1. Prof. Fahad Abdullah Al Zamil Professor & Consultant Pediatrics Infectious Disease Head of Pediatrics Infectious Diseases Unit King Saud University THE PAST, THE PRESENT AND THE FUTURE Schedule

2. Edward Jenner Edward Anthony Jenner (17 May 1749 – 26 January 1823) was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire. Jenner is widely credited as the pioneer of smallpox vaccine, [1] and is sometimes referred to as the "Father of Immunology"; his works have been said to have "saved more lives than the work of any other man". [2][3][4] EnglishBerkeley, Gloucestershire smallpox vaccine [1] [2][3][4]

3. James Phipps James Phipps (1788-1853), as an eight year old boy, and the son of Edward Jenner's gardener, was the first person given the cowpox vaccine by Edward Jenner. Phipps was often used as an living proof that Jenner's vaccine worked.cowpoxEdward Jenner Phipps was exposed to the smallpox virus multiple times over the next twenty years, but successfully resisted infection, proving the efficacy of Jenner's vaccination.smallpox Edward Jenner Vaccinating 8 year old James Phipps on 14 May 1796

4. Louis Pasteur 27 December, 1822 – 28 September, 1895 The great revolution in the vaccination science occurred thanks to the genius French chemist and microbiologist Louis Pasteur who developed an attenuated vaccines to prevent cholera, anthrax and rabies. Louis Pasteur was the first person to use the terms Vaccine and attenuated. His body lies beneath the Institute Pasteur in France

5. Article from the French newspaper “Le Petit Journal” regarding Joseph Meister’s reported suicide during the German occupation of Paris during World War 1. During the German occupation of Paris, Meister committed suicide by shooting himself with his World War I service revolver rather than allow German soldiers enter Pasteur’s crypt(secret burial place or tomb).ParisWorld War Irevolver

6. Expanded Program of Immunization in Saudi Arabia 1979: decision to release birth certificate of new born babies only with a proof of completion of the primary series vaccination (6 months after birth) 1982: extended to be 9 months after birth –To ensure high coverage of measles vaccination 1991: 1st uniform EPI was released 2002 2009: modifications in the EPI schedule Meshkhas AA. Guidelines to Expanded Program of Immunization staff (Arabic title). Riyadh: Saudi Ministry of Health; 2006.

9. Expanded Program of Immunization in Saudi Arabia - 1991 Meshkhas AA. Guidelines to Expanded Program of Immunization staff (Arabic title). Riyadh: Saudi Ministry of Health; 2006. AGEEPI 1991 At birthBCG HepB 1 6 weeksDTwP 1 HepB 2 OPV 1 2 months 3 monthsDTwP2 OPV 2 4 months 5 monthsDTwP 3 OPV 3 6 monthsMeasles HepB 3 9 months 12 monthsMMR 18 monthsDTwP 4 OPV 4 24 monthsDTwP 5 OPV 5 4-6 years

10. Expanded Program of Immunization in Saudi Arabia - 2002 Meshkhas AA. Guidelines to Expanded Program of Immunization staff (Arabic title). Riyadh: Saudi Ministry of Health; 2006. AGEEPI 1991EPI 2002 At birthBCG HepB 1 6 weeksDTwP 1 HepB 2 OPV 1 2 months DTwP-Hib 1 HepB 2 OPV 1 3 monthsDTwP 2 OPV 2 4 months DTwP-Hib 2 OPV 2 5 monthsDTwP 3 OPV 3 6 monthsMeasles HepB 3 DTwP-Hib 3 HepB 3 OPV 3 9 months 12 monthsMMRMMR 1 18 monthsDTwP 4 OPV 4 DTwP-Hib 4 OPV 4 24 monthsDTwP 5 OPV 5 MMR 2 DTwP 5 OPV 5 4-6 years

11. Expanded Program of Immunization in Saudi Arabia - 2009 Meshkhas AA. Guidelines to Expanded Program of Immunization staff (Arabic title). Riyadh: Saudi Ministry of Health; 2006. AGEEPI 1991EPI 2002EPI 2009 At birthBCG HepB 1 6 weeksDTwP 1 HepB 2 OPV 1 2 months DTwP-Hib 1 HepB 2 OPV 1 DTwP-Hib 1 -HepB 2 IPV 1 PCV7 1 3 monthsDTwP 2 OPV 2 4 months DTwP-Hib 2 OPV 2 DTwP-Hib 2 -HepB 3 OPV 1 PCV7 2 5 monthsDTwP 3 OPV 3 6 monthsMeasles HepB 3 DTwP-Hib 3 HepB 3 OPV 3 DTwP-Hib 3 -HepB 4 OPV 2 PCV7 3 9 months Measles + MCV4 12 monthsMMRMMR 1 MCV4 MMR 1 OPV 3 Varicella 1 PCV7 4 18 monthsDTwP 4 OPV 4 DTwP-Hib 4 OPV 4 DTwP-Hib 4 OPV 4 HepA 1 24 monthsDTwP 5 OPV 5 MMR2 DTwP 5 OPV 5 HepA 2 4-6 years MMR 2 Varicella 2 DTwP 5 OPV 5

