title: Mortality amongst patients with influenza-associated severe acute respiratory illness, South Africa, 2009-2013.
abstract: BACKGROUND
  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.
  
  
  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<0.001). On multivariable analysis, factors associated with death were age-group 45-64 years (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.01-16.3) and ≥65 years (OR 6.5, 95%CI 1.2-34.3) compared to 1-4 year age-group who had the lowest CFP, HIV-infection (OR 2.9, 95%CI 1.1-7.8), underlying medical conditions other than HIV (OR 2.9, 95%CI 1.2-7.3) and pneumococcal co-infection (OR 4.1, 95%CI 1.5-11.2). The estimated incidence of influenza-associated SARI deaths per 100,000 population was highest in children <1 year (20.1, 95%CI 12.1-31.3) and adults aged 45-64 years (10.4, 95%CI 8.4-12.9). Adjusting for age, the rate of death was 20-fold (95%CI 15.0-27.8) higher in HIV-infected individuals than HIV-uninfected individuals.
  
  
  CONCLUSIONS
  Influenza causes substantial mortality in urban South Africa, particularly in infants aged <1 year and HIV-infected individuals. More widespread access to antiretroviral treatment and influenza vaccination may reduce this burden.
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, University of the Witwatersrand, Johannesburg, South Africa.
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, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Influenza Programme, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.affiliation: Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; University of the Witwatersrand; Johannesburg; South Africa.
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.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: Zoonosis Research Unit, Department of Medical Virology, University of Pretoria.
authors.forename: Marthi
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Department of Medicine, Pietermaritzburg Metropolitan Hospital, Pietermaritzburg, South Africa; Department of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Halima
authors.initials: H
authors.lastname: Dawood
authors.affiliation: Department of Paediatrics, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Meera
authors.initials: M
authors.lastname: Chhagan
authors.affiliation: School of Pathology, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Summaya
authors.initials: S
authors.lastname: Haffejee
authors.affiliation: Department of Medicine, Klerksdorp Tshepong Hospital; Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Variava
authors.affiliation: 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.
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; Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, 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; Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, 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, United States of America; Influenza Programme, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa.
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.
authors.forename: Babatyi
authors.initials: B
authors.lastname: Malope-Kgokong
authors.affiliation: Zoonosis Research Unit, Department of Medical Virology, University of Pretoria; Global Disease Detection, United States 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, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; University of the Witwatersrand; Johannesburg; South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D000208:Acute Disease / Q000453:epidemiology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006761:Hospitals; D006801:Humans; D015994:Incidence; D007223:Infant; D007251:Influenza, Human / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications* / Q000453:epidemiology / Q000401:mortality* / Q000821:virology; D012307:Risk Factors; D012621:Seasons; D018571:Sentinel Surveillance; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult