Evidence map›Paper›PMID 24349420›Full record

Trial reportPloS one2013

Elucidating emergence and transmission of multidrug-resistant tuberculosis in treatment experienced patients by whole genome sequencing.

Taane G Clark, Kim Mallard, Francesc Coll, Mark Preston, Samuel Assefa, David Harris, Sam Ogwang, Francis Mumbowa, Bruce Kirenga, Denise M O'Sullivan and 8 more

Abstract readClinical TrialMulticenter Study
In one paragraph

Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2017
    Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Infection & chemotherapy · 2023
    Article
  11. Distribution and origins ofMicrobial genomics · 2023
    Article
  12. Article
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  14. Article
  15. Article
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  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Taane G ClarkFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom ; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Kim MallardFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Francesc CollFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Mark PrestonFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Samuel AssefaFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom ; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
David HarrisWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Sam OgwangJoint Clinical Research Centre, Kampala, Uganda.
Francis MumbowaJoint Clinical Research Centre, Kampala, Uganda ; Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
Bruce KirengaMulago Hospital Tuberculosis Clinic, Mulago Hospital, Kampala, Uganda.
Denise M O'SullivanFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Alphonse OkweraMulago Hospital Tuberculosis Clinic, Mulago Hospital, Kampala, Uganda.
Kathleen D EisenachDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America ; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
Moses JolobaDepartment of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
Stephen D BentleyWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Jerrold J EllnerSection of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
Julian ParkhillWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Edward C Jones-LópezSection of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
Ruth McNerneyFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Funding

Wellcome Trust 063410/ABC/00/ZWellcome Trust 100891
6 · The paper itself

Abstract

backgroundUnderstanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. METHODS AND

findingsWe used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort.

conclusionsWhole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the emergence of resistance and permit early intervention to avoid onward transmission.

Indexed as

Genome, BacterialMutationMycobacterium tuberculosisPolymorphism, GeneticSequence Analysis, DNAAdultFemaleHumansMaleMiddle AgedTuberculosis, Multidrug-ResistantUganda

Identifiers

PMID24349420
PMCPMC3859632

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.