12. Polio Eradication Milestones 1948Poliovirus grown in tissue culture 1955Inactivated polio vaccine (IPV) 1961Attenuated live polio vaccine (OPV) 1974WHO expanded program on Immunization (EPI) 1988WHO committed to global polio eradication by the year 2000 1992No cases detected in the Americas 1997No cases in Western Pacific Region Jan 2009Only four parts of four countries have never interrupted indigenous wild poliovirus transmission

13. Poliomyelitis global annual reported incidence and third-dose polio vaccine coverage 1980-2006 WHO estimates for 2007: 1278 reported cases worldwide The global decline in reported poliomyelitis incidence in the 1980s is consistent with the overall increases in immunization coverage POLIOMYELITIS Global Epidemiology Number of cases Official Coverage WHO/UNICEF estimated coverage number of cases immunization coverge (%) 70000 60000 50000 40000 30000 20000 10000 0 100 90 80 70 60 50 40 30 20 10 0 [1] WHO. Vaccine preventable diseases monitoring system Global Summary 2007. WHO. Immunization Vaccines and Biologicals. Global and regional summary. Accessed Feb 2008. Available from: http://whqlibdoc.who.int/hq/2007/WHO_IVB_2007_eng.pdf [2] WHO Global Polio Eradication Initiative Wild poliovirus weekly update. Accessed February 2008. Available from: http://www.polioeradication.org/casecount.asp [3] WHO. Global Polio Eradication Initiative Strategic Plan 2004-2008. 2003

14. Polio Eradication Progress 1988-2006 WHO. Progress Towards Global Immunization Goals 2007. Accessed February 2008. Available from: http://www.who.int/immunization_monitoring/data/SlidesGlobalImmunization.pdf WHO Global Polio Eradication Initiative Wild poliovirus weekly update. Accessed February 2008. Available from: http://www.polioeradication.org/casecount.asp In 2007 4 countries were still endemic (India Pakistan Afghanistan and Nigeria) and represented nearly 92% of the global cases 1988 2009 Endemic with wild polio virus (4 Countries) Certified Polio-free regions (114 countries) Not Certified but non-endemic (73 countries) POLIOMYELITIS Global Epidemiology

16. Wild Polio Cases 2009200820072006 Globally1,6001,6489921,997

17. WHO Strategies for Polio Eradication  High routine immunization coverage  National immunization days (NIDS)  Acute flaccid paralysis (AFP) surveillance  Mopping up

18. Poliovirus Eradication Targets 2010 - 2013 * validated when >6 months without a case genetically linked to a 2009 importation (i.e. by end–2010). ** validated when > 12 months without a case genetically linked to the re-established virus (by end–2011). *** validated when > 12 months without a case genetically linked to an indigenous virus (by end–2012). **** validated when ≥ 12 months without a case genetically linked to an indigenous virus (by end–2013). † 'certification will require at least 3 years of zero polio cases in the presence of appropriate surveillance across an entire epidemiologic region.

19. Poliovirus Vaccines IPVOPV ExpenseMoreLess Virus excretion, spreadNoneYes Humoral immunityYes Mucosal immunityNoYes Prevents paralysisYes Rare paralytic sequelaNoYes

20. Seroconversion Rates for Poliovirus Type 1, 2 and 3 After 3 Doses Of Inactivated Poliovirus Vaccine, By Study Arm, Puerto Rico. EPI arm at 6, 10 & 14 wks. US arm at 2, 4 & 6 mos JID 2007;195:12-20 Polio type 1 P<.001 Polio type 2 P ≤.001 Polio type 3 P =.08

21. Paralytic Poliomyelitis Cases United States 1960-1994

22. Vaccination Coverage in Saudi Arabia From 2000- 2008

23. Polio Incidence, KSA 1980 – 2007

24. 2007 Global Figures 279,006 reported cases 197,000 estimated deaths (2007) 82% estimated MCV coverage 60% of countries reached≥ 90% MCV Coverage

25. 736 Cases by Age 18% 22% 18% 11% 31%  1 yrs 1-4 yrs 5-14 yrs 15-19 yrs > 20 yrs Measles Outbreak KSA, January – February 2007

26. Measles Outbreak KSA, 2007 Preliminary Information 1.Approximately ¼th the cases were in those less than 1 year of age 2.Second MMR coverage had been poor ~ 50%

