Pneumonia: Past and Present

1. Pneumonia: Past and Present Dr. Pushpa Raj Sharma Professor of Child Health Institute of Medicine

2. Disease Pattern

3. Epidemiology • Each year, acute respiratory infections • cause approximately 2-3 million deaths among children <5 years old and are the leading cause of death in this age group. • About 1% of pneumonia cases result in sequelae (e.g., bronchiectasis) • Identifying the cause of community-acquired pneumonia is more difficult in children

4. Children with ARI presenting in OPD Place % of children London (UK) 35.0 Herston (Australia) 34 Ethiopia (Whole country) 25.5 Sau aulo (Brazil) 41.8 India 38.9 Nepal 37.6

5. Number of Pneumonia Episodes Per Year in Childeren Under 5 Years Place Annual Incidence per 100 Seattle (USA) 3.0 Gadchiorili (India) 13.0 Basse, (Gambia) 17.0 Bankok (Thailand) 7.0 Nepal 16.5

6. Epidemiology • A lower respiratory tract infection (LRI) develops in one in three children in the first year of life. • Twenty-nine percent of these children develop pneumonia • Approximately 10-20% of all children <5 years old in developing countries develop pneumonia each year

7. Risk Factors • Significant risk factors were younger age (2-6 months), low parental education, smoking at home, prematurity, weaning from breast milk at < 6 months, a negative history of diphtheria, pertussis and tetanus vaccination, anaemia and malnutrition. • Trop Doct 2001 Jul;31(3):139-41

8. Pathology

9. Pathology

10. Currently pneumonias are defined as either community-acquired (CAP) or nosocomial or hospital-acquired . • CAP is defined as an infection acquired in the community setting; the definition varies and it may or may not include infections acquired in a nursing home or long-term care facility Types of Pneumonia

11. The exact incidence varies but in a meta-analysis of 122 cases of CAP, it accounted for 66% of cases in which a microbiological diagnosis was made. • Exact incidences of the various aetiologic organisms are not known. Aetiological agents

12. Diagnosis Clinical evaluation of pneumonia • Cough, Grunting, Chest pain, • Tachypnea. Retractions, • Signs of consolidation, • Crackles Wheezing , • Cyanosis, • Abdominal pain , Drooping of shoulder.

13. Mechanism of coughBronchioles and Respiratory bronchiole alveolus

14. Signs of Pneumonia

15. Symptoms and Signs in Pneumonia

16. Comparison of Methods for the Detection of Pneumonia in Children Method Sensitivity Specificity Stethoscope 53% 59% (crepetations) Simple clinical signs 77% 58% (fast breathing or chest indrawing) Note: Pneumonia diagnosis confirmed by Chest X-ray

17. Diagnosis Diagnostic evaluation of lower respiratory infections: • WBC count Blood cultures • C-reactive protein • Chest radiograph. • Bacterial antigen assays • Nasopharyngeal cultures

18. Recent studies have concluded that generally radiology is not helpful for determining the aetiology of the infection. • The diagnosis of pneumonia is based on a history of respiratory tract infection and the radiological finding of new pulmonary infiltrates Diagnosis

19. Clinical Diagnosis • Tachypnoea according to the usual WHO criteria. • Auscultatory signs have lower specificity. • Acute phase reactants cannot be relied for aetiological diagnosis. • Blood culture positivity in only <10% • Viral antigen detection not available.

20. Pneumonia and Vitamin A • Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight childrenfrom ALRI and paradoxically increased ALRI in normal childrenwith body weight over  -1 SD in Ecuadorian Children . • Large doses of vitamin A had no protectiveeffect on the course of pneumonia in hospitalized Tanzanian children.

21. Pneumonia and Zinc Reduction in all respiratory diseases. (Indian J Pediatr 1995; 62,181-93 2.5 fold decrease in respiratory infection. (Am J Clin Nutr; 1996; 63; 514-9 Significant reduction in upper respiratory tract disease. (Am J Clin. Nutr. 1996; 63;514-9) Reduction of 45% incidence of lower respiratory tract infection. (PEDIATRICS 1998; 102 ;1-5)

22. Compositions of cough mixtures available Category A - Only Antitussive F - Expectorant + Antitussive B - Only expectorant G - Expectorant + Bronchodilator C - Only mucolytics H - Expectorant + Mucolytics D - Only bronchodilator I - Expectorant + Antihistamines E - Only Antihistamine J - Having more than 2 of the A,B,C,D,E. K - Bronchodilator + Antihistamine

23. Tablets/capsules 19 23.75% Liquid/Syrups 56 70.00% Other forms 5 6.25% TOTAL 80 100% Formulations available Type of Formulation

24. Role of cough mixtures in pneumonia

25. Over the counter cough mixtures • No well-controlled studies supporting the use of codeine or dextromethorphan as antitussives for children have been published, and indications for their use have not been established. • Cough due to URTI can often be treated with non-drug measures (fluids and humidity). • Pediatric dosages of antitussives are extrapolated from adult data and thus are imprecise for children. • Significant adverse effects of their use have been documented. • Clinicians should tell parents and patients about these concerns.

26. Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults BMJ 2002;324:329 ( 9 February ) • Conclusion: Over the counter cough medicines for acute cough cannot be recommended because there is no good evidence for their effectiveness. Even when trials had significant results, the effect sizes were small and of doubtful clinical relevance. Because of the small number of trials in each category, the results have to be interpreted cautiously.

27. Various guidelines have been developed. • Once treatment has begun, no change in medication is indicated within the 1st 72 hours unless a specific organism is identified and is not covered by the current medication . Treatment Treatment must assess the severity of the illness, appropriate setting for treatment (outpatient vs. inpatient), socioeconomic conditions, and local susceptibilitypatterns of common pathogens.

28. Causative Agents • In Africa and South America (8 studies), bacteria were recovered from 56% (range 32%-68%) of severely ill children studied by lung aspirate. The most often isolated bacteria were Streptococcus pneumoniae (33%) and Haemophilus influenzae (21%) • Braz J Infect Dis 2001 Apr;5(2):87-97

29. polyribosyl ribitol phosphate (PRP) capsule is an important virulence factor which renders type b H. influenzae resistant to phagocytosis by PMNs in the absence of specific anticapsular antibody . • produce IgA protease which may facilitate attachment to mucosal surfaces • treatment with a combination of amoxicillin and clavulanic acid (Augmentin) or TMP/SMX is effective against þ-lactamase-producing strains Haemophilus influenzae

30. Ccapsular polysaccharide is most important virulence factor; approximately 85 capsular types • Penicillin is drug of choice for susceptible organisms (MIC = 0.06 µg/mL) . • Vaccine contains 23 most common capsular serotypes Streptococcus pneumoniae

31. special attachment organelle; attach to epithelium via protein adhesins on the attachment organelle; major adhesin is a 170-kilodalton (kDa) protein, named P1 • bacteria injure mucosa by producing oxidants (hydrogen peroxide & superoxide radicals) which cause ciliostasis and epithelial necrosis thus inhibiting normal clearance mechanisms Mycoplasma pneumoniae

32. Integrated Management of Childhood Illnesses Does the child have cough or difficulty in breathing? If Yes Ask:Signs Clsssify as For How Long? Any general danger sign or Severe Chest indrawing or pneumonia Stridor Look, Listen Fast breathing Pneumonia Count the breaths Chest indrawing No signs of pneumonia No Pneumonia: Stridor or very severe disease cough or cold

33. Birth to 20 days: Admission 3 weeks to 3 months: Afebrile: oral erythromycin Febrile: add cefotaxime 4 months to 5 years: Amoxycillin 80mg/kg/dose 6-14 years: Erythromycin Suggested Drug Treatment NEJM

34. Prevention • Within two years of the introduction of routine Hib vaccination of infants in the UK, the risk of serious Hib infection had fallen from 1:600 to 1:30,000 by 5 years of age Eur J Clin Microbiol Infect Dis 1995 Nov;14(11):935-48 • It is important that these highly effective vaccines should be made available to children in the developing countries. Acta Paediatr 2001 May;90(5):473-6

35. SummaryPneumonia in children in the age group of 2 months to 5 years • Pneumonia is the commonest cause of mortality • Fast breathing in a child with cough or difficulty breathing is highly sensitive and specific for diagnosis • Co-trimoxazole is the effective treatment for community pneumonia in children • Cough mixtures are not useful but harmful. • Cough persists for few weeks.

36. Strains are classified as either serotypable (if they display a capsular polysaccharide antigen) or nontypable (no capsule); seven generally recognized serotypes: a, b, c, d, e, e' and f; H. influenzae type b (Hib) is the most virulent • Nontypable H. influenzae strains colonize the nasopharynx of most normal children. Haemophilus influenzae

37. Approximately 20-30% of isolates are beta-lactamse positive. • Treatment with either amoxicillin/clavulanic acid or TMP/SMX is effective against þ-lactamase-producing strains. Haemophilus influenzae

38. Data suggest that repeated infections are required before symptomatic disease occurs - antibodies to M. pneumoniae can be found in most children age 2 - 5 years while illness occurs with greater frequency among older children and young adults . • Resistant to antibiotics that inhibit bacterial cell wall synthesis (e.g., penicillin, cephalosporins, vancomycin) Mycoplasma pneumoniae

39. encapsulated organisms can penetrate the epithelium of the nasopharynx and invade blood capillaries directly; nontypable strains are less invasive, but they, as well as typable strains, induce an inflammatory response that causes disease Structure, Virulence Factors and Pathogenesis

40. M. pneumoniae acts as a superantigen (macrophage activation, cytokine induction) and stimulates inflammation; pneumonia is induced largely by local immunologic and phagocytic responses to the parasites. • some children may develop cold agglutinins as a result of infection. Mycoplasma pneumoniae

41. Secretory IgA protease - inhibits function of secretory IgA which normally binds bacteria to mucin to facilitate clearance from the respiratory tract • Pneumolysin - creates pores in and destroys ciliated epithelial cells • Hydrogen peroxide - reactive 02 intermediate causes tissue damage Structure, Virulence Factors and Pathogenesis