title: Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009-2012.
abstract: BACKGROUND
  Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged <5 years.
  
  
  METHODS
  We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators.
  
  
  RESULTS
  We enrolled 8723 children aged <5 years with LRTI, including 64% <12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446-10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1-1.7)], be hospitalized >7 days (OR: 3.8, 95% CI: 2.8-5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6-6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2-6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1-5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7-17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2-55.9) were associated with death.
  
  
  CONCLUSIONS
  HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.
authors.affiliation: From the *Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service; †School of Public Health, Faculty of Health Sciences, University of the Witwatersrand; ‡Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand; §Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa; ¶Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA; ‖Influenza Programme, Centers for Disease Control and Prevention-South Africa, Pretoria; **Department of Medicine, Pietermaritzburg Metropolitan Hospital; ††Department of Medicine, University of KwaZulu Natal; ‡‡Department of Paediatrics, Pietermaritzburg Metropolitan Hospital §§School of Pathology, University of KwaZulu Natal, Pietermaritzburg; ¶¶Department of Medicine, Klerksdorp Tshepong Hospital, Klerksdorp; ‖‖Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand; ***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; and §§§Zoonoses Research Unit, Department of Medical Virology, University of Pretoria, Gauteng, South Africa.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.forename: Michelle
authors.initials: M
authors.lastname: Groome
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.forename: Marthi
authors.initials: M
authors.lastname: Pretorius
authors.forename: Orienka
authors.initials: O
authors.lastname: Hellferscee
authors.forename: Halima
authors.initials: H
authors.lastname: Dawood
authors.forename: Meera
authors.initials: M
authors.lastname: Chhagan
authors.forename: Fathima
authors.initials: F
authors.lastname: Naby
authors.forename: Summaya
authors.initials: S
authors.lastname: Haffejee
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Variava
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kahn
authors.forename: Susan
authors.initials: S
authors.lastname: Nzenze
authors.forename: Akhona
authors.initials: A
authors.lastname: Tshangela
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.forename: Adam L
authors.initials: AL
authors.lastname: Cohen
authors.forename: Babatyi
authors.initials: B
authors.lastname: Kgokong
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D001996:Bronchopneumonia / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D002675:Child, Preschool; D060085:Coinfection / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality / Q000821:virology; D005260:Female; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009305:Nasopharynx / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology / Q000382:microbiology; D011024:Pneumonia, Viral / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology; D016019:Survival Analysis; D014780:Viruses / Q000145:classification / Q000302:isolation & purification*
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