Rotavirus Vaccine

Updates & WHO Position Vikash R. Keshri Dept. of Community Medicine Rotavirus Vaccine

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 deaths Number of deaths due to rotavirus-related diarrhoea (and proportion of the worldwide 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 • Nutritionalstatus: 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 Exclusive Breast feeding Improved water quality Vaccination Good sanitation and hygiene PREVENTION

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 pentavalent bovine–human reassortant rotavirus vaccine (RotaTeq™). • Contains 5 reassortant rotaviruses developed • from human and bovine (WC3) parent rotavirus strains. • The monovalent human rotavirus vaccine (Rotarix™) • Multiple passages in tissue culture resulting in attenuated vaccine strain, RIX4414

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.

weeks weeks Rota 1 Rota 2 Birth Birth 10 10 15 15 6 6 32 32 Rota 1 Rota 2 Optimal Age:

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.

Rotavirus Vaccine and Intussusception: Source: Guillermo M R et al.. Safety and Efficacy of an Attenuated Vaccine against 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

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?

Rotavirus Vaccine