title: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in children.
abstract: BACKGROUND
  Paradoxical tuberculosis (TB)-associated Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of combination antiretroviral treatment (cART) initiation in adults residing in resource-limited regions. Little is known about the burden and presentation of TB-IRIS in children initiating cART while receiving TB treatment.
  
  
  METHODS
  Prospective cohort study of South African children initiating cART while on TB treatment. Children were assessed clinically and by chest x-ray before starting cART and at 2, 4, 6, and 12 weeks post cART initiation. All children who presented with any signs or symptoms suggestive of paradoxical TB-IRIS were classified according to the consensus adult TB-IRIS case definition developed by the International Network for Study of HIV-associated IRIS (INSHI) and reviewed by an independent expert panel.
  
  
  RESULTS
  In 7 of the 104 children enrolled in the cohort, symptoms and/or clinical or radiological signs suggestive of paradoxical TB-IRIS developed after a median of 14 days of cART. In two of these cases, there was agreement between the INSHI case definition and the expert panel. In an additional 3 cases, the INSHI criteria were fulfilled but the expert panel made an alternative diagnosis of pneumonia (n = 2) and poor adherence to cART (n = 1).
  
  
  CONCLUSIONS
  The burden of paradoxical TB-IRIS in children with underlying TB initiating cART is low. Including response to antibiotic treatment for pneumonia as a criterion for an alternative diagnosis may improve the specificity of the INSHI case definition.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Rie
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Shobna
authors.initials: S
authors.lastname: Sawry
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Ruth
authors.initials: R
authors.lastname: Link-Gelles
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa.|National Research Foundation/Department of Science and Technology: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Shabir
authors.initials: S
authors.lastname: Madhi
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Lee
authors.initials: L
authors.lastname: Fairlie
authors.affiliation: Division of Paediatric Pulmonology, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Charl
authors.initials: C
authors.lastname: Verwey
authors.affiliation: Department of Diagnostic Radiology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nasreen
authors.initials: N
authors.lastname: Mahomed
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: David
authors.initials: D
authors.lastname: Murdoch
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced* / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects; D013019:South Africa; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology; D014388:Tuberculosis, Lymph Node / Q000188:drug therapy / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D019438:Ritonavir
keywords: Africa; HIV; IRIS; TB; antiretroviral treatment