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
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research article
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Genotypic characterization of Mycobacteria tuberculosis ( Mtb ) isolates in pulmonary tuberculosis is well documented; however, there is dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigate Mtb drug resistance and transmission patterns in EPTB patients diagnosed and treated in the Tshwane metropolitan, South Africa.
Methods
Consecutive Mtb culture-positive non-pulmonary isolates underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. The Genotype MTBDR plus assay was used for isoniazid and rifampin susceptibility testing. Ensembles of machine learning (ML) algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and their corresponding 95% confidence intervals (CI). Based on ML outputs, we examined factors associated with EPTB sites, drug resistance and clustering for the period between July 1 st , 2014 and January 31 st , 2015.
Results
A total of 75 isolates were identified during study period: we excluded 5 (7%) Mycobacterium bovis isolates. The overall proven EPTB incidence of 4.43 (95% CI: 3.72-5.23) per 100,000 population per year is lower than prior reports. However, the frequency distribution across most frequently encountered EPTB disease sites, including pleura, peritoneum, meninges and skin, were consistent with those reports. The largest cluster comprised of 25 (36%) Mtb strains belonged to East Asian lineage. East Asian lineage was significantly more likely to occur within a chain of EPTB transmission when compared to 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 city of Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages, and each of these are likely to be clustered, suggesting on-going EPTB disease transmission. On the other hand, 25% of the drug resistance is attributable to sanctuary EPTB sites notorious for poor rifampin penetration, suggesting role for poor drug dosing.
Keywords
Stochastic gradient boosting, spoligotypes, number needed to screen, attributable risk
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
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
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
Version 1
Posted 07 Sep, 2019
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
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
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
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
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
Version 1
Posted 07 Sep, 2019
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
Genotypic characterization of Mycobacteria tuberculosis ( Mtb ) isolates in pulmonary tuberculosis is well documented; however, there is dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigate Mtb drug resistance and transmission patterns in EPTB patients diagnosed and treated in the Tshwane metropolitan, South Africa.
Methods
Consecutive Mtb culture-positive non-pulmonary isolates underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. The Genotype MTBDR plus assay was used for isoniazid and rifampin susceptibility testing. Ensembles of machine learning (ML) algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and their corresponding 95% confidence intervals (CI). Based on ML outputs, we examined factors associated with EPTB sites, drug resistance and clustering for the period between July 1 st , 2014 and January 31 st , 2015.
Results
A total of 75 isolates were identified during study period: we excluded 5 (7%) Mycobacterium bovis isolates. The overall proven EPTB incidence of 4.43 (95% CI: 3.72-5.23) per 100,000 population per year is lower than prior reports. However, the frequency distribution across most frequently encountered EPTB disease sites, including pleura, peritoneum, meninges and skin, were consistent with those reports. The largest cluster comprised of 25 (36%) Mtb strains belonged to East Asian lineage. East Asian lineage was significantly more likely to occur within a chain of EPTB transmission when compared to 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 city of Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages, and each of these are likely to be clustered, suggesting on-going EPTB disease transmission. On the other hand, 25% of the drug resistance is attributable to sanctuary EPTB sites notorious for poor rifampin penetration, suggesting role for poor drug dosing.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Loading...