Control of Acute Respiratory Infections in         children(or winning the battle against childhood               pneumoni...
Pathogens causing pneumonia in               childrenAt least 1 respiratory pathogen was identified in 79% (122 of 154) of...
Childhood pneumonia is the leading            cause of death in children <5 years.                                        ...
Pneumonia kills more children than               any other illness.                                                       ...
Pneumonia is the number 1 KILLER             of Filipino children 1-59 mos of                            age!             ...
Our children are most                vulnerable to pneumonia !               350000                                       ...
Slidecourtesy ofGSK
Etiology of pneumonia          Pathogens causing pneumonia in children          At least 1 respiratory pathogen was identi...
Table 2.1. Review of 15 studies that reported results of 1133 lung aspirates in hospitalized children without prior antibi...
Factors to consider in the Control of           ARI in childrenDisease Burden – Developing CountriesRisk Factors – Lack of...
ARI study group (Circa 1981-1990)Main goal: To conduct studies that would help DOH programs forthe control of childhood pn...
Assumptions supporting the early development of WHO-ARI Control Program1. High mortality from ARI – due to  a. pneumonia (...
2. High mortality from pneumonia was due to a high incidenceof bacterial pneumoniaa. Streptococcus pneumoniae and Haemophi...
Tupasi TE, Lucero MG, Magdangal DM et al. Reviews Inf Dis 1990
WHO – PNEUMONIA CONTROL PROGRAM:    The ARI Bohol study 1983-1990
Table 5.8: Cause-specific age-standardized mortality rates for children 0-4                 years by time and area, and ef...
Polysaccharide vaccine ----Immunogenic only in adultsPolysaccharide vaccine conjugated toprotein carrier = Immunogenic in ...
CONCLUSION: THIS HEPTAVALENT PNEUMOCOCAL CONJUGATEVACCINE APPEARS TO BE HIGHLY EFFECTIVE IN PREVENTING INVASIVEDISEASE IN ...
Efficacy of an 11-valent pneumococcal conjugatevaccine (11PCV) in preventingradiographically confirmed pneumonia in childr...
Endpoint            11PCV                  Placebo              Vaccine                                                   ...
Cochrane Database of Systematic Reviews 2009, Issue 4.Art. No.: CD004977. DOI: 10.1002/14651858.CD004977.pub2.Lucero M, Du...
POOLED VACCINE EFFICACY AGAINST INVASIVE PNEUMOCOCCAL DISEASE WAS 80%.POOLED VACCINE EFFICACY AGAINST RADIOGRAPHIC PNEUMON...
ARI study group (Circa 1981-1990)Main goal: To conduct studies that would help DOH programs forthe control of childhood pn...
ARI study group (Circa 1991- 2000)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumon...
ARI study group (Circa 2001-2012)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumoni...
RITM-TOHOKU STUDY ON VIRAL AGENTS IN CHILDHOODPNEUMONIA, TACLOBAN, PHILIPPINES 2007-2011
ARI study group (2001-2012 and beyond – FUTURE STUDIES)Main goal: To conduct studies that would help the DOH in thecontrol...
Invasive Pneumococcal Disease (IPD) Caused by Nonvaccine SerotypesAmong Alaska Native Children With High Levels of 7-Valen...
ARI study group (2001-2012 and beyond – FUTURE STUDIES)Main goal: To conduct studies that would help the DOH in thecontrol...
VACCINATION AND THE PEDIATRIC MICROBIOME (2012-2014)Collaborative study with Jay Craig Venter Institute (JCVI), MarylandEx...
