title: Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.
abstract: The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV.
  
  
  
  Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV.
  
  
  
  Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine effectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV.
  
  
  
  Our results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries.
  
  
  
  Gavi, The Vaccine Alliance.
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: cherylc@nicd.ac.za.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Claire
authors.initials: C
authors.lastname: von Mollendorf
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Linda
authors.initials: L
authors.lastname: de Gouveia
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Sarona
authors.initials: S
authors.lastname: Lengana
authors.affiliation: Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Susan
authors.initials: S
authors.lastname: Meiring
authors.affiliation: Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Quan
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Arthermon
authors.initials: A
authors.lastname: Nguweneza
authors.affiliation: Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: David P
authors.initials: DP
authors.lastname: Moore
authors.affiliation: Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Gary
authors.initials: G
authors.lastname: Reubenson
authors.affiliation: Dr George Mukhari Hospital, Paediatrics Department, Medunsa University, Johannesburg, South Africa.
authors.forename: Mamokgethi
authors.initials: M
authors.lastname: Moshe
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Johannesburg, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Red Cross War Memorial Children's Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.affiliation: Universitas and Pelonomi Hospitals, Department of Paediatrics and Child Health, University of the Free State, Bloemfontein, South Africa.
authors.forename: Ute
authors.initials: U
authors.lastname: Hallbauer
authors.affiliation: Tygerberg Hospital, and the Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
authors.forename: Heather
authors.initials: H
authors.lastname: Finlayson
authors.affiliation: Charlotte Maxeke Johannesburg Academic Hospital, Paediatrics Department, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sheeba
authors.initials: S
authors.lastname: Varughese
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Zell
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Johannesburg, South Africa.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Whitney
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Pathology, University of the Witwatersrand, Johannesberg, South Africa; Hubert Department of Global Health, Rollins School of Public Health, and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011008:Pneumococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines; D065288:Serogroup; D013019:South Africa; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate