Rotavirus vaccine presentation Rotateq 28 june 2013

3,234 views

Published on

Rotateq presentation for Small Group Meet,

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
3,234
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
371
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • This is a common misunderstanding. Parents cannot prevent their children from getting a rotavirus infection. The primary mode of rotavirus transmission is fecal to oral. Rotavirus is highly communicable and transmissible. Close person-to-person contact and environmental surfaces are common vectors of transmission. It is impossible to keep contaminated fingers and objects from going into children's mouths. Even if a child is not cared for in a daycare setting, he or she is likely to have contact with other children or objects that other children have touched. Rotavirus is an extremely hardy pathogen. The incubation period is 1-3 days and large quantities of virus are shed in stool from just prior to onset of symptoms until about 10 days after onset.[1] Rotavirus is highly transmissible. Under experimental conditions, almost 50% of rotavirus remains viable on contaminated hands for 60 minutes.[1]
  • Rotavirus has a worldwide distribution, and is found in both developed and developing countries. Prevalence varies by geographic region.[15] The greatest burden of diseases is in Africa, India, and south Asia.
  • Recent information about the risk for intussusception comes from studies conducted in Mexico[28] and Brazil.[29] In Mexico there was a > fivefold increased risk within the first 7 days after the first vaccine dose, equating to an intussusception rate of 1 in 51,000 vaccinated infants.[28] In Brazil, there was an approximate twofold increased risk within 7 days of the second dose, equating to an intussusception rate of 1 in 68,000 vaccinated infants.[29] Although 2 additional deaths would be expected to occur as a result of intussusception in Mexico, 663 childhood deaths and 11,551 hospitalizations would be prevented.[28] In Brazil, 5 additional deaths would be expected, but 1300 childhood deaths and 80,000 hospitalizations would be prevented.[29] Data from Australia also suggest an increased risk for intussusception in the immediate window after the first dose for both RotaTeq and Rotarix, but no increase in the overall risk.[30]
  • Rotavirus vaccine presentation Rotateq 28 june 2013

    1. 1. Rotavirus: Dilemma of Developing Countries Rotavirus Vaccine: Recent Updates from  IAPCOI Consensus Recommendations and  WHO Position Paper Facilitator: Dr Gaurav Gupta 28th June 2013
    2. 2. What’ s this talk going to be about ? • Rationale of RV vaccine – Morbidity & Mortality in India – Relevance to Pvt Practitioners • Differences between Rotarix & Rotateq – 3 doses v/s 2 doses – Cross Protection – Heterotypic v/s homotypic immunity (in Indian context) – Human v/s Bovine strain immunogenicity • Safety concerns with RV vaccines • Latest WHO & IAP Guidelines • CME
    3. 3. My pediatric cohort High socio- economic status. High level of sanitation and hygiene. East and Prompt Access to health care facilities. Disease is not VERY severe in them. NO WORRIES AT ALL? Well Nourished, less chance of nutrient deficiency Robust Immunity Then why did developed world e.g. US start with rotavirus vaccine
    4. 4. Rationale for Rotavirus Vaccination as a public health measure for prevention of rotavirus disease in U.S.1 1 Rates of rotavirus illness among children in industrialized and less developed countries were similar, indicating that clean water supplies and good hygiene have little effect on virus transmission; Therefore, further improvements in hygiene in the United States were unlikely to have a substantial impact on disease prevention 2 In the US, a high level of rotavirus morbidity continued in the prevaccine era despite available therapies. e.g. Rate of hospitalizations for gastroenteritis in young children declined only modestly during 1979−1995 despite the widespread availability of oral rehydration solutions in the treatment of dehydrating gastroenteritis 3 Studies of natural rotavirus infection: indicated that initial infection protects against subsequent severe gastroenteritis, (although subsequent asymptomatic infections and mild disease still might occur) Therefore, vaccination early in life, which mimics a child’s first natural infection, should prevent the majority of cases of severe rotavirus disease and their sequelae 1. Morbidity and Mortality Weekly Report. February 6, 2009 / Vol. 58 / No. RR-2 EVEN “DEVELOPED WORLD “ HAS CHOSEN ROTAVIRUS VACCINATION
