The Promise of Introducing Rubella Containing Vaccines on the Impact of Rubella and Measles Control GAVI Partners Forum 4 6 December 2012, Dar es Salaam, Tanzania Maya van den Ent, MPH, UNICEF Peter Strebel, MD, MPH, WHO Steve Cochi, MD, CDC Susan Reef, MD, CDC Robert Kezaala, MD, UNICEF UNICEF/MLWB2010-112/Noorani;
Outline The clinical manifestations of Congenital Rubella Syndrome (CRS) Burden and cost of CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles and rubella
The clinical manifestations of Congenital Rubella Syndrome (CRS) Burden and Cost of CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles and rubella
Congenital Rubella Syndrome Infection early in pregnancy most dangerous (<12 weeks gestation) Weeks 1-10 90% CRS* Weeks 11-12 33% Weeks 13-14 11% Weeks 15-16 24% Weeks > 17 0% May lead to fetal death or premature delivery Organ specificity generally related to stage of gestational infection *Miller E. Lancet 1982;2:781-4.
Congenital Rubella Syndrome Hearing Impairment Cataracts Heart defects Microcephaly Developmental Delay Bone alterations Liver and spleen damage
Congenital Rubella Syndrome Ages 1 40 years 1966 1970 2005 Courtesy: Dr Louis Z Cooper
Among the most tragic infectious diseases of humans are those that pass from the pregnant woman to her unborn child.
The clinical manifestations of Congenital Rubella Syndrome (CRS) Burden and Cost of CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles and rubella
Average incidence of CRS per 100,000 live births, 2008 Average CRS incidence per 100,000 live births <50 50-<100 100-<150 >150 No data Source: Vynnycky, Adams, HPA,et al (in preparation)
CRS burden estimates, globally * and by region, 1996 and 2008 Regions 1996 2008 Est. CRS Cases Range Est. CRS Cases Range GLOBAL 120,342 25,245 285,089 111,888 16,369-287,754 150,000 100,000 50,000 0 AFR AMR EMR EUR SEAR WPR *unpublished, Adams E, Vynnycky E Est. CRS Cases 1996 Est. CRS Cases 2008 All member states
Cost of CRS (2) Between 1980 and 2010, 26 economic analyses were published 20 studies high-income countries 5 studies middle-income countries 1 study lower middle-income country No studies conducted in low-income countries Findings CRS is costly Lifetime costs $ 50,000 (Barbados) $ 98,734 (Oman) - $ 514,853 (Canada) Rubella vaccination programs are economically justifiable and demonstrated cost-effectiveness or cost-benefit ratios in high-income and middle-income countries
The clinical manifestations of Congenital Rubella Syndrome Burden and Cost of CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles and rubella
Countries using rubella vaccine in their national immunization system 1996 65 countries 12% of birth cohort 2011 130 countries 41% of birth cohort RCV Users: GNI per capita $6,300 0 900 1'800 3'600 Kilometers Source: WHO/IVB database and the "World Population Prospects: the 2010 Revision", New York, UN 194 WHO Member States. Date of slide: 1 October 2012. RCV non-users: GNI per capita $635 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 2012. All rights reserved 13
The clinical manifestations of Congenital Rubella Syndrome Burden and Cost of CRS Burden of rubella and CRS Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles UNICEF 2010/Habibul and rubella Haque/Drik
2011 WHO rubella position paper Burden of CRS greatest in regions where most of the countries are not using rubella vaccine and that have no regional control goal Risk of CRS is greater than the risk of a paradoxical effect WHO recommends countries use the opportunity offered by accelerated measles control and elimination activities to introduce RCVs
Moving towards Rubella and CRS Elimination Primary goal is prevention of congenital rubella infection including CRS General approaches: Reduce CRS only by immunizing adolescent girls or women of childbearing age Interrupt rubella virus transmission and eliminate rubella + CRS Preferred approach: interruption of rubella virus transmission leading to elimination of rubella and CRS Start with a wide age-range SIA giving MR or MMR Immediately introduce MR or MMR in routine Follow-up SIAs should give MR Wkly Epid Rec, 15 July 2011; 86(29):301-316
Optimal Age for RCV1 Only 1 dose of RCV is needed Excellent immunogenicity (>95% at 9 months) Transmissibility of rubella << measles Give it with MCV1 Higher coverage (avoid drop out between MCV1 MCV2) Ensure protection before exposure Either M, MR or MMR can be used for routine MCV2 Logistic advantages using same vaccine
WHO preferred approach Additional recommended vaccination strategies: Target adolescent girls and/or women of child-bearing age Vaccination of health care workers, male and female To avoid potential increase in CRS incidence, countries need to achieve and maintain coverage 80% through routine or SIAs Integrate field and laboratory surveillance for rubella with measles
The case of Congenital Rubella Syndrome Burden of rubella and CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and cost implications Opportunity combining measles and rubella
By end 2015: Goals Reduce global measles mortality by at least 95% compared with 2000 estimates Achieve regional measles and rubella/crs elimination goals Measles: The American, European, W. Pacific, and E. Mediterranean Rubella: The American and European By end 2020: Achieve measles and rubella elimination in at least five WHO regions 20
