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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

Cohen, Cheryl MD*†; Walaza, Sibongile MD*†; Moyes, Jocelyn MD*†; Groome, Michelle MD‡§; Tempia, Stefano PhD¶‖; Pretorius, Marthi MSc*; Hellferscee, Orienka MSc*; Dawood, Halima MD**††; Chhagan, Meera MD‡‡; Naby, Fathima MD‡‡; Haffejee, Summaya MD§§; Variava, Ebrahim MD¶¶‖‖; Kahn, Kathleen MD***†††‡‡‡; Nzenze, Susan MD‡§; Tshangela, Akhona BSc*; von Gottberg, Anne MD*‡; Wolter, Nicole PhD*‡; Cohen, Adam L. MD¶‖; Kgokong, Babatyi PhD*; Venter, Marietjie PhD*§§§; Madhi, Shabir A. PhD*‡§

The Pediatric Infectious Disease Journal: January 2015 - Volume 34 - Issue 1 - p 66–72
doi: 10.1097/INF.0000000000000478
HIV Reports

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.

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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

Accepted for publication May 19, 2014.

The authors have no conflicts of interest to disclose.

This study received funding from the National Institute for Communicable Diseases of the National Health Laboratory Service and was supported in part by funds from the United States Centers for Disease Control and Prevention (CDC), Atlanta, Georgia Preparedness and Response to Avian and Pandemic Influenza in South Africa (Cooperative Agreement Number: U51/IP000155-04). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC. The funders had no role in study design, implementation, manuscript writing or the decision to submit for publication. The corresponding author had full access to all the data in the study and takes final responsibility for the decision to submit for publication.

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Address for correspondence: Cheryl Cohen, MD, Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Gauteng, South Africa. E-mail:

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