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
ARI - RITM Research Forum
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ARI - RITM Research Forum

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Presentation given by Dr. Marilla Lucero in the 31st Anniversary Celebration of the Research Institute for Tropical Medicine

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Transcript of "ARI - RITM Research Forum"

  1. 1. Control of Acute Respiratory Infections in children(or winning the battle against childhood pneumonia) Marilla Lucero RITM Research Forum April 23, 2012
  2. 2. Pathogens causing pneumonia in childrenAt least 1 respiratory pathogen was identified in 79% (122 of 154) of the patients. Pediatrics 2004 113: 701-7
  3. 3. Childhood pneumonia is the leading cause of death in children <5 years. 156 million new episodes worldwide Pneumonia is responsible for ~19% of all deaths in children < 5 years (70% in sub-Saharan Africa and South-East Asia) More than 2 million deaths/year due to pneumonia in children <5 years Slide courtesy ofRudan I. et al. Bull World Health Org. 2008, 86(5): 408-41 GSK
  4. 4. Pneumonia kills more children than any other illness. Pneumonia kills more children than AIDS, malaria and measles combined! Slide courtesy ofAdapted from Figure 4 of Black RE, et al. Lancet 2010;375:1969–1987. GSK
  5. 5. Pneumonia is the number 1 KILLER of Filipino children 1-59 mos of age! HIV Deaths 0% Pertussis 0% Pneumonia Injury Measles Diarrhea 1% accounts for NCD 8% 12% Meningitis 6% Malaria 34% of 16% 0% deaths in Other infections Filipino 23% Pneumonia children <5 yrs 34% old. SlideBlack RE et al for the Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national courtesy ofcauses of child mortality in 2008: a systematic analysis. Lancet 2010; 375: 1969–87 GSK
  6. 6. Our children are most vulnerable to pneumonia ! 350000 37 Filipino children 1-59 300000 months of age die from pneumonia every day 250000 (Black et al 2010,No. of cases Lancet) 200000 150000 100000 50000 0 < 1 yr 1-4 yrs 5-14 yrs 15-49 yrs50-64 yrs > 65 yrs Pneumonia and LRTI Slide courtesy of FHSIS NEC-DOH 2008 Report GSK
  7. 7. Slidecourtesy ofGSK
  8. 8. Etiology of pneumonia Pathogens causing pneumonia in children At least 1 respiratory pathogen was identified in 79% (122 of 154) of the patients.Pediatrics 2004 113: 701-7 Slide courtesy of GSK
  9. 9. Table 2.1. Review of 15 studies that reported results of 1133 lung aspirates in hospitalized children without prior antibiotic therapy Source: Berman S.: Acute Respiratory Infections. Infect Dis Clin North Am. 1991Bacterial Positive Number Number of studies with isolation rates of:Pathogens isolations (%) of studies ≤10% 11%-30% 31%-50% >50%Total pathogens 61 15 0 1 3 11Streptococcus 27 11 0 5 4 2pneumoniaeHaemophilus 26 11 1 8 2 0influenzaeStaphylococcus 17 9 4 4 1 0aureus
  10. 10. Factors to consider in the Control of ARI in childrenDisease Burden – Developing CountriesRisk Factors – Lack of immunization,Malnutrition etcEtiology – Streptococcus pneumoniae,Haemophilus influenzae
  11. 11. ARI study group (Circa 1981-1990)Main goal: To conduct studies that would help DOH programs forthe control of childhood pneumonia1. Etiology studies: Hospital-based studies on etiology2. Risk Factors: Community-based studies on child-care practices Risk Factors for Morbidity3. Treatment: Clinical trials on antibiotics against pneumonia4. Diagnosis of pneumonia in the Field: Study of signs and symptoms of childhood pneumonia5. Field trial of the WHO ARI control program
  12. 12. Assumptions supporting the early development of WHO-ARI Control Program1. High mortality from ARI – due to a. pneumonia (70% of deaths) b. vaccine-preventable ARI: diphtheria, pertussis (whooping cough), and measles (30% of deaths).
  13. 13. 2. High mortality from pneumonia was due to a high incidenceof bacterial pneumoniaa. Streptococcus pneumoniae and Haemophilus influenzaeb. Sp and Hi - sensitive to co-trimoxazole, penicillin, amoxicillin, chloramphenicolc. pneumonia diagnosis and severity - determined by simple meansd. mothers could be trained to recognize the danger signs of pneumoniae. community health workers could be trained to diagnose and treat pneumonia correctly.3. Programs based on the treatment of pneumonia withantimicrobial agents would reduce mortality from pneumoniain developing countries
  14. 14. Tupasi TE, Lucero MG, Magdangal DM et al. Reviews Inf Dis 1990
  15. 15. WHO – PNEUMONIA CONTROL PROGRAM: The ARI Bohol study 1983-1990
  16. 16. Table 5.8: Cause-specific age-standardized mortality rates for children 0-4 years by time and area, and efficacy index E (%)Cause of death Death rate Efficacy of 2-sided (per 1000 person-years) intervention (%) p value (E)All causes NIA IAYears 1-4 14.95 17.08 22.50 0.009Years 5-6 11.96 10.59PneumoniaYears 1-4 3.96 5.08 49.76 0.001Years 5-6 3.15 2.03Spin -offYears 1-4 6.92 7.54 27.98 0.039Years 5-6 5.9 4.63Non-targetYears 1-4 4.06 4.46 -22.52 0.401Years 5-6 2.92 3.93
  17. 17. Polysaccharide vaccine ----Immunogenic only in adultsPolysaccharide vaccine conjugated toprotein carrier = Immunogenic in infantsHib conjugate vaccine proven to beefficacious in reducing Hib invasivedisease
  18. 18. CONCLUSION: THIS HEPTAVALENT PNEUMOCOCAL CONJUGATEVACCINE APPEARS TO BE HIGHLY EFFECTIVE IN PREVENTING INVASIVEDISEASE IN YOUNG CHILDREN.
