rotavirus vaccine vikash keshri
TRANSCRIPT
1
Rotavirus Vaccine Updates & WHO Position
Vikash R. Keshri Dept. of Community Medicine
• Introduction• Problem statement• Epidemiology• Rotavirus Vaccines• Evidences for WHO Position• WHO position • Recommendations in India
Introduction:• Rotaviruses; leading cause of severe,
dehydrating diarrhoea in children <5 years globally.
• Estimated >25 million outpatient visits and >2 million Hospitalizations.
• Severe rotavirus gastroenteritis largely limited to children aged 6–24 months.
• The primary infection usually most significant but Re infection also occurs.
Problem Statement
Problem Statement…….....
Countries with the greatest number of rotavirus-related deathsNumber of deaths due to rotavirus-related diarrhoea (and proportion of theworldwide total).Source: Lancet Infect Dis 2012; 12: 136–41
Epidemiology:AGENT• Derived from the Latin word Rota, means
“wheel,”• Classified as a genus in the family of Reoviridae.
• Double-stranded RNA virus• Composed of three concentric shells that
enclose 11 gene segments.• Two important proteins—VP7, or G-
protein, and VP4, or P-protein.• Five strains (G1–4, G9) account for 90%
cases.• G1 strain account > 75%.
• Very stable and may remain viable in the environment for weeks or months if not disinfected.
Host Factor:• Reservoir: Human• Age; - Most commonly 6 months to
3 years of age • Sex; - Incidence is equal• Immunity- Primary Infection render immunity
but re-infection can occur• Nutritional status: Malnutrition Important
contributory factor. Mortality several times higher in
malnutrition cases
Environmental Factor
• Geographic Region: Throughout world but varies from country to
country
• Seasonal: During rainy and winter season.
• Period of Communicability: From 2 days before to 10 days after onset.
• Poor socio- economic condition.
• Poor sanitation
Mode of Transmission
• Feco – Oral Route
• Rotaviruses are shed in very high concentrations (>10¹² particles/gram) and for many days in the stools and vomitus.
Clinical Features & Diagnosis
Watery Diarrhea Fever Vomiting
Rapid test Kit Using EIA
Prevention and Control
Good sanitation and hygiene
Exclusive Breast feeding
Improved water quality
PREVENTIONVaccination
Rotavirus Vaccine History:• Rota Shield (Wyeth- Lederle) licensed in the
United States in 1998.• Shortly Recommended for routine use in US
infants.• Extensive evaluations before licensure
indicated vaccine safe and efficacious.• After first of the 3 oral vaccine doses.• Excess number of cases of intussusceptions
reported.• Predominantly in infants >3 months of age.• Consensus attributable risk of 1 per 10 000
vaccinated infants.
Withdrawn from market.
Rotavirus: Current Vaccines
• The monovalent human rotavirus vaccine (Rotarix™)
• Multiple passages in tissue culture resulting in attenuated vaccine strain, RIX4414
• The pentavalent bovine–human reassortant rotavirus vaccine (RotaTeq™).
• Contains 5 reassortant rotaviruses developed
from human and bovine (WC3) parent rotavirus strains.
Rotarix Vaccine• Approved in 2008.• Live attenuated vaccine.• Vaccine strain and characteristics:
Originates from a G1P[8] strain isolated from a case of infantile gastroenteritis.
Undergoes multiple passages in tissue culture, and the resulting attenuated vaccine strain, RIX4414.
• Storage: lyophilized vaccine should be kept at 2–8 °C in
its original package, protected from light. Should not be frozen. Vaccine shelf-life is 3 years.
Optimal Age:
Rota 1 Rota 2
6Birth 10 15 32weeks
Rota 1
Rota 2
6Birth 10 15 32weeks
Administration
Administered orally in a 2-dose schedule.
Route: Oral– Dilution: Reconstitution in calcium carbonate
buffer contained in a single-dose, pre-filled oral applicator given promptly.
Dose: Consists of two 1-mL doses. Infant Feeding No evidence to suggest that breast-
feeding reduced the protection.
Indication and precaution: Prevention of rotavirus gastroenteritis caused
by G1 and non-G1 types (G3, G4, and G9). Approved for use in infants 6 weeks to 32
weeks only.
Contraindication: Hypersensitivity Gastrointestinal Tract Congenital Malformation History of Intussusception Severe Combined Immunodeficiency Disease
Warnings and Precautions: Latex Gastrointestinal Disorders: Administration of
ROTARIX should be delayed in infants suffering from acute diarrhea or vomiting.
Altered Immunocompetence Shedding and Transmission:
Possibility that the live vaccine virus can be transmitted to non-vaccinated contacts. Intussusception
• Adverse Reactions: Common (≥5%) solicited adverse events
includes:– Fussiness/irritability, – Cough/runny nose, – Fever, – Loss of appetite, and vomiting.
RotaTeq Vaccine:
• Initial approval in US 2006.• Rotavirus Vaccine, Live, Oral, Pentavalent• Vaccine strain and characteristics:
Contains 5 reassortant rotaviruses developed from human and bovine (WC3) parent rotavirus strains.
• Storage:• In refrigerated at 2–8 °C for up to 24 months.• No preservatives or thimerosal.• After removal from refrigeration, the vaccine
should be used promptly.
