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Facilitator - Dr Gaurav Gupta
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
Almost every child infected by 2 years
          irrespective of Socio Economic Class

Rotavirus is:
Highly Contagious: Person to person, feco-oral,
  respiratory droplets

Resistant to inactivation: Most soaps and disinfectants
  not effective

Highly Stable: Retains infectivity for several weeks
Number of deaths due to
                                                                                                    rotavirus disease (and
                                                                                                  percentage of the global
                                                                                                 total) in 10 countries with
                                                                                                   the greatest number of
                                                                                                   deaths due to rotavirus
                                                                                                           disease.




                             23% of all deaths due to rotavirus disease occurred in India

Adapted from: Umesh Parashar, Global Mortality Associated with Rotavirus among Children • JID 2009:200 (Suppl 1) • S9-15
Other
                                                   G9P[6]
                                                                         7%
                                             G9P[8] 1%
                                                3%
                                    G4P[8]
                                     9%
                               G3P[8]
                                3%


                           G2P[4]
                            12%                                                                                G1P[8]
                                                                                                                65%




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.
IRSN Data
                                                                                     G12 P[4][6][8],
                                                                                          6.5%
                                    G9 P[8], 8.5%




                                                                                                                                                      G2 P[4], 25.7%


                             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.
RISK                                                                              EVENTS

         1 in every 177-196 children                                                                             122,000-153,000
                                                                        Deaths

         1 in every 31-59 children                                                                               457,000-884,000
                                                               Hospitalizations

         1 in every 13 children                                                                                          2 million
                                                               Outpatient Visits

                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
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
21
Vaccines should mimic the natural infection
              Predominance of individual serotypes
                    pattern                                               can vary
                      from A multivalent vaccine is by geographic region.1
                            year to year and expected to give more
                     Primary infections are usually associated with
                            diverse protection against multiple serotypes
                            with the 1st dose
                      more severe disease than subsequent
                      infections.2 are expected to give good protection
                            2 doses
                            against moderate to severe diarrheas
                     Protection against disease is thought to
                      increase with each subsequent protection 2
                            3 doses are expected to give good infection.
                            against mild diarrheas as well
                     Immunity following primary infection is
                      thought to be predominantly serotype specific.2


1. Santos N et al. Rev Med Virol. 2005;15:29–56. 2. Velázquez FR et al. N Engl J Med. 1996;335:1022–1028.
SEROTYPE-SPECIFIC
                                                       (HOMOTYPIC)
                                    Immune Response
                                               First infection elicited a HOMOTYPIC
                                               protective response

                                               Second & subsequent“CROSS-PROTECTIVE”
                                                                       infections
                                                                    (HETEROTYPIC)
                                               elicited a HETEROTYPIC protective
                                               response
                                                              1     2       3
                                                             Number of Infections
                                                      (Graph for illustrative purposes only)

• After primary infection, antibody response appears to be predominantly serotype specific (homotypic).1,2
• After subsequent infections, a broadened, cross-reactive (heterotypic) antibody response can occur.1,2


1. Cortese MM et al. MMWR Morb Mort Wkly Rep. 2009;58(RR02):1–25. 2. Jiang B et al. Clin Infect Dis. 2002;34:1351–1361.
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
   A bit about diarrhea & ORS
   Epidemiology & disease burden of Rotavirus
   Efficacy of Rotavirus vaccine incl differences
    between Rotarix v/s Rotateq
   Special issues with RV vaccines
   CME
   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
   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
   An infant with short bowel syndrome
   An infant with HIV
   An infant with severe combined
    immunodeficiency disease
   An infant with spina bifida
   An infant with short bowel syndrome
   An infant with HIV
   An infant with severe combined
    immunodeficiency disease
   An infant with spina bifida
   Mexico
   Africa
   Brazil
   India
   Mexico
   Africa
   Brazil
   India
   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
   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
   Hirschspung disease
   HIV
   Malabsorption syndrome
   Severe combined immunodeficiency syndrome
   Hirschspung disease
   HIV
   Malabsorption syndrome
   Severe combined immunodeficiency syndrome
   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
   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
   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
   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
   The ACIP, AAP & IAP recommend Rotarix®
    because it can be administered in a 2-dose
    series
   The ACIP, AAP & IAP recommend RotaTeq®
    because it is more effective in preventing
    severe rotavirus disease
   The ACIP, AAP & IAP recommend Rotarix ®
    when initiation of the vaccine series is delayed
   The ACIP, AAP & IAP do not recommend one
    vaccine over the other
   The ACIP, AAP & IAP recommend Rotarix®
    because it can be administered in a 2-dose
    series
   The ACIP, AAP & IAP recommend RotaTeq®
    because it is more effective in preventing
    severe rotavirus disease
   The ACIP, AAP & IAP recommend Rotarix ®
    when initiation of the vaccine series is delayed
   The ACIP, AAP & IAP do not recommend one
    vaccine over the other
   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
   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
   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 convinve
    parents ?

