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. 2022 Nov 4;17(11):e0277255. doi: 10.1371/journal.pone.0277255

Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study protocol

Isdore Chola Shamputa 1,*, Duyen Thi Kim Nguyen 2,3, Doaa Higazy 4, Amani Abdelhadi 5, Hope MacKenzie 6, Michelle Reddin 2, Kimberley Barker 2, Duncan Webster 6,7,8
Editor: Jinsoo Min9
PMCID: PMC9635694  PMID: 36331954

Abstract

Introduction

Immigrants from high tuberculosis-burdened countries have been shown to have an increased risk of latent tuberculosis infection (LTBI). To reduce the risk of increased tuberculosis cases in Canada, the country has a comprehensive immigration medical examination process that identifies individuals with active tuberculosis using chest X-ray; however, it fails to identify LTBI. The lack of LTBI identification is concerning because immigrants with LTBI are at an increased risk of developing active tuberculosis within their first few years of migration due to stressful experiences common to many immigrants.

Objectives

The goal of this pilot study is to improve the current LTBI screening protocols among immigrants from high tuberculosis incidence countries and to better prevent and manage tuberculosis cases, by introducing an LTBI screening pilot program. The objectives are threefold: 1) to screen LTBI in immigrants from high tuberculosis incidence countries, including immigrants identified as being at risk of LTBI by the NB health care system, using the QuantiFERON-TB Gold Plus interferon-gamma release assay (IGRA); 2) to offer LTBI treatment and supports to those identified as having LTBI; and 3) to assess immigrant and health care providers (HCPs) satisfaction of the LTBI screening pilot program.

Methods

This cross-sectional study seeks to recruit 288 participants. Participants will be recruited via posters, social media platforms, invitations at immigrant wellness check-ups, presentations to local ethnocultural groups, and by snowball sampling. Consenting participants will be asked to submit a blood sample for LTBI screening; if positive, participants will be assessed and offered treatment for LTBI based on clinical assessment. Participants and HCPs’ feedback will be gathered via short questionnaires. For the quantitative portion of the study, descriptive statistics will be used to summarize participant characteristics and feedback. Simultaneous logistic regression will be performed to identify variables associated with the IGRA test outcome and evidence of increased CD8 T-cell immune response among those found to be LTBI-positive. Qualitative results will be analyzed using inductive thematic analysis.

Discussion

The findings from this study will allow us to understand the role of the IGRA LTBI screening assay and its feasibility and acceptability by immigrants and HCPs in New Brunswick. The findings will additionally provide information on the enhancers and barriers of LTBI screening and management useful in determining how best to expand the LTBI screening program if deemed appropriate.

Introduction

Tuberculosis (TB) is a major public health problem worldwide. It is estimated that a quarter of the planet’s population is infected with Mycobacterium tuberculosis, the bacteria that causes TB. In 2019, an estimated 10 million people suffered from active TB, and 1.4 million died from the disease [1]. The majority of people suffering from TB reside in low- and middle-income countries [1]. However, due to increased immigration and international travel, there is a growing number of TB cases being reported in high-income countries, with immigrants showing an increased risk of having latent TB infection (LTBI) and developing active TB within the first five years of migration [2]. Stressful living conditions, such as food insecurity, low-language fluency, cultural barriers, and housing insecurity, disproportionately affect recent immigrants and increase the likelihood of activating TB among LTBI-positive immigrants post-migration [3].

About 71% of TB cases in Canada are among non-Canadian-born individuals from high-TB incidence countries. In New Brunswick (NB), the number of incoming immigrants has increased sixfold in the last two decades [4]. NB has recently increased its intake of immigrants even more significantly, with the introduction of the Atlantic Immigration Program, which welcomed 16,000 immigrants to NB in the last three years alone [5]. Through a population growth strategy, NB aims to accept 7,500 more immigrants per year until 2024, the maximum allowed by the federal government [6]. With the foreseeable increase in NB’s immigrant population, many from high-burden TB countries, it is imperative that the province’s health care system prepare to prevent and manage the potential increased incidence of easily transmissible diseases, such as TB. Strategies directed toward improved LTBI surveillance, integrated LTBI screening, and proper active TB management may decrease the rate of infectious TB cases and reduce transmission and secondary cases [7,8]. To the best of our knowledge, this study is unique in Atlantic Canada.

