Community acquired pneumonia in children Dr. Joram Nyandat Consultant Paediatrician Moi Teaching & Referral Hospital

Pneumonia: Definition Pneumonia and pneumonitis ⇥ Strictly represent any inflammatory condition involving the lungs, which include the visceral pleura, connective tissue, airways, alveoli, and vascular structures. Lower respiratory tract infection (LRTI) ⇥ Frequently used interchangeably to include bronchitis, bronchiolitis, and pneumonia, or any combination of the three.

Pneumonia: Definition Pneumonia ⇥ A condition typically associated with fever, respiratory symptoms, and evidence of parenchymal involvement, either by physical examination or the presence of infiltrates on chest radiography. Community acquired pneumonia ⇥ A clinical diagnosis of pneumonia caused by a community acquired infection in a previously healthy child

Epidemiology 4 INCIDENCE Developed countries ⇥ 3.3 per 1000 in children < 5 years and 1.45 per 1000 in children 0 to 16 years ⇥ Approximately one-half of children < 5years with CAP require hospitalization Developing Countries ⇥ 231 per 1000 in children < 5 years ⇥ 50 to 80 percent of children with severe pneumonia required hospitalization

Hospital-acquired pneumonia ⇥ Occurs ≥48 hours after admission and does not appear to be incubating at the time of admission. ⇥ Usually caused by gram-negative bacilli or S. aureus. ⇥ Frequently occurs in intensive care units where mechanical ventilation, indwelling catheters, and administration of broad- spectrum antibiotics

Epidemiology SEASONALITY ⇥ Although both viral and bacterial pneumonia occur throughout the year, they are more prevalent during the colder months, presumably because direct transmission of infected droplets is enhanced by indoor crowding. ⇥ In tropical regions, peaks of infection follow no common pattern MORTALITY ⇥ 2 nd most common cause of mortality among children ≤19 years worldwide (31.1 per 100,000 population) ⇥ Second only to neonatal/preterm birth complications

Risk factors 7 ⇥ Lower socioeconomic status Correlates best with family size, a reflection of environmental crowding. ⇥ Presence of school-age children Often introduce respiratory viral agents into households, resulting in secondary infections in their parents and siblings ⇥ < 5 years old are at greatest risk (In otherwise healthy children) ⇥ Boys have a higher incidence across all ages.

Other risk factors ⇥ Prematurity ⇥ Immunodeficiency (congenital & acquired) ⇥ Chronic respiratory disease (BPD, asthma, cystic fibrosis) ⇥ Neuromuscular disorders ⇥ Sickle cell disease ⇥ Congenital Heart Diseases ⇥ Gastrointestinal disorders (e.g., GERD, tracheoesophageal fistula)

Risk factors ⇥ Exposure to cigarette smoke Compromises natural pulmonary defence mechanisms by disrupting both muco-ciliary function and macrophage activity.

Protective factors Effect of vaccines ⇥ Immunization with the Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines protects children from invasive disease ⇥ Pneumococcal vaccination also reduces the risk (31% reduction) of viral pneumonia (influenza A/B, parainfluenza types 1 to 3, respiratory syncytial virus, adenovirus)

Aetiology: Respiratory viruses ⇥ Respiratory viruses are common, particularly in infants ⇥ Accounting for 30-67% of hospitalised cases. ⇥ Respiratory syncytial virus accounts for 30% of viral aetiology ⇥ Other viruses include parainfluenza, influenza, and human metapneumovirus.

Aetiology: Bacterial causes ⇥ Streptococcus pneumoniae is the commonest bacterial cause across all ages, accounting for % of cases. ⇥ Other bacterial causes include group A streptococcus and, in infants, group B streptococcus

Etiology by age group months CommonLess common Streptococcus pneumoniae Chlamydia pneumoniae Respiratory viruses Enterovirus Group A streptococcus Group B streptococcus Haemophilus influenzae

Etiology by age group (Cont.) 14 <5 years CommonLess common Streptococcus pneumoniae Respiratory viruses Mycoplasma pneumoniae Group A streptococcus Haemophilus influenzae Staphylococcus aureus

Community acquired pneumonia (CAP) Etiology by age group (Cont.) 15 ≥ 5 years CommonLess common Streptococcus pneumoniae Mycoplasma pneumoniae Respiratory viruses Staphylococcus aureus Chlamydia pneumoniae Mycobacterium spp

