title: High Genotypic Discordance of Concurrent Mycobacterium tuberculosis Isolates from Sputum and Blood of HIV-Infected Individuals.
abstract: BACKGROUND
  Among HIV-infected individuals with CD4 less than 200 cells/mm3, tuberculosis often has an atypical presentation, is more likely to be disseminated and is diagnostically challenging. We sought to understand the genotypic discordance of concurrent sputum and blood M. tuberculosis (MTB) isolates from HIV-infected individuals.
  
  
  METHODS
  From a prospective diagnostic accuracy study with 182 HIV-infected culture-positive TB adults, isolates were obtained from 51 of 66 participants who were MTB culture-positive by both sputum and blood. Isolates were subjected to susceptibility testing to 1st line drugs, spoligotyping and 24 locus- MIRU-VNTR.
  
  
  RESULTS
  The median age of the participants was 31 (IQR; 27-38) years and 51% were male. The median CD4 count was 29 (IQR; 10-84) cells/mm3 with 20% taking ART; 8.0% were previously treated for TB, and 63% were AFB smear-negative. The isolates belonged to two of the main global MTB-lineages; East-African-Indian (L3) 17 (16.7%) and Euro-American (L4) 85 (83.3%). We identified 26 (51.0%) participants with discordant MTB-genotypes between sputum and blood, including two patients with evidence of mixed infection in either compartment. Having discordant MTB-genotypes was not predicted by the MTB-lineage in either blood or sputum, CD4 cell count, or any other clinical characteristic.
  
  
  CONCLUSIONS
  There is a high genotypic discordance among M. tuberculosis concurrently isolated from sputum and blood of HIV-infected individuals. These findings suggest that infection with more than one strain of M. tuberculosis occurs in at least half of patients with advanced HIV infection.
authors.affiliation: Department of Medical Microbiology, College of Health Sciences Makerere University, Kampala, Uganda; Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Unit of Mycobacteriology Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Willy
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; KNCV Tuberculosis Foundation, The Hague, Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Infectious Diseases Institute, College of Health Sciences Makerere University, Kampala, Uganda.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakiyingi
authors.affiliation: Department of Medical Microbiology, College of Health Sciences Makerere University, Kampala, Uganda.
authors.forename: Gerald
authors.initials: G
authors.lastname: Mboowa
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Armstrong
authors.affiliation: Infectious Diseases Institute, College of Health Sciences Makerere University, Kampala, Uganda; Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Department of Medical Microbiology, College of Health Sciences Makerere University, Kampala, Uganda; Infectious Diseases Institute, College of Health Sciences Makerere University, Kampala, Uganda.
authors.forename: Moses L
authors.initials: ML
authors.lastname: Joloba
authors.affiliation: Unit of Mycobacteriology Institute of Tropical Medicine, Antwerp, Belgium; Division of Infectious Diseases, New York University, New York, NY, United States of America.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000382:microbiology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D010802:Phylogeny; D013183:Sputum / Q000382:microbiology*