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Research article
Jotam G Pasipanodya(New Corresponding Author)
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Background There is a general dearth of information on extrapulmonary tuberculosis (EPTB). We investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan, South Africa. Methods Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent further mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDR plus assay was used to test for isoniazid and rifampin susceptibility. ML algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results Of the 70 isolates examined, the largest cluster comprised of 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and skin TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor. Conclusions Majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the resistance.
Keywords
Stochastic gradient boosting, spoligotypes, number needed to screen, attributable risk
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View the published article at BMC Infectious Diseases.
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Editorial decision: Minor revision
On 08 Jul, 2020
Editor assigned
On 05 Jul, 2020
Submission checks complete
On 04 Jul, 2020
Editor invited
On 04 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 03 Jul, 2020
Editor assigned
On 29 Mar, 2020
Submission checks complete
On 28 Mar, 2020
Editor invited
On 28 Mar, 2020
Version 2
Posted 02 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 12 Mar, 2020
Editor assigned
On 02 Mar, 2020
Submission checks complete
On 01 Mar, 2020
Editor invited
On 01 Mar, 2020
No comments provided
Editorial decision: Major revision
On 23 Nov, 2019
Review #2 received
Received 16 Nov, 2019
Reviewer #2 agreed
On 03 Nov, 2019
Review #1 received
Received 13 Oct, 2019
Reviewer #1 agreed
On 04 Oct, 2019
Reviewers invited
Invitations sent on 08 Sep, 2019
Editor assigned
On 03 Sep, 2019
Submission checks complete
On 03 Sep, 2019
Editor invited
On 03 Sep, 2019
First submitted
On 27 Aug, 2019
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Subject Areas
Infectious Diseases
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A new preprint design is coming!
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See the published version of this preprint at BMC Infectious Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Jotam G Pasipanodya(New Corresponding Author)
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Infectious Diseases.
No community comments so far
Editorial decision: Minor revision
On 08 Jul, 2020
Editor assigned
On 05 Jul, 2020
Submission checks complete
On 04 Jul, 2020
Editor invited
On 04 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 03 Jul, 2020
Editor assigned
On 29 Mar, 2020
Submission checks complete
On 28 Mar, 2020
Editor invited
On 28 Mar, 2020
Version 2
Posted 02 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 12 Mar, 2020
Editor assigned
On 02 Mar, 2020
Submission checks complete
On 01 Mar, 2020
Editor invited
On 01 Mar, 2020
No comments provided
Editorial decision: Major revision
On 23 Nov, 2019
Review #2 received
Received 16 Nov, 2019
Reviewer #2 agreed
On 03 Nov, 2019
Review #1 received
Received 13 Oct, 2019
Reviewer #1 agreed
On 04 Oct, 2019
Reviewers invited
Invitations sent on 08 Sep, 2019
Editor assigned
On 03 Sep, 2019
Submission checks complete
On 03 Sep, 2019
Editor invited
On 03 Sep, 2019
First submitted
On 27 Aug, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Infectious Diseases.
Background There is a general dearth of information on extrapulmonary tuberculosis (EPTB). We investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan, South Africa. Methods Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent further mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDR plus assay was used to test for isoniazid and rifampin susceptibility. ML algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results Of the 70 isolates examined, the largest cluster comprised of 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and skin TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor. Conclusions Majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the resistance.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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