27. Measles Cases by Month till July 2007

28. Measles by Regions till July 2007

29. Decisions 1.Measles vaccination campaigns 2.Re-introduce measles vaccine age 9 months 3.Enforcement of 2 nd MMR dose Measles Outbreak KSA, 2007

30. Measles cases by regions, 2008

31. International Measles Outbreaks 2011 By Vincent Iannelli, M.D., About.com GuideVincent Iannelli, M.D. Updated October 23, 2011 International Measles Outbreaks Quebec, Canada - 742 cases (most since mid-1990s) France - over 13,957 cases in 2011 Spain - 1,637 cases in 2011 Romania - 2,765 cases in 2011, including 582 cases of pneumonia and 3 cases of encephalitis and 1 death Italy - over 4,300 cases in 2011, including new outbreaks with 1,500 cases in Bolzano, Italy which is "known to have the lowest measles vaccination uptake" in Italy and strong "vaccination opposition" and the Lazio region (over 1,000 cases) Germany - 1,480 cases and 1 death in 2011 UK - 804 cases so far this year (up from 374 in 2010) New Zealand - just over 358 cases (most in Auckland) Switzerland - 651 cases in 2011 Belgium - 515 cases in 2011 Ireland - at least 173 cases in 2011 Bulgaria - 24,000 cases and 24 deaths in 2010 Southern Africa, including measles outbreaks in Lesotho, Malawi, Namibia, Mozambique, South Africa, Zambia, and Zimbabwe Eastern Africa, including measles outbreaks in Ethiopia and Kenya

32. Varicella Complications in Healthy Children  Bacterial Infections – St. aureus, GAS Skin and subcutaneous Toxic shock syndrome, Osteomyelitis  CNS – Acute cerebellar ataxia, encephalitis  Pneumonia  Reyes’ syndrome (rare)  Hepatitis (rare)

33. Varicella Vaccine  Live attenuated  Safety: mild rash, (5-10%) after one month  Over 95% of children  13 yrs seroconvert after 1 dose  Adolescents and adults respond less well (require 2 doses)

34. No. of Reported Cases Of Varicella Disease Among Persons Of All Age Groups And Estimated Annual Vaccination Coverage Among Children Aged 19-35 Months MMWR June 22, 2007 NumberPercentage 100 80 60 40 20 0

35. Varicella-related hospitalization rates among persons aged <50 years, by year and age group United States, 1994-2002 Rate / 100,000 JAMA 2005;294:797-802

36. Varicella-related Mortality Rates, By Year And Underlying And Contributing Cause Of Death United States, 1990-2001 Rate / 1,000,000 Licensure of varicella vaccine N Engl J Med 2005;352:350-8

37. Recommendation of ACIP for Prevention Of Varicella – United States 1996, 1999 and 2007 Category1996 recommendations 1999 recommendations 2007 recommendations Routine childhood schedules 1 dose recommended at age 12-18 months No change2 doses recommended 1 st dose at age 12- 15 months 2 nd dose at age 4-6 years Adults and adolescents aged ≥ 13 years 2 doses, 4-8 weeks apart No change

38. The Prevalence Of Chickenpox in Saudi Arabia National Guard (Riyadh)MOH 0 500 1000 1500 2000 2500 3000 Rate per 100,000 (MOH) No. of Cases in the National Guard (Riyadh) Int’l J Inf Dis 2006 (10):156-161

39. The Incidence Of chickenpox Among The National Guard population Total Number: 3,802 No. of reported chicken pox cases Int’l J Inf Dis 2006 (10):156-161

40. The Outcome of 3802 Patients With Chickenpox During 1 June 2001 to 30 December 2003 VariableN% Total number of complications581.5 Skin and soft tissue infections 2031 Pneumonia 1628 Bacteremia 610 Encephalitis/cerebellitis 47 Necrotizing fasciitis 47 Neonatal varicella 23 Other 610 Hospitalization782 Mortality20.05 Int’l J Inf Dis 2006 (10):156-161

41. Geographic Distribution of HAV Infections

42. Etiology of Icteric Hepatitis in 133 Saudi patients from June 1993 – May 1994 TOTALNANBN C CMVHCVHBVHAV 765373451-12 years 5730-20146  12 years 133353271751Total (100)(26.3)(2.3)(20.3)(12.8)(38.3)(%) Arif, et al. 1995

43. Summary of the studies on anti- HAV IgG prevalence in Saudi Arabia (1986-2006) Percent anti- HAV (IgG) Age Group (years) No. of Subjects Area (Region) YearReference No. 76.51-151015Western1986Ramia et.al 796-185876Eastern1987Fathalla et.al 921-102582All Regions1989El-Hazmi 52.41-104375All Regions1989Al-Rashed 50.51-124575All Regions1989Al-Faleh et.al. 24.71-12243Central (Riyadh) 1995Arif M et.al. 30.21-15592Central (Riyadh) 1996Khalil et.al. 24.91-125355All Regions1997Al-Faleh 28.9All (mostly children) 2399Central (Riyadh) 2005Al Muneef

