Roger I. Glass, M.D., Ph.D. Director, Fogarty International Center Associate Director for International Research, NIH

Transcription

1 Rotavirus Vaccines: Prioritization for Introductions- National & International Case Studies Fondation Merieux Conference Center November 27, 2012 Roger I. Glass, M.D., Ph.D. Director, Fogarty International Center Associate Director for International Research, NIH

2 National RV introductions: 38 countries, Sept 1,2012 Americas Bolivia Brazil Cayman Islands Colombia Dominican Rep. Ecuador El Salvador Guatemala Guyana Honduras Mexico Nicaragua Panama Paraguay Peru United States Venezuela Europe Austria Belgium Finland Israel Luxembourg Moldova Not GAVI-eligible GAVI-eligible Africa Botswana Ghana Morocco Rwanda South Africa Sudan Is th Middle East Bahrain Iraq Qatar Yemen Western Pacific Australia Marshall Islands Micronesia Palau Asia Philippines Is this a funny picture?

3 Millions Institute of Medicine Estimates of Rotavirus Deaths k k 453k Diarrheal Deaths (% of total deaths) 4.6m 3.3m High priority for 275k Developing Countries No need for an RV Vaccine for the United 2012 States! 1.8m 1.3m 1.2m 0 (18%) (15%) (11%)

4 1986 The Challenge- Creating Evidence How can you assess the burden of a disease that is Rarely diagnosed by lab assay? Has no ICD code? No name recognition Symptoms indistinguishable from other childhood diarrheas? Requires no specific treatment besides rehydration? Meager budget & staff! 4

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6 Burden of Rotavirus in the US Risk 1 : 10 6 Events Deaths 1 : ,000 Hospitalizations 1 : 7 1 : ,000 Outpatient visits 3.2 Million episodes Cost: $400 M medical; >$1 B total

7 Estimated global distribution of the ~500,000 annual deaths caused by rotavirus 85% of deaths in low income countries 1 dot = 1000 deaths Parashar,

8 RV Disease Burden- Developing Countries Risk Events 1 : 285 `500,000 deaths 1 : 58 1 : 5 1 : million inpatient visits 24 million outpatient visits 114 million episodes 5% of all deaths in children < 5 1 in ~250 children will die of RV

9 Recommended Childhood Immunization Schedule United States, January December 1999 Age Birth mo mos mos mos mos mos mos yrs yrs yrs Vaccine Hepatitis B Hep B Diphtheria, Tetanus, Pertussis Hep B DTaP DTaP Hep B DTaP DTaP DTaP Hep B Td H. influenzae type b Hib Hib Hib Hib Polio IPV IPV Polio Polio Rotavirus Rv Rv Rv Measles, Mumps, Rubella MMR MMR MMR Varicella Var Var Discussions with ACIP 1995 onwards!

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11 Let s reassess the risks and benefits of RV vaccine Benefits Risks 1 death in 250 children 600,000 deaths/ yr 25-50% of D admissions 1 IS in 30,000 vaccinees? 3500 severe IS cases

12 Volume 354 January 5, 2006 Number 1 Safety and Efficacy of a Pentavalent Human Bovine (WC3) Reassortant Rotavirus Vaccine Timo Vesikari, M.D., David O. Matson, M.D., Ph.D., Penelope Dennehy, M.D., Pierre Van Damme, M.D., Ph.D., Mathuram Santosham, M.D., M.P.H., Zoe Rodriguez, M.D., Michael J. Dallas, Ph.D., Joseph F... Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis Guillermo M. Ruiz-Palacios, M.D., Irene Pérez-Schael, M.Sc., F. Raúl Velázquez, M.D., Hector Abate, M.D., Thomas Breuer, M.D., SueAnn Costa Clemens, M.D., Brigitte Cheuvart, Ph.D., Felix Espinoza, M.D., Paul Gillard, M.D., Bruce L. Innis, M.D., Yolanda Cervantes, M.D.,, Live oral vaccines Tested in >60,000 infants each Both safe & effective >85% After Intussusception, would vaccine be used?

13 CDC Advisory Committee on Immunization Practices (ACIP) Feb Draft-- Recommendations for Pentavalent Bovine-Human Rotavirus Vaccine (PRV) Routine immunization of infants with 3 doses of PRV at 2, 4, and 6 months of age Three doses at 2, 4, and 6 months of age Dose 1 between 6-12 weeks of age All doses by 32 weeks of age 4-10 week interval between doses In press: MMWR, 2006

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15 Impact of Rotavirus Vaccine in the US A Review of studies Worcester, MA 5 95% reduction Hospitalization, ED,* Outpatient New York State 6 85% reduction Hospitalization/ED Kansas City, MO 4 88% reduction Hospitalization Philadelphia, PA 1 87% reduction in Community acquired cases (Children's Hosp.) Galveston, TX 3 94% reduction Hospitalization or ED Consequences have been enormous! Greater than rates of immunization! Philadelphia, PA 2 94% reduction Hospitalization (St Chris) *ED = emergency department 15

16 Childhood Diarrhea Deaths after Rotavirus Vaccination in Mexico Richardson V etal. NEJM 2012

17 Overview of DB/Surveillance networks EURO EMRO ARSN PAHO RV Surv Network Supplements! WHO African RV Network 17

18 What about the developing world where children die from rotavirus diarrhea? Can rotavirus vaccines prevent severe disease and death among childrens in the poorest developing countries and if so, how rapidly can these vaccines be introduced? 18