  19. 19. Efficacy of an 11-valent pneumococcal conjugatevaccine (11PCV) in preventingradiographically confirmed pneumonia in children < 2years of age:a randomized, double-blind, placebo-controlled trialin the PhilippinesSponsor: ARIVAC ConsortiumSEROTYPES11-valent pneumococcal conjugate vaccine (11PCV) or saline placebo (randomized 1:1)• 11PCV with serotypes: 1, 3, 5, 7F, 4, 6B, 9V, 14, 18C, 19F, 23F
  20. 20. Endpoint 11PCV Placebo Vaccine Efficacy N Rate N RateRadiographic 93 1040 120 1349 22.9 pneumonia (-1.1;41.2)WHO clinical 0.1pneumonia 934 10,448 930 10,454 (-9.4;8.7)
  21. 21. Cochrane Database of Systematic Reviews 2009, Issue 4.Art. No.: CD004977. DOI: 10.1002/14651858.CD004977.pub2.Lucero M, Dulalia V, Nillos L et al. META-ANALYSIS OF PNEUMOCOCCAL CONJUGATE VACCINES
  22. 22. POOLED VACCINE EFFICACY AGAINST INVASIVE PNEUMOCOCCAL DISEASE WAS 80%.POOLED VACCINE EFFICACY AGAINST RADIOGRAPHIC PNEUMONIA WAS 19%.POOLED VACCINE EFFICACY AGAINST WHO-Defined Clinical PNEUMONIA WAS 6%.
  23. 23. ARI study group (Circa 1981-1990)Main goal: To conduct studies that would help DOH programs forthe control of childhood pneumonia1. Etiology studies: Hospital-based studies on etiology2. Risk Factors: Community-based studies on child-care practices Risk Factors for Morbidity3. Treatment: Clinical trials on antibiotics against pneumonia4. Diagnosis of pneumonia in the Field: Study of signs and symptoms of childhood pneumonia5. Field trial of the WHO ARI control program
  24. 24. ARI study group (Circa 1991- 2000)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumonia1. Hib conjugate vaccine immunogenicity studies2. Pneumococcal conjugate vaccine immunogenicity studies3. Pneumococcal conjugate vaccine trial
  25. 25. ARI study group (Circa 2001-2012)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumonia1. Influenza studies (Surveillance, Burden of Disease)2. Etiology studies on childhood pneumonia (RITM-TOHOKU)3. Monitoring of novel viruses (RITM-TOHOKU)
  26. 26. RITM-TOHOKU STUDY ON VIRAL AGENTS IN CHILDHOODPNEUMONIA, TACLOBAN, PHILIPPINES 2007-2011
  27. 27. ARI study group (2001-2012 and beyond – FUTURE STUDIES)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumonia1. Influenza studies (Surveillance, Burden of Disease)2. Etiology studies on childhood pneumonia (RITM-TOHOKU)3. Monitoring of novel viruses (RITM-TOHOKU)4. Etiology studies – adult pneumonia (RITM-TOHOKU)5. Other vaccine studies (RSV, Other PCVs?)6. Monitoring of pneumococcal strains from IPD cases7. MICROBIOME STUDIES
  28. 28. Invasive Pneumococcal Disease (IPD) Caused by Nonvaccine SerotypesAmong Alaska Native Children With High Levels of 7-ValentPneumococcal Conjugate Vaccine Coverage. Singleton, Henessy, Bulkow etal. REPLACEMENT PHENOMENON
  29. 29. ARI study group (2001-2012 and beyond – FUTURE STUDIES)Main goal: To conduct studies that would help the DOH in thecontrol of childhood pneumonia1. Influenza studies (Surveillance, Burden of Disease)2. Etiology studies on childhood pneumonia (RITM-TOHOKU)3. Monitoring of novel viruses (RITM-TOHOKU)4. Etiology studies – adult pneumonia (RITM-TOHOKU)5. Other vaccine studies (RSV, Other PCVs?)6. Monitoring of pneumococcal strains from IPD cases7. MICROBIOME STUDIES
  30. 30. VACCINATION AND THE PEDIATRIC MICROBIOME (2012-2014)Collaborative study with Jay Craig Venter Institute (JCVI), MarylandExploratory study to define the nasopharyngeal (NP) microbiome (collection of microbes) from birth to 12 months of age using metagenomic DNA sequencing techiniquesWhat organisms comprise the microbiome? Abundances? Relative abundance over time.Does microbiome structure change with infants’ health?Change of microbiome after vaccination with PCV?Findings could lead to development of tool to identify children at risk for disease because of an altered NP microbiome.THANK YOU!

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