44. Proportion of HAV Positives According to Socio-economic Level In 490 Children 45- 40- 35- 30- 25- 20- 15- 10- 5- 0- High Medium Low Khalil, et al. Ann Saudi Med 1998; 18(1):18-21

45. Hepatitis A Seroprevalence By Age Group (2005) Vaccine 24 (2006) 5599-5603 <88-11 12-15  16

46. Prevalence Rates (%) of anti-HAV among Saudi children 1- 12 years old in 1989 and 1997 according to region ANTI-HAV REGION 1997 N=5,355 1989 N=4,575 16.039.0Riyadh 31.662.7Gassim 20.456.0Hail 28.259.5Medina 20.155.0Makkah 19.044.5Aseer 22.140.6Al-Baha 82.080.0Jizan 50.379.1Najran 47.060.4Al-Jouf 45.676.0Tabouk 18.238.4Dammam 17.551.0Jeddah 9.019.0Taif 24.950.5TOTAL Al Faleh, et al.BJ Infect.1992;24:197-206 Al Faleh, et al. Saudi Med J. 1999;20(9);678-681

47. HAV Summary HAV seroprevalence surveys in Saudi Arabia indicate shifting pattern from high to intermediate endemicity Remaining foci of high endemicity in some regions and in the surrounding countries,  mobility and  older susceptible population pose a real risk for outbreaks Outbreaks expected to result in more severe forms of disease   healthcare cost Universal hepatitis A vaccination for all children in Saudi Arabia is indicated

48. Reported Hepatitis A Outbreaks in Saudi Arabia AuthorControl Method No. of Cases AreaYear Dehish et.al.IG72Afif, Riyadh1997 Khaledi et.alIG63Jizan2002 Basurrah et.alIG114Bisha2003 Al Saleh et.alIG110Al Berk, Asir2004 Al Hayani, et alIG105Al Qassiem2006 Saudi Epidemiol Bulletin

49. S. Pneumoniae Disease Burden in Children Otitis media Pneumonia Bacteremia Meningitis Disease severity For each case of pneumococcal meningitis in a year: X 1000 to 10,000 X 100 to 1000 X 10 Prevalence Invasive Non-invasive Adapted from: American Academy of Pediatrics. Pediatrics. 2000;106:367-376 & CDC :MMWR. Prevention of Pneumococcal Dis. 1997;46:1-24

50. In Saudi Arabia, 49 % of Pneumococci are Penicillin-Resistant

51. Cycle of Antibiotic Resistance Prevalence of: Serious disease Difficult-to-treat disease Prevalence of: Serious disease Difficult-to-treat disease Prevalence of resistant strains Prevalence of resistant strains Use of antibiotics Use of antibiotics

52. Meningitis in Saudi Children under 5 Years of Age Etiology# of Cases (%)Incidence/100,000 H. influenzae type B58 (28)17 N. meningitides37 (18)11 S. pneumoniae23 (11)7 Other bacteria23 (11)7 Aseptic67 (32)19 Total208 (100)61 Y Al Mazrou et. al. J trop pediatr 2004; 50(3): 131-6

53. Source: Active Bacterial Core Surveillance Invasive Pneumococcal Disease Incidence by Age Group Age Group (Yrs) Rate per 100,000 Population

54. Yearly Statistics of Paediatrics Patients (CSF Culture), K.K.U.H. Al Zamil FA. J Egypt Public Health Assoc. 2008;83(1-2):35-47 Number of patients

55. Yearly Statistics of Paediatrics Patients (Blood Culture), K.K.U.H. Number of patients Al Zamil FA. J Egypt Public Health Assoc. 2008;83(1-2):35-47

56. –Most important virulence factor –Protects against phagocytosis by granulocytes and macrophages –Elicits a T-cell-independent (not boostable) immune response –Approximately 90 serotypes identified bases on its antigenic composition Streptococcus Pneumoniae: Polysaccharide Capsule

57. RESULTS:RESULTS: Isolates from 78 patients, 72% of whom were children, were studied. Eighty-eight percent of the isolates belonged to only 10 serogroups/serotypes, namely 6 and 19, 1 and 15, 14 and 23, 7, 18 and 22, in descending order of frequency. Potential coverage of the 7-valent, 9-valent, and 11-valent conjugate vaccines were 54%, 65% and 73%, respectively. The rate of reduced penicillin susceptibility in the serogroups represented in the 7-valent conjugate vaccine was significantly higher than in the non-vaccine serogroups (62% vs. 25%; p=0.0023) Ann Saudi Med 25(2) March-April 2005 Streptococcus pneumoniae serotypes/serogroups causing invasive disease in Riyadh, Saudi Arabia: extent of coverage by pneumococcal vaccines Abdulrahman Al-Mazrou, MD, FRCP(C); Kingsley Twum-Danso, FRCPath; Fahad Al Zamil, ABP; Abdelmageed Kambal, FRCPath Dr. Fahad Al Zamil

