title: Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study.
abstract: BACKGROUND
  The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme.
  
  
  METHODS
  This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247.
  
  
  RESULTS
  Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69).
  
  
  CONCLUSIONS
  Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries.
  
  
  BACKGROUND
  GAVI Alliance (with support from PATH).
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: groomem@rmpru.co.za.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Groome
authors.affiliation: National Institute for Communicable Diseases: a Division of National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Nicola
authors.initials: N
authors.lastname: Page
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Cortese
authors.affiliation: School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases: a Division of National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
authors.affiliation: Department of Paediatrics, Ngwelezane Hospital, Empangeni, South Africa.
authors.forename: Constant N
authors.initials: CN
authors.lastname: Kapongo
authors.affiliation: Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Christine
authors.initials: C
authors.lastname: Mulligan
authors.affiliation: Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Ralph
authors.initials: R
authors.lastname: Diedericks
authors.affiliation: School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases: a Division of National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Fleming
authors.affiliation: MRC/Diarrhoeal Pathogens Research Unit, Department of Virology, Medunsa Campus, University of Limpopo/National Health Laboratory Service, Pretoria, South Africa.
authors.forename: Mapaseka
authors.initials: M
authors.lastname: Seheri
authors.affiliation: MRC/Diarrhoeal Pathogens Research Unit, Department of Virology, Medunsa Campus, University of Limpopo/National Health Laboratory Service, Pretoria, South Africa.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mphahlele
authors.affiliation: National Institute for Communicable Diseases: a Division of National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Centre for Global Health Research, Umeå University, Umeå, Sweden; INDEPTH Network, Accra, Ghana.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kahn
authors.affiliation: Department of Paediatrics and Child Health, University of KwaZulu-Natal, South Africa.
authors.forename: Meera
authors.initials: M
authors.lastname: Chhagan
authors.affiliation: PATH, Seattle, WA, USA; MRC/Diarrhoeal Pathogens Research Unit, Department of Virology, Medunsa Campus, University of Limpopo/National Health Laboratory Service, Pretoria, South Africa; Bill & Melinda Gates Foundation, Seattle, Washington, USA.
authors.forename: A Duncan
authors.initials: AD
authors.lastname: Steele
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
authors.affiliation: Stat-Epi Associates Inc, FL, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Zell
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases: a Division of National Health Laboratory Service, Sandringham, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D016022:Case-Control Studies; D003967:Diarrhea / Q000517:prevention & control*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D008297:Male; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012424:Rural Population; D013019:South Africa / Q000453:epidemiology; D013383:Suburban Population; D013997:Time Factors; D014505:Urban Population
chemical_list: D022243:Rotavirus Vaccines