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Risk Factors for Invasive Pneumococcal Disease Among Children Less Than 5 Years of Age in a High HIV Prevalence Setting, South Africa, 2010 to 2012

von Mollendorf, Claire MBBCh, MSc*†; Cohen, Cheryl MBBCh, FCPath (SA) Micro*†; de Gouveia, Linda ND MedTech (Micro)*; Naidoo, Nireshni MSc*†; Meiring, Susan MBChB; Quan, Vanessa MBBCh, MPH; Lindani, Sonwabo BCur (ED et Admin); Moore, David P. MBBCh, FCPaed (SA)§¶; Reubenson, Gary MBBCh, FCPaed (SA); Moshe, Mamokgethi MBChB, FCPaed (SA)**; Eley, Brian MBChB, FCPaed (SA)††; Hallbauer, Ute M. MBBCh, FCPaed (SA)‡‡; Finlayson, Heather MBChB, FCPaed (SA)§§; Madhi, Shabir A. MBBCh, PhD*§¶; Conklin, Laura MD¶¶; Zell, Elizabeth R. MStat¶¶; Klugman, Keith P. MBBCh, PhD¶‖‖; Whitney, Cynthia G. MD, MPH¶¶; von Gottberg, Anne MBBCh, PhD; for the South African IPD Case–Control Study Group

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0000000000000484
Original Studies

Background: Invasive pneumococcal disease (IPD) causes significant disease burden, especially in developing countries, even in the era of pneumococcal conjugate vaccine and maternal-to-child HIV transmission prevention programs. We evaluated factors that might increase IPD risk in young children in a high HIV prevalence setting.

Methods: We conducted a case–control study using IPD cases identified at 24 Group for Enteric, Respiratory and Meningeal disease Surveillance—South Africa program sites (2010–2012). At least 4 controls were matched by age, HIV status and hospital to each case. Potential risk factors were evaluated using multivariable conditional logistic regression.

Results: In total, 486 age-eligible cases were enrolled. Factors associated with IPD in HIV-uninfected children (237 cases, 928 controls) included siblings <5 years [adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI): 1.16–2.46], underlying medical conditions (aOR = 1.99, CI 1.22–3.22), preceding upper respiratory tract infection (aOR = 1.79, CI 1.19–2.69), day-care attendance (aOR = 1.58, CI 1.01–2.47), perinatal HIV exposure (aOR = 1.62, CI 1.10–2.37), household car ownership (aOR = 0.45, CI 0.25–0.83) and ≥2 7-valent pneumococcal conjugate vaccine doses (aOR = 0.67, CI 0.46–0.99). Among HIV-infected children (124 cases, 394 controls), IPD-associated factors included malnutrition (aOR = 2.68, CI 1.40–5.14), upper respiratory tract infection (aOR = 3.49, CI 1.73–7.03), tuberculosis in the last 3 months (aOR = 5.12, CI 1.69–15.50) and current antiretroviral treatment (aOR = 0.13, CI 0.05–0.38).

Conclusion: Previously identified factors related to poverty, poor health and intense exposure continue to be risk factors for IPD in children. Ensuring delivery of pneumococcal conjugate vaccine and antiretroviral treatment are important for improving disease prevention.

Author Information

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; Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; §Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Gauteng, South Africa; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand; Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; **Dr George Mukhari Hospital, Paediatrics Department, Medunsa University, Gauteng, South Africa; †Red Cross War Memorial Children’s Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape; ‡Universitas and Pelonomi Hospitals, Department of Paediatrics and Child Health, University of the Free State, Bloemfontein, Free State, South Africa; §§Tygerberg Hospital and Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, Western Cape, South Africa; ¶ National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention; and ‖Hubert Department of Global Health, Emory University, Atlanta, GA.

Accepted for publication June 30, 2014.

This manuscript has been supported by NICD/NHLS and the Global Alliance for Vaccines and Immunisation (GAVI)—Accelerated Vaccine Initiative-Special Studies Team.

K.P.K. and S.A.M. have received research funding and honoraria from Pfizer and GlaxoSmithKline. A.v.G. has received research funding from Pfizer. C.v.M. has received honoraria from Pfizer. G.R. has received honoraria and conference support from Pfizer and Sanofi. C.C., L.d.G., N.N., S.L., S.M., V.Q., D.P.M., M.M., B.E., U.M.H., H.F., L.C., E.R.Z., and C.G.W. report no conflicts of interest.

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

Address for correspondence: Claire von Mollendorf, MBBCh, MSc, Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Private Bag X4, Sandringham, 2131, Gauteng, South Africa. E-mail:

© 2015 by Lippincott Williams & Wilkins, Inc.