Emerging concepts in pneumococcal disease prevention in India sept 2011

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Latest information about Pneumococcal disease and its prevention from Indian perspective - as of sept 2011.
Covers latest Pneumonet data, and review from other studies like IBIS, ANSORP etc.

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  • Key Points Welcome to the CME on Pneumococcal infections and their prevention in children
  • 26
  • Key Points As per the O’Brien report in Lancet 2009, India tops the countries with the greatest number of pneumococcal deaths in children under 5 years, ahead of China which has a higher population.
  • Key Points The Millennium Development Goal 4 aims to reduce mortality in children younger than 5 years by two-thirds between 1990 and 2015. However looking at this graph for 60 priority countries (including India), it seems we are still far away from that goal.
  • Key Points PneumoNET is the recent study that has been done to assess the burden of invasive pneumococcal disease in India
  • Key Points There is a paucity of data from India (and also Asia) on the disease burden due to Streptococcus pneumoniae (SP). Data on IPD are scarce. Hence this study was planned first to form a network of hospitals in India and conducted to assess the burden of invasive pneumococcal disease). One year data will be discussed.
  • Key Points The primary objective of this study was to Estimate incidence rates of IPD and pneumonia, as well as serotype distribution and antibiotic susceptibility of SP in children aged 28 days to <60 months in a defined target population in India. The secondary objectives were Estimate the incidence rate of clinical pneumonia and chest radiograph-confirmed pneumonia with or without pneumococcal bacteremia. Describe the antibiotic resistance rates of invasive SP isolates. Describe the serotype distribution of resistant SP isolates.  
  • Key Points This was a two-year active, prospective, hospital-based surveillance study of IPD and pneumonia in children aged 28 days to <60 months presenting at 1 of 3 hospitals in Bangalore South Zone, India. The population under surveillance in and around the area was defined demographically and geographically to estimate pneumococcal disease rates.   After obtaining the basic history from the suspected cases, a blood specimen was collected upon enrolment. Cerebrospinal fluid (CSF) was collected for culture with suspected meningitis. Specimens from other sterile sites (e.g. pleural fluid) were collected as per routine medical practice. All samples underwent bacterial culture at the local laboratory, according to standard methodology, for identification of pathogens and reported microbiologic results as per their standard operating procedures. SP isolates were sub-cultured and sent to the central laboratory for confirmation of identification, serotyping and susceptibility testing. A chest radiograph (CXR) was obtained for children with clinically suspected pneumonia. The study included children residing within the defined catchment area aged 28 days to ≤36 months with a measured temperature or history of measured temperature ≥39.0°C in 24 hours prior to screening, or clinical suspicion of pneumonia, meningitis, sepsis, or other IPD regardless of temperature; OR children aged >36 months to <60 months with clinical suspicion of pneumonia, meningitis, sepsis, or other IPD regardless of temperature.
  • Key Points A total of 5,249 subjects were enrolled into the study from the calculated at-risk population of 112,483 children aged between 28 days and <60 months who resided within the defined catchment area in Bangalore. Mean age was 19.8 months and 66.5% of subjects were aged 28 days to <24 months ( Table 1 ). Overall 17 children were diagnosed with IPD. Prior pneumococcal conjugate vaccination occurred in 0.3% of all enrolled subjects and none of the IPD cases. Hospitalization was required for 17.5% of the subjects enrolled and occurred more commonly in those aged <24 months
  • Key Points 17 subjects with IPD resulted in an overall estimated incidence rate for IPD of 15.11 per 100,000 children. Six of the 17 cases occurred in subjects aged 6 months to <12 months, resulting in an estimated incidence rate of 46.01 per 100,000 for this specific age group ( Table 2 ). Final IPD cases observed were pneumonia in 12 subjects, meningitis in 3 subjects, and bacteraemia in 2 subjects. The overall estimated incidence rates for pneumonia, meningitis, and bacteraemia were 10.67, 2.67, and 1.78 per 100,000 children, respectively
  • Key Points Overall, positive culture growth was obtained in 432 (8.2%) of the 5,249 enrolled subjects. Percentages of total growth were as follows: Salmonella sp . 60 (13.9%); Streptococcus pneumonia 27 (6.3%); Staphylococcus hominis 41(9.5%); Micrococcus sp . 32 (7.4%); Staphylococcus epidermidis 24 (5.6%); Staphylococcus aureus 19 (4.4%). SP was detected and serotype information obtained in 17 subjects (n=18 serotypes). In 1 subject isolates grown from CSF and blood were of 2 different serotypes (CSF=6A and blood=3). Distribution of the serotypes isolated is shown in Table 3 ; 6A and 5 were seen most frequently. The serotype coverage offered by PCV7, PCV10, and PCV13 was 27.77%, 55.55%, and 100%, respectively. Four of the 18 isolates were resistant to trimethoprim/sulfamethoxazole, 3 to erythromycin, and 1 to ceftriaxone. Antibiotic resistance was observed for serotypes 6A, 14, 1, 3, and 19A.