58. CONCLUSION: CONCLUSION: The currently available 7-valent pneumococcal conjugate vaccine provides sub-optimal coverage to serogroups causing invasive diseases in our community. However, this vaccine would be a useful adjunct to penicillin prophylaxis in at- risk patients in the community. The effectiveness of the vaccine would be greater if serotype 15 could be included. Ann Saudi Med 25(2) March-April 2005 Cont. Streptococcus pneumoniae serotypes/serogroups causing invasive disease in Riyadh, Saudi Arabia: extent of coverage by pneumococcal vaccines Abdulrahman Al-Mazrou, MD, FRCP(C); Kingsley Twum-Danso, FRCPath; Fahad Al Zamil, ABP; Abdelmageed Kambal, FRCPath Dr. Fahad Al Zamil

59. Haptavalent Conjugate Pneumococcal Vaccine 1.Contains: serotypes 4, 6B, 9V, 14, 18C, 19F and 23F 2.Potentially prevents: 86% of bacteremia, 83% of meningitis and 65% of otitis media in children <6 years

60. Invasive Pneumococcal Disease (IPD) Coverage for the 7 Serotypes in Prevnar COUNTRYAGEDISEASE COVERAGE France<283% Spain<580% Germany<576% Italy<579% US<580%

61. Safety  The most frequently reported adverse events included injection site reactions, fever ( ≥ 38 o C/100.4 o F), irritability, drowsiness, restless, sleep, decreased appetite, vomiting, diarrhea, and rash

62. Episodes of AOM from Various Causes 7PCV x Control Eskola J et al, NEJM, 2001;344:403-409 Vaccine N = 831 Control N = 831 VE (%) 95% Cl Culture-confirmed pneumococcus2714143421 to 45 Pneumococcal serotypes included in the vaccine (all combined) 1072505744 to 67 Cross-reactive pneumococcal serotypres (all combined) 41845127 to 67

63. Efficacy of PCV Clinical Studies of PCV in CXR-positive Pneumonia 1.Black SB, et al. Pediatr Infect Dis J. 2002;21:810-815. 2.Hansen J, et al. Pediatr Infect Dis J. 2006;25:779-781. Study Efficacy (95% CI) [CXR-positive Pneumonia † (ITT)] PCV7 United States—NCKP 1 18% (5-29) Re-analysis of NCKP (WHO criteria) 2 26% (7-41) Investigational PCV9* South Africa 3 Total population17% (4-28) HIV-negative20% (2-35) HIV-positive13% (-7-29) The Gambia 4 36% (27-43) *Investigational 9-valent pneumococcal conjugate vaccine † All-cause hospitalization and mortality reduced by 15% and 16%, respectively CXR=chest x-ray; NCKP=Northern California Kaiser Permanente 3.Klugman KP, et al. New Engl J Med. 2003;349:1341-1348. 4.Cutts F, et al. Lancet. 2005;365:1139-1146. Efficacy of PCV7 and PCV9* in Radiologically Confirmed Pneumonia 1-4 PCV decreases radiologically documented alveolar pneumonia 1-4

64. Changes in Incidence Rate of IPD among Children Aged  5 years before and after introduction of PCV7, by age – Active Bacterial Core Surveillance, Eight States, 1998-2005 Rate / 100,000 Population Year Age (yrs) MMWR. 2008;57(06):144-148 19981999200020012002200320042005 0 50 100 150 200 250 <1 1 2 3 4 PCV7 introduced

65. AOM Antibiotic resistance Herd immunity Pneumonia IPD Effectiveness of PCV PCV Effectiveness

66. PREVENAR introduced Choi EH, et al. Emerg Infect Dis. 2008;14:275-281. Increasing Proportion of 19A Isolates in Children <5 Years of Age Prior to Introduction of PREVENAR * Into Korea in 11/2003 % Isolates p=0.005 Serotype Epidemiology Replacement With 19A (Korea) Year A cause-and-effect relationship between PREVENAR and increasing 19A cannot be determined, as evidenced by increased 19A prior to the introduction of PREVENAR in S. Korea

67. 67 EndpointNumber of episodes Vaccine Efficacy P value 11Pn-PDHAV % 95% CI Clinical episodes 333499 33.6 20.8 to 44.3 <0.001 Culture confirmed bacterial episodes 178306 42.1 27.7 to 53.7 <0.001 Recurrent AOM 818 55.6 -1.9 to 80.7.052 Placement of Vent. Tube 410 60.2 -26.7 to 87.5.119 *As confirmed by both pediatrician and ENT POET impact on recurrent disease and ear-tube placements Prymula R, et al. Lancet 2006;367:740-748.

