title: Prospective cross-sectional evaluation of the small membrane filtration method for diagnosis of pulmonary tuberculosis.
abstract: Smear microscopy has suboptimal sensitivity, and there is a need to improve its performance since it is commonly used to diagnose tuberculosis (TB). We prospectively evaluated the diagnostic accuracy of the small membrane filtration (SMF) method, an approach that uses a vacuum manifold and is designed to concentrate bacilli onto a filter that can be examined microscopically. We enrolled hospitalized adults suspected to have pulmonary TB in Kampala, Uganda. We obtained a clinical history and three spontaneously expectorated sputum specimens for smear microscopy (direct, concentrated, and SMF), MGIT (mycobacterial growth indicator tube) 960 and Lowenstein-Jensen (LJ) cultures, and Xpert MTB/RIF testing. We performed per-specimen (primary) and per-patient analyses. From October 2012 to June 2013, we enrolled 212 patients (579 sputum specimens). The participants were mostly female (63.2%), and 81.6% were HIV infected; their median CD4 cell count was 47 cells/μl. Overall, 19.0%, 20.4%, 27.1%, 25.2%, and 25.9% of specimens tested positive by direct smear, concentrated smear, MGIT culture, LJ culture, and Xpert test, respectively. In the per-specimen analysis, the sensitivity of the SMF method (48.5%; 95% confidence interval [CI], 37.4 to 59.6) was lower than those of direct smear (60.9%; 51.4 to 70.5 [P = 0.0001]) and concentrated smear (63.3%; 53.6 to 73.1 [P < 0.0001]). Subgroup analyses showed that SMF performed poorly in specimens having a low volume or low bacterial load. The SMF method performed poorly compared to standard smear techniques and was sensitive to sample preparation techniques. The optimal laboratory SMF protocol may require striking a fine balance between sample dilution and filtration failure rate.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA edward.jones@bmc.org.
authors.forename: Edward
authors.initials: E
authors.lastname: Jones-López
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
authors.forename: Moises
authors.initials: M
authors.lastname: Palaci
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Carol
authors.initials: C
authors.lastname: Kayiza
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Armstrong
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakiyingi
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Willy
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Gaeddert
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kubiak
authors.affiliation: Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Almeida Júnior
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001431:Bacteriological Techniques / Q000379:methods*; D003430:Cross-Sectional Studies; D005260:Female; D005374:Filtration / Q000379:methods*; D006801:Humans; D008297:Male; D008566:Membranes; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D014454:Uganda; D055815:Young Adult