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N. meningitidis; From Global to Local Perspectives Professor Fahad Al-Zamil Professor and Consultant Pediatric Infectious Diseases, Head of Infectious.

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Presentation on theme: "N. meningitidis; From Global to Local Perspectives Professor Fahad Al-Zamil Professor and Consultant Pediatric Infectious Diseases, Head of Infectious."— Presentation transcript:

1 N. meningitidis; From Global to Local Perspectives Professor Fahad Al-Zamil Professor and Consultant Pediatric Infectious Diseases, Head of Infectious Disease Unit King Saud University

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, Gloucestershiresmallpox vaccine [1] [2][3][4]EnglishBerkeley, Gloucestershiresmallpox vaccine [1] [2][3][4]

3 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 JennercowpoxEdward 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 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  Joseph Meister (21 February 1876 - 16 June 1940) was the first person to be inoculated against rabies by Louis Pasteur, and the first person to be successfully treated for the infection. inoculatedrabiesLouis Pasteur  In 1885, nine-year-old Meister was bitten by a rabid dog after provoking it by poking it with a stick. Pasteur decided to treat the boy with a rabies virus grown in rabbits and weakened by drying, a treatment he had earlier tried on dogs. The treatment was successful and the boy did not develop rabies. Joseph Meister

6 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

7  Meningococcal Disease  Global epidemiology  Local epidemiology  Shortcomings of Meningococcal polysaccharide vaccines  Conclusion

8 8  Four-month-old female with gangrene of hands and lower extremities due to meningococcemia

9 9 Four-month-old female with gangrene of feet due to meningococcemia

10 10 Four-month-old female with gangrene of hands due to meningococcemia

11 11 Four-month-old female with gangrene of hand due to meningococcemia

12 12 Neisseria meningitidis; The pathogen  Strictly human pathogen  Transmission by aerosol droplet, crowding facilitates  Asymptomatic carriage in 10-30%  Under 1% of carriers become symptomatic  Invasive diseases include: meningitis, meningococcemia, pneumonia, septic arthritis  High capacity DNA transformation and recombination systems allow acquisition of genes by horizontal gene transfer

13 13 Difficult to Diagnose, Rapidly Lethal 1 Reference: 1. Thompson MJ, et al. Lancet. 2006;367(9508):397-403. 12–15 hours Characteristic 15–~24 hours Late 4–8 hours Nonspecific Typical time course of meningococcemia and meningitis Fever, irritability, nausea or vomiting, drowsiness, poor appetite, sore throat, coryza, general aches Hemorrhagic rash, neck pain, meningismus, photophobia Confusion or delirium, seizure, unconsciousness; possible death Hospital admission at median of ~19 hours

14 14 Meningitis  Fever and headache (flu-like symptoms)  Stiff neck  Altered mental status  Seizures 3%–10% fatality rate Meningococcemia  Rash  Vascular damage  Disseminated intravascular coagulation  Tissue damage  Shock  Death within 24 hours 20%–40% fatality rate Clinical Presentation Apicella MA. In: Principles and Practice of Infectious Diseases. 1995:1896-1909; Jodar L, et al. Lancet. 2002;359:1499; Granoff DM, et al. In: Plotkin SA, ed. Vaccines. 4 th ed. Philadelphia: W.B. Saunders Co; 2004; Rosenstein NE, et al. N Engl J. 2001;344:1378

15 15 Serious Outcomes of Meningococcal Disease  Death (10%  15%)  Long-term sequelae (10%  15%) – Deafness – Cranial nerve palsy – Retardation – Limb loss Granoff DM, et al. In: Plotkin SA, ed. Vaccines. 4 th ed. Philadelphia: W.B. Saunders Co; 2004

16  Meningococcal Disease  Global epidemiology  Local epidemiology  Shortcomings of Meningococcal polysaccharide vaccines  Conclusion