This study uses the QuantiFERON-TB Gold Plus (QFT-Plus) interferon-gamma release assay (IGRA) (QIAGEN), which elicits both CD4 and CD8 T-cell response as a screening assay for LTBI [9,10]. The IGRA is available in Saint John, NB; the only laboratory processing and analyzing IGRA’s in Atlantic Canada. Compared to traditional LTBI screening tools, such as the tuberculin skin test, the IGRA requires a single blood draw, is not affected by the bacille Calmette-Guerin vaccination or previous exposure to most non-tuberculous mycobacteria, and has fewer issues with inter-rater reliability [11,12]. Thus, the IGRA is an excellent means to screen for LTBI, as it 1) provides more accurate identification of LTBI cases, 2) thus helping to ensure the optimal management of patients, and 3) with associated programming may help reduce the transmission of TB by individuals progressing from LTBI to active TB.

Statement of objectives

To improve the current TB screening protocols used in NB, and to better prevent and manage TB cases, our goal is to implement a LTBI screening pilot program in southern NB, using the IGRA as the primary screening method.

To achieve our goal, our objectives are threefold:

  1. to screen LTBI in 288 immigrants from high TB incidence countries (as identified by ≥40/100 000 population) [2], including immigrants identified as being at risk of LTBI by the NB health care system, using the IGRA;

  2. to offer LTBI treatment and supports to those identified as LTBI-positive; and

  3. to assess newcomer and HCPs’ satisfaction with the LTBI screening pilot program.

This study builds upon our previous research, which investigated the knowledge, attitudes, and beliefs of 43 newcomers in southern NB regarding LTBI. Our previous study identified several key findings: 1) Most of the participants were willing to get tested and treated for LTBI; 2) participants desired an increased awareness of LTBI; 3) participants emphasized the importance of supporting people with an LTBI diagnosis, and 4) participants shared a common experience of general stigma associated with TB [13].

Materials and methods

Our study will employ a cross-sectional study design, and will be guided by the sex-gender-based analysis plus approach [14] and an equity, diversity, and inclusion lens [15].

Participants

To ensure our study has adequate power to detect statistical significance (α level = 0.05), we aim to recruit 288 participants [16]. In an effort to be as inclusive as possible, four broad eligibility criteria will guide recruitment. Potential participants must be: 1) born outside of Canada; 2) 19-years of age or older at the time of consent; 3) came from, or resided in, a country with a TB incidence of ≥40/100 000 population [2] before arriving in Canada [17], are at high-risk of TB (e.g., having a TB-positive partner), or government assisted refugees who participate(d) in a Post Arrival Health Assessment by the NB Public Health and are (were) tested for LTBI; and 4) a resident in southern NB (i.e., Charlotte, Saint John, and Kings counties, extending from Sussex to St. Stephen). To conduct stratified analyses on several key factors, we aim to have a broad and balanced participant recruitment based on gender, sex, ethnicity, age, immigration stream, and year of arrival to Canada.

Recruitment

Materials

We will examine the implementation and satisfaction of the LTBI screening pilot program using several data collection tools. All data collection tools for immigrants are available in seven languages (English, French, Tagalog, Somali, Farsi/Dari, Mandarin, and Spanish) for enhanced comprehension (S1 and S2 Appendices).

  1. Participant demographics questionnaire and history. We will collect key demographic information relevant to our understanding of LTBI and the screening process, such as sex and gender, country of origin, date of arrival to Canada, immigration stream of entry (S3 Appendix). We will also measure factors that may intersect with sex and gender, such as ethnicity, and age [18].

