1. Hot Topics In Infectious Diseases Robert S. Baltimore, MD Professor of Pediatrics and Epidemiology Annual School Health Conference May 20, 2010

2. Outline-Issues 1. Review of Novel Influenza virus H1N1 2009-2010 2. Recommendations for influenza prevention for 2010-2011 3. New vaccine to prevent pneumococcal infection--- Prevnar 13

3. PHIL ID #11214 Photo Credit: C. S. Goldsmith and A. Balish, CDC Download High Resolution Download High Resolution Description: Negative stain EM image of the 2009 H1N1 Influenza A/CA/4/09

4. Structure of the influenza virion. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to ribonucleoproteins (RNPs).virionhemagglutinin neuraminidasegenome National Institutes of Health;

7. Influenza: Antigenic Drift and Shift Hemagglutinin Neuraminidase Influenza Virus Drift Shift

9. N Engl J Med 360;25 june 18, 2009

11. CT Data As of 4 Dec 2009 1 May 2010

17. Childhood Deaths Since April 2009, the CDC has received reports of 329 pediatric deaths that have been confirmed to be associated with the influenza virus. Of these pediatric deaths, 278 have been confirmed to be associated with the 2009 H1N1 virus. This represents much more pediatric mortality associated with influenza than is seen during a typical influenza season.

19. Pandemic (H1N1) 2009 - WHO Update 98 - ------------------------------------ As of 25 Apr 2010, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 17919 deaths. The WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and Member States and through monitoring of multiple sources of information. Situation update: - ----------------- The current situation is largely unchanged since the last update. The most active areas of transmission of pandemic influenza H1N1 virus continue to be parts of West and Central Africa with some focal areas of activity in South and Southeast Asia. Pandemic influenza activity H1N1 remains low in much of the temperate areas of both the northern and southern hemispheres. Seasonal influenza type B virus is the predominant influenza virus, though also at low levels of circulation, across East Asia, Northern and Eastern Europe. Influenza type B viruses have also been detected in Central Africa and this week in West Africa. Seasonal influenza H3N2 viruses have continued to be detected in South and Southeast Asia, as well as sporadically in some countries of West and Central Africa, and Eastern Europe.

20. Schools Connecticut State Department of Education October 2009 Reminders and Updates on H1N1 Influenza Guidance for Schools The Connecticut Department of Public Health (DPH) along with the Connecticut State Department of Education (CSDE) has developed guidance for school nurses regarding H1N1 influenza which is available at http://www.ct.gov/ctfluwatch/lib/ctfluwatch/h1n1/school_nurse_guidance.pdf. Reporting School Closures: School districts are asked to report all school closings due to H1N1 influenza to the CDC through the CSDE Web site at http://www.sde.ct.gov/sde/cwp/view.asp?a= 2604&Q=322396. The CDC provides updates on school closures to the CSDE as they are reported.

21. Schools- CDC Recommendations Encourage Vaccination Against Flu Advise the sick to stay home Separate sick students and staff (for those ill separate room—go home) Discourage attendance at school events by sick people Respiratory etiquette and hand hygiene Perform environmental cleaning (no additional disinfection beyond routine cleaning) Early treatment of students and staff at high risk for complications Consider selective school dismissal

22. Consider school dismissals: School and health officials should work closely to balance the risks of flu in their community with the disruption dismissals will cause in both education and the wider community and should clearly state the reason for school dismissal. Reactive dismissals might be appropriate when schools are not able to maintain normal functioning for example, when a significant number and proportion of students have documented fever while at school despite recommendations to keep sick children home. Preemptive dismissals can be used proactively to decrease the spread of flu. CDC may recommend preemptive school dismissals if the flu starts to cause severe disease in a significantly larger proportion of those affected. CDC Guidance for State and Local Public Health Officials and School Administrators for School (K-12) Responses to Influenza during the 2009- 2010 School Year February 22, 2010, 4:30 PM ET