17 17 Adapted from Granoff DM, Feavers IM, Borrow R. Meningococcal vaccines. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th ed. Philadelphia: Saunders; 2004: 959-87 N. meningitidis Serogroup Characteristics A  Leading cause of disease worldwide due to large African epidemics  Major cause of endemic disease in Africa, China, Russia, India  Rare in Americas, Western Europe B  Major cause of endemic disease in Europe, the Americas, Southeast Asia, Oceana C  Major cause of endemic disease in Europe, the Americas, Oceania Y  Small percentage of infections worldwide  Increasing problem in North America among adolescents W-135  Small percentage of infections worldwide  Recent worldwide outbreaks related to Hajj pilgrimage  Potential agent for large-scale epidemics (Africa) X, 29E, Z, …  Very rare cause of infections worldwide

18 18 * Provisional data (N is total serogrouped strains. Other includes other serogroups and non groupable strains) AFRICAN MENINGITIS BELT 2003-2004 (n=501) Other 1,2% A 79% W-135 20% AUSTRALIA 2004 (n=335) C 21% A 0,3% B 73% W-135 3,6% Y 2,4% WESTERN EUROPE 2002 (n=3,982) A 0,1% C 29% Other 1,0% B 64% W-135 3,6% Y 2,3% RUSSIA 2002-2004 (n=1,899) B 32% A 36% C 22% Other 10% CHILE 2003 (n=193) Other 5% C 14% B 78% W-135 1% Y 2% UNITED STATES 2003 (n=200) Y 27% C 21% B 44% Other 6% W-135 2% TAIWAN 2001 (n=43) Y 19% A 4,7% W-135 41% B 33% C 2,3% THAILAND 2001 (n=36) Other 2% B 81% W-135 17% SAUDI ARABIA 2002 (n=21) B 10% W-135 76% A 14% BRAZIL 2003 Sao Paulo state (n=426) B 39% C 57% Other 4% COLOMBIA 2004 (n=37) Y 32% B 51% W-135 3% C 14% NEW ZEALAND 2004 (n=252) C 8% Other 0,8% B 87% W-135 3,6% Y 0,4% SOUTH AFRICA 2005 (n=414) Other 0,5% C 5% B 14% W-135 62% A 6% Y 13% URUGUAY 2001 (n=53) C 11% B 83% Other 6% Canada 2003* (n=148) Y 25% C 24% B 43% Other 1% W-135 7% AFRICAN MENINGITIS BELT 2003-2004 (n=501) Other 1,2% A 79% W-135 20% AUSTRALIA 2004 (n=335) C 21% A 0,3% B 73% W-135 3,6% Y 2,4% WESTERN EUROPE 2002 (n=3,982) A 0,1% C 29% Other 1,0% B 64% W-135 3,6% Y 2,3% RUSSIA 2002-2004 (n=1,899) B 32% A 36% C 22% Other 10% CHILE 2003 (n=193) Other 5% C 14% B 78% W-135 1% Y 2% UNITED STATES 2003 (n=200) Y 27% C 21% B 44% Other 6% W-135 2% TAIWAN 2001 (n=43) Y 19% A 4,7% W-135 41% B 33% C 2,3% THAILAND 2001 (n=36) Other 2% B 81% W-135 17% SAUDI ARABIA 2002 (n=21) B 10% W-135 76% A 14% BRAZIL 2003 Sao Paulo state (n=426) B 39% C 57% Other 4% COLOMBIA 2004 (n=37) Y 32% B 51% W-135 3% C 14% NEW ZEALAND 2004 (n=252) C 8% Other 0,8% B 87% W-135 3,6% Y 0,4% SOUTH AFRICA 2005 (n=414) Other 0,5% C 5% B 14% W-135 62% A 6% Y 13% URUGUAY 2001 (n=53) C 11% B 83% Other 6% Canada 2003* (n=148) Y 25% C 24% B 43% Other 1% W-135 7% Global Serogroup Distribution in the early 2000’s

