified oxygen Croup tents Croup Treatment Epinephrine • anti-inflammatory activity decreases subglottic edema • can improve stridor, decrease need for hospitalization & intubation and decrease mortality rates • onset: 10 to 30 minutes • duration of effect: 2 hours Croup Treatment Racemic epinephrine inhalation • Dose: 0.5 mL of 2.25% solution in 3 mL 0.9% NaCl q1-2h up to q20 minutes l-epinephrine inhalation • 1:1,000 solution (1 mg/mL) • dose: 2-5 mL q1-4 hours • as effective as racemic epinephrine Side effects Croup Treatment • Corticosteroids (moderate-severe Croup) Dexamethasone 0.6 mg/kg IV/IM x1 • oral versus parenteral • Budesonide inhalation • strong topical effects with low systemic activity • 2 mg x1, repeated q12-24h prn Croup: Canadian Study N Engl J Med 2004;351:1306-13 Randomized, double-blind, multi-centre study (n= 720 children, mild Croup) Dexamethasone 0.6 mg/kg oral or placebo Primary & secondary outcomes Dexamethasone effective treatment for mild Croup Pertussis Whooping cough syndrome 100 Day Cough “Intense cough” Epidemiology Seasonal, fall and winter Transmission by coughing All ages, 60% under 5 years Pertussis Microbiology Bordetella pertussis Bordetella parapertussis, Bordetella bronchiseptica, adenovirus Pertussis Pathophysiology: Inhalation of organism Adherence to ciliated cells Proliferation and spread Paralysis of cilia Production and accumulation of mucous Possible progression to pneumonia Pertussis Complications Hospitalization Pneumonia Central nervous system • encephalopathy • seizures Mortality Pertussis Complications by Age Pneumonia Hospitalization 70 60 Percent 50 40 30 20 10 0 <6 m 6-11 m 1-4 y 5-9 y Age group (yrs) *Cases reported to CDC 1997-2000 (N=28,187) 10-19 y 20+ y Pertussis Treatment • Supportive • oxygen • suctioning • Antibiotics Pertussis Antibiotics Erythromycin estolate 40 mg/kg/day po QID x 10-14 days Clarithromycin 15 mg/kg/day po BID X 10 days Azithromycin 10mg/kg/day po x 1 day, then 5 mg/kg/day po daily x 4 days Cotrimoxazole 8 mg TMP /kg/day po BID Pertussis: Canadian Study Pediatrics 2004;114(1):e96 Randomized, multi-centre study comparing azithromycin and erythromycin estolate (n=477, 6 months - 16 years) Outcomes: bacterial cultures, serology & PCR, ADRs, compliance and symptoms As effective, fewer ADRs & good compliance Pertussis Prevention Highly communicable Household contacts Same drugs as for treatment Pertussis Prevention Acellular pertussis vaccine (DTaP) Part of routine immunization schedule: Administration: 2, 4, 6 and 18 months with booster at 4 to 6 years Bronchiolitis Definition: acute respiratory illness resulting from inflammation of small airways, characterized by wheezing and caused by viral infection Bronchiolitis Epidemiology Young children Peak incidence between 2 to 6 months Winter and early spring Bronchiolitis Microbiology Respiratory syncytial virus (RSV) Parainfluenza Influenza A & B Adenoviruses Transmission by direct contamination Bronchiolitis Pathophysiology Viral replication in bronchioles Necrosis of ciliated cells Increased mucous secretions Bronchial plugging with obstruction Hypoxia Bronchiolitis Clinical Presentation Fever Nasal discharge Dry cough Wheeze Usually self-limiting Asthma, pneumonia, CHF, cystic fibrosis Bronchiolitis Progression Risk factors Tachypnea Irregular breathing Cyanosis or pallor Apnea Mortality Bronchiolitis Treatment Supportive • oxygen • hydration • suctioning Inhaled beta-agonists (salbutamol) • controversial Racemic or l-epinephrine • vasoconstricts mucosa to reduce edema Bronchiolitis Treatment Corticosteroids • oral versus inhaled Ribavirin • controversial • modest clinical benefit • no effect on hospital stay Bronchiolitis Prevention Passive immunization • given monthly through RSV season • RSV Immune Globulin (RSVIVIG, Respigam): blood product Palivizumab • monoclonal antibody • IM injection monthly during RSV season • costly Bronchiolitis Palivizumab (Synagis®) Approved in Canada in June of 2002 Formerly required Special Access Programme authorization Manufacturer: MedImmune Inc. Distributor: Abbott Laboratories Funding provided by Canadian Blood Services (CBS) if patients meet high risk criteria Bronchiolitis Palivizumab Criteria Children < 24 months of age with BPD/CLD and who have required oxygen or medical treatment within 6 months of RSV season Premature infants born at 32 weeks gestation and aged 6 months at start of RSV season Children < 24 months of age with hemodynamically significant heart disease Other: 33-35 week gestation infants at risk, immune deficiency Canadian Paediatric Society Guidelines Bronchiolitis Prevention Active immunization • RSV vaccine • Being researched Pediatric Infectious Disease References Red Book http://www.cps.ca The Hospital for Sick Children Formulary Pediatric Dosage Handbook Infectious Diseases Handbook Nelson’s Pocket Book of Pediatric Antimicrobial Therapy Nelson Essentials of Pediatrics QUESTIONS?