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CHILDHOOD Hib : NEARLY ELIMINATING THE THREAT OF BACTERIAL

By “teaching” the immune system to defend against TYPE B (Hib) , vaccines prevent serious illness, disability, and death from dozens of infectious diseases,1 making vaccines • Bacterial infection spread by direct person-to-person one of the most important achievements ever. contact as well as coughing and sneezing As a leader in biomedical research, NIH has contributed to • Causes , bacterial meningitis, , infection the development of many vaccines throughout its history – of the blood, and swelling of the throat and joints one standout has nearly eliminated Haemophilus • Long-term consequences can include deafness, influenzae type b (Hib) infection in the U.S. Once the leading blindness, brain damage, and intellectual disability cause of bacterial meningitis in children, Hib infection can result in serious, long-term disability and death. Today, • Predominately affects young children, especially infants the near elimination of Hib has had profound benefits Also see Hib information provided by the Centers for 2 throughout the world. NIH, in concert with many other Disease Control and Prevention (CDC): governmental, non-profit, and private organizations, played http://www.cdc.gov/vaccines/vpd-vac/hib.htm a key role in making an effective Hib vaccine a reality, resulting in thousands of lives saved.3 Hib : THEN AND NOW

THEN More than 20,000 NOW Cases have • Antibiotics were not always cases of Hib were • Highly effective Hib dropped by more prescribed at the right time vaccines have been in use reported in the than 99%, with and dose. Even with effective since the late 1980s.5 antibiotic treatment, 5 percent U.S. each year.8 • More than 90% of children only around 40 of those who contracted the in the U.S. received a Hib reported in 2009.9 infection died.4 vaccine in 2014.7 • Hib was the leading cause of bacterial meningitis • The CDC predicts that more and acquired intellectual disability in children – most of than 19,000 cases whom were under 5 years of age.6 and 700 Hib-related deaths will be prevented over • Upwards of 1,000 children died from Hib every the lifespan of the 4 million U.S. children born in year and 6,000 suffered from deafness, seizures, 2009 alone.11 intellectual disability, or brain damage primarily due • For the group of children born in 2009, Hib to bacterial meningitis.10 is predicted to save $1.8 billion in direct costs and • $2 billion per year in health care costs were attributed $3.7 billion in total societal costs.13 to Hib and related illnesses in 1968.12 1980 FDA scientists (who 1984 RESEARCH-TO-PRACTICE later moved to NIH) linked Hib sugar NIH and FDA scientists MILESTONES FOR THE chains to immune- found that this conjugate stimulating proteins vaccine triggered immune PROTECTING (e.g., from diphtheria), responses in appropriate INFANTS WITH A producing a “conjugate animal models.24 Hib VACCINE vaccine.”23 NEXT-GENERATION For more information on the supporting evidence and research sponsors for CONJUGATE these milestones, see the Web appendix. VACCINE

The first attempts at developing 1930s 1968 1993 a Hib vaccine focused on the sugar chains – researchers worked Hib (seen below right, in photo) on isolating, purifying, and was found to be the primary cause of The developed preparing these chains for clinical bacterial meningitis in children. The bacteria by NIH-funded scientists was use.18 could be distinguished under the microscope licensed, manufactured, and 27 by their unique outer coat.15 Later, scientists commercially distributed. determined this coat was made up of chains NIH-funded clinical 16 trials showed that the of specificsugar molecules. 1985- CDC included the Hib conjugate 1989 conjugate vaccine vaccine in its recommended was safe and effective vaccine schedule.28 25 Because sugar chains typically do not in infants. stimulate immune responses as well as proteins, researchers began to EARLY HIB 1995 look for ways to link the chains to VACCINE FDA approved the bacterial proteins in order to enhance 1987- first4 conjugate 17 1993 their . DEVELOPMENT vaccines for use in infants.26 For their “groundbreaking work and …leadership in the development and By deactivating disease-causing commercialization of the [Hib] 1985 components of bacteria, vaccines vaccine,” the Albert and Mary were developed to prevent Lasker Foundation awarded 1920s and diphtheria.14 These advances The Food and Drug Administration (FDA) approved their prestigious Clinical would later help enhance the the first Hib vaccines (including from Praxis Biologics) Medical Research Award effectiveness of Hib vaccines. for use in children two years of age,21 while researchers (often referred to as the explored ways to make the vaccines more effective “American Nobels”) to four 22 in infants. NIH-supported scientists.29 NIH’s National Institute of Allergy and Infectious Diseases provided grant NIH-funded clinical trials Scientists leading funding to Drs. Porter FOUNDATIONAL found that these early Hib these clinical trials Anderson and David Smith. vaccines worked well founded a company, Drs. Rachel Schneerson and RESEARCH 1970s for children over age 2, called Praxis Biologics John Robbins performed the but were not as effective (now incorporated into majority of their research 19 Wyeth), to develop and in infants. 1983 within the intramural produce vaccines for laboratories of the Eunice children, including Kennedy Shriver National Hib vaccines.20 Institute on Child Health and indicates NIH-funded milestones Human Development. 1977: A young girl receives a vaccination, administered by a public health nursing practitioner IMPACTS OF Hib VACCINES

HIB DISEASE NEARLY ELIMINATED IN THE U.S. HEALTH Incidence of Hib FOLLOWING THE VACCINE • First conjugate vaccine cases declined A FDA Approved Hib Vaccines B Hib Vaccines Added to CDC approved to treat an more than Childhood Vaccine Schedule 30 infectious disease. 99% following 25 • More than 90% of children availability of the in the U.S. receive the conjugate vaccine.32 20 A

31 Incidence Hib vaccine. A

15 SOCIETY • Hospitalization for Hib- 10 meningitis costs upwards For children born of $38,000 depending on B in 2009 alone, 5 the severity of the disease.36 Hib vaccination • NIH-supported researchers saves $3.7 billion, started a company and 1980 1985 1990 1995 2000 2005 2010 including more Years successfully moved Hib and than $1.8 billion other experimental vaccines in direct treatment Figure Legend: The CDC-estimated annual incidence of through the full product costs.35 invasive Hib disease (per 100,000 people) is shown here for development pipeline.37 U.S. children less than five years of age from 1980 to 2012. Once approved and licensed, the use of Hib vaccines resulted in a rapid decline of Hib cases and the disease has KNOWLEDGE been nearly eliminated in the United States.33 • Hib vaccine research provided fundamental understanding of how the infant immune system works, stimulating new strategies HEALTH IMPACT OF ROUTINE CHILDHOOD for developing effective vaccines for infants. 34 • The Hib conjugate vaccine technology has been FOR Hib: U.S. 1994-2013 applied to create several vaccines against Illnesses Hospitalizations Deaths other disease-causing bacteria, such as Prevented: Averted: Avoided: pneumococci, meningococci, Salmonella typhi, group B streptococci, and E coli.38 361,000 334,000 13,700

CHILDHOOD VACCINES: OVERALL IMPACT ON SOCIETY The Hib vaccine success story highlights how continued scientific investment leads to new tools that prevent deadly diseases and improve the lives of people around the world. The Hib vaccine is one of many childhood vaccines, and the CDC projects that over the lifespan of the 4 million U.S. children born in 2009 alone, childhood vaccination overall will:

save prevent reduce direct save 42,000 20 million health care costs by $68.8 billion lives cases of disease $13.5 billion in indirect costs39

For references, supplementary information, and more on the impact of NIH, please visit http://www.nih.gov/impact