  • Key Points Overall, positive culture growth was obtained in 432 (8.2%) of the 5,249 enrolled subjects. Percentages of total growth were as follows: Salmonella sp . 60 (13.9%); Streptococcus pneumonia 27 (6.3%); Staphylococcus hominis 41(9.5%); Micrococcus sp . 32 (7.4%); Staphylococcus epidermidis 24 (5.6%); Staphylococcus aureus 19 (4.4%). SP was detected and serotype information obtained in 17 subjects (n=18 serotypes). In 1 subject isolates grown from CSF and blood were of 2 different serotypes (CSF=6A and blood=3). Distribution of the serotypes isolated is shown in Table 3 ; 6A and 5 were seen most frequently. The serotype coverage offered by PCV7, PCV10, and PCV13 was 27.77%, 55.55%, and 100%, respectively. Four of the 18 isolates were resistant to trimethoprim/sulfamethoxazole, 3 to erythromycin, and 1 to ceftriaxone. Antibiotic resistance was observed for serotypes 6A, 14, 1, 3, and 19A.
  • Key Points This is the first study documenting the prevalence of the emerging serotypes (3, 6A and 19A) in Indian context. Serotypes 3, 6A and 19A were responsible for 44.45% of the disease caused by SP and this is a big number. This also points towards a trend of increasing prevalence of these emerging serotypes. This study also documents the presence of serotypes 1 and 5 (both 27.78%). The sample size was small (n=18 isolates). Just compare to IBIS which was done over 4 years, and there also the sample size was 103 (children less than 5 years). It is very difficult to isolate, and culture SP. But looking at the results, the trend is evident. The serotypes covered by PCV13 are there in India The overall incidence of IPD was 15.11 per 100,000 children and this is a high number. The incidence is very high in the first year of life. This finding covers up for the limited sample size in this 1 year population. When it came to antibiotic resistance, four of the 18 isolates were resistant to trimethoprim/sulfamethoxazole, 3 to erythromycin, and 1 to ceftriaxone. Antibiotic resistance was observed for serotypes 6A, 14, 1, 3, and 19A. Observe here that antibiotic resistance has been seen with the 3 emerging serotypes (3, 6A, and 19A), thus justifying why these are included in PCV13 The highest incidence of clinical pneumonia and chest X-ray plus pneumonia was in children less than 6 months of age. This again supplements the findings from CHERG report and the Million Death Study (Pneumonia remains the leading cause of neonatal mortality in India). The study analysis is only for the first year only. We await the results of the 2 nd year
  • Key Points Recently there has been an increase in serotype 19A. In fact in USA, it represents 5% of all isolates and is the most common non vaccine serotype displaying penicillin resistance.
  • Key Points Before the PneumoNET study, the first report on 19A incidence in India came out in the ANSORP study done in 10 Asian countries. In fact the incidence of serotype 19A was high in India (13%) and the clone ST320 associated with multidrug resistance was present in 66.6% of isolates. This report clearly demonstrates the rising incidence of serotype 19A in the country.
  • Key Points With over a decade of use across the world, PCV7 has NOT ONLY demonstrated its effectiveness in reducing IPD, Pneumonia, OM BUT ALSO has played a vital role in decreasing NP carriage, Antibiotic resistance, and visits to health care professionals. Thus truly demonstrating cost-effectiveness
  • Key Points PCV7 has a proven efficacy and over the last decade has shown the real world effectiveness in reducing the burden of IPD, Pneumonia, OM, and nasopharyngeal carriage. Also it has demonstrated herd immunity
  • Key Points This slide provides an overview of some of the key serotypes not included in PREVENAR that cause pneumococcal disease worldwide.
  • Key Points At the request of WHO, PneumoADIP researchers at the Johns Hopkins University School of Medicine conducted an analysis of the estimated serotype distribution of ENI among children <5 years of age worldwide. 1 Every WHO region was represented in the analysis, which was comprised of data from 169 studies conducted from 1980 to 2007. 1 The data above show the estimated coverage of ENI in young children (<5 years of age) by each of 3 pneumococcal conjugate vaccines, according to WHO region. PCV13 has the potential to cover at least 73.9% of the ENI in young children worldwide. 2 References GAVI PneumoADIP. Baltimore, MD: Johns Hopkins School of Public Health. November 30, 2008. http://www.vaccineamc.org/files/TPP_codebook.pdf. Accessed September 7, 2009. Dinleyici E, et al. Expert Rev Vaccines. 2009;8:977-986.
  • Key Points PCV13 has been tested for immunogenicity and safety in different clinical programs in various countries of the world including India.