Etiology by age group (Cont.) 16 Immunocompromised (all ages) Common As with age group plus Fungi,Burkholderia, Pseudomonas, and mycobacterium spp

PATHOGENESIS ⇥ Pneumonia occurs because of an impairment of host defences, invasion by a virulent organism, and/or invasion by an overwhelming inoculum ⇥ Typically follows an upper respiratory tract illness that permits invasion of the lower respiratory tract by bacteria, viruses, or other pathogens that trigger the immune response and produce inflammation The lower respiratory tract air spaces fill with white blood cells, fluid, and cellular debris.

Pathogenesis ct ⇥ This process reduces lung compliance, increases resistance, obstructs smaller airways, and may result in collapse of distal air spaces, air trapping, and altered ventilation-perfusion relationships ⇥ Severe infection is associated with necrosis of bronchial or bronchiolar epithelium and/or pulmonary parenchyma

⇥ The agents causing LRTI are most often transmitted by droplet spread resulting from close contact with a source case. ⇥ Contact with contaminated fomites may be important in the acquisition of viral agents ⇥ Most typical bacterial pneumonias are the result of initial colonization of the nasopharynx followed by aspiration or inhalation of organisms. ⇥ Invasive disease most commonly occurs upon acquisition of a new serotype of the organism with which the patient has not had previous experience Pathogenesis: Acquisition

⇥ Occasionally, a primary bacteraemia may precede the pneumonia. ⇥ Atypical bacterial pathogens attach to respiratory epithelial membranes through which they enter cells for replication. ⇥ The viral agents that cause pneumonia proliferate and spread by contiguity to involve lower and more distal portions of the respiratory tract.

Pathogenesis: Normal host defence ⇥ The pulmonary host defence system includes: ⇥ Anatomic and mechanical barriers Particles >10 microns are efficiently filtered by hairs in the anterior nares or are trapped on mucosal surfaces. Local production of complement and IgA Bacterial interference from resident flora

Pathogenesis: Normal host defence ⇥ Humoral immunity ⇥ Secretory IgA is the major immunoglobulin produced in the upper airways ⇥ IgG and IgM enter the airways and alveolar spaces predominantly via transudation from the blood and act to opsonize bacteria, activate complement, and neutralize toxin

Pathogenesis: Normal host defence ⇥ Phagocytic activity Two populations of phagocytic cells in the lung: polymorphonuclear leukocytes from the blood and macrophages Alveolar macrophage located in the alveolar fluid is the first phagocyte encountered. If overwhelmed, it can become a mediator of inflammation and produce cytokines that recruit neutrophils Interstitial macrophages located in the lung connective tissue serve as both as phagocytic cells and antigen-processing cells

⇥ Cell-mediated immunity Especially important against viruses and intracellular microorganisms that can survive within pulmonary macrophages. Lymphocytes play three critical roles: the production of antibody, cytotoxic activity, and the production of cytokines.

Pathologic patterns of pneumonia: Bacterial ⇥ There are five pathologic patterns of bacterial pneumonia Lobar pneumonia – Involvement of a single lobe or segment of a lobe. This is the classic pattern of S. pneumoniae pneumonia. Bronchopneumonia – Primary involvement of airways and surrounding interstitium. This pattern is sometimes seen in Streptococcus pyogenes and Staphylococcus aureus pneumonia. Necrotizing pneumonia-associated with aspiration pneumonia and pneumonia resulting from S. pneumoniae, S. pyogenes, and S. aureus. Caseating granuloma -as in tuberculous pneumonia. Interstitial and peribronchiolar with secondary parenchymal infiltration – Typically occurs when a severe viral pneumonia is complicated by bacterial pneumonia.

Pathologic patterns of pneumonia: Viral ⇥ There are two major pathologic patterns of viral pneumonia Interstitial pneumonia Parenchymal infection.

