Center for Communicable Diseases Control New Vaccines Hossein Masoumi Asl Center for Communicable Diseases Control

Global Immunization Vision and Strategy (GIVS): Implications for Immunization Policy Development

Realizing the vision Four strategic areas Reaching more people Introducing new vaccines and technologies Synergies with other interventions in health systems context Global interdependence … Context : - Remarkable progress… but * Coverage stagnation/disparities * Fragmentation of EPI - GIVS offers a unifying vision of immunization main thrusts for 2006-15

Goals By 2010: 90% routine vaccination coverage nationally and 80% in all districts 90% reduction of global mortality due to measles (compared to 2000) By 2015: Maintain Coverage achievement (80%-90%) 2/3 reduction of global childhood mortality and morbidity due to VPDs (compared to 2000) [MDG4]

Under-Five Child Mortality Global Distribution of Cause-Specific Child Deaths Under-nutrition (underlying cause) IMMUNIZATION POTENTIAL: ~25% CHILD MORTALITY REDUCTION BY 2015 Source: 2005 World Health Report

Leading causes of vaccine-preventable deaths in children under 5 years old Source/credits: The Global Burden of Disease: 2004 update, * WHO/IVB estimates based on GBD estimates, deaths for 2000 ** WHO/IVB estimates based on GBD estimates, 2004 update As at February 2009

Preventable with (current) expected improvements in coverage Preventable if coverage is scaled up to 90% and widespread use of new vaccines 60%-70% reduction in rate GIVS GOAL by 2015: Two-thirds reduction of global childhood morbidity and mortality due to VPDs compared to 2000 levels Not preventable by 2015 Source: Lara's calculations on 22 Oct 2004, based on files developed for IFFI project. Mortality averted based on "existing vaccines" includes tetanus (neonatal and other), pertussis, diphtheria, measles, YF, and Hib. Polio is not shown (very little mortality), and Hepatitis B is also not shown (primarily causes mortality in adults; also, the impact of vaccination on HepB mortality will not really be seen by 2015). Mortality based on "near term vaccines" includes JE, Mening A/C, Pneumo, and Rotavirus, based on expected date of introduction/availability, and assuming the vaccine is relatively effective (ie 80% efficacy). Mortality curves are calculated based on expected improvements in coverage: The top line shows the expected mortality rate due to VPD if coverage stayed constant at 2003 levels; the yellow difference is obtained by projections of improvements in coverage, given current trends. The blue difference is if coverage is scaled up to 90% by 2015. Includes the impact of campaigns for measles, tetanus, and yellow fever. We have not made big gains since 2000 in reducing the VPD mortality rate, but even in the year 2000, there were averting 2-3 million deaths per year from VPD.

WHO estimates 2.7M childhood deaths from vaccine preventable illnesses Pneumococcal, Rota & Hib account for two thirds of the vaccine preventable deaths among children

GIVS Strategic Area 2: Introducing new vaccines and new technologies OBJECTIVES Empowerment for country decision making Making vaccines available New vaccines also for the disadvantaged Research and development for needed vaccines MAIN STRATEGIES Country capacity for informed decision making Effective and sustainable supply of new vaccines Research & Development

What are the new vaccine in our country?

Hib Vaccine, 2008 No (21 countries or 11%) Yes (133 countries or 69%) Highlight: India (IRC approved), Nigeria (IRC conditional approval) Not introduced: AFRO: Botswana, Cape Verde. EMRO: Egypt, Iran, Iraq and Tunisia. EURO: Bulgaria, Romania, Russian Federation, Turkmenistan. SEARO: Maldives and Thailand. WPRO: China, Cook Islands, Japan, Nauru, Philippines, Rep of Korea, Singapore, Tuvalu and Vanuatu. Yes Part of the country are: Belarus, Pakistan and Sudan (only North Sudan introduced) 2009 and/or GAVI Approved: AFRO: Cameroon, Comoros, Congo, Côte d'Ivoire, DRC, Equatorial Guinea, Gabon, Mauritania, Mozambique, Namibia, Sao Tome Y Principe, Seychelles, Swaziland and United Rep. Of Tanzania. EMRO: Afghanistan. EURO: Albania, Armenia, Georgia, Kyrgyzstan, Rep. of Moldova and Uzbekistan. SEARO: Bangladesh, Bhutan and Nepal. WPRO: Lao and Vietnam. In addition, Cambodia was approved and said they will introduce in January 2010. Applied not yet approved is: Azerbaijan, India and Nigeria Never applied is DPRK, Haiti, Indonesia, Myanmar, Somalia and Timor Leste No (21 countries or 11%) Yes (133 countries or 69%) Yes-- part of country (3 countries--2%) Intro 2009 or GAVI Approved (27 countries-4%) Applied for GAVI Support (3 countries--2%) Never Applied (6 countries--3%) Source: WHO/IVB database, 193 WHO Member States. Data as of June 2009 Date of slide: 11 June 2009 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2009. All rights reserved

