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Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum

Overview of attention for article published in BMC Infectious Diseases, July 2018
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  • Above-average Attention Score compared to outputs of the same age (59th percentile)

Mentioned by

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7 tweeters

Citations

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1 Dimensions

Readers on

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19 Mendeley
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Title
Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum
Published in
BMC Infectious Diseases, July 2018
DOI 10.1186/s12879-018-3213-7
Pubmed ID
Authors

Nicholas D. Walter, Camille M. Moore, Xavier A. Kayigire, Christian Dide-Agossou, William Worodria, Laurence Huang, Charles K. Everett, Gary S. Schoolnik, Payam Nahid, J. Lucian Davis

Abstract

According to the traditional tuberculosis (TB) treatment paradigm, the initial doses of treatment rapidly kill most Mycobacterium tuberculosis (Mtb) bacilli in sputum, yet many more months of daily treatment are required to eliminate a small, residual subpopulation of drug-tolerant bacilli. This paradigm has recently been challenged following the discovery that up to 90% of Mtb bacilli in sputum are culturable only with growth-factor supplementation. These "differentially culturable" bacilli are hypothesized to be more drug-tolerant than routinely culturable bacilli. This hypothesis implies an alternative paradigm in which TB treatment does not rapidly reduce the total Mtb population but only the small, routinely culturable subpopulation. To evaluate these competing paradigms, we developed a culture-independent method for quantifying the viable fraction of Mtb bacilli in sputum during treatment. We used GeneXpert MTB/RIF to quantify Mtb DNA in sputa collected longitudinally from Ugandan adults taking standard 4-drug treatment for drug-susceptible pulmonary TB. We modeled GeneXpert cycle thresholds over time using nonlinear mixed-effects regression. We adjusted these models for clearance of DNA from killed-but-not-yet-degraded bacilli, assuming clearance half-lives ranging from 0 to 1.25 days. We used a convolution integral to quantify DNA from viable bacilli only, and converted cycle thresholds to Mtb genomic equivalents. We replicated our results in a South African cohort. We enrolled 41 TB patients in Uganda. Assuming a DNA-clearance half-life of 0 days, genomic equivalents of viable sputum bacilli decreased by 0.22 log/day until 8.8 days, then by 0.07 log/day afterwards. Assuming a DNA-clearance half-life of 1.25 days, genomic equivalents of viable bacilli decreased by 0.36 log/day until 5.0 days, then by 0.06 log/day afterwards. By day 7, viable Mtb had decreased by 97.2-98.8%. We found similar results for 19 TB patients in South Africa. Using a culture-independent method, we found that TB treatment rapidly eliminates most viable Mtb in sputum. These findings are incompatible with the hypothesis that differentially culturable bacilli are drug-tolerant. A culture-independent method for measuring viable Mtb in sputum during treatment corroborates the traditional TB treatment paradigm in which a rapid bactericidal phase precedes slow, elimination of a small, residual bacillary subpopulation.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 26%
Student > Master 4 21%
Other 2 11%
Student > Bachelor 1 5%
Student > Ph. D. Student 1 5%
Other 3 16%
Unknown 3 16%
Readers by discipline Count As %
Medicine and Dentistry 6 32%
Immunology and Microbiology 4 21%
Computer Science 1 5%
Agricultural and Biological Sciences 1 5%
Biochemistry, Genetics and Molecular Biology 1 5%
Other 2 11%
Unknown 4 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 April 2019.
All research outputs
#5,024,380
of 15,915,110 outputs
Outputs from BMC Infectious Diseases
#1,692
of 5,796 outputs
Outputs of similar age
#107,349
of 277,586 outputs
Outputs of similar age from BMC Infectious Diseases
#1
of 1 outputs
Altmetric has tracked 15,915,110 research outputs across all sources so far. This one is in the 48th percentile – i.e., 48% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,796 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 277,586 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them