  2. Participant survey. Participant feedback regarding their experience of the pilot screening program will be gathered through a series of 5-point Likert scales and open-ended questions (S2 Appendix). Participants have the option to complete the questionnaire in hard copy or online. Questions will relate to equity, diversity, and inclusion, such as barriers and enablers of LTBI testing, including language, cultural issues, accessibility of the blood collection facility, their interaction with the health care professionals, and ease/difficulty of participating in this study.

  3. HCP survey. HCP demographic information and feedback will be gathered via a questionnaire, and feedback questions will address barriers and enablers of the pilot screening program, such as challenges encountered during their interactions with the participants and management and follow-up (S4 Appendix).

Procedure

This study is being conducted in multiple steps, with some steps occurring concurrently.

1) Developing and pilot testing questionnaires

Participant questionnaires and health care questionnaires were pilot-tested with a sample of immigrants and HCPs, respectively, for clarity, coherence, and time of completion [19]. To help prevent respondent fatigue, we aimed to have the survey completed in under 10 minutes [20] and written at a grade 3 level for maximum comprehension [19].

2) Research ethics board approval

This study received ethics approval from; 1) the Horizon Health Network; and 2) the University of New Brunswick Research Ethics Boards (reference numbers: 033–2021 and 2021–3046, respectively).

3) Recruitment

Participants are being recruited through several mediums, including posters distributed by newcomer-serving organizations and their various social media platforms, invitations at newcomer wellness check-ups, through presentations to local ethnocultural groups, and snowball sampling. As indicated above, recruitment materials are available in seven of the most commonly spoken languages among immigrants in southern NB.

4) LTBI screening

Interested participants are screened virtually by a research team member to ensure they meet the eligibility criteria, are provided with study information, and understand the consent form. If the criterion is met and participants demonstrate a clear understanding of the informed consent form, then oral informed consent will be obtained by a research team member before participating in the study. Participants will receive an e-gift card of $20 after blood collection and another $20 e-gift card after completing the online participant survey for a total of $40 compensation for their time.

5) Sample collection

Blood samples will be collected by a certified phlebotomist at the Young Men Christian Association of Greater Saint John on dedicated days following existing coronavirus disease 2019 operational protocols. Alternate blood collection sites include the Saint John Regional Hospital, Saint Joseph’s Hospital, the Uptown Community Clinic in Saint John, Charlotte County Hospital, the Fundy Health Clinic and Sussex Hospital.

6) Laboratory analyses and tuberculosis testing results

The IGRAs will be analyzed at the Saint John Regional Hospital’s Microbiology Laboratory according to the recommended protocols [21]. IGRA results and associated diagnostic data will be accessed by the research team via electronic TB client registration systems at the Saint John Regional Hospital and the NB Public Health data system for all participants diagnosed with latent or active TB. IGRA results will be communicated to participants by the attending HCPs following existing Horizon Health Network procedures. Positive results will be assigned appropriate triaging for follow-up and treatment.

7) LTBI follow-up for LTBI-negative participants Individuals with a negative test are being contacted with their results by an HCP.

8) LTBI follow-up and supports for LTBI-positive participants

Individuals with positive test results will undergo a further clinical assessment to determine the need for additional testing to rule out an active TB diagnosis. Those with confirmed LTBI will be counselled, offered treatment, and uniquely managed for optimal care. Participants with confirmed active TB will be treated according to appropriate protocols [22]. All individuals will be provided counseling and written information with regards to TB/LTBI, and information pertaining to relevant medications. Support and follow-up will be provided during treatment to ensure adherence, and to address stigma- and treatment-related concerns.

9) Participant and HCP surveys

Participant questionnaires will be administered virtually by a research team member after i) the participant has received a negative IGRA result, ii) after the completion of treatment for those with a positive IGRA result, were assessed by an HCP, offered and agreed to be treated, or iii) after receiving a positive IGRA result, were assessed by an HCP, offered but declined treatment. Questionnaires will be administered to all HCPs once our study has reached its goal of 288 participants. The data will be linked to previous demographic information and test results using unique, de-identifiable codes.

Data analysis plan

To help monitor and ensure we meet our recruitment goals, we will conduct data collection and data analyses concurrently.