Morbidity: Mortality: Disability Global Burden of Hib diseases ( WHO Estimates - Children < 5 years old) Morbidity: 3 million children with serious illness/ year ~20% of severe pneumonia Mortality: 450,000 deaths/year >1000 preventable deaths every day 1 in 25 child deaths Disability 15-35% of survivors of Hib meningitis suffer lifelong consequences (paralysis, hearing loss, mental retardation, speech problems, learning problems) Acute respiratory infections (2 million deaths each year) are the leading infectious cause of death in children 1mo to 5 years of age. S. pneumo causes approximately 800,000 of those deaths, Hib accounts for almost 400K. Diarrheal diseases are the second leading cause of death with 1.7M deaths – 500K are estimated to be due to rotavirus. Other leading causes of death include Malaria (853), Measles (395) HIV aids (321)

Estimated total Hib disease cases: Estimated total Hib deaths: Burden of Hib disease in the EMR ( WHO Estimates - Children < 5 years old) Estimated total Hib disease cases: 1,140,271 Hib cases/year Estimated total Hib deaths: 49,457 deaths

Hib conjugate vaccines Available since early 1990s Excellent safety record Over 95% efficacy against invasive disease Compatible with EPI schedules Vaccination Interrupts transmission and protects community (Indirect Effect or Herd Immunity)

discontinued (1 country) Plans not clear (3 countries) Hib Vaccine introduction in the EMR Palestine Bahrain introduced (17 countries) discontinued (1 country) Plans not clear (3 countries) No plans (not eligible for GAVI support)

Estimated burden of Hib and pneumococcus for < 5 children

Lumbar Puncture for Detection of Meningitis in Age 2 m – 5 y /100,000 (Population: 491,891) Sep. 2004 -,Mar. 2006 - IRAN No. of highly suspicious No. of Other bacteria N.meningitidis No. of S.pneumoniae No. of H.influenzae Viral LP No. of proven & H.S. Bacterial Men. Abnormal LP N0. of LP 63 45% 16 12% 6 4% 23 17% 30 22% 265 66% 138 34% 403 21% 1874 Incidence rate of H. influenzae Meningitis : 4/100,000/year in 2m-5y children

Estimation of budget needed for Hib vaccine integration Total population: 70,000,000 # of children < 5y: 5,600,000 # of children < 1y: 1,200,000 # of H. influenza meningitis in <5y / Year: 290 # of other invasive H. influenza infections in <5y / Year: ? Cost of vaccine for 3 doses per child: 10 USD Annual budget only for vaccine: 14,000,000 USD

Rotavirus disease and Rotavirus vaccines

Selected hospitals in 5 cities , I.R.IRAN

Rotavirus Gastroenteritis Surveillance Data (Iran, 2006-2008)

Total Sentinel site (province/hospital) Total number of hospitalizations for children <5 years Total number of hospitalized diarrhoea cases* # suspected cases of rotavirus gastroenteritis # stool specimens collected # stool specimens tested Results % Pos. results Neg. Shiraz Dastgheib 13330 4493 3725 1910 1031 (54) 782 Tabriz Kodakan 21362 2095 1506 682 356(52) 318 Mashad Sheikh 3629 944 525 443 423 160(38) 236 Bandarabas 16053 3337 1688 1623 1628 922(57) 634 Tehran Markaztebi 22430 2721 824 312(38) 415 Total 76804 13590 8268 5487 2781 (51) 2385

Morbidity of Rotavirus gastroenteritis Rotavirus detection among AGE cases Hospital-based surveillance network, EMR

Burden of rotavirus disease Estimated Rotavirus mortality for children <5 years, 2004 (as of 31 March 2006) Global: 527000 deaths annually EMR: 61,164 Deaths annually

Two Rotavirus Vaccines Human G1P[8], lyophilized, orally administered Two dose schedule with EPI Bovine-human pentavalent human G1, G2, G3 and G4; bovine G6, P[8] reassortant, Liquid Three dose schedule with EPI Rotarix® GSK RotaTeq® Merck