    5. 5. RV protection after natural infection a) Indian and Mexico study Setting Velazquez et al1 Community setting in outskirts of Mexico. Year of study 1987 - 1990 Enrollment and sample size 200 Newborns betwn Oct 1987 – Oct 1988 Follow up Birth cohort F/u 2 years. 3699 (77%) child months followup. Visits, stool samples 1/week, 1/week + Diarrhea Testing for Rota G typing Blood sample First wk and every 4 months Primary Infections 52% (i.e. remaining were reinfections) Infections by 6 months of age 34% Protective Efficacy for Mod. to Sev. Diarrhea 100 % after two infections. 1. Velazquez et al. Rotavirus Infection In Infants As Protection Against Subsequent Infections. N Engl J Med 1996;335:1022-8. 2. Gladstone et al. Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. N Engl J Med 2011;365:337-46. Gladstone et al2 Community setting in three areas of Vellore, India. 2002 - 2006 452 Newborns betwn Mar 2002 – August 2003 Birth cohort F/u 3 years. 13340 child-months (99.5%) follow up. 373 children completing study 2/week, 1 in 2 weeks + Diarrhea G and P typing At birth/first week and every six mth RESULTS 33.6% (i.e.remaining were reinfections) 53% 79% after three infections
    6. 6. RV protection after natural infection 1. Velazquez et al. Rotavirus Infection In Infants As Protection Against Subsequent Infections. N Engl J Med 1996;335:1022-8. 2. Gladstone et al. Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. N Engl J Med 2011;365:337-46. b) Results from Mexican & Vellore Cohort 38 62 7473 75 99 87 100 0 20 40 60 80 100 120 1 2 3 Asymptomatic Infection Mild Diarrhea Moderate to Severe Diarrhea 24 33 4644 72 79 18 57 79 0 20 40 60 80 100 120 1 2 3 In general, in Vellore Cohort, the efficacy of natural infection in protecting against subsequent outcomes was less as compared to Mexico cohort (The two cohorts were from different settings and this graph is for presentation purpose only)
    7. 7. 3. Rotavirus vaccine efficacy e) Indian Immunogenicity Data 1. Human Vaccines 5:6, 414-419; June 2009. 2. Human Vaccines & Immunotherapeutics 9:1, 178–182; January 2013; 3. The Journal of Infectious Diseases 2009; 200:421–9, 4. Indian Pediatrics . Volume 49. JULY 16, 2012 Vaccine Setting Results RV11 Safety and Immunogenicity. 2 dose schedule, Starting at 8-10 weeks No Concomitant OPV Seroconversion was 58.3%,after 2nd dose. RV52 Safety and Immunogenicity. 3 dose schedule, starting at 6 weeks Concomitant OPV administered Seroconversion was 82.35% after 3rd dose 116 E3 Safety and Immunogenicity, Dose Escalation study. 3 dose schedule. Vaccine or placebo received at 8-12- 16 weeks. No Concomitant OPV. 1 X 105 FFU 116E (Phase III trial conducted with higher dose and 3 dose schedule)4 Seroconversion was 89.7% after 3rd dose
    8. 8. 3. Rotavirus vaccine efficacy WHO • There is currently insufficient evidence to make a general recommendation on the need for a third dose of RV1 in the primary series. • Further adequately powered studies would be helpful to explore whether additional doses have a favourable risk/benefit ratio in high mortality settings and whether partial vaccination is also efficacious against severe rotavirus diarrhoea. WHO Position Paper Jan 2013. WER No. 5, 2013, 88, 49–64
    9. 9. Global Distribution of Rotavirus Serotypes1 G1P[8] 65% G3P[8] 3% G4P[8] 9% G9P[6] 1%G9P[8] 3% Other 7% G2P[4] 12% Other=untypeable and rare G-P combinations. 1. Santos N, Hoshino Y. Rev Med Virol. 2005;15:29–56. Reproduced by permission of John Wiley & Sons Limited.
