title: Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants.
abstract: BACKGROUND
  Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa.
  
  
  METHODS
  We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators.
  
  
  RESULTS
  We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU.
  
  
  CONCLUSIONS
  HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
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, 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.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; Influenza Programme and.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.affiliation: Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases.
authors.forename: Michelle
authors.initials: M
authors.lastname: Groome
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.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, Pretoria, South Africa;
authors.forename: Marthi
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Departments of Paediatrics, Pietermaritzburg Metropolitan Hospitals, University of KwaZulu-Natal, KwaZulu-Natal South Africa;
authors.forename: Fathima
authors.initials: F
authors.lastname: Naby
authors.affiliation: Department of Paediatrics, Klerksdorp Hospital, Northwest Province, South Africa;
authors.forename: Omphile
authors.initials: O
authors.lastname: Mekgoe
authors.affiliation: MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, and Centre for Global Health Research, Umeå University, Umeå, Sweden; and INDEPTH Network, Accra, Ghana.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kahn
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, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
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, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; Influenza Programme and.
authors.forename: Adam L
authors.initials: AL
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.
authors.forename: Claire
authors.initials: C
authors.lastname: von Mollendorf
authors.affiliation: Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, Pretoria, South Africa; Global Disease Detection, US Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa;
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D005260:Female; D015658:HIV Infections; D017052:Hospital Mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007223:Infant; D007251:Influenza, Human / Q000453:epidemiology; D008297:Male; D029121:Metapneumovirus / Q000302:isolation & purification; D018184:Paramyxoviridae Infections / Q000453:epidemiology; D011446:Prospective Studies; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000401:mortality; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014777:Virus Diseases / Q000453:epidemiology*