Elsevier

The Lancet

Volume 368, Issue 9532, 22–28 July 2006, Pages 323-332
The Lancet

Review
Rotavirus vaccines: current prospects and future challenges

https://doi.org/10.1016/S0140-6736(06)68815-6Get rights and content

Summary

Rotavirus is the most common cause of severe diarrhoea in children worldwide and diarrhoeal deaths in children in developing countries. Accelerated development and introduction of rotavirus vaccines into global immunisation programmes has been a high priority for many international agencies, including WHO and the Global Alliance for Vaccines and Immunizations. Vaccines have been developed that could prevent the enormous morbidity and mortality from rotavirus and their effect should be measurable within 2–3 years. Two live oral rotavirus vaccines have been licensed in many countries; one is derived from an attenuated human strain of rotavirus and the other combines five bovine-human reassortant strains. Each vaccine has proven highly effective in preventing severe rotavirus diarrhoea in children and safe from the possible complication of intussusception. In developed countries, these vaccines could substantially reduce the number and associated costs of child hospitalisations and clinical visits for acute diarrhoea. In developing countries, they could reduce deaths from diarrhoea and improve child survival through programmes for childhood immunisations and diarrhoeal disease control. Although many scientific, programmatic, and financial challenges face the global use of rotavirus vaccines, these vaccines—and new candidates in the pipeline—hold promise to make an immediate and measurable effect to improve child health and survival from this common burden affecting all children.

Section snippets

Burden of disease

Rotavirus infects all children early in life and although most first infections cause mild diarrhoea, 15–20% need treatment at a clinic, and 1–3% lead to dehydration needing hospitalisation (figure 1). The virus can be identified in 15–35% of children younger than 5 years treated in outpatient settings for diarrhoea and in 25–55% of those hospitalised.4, 11 About 600 000 children die every year from rotavirus, mainly in developing countries, and this figure represents about 5% of all deaths in

Rotavirus vaccines

The large burden of rotavirus disease has led many groups reviewing the need for new vaccines to select rotavirus as a high priority target for accelerated vaccine development. WHO's Diarrhoeal Disease Control Programme was the first to make this recommendation, which has been reaffirmed repeatedly by other international review groups, such as the Institute of Medicine (1985–86),52 the Children's Vaccine Initiative (1996), the Bill and Melinda Gates Foundation which funded the Children's

Challenges: scientific, logistic, financial

Many challenges remain before we can assess the full global effect that rotavirus vaccines can have to prevent severe and fatal cases of rotavirus infection in children. The question remains, will such live oral vaccines work as well in children in the poorest developing countries as they have in middle-income and developed countries where the original trials were done?10 Unlike parenteral vaccines, live oral vaccines against polio, cholera, and typhoid have not worked equally well in

Looking to the future

A new generation of rotavirus vaccines will soon be licensed in many countries and available for more widespread use. Early introduction into the private markets of these countries could lead to appreciable reductions in health-care costs and burden of disease within 2–4 years. Identifying the full value of these vaccines to prevent mortality from rotavirus in developing countries is still several years away and each of the vaccines must first show its effectiveness in poor populations in

References (110)

  • T Vesikari et al.

    Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants

    Vaccine

    (2004)
  • MC Georges-Courbot et al.

    Evaluation of the effiacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa

    Res Virol

    (1991)
  • BK Das et al.

    Characterization of the G serotype and genogroup of New Delhi newborn rotavirus strain 116E

    Virology

    (1993)
  • GL Barnes et al.

    Early phase II trial of human rotavirus vaccine candidate RV3

    Vaccine

    (2002)
  • B Jiang et al.

    Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles

    Vaccine

    (1999)
  • AH Choi et al.

    Intranasal administration of an Escherichia coli-expressed codon-optimized rotavirus VP6 protein induces protection in mice

    Protein Expr Purif

    (2004)
  • P Hanlon et al.

    Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants

    Lancet

    (1987)
  • M Kosek et al.

    The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000

    Bull World Health Organ

    (2003)
  • Millenium Development Goals Report

    (2005)
  • J Bresee et al.

    First report from the Asian Rotavirus Surveillance Network

    Emerg Infect Dis

    (2004)
  • NA Cunliffe et al.

    Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization

    Bull World Health Organ

    (1998)
  • EM Kane et al.

    The epidemiology of rotavirus diarrhea in Latin America. Anticipating rotavirus vaccines

    Rev Panam Salud Publica

    (2004)
  • UD Parashar et al.

    Global illness and deaths caused by rotavirus disease in children

    Emerg Infect Dis

    (2003)
  • U Parashar et al.

    Rotavirus and severe childhood diarrhea

    Emerg Infect Dis

    (2005)
  • HF Clark et al.

    Rotavirus vaccines

  • RI Glass et al.

