title: Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009-2013.
abstract: BACKGROUND
  High antenatal human immunodeficiency virus (HIV) seroprevalence rates (∼ 30%) with low perinatal HIV transmission rates (2.5%), due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed but uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants.
  
  
  METHODS
  We conducted a cross-sectional study of infants aged <1 year with IPD enrolled in a national, laboratory-based surveillance program for incidence estimations. Incidence was reported for 2 time points, 2009 and 2013. At enhanced sites we collected additional data including HIV status and in-hospital outcome.
  
  
  RESULTS
  We identified 2099 IPD cases in infants from 2009 to 2013 from all sites. In infants from enhanced sites (n = 1015), 92% had known HIV exposure status and 86% had known outcomes. IPD incidence was highest in HIV-infected infants, ranging from 272 to 654 per 100,000 population between time points (2013 and 2009), followed by HEU (33-88 per 100,000) and HIV-unexposed and uninfected (HUU) infants (18-28 per 100,000). The case-fatality rate in HEU infants (29% [74/253]) was intermediate between HUU (25% [94/377]) and HIV-infected infants (34% [81/242]). When restricted to infants <6 months of age, HEU infants (37% [59/175]) were at significantly higher risk of dying than HUU infants (32% [51/228]; adjusted relative risk ratio, 1.76 [95% confidence interval, 1.09-2.85]).
  
  
  CONCLUSIONS
  HEU infants are at increased risk of IPD and mortality from IPD compared with HUU children, especially as young infants. HEU infants, whose numbers will likely continue to increase, should be prioritized for interventions such as pneumococcal vaccination along with HIV-infected infants and children.
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service School of Public Health, Faculty of Health Sciences.
authors: Claire
authors: C
authors: von Mollendorf
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
authors: Anne
authors: A
authors: von Gottberg
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia Influenza Division, Centers for Disease Control and Prevention, Pretoria.
authors: Stefano
authors: S
authors: Tempia
authors: Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg.
authors: Susan
authors: S
authors: Meiring
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service.
authors: Linda
authors: L
authors: de Gouveia
authors: Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg.
authors: Vanessa
authors: V
authors: Quan
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service.
authors: Sarona
authors: S
authors: Lengana
authors: Pediatric Infectious Diseases Unit, Steve Biko (Pretoria Academic Hospital) and Kalafong Hospital, University of Pretoria, Gauteng.
authors: Theunis
authors: T
authors: Avenant
authors: Pediatric Infectious Diseases Unit, Steve Biko (Pretoria Academic Hospital) and Kalafong Hospital, University of Pretoria, Gauteng.
authors: Nicolette
authors: N
authors: du Plessis
authors: Red Cross War Memorial Children's Hospital, Department of Paediatrics and Child Health, University of Cape Town.
authors: Brian
authors: B
authors: Eley
authors: Tygerberg Hospital and Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, Western Cape.
authors: Heather
authors: H
authors: Finlayson
authors: Department of Paediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg.
authors: Gary
authors: G
authors: Reubenson
authors: Department of Paediatrics and Child Health, Dr George Mukhari Hospital, Medunsa University, Tshwane, Gauteng Province, South Africa.
authors: Mamokgethi
authors: M
authors: Moshe
authors: International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors: Katherine L
authors: KL
authors: O'Brien
authors: Hubert Department of Global Health, Rollins School of Public Health Division of Infectious Diseases, School of Medicine, Emory University.
authors: Keith P
authors: KP
authors: Klugman
authors: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Cynthia G
authors: CG
authors: Whitney
authors: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service School of Public Health, Faculty of Health Sciences.
authors: Cheryl
authors: C
authors: Cohen
mesh_terms: D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000382:microbiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011008:Pneumococcal Infections / Q000150:complications / Q000453:epidemiology* / Q000401:mortality* / Q000821:virology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D012044:Regression Analysis; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors
chemical_list: D022242:Pneumococcal Vaccines
keywords: HIV exposure; South Africa; Streptococcus pneumoniae; children; pneumococcal conjugate vaccine