    10. 10. Rotavirus Strains Diversity in India G2 P[4], 25.7% G12 P[4][6][8], 6.5% G9 P[8], 8.5% G1 P[8], 22.1% Unique features: Diversity of rotavirus strains & mixed infections. Need for vaccines formulated against a broad range of strains.2 It is found that the predominant Rota Virus strain (type) in cities varied from year to year and from city to city. 3 1. The Journal of Infectious Diseases 2009; 200:S147–53. 2. Indian J. Med Res 118, Aug 2003, Pg 59-67 3. Journal of Clinical Microbiology. Oct 2001, Pg 3524-3529. IRSN Data
    11. 11. Rotavirus Disease Burden In India 122,000-153,000 457,000-884,000 2 million Estimated annual number and risk of death, hospitalization, and outpatient visits due to rotavirus diarrhea in children <5 years of age in India. Adapted from: J. E. Tate et al. Disease and economic burden of rotavirus diarrhea in India/Vaccine 27 S (2009) F18–F24 EVENTSRISK 1 in every 177-196 children 1 in every 31-59 children 1 in every 13 children Deaths Hospitalizations Outpatient Visits
    12. 12. 21
    13. 13. 4. Serodiversity c) Serotype-wise efficacy in Phase III CT of RV1 Vaccines1 Efficacy of RV1 against Severe RVGE according to clinical case definition (%) Vaccine (N = 9009) Placebo Group (N = 8858): G1P(8) 91.8 G3P[8], G4P[8], 9P[8] 87.3 G2P[4] 41.0 Efficacy against severe rotavirus gastroenteritis with a score of ≥11 on the Vesikari scale (%) Vaccine Group (N = 9009) Placebo Group (N = 8858): G1P(8) 90.8 G3P[8], G4P[8], G9P[8] 86.9 G2P[4] 45.4 41 87.3 91.8 90.8 86.9 45.4 1. Palacio R et al. N Engl J Med 2006;354:11-22.
    14. 14. Rotavirus Strains Diversity in India G2 P[4], 25.7% G12 P[4][6][8], 6.5% G9 P[8], 8.5% G1 P[8], 22.1% 1. The Journal of Infectious Diseases 2009; 200:S147–53. 2. Indian J. Med Res 118, Aug 2003, Pg 59-67 3. Journal of Clinical Microbiology. Oct 2001, Pg 3524-3529. IRSN Data
    15. 15. 4. Serodiversity d) Serotype-wise efficacy in Phase III CT of RV51 Clinical Efficacy of RV5 against RVGE of Any Severity. (%) Vaccine (N = 2834) Placebo (N = 2839): G1 74.9 G2 63.4 G3 82.7 G4 48.1 G9 65.4 Reduction in number of hospitalizations and ED visits (%): Vaccine (N = 34,035) Placebo (N = 34,003) G1 95.1 G2 87.6 G3 93.4 G4 89.1, G9 100.0 G12 100.0 74.9 63.4 82.7 48.1 65.4 95.1 87.6 93.4 89.1 100 100 1. Vesikari T. et al. N Engl J Med 2006;354:23-33.
    16. 16. As humans are the natural hosts for these strains, it has been suggested that – The immune responses they stimulate in infected humans, even after growth in cell culture, may be greater and more consistent than those elicited after administration of animal strains. WHO Immunological Basis of Immunization. Module 21 Rotavirus • Not all vaccines derived from human rotavirus strains elicit greater immune responses, or protection in immunized subjects than found after immunization with animal strains (Flores et al., 1990; Vesikari et al., 1991b). • A reassortment vaccine (human + bovine) like RV5 may actually enhance the immunogenicity to RV surface antigens VP4 & VP7. (Vaccines, Plotkin. 6th Edition, 2013) a) Human Vs Human bovine reassortment vaccine
    17. 17. After a primary, natural rotavirus infection, infants develop virus- specific neutralizing antibodies in serum directed against the infecting G type at levels greater than those directed against other G types. Protection against rotavirus disease in adults challenged with a virulent human rotavirus strain G1P1A(8) co-related with antibodies directed against homotypic VP4 and VP 7. This may explain in part, why heterotypic protection after administration of vaccines such as WC3, RRV, Rotarix is inconsistent. Inconsistent Heterotypic Protection of Rotavirus Vaccines: Plotkins textbook 6th ed. Clarke H F, Offit P A, Parashar U D. Rotavirus Vaccines. In: Plotkin SA, Orenstein WA, Offit PA eds. Vaccines. 6th ed. Chapter 30. Philadelphia, PA: Saunders Elsevier 2012
    18. 18. WHO • Rotavirus vaccines should be included in all national immunization programmes and considered a priority, particularly in countries with high RVGE-associated fatality rates, such as in south and south-eastern Asia and sub-Saharan Africa. • Though RV Vaccines efficacy is less, it has huge impact. IAPCOI • still believes that in developing countries with high rotavirus disease incidence, even moderate to low vaccine efficacy translates into significant numbers of severe rotavirus gastroenteritis cases prevented and into significant public health impact. c. WHO and IAPCOI Rotavirus vaccines WHO position paper – January 2013. WER No. 5, 2013, 88, 49–64 Indian Pediatrics . Volume 49. JULY 16, 2012