Measles and Rubella Elimination Goals by WHO Region, February 2012 Americas, Europe, E. Mediterranean, W. Pacific, Africa have measles elimination goals Americas and Europe have rubella elimination goals 2015 2015 2000 2010 2020 2015 2012 2015*) *) WPR: Rubella / CRS Reduction by 2015 SEAR: 95% Measles Mortality Reduction by 2015
Priorities Reach the 2015 measles mortality reduction goal and regional elimination targets Strengthen immunization systems 68 priority countries Low and lower-middle income countries High measles burden (low MCV1 coverage) High rubella/crs burden (not using RCV) 22
UNICEF 2010/Habibul Haque/Drik The case of Congenital Rubella Syndrome Burden of rubella and CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications Opportunity combining measles and rubella
Time Line Rubella vaccine introduction Timeline before introduction Issue 2 years before Burden assessment & Advocacy 1.5 year before GAVI Application 9 month before SIA planning Introduction Catch up SIA implementation Introduction in Routine Immunization
Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov No. of Cases Decision making Rubella vaccine introduction : Example from Nepal Information examined Rubella epidemiology > 95% of rubella cases were less than 15 years of age; Sero - prevalence study conducted 91% of women 15-39 years of age have acquired rubella immunity Estimated CRS burden Using sero prevalence study and modeling, approximately 1,400 infants born with CRS or 192/100,000 live births in 2008; Documented the presence of CRS among students attending a school for the deaf Decision Introduce MR through wide age campaign targeting persons aged 9 months -14 years followed by MR in routine at 9 months 1600 1400 1200 1000 800 600 400 200 0 Confirmed Measles and Rubella Cases, Nepal, 2003-2010 Note: Rubella IgM test started from Jan 2004 Catch-up Measles Campaign 2003 2004 2005 2006 2007 2008 2009 2010 Months and Year Measles Cases * Includes labconfirmed and epilinked cases Follow-up Measles Campaign Rubella Cases Data source: WHO-IPD, as of 28 Dec 2010
Budget Implications (1) Vaccine cost (UNICEF) Measles: $0.27 per dose MR: $0.52 per dose Routine Immunization At least one dose Rubella containing vaccine Follow-up campaigns with Rubella containing vaccine (MR or MMR) Surveillance
Budget Implications (2) GAVI support : Bundled MR vaccine for catch-up campaign Operational costs ($0.65 per child) Vaccine introduction grant $100,000 or 0.80 per child targeted for routine 1 st dose what ever is highest Countries responsible for: Remainder of operational costs for catch-up campaign Sustainable financing of MR vaccine for routine 1 st dose, Subsequent follow-up campaigns (MRI supported) Vaccination of women of child-bearing age
2013 Bangladesh Cambodia Cape Verde Ghana Kiribati Rwanda Nepal Senegal Samoa Solomon Islands Vanuatu Vietnam Projected Rubella introductions, GAVI and non-gavi, 2013-2018 2014 Benin Botswana Djibouti Gambia Lesotho Mali Pakistan Papua New Guinea South Africa Sudan Tanzania 2015 Afghanistan Burundi Cameroon Korea, DPR? Eritrea Kenya Myanmar Namibia Philippines Sao Tome e Principe Somalia South Sudan Uganda Yemen Zimbabwe 2016 Burkina Faso Central African Republic Comoros Congo, DR Congo, Rep Ethiopia Madagascar Malawi Mozambique Niger Swaziland Timor Leste Togo Zambia 2017 Angola Cote d'ivoire Gabon Liberia Mauritania Nigeria 2018 Chad Equatorial Guinea Guinea Guinea-Bissau Sierra Leone (total includes India and Indonesia) 2013 2014 2015 2016 2017 2018 Total by 2020 11 11 15 14 6 5 64 Based on projections from WHO, UNICEF, and GAVI Strategic Demand Forecast, September 2012 (subject to change); India and Indonesia plans are uncertain
The case of Congenital Rubella Syndrome Burden of rubella and CRS Rubella vaccine use Rubella Position Paper New Strategic Plan Timelines and budget implications UNICEF 2010/Habibul Haque/Drik Opportunity combining measles and rubella
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 confirmed measles cases MCV1 coverage Measles cases and routine MCV1 coverage, Zambia, 1999 2011 40,000 30,000 Under 15 campaign Under 5 campaign 100% Under 15 campaign (sub national) 20,000 Under 5 campaign 50% 10,000-0% confirmed measles cases MCV1 coverage
Confirmed Measles Cases 0-8 months 9-11 months 1-4 years 5-9 years 10-14 years 15-19 years 20-24 years 20-24 years >25 years Measles cases by age, Zambia 2010-2011 8000 6000 4000 2000 0 Under Five Follow up campaign Catch -up campaign Age
Measles & Rubella Raising age of children affected by measles In 2012, 7 out of the 27 countries funded by MR Initiative, targeted children older than five years during the campaigns MR campaigns for 9 months 14 years: opportunity to control measles in older agegroups
Rubella coverage in infants & Measles and Rubella cases in the Americas, 1982 2012 Measles Catch-up campaigns MR Speed-up campaigns Follow-up campaigns 33
Summary High Cost of CRS CRS burden highest in regions and countries not using rubella vaccine Case for rubella introduction: More Rubella and CRS cases detected, as surveillance improves New position paper on rubella New Strategic Plan integrating rubella with measles New GAVI funding for rubella Cheap, safe, effective vaccine available Use MR catch-up campaigns to boost measles control
