title: Influenza virus infection is associated with increased risk of death amongst patients hospitalized with confirmed pulmonary tuberculosis in South Africa, 2010-2011.
abstract: BACKGROUND
  Data on the association between influenza and tuberculosis are limited. We describe the characteristics of patients with laboratory-confirmed tuberculosis, laboratory-confirmed influenza and tuberculosis-influenza co-infection.
  
  
  METHODS
  Patients hospitalized with severe respiratory illness (acute and chronic) were enrolled prospectively in four provinces in South Africa. Naso/oropharyngeal specimens were tested for influenza virus by real time reverse transcriptase polymerase chain reaction. Tuberculosis testing was conducted as part of clinical management.
  
  
  RESULTS
  From June 2010 through December 2011, 8032 patients were enrolled and influenza testing was conducted on 7863 (98%). Influenza virus was detected in 765 (10%) patients. Among 2959 patients with tuberculosis and influenza results, 2227 (75%) were negative for both pathogens, 423 (14%) were positive for tuberculosis alone, 275 (9%) were positive for influenza alone and 34 (1%) had influenza and tuberculosis co-infection. On multivariable analysis amongst individuals with symptoms for ≥7 days, tuberculosis influenza co-infection was associated with increased risk of death, (adjusted relative risk ratio (aRRR) (6.1, 95% confidence interval (CI) 1.6-23.4), as compared to tuberculosis only infection. This association was not observed in individuals with symptoms for <7 days (aRRR.0.8, 95% CI 0.1-7.0).
  
  
  CONCLUSIONS
  Tuberculosis and influenza co-infection compared to tuberculosis single infection was associated with increased risk of death in individuals with symptoms ≥7 days. The potential public health impact of influenza vaccination among persons with laboratory-confirmed tuberculosis should be explored.
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. sibongilew@nicd.ac.za.|School of Public Health, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. sibongilew@nicd.ac.za.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: US Centres for Disease Control and Prevention, Atlanta, GA, USA. stefanot@nicd.ac.za.|US Centres for Disease Control and Prevention, Pretoria, South Africa. stefanot@nicd.ac.za.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.affiliation: Pietermaritzburg Metropolitan Hospital Complex, KwaZulu- Natal, South Africa. halimadawood@gmail.com.
authors.forename: Halima
authors.initials: H
authors.lastname: Dawood
authors.affiliation: Tshepong Hospital, North West Province, South Africa. variava@worldonline.co.za.|Faculty of Medicine, University of Witwatersrand, Johannesburg, South Africa. variava@worldonline.co.za.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Variava
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. jocelynm@nicd.ac.za.|School of Public Health, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. jocelynm@nicd.ac.za.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: US Centres for Disease Control and Prevention, Atlanta, GA, USA. dvj1@cdc.gov.|US Centres for Disease Control and Prevention, Pretoria, South Africa. dvj1@cdc.gov.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Cohen
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. nicolew@nicd.ac.za.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit and Department of Science and Technology/National Research Foundation: Vaccine-Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa. groomem@rmpru.co.za.
authors.forename: Michelle
authors.initials: M
authors.lastname: Groome
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. clairevm@nicd.ac.za.|School of Public Health, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. clairevm@nicd.ac.za.
authors.forename: Claire
authors.initials: C
authors.lastname: von Mollendorf
authors.affiliation: MRC/Wits Rural Public Health and Health Transition Research Unit (Agincourt), Bushbuckridge, South Africa. kathleen.kahn@wits.ac.za.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kahn
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. Marthi.Pretorius@up.ac.za.
authors.forename: Marthi
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. yds8@cdc.gov.|Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, Pretoria, South Africa. yds8@cdc.gov.
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. shabirm@nicd.ac.za.|Medical Research Council: Respiratory and Meningeal Pathogens Research Unit and Department of Science and Technology/National Research Foundation: Vaccine-Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa. shabirm@nicd.ac.za.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Private Bag X4, Sandringham, 2131, Johannesburg, Gauteng, South Africa. cherylc@nicd.ac.za.|School of Public Health, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. cherylc@nicd.ac.za.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D062486:Public Health Surveillance; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000401:mortality* / Q000821:virology; D055815:Young Adult