The Conquest ofofof HibHib

Mathuram Santosham Baltimore, MD, USA

Center for American Indian Health – Center for American Indian Health‐JH collaboration

Haemophilus influenzae

Haemophilus = ‘blood’- loving influenzae = fr. latin: influentia: epidemic disease – evil influence

Rotavirus Epidemic Oct –Dec 1981 White Mountain Apppache Tribe Oct – Dec 81 5C5 Cases of fI Invas ive Hib DiDiDisease Annual Incidence of Hib in Children Under 5 Years in Non --industrialized Countries

Alaska Eskimos

Apache

Navajo

Aboriginals

Gambia

Niger

Sinegal

S. Africa (Black)

Chile

Brazil

Argentina

Israel

Kuwait

Qatar

Hefel, China

Vietnamese

Malaysia

Fiji

0 50 100 150 200 250 300

Modified from Bjlimer, J Infect Dis, 1992; 165(1):S29-32Cases per 100,000 Children < 5 Years Cumulative Proportion of H. influenzae Meningitis Cases, by AfAge, from ThGbiUitdSttdFildThe Gambia, United States, and Finland HHH. InfluenzaeInfluenzae type b ( (typeb HibHib)) Donna Ambrosino

George Siber Hyperimmune Globulin

Polyvalent Pneumococcal, type b, Meningococcus A , C , Y , and W --135135135 Bacterial Polysaccharide Immune Serum Globulin (BPIG)

Hib Conjucate Chemical structure

DD DD DD DD PRPPRP--TT TT TTTT PRPPRP--DD ProHIBITProHIBITProHIBIT™ no longer marketed TT ActAct--HIB™HIB™ ((Aventis Pasteur) HIBERIX™ (SB)(SB)

KEYKEY OMPOMP CC CC Bigeneric spacerspacer

CC CC Polyyysaccharide PRPPRP--OMPOMP HbOCHbOC PEDVAX HIB™ (MSD)(MSD) Oligosaccharid HIB TITER™ ee ( Lederle) Comparative Immunogenicity of Hib Conjugate Vaccines in Alaska Native Infants Vaccines administered at 2, 4, and 6 months, except PRPPRP--OMPOMP at 2 and 4

100

10 HbOC PRP-D PRP-OMP GMT 1 PRP-T-liq PRP-T-lyoph 0.1

0.01 24679-1215-18 Age (months)

Bulkow et al, Pediatr Infect Dis J 1993; 12:484-92

Janne Croll Ray Reid

HibHib--OMPC Efficacy Trial Navajo Indian Reservation

Hib Cases Prior to Age 15 Months After 1 Dose # Received # of Hib Cases 1 dosedose1

Vaccine 2588 0 Placebo 2602 21

P<0.001; Vaccine Efficacy 100% (CI 8181--100)100)

Santosham: N Engl J Med 1991; 1;32:1767 HibHib--OMPCOMPC Vaccine Efficacy Trial Navajo Indian Reservation

Hib Cases Prior to Age 18 Months Between First and Second Doses No. received Cases 1d1 dose ofHibf 2,588 0

Placebo 2,602 8

p < 0.005; Vaccine Efficacy 100% (95% CI 4141--100)100)

Adapted from N Engl J Med, 1991; 324:1767-72

Invasive Haemophilus influenzae type a and type b disease amonggj Navajo and White Mountain Apache children aged <5 years, 1988-2003 (Millar et al. 2005)

360

320 Type a Type b 280 en <5 y rr 240

200 0 000 child 00 160

120 ases per 1

CC 80

40

0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Year AgeAge--SpecificSpecific Incidence Rates of H. influenzae Meni ng it is in t he Un ite d States, 1980--19911991

Wenger, Pediatr Infect Dis J, 1998;17(9):S132-6 Percentaggge decline in incidence Hib following vaccine introduction

120% Fin lan d 100% Netherlands

ine UK ll 80% Ireland 60% Israel tage dec 40%

Percen 20%

0% -1 0 1 2 3 4 5 6 YltititdtiYear relative to introduction

EU-IBIS Before Hib Initiative

Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Potential for introducing Hib vaccine in India ‐ 2000

Birth cohort: 27 million per year

“An Impossible Dream” World Map Redrawn Based on Child Deaths

http://www.viewsoftheworld.net/wp‐content/uploads/2012/05/StC_MortalityUnderAge5Map.jpg Scottsdale Hib Meeting 2002 GAVI Hib Initiative A Global Partnership Men ingiti s and P neumoni a P reventi on

At the start of Hib Initiative

Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Importance of “face to face” communication Hib Initiative: Regional Forums

Europe & Eurasia 15 countries

Asia and South-East Asia Eastern Mediterranean 13 countries 10 countries

East & Southern Africa West & Central Africa 15 countries 20 countries

73 GAVI and non-GAVI countries participated in regional forums GAVI countries Where am I? You must be a researcher Because what you told me is absolutely correct but completely useless Yes, how did you know?

You’ re 30 metres above the ground in a balloon Yes. How did you know? You must be a policy maker Because you don’t know where you are or where you’i’re going, and now you’ ’blire blaming me…. Lois Privor ––DummDumm DiDiDirector -commun iiiiications More Than A Pinprick: A Sly Fudging of Facts Is Pushing India Into Buying Vaccines Backed By The WHO That May Have Killed Children in Other Countries June 2010

WHO Plugs for Hib Vaccine in India, Critics Say It Is Expensive and Unnecessary September 2007

Vaccines: Policy for public good or private profit? January 2008

Pentavalent Vaccine Unsafe, Say Experts January 2013 PbliPublic Interest Lit igat ion to bloc k the idiintroduction of Hib‐containing combination vaccine in India, 2010 Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014.

Sources: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS). April 2014. GAVI Alliance: http://www.gavialliance.org/support/nvs/pentavalent/# Gary Darmstadt Richard E. Besser Ruth Karron

Chris Duggan

William Moss Samir Saha

Abdullah Baqui Kate O’Brien

Allison Barlow Orin Levine Aim Hi gh an d Far “I hav e a dream that m y fo ur little children will one da y li ve in a nation where they will not be judged by the color of their skin, but by the content of their character” Ciro De Quadros Florence Nightingale 1864

You will have much opposition to encounter but great works do not prosper without great opposition

www.HibAction.org Climb ev ery mo untain , shore, ev ery stream,,y follow every rainbow until you meet your dream