24. Why were older people largely spared? Seroprevalence studies, which monitor antibodies that react with the virus, suggest an explanation for this. Serum samples taken in England before the start of the pandemic show that older people had stronger antibody reactions to H1N1 than young people, probably as a result of previous exposure to strains with similarities to the new virus

25. Q. How can healthcare facilities eliminate sources of infection and transmission within their facilities? Healthcare facilities will want to use a multi-level approach, called the hierarchy of controls, that includes both administrative controls and engineering controls to eliminate sources of infection and prevent transmission within their facility. To ensure a comprehensive infection control strategy, healthcare facilities will want to: Vaccinate their workforce with seasonal and 2009 H1N1 vaccines. Keep sick workers at home. Enforce respiratory hygiene and cough etiquette. Enhance hand hygiene compliance. Establish facility access control measures and triage procedures. Manage visitor access and movement within the facility. Control patient placement and transport. Apply isolation precautions.

26. Q. What personal protective equipment should be worn by healthcare personnel? Standard precautions should be followed for all patient care. For any activity that might generate splashes of respiratory secretions, gowns along with eye protection should be worn. Healthcare workers who are in close contact with patients suspected or confirmed to have 2009 H1N1 influenza should wear a fit- tested, disposable N95 respirator.

28. Update on Influenza Vaccine

29. CDC Recommendations for childhood flu vaccination Before 2002Only children >6 months with certain medical conditions 2002-20046-23 months encouraged when feasible 2004-20056-23 months recommended 2006-6- 59 months recommended 2010Everyone over 6 months old

31. This new recommendation includes all healthy people 19 through 49 years of age, the only portion of the U.S. population not included in previous ACIP influenza immunization recommendations. Before this new universal policy, the vaccine already was earmarked for about 85% of the population, based on age, having a chronic health condition or being in contact with someone in a high-risk group. Risk-based priorities will be eliminated once the universal recommendation takes effect in the 2010-’11 seasonal influenza season. Universal vaccination against influenza is especially beneficial for infants younger than 6 months of age because they are at high risk for significant morbidity and mortality due to the virus, but cannot be given influenza vaccine. When everyone in an infant’s immediate environment has been vaccinated, this “cocooning” effect reduces the infant’s exposure to the virus.

32. Influenza Virus A/Fujian/411/2002 (H3N2) Neuraminidase Hemagglutinin Type of nuclear material Virus type Geographic origin Strain number Year of isolation Virus subtype

33. The three strains of influenza virus to be included in the 2010-’11 vaccine include: The 2009 H1N1 influenza virus, which will be called “A/California/7/2009 (H1N1),” An A/Perth/16/2009 (H3N2)-like virus and a B/Brisbane/60/2008-like virus A seasonal influenza A (H1N1) component is not included in the 2010--11 formulation, The 2010-2011 Flu Vaccine

34. Previous recommendations include: (ACIP) 2 doses of vaccine to all children aged 6 months--8 years if they have not been vaccinated previously at any time with either LAIV (doses separated by >4 weeks) or TIV (doses separated by >4 weeks), if possible completed by December. children aged 6 months--8 years who received only 1 dose in their first year of vaccination receive 2 doses the following year all persons, including school-aged children, who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated immunization providers should offer influenza vaccine and schedule immunization clinics throughout the influenza season encourage health-care personnel vaccination as a measure of patient safety and quality improvement programs. (e.g., obtaining signed statements from HCP who decline influenza vaccination)

35. New Flu Vaccine for “Elderly” On December 23, 2009, the FDA licensed an injectable inactivated trivalent influenza vaccine (Fluzone High-Dose, Sanofi-Pasteur) containing an increased amount of influenza virus hemagglutinin antigen compared with other inactivated influenza vaccines it is licensed as a single dose for use among persons aged ≥65 years and will be available beginning with the 2010--11 influenza season The Advisory Committee on Immunization Practices (ACIP) reviewed data from prelicensure clinical trials on the safety and immunogenicity of Fluzone High- Dose and expressed no preference for the new vaccine over other inactivated trivalent influenza vaccines.