  • Key Points PCV13 is indicated for Normal Healthy Children. But the question always everybody asks is whether it has a role in high risk children. The MMWR 2011 recommendations now extend the use of PCV13 beyond 2 years. i.e. it can be used in children from 2-18 years of age in high risk children. PPV23 can then be used after PCV13 administration.
  • Key Points The IAP Immunization Guidebook 2011 also recommends that PPV23 should be administered after PCV among high risk children aged 2-18 years as mentioned in the slide. It is but apparent that pneumococcal disease is a serious problem and needs to be prevented
  • Key Points Which vaccine to use where? This is the questions most of us have in mind. The above table shows the differences between the two vaccines.
  • Key Points Pneumococcal disease is the #1 vaccine-preventable cause of death worldwide in children aged <5 years 1 Prevenar 13 offers the broadest coverage of pneumococcal serotypes available in a conjugated vaccine 2,3 Prevenar 13, built on the scientific foundation of Prevenar, includes 6 additional serotypes 4 Convenient transition to Prevenar 13 can be done at any point in the recommended vaccination schedule 4 A single dose of Prevenar 13 in children previously vaccinated with Prevenar provides protection against 6 additional serotypes 5 References WHO 2004 Global Immunization Data. http://www.who.int/immunization_monitoring/ data/GlobalImmunizationData.pdf. Accessed September 3, 2009. Dinleyici E, et al. Expert Rev Vaccines. 2009;8:977-986. GAVI Pneumococcal AMC TPP, Nov 2008. http://www.vaccineamc.org/files/TPP_codebook.pdf. Accessed September 3, 2009. Prevenar 13. Summary of Product Characteristics. Wyeth Pharmaceuticals. Data on file, Pfizer Inc.
  • Emerging concepts in pneumococcal disease prevention in India sept 2011

    1. 1. Emerging Concepts in Pneumococcal Disease prevention in India Dr Gaurav Gupta, Pediatrician, Member AAP, IAP, Charak Clinics, Mohali
    2. 2. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    3. 3. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    4. 4. Pneumococcal Disease <ul><li>S. pneumoniae first isolated by Pasteur in 1881 </li></ul><ul><li>90 known serotypes </li></ul><ul><li>First U.S. vaccine in 1977 (14 valent PPV) </li></ul><ul><li>PCV 7 launched in 2000 </li></ul><ul><li>Polysaccharide capsule important virulence factor </li></ul><ul><li>Type-specific antibody is protective </li></ul>
    5. 5. DISEASES CAUSED BY STREPTOCOCCUS PNEUMONIAE <ul><li>Non-invasive disease </li></ul><ul><li>Sinusitis </li></ul><ul><li>Otitis media </li></ul><ul><li>Pneumonia </li></ul>Musher, in Principles and Practice of Infectious Diseases, 1995 <ul><li>Invasive disease </li></ul><ul><li>Bacteraemia (blood) </li></ul><ul><li>Meningitis (CNS) </li></ul><ul><li>Endocarditis (heart) </li></ul><ul><li>Peritonitis (body cavity) </li></ul><ul><li>Septic arthritis (bones and joints) </li></ul><ul><li>Others (appendicitis, salpingitis, soft-tissue infections) </li></ul>PNEUMOCOCCAL INFECTION
    6. 6. Strep Pneumoniae in developing countries
    7. 7. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    8. 8. Child DEATHS Each Dot = 5,000 child deaths Black RE. The Lancet 2003; 361: 2226-2234 We are No. 1
    9. 9. PNEUMONIA AND INDIA Pneumonia remains the leading killer of children 1 410,000 children < 5 die of pneumonia every year 1,2 25% of all child deaths are due to pneumonia 3 Meta-analysis of 4 CTs suggest 30-40% of all severe pneumonia in children is pneumococcal. In Indian context, around 123,000 to 164,000 children <5 years die annually from pneumococcal pneumonia 1 <ul><li>Levine OS et al Indian Pediatrics 2007; 44:491-496 </li></ul><ul><li>Pneumonia – The forgotten killer of children, WHO, UNICEF, 2006 </li></ul><ul><li>Thacker N. IPD burden - An Indian Perspective. Pediatrics Today 2006; 9(4): 208-213 </li></ul>
    10. 10. Countries with the greatest number of pneumococcal deaths among children under 5 years O,Brien K, et al. Lancet. 2009;374:893-902. PNEUMOCOCCAL DISEASE BURDEN TOP TEN 1
    11. 11. Strep Pneumoniae & Pneumonia – Indian Disease Burden <ul><li>In India, Pneumonia is the single most important cause of death among children in the postneonatal period, contributing as much as 27.5% of total under-five mortality </li></ul><ul><li>It appears that about 10-15% of childhood pneumonias are caused by H. influenzae and RSV each; and 12-35% by pneumococcus. * </li></ul>* Mathew J et al. ARI & Pneumonia in India – A systematic review . Indian Pediatrics, March 2011
    12. 12. We are missing the target (Millennium Development Goal 4) AAR =average annual rate of reduction MDG=millennium development goal U5MR in 2015 at current AAR MDG Target U5MR in 2015 85 38 Under-five mortality ratio (U5MR) projections 60 priority countries Source: UN Population Division World Population Prospects, 2004.
