1. Vaccines What is new ? Umayya M.Musharrafieh, MD American University of Beirut Medical Center November 10-12, 2006

2. Background  Rota virus is the most common cause of severe gastroenteritis  It is responsible for half a million death /year among children <5 years in developing world  In USA, rota viruses are responsible for 5%-10% of all gastrointestinal episodes, 30%-50% of all hospitalization for diarrhea, and nearly every child is infected with rota vrus by age 5 years

4. Rational for Rotavirus Vaccination  Rates of rotavirus illness are similar in developing and less- developed countries, with little role for clean water supplies and good hygiene on virus transmission  High level of rotavirus morbidity continue to occur despite available therapies  Studies of natural rotavirus infection indicate that initial infection protects against subsequent severe gastroenteritis

6. Rotavirus Vaccine  In 1998, a rhesus-based tetravalent rotavirus RRV-TV vaccine was introduced  Withdrawn because of risk of intussusceptions within 3-14 days after receipt of first dose, and the risk was 1/10,000 vaccine recipients  Risk of intussusceptions with RRV-TV increased with age, and high in infants vaccinated after 60 days of age  RRV-TV was associated also with a spectrum of other GE symptoms, including gastroenteritis and blood in stools

7. Rotavirus Vaccine  In June 2006, a monovalent vaccine based on an attenuated human strain has shown clinical efficacy of 85% with no increase in intussusceptions  In USA, a live,oral vaccine that contains five reassortant rotaviruses developed from human and bovine parent rotavirus strains  This rota virus vaccine has been tested on a large scale of 70,0000 infants in 11 countries

8. Immunogencity  Sera collected before vaccination and 2 weeks after the third dose, and seroconversion was defined as a threefold or greater rise for IgA antibody titer from baseline  Seroconversion rates were 93%-100% among 4399 vaccine recipients versus 12%- 20% in 397 recipients of the placebo

9. Immunogencity  When administered simultaneously, a 3- dose series of the vaccine does not diminish the immune response to HiB vaccine, inactivated polio (IPV), pneumococcal conjugate vaccine, diphteria and tetanus antigens in DTaP

10. Efficacy  Efficacy of the vaccine after completion of- 3-dose regimen against diarrhea of any severity was74% and against severe diarrhea 98%  In a study on 5673 children rota virus vaccine reduced the incidence of office visits by 86%,and ED visits by 94% and hospitalization by 96%

11. Adverse Events Post-Vaccination  Intussusceptions a. The risk of intussusceptions was evaluated in 71,725 persons in phase III trials b. For the 42-day post-vaccination, six cases of IS were observed in the vaccine group vs. five in the placebo c. for the 1-year follow-up period after administration of first dose, 13 cases of intussusception were in vaccine group vs.15 cases in placebo group

12. Other Adverse Events No death were attributed to vaccinations In a 42-day period post-vaccination, vaccinees had a small but statistically significantly greater rate of certain symptoms:  1%excess vomiting  3% excess of diarrhea,  1% excess nasopharyngitis  2% OM  0.4% bronchospasm

13. Other Adverse Events  Incidence of fever and hematochezia were similar in vaccines and placebo  No cases of intussusception were reported among preterm infants and the incidence of serious adverse events was similar in preterm vaccines and placebo

14. Routine Administration  ACIP recommends routine vaccination of infants with 3-doses of rotavirus vaccine administered orally at 2,4, and 6 months  First dose between 4-10 weeks, subsequent doses should be administered by age 32 weeks  All 3 doses should be given by age 32 weeks

15. Routine Administration  Vaccination should not be administered after 12 weeks of age because of lack of data on safety in older infants  Infants with rotavirus gastroenteritis before vaccination should still initiate or complete vaccination  Breastfed infants can receive the vaccine

16. Contraindications and Precautions  Hypersensitivity to any component of the vaccine  Altered immune response (blood dyscrasia, immuno- suppressed therapy, primary or acquired immunodeficiency, received blood transfusion or immunoglobulin within 42-days)  Acute gastroenteritis  Moderate to severe illness  Pre-existing chronic gastrointestinal disease  Intussusceptions

17. Special Situations  Premature Infants(<37 weeks’ gestation)  Exposure of immunocompromised persons to vaccinated infants  Exposure of pregnant women to vaccinated infants  Regurgitation of the vaccine  Hospitalization after vaccination

