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Pneumonia in Developing Countries: Still Unresolved Problem

Pneumonia in Developing Countries: Still Unresolved Problem. Dr. Pushpa Raj Sharma Professor, Department of Child Health Institute of Medicine Kathmandu, Nepal. This Presentation. Epidemiology Risk factors Aetiological agents Clinical syndromes Investigations Treatment

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Pneumonia in Developing Countries: Still Unresolved Problem

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  1. Pneumonia in Developing Countries: Still Unresolved Problem Dr. Pushpa Raj Sharma Professor, Department of Child Health Institute of Medicine Kathmandu, Nepal

  2. This Presentation • Epidemiology • Risk factors • Aetiological agents • Clinical syndromes • Investigations • Treatment • Future implications

  3. A case: • 4 months old • One day history of excessive crying • Sent home with the diagnosis of windy colic with anti-spasmodics • Next day: • Grunting, respiratory distress, fever. • Admitted, IV ceftriaxone.

  4. Case (contd) • Second day: • Mother felt child is better but continues to be tachypnoeic, chest indrawing, fever persisting. • Vancomycin added with oxygen

  5. Case (contd) • Third day • Severe respiratory distress • Pus drained through water seal drainage • Antibiotics contd. • Discharged after 2 wk. Strepto.pneumoniae isolated

  6. Total live births and surviving infants in South East Asia Worlds population prospects. 2004 Revision. New York, United Nations, 2005

  7. Leading infectious causes of mortality, 2000 estimates

  8. Burden of Pneumonia South Asia • Population of approximately 667 million • Approximately 170 million infants and children, (about one-third of all the children in developing countries). 60240 18240 135600 82320 576480 ,1000 Unicef (www.childinfo.org) and Hyder et al ; Extrapolated from Black et al

  9. MONTH OF Feb. 2006

  10. Hospital Admissions Then and Now NEPAS J 1988; 7; 1-8

  11. Age distribution of pneumonia in hospital

  12. Burden of Disease • ARI episodes/child/year in U5: 5-9 • Pneumonia in ARI: 1:30-50 (2-3% of all ARI). • Most of these pneumonia are bacterial in developing countries. • Deaths in ARI are mostly due to pneumonia • Duration of illness who died from pneumonia: 3.5 days (Jumla Nepal)

  13. Acute respiratory infection prevalence in under 5 children by socioeconomic status in selected countries Based on World Bank data 2000.

  14. Risk Factors • In a multivariate analysis, the variables found to be most closely associated with mortality were breastfeeding, education of the father, the number of under-fives, family income and birth weight. Having a low weight-for-age was also strongly associated with mortality but the retrospective nature of the study makes this finding difficult to interpret. Int J Epidemiol. 1989 Dec;18(4):918-25.

  15. Risk Factors contd. • Current and past malnutrition were associated with acute lower respiratory infection (ALRI), even after adjusting for potential confounders (odds ratio: 2.03; 95% confidence interval: 1.202.43). Decreasing malnutrition along with timely and proper treatment of ARI may improve children's health in developing countries. Acta Paediatr. 2000 May;89(5):608-9.

  16. Risk Factors: Too many ………….. A study conducted by the World Bank found that the share of brick kilns in the valley's air pollution was 28 per cent while that of domestic fuel burning was 25 per cent, cement factory 17 per cent, vehicle emission 12 per cent and road dust 9 per cent. The study estimated that dust particles in the air cause 18,863 cases of asthma and 4,847 cases of bronchitis in Kathmandu every year.

  17. Risk Factors contd Indoor Air Pollution Emissions Along The Household Fuel Ladder Smith et al.98

  18. N. America and Europle(nine studies /range: 43-80%) Aetiology of pneumonia established in 62%: S. pneumoniae 22% RSV 20% H. influenzae 7% M. pneumoniae 15% Africa and S. America(eight studies/ range: 32-68%) Aetiology of pneumonia established in 56%: S. pneumoniae 33% H. influenzae 21% RSV M. pneumoniae Aetiology:

  19. Aetiology: Viruses isolated from children with ARI (n=287) Unpublished report: CHRP; IOM

  20. Aetiology based on lung aspirates

  21. Aetiology: Yield from cultures of lung puncture on 755 neonates who were stillborn or died in the first 72 hours of life Naeye RL, Dellinger WS, Blanc WA. Fetal and maternal features of antenatal bacterial infections. J Pediatr 1971;79:733–9.