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Rotavirus disease & prevention - the Indian context

  • 1. Facilitator - Dr Gaurav Gupta
  • 2. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 3. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 4.
  • 5.
  • 6.
  • 7. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 8.
  • 9. Almost every child infected by 2 years irrespective of Socio Economic Class Rotavirus is: Highly Contagious: Person to person, feco-oral, respiratory droplets Resistant to inactivation: Most soaps and disinfectants not effective Highly Stable: Retains infectivity for several weeks
  • 10.
  • 11. Number of deaths due to rotavirus disease (and percentage of the global total) in 10 countries with the greatest number of deaths due to rotavirus disease. 23% of all deaths due to rotavirus disease occurred in India Adapted from: Umesh Parashar, Global Mortality Associated with Rotavirus among Children • JID 2009:200 (Suppl 1) • S9-15
  • 12.
  • 13. Other G9P[6] 7% G9P[8] 1% 3% G4P[8] 9% G3P[8] 3% G2P[4] 12% G1P[8] 65% 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.
  • 14. IRSN Data G12 P[4][6][8], 6.5% G9 P[8], 8.5% G2 P[4], 25.7% 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.
  • 15.
  • 16.
  • 17. RISK EVENTS 1 in every 177-196 children 122,000-153,000 Deaths 1 in every 31-59 children 457,000-884,000 Hospitalizations 1 in every 13 children 2 million Outpatient Visits 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
  • 18.
  • 19. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 20.
  • 21. 21
  • 22. Vaccines should mimic the natural infection  Predominance of individual serotypes pattern can vary from A multivalent vaccine is by geographic region.1 year to year and expected to give more  Primary infections are usually associated with diverse protection against multiple serotypes with the 1st dose more severe disease than subsequent infections.2 are expected to give good protection 2 doses against moderate to severe diarrheas  Protection against disease is thought to increase with each subsequent protection 2 3 doses are expected to give good infection. against mild diarrheas as well  Immunity following primary infection is thought to be predominantly serotype specific.2 1. Santos N et al. Rev Med Virol. 2005;15:29–56. 2. Velázquez FR et al. N Engl J Med. 1996;335:1022–1028.
  • 23. SEROTYPE-SPECIFIC (HOMOTYPIC) Immune Response First infection elicited a HOMOTYPIC protective response Second & subsequent“CROSS-PROTECTIVE” infections (HETEROTYPIC) elicited a HETEROTYPIC protective response 1 2 3 Number of Infections (Graph for illustrative purposes only) • After primary infection, antibody response appears to be predominantly serotype specific (homotypic).1,2 • After subsequent infections, a broadened, cross-reactive (heterotypic) antibody response can occur.1,2 1. Cortese MM et al. MMWR Morb Mort Wkly Rep. 2009;58(RR02):1–25. 2. Jiang B et al. Clin Infect Dis. 2002;34:1351–1361.
  • 24.
  • 25.
  • 26.
  • 27.
  • 28.
  • 29.
  • 30.
  • 31. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 32.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37.
  • 38. A bit about diarrhea & ORS  Epidemiology & disease burden of Rotavirus  Efficacy of Rotavirus vaccine incl differences between Rotarix v/s Rotateq  Special issues with RV vaccines  CME
  • 39. 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
  • 40. 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
  • 41.
  • 42. An infant with short bowel syndrome  An infant with HIV  An infant with severe combined immunodeficiency disease  An infant with spina bifida
  • 43. An infant with short bowel syndrome  An infant with HIV  An infant with severe combined immunodeficiency disease  An infant with spina bifida
  • 44. Mexico  Africa  Brazil  India
  • 45. Mexico  Africa  Brazil  India
  • 46. 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
  • 47. 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
  • 48. Hirschspung disease  HIV  Malabsorption syndrome  Severe combined immunodeficiency syndrome
  • 49. Hirschspung disease  HIV  Malabsorption syndrome  Severe combined immunodeficiency syndrome
  • 50. 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
  • 51. 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
  • 52. 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
  • 53. 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
  • 54. The ACIP, AAP & IAP recommend Rotarix® because it can be administered in a 2-dose series  The ACIP, AAP & IAP recommend RotaTeq® because it is more effective in preventing severe rotavirus disease  The ACIP, AAP & IAP recommend Rotarix ® when initiation of the vaccine series is delayed  The ACIP, AAP & IAP do not recommend one vaccine over the other
  • 55. The ACIP, AAP & IAP recommend Rotarix® because it can be administered in a 2-dose series  The ACIP, AAP & IAP recommend RotaTeq® because it is more effective in preventing severe rotavirus disease  The ACIP, AAP & IAP recommend Rotarix ® when initiation of the vaccine series is delayed  The ACIP, AAP & IAP do not recommend one vaccine over the other
  • 56. 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
  • 57. 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
  • 58. 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 convinve parents ?

Notas del editor

  1. 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&apos;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]
  2. 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.
  3. Recent information about the risk for intussusception comes from studies conducted in Mexico[28] and Brazil.[29] In Mexico there was a &gt; 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]
  4. Some clinicians are hesitant to administer rotavirus vaccines to infants or children with certain preexisting conditions, but there are only a few true contraindications. * Infants with severe latex allergy may receive RotaTeq.[21,22]
  5. Recommendations for routine vaccination have not been made for children with these conditions. The potential risks and benefits of vaccine administration should be weighed for each patient, and consultation with an infectious disease specialist or immunologist should be considered. Some experts recommend that children at risk for a latex allergy developing (eg, children with spina bifida)* should preferably receive RotaTeq to minimize latex exposure. If RotaTeq is unavailable, Rotarix should be administered because the benefit of vaccination is considered greater than the risk for sensitization.[21,22] Caution should also be exercised when considering administration of the rotavirus vaccine to an infant residing in a household or in close contact with a person with known severe compromised immune function. It has been argued that the risk for transmission of a vaccine strain with associated clinical symptoms is much lower than the risk for wild-type rotavirus disease from an unvaccinated child.[7] *If RotaTeq is unavailable, Rotarix should be administered because the benefit of vaccination is considered greater than the risk for sensitization.[21,22]