19 Association between Rotavirus Vaccination & Rotavirus Disease Requiring Hospital Admission or IV Rotavirus Group Hospital Admission or IV Hospital Admission Cases Control VE Percent immunized 76% 83% 46 (158/209) (868/1044) (18 to 64) 74% 82% 44 (143/192) (792/964) (15 to 63) IV 75% (138/184) 83% (762/918) 48 (19 to 66) 19 M. Patel, etal. JAMA 2009

20 Relationship between RV Vaccine Efficacy & Per Capita Gross Income 20 Tony Nelson, Lancet 2010

21 Is the glass or??? 21

22 WHO Recommends Global Use of Rotavirus Vaccines 5 JUNE 2009 GENEVA/SEATTLE -- WHO has recommended that rotavirus vaccination be included in all national immunization programs to provide protection against a virus that is responsible for more than 500,000 diarrheal deaths and 2 million hospitalizations every year among children. More than 85% of these deaths occur in developing countries in Africa and Asia. Schedule: 2 doses 6 & 10 weeks First dose 6-15 wks; last 32 wks Given with EPI vaccines Recommendations extended to Rotateq ~ 12/09 22

23 Rotarix in Africa Immune Response Efficacy South Africa 6-10 wks 36%? wks 60% 72% Malawi 6-10 wks????? wks?? 49% What level of efficacy should we expect in Malawi with 6-10 week schedule? 23

24 Nicaragua: Launch National Vaccination Campaign October 27 th

25 Antibody titers in breast milk specimens from India, Vietnam, Korea and United States IgA Rotarix India US RotaTeq(G1) 116E Indian women had the highest IgA and neutralizing titers against rotavirus vaccine strains 25 B. Jiang, PIDJ2010

26 How could we improve the current vaccines? Maternal antibodies Delay immunization - increase potency of vaccine, add booster dose (3 rd dose for Rotarix) Breastfeeding withhold breastfeeding for some time before/after immunization Microbes Separate from OPV / probiotics Malnutrition add zinc, vit A Research today might improve outcomes tomorrow! 26

27 What are the alternatives? Live oral vaccines Neonatal strains 116E India RV3 Australia- Indonesia Rotashield revisited UK Bovine reassortants Parenteral vaccines Inactivated virus (IRV) Virus Like particles (VLPs) Expressed proteins- VP6, VP4 27

28 National RV introductions: 38 countries, Sept 1,2012 Americas Bolivia Brazil Cayman Islands Colombia Dominican Rep. Ecuador El Salvador Guatemala Guyana Honduras Mexico Nicaragua Panama Paraguay Peru United States Venezuela Europe Austria Belgium Finland Israel Luxembourg Moldova Not GAVI-eligible GAVI-eligible Africa Botswana Ghana Morocco Rwanda South Africa Sudan Is th Middle East Bahrain Iraq Qatar Yemen Western Pacific Australia Marshall Islands Micronesia Palau Asia Philippines Is this a funny picture?

29 $0.20-$0.30 /dose -5 years

30 GLOBAL HEALTH Vaccine campaign to target deadly childhood diarrhoea Programme to guard against second-biggest killer of under-fives rolls out across Africa. BY DECLAN BUTLER 29 SEPTEMBER 2011 VOL 477 NATURE

31 Drug firms cut vaccine prices to the developing world* Industrialized Countries PAHO GAVI / UNICEF GSK $ /course Merck $ /course $15/course $15.45/ course $5/course [up to 125 M doses; over 5 yrs] $10.50/course [for volume over 30 M] Bharat Biotech ~ $3/course 3 doses/course: Merck, Bharat Biotech 2 doses/course: GSK * Applies to GAVI tenders 31

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34 Who Will Supply Rotavirus Vaccine to the World? GSK China India Merck Brazil Vietnam Big Pharma Indonesia Germany Emerging Manufactures

35 Projected health and economic impact of rotavirus vaccination in GAVI-eligible countries: million deaths averted Annual and cumulative deaths averted, Atherly, D etal. Vaccine, 2010

36 Millions Estimates of Rotavirus Deaths: k 0.5 Diarrheal Deaths (% of total deaths) 4.6m 3.3m 1.8m (18%) 527k??? 1.3m (15%) k m (11%) 2012

37 How will the vaccine work in the field? Better? Worse? Herd protection Reduced force of infection Older age of disease Delayed immunization will maternal Ab over time Delayed immunization = more early disease Poor coverage of most needy groups The only way to find out is to try the vaccine and measure the impact! 37

38 The vision for the DoV is a world in which all individuals and communities enjoy lives free from vaccine-preventable diseases. Its mission is to extend, by 2020 and beyond, the full benefits of immunization to all people, regardless of where they are born, who they are, or where they live.

39 Reaching Universal RV immunization 39 countries have introduced RV vaccines (only 20%). The impact is enormous! Herd effect unanticipated! WHO recommendation & GAVI funding have sparked introductions in low income countries Evaluation of impact essential to assess lower efficacy but positive herd effects Research essential - to improve existing vaccines, develop less expensive & more effective alternatives Vaccine finance remains a challenge to make programs sustainable 39