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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?