  22. Aetiology: Burden of Hib disease in Nepal(Based on Hib Rapid Assessment Tool of WHO) *per 100,000 U5s Paper presented at the WHO dissemination seminar by Dr. Fiona Russeli et al

  23. Fever > 38.50C Respiratory rate >50/min Chest recession Wheeze is not a sign of primary bacterial LRTI (except in mycoplasma) Other viruses may be concurrent Clinical and radiological signs of consolidation rather than collapse. Infants and young children Wheeze Fever< 38.50C Marked recession Hyperinflation Respiratory rate normal or raised Hyperinflation and patchy collapse in 25% Lobar collapse when severe Bacterial or Viral? LOOKS SICK

  24. Atypical Pneumonia • Clark J, Archives Disease Childhood 2003 Mean age of children with M pneumoniae 3.5 yrs • Block S, Paediatric Infectious Disease Journal 1995 23% of 3-4 year old children had M pneumoniae

  25. Signs of Pneumonia

  26. Symptoms and Signs in Pneumonia

  27. 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

  28. Comparison of total leucocyte counts in different age group with clinically diagnosed as pneumonia

  29. Diagnostic value of total leucocyte count in radiologically positive cases:sensitivity: 33.7% and specificity: 71.8%

  30. Indications for CXR in either primary care or hospital • • For diagnosis of child <5 years with fever of 39°C of unknown origin • • If complication (for example, pleural effusion) suspected • • Atypical symptoms or unresponsive to treatment • • For follow up of children with lobar collapse or ongoing symptoms

  31. Laboratory studies* • Complete blood count Not helpful in distinguishing etiology • Erythrocyte sedimentation rate Not helpful in distinguishing etiology • C-reactive protein level Not helpful in distinguishing etiology • Gram stain and culture Helpful if specimen is adequate • Polymerase chain reaction Helpful with Mycoplasma and Chlamydia infections • Rapid viral antigen testing Useful if available • Serologies Not helpful in acute settings • Imaging Chest radiograph*Not helpful in distinguishing etiology*-Not routinely recommended. *Pediatr Infect Dis J 2002;21:592-8, 613-4.

  32. Clinical Diagnosis • Tachypnoea according to the usual WHO criteria: <2 months: 60 2-12 months: 50 !-5 years: 40

  33. Is Co-trimoxazole still the first line of drug for IMCI

  34. Antibiotics for OPD treatment in 4months to 5 year old children • Amoxicillin, 90 mg per kg per day orally in divided doses every 8 hours for 7 to 10 days • A 10 Kg child will need one and half tablet per dose of 250mg/ disp.tab or three tea spoon per dose of 125mg/5ml concentration. N Engl J Med 2002;346:429-37.

  35. Three days versus five days treatment with amoxicillin for nonsevere community acquired pneumonia • Three day courses of amoxicillin are as effective as five days without increasing risk of relapse or worsened disease. • 15 mg/kg amoxicillin every 8 hourly. Lancet, July 23, 2002 (MASCOT Group) BMJ  2004;328:791 (3 April), (ISCAP Group)

  36. Time for temperature to settle in the oral and IV groups =IV treatment --------- = oral treatment Wellek logrank test for equivalence P=0.0013 ITT P=0.0001 Probability that the child meets the primary outcome measure after time t Time for temperature to be less than 380C for 24 continuous hours (days) Arch Dis Child Edu Pract 2004; 29-34

  37. Time to resolution of symptoms IV group Time to resolution of symptoms oral group Number of children Number of children Time to resolution of symptoms in days Time to resolution of symptoms in days Median of 9 days to full recovery in both arms of the study Arch Dis Child Edu Pract 2004; 29-34