19. Human Papilloma Virus Vaccine Papillomaviruses are diverse group of DNA-based viruses that infect skin and mucous membranes More than 100 different HPV viruses have been characterized A separate group of 30 HPV are typically transmitted thru sexual contact Genital HPV is very common with 75% of women will become infected at some time during adulthood

22. Pap Smear Cervical pap smear testing is used to detect HPV- induced cellular abnormalities In absence of pap testing or RX, about 1% of women with genital HPV infection will proceed to CC Although pap smear has reduced incidence and lethality of CC, the disease still kills thousands women /year

23. Pap Smear Pap smear is an effective strategy for reducing risk of CC Even newer liquid-based cytology method may miss 15-35% of CIN3’s cancers HPV testing to all women over 30 years improves sensitivity to cytology to 100% HPV testing can serve as an adjunct to pap smear and may be ordered in response to abnormal pap smear

24. Recommendations for the Use of Quadrivalent HPV Vaccine Routine vaccination with 3 doses is recommended for females 11-12 years of age. Vaccine can be started in females as young as 9 years Catch-up vaccination is recommended for females 13-26 years of age who have not been vaccinated previously or who have not completed the full vaccine series (the vaccine should be administered before potential exposure to HPV thru sexual contact)

25. Recommendations for the Use of Quadrivalent HPV Vaccine The vaccine protects against 4 types of HPV, which are responsible for 70% of CC and 90% of genital warts Vaccine is administered in 3 dose schedule Second and third dose should be administered 2 and 6 months after the first dose The vaccine can be administered at the same time when other vaccines are provided,such as Tdap,Td and MCV4

26. Safety and Efficacy The HPV vaccine has been tested on 11,000 females (9-26 yrs), and was found safe Efficacy studies on young women 16-26yrs showed efficacy of 100% against targeted types 99% of vaccinated subjects demonstrate elevated titers after vaccination Current studies indicate that the vaccine is effective up till 5 yrs

27. Special Situations Quadrivalent HPV vaccine can be given to females who have an equivocal or abnormal Pap smear, or genital warts, CC screening recommendations have not changed for females who receive the HPV vaccine Patients should be informed that the vaccine will not have any therapeutic effect on existing Pap smear abnormalities, HPV infection or genital warts.

28. Special Situations Contraindication to the use of the vaccine is for people with history of immediate hypersensitivity to yeast or any vaccine component Quadrivalent HPV vaccine can be administered to females with minor illnesses( diarrhea,or mild URTI,with or without fever) Vaccination of people with moderate or severe acute illness should be deferred until after illness improves

30. Meningococcal vaccine ACIP previously recommended tetravalent meningococcal (A,C,Y,W-135) polysaccharide (MSP4) Certain high –risk children and adolescents Travelers to hyper-endemic areas People with certain medical conditions For control of meningococcal outbreaks

31. Meningococcal vaccine A new tetravalent vaccine (A,C,Y,W-135) conjugate vaccine (MCV4) was licensed for use in people 11-55 years Three studies in USA addressed the risk of meningococcal disease among college students In 2000, ACIP and AAP concluded that college students living in dormitories are at an increased risk of meningococcal disease relative to other people of their age

32. Meningococcal vaccine Two vaccines: MPSV4 introduced in 1981 for ≥ 2 years and adults MCV4 in 2005 for children older than 11 years through 55 years

33. MPSV4 VS. MCV4 A T-cell independent antigen, does not elicit T lymphocytes, no long immunity Vaccine efficacy declines rapidly in children Hypo-responsiveness to subsequent doses Does not sustain reduction in nasopharyngeal carriage T-cell dependent antigen, long-lasting immunity Duration of protection not known but > 3 yrs Increase in immune response with subsequent doses Reduces nasopharyngeal carriage

34. Recommendations Two cohorts should be immunized: Young adolescents at the 11 to 12 year visit Adolescents at high school entry or 15 years Entering college students who plan to live in dormitories (MCV4)

35. Recommendations People at an increased risk of MD should be immunized with MCV4 if they are at least 11 years and include: a. terminal complement deficiency or anatomic asplenia b. Hyepr-endemic areas HIV patients if they are 11 years

