PONE-D-23-15403Strategies to resolve the gap in Adolescent Tuberculosis care at four health facilities in Uganda: The TEEN TB pilot projectPLOS ONE

Dear Dr. Omongot,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Although the study has merit it fails to add to the existing knowledge base in this area. There have been numerous studies that have been published in this area of research (covering broader aspects) and from similar settings. For example:

Muttamba W, Bbuye M, Baruch Baluku J, Kyaligonza S, Nalunjogi J, Kimuli I, Kirenga B. Perceptions of Adolescents and Health Workers Towards Adolescents’ TB Diagnosis in Central Uganda: A Cross-Sectional Qualitative Study. Risk Management and Healthcare Policy. 2021 Nov 30:4823-32.

Ssengooba W, Kateete DP, Wajja A, Bugumirwa E, Mboowa G, Namaganda C, Nakayita G, Nassolo M, Mumbowa F, Asiimwe BB, Waako J. An early morning sputum sample is necessary for the diagnosis of pulmonary tuberculosis, even with more sensitive techniques: a prospective cohort study among adolescent TB-suspects in Uganda. Tuberculosis research and treatment. 2012 Dec 4;2012.

Maleche-Obimbo E, Odhiambo MA, Njeri L, Mburu M, Jaoko W, Were F, Graham SM. Magnitude and factors associated with post-tuberculosis lung disease in low-and middle-income countries: A systematic review and meta-analysis. PLOS Global Public Health. 2022 Dec 20;2(12):e0000805.

Reviewer #2: Review Reports

Title: Strategies to resolve the gap in Adolescent Tuberculosis care at four health facilities in Uganda: The TEEN TB pilot project

Manuscript Number: PONE-D-23-15403

Review Comments

� The title can be resentenced

� The background is inadequate and needs strength for its contents.

� The abstract is too long.

� Why you have used both the P value and the confidence interval at the same time? The result section fails to compare the before after results of the intervention.

� The manuscript fails to meet the standard guideline of PONE E.g. The study setting come after the study design

� What is the specific study design used?

� Did the diagnostic capacity or positive predictive rate of t both Gene expert and smear microscopy equal? Why you have used either of the test equally otherwise?

� What type of specific consents were used for those less than 15, 15-18 and greater than 18 years?

� How do you differentiate that the adolescents had arrived to the community due to your particular intervention?

� What are the specific interventions? What is the dose, schedule, the information conveyer quality? Means of delivery? Cultural appropriateness and language of the intervention needs detail explanation?

� What was done to ensure data quality?

� What does descriptive univariate analysis mean?

� The results, discussion, conclusion and recommendation needs major revision in line with the objective.

Regards,

Reviewer #3: Dear Author.

Thank you for the above study.

I must say that it is very relevant and well conducted by your team.

Due to the period in which the study was conducted and the prevailing epidemiology, I think your study was too quiet about Covid-19 impact. It affected your results which I was expecting you to rigorously discuss in the discussion section.

I think the impact of covid 19 is beyond the restriction of movement as you mentioned in the conclusion section. The periscope of infectious diseases cannot be turned away from Covid at the time when your study was conducted... there is a lot of studies on this: TB and Covid-19.

My OTHER COMMENTS ARE AS BELOW: please attend to them as in the attached document:

Thank you.

Strategies to resolve the gap in Adolescent Tuberculosis care at four health facilities in

Uganda: The TEEN TB pilot project.

Consider a short title that captures the attention of the reader e.g. " Adolescent Tuberculosis care in Uganda: Participatory action research"

This is a well written abstract. The chronology and clarity of the content are commendable. Thank you.

Overall, this is a good introduction with a precise expression of the social values of the study and a focused scientific values . please address the comment below

Thank you for this comparative epidemiology. I think it would have been better comparing 2021 with a year before the Covid -19 pandemic.

The reason for this is obvious from infectious disease perspective.