    13. 13. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    14. 14. PneumoNET Pan Asia Epidemiologic surveillance network to assess the burden of invasive pneumococcal disease (IPD) Nisarga RG, Balter I, Premalatha R et al, Prospective, Multinational, Active, Hospital-Based Epidemiologic Surveillance for IPD and Pneumonia Burden Among Children in Bangalore South Zone, Bangalore, India. Poster presented at the 29th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), 7–11 June 2011, The Hague, Netherlands
    15. 15. PNUEMONET… (1 year data) <ul><li>BACKGROUND </li></ul><ul><li>S. pneumoniae - key cause of meningitis, pneumonia and other invasive diseases leading to high morbidity/mortality in children worldwide </li></ul><ul><li>Information in countries varies between countries not robust, and usually coming from passive microbiology surveillance data </li></ul><ul><li>Study done at 3 hospitals in Bangalore South Zone (Kempegowda Institute of Medical Sciences Hospital, Vanivilas Hospital, and Indira Gandhi Institute of Child Health) </li></ul>
    16. 16. PNUEMONET… (1 year data) <ul><li>OBJECTIVES </li></ul><ul><li>Primary </li></ul><ul><ul><ul><li>Estimate - Incidence rates of IPD and pneumonia, </li></ul></ul></ul><ul><ul><ul><li>Serotype distribution and antibiotic susceptibility of SP </li></ul></ul></ul><ul><ul><ul><li>in children aged 28 days to <60 months in a defined target population in India </li></ul></ul></ul><ul><li>Secondary </li></ul><ul><ul><ul><li>Describe the antibiotic resistance rates of invasive SP isolates </li></ul></ul></ul><ul><ul><ul><li>Describe the serotype distribution of resistant SP isolates </li></ul></ul></ul><ul><ul><ul><li>Estimate the incidence rate of clinical pneumonia and chest </li></ul></ul></ul><ul><ul><ul><li>radiograph-confirmed pneumonia with or without pneumococcal </li></ul></ul></ul><ul><ul><ul><li>bacteremia </li></ul></ul></ul>
    17. 17. PNUEMONET… (1 year data) <ul><li>DESIGN OF THE STUDY </li></ul><ul><li>Two -year active, prospective, hospital-based surveillance study of IPD and pneumonia </li></ul><ul><li>Children aged 28 days to <60 months </li></ul><ul><li>History taken </li></ul><ul><li>Blood sample </li></ul><ul><li>Cerebrospinal fluid (CSF) was collected for culture with suspected meningitis </li></ul><ul><li>Specimens from other sterile sites (e.g. pleural fluid) were collected as per routine </li></ul><ul><li>medical practice </li></ul><ul><li>All samples underwent bacterial culture for identification of pathogens </li></ul><ul><li>SP isolates were sub-cultured, serotyped and tested for antibiotic susceptibility </li></ul><ul><li>Chest radiograph (CXR) was obtained for children with clinically suspected pneumonia </li></ul>
    18. 18. PNUEMONET … (1 year data) RESULTS 1) Demographics <ul><li>SD – Standard Deviation </li></ul>SD – Standard Deviation Table 1: Demographics of Enrolled Children Variable N = 5,249 Age in months (Mean + SD) 19.8±13.9 <ul><li>Age group n (%) </li></ul><ul><li>28 days to <6 months </li></ul><ul><li>6 months to <12 months </li></ul><ul><li>12 months to <24 months </li></ul><ul><li>24 months to <36 months </li></ul><ul><li>36 months to <60 months </li></ul>806 (15.4) 1,132 (21.6) 1,551 (29.5) 1,082 (20.6) 678 (12.9) <ul><li>Gender, n (%) </li></ul><ul><li>Male </li></ul><ul><li>Female </li></ul>2,901 (55.3) 2,348 (44.7)
    19. 19. PNUEMONET … (1 year data) RESULTS 2) Incidence Rates * Calculated using number of cases divided by number in At-risk population * Calculated using number of cases divided by number in At-risk population <ul><li>Final IPD cases observed were pneumonia (n=12), meningitis (n=3), bacteraemia (n=2) </li></ul><ul><li>Overall estimated incidence rates for pneumonia, meningitis, and bacteraemia were 10.67, </li></ul><ul><li>2.67, and 1.78 per 100,000 children, respectively </li></ul>Table 2: Incidence Rates of IPD by Age Group Age Group No. of Cases No. in At-risk Population Incidence Rate per 100,000 children* (95% CI) 28 days to <6 months 3 8,186 36.65 (7.56–107.10) 6 months to <12 months 6 13,040 46.01 (16.89–100.15) 12 months to <24 months 3 22,777 13.17 (2.72–38.49) 24 months to <36 months 4 22,470 17.80 (4.85–45.58) 36 months to <60 months 1 46,010 2.17 (0.06–12.11) Overall 17 112,483 15.11 (8.80–24.20)