Rotavirus vaccine introduction in the EMR Palestine Bahrain Introduced (2) introduction 2010/2011 (4) Applying to GAVI for 2011-2013 (4) Considered (2) No plans (10)

Estimation of budget needed for Rotavirus vaccine integration Percent of admitted diarrheal cases attribute to rotavirus: 32% Estimation of annual admission: 15000- 19000* Total number of rotavirus death/year: ? Annual budget only for vaccine: 24,000,000 US$ Need to cold chain will be 4 fold (due to Hib & rotavirus vaccines *: Parashar UD, et al, Global illness and death caused by rotavirus disease in children, Emerging Infectious Diseases . Vol. 9, No. 5, May 2003

Pneumococcal diseases and Pneumococcal conjugate vaccines

Morbidity: ~ 14 million cases Global Burden of pneumococcal diseases ( WHO Estimates - Children < 5 years old) Morbidity: ~ 14 million cases Most common cause of bacterial pneumonia among children Mortality: ~ 840,000 deaths WHO Estimates 2008

Regional of pneumococcal diseases ( WHO Estimates - Children < 5 years old) Morbidity: ~ 1.5 million cases Mortality: ~ 100,000 deaths WHO Estimates 2008

Incidence of IPDs (per 100,000 Children under Age 5) <1000 1000-<2000 2000-<3000 > 3000 The boundaries in the map doesn’t represent official WHO position

S. pneumoniae Mortality (per 100,000 Children under Age 5) <10 10- <100 100-<300 * HIV+ deaths excluded 300-<500 >500 The boundaries in the map doesn’t represent official WHO position

Estimated burden of Hib and pneumococcus for < 5 children

Pneumococcal Conjugate Vaccines Safe and effective: over 95% efficacy against invasive disease Compatible with EPI schedules, suitable for < 2 years children Vaccination Interrupts transmission and protects community (Indirect Effect or Herd Immunity) Available vaccines 7-valent: serotypes 4, 6B, 9V, 14, 18C, 19F, 23F 10-valent: 7-valent + 1, 5, 7F In the pipelines 13-valent: 10-valent + 3, 6A, 19A

WHO position on use of 7 valent pneumococcal vaccine Recognizing the heavy burden of pneumococcal disease occurring in young children and the safety and efficacy of PCV-7 in this age group, WHO considers that it should be a priority to include this vaccine in national immunization programmes, particularly in countries where mortality among children aged <5 years is >50/1000 live births or where >50 000 children die annually. Despite the absence of some serotypes that are important causes of pneumococcal disease in developing countries, PCV-7 can prevent substantial mortality and morbidity in these countries. Once other pneumococcal vaccines offering similar or wider protection become available, countries will be able to decide whether to switch to a different formulation.

Pneumococcal vaccine introduction in the EMR Palestine Bahrain Introduced (6) introduction 2010(1) Planned 2010/2011(2) Applying for 2010-2011(3) Plans not clear/no plans (10)

Status of AAP/CDC recommendations*** DTaP-IPV/Hib (PENTACEL™) Vaccine Manufacturer BLA submitted to FDA BLA age indications** FDA licensure Status of AAP/CDC recommendations*** DTaP-IPV (KINRIX) GlaxoSmithKline (GSK) Jun-2007 4 through 6 years of age Licensed 24-Jun-08 AAP: aapnews.aappublications.org/cgi/content/full/29/8/20 CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5739a4.htm DTaP-IPV/Hib (PENTACEL™) sanofi pasteur Jul-2005 2, 4, 6, and 15 through 18 months of age Licensed 20-Jun-08 AAP: aapnews.aappublications.org/cgi/content/full/29/8/1-b CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5739a5.htm Hib(Hiberix) Mar-2009 Booster dose in children 15 months through 4 years of age Licensed 19-Aug-09 CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5836a5.htm Hepatitis A (VAQTA®) Merck Supplement to original BLA Greater than or equal to 12 months of age Licensed 11-Aug-05 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;120/1/189 CDC: cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm CDC for post-exposure and for international travelers cdc.gov/mmwr/preview/mmwrhtml/mm5641a3.htm Hepatitis A (HAVRIX®) Licensed 17-Oct-05

Vaccine Manufacturer BLA submitted to FDA BLA age indications** FDA licensure Status of AAP/CDC recommendations*** Hepatitis A and Hepatitis B (TWINRIX®) GlaxoSmithKline (GSK) Supplement to original BLA: accelerated dosing Greater than or equal to 18 years of age 0, 7, and 21 through 30 days and 12 month booster Licensed 28-Mar-07 CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5640a5.htm Herpes zoster vaccine (ZOSTAVAX®) Merck Apr-2005 Greater than or equal to 60 years of age Licensed 25-May-06 ACIP: cdc.gov/mmwr/preview/mmwrhtml/rr57e0515a1.htm HPV4 (GARDASIL®) Dec-2005 Females 9 through 26 years of age (3 doses) Licensed 8-Jun-06 ACIP: cdc.gov/mmwr/preview/mmwrhtml/rr56e312a1.htm ACIP Provisional: cdc.gov/vaccines/recs/provisional/downloads/hpv-vac-dec2009-508.pdf AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;120/3/666 Supplement to original BLA Males 9 through 26 years of age Licensed 16-Oct-09 ACIP Provisional: cdc.gov/vaccines/recs/provisional/downloads/hpv-vac-dec2009-508.pdf 27 through 45 years of age To be reviewed Pending FDA licensure HPV2 (Cervarix™) Mar-2007 10 through 25 years of age Influenza vaccines - TIV varies n/a See recommendations AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;124/4/1216 CDC: cdc.gov/mmwr/preview/mmwrhtml/rr5808a1.htm CDC Seasonal: cdc.gov/flu CDC H1N1: cdc.gov/h1n1 Influenza - LAIV-T (FluMist®) MedImmune 24 months to 49 years of age Licensed 19-Sep-07

Vaccine Manufacturer BLA submitted to FDA BLA age indications** FDA licensure Status of AAP/CDC recommendations*** Japanese Encephalitis (IXIARO) Intercell Biomedical Dec-2007 Greater than or equal to 17 years of age Licensed 30-Mar-09 ACIP Provisional: cdc.gov/vaccines/recs/provisional/downloads/je-july2009-508.pdf MCV4 (Menactra®) sanofi pasteur Dec-2003 11 through 55 years of age Licensed 14-Jan-05 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;116/2/496 CDC: cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm Supplement to original BLA March 2005 2 through 10 years of age only for children at high risk Licensed 18-Oct-07 ACIP: cdc.gov/mmwr/preview/mmwrhtml/mm5717a4.htm MCV4 (Menveo™) Novartis Aug-2008 To be reviewed Pending FDA licensure MenCY-Hib (MenHibrix™) GlaxoSmithKline (GSK) 2009 2, 4, 6 and 12 months of age MMRV (ProQuad®) Merck Aug-2004 Same as for MMR dose 1 or dose 2; 12 months through 12 years of age Licensed 6-Sep-05 CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5447a4.htm CDC Update: cdc.gov/vaccines/recs/provisional/downloads/mmrv-oct2009-508.pdf

Vaccine Manufacturer BLA submitted to FDA BLA age indications** FDA licensure Status of AAP/CDC recommendations*** PCV13 (Prevnar 13®) Wyeth Mar-2009 2 months through 5 years of age To be reviewed Pending FDA licensure Rotavirus (ROTATEQ®) Merck Apr-2005 2, 4, and 6 months of age Licensed 3-Feb-06 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;123/5/1412 ACIP: cdc.gov/mmwr/PDF/rr/rr5802.pdf Rotavirus (ROTARIX®) GlaxoSmithKline (GSK) Jun-2007 2 and 4 months of age Licensed 3-Apr-08 Tdap (BOOSTRIX®) Jul-2004 10 through 18 years of age Licensed 3-May-05 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;117/3/965 CDC: cdc.gov/mmwr/preview/mmwrhtml/rr5503a1.htm Supplement to original BLA 19 through 64 years of age Licensed 4-Dec-08 CDC: cdc.gov/mmwr/preview/mmwrhtml/mm5814a5.htm Tdap (ADACEL™) sanofi pasteur Aug-2004 11 through 64 years of age Licensed 10-Jun-05 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;117/3/965 CDC Adolescent: cdc.gov/mmwr/preview/mmwrhtml/rr5503a1.htm CDC Adult: cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm ACIP in Pregnancy: cdc.gov/mmwr/preview/mmwrhtml/rr5704a1.htm Varicella virus second dose (Varivax®) Supplement to original BLA: second dose 12 months to 12 years of age (3 month minimum interval) Licensed 5-Apr-05 AAP: aappolicy.aappublications.org/cgi/content/full/pediatrics;120/1/221 CDC: cdc.gov/mmwr/preview/mmwrhtml/rr5604a1.htm