Multidrug-Resistant Tuberculosis in Rural Eastern Cape, South Africa: Clinical, Bacteriological, and Programmatic Predictors of Poor Treatment Outcomes

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

* Firstly, I would like to express my gratitude to the authors for their efforts in this manuscript .This is a strong, well-structured, programmatically relevant study addressing MDR-TB predictors in a rural high-burden setting. The integration of clinical governance and community engagement into epidemiological analysis is innovative and contextually valuable.  However I have a few constructive comments to enhance the clarity and quality of the paper

1-Timeline Inconsistency (Critical)

Abstract: Diagnosed between 2018–2022

Methods:Diagnosed between 2020–2024

This must be corrected immediately

2-Culture Positivity as Predictor (Conceptual Issue)

Adjusted OR ≈ 27 is extremely high.

You must clarify:

• Was culture performed at baseline only?
• Was culture positivity universal testing or selective?
• Could culture positivity reflect diagnostic pathway bias?
• Are you modeling biological severity rather than true “predictor”?

Currently, interpretation suggests causality, but this may be reverse association.

I recommend adding:

“Culture positivity likely reflects higher bacillary burden rather than being a causal determinant of MDR.”

3- Overinterpretation of INH Mutation Findings

You report:

• 3 Hr-TB cases
• Yet extensive mutation interpretation

With n=3, any inference beyond description is statistically unstable.

You should:

• Clearly state exploratory nature
• Avoid broad regional generalization
• Reduce mechanistic discussion tone

 

4- HIV as Predictor — Needs Deeper Interpretation

HIV aOR ≈ 2.8–2.9

You should clarify:

• Is this due to immunosuppression?
• Increased healthcare exposure?
• ART status?
• CD4 count available?

 

5- Minor Corrections

• “cultural positivity” → should be “culture positivity” (Section 4.4 typo).
• Ensure consistent reporting of OR values (some rounded, some precise).
• Remove redundancy of Figure 1 and Figure 2 if similar.

.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer 1,

I hope this message finds you well. We would like to express our sincere gratitude for the valuable feedback you provided on our manuscript. Your insightful comments have significantly enhanced the overall rigour and readability of our work. Attached are my detailed responses to each of your suggestions. We greatly appreciate your time and effort in reviewing our work, and we believe that your insights have led to meaningful improvements.

Thank you once again for your support.

Kind regards,  
Dr. Dlatu

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Review report

 

The authors display an analysis study on resistance TB infections in Eastern Cape (South Africa). The authors use bacteriologically confirmed cases to analyze predictors and correlations between TB infections, resistant TB infections (MDR-TB, DR-TB, Hr-TB) in 477 cases. The study extends previous research to local and context-specific cases in this area of Eastern Cape.

The display of data, and figures is severely lacking in quality, and needs to be improved.

 

1. In Figure 1, the CI should be plotted as error bars on the bin-data, then in the legend reported what the error bars represent. This gives the reader immediate impression of the variability and confidence in the data.
2. Figure 1. Sex should be plotted (not Male) and the same bar with CI as errorbars plotted.
3. Figure 1. Full descriptors of data should be on x axis. HIV_pos – either “HIV positive”, or “HIV+”.
4. Figure 1. The legend should briefly reiterate what statistical analysis is used to obtain confidence intervals and statistical significance (from Methodology)
5. There are two figure 2… the first “Figure 2. Bivariate logistic regression (predictors of MDR-TB).” is not referenced in the text. Here the y-axis needs to be changed as I mentioned for x-axis in figure 1. It lacks the legend, and the explanation of the data points and errorbars on them (the spread and its meaning)
6. Why are two different Figure 2. Showing different numbers, while both showing “predictors of MDR- TB among 477 patients”? Unadjusted numbers from bottom Figure 2 do not match the Figure 2 above.
7. While this sentence is mentioned in 4.3 “Our findings corroborate WHO data indicating that MDR-TB is concentrated among previously treated individuals, often due to acquired resistance or sustained community transmission”, previous section clearly emphasized that most of the cases are first time infections and preventive strategies are needed rather than preventing recurrent infections. These paragraphs need to be in line.
8. Discussion is severely lacking in depth. A 1-2 sentence per each important point is insufficient, for example 4.4 and 4.5 need to be expanded and elaborated in the broader context of TB studies. Particularly the difference between predictors in the setting of correlating variables and causting variables, distinguishing the diagnostic tests from preventive tests and measures. Other sections of the discussion need to be expanded to reflect the state of the TB-resistance research field and how this data and work fit in.

 

Author Response

Dear Reviewer 2,

I appreciate you taking the time to review our manuscript. Your insights have raised some crucial points, and I’ve attached my comments for your consideration. Thank you for shedding light on these important issues.

Best regards,  

Dr Dlatu 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

None

Author Response

Dear Reviewer 3,

 

Thank you so much. 

Dr Dlatu

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

While the accompanying report that is response to reviewer comments includes "We thank the reviewer for this important observation. We have corrected figure 1"... None of my comments regarding this figure were addressed. CI intervals are written in the Fig legend, instead of presented as error bars on the bin plots. Bin labelling remains the same, and is different between different Figures for example (HIV_pos vs HIV positive, etc).

 

There are still two Figures labelled as Fig. 2.

 

Overall the authors need to improve addressing the reviewers comments.

Author Response

Dear Reviewer 2,

I hope this message finds you well. We would like to express our gratitude for taking the time to review our manuscript and provide feedback. Your insights are invaluable in helping us enhance the rigour and quality of our work. Attached are the reviewers' comments for your reference.

Thank you once again for your support.

Kind regards,

Dr Dlatu

 

Author Response File: Author Response.pdf