Statistical analyses

Underlying our analyses will be the sex-gender-based analysis plus (SGBA+) approach, and an equity, diversity, and inclusion lens. Descriptive statistics (i.e., frequencies, means, and ranges) will be computed to summarize participant characteristics and feedback. Simultaneous logistic regression will be performed to identify variables associated with the IGRA test outcome (positive or negative) and evidence of increased CD8 T-cell response among those found to be LTBI-positive. Predictors for the logistic regression will be age, sex, gender, country of origin, immigration stream, and the presence of co-morbidities. Power analysis for the logistic regression using the 10 events per predictor variable rule of thumb [(10* k)/p, where k is the number of predictors (6 predictors), and p is the lowest event rate] and assuming a conservative 25% event rate for LTBI, indicates a minimum sample size of 240 participants is required to power the regression. To account for potential participant, drop-out, an additional 20% will be added to the sample size, leading to a need for 288 participants. An alpha of 0.05 will be used for the regression analysis. All statistical analyses will be performed using Stata statistical software (version 16; StataCorp, 2019) [23] and/or IMB SPSS Statistics software, version 27 (Armonk, NY) [24].

Qualitative analyses

All qualitative feedback will be inputted into Microsoft Excel and Word for coding and thematic analyses as described elsewhere [25]. Briefly, two research team members will independently familiarize themselves with all of the data. Next, initial codes will be generated independently and collaboratively with a third-team member. Subsequently, codes will be integrated into emerging themes; these will be reviewed by the entire team and modified if necessary.

Data security

Our data will be confidential (i.e., de-identified) and triple safeguarded: 1) data files will remain password protected; 2) laptops/Personal Computers will also be password-protected; and 3) laptops/Personal Computers will remain in a locked and secured possession of the users.

All electronic data will be stored on a secure University of New Brunswick Saint John drive that will only be accessed by members of the study team. In addition, the master record will be password protected for additional security. All paper data will be shredded, and computer files will be permanently deleted after 5 years to allow for the dissemination of study findings. Data will be reported in aggregate form. For the purposes of identifying interested individuals who wish to be contacted with the final report, it is necessary to maintain identifiers in the individual consent forms.

Participant recruitment for this study has started and will continue until we reach our targeted sample size.

Discussion

This study seeks to improve the current LTBI screening protocols among immigrants from high TB incidence countries and to better prevent and manage TB cases in southern NB. At the completion of this study, it is anticipated that i) we will understand the role of the IGRA LTBI screening assay and its feasibility and acceptable by immigrants and HCPs, and ii) the findings will avail information on the enhancers and barriers of LTBI screening and management that will be useful in determining how best to expand the program province-wide if deemed appropriate.

Identifying and treating individuals with LTBI will reduce the pool of individuals with LTBI, thereby lowering their potential to develop active TB. In turn, this will potentially reduce health costs associated with the transmission, contact tracing, treatment of active TB, and follow-up of TB patients with the promotion of a healthier NB population. Further, the detection and treatment of individuals with LTBI have several other advantages; first, given that an estimated one-quarter of the world’s human population is infected with TB [1], detecting and treating LTBI is one of the critical strategies for the elimination of TB as a global public health threat [26]. Second, mathematical modeling studies have demonstrated that through screening and control strategies targeting LTBI, the development of active TB can be reduced between 20.6 [27] and 40% on a population level [28]. Third, the prevention of active TB by detecting and treating individuals with LTBI can also help prevent numerous health problems and post-TB sequelae that may be experienced by individuals despite adequate and successful treatment of active TB [29]. In addition, the model that this research will develop may benefit the prevention and control of other diseases in NB. Thus, our research will likely significantly impact keeping Canadians, and New Brunswickers in particular, safe. Finally, the findings of this study will help lobby for the development of an LTBI program among immigrants from high TB-incidence countries in southern NB.