36. Why Vaccinate Young Children? Glezen observed that influenza hospitalization rates in the youngest children are equivalent to those in the elderly. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev 1982. 4:25-44. Using a large database of children in Tennessee, investigators more recently showed that showed that in a typical year that 6-15% of children under 15 years of age visit a physician and 3-9% receive antibiotics as a consequence of influenza Neuzil KM, Mellen, et al. The effect of influenza on hospitalizations, outpatient visits and courses of antibiotics in children. N Engl J Med 2000;342:225-31

37. Why Vaccinate Young Children? In Northern California and the state of Washington, the rate of hospitalization for influenza for healthy children under 2 years of age was 193-231 per 100,000, which is 12 times as high as the rate for healthy children 5-17 years and approaches that for children 5-17 years with chronic health condition Izurieta HS, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-9. School aged children and children in daycare have a central role in the spread of influenza virus because they have high attack rates and shed virus at higher titers and for twice as long as adults Reichert TA, et al The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med 2002;344:889-96. Glezen WP,et al. Influenza virus infections in infants. Pediatr Infect Dis J 1997;16:1065

38. High Risk Medical Conditions: –Chronic cardiac or pulmonary disorder –Diabetes mellitus –ESRD/renal insufficiency –Immunosuppression –Sickle-cell disease –Long-term aspirin therapy Other Pediatric Recipients of Influenza Vaccine

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42. Most experts (including AAP) view the protection of more children against the known risks of influenza more important than the theoretic risk of small amounts of thimerosal in influenza vaccine. Removal of thimerosal from TIV results in wastage of one third of doses produced. Thimerosal and Flu Vaccine

43. Influenza Vaccination of Pregnant and Breastfeeding Women  Several studies have documented increased risk of complications, hospitalization, and death from influenza during pregnancy.  A study of over 2,000 pregnant women vaccinated with influenza vaccine showed no adverse effects, although additional studies are needed to confirm the safety of vaccination during pregnancy.  In a study only of OBGYNs 39% gave influenza vaccine to pregnant patients.  Pregnant women with medical conditions that increase risk for complications from influenza should be vaccinated regardless of the stage of pregnancy  Breast-feeding is not a contraindication for influenza vaccine.

44. Prevnar 13 In February 2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) was licensed by the Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices (ACIP) for prevention of invasive pneumococcal disease in children; PCV13 succeeds the 7-valent (PCV7) used in the routine childhood immunization schedule since 2000.

46. Prevnar 13 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Prevnar 13  is a vaccine approved for use in children 6 weeks through 5 years of age (prior to the 6th birthday). Prevnar 13 is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Prevnar 13 is also indicated for the prevention of otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A.

48. Serotype-specific antipolysaccharide IgG antibody and functional opsonic antibody responses…. PCV13 is at least as immunogenic as PCV7 for the 7 common serotypes and is notably more immunogenic for the additional 6 serotypes. Despite the increased antigenic load, PCV13 does not interfere with immune responses to concomitantly administered vaccine antigens, and its safety and tolerability profile seems to be similar to that of PCV7. PCV13 should supplant the current PCV 7 for routine use in infants to broaden coverage against major pneumococcal serotypes important in invasive pneumococcal disease and acute otitis media. Bryant, K.A., et al Safety and Immunogenicity of a 13- Valent Pneumococcal Conjugate Vaccine. Pediatrics 2010; 125: 866 (May) From May Pediatrics

49. Based on available safety, immunogenicity and disease burden data, ACIP recommends that a single supplemental PCV13 dose be given to healthy children aged 14–59 months and to children with underlying medical conditions up to age 71 months who already have completed a schedule of PCV7. In one study, a single dose of PCV13 in children aged ≥12 months who had received 3 previous doses of PCV7 induced an antibody response comparable to the 3-dose infant PCV13 series, and the safety profile of this supplemental dose was comparable to that after a fourth dose of PCV13 ACIP recommendation

52. Pfizer told the committee it would charge $108 a dose for the new product, 30 percent higher than the $83 a dose it charged for Prevnar 7.