Clinical presentation ⇥ The clinical presentation varies depending on the responsible pathogen, the particular host, and the severity ⇥ The presenting signs and symptoms are nonspecific Fever + cough is suggestive of pneumonia Other respiratory findings (e.g., tachypnoea, increased work of breathing) may precede the cough. Cough may not be a feature initially since the alveoli have few cough receptors. Cough begins when the products of infection irritate cough receptors in the airways. Neonates and young infants may present with difficulty feeding, restlessness, or fussiness

Clinical presentation ⇥ Older children and adolescents Pleuritic chest pain Abdominal pain-referred pain from the lower lobes Nuchal rigidity-referred pain from the upper lobes ⇥ Walking pneumonia" is a term that is sometimes used to describe pneumonia in which the respiratory symptoms do not interfere with normal activity.

Clinical evaluation Objectives ⇥ Identification of the clinical syndrome (e.g., pneumonia, bronchiolitis, asthma) ⇥ Consideration of the etiologic agent (e.g., bacteria, virus) ⇥ Assessment of the severity of the illness

History Significance Age Viral most common in infants and preschool children Atypical bacterial pathogens are more common in school-age children Recent viral URTIMay predispose to bacterial superinfection Associated symptoms Mycoplasma pneumoniae is often associated with extrapulmonary manifestations (e.g., headache, photophobia, rash) Cough, chest pain, shortness of breath, difficulty breathing "Classic" features of pneumonia, but nonspecific Increased work of breathing in the absence of stridor or wheezing Suggestive of severe pneumonia

HistorySignificance Fluid and nutrition intakePoor feeding suggests severe illness Choking episodeMay indicate foreign body aspiration Duration of symptoms Chronic cough (>4 weeks) suggests aetiology other than acute pneumonia Previous episodes Recurrent episodes may indicate aspiration, congenital/acquired anatomic abnormality, cystic fibrosis, immunodeficiency, asthma, missed foreign body Immunization status Completion of immunizations for Haemophilus influenzae type b, S. pneumoniae, Bordetella pertussis, and seasonal influenza decreases, risk of infection Previous antibiotic therapyIncreases the likelihood of antibiotic-resistant bacteria Choking episodeMay indicate foreign body aspiration

HistorySignificance Exposure to tuberculosisMay indicate Mycobacterium tuberculosis infection Sick contactsMore common with viral etiologies History of Travel COVID-19 Day care center attendanceExposure to viruses and antibiotic-resistant bacteria

General appearance (state of awareness, cyanosis) Most children with radiographically confirmed pneumonia appear ill Vital signs TemperatureFever may be the only sign of pneumonia Respiratory rate Tachypnoea is less predictive of radiographically confirmed pneumonia than hypoxemia or increased work of breathing Tachypnoea correlates with hypoxemia Absence of tachypnoea helps to exclude pneumonia

Degree of respiratory distress Respiratory distress is more specific than fever or cough for lower respiratory infection Tachypnea HypoxemiaPredictive of pneumonia Increased work of breathing: RetractionsMore common in children with pneumonia Nasal flaring More common in children with pneumonia than without; absence does not exclude pneumonia GruntingSign of severe disease and impending respiratory failure Accessory muscle useSign of severe disease Head bobbingSign of severe disease Lung examination CoughNonspecific finding of pneumonia Auscultation Findings suggestive of pneumonia include: crackles (rales, crepitations), decreased breath sounds, bronchial breath sounds, egophony, bronchophony, and whispered pectoriloquy Wheezing more common in viral and atypical pneumonias Tactile fremitusSuggestive of parenchymal consolidation Dullness to percussionSuggestive of parenchymal consolidation or pleural effusion Mental statusAltered mental status may be a sign of hypoxia

CAP assessment 35 It is difficult to distinguish clinically between bacterial and viral aetiologies. Consider bacterial pneumonia in children presenting with persistent or recurrent fever ≥38.5°C over the preceding hours with chest wall recession and tachypnea

CAP assessment (Cont.) 36 Assess the likelihood and severity of CAP by : FeverBreathlessness TachypneaChest wall recession CoughChest pain Respiratory rate and dyspnea are useful measures of severity and predict oxygen requirement

Assessment in the community 37 Focus the examination on defining severity and identify children with underlying conditions who are at increased risk. Hypoxemia increases mortality risk, and oxygen saturations <95% in room air are a key indicator for hospital assessment

Assessment in hospital 38 All children require pulse oximetry. Level of C reactive protein is not useful to differentiate viral and bacterial causes, but it can guide investigation and management of CAP complicated by effusions, empyema, or necrosis. Urinary pneumococcal antigen detection has a high sensitivity but very low specificity. If it is available, consider using it as a negative predictor.