    Rotavirus vaccines: targeting the developing world

    J Infect Dis

    (2005)
  • SM Cook et al.

    Global seasonality of rotavirus infections

    Bull World Health Organ

    (1990)
  • V Jain et al.

    Epidemiology of rotavirus in India

    Indian J Pediatr

    (2001)
  • S Villa et al.

    Seasonal diarrrhoeal mortality among Mexican children

    Bull World Health Organ

    (1999)
  • UD Parashar et al.

    The global burden of diarrhoeal disease in children

    Bull World Health Organ

    (2003)
  • M Lynch et al.

    The pathology of rotavirus-associated deaths, using new molecular diagnostics

    Clin Infect Dis

    (2003)
  • JA Carlson et al.

    Fatal rotavirus gastroenteritis: an analysis of 21 cases

    Am J Dis Child

    (1978)
  • AZ Kapikian et al.

    Rotaviruses

  • MK Estes

    Rotaviruses and their replication

  • JM Ball et al.

    Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein

    Science

    (1996)
  • TK Fischer et al.

    Rotavirus antigenemia in patients with acute gastroenteritis

    J Infect Dis

    (2005)
  • M Lynch et al.

    Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review

    Clin Infect Dis

    (2001)
  • X-L Pang et al.

    Detection of rotavirus RNA in cerebrospinal fluid in a case of rotavirus gastroenteritis with febrile seizures

    Pediatr Infect Dis J

    (1996)
  • H Ushijima et al.

    Detection and sequencing of rotavirus VP7 gene from human materials (stools, sera, cerbrospinal fluids, and throat swabs) by reverse transcription and PCR

    J Clin Microbiol

    (1994)
  • HG Cicirello et al.

    High prevalence of rotavirus infection among neonates born at hospitals in Delhi, India: predisposition of newborns for infection with unusual rotavirus

    Pediatr Infect Dis J

    (1994)
  • PE Kilgore et al.

    Neonatal rotavirus infection in Bangladesh: strain characterization and risk factors for nosocomial infection

    Pediatr Infect Dis J

    (1996)
  • AI Omoigberale et al.

    Nosocomial rotavirus infection in newborns

    East Afr Med J

    (1995)
  • RF Bishop et al.

    Clinical immunity after neonatal rotavirus infection: a prospective longitudinal study in young children

    N Engl J Med

    (1983)
  • FR Velazquez et al.

    Cohort study of rotavirus serotype patterns in symptomatic and asymptomatic infections in Mexican children

    Pediatr Infect Dis J

    (1993)
  • JR Gentsch et al.

    Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs

    J Infect Dis

    (2005)
  • U Desselberger et al.

    Rotavirus epidemiology and surveillance

    Novartis Found Symp

    (2001)
  • Y Koshimura et al.

    The relative frequencies of G serotypes of rotaviruses recovered from hospitalized children with diarrhea: a 10-year survey (1987–1996) in Japan with a review of globally collected data

    Microbiol Immunol

    (2000)
  • N Santos et al.

    Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine

    Rev Med Virol

    (2005)
  • M Iturriza-Gomara et al.

    Molecular epidemiology of human group A rotavirus infections in the United Kingdom between 1995 and 1998

    J Clin Microbiol

    (2000)
  • M Ramachandran et al.

    Unusual diversity of human rotavirus G and P genotypes in India

    J Clin Microbiol

    (1996)
  • Cited by (420)

    • Rotavirus and Other Viral Diarrhoea

      2023, Manson's Tropical Diseases, Fourth Edition
    • Genotype distribution and evolutionary analysis of rotavirus associated with acute diarrhea outpatients in Hubei, China, 2013–2016

      2022, Virologica Sinica
      Citation Excerpt :

      From 1994 to 2014, 40% of diarrhea-related hospitalizations and 30% of diarrhea-related outpatients among children under 5 years old in China were caused by RVAs (Wu et al., 2016). The great diversity of predominant genotypes of RVAs may affect the efficacy of rotavirus vaccination programs (Akran et al., 2010; Aminu et al., 2010; Arista et al., 2006; Glass et al., 2006; Todd et al., 2010). Because of the significant fluctuation of circulating genotypes of RVAs in different research periods and populations, continued surveillance programs in the pre- and post-vaccination eras have been carried out.

    • Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

      2021, EClinicalMedicine
      Citation Excerpt :

      Interventions targeting EED may therefore not be effective in improving oral RVV performance, and further studies are needed to better understand the impact of the intestinal milieu on oral vaccine immunogenicity. Increased coverage of oral rotavirus vaccines (RVV) has contributed to global declines in diarrheal disease burden [1]. However, these vaccines fail to reach their full potential in regions of high child mortality.

    View all citing articles on Scopus
    View full text