    20. 20. PNUEMONET… (1 year data) RESULTS 3) BACTERIOLOGY AND ANTIBIOTIC RESISTANCE a – In 1 subject 2 different serotypes were obtained from blood and CSF (6A in CSF and 3 in blood) b – Antibiotic susceptibility was determined for 17 isolates only Table 3: Serotype Distribution and Antibiotic Resistance of IPD Isolates From Children Aged 28 Days to <60 Months (18 Isolates a ) Serotype N (%) Antibiotic Resistance b 6A 5 (27.78%) Erythromycin (2 isolates) Ceftriaxone (1 isolate) 5 3 (16.67%) 1 2 (11.11%) Trimethoprim/Sulfamethoxazole (1 isolate) 3 2 (11.11%) Trimethoprim/Sulfamethoxazole (1 isolate) 14 2 (11.11%) Erythromycin (1 isolate) Trimethoprim/Sulfamethoxazole (1 isolate) 9V 1 (5.56%) 19F 1 (5.56%) 18C 1 (5.56%) 19A 1 (5.56%) Trimethoprim/Sulfamethoxazole (1 isolate)
    21. 21. PNUEMONET… (1 year data) RESULTS 4) BACTERIOLOGY AND ANTIBIOTIC RESISTANCE <ul><li>Serotypes 6A and 5 were seen most frequently. </li></ul><ul><li>The serotype coverage offered by PCV7, PCV10, and PCV13 was 27.77%, 55.55%, and 100%, respectively. </li></ul><ul><li>Four of the 18 isolates were resistant to trimethoprim/ </li></ul><ul><li>sulfamethoxazole, 3 to erythromycin, and 1 to ceftriaxone </li></ul>
    22. 22. PNUEMONET… (1 year data) <ul><li>KEY MESSAGES </li></ul><ul><li>IPD and Pneumonia - important causes of morbidity in the children <5 </li></ul><ul><li>years </li></ul><ul><li>Most common IPD was pneumonia – 12/17 subjects (10.67 per 100,000) </li></ul><ul><li>Highest incidence of ClinPn and CXR+Pn was in children < 6 months </li></ul><ul><li>Antibiotic resistance observed for serotypes 6A, 14, 1, 3 and 19A </li></ul><ul><li>Second year results awaited </li></ul>
    23. 23. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    24. 24. Antimicrobial resistance data – Other studies <ul><li>IBIS (Lancet.1999) </li></ul><ul><ul><li>56% cotrimoxazole resistance. </li></ul></ul><ul><ul><li>Resistance to penicillin rare (1.3%), </li></ul></ul><ul><ul><li>No resistance to third generation cephalosporins. </li></ul></ul><ul><li>ISCAP trial (BMJ. 2004) </li></ul><ul><ul><li>Cotrimoxazole 66.3%, </li></ul></ul><ul><ul><li>Chloramphenicol 9.0%, </li></ul></ul><ul><ul><li>Oxacillin 15.9% </li></ul></ul><ul><ul><li>Erythromycin 2.8%. </li></ul></ul><ul><li>Conclusion - Variable resistance to common antibiotics; penicillin resistance is uniformly low and cotrimoxazole resistance high. * </li></ul>* Mathew J et al. ARI & Pneumonia in India – A systematic review . Indian Pediatrics, March 2011
    25. 25. 19A Streptococcus pneumoniae <ul><li>Recently there has been an increase in the number of infections caused by serotype 19A in countries that have incorporated PCV7 into national schedules as well as those that have not 1-3 </li></ul><ul><li>Globally serotype 19A represents ~5% of all isolates and in t he U.S. represents the most common non-vaccine serotype 4-5 </li></ul><ul><li>IPD infections: 301% increase in children <5 years of age </li></ul><ul><li> 173% increase in adults >80 years of age </li></ul><ul><li>OM infections: Reports of multidrug resistant cases 6 </li></ul><ul><li>Usually serotype 19A is penicillin resistant </li></ul><ul><li>Singleton RJ, et al. JAMA .2007:297:1784-1792. </li></ul><ul><li>Pai R, et al. J Infect Dis. 2005;192:1988-1995. </li></ul><ul><li>Dagan R, et al. Poster presented at . 47 th Interscience Conference on Antimicrobial </li></ul><ul><li>Agents and Chemotherapy (CIAAC); September 17-20, 2007; Chicago, IL. </li></ul><ul><li>4. PneumoADIP, GSP Summary Report for Sage 2007. </li></ul><ul><li>5. Kaplan SL, et al. Pediatrics . 2010; 125:429-436. </li></ul><ul><li>Pichichero ME, Case JR. JAMA . 2007:298:1772-1178. </li></ul><ul><li>Harrison CJ, et. J Antimicrob Chemother . 2009:511-519. </li></ul>