35 Thank you.
Measles Rubella Resources WHO Position Papers Measles: http://www.who.int/entity/wer/2009/wer8435.pdf Rubella: http://www.who.int/entity/wer/2011/wer8629.pdf Measles mortality estimation, 2000-2010 http://www.thelancet.com/journals/lancet/article/piis0140-6736(12)60522-4/abstract Measles global progress supplement, J Infect Dis 2011; 204(suppl1) http://jid.oxfordjournals.org/content/vol204/suppl_1/index.dtl Rubella elimination in the Americas supplement, J Infect Dis 2011; 204(suppl2) http://jid.oxfordjournals.org/content/vol204/suppl_2/index.dtl Immunologic Basis for Immunization Measles (module 7): http://whqlibdoc.who.int/publications/2009/9789241597555_eng.pdf Rubella (module 11): http://whqlibdoc.who.int/publications/2008/9789241596848_eng.pdf Outbreak response guidelines: http://whqlibdoc.who.int/hq/2009/who_ivb_09.03_eng.pdf Global Measles and Rubella Strategic Plan http://whqlibdoc.who.int/publications/2012/9789241503396_eng.pdf
Extra slides
Proportion of countries offering rubella vaccine in routine by WHO region, 2000 2011 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 * Apparent decrease in 2011 because South Sudan joined EMRO but does not offer rubella vaccine in routine AFR AMR EMR* EUR SEAR WPR Global 60 countries yet to introduce rubella vaccine 38
Distribution of reported rubella genotypes, 2011. Data as of 3 August 2012 West Europe 2011 120 countries reporting laboratory confirmed rubella 12 countries reporting genotype information Legend 1a 1E 1j 2B Pie slice size proportional to the number of years each genotype was reported 2005-2011. 5 1 0 2'500 5'000 Kilometers Acknowledgement: WHO LabNet. 39 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 2011. All rights reserved.
WHO Region Reported Cases of Rubella and Congenital Rubella Syndrome, by WHO Region, 2011 No. of member states in region Member states reporting rubella No. % No. of rubella cases Rubella incidence per million population Member states reporting CRS No. % No. of CRS cases AFR 46 40 87% 16,190 19 16 35% 0 AMR 35 34 97% 5 0 34 97% 2 EMR 22 17 81% 2,749 4.5 9 43% 2 EUR 53 39 75% 7,761 8.6 40 77% 6 SEAR 11 10 100% 9,804 5.4 4 40% 3 WPR 27 24 89% 76,022 42 18 67% 201 Global 194 164 86% 112,531 16 121 63% 214 Data received at WHO as of 14/07/2012
Updated estimates of the burden of CRS globally * in 1996 and 2008 Regions 1996 2008 Est. CRS Cases Range Est. CRS Cases Range AFR 31,133 6127 71,017 42,440 9130-97,228 AMR 9,701 2605 19,274 24 0-301 EMR 9,265 3054 22,287 5,895 69-20,384 EUR 9,509 5742 13,240 243 12-1949 SEAR 50,637 3644 141,432 52,643 3418-149,274 WPR 10,098 3495 17,839 10,641 3741-18,618 GLOBAL 120,342 25,245 285,089 111,888 16,369-287,754 *unpublished, Adams E, Vynnycky E All member states
Updated estimates of the burden of CRS globally * in 1996 and 2008 1996 2008 Regions Est. CRS Cases Range Est. CRS Cases Range GLOBAL 120,342 25,245 285,089 111,888 16,369-287,754 *unpublished, Adams E, Vynnycky E All member states
Cost of CRS (1) The Rubella Project 1000 Patients from metropolitan New York Impact in USA > 1% of pregnancies Financial Costs for those in congregate supported housing: ~$175,000 /person/ year Human costs: immeasurable Courtesy: Dr Louis Z Cooper
Benefit Cost Ratios selected vaccines Vaccine Country Benefit Cost Ratios MMR Barbados 4.7 Guyana 38.8 Caribbean 13.3 Hepatitis B China 42 48 Israel 2.8 Hib Chile 1.7 Israel 1.5 South Africa 1.3 1.4 Source: Hinman et al 2002
Annual # of Doses Given (millions) Cumulative # since 2012 (millions) Projected annual and cumulative number 300 250 200 150 100 50 0 of MR vaccine doses, 2012-2018 Catch-up campaigns Sudan Pakistan Bangladesh Kenya Indonesia India India India Ethiopia DR Congo Nigeria 2012 2013 2014 2015 2016 2017 2018 Based on GAVI Strategic Demand Forecast, September 2012 (subject to change); No vaccines for follow-up campaigns nor routine immunization included in the forecast India and Indonesia plans are uncertain 1400 1200 1000 800 600 400 200 0