Knowledge translation and exchange efforts will be a central component of our goals and will be conducted using several approaches to reach the widest audience. First, at the end of the study, we will hold an end-of-grant virtual workshop and multiple presentations for all interested diverse stakeholders (e.g., study participants, HCPs, newcomer serving agencies, ethnocultural groups, officials from the NB Ministry of Health) to disseminate our findings, gather feedback, and address questions. Second, using our subscription to Canva (i.e., an infographic maker), we will create a series of infographics-based results and experience conducting this study. Infographics will also be created for dissemination across social media platforms. Third, to reach the academic and clinical community, we will present our findings at local, provincial, national, and/or international conferences and publish the results in peer-reviewed journals. We aim to publish in at least one open-access peer-reviewed journal article to increase the reach of our findings. Finally, we will submit a written final project report to the Assistant Dean of Dalhousie Medicine NB Research and to the Government of NB’s Office of the Chief Medical Officer of Health (Public Health). A copy of the findings will also be shared with participants who desire to receive one.

Supporting information

S1 Appendix. Informed consent form in multiple languages.

(PDF)

Click here for additional data file. (6.3MB, pdf)
S2 Appendix. Participant surveys multiple languages.

(PDF)

Click here for additional data file. (338.6KB, pdf)
S3 Appendix. LTBI indicator form.

(PDF)

Click here for additional data file. (69.4KB, pdf)
S4 Appendix. Health care practitioner survey.

(PDF)

Click here for additional data file. (98KB, pdf)

Acknowledgments

We would like to acknowledge Dr. Andrew Flewelling for assistance with sample size calculation and Clara Kelly for help with participant recruitment.

Data Availability

No datasets were generated or analyzed during the current study. All relevant deidentified data will be made publicly available when the study is completed and published.

Funding Statement

This project was supported by a grant from the Chesley Family Research Award (https://medicine.dal.ca/) and the New Brunswick Health Research Foundation (https://nbhrf.com/en/) (ICS, DTKN, DH, AA, HM, KB, DW). The study also received funding from the New Brunswick Innovation Fund (Emerging projects ref #: EP_2022_017) (https://nbif.ca) (ICS, DTKN, DH, AA, HM, KB, DW), the University of New Brunswick (Student Work Program) (https://www.unb.ca) (ICS), New Brunswick Health Research Fund (ICS) and in-kind donation of interferon gamma release assay (QuantiFERON®-TB Gold Plus) tests from Qiagen Inc (https://www.qiagen.com/us) (ICS, KB, DW). The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

Decision Letter 0

Jinsoo Min

11 Aug 2022

PONE-D-22-13477Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study ProtocolPLOS ONE

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Reviewer #2: Yes

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Reviewer #2: No

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Reviewer #1: The protocol was well detailed but only deficient in the patient consent section. This is not detailed and considering the need to have a full disclosure the clients the consent form must be very detailed as such information as ; details of the study, purpose, procedures, risks or discomfort, costs to participants and confidentiality were not well presented

Reviewer #2: Thank you for the opportunity to review this manuscript. This study protocol describes a plan to for a pilot study to systematically screen newcomers from TB endemic countries for latent tuberculosis infection, using IGRA tests. My comments are provided to help strengthen the protocol and this manuscript.

Abstract – the abstract includes only the Introduction, objectives and methods sections, but would be better to summarize all sections of the manuscript, including the analysis plan, discussion, etc.

Recruitment – over 19 years of age – please explain why recruitment does not include adults aged 18 years

Delighted to see the intent to apply a SGBA approach. When referring to gender, in the participant recruitment (line 113), for example, will this be a demographic question about self-identity? In the demographics questionnaire, how will “culture” be defined, in comparison to ethnicity for example or country of origin? Similarly, in the participant survey (Likert scales) how will “cultural issues” be presented to respondents as something to comment on?

HCP survey – Please spell out what is meant by HCP when it is first used. What demographic information will be collected from providers? It will be important to consider gender and sex among this study population as well as the newcomer population. How many HCPs will be recruited to the study? Was the survey piloted for HCP also written at a grade 3 level?