36. Recommendations Children 2-10 years at increased risk should be immunized with MPSV4 People who wish to decrease their risk may take MCV4 For control of outbreaks Immunization with MCV4 may be indicated for adolescents previously immunized with MPSV4

38. Pneumococcal Disease S. Pneumoniae causes 3,300 cases of meningitis,100-135,000 of pneumonia and 6 million cases of OM per year S. Pneumoniae has become the leading cause of bacterial meningitis in USA Importance of immunization is heightened because of increased proportion of antibiotic resistance

39. Pneumococcal Disease Risk factors for invasive disease include age,race, use of AB, day care attendance, exposure to passive smoking, and chronic medical problems. Hemoglobinopathies Functional and anatomic asplenia

40. Conjugate Pneumococcal vaccine Two vaccines available: Older 23-valent polysaccharide vaccine (PPV) New 7-valent pneumococcal conjugate vaccine (PCV)

41. PPV vs. PCV PPV contains T-cell independent antigens-no anamenstic response Effective in adults and older children (not in <2 years) Does not reduce naso- pharyngeal colonization PCV is more immunogenic elicit a T-dependant immune response Effective in children and most invasive serotypes are covered Reduces nasopharyngeal colonization

42. Conjugate Pneumococcal vaccine Efficacy Adverse reactions Contraindication and precautions Administration

43. Children for whom PCV is recommended ACIP,AAP and AAFP recommend using PCV for routine infant immunization and catch-up vaccination of children 23 months and younger. They also recommend its use for children 24 to 59 months of age who have high risk : A. hemoglobinopathies, asplenia, HIV, renal failure B. Chronic disease (cardiac, pulmonary, CSF leaks, DM)

44. Children for whom PCV should be considered All children aged 24-59 months, with priority to Children aged 24-35 months Children who attend day-care centers Children of African- American origin PCV is not approved for use in adults, no efficacy data are available for its use in older adults PCV should not replace polysaccharide vaccine in older children and adults

45. Schedule for Catch-up Administration of PCV in Unvaccinated children Age at first dose Primary booster 2-6mos 3 doses,2 mos 1 dose (12-15mos) apart 7-11mos 2 doses,2 mos 1 dose (12-15 mos) apart 12-23 mos 2 doses,2 mos - apart 24-59 mos Healthy one dose - Sickle,asplenia or 2 doses,2 mos apart - immunocompromised -

47. Pertussis Immunization in Adults Pertussis is a highly contagious RTI Vaccines has decreased the annual incidence of pertussis from 157/100,000 persons in pre- vaccination era to 1/100,000 persons Vaccine has not decreased the incidence of disease in older persons or outbreaks, nor has it eliminated the transmission of infections to un-immunized children

48. Pertussis Immunization in Adults Pertussis vaccines have not been recommended for persons >6 years of age, keeping the disease circulating among adults and creating a source of contagion for children Most adult cases are not suspected, detected, or reported Possibility of a case of pertussis is usually considered only when it occurs in association with whooping cough in children

49. Pertussis Immunization in Adults Many factors contribute to failure of detection Lack of clinical awareness Lack of availability and in sensitivity of culture and PCR assay Lack of standardized serologic testing for pertussis Difficulty obtaining adequate specimens Absence of clear serologic diagnostic criteria

50. Pertussis Immunization in Adults The ACIP,on October 2005, recommended routine use of a single dose of Tdap for adults 19-64 yr of age On Feb 22, 2005, ACIP recommended Tdap for health care personnel as soon as feasible

51. Recommendations for a single dose of Tdap Adolescents 11-18 yrs should receive a single dose of Tdap if they have completed childhood schedule Adults 19-64 yrs should receive a single dose of Tdap to replace a single dose of Td if they received the last shot >10 yrs Tdap may be given at an interval shorter than 10 yrs since receipt of last toxoid-tetanus shot The dose of Tdap replaces the next scheduled booster of Td

52. Recommendations for a single dose of Tdap Prevention of pertussis among infants,12 months of age by vaccinating adult contacts: Tdap should be given one month prior to contact and women should receive Tdap in the immediate post-partum period if not previously vaccinated Health care personnel: Priority to HCW in contact with infants < 12 months of age, and they are encouraged to receive a Tdap as soon as 2 yrs since last Td

53. Special Situations Tetanus prophylaxis for wound management Incomplete or unknown vaccination history History of pertussis Pregnancy Adults 65 yrs