    26. 26. 19A S. pneumoniae: INDIA <ul><li>Serotype 19A - key emerging problem in 10 Asian countries including India </li></ul><ul><li>Of invasive S. pneumoniae isolates 91/1637 (5.6%) were serotype 19A </li></ul><ul><li>Prevalence was high in India (13.0%), Japan (11.1%), Korea (9.9%), Malaysia </li></ul><ul><li>(9.1%), and Saudi Arabia (9.0%), but low in Hong Kong (3.1%) Taiwan (4.8%), </li></ul><ul><li>Thailand (5.2%), the Philippines (1.7%), and Vietnam (0.4%) </li></ul><ul><li>ST320 as the most prevalent clone among 19A was identified (MDR) – a global </li></ul><ul><li>emerging problem </li></ul><ul><li>ST320 isolates were evident in Hong Kong , India , Korea, Malaysia, Saudia, Taiwan </li></ul><ul><li>In India ST 320 was present in 66.6% of 19A </li></ul><ul><li>First published article that documents 19A incidence in India </li></ul>Juyoun S, Jin YB, So HK et al. Predominance of ST320 among Streptococcus pneumoniae serotype 19A isolates from 10 Asian countries. Journal of Antimicrobial Chemotherapy Advance 2011; 66: 1001–1004
    27. 27. Serogroup distribution in India Prospective multicentre hospital surveillance of Streptococcus pneumoniae disease in India IBIS Group. The Lancet 1999; 353: 1216-1221 6A+6B 19A+19F 14 4 5 7 1 23 18 9 IBIS Group. The Lancet 1999; 353: 1216-1221
    28. 28. Serogroup distribution of SP in India – Summary of 4 studies <ul><li>Among 150 clinical isolates * from invasive pneumococcal infections, 59.3% belonged to serotypes 1 , 6, 19 , 5 , 23 and 7 . </li></ul><ul><ul><li>Serotype 1 was the commonest isolate in meningitis and empyema. </li></ul></ul><ul><li>Among 42 pneumococcal strains **, over one-third in children were serotypes 5 , 6 and 7 </li></ul><ul><li>ANSORP Study - 1105 isolates from 4963 children across 11 countries Nasopharyngeal carriage </li></ul><ul><ul><li>Prevalence was 22.3%; highest in India (43.2%) and lowest in Singapore (9%) </li></ul></ul><ul><ul><li>Most common were 6 , 23, 19 and 14 which comprised 60% of the isolates </li></ul></ul><ul><li>PNEUMONET – 6 A , 5 , 1 , 3 & 14 were commonest strains </li></ul>* Kanungo R. Indian J Med Res. 2001 ** John TJ. Indian J Med Res.1996
    29. 29. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    30. 30. Impact of Vaccination With PCV7 IPD=invasive pneumococcal disease. OM=otitis media. IPD Pneumonia Antibiotic Resistance and Use of Antibiotics OM Carriage Indirect Effect Office Visits Cost-effectiveness
    31. 31. Efficacy and Effectiveness of PCV7 <ul><li>Proven Efficacy: </li></ul><ul><ul><li>Invasive disease </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>OM </li></ul></ul><ul><li>Proven Effectiveness: </li></ul><ul><ul><li>Invasive disease </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>OM </li></ul></ul><ul><ul><li>NP colonization </li></ul></ul><ul><ul><li>Herd immunity </li></ul></ul>
    32. 32. Key Serotypes Worldwide <ul><li>Hausdorff WP. Vaccine. 2007;25:2406-2412. </li></ul><ul><li>Hausdorff WP, et al. Lancet Infect Dis. 2005;5:83-93. </li></ul><ul><li>GAVI Pneumococcal AMC TPP, Nov 2008. http://www.vaccineamc.org/ files/TPP_codebook.pdf. Accessed September 3, 2009. </li></ul><ul><li>Ruckinger S, et al. Pediatr Infect Dis J. 2009;28:118-122. </li></ul><ul><li>Rodgers GL, et al. Vaccine . 2009;27:3802-3810. </li></ul><ul><li>Pichichero ME, Casey JR. JAMA . 2007;298:1772-1778. </li></ul><ul><li>Rajasingham CR, et al. Pediatr Infect Dis J . 2008;27:771-775. </li></ul><ul><li>Kyaw MH, et al. N Engl J Med . 2006;354;1455-1463. </li></ul><ul><li>Dagan R, et al . J Infect Dis. 2009;199:776-785. </li></ul>Serotype Clinical Implications Serotype 1 High prevalence in many regions of the world Associated with Epidemic outbreaks 1 Causes complicated pneumonia (with empyema) , especially in children aged 2 -5 years 2 Serotype 5 Associated with Epidemic outbreaks (along with serotype 1 account for 29 % IPD in India) Common serotype in Latin America and Africa 3 <ul><ul><li>Serotype 7F </li></ul></ul><ul><ul><li>Increasingly important cause of IPD , particularly in Europe and North America </li></ul></ul><ul><ul><li>High case-fatality rate compared with other serotypes 4 </li></ul></ul><ul><ul><li>Serotype 3 </li></ul></ul>Among the most common isolates in older children. 5,6 Associated with severe childhood pneumonias & lung necrosis 2 <ul><ul><li>Serotype 6A </li></ul></ul>Associated with antibiotic resistance 2 Commonly found in nasopharyngeal isolates 2 <ul><ul><li>Serotype 19A </li></ul></ul>Increasingly important cause of serious pneumococcal disease 7-9 Most common serotype in nasopharyngeal colonisation 9 Increasingly resistant to antibiotics and has been associated with multidrug resistance 9