68. PCV746B9V1418C19F23F PCV7 13 46B9V1418C19F23F 1356A7F19A With six additional serotypes PCV7 13 offers the broadest serotype coverage against pneumococcal disease PCV13 contains the same carrier protein – CRM 197, a carrier protein used in bacterial conjugate vaccines for more than 20 years PCV 13

69. Global IPD serotype distribution among children <5 years – before pneumococcal conjugate vaccination *Weighted by regional disease burden Serotype Serotyped isolates (%) Cumulative distribution (%) Serotypes by rank order and cumulative serotype distribution Pneumococcal Global Serotype Project (version 2), 30 November 2008. Prepared by GAVI’s PneumoADIP Prevenar 13 contains the 13 serotype causing most of IPD in children < 5 years.

70. 70 Rationale for inclusion of additional serotypes in PCV13 Serotype 1 Important cause of pneumococcal disease in many regions Cause of epidemic disease Important cause of pneumococcal pneumonia, predominant serotype in empyema in children Serotype 5 Cause epidemic disease Among the leading serotypes in Africa and South America Serotype 7F Important cause of pneumococcal disease globally, increasing in many European countries Higher case fatality reported from Germany Serotype 3 Important cause of pneumococcal disease including pneumonia and AOM Increasingly reported in IPD in Europe Among the leading serotypes in CAP and IPD in adults Serotype 6A Commonly found in carriage and frequently antibiotic resistant Important cause of pneumococcal disease, particularly AOM Decrease in 6A pediatric IPD following use of PCV7, remaining disease may be mostly 6C Serotype 19A Commonly found in carriage and frequently antibiotic resistant Significantly increased in IPD globally Commonly found in AOM 19F antibodies from PCV7 vaccination do not cross-protect for 19A infection Dagan et al. J Infect Dis 2008;197(8):1094-102. Dagan et al. Clin Infect Dis 2000;30(2):319-21. Brueggemann et al. Journal of Clinical Microbiology 2003;41(11):4966-70, Gratten Med J Aust 1993;158(5):340-2, Nunes et al. Clin Microbiol Infect 2008;14(1):82-4, Romney et al. Clin Infect Dis 2008;47(6):768-74, Ruckinger et al. Pediatr Infect Dis J 2009;28(2):118-22, Whitney et al. Lancet 2006;368(9546):1495-502, Dagan & Klugman Lancet Infect Dis, 8(12), 785-795 (2008), Byington et al. Pediatr Infect Dis J, 25(3), 250-254 (2006), Fletcher et al. Pediatr Infect Dis J, 25(6), 559-560 (2006), Cohen et al. Vaccine, (2009) in press, Hausdorff WP, Vaccine, 25(13), 2406-2412 (2007), Imohl et alClin Microbiol Infect, (2009), in press)

71. WHO considers that pneumococcal conjugate vaccine should be a priority for inclusion in national childhood immunization programmes. Weekly Epid. Record; 23 March 2007

72. Posted on the Pediatric SuperSite on October 27, 2011 Invasive pneumococcal disease decreased after introduction of PCV13 IDSA 49th Annual Meeting Sheldon L. Kaplan Kaplan’s research, which was presented at the IDSA 49th Annual Meeting, highlighted a 75% reduction in invasive pneumococcal infections in children after the 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar, Pfizer) was introduced in 2000. In 2005, prevalence of non-PCV7 serotypes of invasive pneumococcal disease — particularly 19A — had increased. The current study reports on early data for invasive pneumococcal disease in children after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13, Pfizer) in February 2010.pneumococcal infections in children “After PCV13, we saw a 45% decline in serotype 19A,” Kaplan said. “This is a very encouraging result.”

73. Childhood Immunization Schedule in Saudi Arabia Future Plans 1.Universal Meningococcal conjugate vaccine 2.Acellular pertussis vaccine 3.Rotavirus vaccine 4.HPV

74. Causes of 4.1 million deaths in under-five (out of 10.5 million total deaths) in 2002 Source: World Health Report 2004 34% 27% Available New Vaccines

75. Four-month-old female with gangrene of hands and lower extremities due to meningococcemia

76. Four-month-old female with gangrene of feet due to meningococcemia

77. Four-month-old female with gangrene of hands due to meningococcemia

78. Four-month-old female with gangrene of hand due to meningococcemia

79. Reported Cases of Meningococcal Disease Saudi Arabia, 1970 – 2008 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