19 19 General Epidemiological Pattern of Invasive Meningococcal Disease Different populations have widely varying incidence rates of invasive meningococcal infection [1] World Health Organization. Control of Epidemic Meningococcal Disease. WHO Practical Guidelines. WHO/EMC/BAC/98.3. 2nd ed. Geneva, Switzerland, World Health Organization, 1998. Available at: http://www.who.int/emc-documents/meningitis/whoemcbac983c.html. Accessed April 12, 2005. [2] WHO. Wkly Epidemiol Rec 2003;78:294- 6; [3] Wilder-Smith A, et al. Clin Infect Dis 2003;36:679-83; [4] Harrison LH, et al. JAMA 2001;286:694-9; [5] CDC. MMWR Recomm Rep 2000;49(RR-7):11-20; [6] Neal KR, et al. Epidemiol Infect 1999;122:351-7; [7] Brundage, JF, et al. Clin Infect Dis 2002;35:1376-81; [8] Spiegel A, et al. Santé 1996;6:383-8; [9] CDC. MMWR Morbid Mortal Wkly Rep 2004;51(53):1-84; [10] Squires SG, et al. Can Commun Dis Rep 2004; 30:17-28; [11] European Union Invasive Bacterial Infection Surveillance network. Invasive Neisseria meningitidis in Europe 2002. Dec 2003. Available at http://www.euibis.org/documents/2002_meningo.pdf. Accessed April 12, 2005.http://www.who.int/emc-documents/meningitis/whoemcbac983c.htmlhttp://www.euibis.org/documents/2002_meningo.pdf

20 20 Hajj and Umra Visitors E.Asia & Pacific 169,437 visitors Africa 369,727 visitors Americas 7,576 visitors Europe 168,946 visitors Middle East 3,449,212 visitors South Asia 1,755,992 visitors Map courtesy of BYU Geography Department, Data from Kingdom of Saudi Arabian Department of Tourism 2007

21  Meningococcal Disease  Global epidemiology  Local epidemiology  Shortcomings of Meningococcal polysaccharide vaccines  Conclusion

22 22 Reported Cases of Meningococcal Disease Saudi Arabia, 1970 – 2008 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

23 23 Reported Cases of Meningococcal Disease Saudi Arabia, 1994 – 2008 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

24 24 Meningococcal Cases by Region, Saudi Arabia, 1999 - 2003 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

25 25 Meningococcal Cases by Age Group, Saudi Arabia, 1999 - 2003 Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009

26 26 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

27  Meningococcal Disease  Global epidemiology  Local epidemiology  Shortcomings of Meningococcal polysaccharide vaccines  Conclusion

28 28 Shortcomings of current of polysaccharide Vaccine  T-cell-independent immune response producing no memory  Absence of herd immunity in unvaccinated population  No effect on carriage status  Frequent revaccination needed each 3 years.  Hypo-responsiveness occurred upon revaccination.  No Boosting effect.  Poor immunogenicity among the younger age groups. Dose those shortcomings of local impact?

29 29 Demonstrated hyporesponsiveness upon MPSV repeated vaccination  Serogroup C rSBA titers pre and 1month post MPSV vaccination 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

30 30 AlMazrou Y, Khalil M, Borrow R, et al. Serologic responses to ACYW135 polysaccharide meningococcal vaccine in Saudi children under 5 years of age. Infection and Immunity 2005;73:2932-39.

31 31  In Saudi Arabia, very young children demonstrated relatively poor immune response to Meningococcal Polysaccharide Vaccine  AL-Mazrou Y, Khalil M, Borrow R et al. Serologic Responses to ACYW135 Polysaccharide Meningococcal Vaccine in Saudi Children under 5 Years of Age. Infect Immun. 2005;73:2932-39

32 32 Conclusion  Meningococcal disease is sever and devastating.  Saudi Arabia is at high risk due to several factors  The currently used MPSV4 having several limitations.  The solution is to shift to the modern MCV4

33 33 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


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