    19. 19. In which one of these patients should you not recommend receiving a first dose of rotavirus vaccine? • A 10-week-old boy born HIV positive • A 16-week-old adopted girl from unknown parentage • A 12-week-old premature stable boy in the neonatal intensive care unit • A 13-week-old girl who is breastfeeding
    20. 20. In which one of these patients should you not recommend receiving a first dose of rotavirus vaccine? • A 10-week-old boy born HIV positive • A 16-week-old adopted girl from unknown parentage • A 12-week-old premature stable boy in the neonatal intensive care unit • A 13-week-old girl who is breastfeeding
    21. 21. The potential for decreasing the burden of rotavirus disease, including mortality, is greatest in: • Mexico • Africa • Brazil • India
    22. 22. The potential for decreasing the burden of rotavirus disease, including mortality, is greatest in: • Mexico • Africa • Brazil • India
    23. 23. Which of the following children should be given a first dose of rotavirus vaccine? • A full-term 5-week-old infant • A full-term 33-week-old infant • A full-term 16-week-old infant • A preterm 8-week-old infant
    24. 24. Which of the following children should be given a first dose of rotavirus vaccine? • A full-term 5-week-old infant • A full-term 33-week-old infant • A full-term 16-week-old infant • A preterm 8-week-old infant
    25. 25. Which of the following is a contraindication to rotavirus vaccination in infants and small children? • Hirschspung disease • HIV • Malabsorption syndrome • Severe combined immunodeficiency syndrome
    26. 26. Which of the following is a contraindication to rotavirus vaccination in infants and small children? • Hirschspung disease • HIV • Malabsorption syndrome • Severe combined immunodeficiency syndrome
    27. 27. The classic clinical triad of rotavirus gastroenteritis consists of: • Intermittent fever, diarrhea, and abdominal pain • Low-grade fever, vomiting, and copious, watery diarrhea • Projectile vomiting, abdominal pain, and watery diarrhea • Vomiting, fever greater than 102°F, and intermittent diarrhea
    28. 28. The classic clinical triad of rotavirus gastroenteritis consists of: • Intermittent fever, diarrhea, and abdominal pain • Low-grade fever, vomiting, and copious, watery diarrhea • Projectile vomiting, abdominal pain, and watery diarrhea • Vomiting, fever greater than 102°F, and intermittent diarrhea
    29. 29. According to recommendations from the IAP, at what age should the patient have received her initial dose of rotavirus vaccine? • Between 8 weeks and 32 weeks • Between 6 weeks and 14 weeks, 6 days • Between 12 weeks and 24 weeks • Between 4 weeks and 14 weeks, 6 days
    30. 30. According to recommendations from the IAP, at what age should the patient have received her initial dose of rotavirus vaccine? • Between 8 weeks and 32 weeks • Between 6 weeks and 14 weeks, 6 days • Between 12 weeks and 24 weeks • Between 4 weeks and 14 weeks, 6 days
    31. 31. A parent wants assurance that her son will not develop intussusception from a rotavirus vaccine. What should you tell her? • The benefit of preventing severe rotavirus gastroenteritis outweighs the small potential risk for intussusception • There is no risk for intussusception from rotavirus vaccination • No association between RV vaccines and intussusception has been observed in either pre- or postlicensure studies • RotaShield® was taken off the market, but not because of an association with intussusception
    32. 32. A parent wants assurance that her son will not develop intussusception from a rotavirus vaccine. What should you tell her? • The benefit of preventing severe rotavirus gastroenteritis outweighs the small potential risk for intussusception • There is no risk for intussusception from rotavirus vaccination • No association between RV vaccines and intussusception has been observed in either pre- or postlicensure studies • RotaShield® was taken off the market, but not because of an association with intussusception
    33. 33. FINALLY, Why are we not using more rotavirus vaccine? • Concerns regarding RV burden in India? • Concerns regarding RV vaccine efficacy? • Concerns regarding LM / admission with AGE after RV vaccine? • Cost of vaccine • Side-effects of vaccine • Short window period for vaccination • Lack of patient awareness/ unable to convince parents ?

    ×