Please look into this. Data from 2018 could be better. thanks

Are you referring to TB notification surveillance?

If not, please substantiate your comment.

If yes, this comment is incorrect. TB notification exists as part of the standard of care of TB as an infectious communicable disease for every country under WHO.

I think you need to talk briefly about these study sites. why are they important to this study? what is the basis for their selection as a study site?

Good description of the study sites. Ignore the question about this above

Rather use: Unintentional weight loss or noticeable unintentional weight loss or just " weight loss"

Good description of the data collection procedure. Thanks

Good description of the steps in the data analysis

It is good that the clinical characteristic question addressed the knowledge about HIV due to its relevance in TB disease. I would have expected the same knowledge to be explored wrt Covid-19, due to its relevance at the period of your study and its impact on TB during the pandemic.

I think you may need to defend the clinical significance of this in the "discussion section". The fact that it is statistically insignificant (P= 0.170) doesn’t necessarily means that it is the same clinically.

I am of the opinion that you should separate the " Limitation of the study" from the conclusion.

Most of what you mentioned here are limitations.

Reviewer #4: I would like to congratulate the authors for this important work. This project may be an important input to the National TB and Leprosy Programs to strength the effort to control, prevent, and eliminate TB. Having said this, the study needs major revision that needs to be revised carefully.

Specific comments

Abstract

• It is not clear how the total study participants were 394 in fact the average number of adolescents screened increased by 94% from 159 to 309 that gives a total of 394. Please clarify in detail. If it was a daily/monthly average of the four sites? Specially describe the detail in the methods section.

• What type of randomized control trial? Is it cluster/population/community based or individual based?

Introduction

• No comment

Methods

• Describe who collected the socio-demographic and clinical data

• In the project settings section;

o Describe how the four health facilities are selected from the whole health facilities in the country? Please justify it. It is not realistic to randomly select four hospitals across the health facilities in the country. Two were from urban and two from rural, it seems purposively selected.

o Are all four health facilities are hospitals? You described that the study included health centers and district level hospitals? But all four were hospitals.

• In the data collection section;

o You described an idea already described in the previous section “Adolescents (10-19 years) who came to the project health facilities were identified from the service delivery points (OPD, ART clinic, MRH clinic, TB clinic and wards) and screened for TB using the national screening algorithm. Those with at least one of the TB symptoms and not on anti-TB treatment were considered eligible and were consented (≥ 18years) or assented (≤ 18 years) by their parents or health workers and enrolled into the project.”

o Describe about how data quality is maintained? Please describe one paragraph about data quality?

o How did you control if one individual came before and after intervention?

• In the data management/analysis section

o Change bivariate analysis to bi-variable. Univariate analysis includes bi-variable and multi-variable analysis. Bivariate analysis is used when analyzing more than one dependent variables at the same time.

o Describe which T-test was used (independent vs paired)

• Include operational definitions

Result

• Under the clinical characteristics section;

o I prefer to report in the opposite, such that how many smoked.

o 60(15%) of these reported HIV positive status which is a big proportion.

o To calculate the proportion of the participants who reported to have information from the research team, the denominator should be those who heard (326). 266/326=81.6%

o Do all participants visited the health facilities for TB care service? If yes, how many?

• Under the screening for TB section; line 5-10

o It is not clear about the number screened for TB. The sum of the number screened in the four hospitals is bigger than your sample size. Is it about the general population or adolescents who screened for TB? You described that the number of adolescents increased from 159 to 309=468 total adolescents, but the figures talk about 394 adolescents. Please clarify this. This works for all sub sections in the result section. Please early clarify in the methods section or early result section.

• Under the TB presumptive patients section;

o At line two and three, you described that the overall average increase after the intervention was from 13 to 29. However, based on the data from each hospital the sum of all the four hospitals is big number. Generally, the numbers in all the results section including TB testing , TB positive and linkage sections are ambiguous, please clarify in detail

• Under the linkage to TB care and treatment section;

o You described there was 50% (2 to 3.1) increase. How the number of adolescents can be described in decimals (3.1). Is it a mean?

