PMID- 31498808
OWN - NLM
STAT- MEDLINE
DCOM- 20200306
LR  - 20210110
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 9
DP  - 2019
TI  - Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in 
      Kampala-Uganda.
PG  - e0221644
LID - 10.1371/journal.pone.0221644 [doi]
LID - e0221644
AB  - BACKGROUND: Limited data existed exclusively describing Mycobacterium 
      tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in 
      Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 
      sub-lineages and their corresponding clinical phenotypes. METHOD: A total of 141 
      M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using 
      Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the 
      sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat 
      (DR) loci for all the isolates was examined for sub-lineage specific signatures 
      as described in the SITVIT2 database. The infecting sub-strains were matched with 
      patients' clinical and demographic characteristics to identify any possible 
      association. RESULT: The data showed 3 sub-lineages circulating with CAS 1 Delhi 
      accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% 
      (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether 
      the sub-lineages differ in their ability to cause increased severe disease, we 
      used extent of lung involvement as a proxy for severe disease. Multivariable 
      analysis showed no association between M. tuberculosis lineage 3 sub-lineages 
      with severe disease. The risk factors associated with severe disease include 
      having a positive smear (OR = 9.384; CI 95% = 2.603-33.835), HIV (OR = 0.316; CI 
      95% = 0.114-0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034-0.856) and a BCG 
      scar (OR = 0.295; CI 95% = 0.102-0.854). CONCLUSION: In Kampala, Uganda, there 
      are three sub-lineages of M. tuberculosis lineage 3 that cause disease of 
      comparable severity with CAS-Dehli as the most prevalent. Having HIV, 
      lymphadenitis, a BCG scar and a smear negative status is associated with reduced 
      severe disease.
FAU - Wampande, Eddie M
AU  - Wampande EM
AUID- ORCID: 0000-0003-0012-8883
AD  - Department of Medical Microbiology, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
AD  - Department of Veterinary Medicine, Clinical and Comparative medicine, College of 
      Veterinary Medicine, Animal Resources and Bio Security, Makerere University, 
      Kampala, Uganda.
FAU - Naniima, Peter
AU  - Naniima P
AD  - Department of Medical Microbiology, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
FAU - Mupere, Ezekiel
AU  - Mupere E
AD  - Department of Pediatrics and Child Health College of Health Sciences, Makerere 
      University, Kampala, Uganda.
FAU - Kateete, David P
AU  - Kateete DP
AD  - Department of Medical Microbiology, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
FAU - Malone, LaShaunda L
AU  - Malone LL
AD  - Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
AD  - Tuberculosis Research Unit, School of Medicine, Case Western Reserve University 
      and University Hospitals of Cleveland, Cleveland, OH, Uinted States of America.
FAU - Stein, Catherine M
AU  - Stein CM
AD  - Tuberculosis Research Unit, School of Medicine, Case Western Reserve University 
      and University Hospitals of Cleveland, Cleveland, OH, Uinted States of America.
AD  - Department of Population and Quantitative Health Sciences, School of Medicine, 
      Case Western Reserve University, Cleveland, OH, Uinted States of America.
FAU - Mayanja-Kizza, Harriet
AU  - Mayanja-Kizza H
AD  - Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
FAU - Gagneux, Sebastien
AU  - Gagneux S
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Boom, W Henry
AU  - Boom WH
AD  - Tuberculosis Research Unit, School of Medicine, Case Western Reserve University 
      and University Hospitals of Cleveland, Cleveland, OH, Uinted States of America.
FAU - Joloba, Moses L
AU  - Joloba ML
AD  - Department of Medical Microbiology, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
LA  - eng
GR  - N01 AI070022/AI/NIAID NIH HHS/United States
GR  - N01AI70022/AI/NIAID NIH HHS/United States
GR  - 107742/Z/15/Z/WT_/Wellcome Trust/United Kingdom
GR  - R01 AI075637/AI/NIAID NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - N01AI95383/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190909
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - *Genetic Variation
MH  - Genotype
MH  - Humans
MH  - Multivariate Analysis
MH  - Mycobacterium tuberculosis/*genetics/*physiology
MH  - Phenotype
MH  - Risk Factors
MH  - Tuberculosis, Pulmonary/microbiology
MH  - Uganda
PMC - PMC6733460
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/09/10 06:00
MHDA- 2020/03/07 06:00
PMCR- 2019/09/09
CRDT- 2019/09/10 06:00
PHST- 2019/01/30 00:00 [received]
PHST- 2019/08/12 00:00 [accepted]
PHST- 2019/09/10 06:00 [entrez]
PHST- 2019/09/10 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
PHST- 2019/09/09 00:00 [pmc-release]
AID - PONE-D-19-02953 [pii]
AID - 10.1371/journal.pone.0221644 [doi]
PST - epublish
SO  - PLoS One. 2019 Sep 9;14(9):e0221644. doi: 10.1371/journal.pone.0221644. 
      eCollection 2019.