PMID- 29791488
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 5
DP  - 2018
TI  - Comparison of the validity of smear and culture conversion as a prognostic marker
      of treatment outcome in patients with multidrug-resistant tuberculosis.
PG  - e0197880
LID - 10.1371/journal.pone.0197880 [doi]
AB  - BACKGROUND: The World Health Organization (WHO) has conditionally recommended the
      use of sputum smear microscopy and culture examination for the monitoring of
      multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to assess and
      compare the validity of smear and culture conversion at different time points
      during treatment for MDR-TB, as a prognostic marker for end-of-treatment
      outcomes. METHODS: We undertook a retrospective observational cohort study using 
      data obtained from Hunan Chest Hospital, China and Gondar University Hospital,
      Ethiopia. The sensitivity and specificity of culture and sputum smear conversion 
      for predicting treatment outcomes were analysed using a random-effects
      generalized linear mixed model. RESULTS: A total of 429 bacteriologically
      confirmed MDR-TB patients with a culture and smear positive result were included.
      Overall, 345 (80%) patients had a successful treatment outcome, and 84 (20%)
      patients had poor treatment outcomes. The sensitivity of smear and culture
      conversion to predict a successful treatment outcome were: 77.9% and 68.9% at 2
      months after starting treatment (difference between tests, p = 0.007); 95.9% and 
      92.7% at 4 months (p = 0.06); 97.4% and 96.2% at 6 months (p = 0.386); and 99.4% 
      and 98.9% at 12 months (p = 0.412), respectively. The specificity of smear and
      culture non-conversion to predict a poor treatment outcome were: 41.6% and 60.7% 
      at 2 months (p = 0.012); 23.8% and 48.8% at 4 months (p<0.001); and 20.2% and
      42.8% at 6 months (p<0.001); and 15.4% and 32.1% (p<0.001) at 12 months,
      respectively. The sensitivity of culture and smear conversion increased as the
      month of conversion increased but at the cost of decreased specificity. The
      optimum time points after conversion to provide the best prognostic marker of a
      successful treatment outcome were between two and four months after treatment
      commencement for smear, and between four and six months for culture. The common
      optimum time point for smear and culture conversion was four months. At this time
      point, culture conversion (AUROC curve = 0.71) was significantly better than
      smear conversion (AUROC curve = 0.6) in predicting successful treatment outcomes 
      (p < 0.001). However, the validity of smear conversion (AUROC curve = 0.7) was
      equivalent to culture conversion (AUROC curve = 0.71) in predicting treatment
      outcomes when demographic and clinical factors were included in the model. The
      positive and negative predictive values for smear conversion were: 57.3% and
      65.7% at two months, 55.7% and 85.4% at four months, and 55.0% and 88.6% at six
      months; and for culture conversions it was: 63.7% and 66.2% at two months, 64.4% 
      and 87.1% at four months, and 62.7% and 91.9% at six months, respectively.
      CONCLUSIONS: The validity of smear conversion is significantly lower than culture
      conversion in predicting MDR-TB treatment outcomes. We support the WHO
      recommendation of using both smear and culture examination rather than smear
      alone for the monitoring of MDR-TB patients for a better prediction of successful
      treatment outcomes. The optimum time points to predict a future successful
      treatment outcome were between two and four months after treatment commencement
      for sputum smear conversion and between four and six months for culture
      conversion. The common optimum times for culture and smear conversion together
      was four months.
FAU - Alene, Kefyalew Addis
AU  - Alene KA
AUID- ORCID: 0000-0002-1904-4682
AD  - Research School of Population Health, College of Health and Medicine, The
      Australian National University, Canberra, Australian Capital Territory,
      Australia.
AD  - Institute of Public Health, College of Medicine and Health Sciences, University
      of Gondar, Gondar, Ethiopia.
FAU - Viney, Kerri
AU  - Viney K
AD  - Research School of Population Health, College of Health and Medicine, The
      Australian National University, Canberra, Australian Capital Territory,
      Australia.
AD  - Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
FAU - Yi, Hengzhong
AU  - Yi H
AD  - Department of MDR-TB, Internal Medicine, Hunan Chest hospital, Changsha city,
      Hunan Province, China.
FAU - McBryde, Emma S
AU  - McBryde ES
AD  - Australian Institute of Tropical Health and Medicine, James Cook University,
      Townsville, Queensland, Australia.
FAU - Yang, Kunyun
AU  - Yang K
AD  - Department of MDR-TB, Internal Medicine, Hunan Chest hospital, Changsha city,
      Hunan Province, China.
FAU - Bai, Liqiong
AU  - Bai L
AD  - Department of Director's Office, Tuberculosis Control Institute of Hunan
      Province, Changsha city, Hunan Province, China.
FAU - Gray, Darren J
AU  - Gray DJ
AD  - Research School of Population Health, College of Health and Medicine, The
      Australian National University, Canberra, Australian Capital Territory,
      Australia.
FAU - Xu, Zuhui
AU  - Xu Z
AD  - Department of Tuberculosis Control, Tuberculosis Control Institute of Hunan
      Province, Changsha city, Hunan Province, China.
FAU - Clements, Archie C A
AU  - Clements ACA
AD  - Research School of Population Health, College of Health and Medicine, The
      Australian National University, Canberra, Australian Capital Territory,
      Australia.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180523
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers/metabolism
MH  - Cohort Studies
MH  - Culture Techniques
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium tuberculosis/drug effects/growth & development/physiology
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Reproducibility of Results
MH  - Retrospective Studies
MH  - Sputum/*microbiology
MH  - Treatment Outcome
MH  - Tuberculosis, Multidrug-Resistant/*diagnosis/drug
      therapy/*metabolism/microbiology
MH  - Young Adult
PMC - PMC5965863
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/05/24 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/05/24 06:00
PHST- 2018/02/13 00:00 [received]
PHST- 2018/05/10 00:00 [accepted]
PHST- 2018/05/24 06:00 [entrez]
PHST- 2018/05/24 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
AID - 10.1371/journal.pone.0197880 [doi]
AID - PONE-D-18-04907 [pii]
PST - epublish
SO  - PLoS One. 2018 May 23;13(5):e0197880. doi: 10.1371/journal.pone.0197880.
      eCollection 2018.