Indications and Usage
– Prevention of rotavirus gastroenteritis caused by the G1, G2, G3 and G4 serotypes.
– Approved for use in infants 6 weeks to 32 weeks of age.
Dosage and Administration For oral use only. not for injection. Series consists of three ready-to-use liquid
doses. Starting at 6 to 12 weeks of age, Subsequent doses administered at 4- to 10-
week intervals. The third dose should not be given after 32
weeks..
• Dose and Strengths: 2 mL solution contains a minimum of 2.0 – 2.8
x 106
infectious units (IU) per reassortant dose.
• Contraindications: A demonstrated history of hypersensitivity
to the vaccine or any component of the vaccine.
History of Severe Combined Immunodeficiency Disease (SCID).
History of intussusception.
Warnings and Precautions:• No safety or efficacy data available for
immunocompromised (e.g., HIV/AIDS).• No safety or efficacy data available infants
with a history of gastrointestinal disorders. e.g., Active acute gastrointestinal illness, Chronic diarrhea, Failure to thrive, History of congenital abdominal disorders,
and H/o abdominal surgery
• Vaccine virus transmission to non vaccinated contacts reported.
Adverse Reactions:• Most common adverse events included
– Diarrhea, – Vomiting, – Irritability, – Otitis media, – Nasopharyngitis, and bronchospasm.
Use in Specific Populations:• Pediatric Use: Safety and efficacy not established in infants <
6 weeks o or > 32 weeks • Data available from clinical studies support the
use of RotaTeq in Pre-term infants according to their age in weeks.
Evidences for WHO Position
Source: Rotavirus Efficacy and Safety Trial (REST). N Engl J Med 2006;354:23-33.
Source: Rotavirus Efficacy and Safety Trial (REST). N Engl J Med 2006;354:23-33.
Source: Rotavirus Efficacy and Safety Trial (REST). N Engl J Med 2006;354:23-33.
Rotavirus Vaccine and Intussusception:
Source: Guillermo M R et al.. Safety and Efficacy of an Attenuated Vaccineagainst Severe Rotavirus Gastroenteritis. N Engl J Med 2006;354:11-22.
WHO Position:WHO Position on Vaccines: General
Considerations• Vaccines for large-scale public health
interventions should meet the current WHO quality requirements.
• Be safe and significant impact against the actual disease in all target populations.
• If intended for infants or young children, be easily adapted to the schedules and timing of national childhood immunization programmes.
• Don’t interfere significantly with the immune response to other vaccines given simultaneously;
• Be formulated to meet common technical limitations, e.g. in terms of refrigeration and storage capacity.
• Be appropriately priced for different markets
WHO Position on Rotavirus Vaccine 2007
• Main goal of rotavirus vaccination:
Prevent death and severe disease caused by rotavirus.
• 2 rotavirus vaccines proven to be safe and efficacious.
• In industrialized countries, routine immunization has the potential to reduce significantly the large number of emergency consultations & Hospitalizations.
• Save considerable direct and indirect costs associated with acute rotavirus disease in the youngest age groups
• In developing countries; Introduction of vaccines reduce the heavy
burden of severe rotavirus diarrhoea. • WHO strongly recommends;
The inclusion of rotavirus vaccination into the national immunization programmes of regions and countries
Where vaccine efficacy data suggest a significant public health impact and
Where appropriate infrastructure and financing mechanisms are available to sustain vaccine utilization.
Source: Weekly epidemiological record, No. 51-52, 18 December 2009
Source: Weekly epidemiological record, No. 51-52, 18 December 2009
Source: Weekly epidemiological record, No. 51-52, 18 December 2009
Current WHO Position (2010) Newer Evidences:• Trials of rotavirus vaccines ha conducted in
Asian and African countries.• Trials have also included countries where
sanitation is poor and• Where there is high mortality from diarrhoeal
diseases and a high maternal prevalence of HIV.
• Rotarix has been evaluated in Malawi and South Africa.
• RotaTeq has been studied in Ghana, Kenya and Mali in Africa, and in Bangladesh and Viet Nam in Asia.
• SAGE on Immunization and GACVS reviewed new evidences.
• Taking into account new evidence, WHO now recommends infants worldwide be vaccinated against rotavirus.
• WHO recommends rotavirus vaccine for inclusion in all national immunization programmes
• Strongly Recommended in countries where diarrhoeal deaths account for ≥10% of mortality among children aged <5 years.
• First dose of either RotaTeq or Rotarix be administered at age 6–15 weeks.
• The maximum age for last dose should be 32 weeks.
• 2 doses of Rotarix be administered with the first and second doses of DTP rather than with the second and third doses.
• Rotavirus vaccines be part of a comprehensive strategy to control diarrhoeal diseases including interventions: Improvements in hygiene and sanitation, Zinc supplementation, Community-based administration of oral
rehydration solution and Overall improvements in case management
Recommendations in India
• Not included in National Immunization Schedule.
• Indian Academy of Paediatrics recommends but not routine.
• Rotavirus vaccine can be given after discussion with parents
• Dose and Schedule same
Conclusions:• Duration of Protection?• Cost Effectiveness ?• Role other Contributory factors ?• Evidences from developing countries
not convincing.• Even Small no. of serious AEFI
unacceptable?