Assessment in hospital (cont.) 39 Avoid routine chest radiography in children requiring hospital admission Radiographic appearance correlates poorly with clinical signs and outcome Consider radiography:  In severe cases  Where complications such as effusion or empyema are suspected

Investigations 40 Bloods (full blood count, urea and electrolytes, C reactive protein, blood culture Nasopharyngeal secretions and swabs for viral PCR or immunofluorescence detection

2/5/ Chest x ray to assess for effusion or empyema Consider pleural fluid for :  Microscopy, culture (including tuberculosis)  Pneumococcal antigen for PCR  Biochemistry  Cytology (if aspiration required)

criteria for referral to paediatric intensive care 42 Clinical features:  Failure to maintain oxygen saturations >92% with FiO2 60%  Clinical features of shock  Increasing respiratory and heart rates with severe respiratory distress and exhaustion, with or without raised pCO2  Recurrent apnoea or slow irregular breathing

Red flag features for community acquired pneumonia (CAP) 43 History of underlying comorbidities, including:  Bronchopulmonary dysplasia  Disorders of mucus clearance (such as cystic fibrosis)  Congenital heart disease  Immunodeficiency  Severe cerebral palsy

Red flag features for community acquired pneumonia (CAP) (cont.) 44 Relevant medical history :  History of severe pneumonia (inpatient stay requiring oxygen, paediatric intensive care admission, complications of CAP (such as lung abscess, effusion, empyema)  Recurrent pneumonia

CAP management 45 Children with clinical features consistent with CAP require antibiotics.

Antibiotic selection in community acquired pneumonia 46 Preferred route of administration  Oral antibiotics are safe and effective for children even with severe CAP  Use intravenous antibiotics in children who: – Are unable to tolerate oral fluids (such as because of vomiting) or – Have signs of septicaemia or complicated pneumonia

47 Which antibiotic?  Amoxicillin is first line therapy (use macrolides as first line in penicillin allergy)  Macrolides can be added at any age if : o There is no response to first line therapy o Mycoplasma or Chlamydia pneumoniae are suspected o Disease is severe

48 Which antibiotic? (Cont.)  Co- amoxiclav is recommended for pneumonia associated with influenza  Intravenous antibiotic treatment with amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, or ceftriaxone is recommended for severe pneumonia

Outpatient Treatment of Pneumonia Presumed bacterial pneumonia ■ Amoxicillin, oral (90 mg/kg/day in 2 doses) Alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses) Presumed atypical pneumonia ■ Azithromycin oral (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2– 5); ■ Alternatives: oral clarithromycin (15 mg/kg/day in 2 doses for 7-14 days) or oral erythromycin (40 mg/kg/day in 4 doses)

■ Oral amoxicillin (90 mg/kg/day in 2 doses to a maximum of 4 g/day); for children with presumed bacterial CAP who do not have clinical, laboratory, or radiographic evidence that distinguishes bacterial CAP from atypical CAP, a macrolide can be added to a b-lactam antibiotic for empiric therapy; ■ Alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses to a maximum dose of 4000 mg/day

presumed atypical pneumonia ⇥ Oral azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2–5 to a maximum of 500 mg on day 1, followed by 250 mg on days 2–5) ■ Alternative: oral clarithromycin (15 mg/kg/day in 2 doses to a maximum of 1 g/day

Presumed bacterial pneumonia ⇥ Ampicillin or penicillin G; ⇥ alternatives: ceftriaxone or cefotaxime; ⇥ addition of vancomycin or clindamycin for suspected CA- MRSA Presumed atypical pneumonia ⇥ Azithromycin (in addition to ß-lactam, if diagnosis of atypical pneumonia is in doubt);

Supportive therapies and advice for care givers 53 Advice on signs of deterioration, dehydration, and complications Ask the parents or carers to seek further advice if fever persists or symptoms deteriorate despite 48 hours of antibiotic treatment In secondary care, children with oxygen saturations 95% saturation

Supportive therapies and advice for care givers 54 Oxygen can be administered via face mask, nasal cannulae, or head box. Nasogastric feeds can maintain hydration, but if they are not tolerated because of vomiting or severe illness, intravenous fluid replacement may be required, with daily electrolyte monitoring for sodium depletion or syndrome of inappropriate antidiuretic hormone secretion. There is no any benefit from physiotherapy