Figures

• What mean by mean? E.g. Mean of screened?

Tables

• Table 1:

o The sum of the frequencies in each hospital is not equal to the overall frequencies. 159 vs 224+213+185+15? Are these figures talks about adolescents or general population? This applies for all tables and figures. Make it clear.

Discussion

• General;

In many sentences of the discussion section, you described that many studies support the study finding of your study. However, you cited only one reference that needs to be revised. E.G., paragraph two about males vs females, paragraph three about close contact, paragraph four about cigarrete smoking. Since line numbering is not available, difficult to put minor comments specific to the line number.

• Paragraph two you described that more female adolescents participated compared to males and tried to link to a previous study (ref 11). However, your justification may not be correct because among the global TB cases, males are predominant. Better to suggest the possible reason.

• In paragraph three you described majority of the TB positives were students, and close contacts, but I didn't see any result in tables, figures or narratives that described the link of TB positivity with any risk factors/variables in the result section. You have to focus on the main objectives or describe these findings in the result section. Discussing something you did not described in the result section or in the supplementary files is inappropriate. The objectives, the results and discussion should talk about similar things. This works also for cigarrete smoking. Have you done regression analysis or chi-squared test? If yes, what was the p-value?

• You described that some studies have shown close association between TB and cigarrete smoking alcohol consumption. However, you cited only one reference. In addition, why only some studies? Both factors are the known risk factors for TB and included in the five top factors contributing for TB in the Global TB report. Please revise it.

• You discussed about x-ray results. Please describe all parameters in the result section. Then you can discuss it.

• The paragraph “Besides the three key intervention approaches, many received information about TB from the research teams in the health facilities, community village health teams (VHTs) and social media. Apart from lack of information, other similar studies have also documented stigma, delays in diagnosis, long waiting hours, absence of nutritional support and psychosocial support as related factors associated with poor TB health care seeking 8 , 17” is not covered in your study. I suggest removing this paragraph.

• Again, you described many studies/ other studies while citing only one study. Please revise it.

• Please discuss more on the objectives of the study. Focus on the objectives of the study. Discuss more on the intervention model and the results before and after the intervention.

• Is there a statistical difference among the hospitals, among rural and urban hospitals? Please did analysis on this issue, describe in the result section and then discuss if appropriate.

• Please bring the limitations described in the conclusion section at the end of the discussion section in one paragraph. Because the readers should understand the limitations before go to the conclusion.

• Please use similar referencing style. Vancouver vs Harvard?

• Based on the things described in the result section about risk factors for TB, there is data gap not described either with in the manuscript or the supporting information.

Minor comments

• Include line numbering

• In the Abstract section, change Introduction to Background

• In all sections, describe the numbers up to 10 in the full name/words. E.g., change 4 to four.

• In the result of the abstract section, change GeneX-pert to GeneXpert.

• In the data management/analysis section fourth line change the data was cleaned to the data were cleaned.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Adeloye Amoo Adeniji (MBBS; MMed; FCFP; FACRRM)

Reviewer #4: No

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Submitted filename: PONE-D-23-15403.pdf

PONE-D-23-15403R1Strategies to resolve the gap in Adolescent Tuberculosis care at four health facilities in Uganda: The TEEN TB pilot projectPLOS ONE

Dear Dr. Omongot,

Thank you for submitting your manuscript to PLOS ONE with some comments addressed. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Zewdu Gashu Dememew, M.D

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors,

Thank you again for the revision,

However, there are remaining unaddressed issue to your attention. Hope you will attend to these commnest

Regards

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Submitted filename: Feed back_zg Dememew.docx

Strategies to resolve the gap in adolescent tuberculosis care at four health facilities in Uganda: The Teenager's TB pilot project.

PONE-D-23-15403R2

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