    33. 33. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    34. 34. Vaccine Efficacy studies <ul><li>Cochrane review (2009) – 113,044 children worldwide (Africa, US, Finland & Philippines) </li></ul><ul><li>IPD by vaccine serotypes – 80 % </li></ul><ul><li>IPD by any serotype – 58 % </li></ul><ul><li>radiological pneumonia - 27% </li></ul><ul><li>clinical pneumonia 6% </li></ul><ul><li>All-cause mortality 11% </li></ul>Lucero MG, Dulalia VE, Nillos LT, Williams G, Parreño RAN, Nohynek H, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev. 2009;4:CD004977.
    35. 35. Vaccine Efficacy studies <ul><li>Systematic review from developing countries (9 & 11 valent vaccines) </li></ul><ul><li>Radiological pneumonia – 26 % </li></ul><ul><li>Clinical pneumonia 7 % </li></ul><ul><li>Clinically severe pneumonia 7 % </li></ul><ul><li>All-cause mortality 15 % </li></ul>Theodoratou E, Johnson S, Jhass A, Madhi SA, Clark A, Boschi-Pinto C, et al. The effect of Haemophilus influenzae type b and pneumococcal conjugate vaccines on childhood pneumonia incidence, severe morbidity and mortality. Int J Epidemio.l 2010;39 Suppl 1:i172-85
    36. 36. Vaccine Efficacy studies <ul><li>Systematic review (2009) </li></ul><ul><li>IPD by vaccine serotypes – 89 % </li></ul><ul><li>IPD by any serotype – 63% to 74% </li></ul>Pavia M, Bianco A, Nobile CG, Marinelli P, Angelillo IF. Efficacy of pneumococcal vaccination in children younger than 24 months: a meta-analysis. Pediatrics. 2009;123:e1103-10.
    37. 37. S. pneumoniae Conjugate vaccines, Potential vaccine protection Cobertura de serotipos calculada a partir de datos del Global Serotype Project (GSP) 1980 - Jun 2007. Dinleyici E, et al. Expert Rev Vaccines. 2009;8:977-986. GAVI Pneumococcal AMC TPP, Nov 2008. http://www.vaccineamc.org/files/TPP_codebook.pdf. Accessed September 3, 2009. % Neumococcal disease caused by different serotypes included into the conjugated Africa (%) Asia (%) Europa (%) Latin America (%) North América (%) Oceania (%) PCV7 39.3% 48% 67.1% 54.4% 78.1% 64.5% PCV10 62.5% 66.2% 76.2% 73.6% 80.6% 71.1% PCV13 76.9% 73.9% 88% 83.4% 88% 79.1%
    38. 38. Likely PCV 13 efficacy in India <ul><li>The recently introduced 13-valent PCV is expected to cover about three quarters of the serotypes responsible for invasive disease in India, </li></ul><ul><li>PCV are efficacious in reducing disease caused by vaccine-serotypes </li></ul>Mathew J et al. Acute Respiratory Infection and Pneumonia in India: A Systematic Review of Literature for Advocacy and Action: UNICEF-PHFI Series on Newborn and Child Health, India. Indian Pediatrics 2011, 48, pp 191-218
    39. 39. Vaccine safety profile <ul><li>42 studies were included to review safety of PCV. </li></ul><ul><li>Reactogenicity data from some trials suggested that PCV-7 may result in more mild, self-limiting local reactions and fever than control vaccines; although severe adverse events were not increased. </li></ul>Destefano F, Pfeifer D, Nohynek H. Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data. Bull WHO. 2008;86:373-80
    40. 40. Safety & immunogenicity study of PCV 13 from India – non-inferiority <ul><li>Phase 3 double blind multi-centre RCT </li></ul><ul><li>179 children received PCV 13, 176 received PCV 7 </li></ul><ul><li>Responder rates > 80 % for both vaccines for the common serotypes </li></ul><ul><li>Responder rates between 80-99 % against additional 6 serotypes </li></ul><ul><li>Incidence of both local & systemic reactions were similar, and mild </li></ul>Amdekar Y, et al. Safety and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Vaccines in India. 7th International Symposium on Antimicrobial Agents and Resistance, Bangkok, Thailand, March 18-20, 2009
