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RESEARCH ARTICLE

Mortality amongst Patients with InfluenzaAssociated Severe Acute Respiratory Illness, South Africa, 2009-2013 Cheryl Cohen1,2*, Jocelyn Moyes1,2, Stefano Tempia3,4, Michelle Groome5,6, Sibongile Walaza1, Marthi Pretorius8, Halima Dawood15,16, Meera Chhagan14, Summaya Haffejee17, Ebrahim Variava9,10, Kathleen Kahn11,12,13, Anne von Gottberg1,5,7, Nicole Wolter1,5,7, Adam L. Cohen3,4, Babatyi Malope-Kgokong1, Marietjie Venter8,18, Shabir A. Madhi1,5,6

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OPEN ACCESS Citation: Cohen C, Moyes J, Tempia S, Groome M, Walaza S, Pretorius M, et al. (2015) Mortality amongst Patients with Influenza-Associated Severe Acute Respiratory Illness, South Africa, 2009-2013. PLoS ONE 10(3): e0118884. doi:10.1371/journal. pone.0118884 Academic Editor: Benjamin J. Cowling, University of Hong Kong, HONG KONG Received: December 8, 2014

1 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa, 2 School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 3 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 4 Influenza Programme, Centers for Disease Control and Prevention—South Africa, Pretoria, South Africa, 5 Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 6 Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; University of the Witwatersrand; Johannesburg; South Africa, 7 School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 8 Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, 9 Department of Medicine, Klerksdorp Tshepong Hospital, 10 Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 11 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, 12 Centre for Global Health Research, Umeå University, Umeå, Sweden, 13 INDEPTH Network, Accra, Ghana, 14 Department of Paediatrics, University of KwaZulu Natal, Durban, South Africa, 15 Department of Medicine, Pietermaritzburg Metropolitan Hospital, Pietermaritzburg, South Africa, 16 Department of Medicine, University of KwaZulu Natal, Durban, South Africa, 17 School of Pathology, University of KwaZulu Natal, Durban, South Africa, 18 Global Disease Detection, United States Centers for Disease Control and Prevention—South Africa, Pretoria, South Africa * [email protected]

Accepted: January 13, 2015 Published: March 18, 2015 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study received funding from the NICD/ NHLS 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,

Abstract

Introduction Data on the burden and risk groups for influenza-associated mortality from Africa are limited. We aimed to estimate the incidence and risk-factors for in-hospital influenza-associated severe acute respiratory illness (SARI) deaths.

Methods Hospitalised patients with SARI were enrolled prospectively in four provinces of South Africa from 2009–2013. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. The incidence of influenza-associated SARI deaths was estimated at one urban hospital with a defined catchment population.

PLOS ONE | DOI:10.1371/journal.pone.0118884 March 18, 2015

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Influenza-Associated Mortality South Africa

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. Competing Interests: HD has received honoraria from Novartis and MSD and sponsored travel by Mylan. SAM has received honorarium from GSK, Pfizer, Novartis, Sanofi and MERCK. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist.

Results We enrolled 1376 patients with influenza-associated SARI and 3% (41 of 1358 with available outcome data) died. In patients with available HIV-status, the case-fatality proportion (CFP) was higher in HIV-infected (5%, 22/419) than HIV-uninfected individuals (2%, 13/620; p = 0.006). CFPs varied by age group, and generally increased with increasing age amongst individuals >5 years (p