  38. Length of stay in hospital in the IV group Length of stay in hospital in the oral group Length of hospital stay in days Number of children IV Group - median 2.1 days (1.8-2.9) Oral Group - median 1.77 days (1-2.2) P=<0.001 Length of hospital stay in days IV Group - median 2.1 days (1.8-2.9) Oral Group - median 1.77 days (1-2.2) P=<0.001 Arch Dis Child Edu Pract 2004; 29-34

  39. Indications for admission to hospital Older children • Oxygen saturation <92% • Respiratory rate > 50 • Difficulty breathing • Grunting • Signs of dehydration Family not able to support at home > 1 year 120/182 (66%) met 1 or more criteria Thorax. 2002;57;1-24

  40. SWT Therapy • No RCT’s in children • 2 prospective observational studies • Both demonstrate that IV therapy for CAP can be successfully be decreased to 2-4 days Al-Eidan F, Journal Antimicrobial Chemotherapy 1999 Ciommo V, Journal of evaluation in clinical practice 2002

  41. Previous studies comparing macrolides with other groups of antibiotics Only 1 study in children comparing beta-lactams with macrolides Divided children clinically into “atypical” (randomised to azithromycin or erythromycin) or “classic” pneumonia (randomised to amoxicillin or azithromycin) Results – no difference between the 2 groups Kogan et al Pediatric Pulmonology 2003

  42. Indication of macrolide in infant • 3 weeks to 3 months If patient is afebrile: Azithromycin, 10 mg per kg orally on day 1, then 5 mg per kg per day on days 2 through 5or • Erythromycin, 30 to 40 mg per kg per day orally in divided doses every 6 hours for 10 days • Admit if patient is febrile or hypoxic

  43. Vitamin A and pneumonia The evidence did not suggest a significant reduction with vitamin A adjunctive treatment in mortality, measures of morbidity, nor an effect on the clinical course of pneumonia in children with non-measles pneumonia. However, not all studies measured all outcomes, limiting the number of studies that could be incorporate into the meta-analyses, so that there may have been a lack of statistical power to detect statistically significant differences. Cochrane Database Syst Rev. 2005 Jul 20;(3): CD003700.

  44. ZINC AND PNEUMONIA • FINDINGS: In a pooled analysis of trials, zinc supplementation reduced the incidence of pneumonia infection by 41% and daily zinc supplementation reduced the incidence of pneumonia in Delhi children ages 6 to 30 months given vitamin A • IMPLICATION: Zinc reduces the incidence of pneumonia but zinc in combination with vitamin A may be more effective than the administration of either micronutrient alone. Sources: 1Bhutta ZA, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr. 1999 Dec;135(6):689-97. 2Bhandari N, et al. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ. 2002 Jun 8;324(7350):1358.

  45. Pneumonia with associated diseases • Most children in developing countries with recurrent pneumonia diagnosed by WHO criteria do not have evidence of tuberculosis, HIV infection or pulmonary anomalies, but they may be more likely to have asthma, and this should be considered as an alternative diagnosis. Pediatr Infect Dis J. 2002 Feb;21(2):108-12

  46. HibVaccination schedule Recommended vaccination schedule from 2 months old: same schedule as DTP Act-HIB™ 6, 10, 14 weeks booster at 18 months of age 2- 4- 6 months 12-15 months ACIP Recommendation Plotkin S, Vacccine, 3rd ed. 1999

  47. PneumococcalVaccination schedule?? Recommended vaccination schedule from 2 months old: same schedule as DTP PCV 2- 4- 6 months 12-15 months PPV Recommended in addition to the PCV for certain high risk group after two years.

  48. Immunization for common serotypes (pneumococcus) PCV7 (Wyeth) * PCV12 (Wyeth) * * * PCV10 (GSK) * * * *

  49. Areas of continuing uncertainty • • The most useful clinical signs and symptoms that help to predict a diagnosis of pneumonia • • Which children require a chest x ray before treatment • • Which test to detect the causative organism will be sensitive, specific, affordable, and quick and easy to use • • Which antibiotic should be prescribed • • Which route should be used for administering the antibiotic prescribed • • If the intravenous route is used when should a switch to oral antibiotics occur

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