CAP complications 55 Empyema Is the most common complication Risk factors Age >3 years Recent varicella infection

Empyema (cont.) 56 Signs and symptoms Fever >7 daysEvidence of effusion: -Decreased chest expansion -Dull percussion -Reduced or absent breath sounds ± Cyanosis Pleuritic chest pain Severe CAP symptoms No response to 48 hours antibiotics

Empyema (cont.) 57 Investigations Chest x ray Ultrasound scan Blood tests Microbiology

Empyema (cont.) 58 Treatment Referral to tertiary centre High dose IV antibiotics ± Thoracentesis or decortication ± Fibrinolytic therapy Oral antibiotics for further 1-4 weeks

CAP complications (Cont.) Necrotising pneumonia 45 Risk factors Congenital lung abnormalities Bronchiectasis Immunodeficiency Neurological disorders Staphylococcal aureus with PVL toxin PVL = Panton-Valentin leucocidin

Necrotising pneumonia (cont.) 60 Signs and symptoms Insidious onsetProductive foul smelling sputum Persistent feverWeight loss Night sweatsPleuritic chest pain

Necrotising pneumonia (cont.) 61 Investigations Chest x ray CT scan Blood tests Microbiology

Necrotising pneumonia (cont.) 62 Treatment Referral to tertiary centre High dose IV antibiotics (2-3 week course) Prolonged oral antibiotic course ± Surgical intervention

CAP complications (Cont.) 63 Other complications include: Systemic sepsis Haemolytic uremic syndrome Bronchiectasis following severe or complicated CAP

Measurements to reduce CAP incidence 64 The schedule of giving the following vaccines is hopingto reduce CAP incidence: Pneumococcal conjugate vaccine (PCV) Haemophilus influenzae type B (Hib) vaccination Annual influenza vaccine

Measurements to reduce CAP incidence (cont.) 65 Additional pneumococcal, and in some cases influenza, vaccination is provided for high risk children with: asplenia or splenic dysfunction cochlear implants (due to the meningitis risk) chronic disease complement disorders immunosuppression.

Conclusion Pneumonia can be diagnosed clinically when there are signs of a lower respiratory tract infection and wheezing syndromes have been ruled out. 66

Conclusion Blood tests and microbiological investigations are NOT recommended for routine use in the diagnosis and management of CAP. 67

Conclusion CXR does not need to be performed in those with mild disease who will be managed as an outpatient. 68

Conclusion Respiratory viruses are common, particularly in infants, accounting for 30-67% of hospitalised cases 69

Conclusion Streptococcus pneumoniae is the commonest bacterial cause across all ages, accounting for 30-40% of cases. 70

Conclusion For non-severe pneumonia, high dose oral amoxicillin is recommended even for inpatient use.IV benzylpenicillin can be considered if patient is not tolerating oral intake and not vomiting. 71

Conclusion Empyema and necrotizing pneumonia are the most serious complications of Community acquired pneumonia 72

Conclusion To reduce the CAP incidence,the following vaccines have been given : Pneumococcal conjugate vaccine (PCV) Haemophilus influenzae type B (Hib) vaccination An annual influenza vaccine 73

References 77 Thomson A, Harris M. Community- acquired pneumonia in children: what’s new ? Thorax 2011;356:927-8 Clark JE. Determining the microbiological cause of a chest infection. Arch Dis Child 2015;356: Clark JE, Hammal D, Hampton F, Spencer D, Parker L. Epidemiology of community-acquired pneumonia in children seen in hospital. Epidemiol Infect 2007;356: Senstad AC, 2.Surén P, Brauteset L, Eriksson JR, Høiby EA, Wathne KO. Community-acquired pneumonia (CAP) in children in Oslo, Norway. Acta Paediatr 2009;356: Cevey-Macherel M, Galetto-Lacour A, Gervaix A, et al. Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines. Eur J Pediatr 2009;356: Charkaluk M-L, Kalach N, Mvogo H, et al. Assessment of a rapid urinary antigen detection by an immunochromatographic test for diagnosis of pneumococcal infection in children. Diagn Microbiol Infect Dis 2006;356:

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