80. Reported Cases of Meningococcal Disease Saudi Arabia, 1994 – 2008 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

81. Meningococcal Cases by Region, Saudi Arabia, 1999 - 2003

82. Meningococcal Cases by Residency, Saudi Arabia, 1999 - 2003

83. Meningococcal Cases by Age Group, Saudi Arabia, 1999 - 2003

84. Meningococcal Disease by Serogroup* Saudi Arabia, 1994 – 2008 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009 * Cases for whom a serogroup was identified and reported

86. Serogroup CrSBA titers pre and 1 month post vaccination with meningococcal A/C polysaccharide vaccine rSBA GMTs Jokhdar H, Borrow R, Sultan A et al. Immunologic Hyporesponsiveness to Serogroup C but Not Serogroup A following Repeated Meningococcal A/C Polysaccharide Vaccination in Saudi Arabia. Clin Diagn Lab Immunol. 2004;11:83-88 Previous vaccination status

87. Geometric Mean Titers 28D post MCV4 or MPV4 Vaccination Menactra induce significantly higher immune response than MPSV Children Pichichero EM, Casey J, Blatter M et al. Comparative Trial of the Safety and Immunogenicity of Quadrivalent ACYW135 Meningococcal Polysaccharide-Diphtheria Conjugate Vaccine Versus Quadrivalent Polysaccharide Vaccine in Two-to-Ten Year Old Children. Pediatric Infectious Diseases Journal. 2005;24:57-62.

88. World Health Organization, Jemal A, et al. CA Cancer J Clin 2007. Incidence of cancer in Saudi Arabia 2004, National Cancer Registry Cervical Cancer Worldwide second most common cause of cancer-related deaths among women –500,000 cases and 280,000 deaths in 2006 United States –11,150 cases and 3,670 deaths in 2007 –10 women die each day from cervical cancer Saudi Arabia –89 new cases in 2004. –No national screening program. –Late presentation

89. The Nobel Prize in Physiology or Medicine 2008 Harald zur Haussen "for his discovery of human papilloma viruses causing cervical cancer" October 6th 2008

90. Worldwide Most Common HPV Types in Cervical Cancer: Cumulative Prevalence (SCC) Bosch, FX, de Sanjose S. J Natl Cancer Inst Monogr. 2003;31:3-13. Reprinted with permission from Oxford Journals, Oxford University Press. Abdel-Hadi, M, Sughayer, M. 12 th Biennial Meeting of the International Gynecologic Cancer Society. HPV genotypes in cervical cancer in Jordan. 70.4 80.3 73.1 76.9 54

91. Saudi Age-Specific Percentages Source: National Cancer Registry

92. The Burden of Disease Caused by HPV: Beyond the Numbers Financial Emotional Physical 1. Ashing-Giwa KT, Kim J, Tejero JS. Psycho-Oncology. 2004;13:709–728. 2. Taylor CA, Keller ML, Egan JJ. J Nurs Scholarsh. 1997;29:27–32. 3. Insinga RP. Womens Health Issues. 2006;16:236–242. 4. Maw RD, Reitano M, Roy M. Int J STD AIDS. 1998;9:571–578. 5. Anhang R, Gooman A, Goldie SJ. CA Cancer J Clin 2004;54:248–259. Fear of cancer 4,5 Financial burden 1 Stigma 2 Symptoms 1 Negative self-perception 1 Anxiety 1,4,5 Pain 1,4 Depression 1,2 Lost productivity 3 Sexual difficulties 1,5 Social isolation 1,2

93. Saudi Arabia Cervical Cancer Incidence Percentage distribution of cancer incidence among Saudis by sex, according to age group. Source: Saudi Cancer Registry, 2002

94. Saudi Arabia Cervical Cancer Incidence ASR regional distribution of Cervical Cancer in Saudi Arabia Source: Saudi Cancer Registry, 2002

96. 96 Autoimmune-Associated Events, Pooled Safety Dataset Conditions GARDASIL (N = 3092) AAHS Control or Saline Placebo (N = 2303) n (%) Alopecia Areata Ankylosing Spondylitis Arthralgia/Arthritis/Reactive Arthritis Autoimmune Thrombocytopenia Diabetes Mellitus Type 1 Hyperthyroidism Hypothyroidism Inflammatory Bowel Disease Myocarditis Proteinuria Psoriasis Vitiligo 1 (0.0) 30 (1.0) 1 (0.0) 3 (0.1) 0 (0.0) 3 (0.1) 0 (0.0) 1 (0.0) 0 (0.0) 2 (0.1) 0 (0.0) 2 (0.1) 17 (0.7) 0 (0.0) 2 (0.1) 1 (0.0) 0 (0.0) 2 (0.1) 1 (0.0) 0 (0.0) 2 (0.1) 5 (0.2) All Conditions43 (1.4)32 (1.4) N = Number of individuals who received at least one dose of either vaccine or placebo n = Number of individuals with specific new Medical Conditions

97. Cervical cancer age-standardized (ASR) incidence rates in selected countries

98. SUMMARY Cervical cancer remains a problem. Cervical cancer is caused by HPV infection. 70% caused by HPV 16 / 18. Cervical cancer can be prevented. HPV vaccination can prevent up to 70% of cervical cancer cases. HPV vaccine is for prevention as the word vaccine indicates; it is not for treatment. HPV vaccine recommended for teenage girls, before they start sexual contact.

