1. Hot Topics in Pediatric ID Robert J. Leggiadro, MD Chairman Department of Pediatrics Lincoln Medical Center Professor of Clinical Pediatrics Weill Medical College of Cornell University

2. NY Times Headline 10/14/08 Worrisome Infection Eludes a leading Children’s Vaccine

5. Emergence of Pneumococcal Serotype 19A Most common invasive serotype Largest proportion resistant IPD JID 2008; 197:1016-27.

7. From The Journal of Infectious Diseases 197(7):1016–1027. © 2008 by the Infectious Diseases Society of America. For permission to reuse, contact journalpermissions@press.uchicago.edu. Figure 1. Age-specific incidence of invasive pneumococcal disease caused by serotype 19A, 1998–2005

8. Native Alaska Children less than 2 yrs. PCV7 coverage 90% Since 2004 140% ↑ in NV strains 30% 19A; others 3, 6A, 7F Vaccine covered strains ↓ 96%.

9. Copyright restrictions may apply. Singleton, R. J. et al. JAMA 2007;297:1784-1792. Cases of Invasive Pneumococcal Disease by Serotype Among Alaskan Children Younger Than 2 Years, 1995-2000 and 2001-2006

10. Copyright ©2008 American Academy of Pediatrics Ongkasuwan, J. et al. Pediatrics 2008;122:34-39 FIGURE 1 Histogram of the annual number of cases of pneumococcal mastoiditis, and the proportion that were serotype 19A, among children at Texas Children's Hospital between 1995 and June 2007

11. Copyright ©2008 American Academy of Pediatrics Ongkasuwan, J. et al. Pediatrics 2008;122:34-39 FIGURE 4 Histogram of the annual number of total pneumococcal isolates, and the proportion that were serotype 19A, recovered from middle ear fluid cultures obtained from children at Texas Children's Hospital between 1995 and June 2007

12. Emergence of Pneumococcal Serotype 19A Equally capable of IPD, NP colonization and AOM. 9 th most common IPD serotype pre-PCV7; common NP carriage pre-PCV 7 High rate of resistance PCV7 ineffective against 19A

13. Emergence of Pneumococcal Serotype 19A Clonal expansion Capsular switching Selective advantages

14. Emergence of Pneumococcal Serotype 19A PCV7 may not be the only factor Antibiotic (especially macrolide) use impacts serotype distribution Alaska, Barcelona, Israel, China, Belgium White Mountain Apache population has not seen 19A increase

17. Pneumococcal Meningitis Epidemiology in the PCV7 Era 2001 – 2004 compared with 1994 – 1999 2/3 reduction in rates of PM in children less than 2 yrs old 1/3 reduction in rates of PM in adults 65 yrs and older Median age ↑ to 46 yrs from 37 yrs. Overall 3,300 cases, 394 deaths of PM prevented. Clin Infect Dis 2008; 46:1664

18. Epidemic Pneumococcal Meningitis in Africa Ghana, Burkina Faso Concurrent with meningococcal epidemics Dry season Serotype 1 most common

19. Epidemic Pneumococcal Meningitis in Africa Underappreciated burden of pneumococcal disease in sub-Saharan Africa. Unique propensity of serotype 1 S. pneumoniae to cause serious infection and out breaks. Opportunity for prevention through pneumococcal vaccination.

20. Bacteremia among children in Rural Kenya Hospital deaths in children between 60 d and 5 y 8.7% due to pneumococcal bacteremia 4.9% due to H. flu bacteremia Highlights need for prevention through immunization N Engl J Med 2005; 352:39-47.

21. Childhood Bacteremia in Rural Kenya 28% children hospitalized with bacteremia died 26% hospital deaths associated with bacteremia Bacteremia responsible for more deaths than malaria (22%)‏

22. PCV Worldwide Only 26 (14%) of 193 WHO members have introduced PCV7 into their national immunization programs. Primarily high-income countries with relatively few childhood deaths secondary to IPD.

23. IPD Mortality Indicators in Children less than 5 years old More than 50 deaths/1,000 live births 50,000 deaths annually More than 10% deaths secondary to Pn Greater than 1% HIV incidence in adults

24. Pneumococcal Conjugate Vaccines PCV7; 14, 6B, 19F, 9V, 23F, 18C, 4 PCV10; 7 plus 1, 5, 7F PCV 13; 10 plus 3, 6A 19A

27. Role of Bacterial Pneumonia 1918 – 1919 Influenza Pandemic Bacterial pneumonia on autopsy Typical pneumonia features Picture similar to measles 1917-1918 Most influenza typical, including full recovery Mortality reflected bacterial pneumonia rates Higher rates in U.S. military camps Time of onset (10 d) consistent with bacteria pneumonia Early bed rest effective in isolation from bacterial carriers JID 2008; 198:962-70

28. Bacterial Pneumonia and Pandemic Influenza Planning Shift in focus Basic research Pneumocococcal vaccines Source, supply, surge capacity of important antibiotics Inclusion of vancomycin Implications for developing countries Emerg Infect Dis 2008; 14:1187-92