1. WHO/V&B/AVI Choosing the Right Vaccine A brief presentation on hepatitis B & Haemophilus influenzae type b infections and choosing the right vaccines to prevent them ************

2. WHO/V&B/AVI Choosing the Right Vaccine Guiding principles for choosing to introduce a vaccine –Disease burden –Cost benefit –Affordability –Existence of a robust delivery system –Availability of a vaccine –Quality of available vaccine

3. WHO/V&B/AVI Choosing the Right Vaccine WHOs Expanded Programme on Immunization (EPI) –Launched by WHO in 1974 –Initially 6 target diseases (TB, Diphtheria, Pertussis, Tetanus, Measles, Polio) –Hepatitis B added in 1991 –Hib added in 1998 (for those countries with moderate to high burden of Hib disease)

4. WHO/V&B/AVI Choosing the Right Vaccine: Sample EPI Schedule

5. WHO/V&B/AVI Choosing the Right Vaccine Hepatitis B disease –hepatitis B virus (HBV) is a DNA virus whose natural host is man –hepatitis is infection of the liver by the HBV, where the virus predominantly affects the liver cells (hepatocytes) –Outcome of infection death from fulminant hepatitis recovery with life-long immunity development of carrier state/chronic disease

6. WHO/V&B/AVI Choosing the Right Vaccine HBV Transmission –from mother to child (perinatal/vertical) –from child to child –through unsafe injections & blood transfusions –through sexual contact

7. WHO/V&B/AVI Choosing the Right Vaccine Global burden of HBV infection –Approximately 30% of worlds population or about 2 billion people have evidence of infection –About 350 million have chronic HBV infection –Annually about 1 million die from chronic liver disease, including cirrhosis & liver cancer –HBV infections in infants are frequently asymptomatic

8. WHO/V&B/AVI Choosing the Right Vaccine Hepatitis B vaccine –Two types available at present- plasma derived and DNA recombinant vaccines –But in the next few years, plasma derived HepB vaccine will be phased out –Plasma derived vaccine is a blood product whereas DNA recombinant vaccine is genetically engineered –Both are equally safe and effective –All Vaccine Fund supply is DNA recombinant

9. WHO/V&B/AVI Choosing the Right Vaccine Hepatitis B vaccine…contd/ –Hepatitis B vaccine is available as either only hepatitis B or in combination with other vaccines –Combinations of hepatitis B vaccine include DTP-HepB (tetravalent), DTP-HepB+Hib (pentavalent), DTP-HepB-IPV+Hib (hexavalent) & HepB-Hib

10. WHO/V&B/AVI Choosing the Right Vaccine: The issue of a birth dose of HepB vaccine –In many countries perinatal transmission from mothers infected with HBV to their infants is a major source of HBV infections –Infections occur usually at time of births, in utero transmission is relatively rare. –Therefore, the most effective way to prevent perinatal transmission is to give hepatitis B vaccine as soon as possible after birth, preferably within 24 hours

11. WHO/V&B/AVI –Where feasible, a birth dose should be administered to all infants at birth. –However, this is not a practical option in countries where a large proportion of births take place outside health facilities. Choosing the Right Vaccine : The issue of a birth dose of HepB vaccine

12. WHO/V&B/AVI Choosing the Right Vaccine: The issue of a birth dose of HepB vaccine –One alternative is to screen mothers for HBsAg and give a birth dose to those children born to HBsAg positive mothers. But extensive resources are needed to screen pregnant mothers and track infants –Another option is to combine HepB vaccine with that of DTP at 6,10 & 14 weeks –With this schedule, in countries with high perinatal transmission rates, the rate of decline in prevalence of HBV infection will be slower, but may be more practical and feasible

13. WHO/V&B/AVI Choosing the Right Vaccine: The issue of a birth dose of HepB vaccine –In countries where perinatal transmission is not a major source of infection, administration of a birth dose contributes less to overall reduction of hepatitis b infection. –In these countries, the most practical option may be to combine HepB vaccine with that of DTP at 6,10 & 14 weeks

14. WHO/V&B/AVI Choosing the Right Vaccine: The issue of a birth dose of HepB vaccine The decision on whether to introduce a birth dose of hepatitis b vaccine is largely a function of burden of perinatal transmission and programmatic feasibility of administration of a birth dose.

