title: Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology.
abstract: BACKGROUND
  The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.
  
  
  METHODS
  This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.
  
  
  RESULTS
  Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3.
  
  
  CONCLUSIONS
  A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted.
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Department of Medicine, School of Medicine, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakiyingi
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Bareng A S
authors.initials: BA
authors.lastname: Nonyane
authors.affiliation: Department of Medical Microbiology, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Willy
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: Department of Medicine, School of Medicine, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Kirenga
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Department of Medicine, School of Medicine, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lubega
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Department of Medicine, School of Medicine, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Pauline
authors.initials: P
authors.lastname: Byakika-Kibwika
authors.affiliation: Department of Medical Microbiology, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Moses L
authors.initials: ML
authors.lastname: Joloba
authors.affiliation: Boston Medical Center, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
authors.affiliation: Department of Medicine, School of Medicine, Makerere University College of Heath Sciences, Kampala, Uganda.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
mesh_terms: D000328:Adult; D046508:Culture Techniques; D019937:Diagnostic Techniques and Procedures; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000502:physiology*; D012680:Sensitivity and Specificity; D013997:Time Factors; D014376:Tuberculosis / Q000150:complications* / Q000175:diagnosis* / Q000652:urine; D014454:Uganda
chemical_list: D008070:Lipopolysaccharides; C050016:lipoarabinomannan