    41. 41. <ul><li>Brief intro about Pneumococcal Disease </li></ul><ul><li>India – Scope of IPD – morbidity & mortality </li></ul><ul><li>Latest data (Pneumonet) regarding Pneumococcal Disease in India </li></ul><ul><li>Data regarding Pneumococcal serotypes & antimicrobial resistance in India </li></ul><ul><li>Possible Impact of PCV 13 in India </li></ul><ul><li>PCV 13 – Safety & Non-inferiority data from India </li></ul><ul><li>Various schedules </li></ul>
    42. 42. PCV13: Phase 3 Clinical Program Non-inferiority studies Evaluation of different dosing schedules: <ul><ul><li>3+1 Schedule </li></ul></ul>6, 10, 14 weeks, and 12 months 2, 3, 4, and 12-15 months 2, 4, 6, and 12-15 months <ul><ul><li>2+1 Schedule </li></ul></ul>2, 4, and 12 months 3, 5, and 11 months <ul><ul><li>3+0 Schedule </li></ul></ul>6, 10, and 14 weeks PCV 13 can be substituted for PCV 7 at any point in the vaccination schedule New serotype catch-up ( Single dose of PCV13 in children previously vaccinated with PCV7)
    43. 43. Vaccination schedule for 7-18 years – MMWR 2011
    44. 44. Vaccination schedule for high-risk children – IAP 2011 <ul><li>PPSV23 should be administered after PCV among HIGH-RISK children aged 2 –18 years as follows: </li></ul><ul><li>When elective splenectomy, immuno-suppressive therapy, or cochlear implant placement is being planned; PCV and/or PPSV23 vaccination should be completed at least 2 weeks before surgery or initiation of therapy </li></ul><ul><li>Children aged ≥ 2 years with underlying medical conditions should receive PPSV23 after completing all recommended doses of PCV13 </li></ul><ul><ul><li>1 dose of PPSV23 at age ≥ 2 years and at least 8 weeks after the most recent dose of PCV. </li></ul></ul><ul><li>Children who have received PPSV23 previously also should receive recommended PCV doses </li></ul><ul><li>IAP Guidebook on Immunization 2011 </li></ul>
    45. 45. Difference between PCV13 and PPV23 <ul><li>PCV for childhood immunization – WHO position paper Weekly Epidemiological Record. 2007, 12 (82): 93–104. </li></ul><ul><li>Prevenar13 Prescribing Information Wyeth Limited* 2010 (*A subsidiary of Pfizer Inc.) </li></ul><ul><li>23-valent pneumococcal polysaccharide vaccine - WHO position paper. WHO Weekly Epidemiological Record . 2008; 83(42): 373–384 </li></ul>PCV13 1 PPV23 2 Valency 13 valent 23 valent Target population Healthy Children At risk population Minimum age of vaccination > 6 weeks > 2 years (High Risk) Immune response ---- at 6 weeks of age ---- at 2 years of age Strong Strong Absent to weak Moderate to Strong Duration of immunity Long term Short term Vaccine efficacy- children < 2 years Yes None Important reductions in nasopharyngeal carriage Yes No effect Indirect protection Reported Unlikely Important reductions in the prevalence of antibiotic resistant isolates Reported Not established
    46. 46. Summary <ul><li>Pneumococcal disease is the #1 vaccine-preventable cause of death worldwide in children aged <5 years 1 </li></ul><ul><li>Data from India clearly points to vaccine preventable serotypes being common cause of Pneumococcal Disease ! </li></ul><ul><li>PCV13 provides the broadest serotype coverage of any pneumococcal conjugate vaccine 2,3 </li></ul><ul><li>Convenient transition from PCV 7 to PCV13 at any point in the vaccination schedule 4 </li></ul><ul><li>Children who have completed vaccination with PCV 7 should be offered catch-up with PCV 13 5 </li></ul><ul><li>For high risk cases PCV/ PPSV can be given up to 18 years ! </li></ul><ul><li>WHO. http://www.who.int/immunization_monitoring/data/GlobalImmunizationData.pdf. Accessed September 3, 2009. </li></ul><ul><li>Dinleyici E, et al. Expert Rev Vaccines. 2009;8:977-986. </li></ul><ul><li>GAVI Pneumococcal AMC TPP, Nov 2008. http://www.vaccineamc.org/files/TPP_codebook.pdf. Accessed September 3, 2009. </li></ul><ul><li>Prevenar 13. Summary of Product Characteristics. Wyeth Pharmaceuticals. </li></ul><ul><li>Data on file. Pfizer Inc, New York, NY. </li></ul>

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