15. WHO/V&B/AVI Choosing the Right Vaccine Haemophilus influenzae type b diseases –Hib is a major killer - every year more than 400,000 children die due to Hib disease –Six serotypes (types a-f) known to cause disease, but type b is responsible for over 90% of life-threatening Hib infection in children –All serotypes live in nose & throat of people and usually do not cause serious disease –When they cause serious disease, it is mostly in children under five years of age

16. WHO/V&B/AVI Choosing the Right Vaccine The spectrum of Hib diseases –Bacterial meningitis major cause of bacterial meningitis in children 3% to 45% of children with meningitis die (difference in developed/developing countries) 19-45% of children with Hib meningitis suffer neurological complications –Pneumonia 2nd most common cause of bacterial pneumonia in children less than 5

17. WHO/V&B/AVI Choosing the Right Vaccine The spectrum of Hib diseases..contd/ –Septicaemia –Septic arthritis –Osteomyelitis –Cellulitis –Pericarditis

18. WHO/V&B/AVI Choosing the Right Vaccine Haemophilus influenzae type b (Hib) vaccine –Hib vaccine is known as a conjugate vaccine as the bacterial capsular polysaccharide material is linked to tetanus toxoid, diphtheria toxoid, a diphtheria-like protein, or a mix of proteins from other bacteria –All are effective in preventive Hib disease

19. WHO/V&B/AVI Choosing the Right Vaccine There are various formulations of Hib vaccine –Liquid Hib vaccine (monovalent) –Liquid Hib combined with DTP –Liquid Hib & Hepatitis B combined vaccines –Lyophilised (freeze-dried) Hib with saline diluent (monovalent) –Lyophilised Hib vaccine to be used with liquid DTP, DTP-HepB, DTP-IPV, DTaP, or DTaP/IPV in combination

20. WHO/V&B/AVI Choosing the Right Vaccine Is Hib vaccine recommended for all countries? –In industrialised countries of Europe and the Americas, Hib has been in use for almost a decade now –There is enough evidence that Hib disease is a major public health problem in the Americas, Sub-Saharan Africa and the Middle East –There is limited evidence to show that Hib disease is a public health problem in Asia & Eastern Europe

21. WHO/V&B/AVI Choosing the Right Vaccine Combination vaccines –DTP is the earliest combination vaccine in use –In the current Vaccine Fund supplies, combinations include DTP-HepB (tetravalent) or DTP-HepB+Hib (pentavalent), –In future, it is possible to have DTP-Hib or HepB-Hib –In the industrialised countries, there are many different combinations in use

22. WHO/V&B/AVI Choosing the Right Vaccine Why combine vaccines? –More & more vaccines becoming available. So if combined fewer injections, less distress to infants & parents less visits to health facility less injection related complications reduced costs (lower overall cost of vaccination programme) may simplify transportation & storage problem

23. WHO/V&B/AVI Challenges of combined vaccines pharmaceutical immunological clinical regulatory manufacturing public health

24. WHO/V&B/AVI Any interference? –immunogenicity? reactogenicity? shelf-life? stability? manufacturing, supply? antigens preservatives adjuvants contaminants pH stabilizers excipients

25. WHO/V&B/AVI Choosing the Right Vaccine Which vaccine to choose? –For those countries introducing only HepB vaccine without a birth dose, the best choice is a combination of DTP-HepB –For those countries with a birth dose, they may either have monovalent HepB for birth dose and a combination DTP-HepB for the rest or may continue with only monovalent HepB and DTP separately

26. WHO/V&B/AVI Choosing the Right Vaccine Which vaccine to choose? –For those countries introducing both HepB and Hib vaccines, the most efficient choice is the pentavalent (DTP-HepB+Hib), if there is no birth dose for infants for HepB –If birth dose of HepB is necessary, then a combination of DTP-Hib and monovalent HepB may be an alternative choice