99. Date of Web Publication 27-Aug-2009 Conclusion: A high prevalence of HPV-16/18 was found, but with a low rate of progression to CIN. A signifi ­ cant association with abnormal cytology was found only in patients with HPV-16/18 mixed infection. Human papilloma virus-16/18 cervical infection among women attending a family medical clinic in Riyadh Tarfah Al-Muammar 1, Mohammed N Al-Ahdal 2, Ahmed Hassan 1, George Kessie 3, Damian M Dela Cruz 3, Gamal E Mohamed 4 Tarfah Al-MuammarMohammed N Al-AhdalAhmed HassanGeorge KessieDamian M Dela CruzGamal E Mohamed

100. P-777: A bibliometric analysis of prevalence and control of Human Papillomavirus infection among females in the Middle-East Saeed Akhtar 1. 1 Department of Community Medicine, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. Results: Only 12 of 21 countries of the Middle East contributed one or more studies on HPV infection in women. There was no HPV related population-based or clinical research done in remaining countries in the region. Among the women who underwent routine gynecological examination, the prevalence of HPV infection ranged from 4.9% in Lebanon, 13% in Palestine and 31.6% in Saudi Arabia. Among sex workers, the prevalence of HPV infection was about 10% in Turkey. Women with cytological abnormalities had much a higher prevalence of about 80% in Turkey and Saudi Arabia, where it was almost 100% among of women with cervical carcinoma. The predominantly HPV subtypes were HPV-16/18. Conclusions: Available data suggest that the prevalence of HPV infection ranged from 5% to 31% in general population, 80% among women with cytological abnormalities and almost 100% among women with cervical carcinoma. More data are needed to map out the HPV infection load in female population of the region

108. BCG Lymphadenitis

109. Severe suppurative adenopathy post-BCG vaccination.

110. Inoculation site abscess post-BCG vaccination.

111. Suppurative BCG lymphadenitis in right axillary region. The lymph node measures 5 cm in diameter, and is fluctuant in centre and the overlying skin is inflamed

113. Lymphadenitis 12 weeks after vaccination, with infiltration of the skin

114. Outbreak of BCG related lymphadenitis in Saudi children at a university hospital after a change in BCG vaccine Abdulkarim Alrabiaah, a Sarah Alsubaie, a,b Elham Bukhari, a Fahad Alzamil, a Ashry Gad c a Department of Pediatrics, College Of Medicine, King Saud University, Saudi Arabia. Conclusion: We conclude that increased susceptibility to the BCG SSI vaccine might have contributed to the increased incidence of lymphadenitis in these children. Hence, caution should be exercised in switching from one vaccine to another, as is often done in developing countries.

115. BCG Lymphadenitis: A 6 year experience in two Saudi hospitals Conclusion: An increase in BCG lymphadenitis was observed in our population, with an incidence higher than expected. The cause of this increase is likely secondary to changes in the vaccine strain. Medical treatment appears to be effective when used in conjunction with needle aspiration for enlarged lymph nodes. Further research is needed to clarify the exact incidence, etiology and optimal management of BCG lymphadenitis.

116. BCG Lymphadenitis: A 6-year experience in two Saudi hospitals Indian Journal of Pediatrics Conclusion: An increase in BCG lymphadenitis was observed in our population. The cause of this increase is likely secondary to changes in the vaccine strain. Medical treatment appears to be effective when used in conjunction with needle aspiration for enlarged lymph nodes.

117. Number of BCG lymphadenitis cases per year from 2005-2010

118. Age (months)frequency >18(5.5%) 2-360(41%) 3-470(48%) 4-56(4%) 61(0.6%) Table 1: The age distribution of infants with BCG lymphadenitis.

119. *Non-suppurative lymphadenitis that resolved without treatment.58 (40%). * Suppurative lymphadenitis progressed.87 (60%) 1- Ruptures spontaneously & regresses.12 (13.7%) 2-Regresses with fine needle aspiration.30 (34.4%) 3-Regresses with treatment.45 (51.7%) Table 2: Natural course of BCG lymphadenitis during follow up.

120. Expanded Program of Immunization in Saudi Arabia – {2011-the future}