Section 4 LTBI screening – some confounding of screening out participants for their eligibility in the study and screening for LTBI. This should be revised for clarity

LTBI follow- up – this portion will benefit from additional details about how stigma and treatment-related concerns will be addressed. Is this to be accomplished by this study team?

Participant and HCP surveys will be administered after LTBI follow-up – what is that timeframe? Does that refer to completion of treatment? Needs clarification.

Statistical Analyses – “predictors of the logistic regression” will be age, gender, country of origin, etc. I recommend using sex as one of the predictors. The progression of TB and other diseases is entwined with sex – anatomy and physiology, whereas gender – which refers to social norms, roles and identities, will also be important in terms of ability to participate in the study or in follow-up, but for different (social) reason.

Description of qualitative analyses is too brief. Will a constant comparison method be used for the analyses, for example? And how many research team members will be looking for and validating codes and themes?

Discussion: I recommend some mention of the benefit of reducing the burden of TB disease and suffering, not just as a health care cost saving.

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Reviewer #2: Yes: M J Haworth-Brockman

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PLoS One. 2022 Nov 4;17(11):e0277255. doi: 10.1371/journal.pone.0277255.r002

Author response to Decision Letter 0

26 Aug 2022

Responses to Reviewer’s comments

Reviewer #1:

The protocol was well detailed but only deficient in the patient consent section. This is not detailed and considering the need to have a full disclosure the clients the consent form must be very detailed as such information as ; details of the study, purpose, procedures, risks or discomfort, costs to participants and confidentiality were not well presented.

Authors’ response: The information requested is included on the consent form [see a copy of the English version below] [see also S1 Appendix]:

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Informed Consent Form for Participants

Title of Project: Optimizing Tuberculosis Screening for Newcomers in Southern New Brunswick: A Pilot Study

Introduction

We are inviting adults 19 years of age and older to participate in a study on screening for latent tuberculosis infection. The purpose of this study is to gather information to assess the feasibility of implementing a latent tuberculosis infection screening program for newcomers from countries with many cases of tuberculosis.

If you choose to participate, you will be asked to provide about 4 ml of blood for testing latent tuberculosis infection and complete an online survey for approximately 10 minutes about your experience in participating in the study.

Your participation is voluntary, and you may withdraw from the study at any time without penalty. There is no cost for participating in the study. Participants will receive up to $40 in e-gift cards for their time, i.e., $20 after blood collection and another $20 after completing the online survey.

Potential benefits

The potential benefits from participating in this study may include the reassurance that you do not have latent tuberculosis infection (if the test is negative). If the test is positive and you get treated, you will benefit by considerably reducing the chances of suffering from tuberculosis disease, thereby keeping your family and friends safe.

Potential risks:

There is a minimal risk of discomfort, bruising, or infection at that site during blood collection, similar to giving an amount of blood for other medical tests.

Privacy and confidentiality

Protecting your privacy is an important part of this study. Information gathered from this study is strictly confidential, and your information will be anonymized. All electronic data will be stored on a secure drive at the Department of Nursing & Health Sciences at the University of New Brunswick for 5 years to allow for the dissemination of information, after which it will be destroyed. The data will only be accessed by members of the study team.

QUESTIONS

If you have questions after you read this form, ask the research team member assessing you. You should not sign this form or provide verbal consent until you are sure that you understand the study.

This project has been reviewed by the Research Ethics Board of the University of New Brunswick and is on file as REB File #033-2021, Brunswick, and the Horizon Health Network Research Ethics Board and poses minimal risk. In the event that injury, illness or disability results and you believe that it is related to your participation in this study, or if you have any questions about your rights as a research participant, you may contact Dr. Beth Keyes, Chair of the Research Ethics Board at the UNBSJ by phone [506-648-5994] or by email [REB@unb.ca] or Regional Director of Ethics Services, Horizon Health Network Research Ethics Board by phone [506) 648-6094] or by email at [REBOffice@HorizonNB.ca].

PARTICIPANTS STATEMENT

I have read the information about this study and have had the opportunity to discuss this study and my questions have been answered to my satisfaction. I acknowledge that I have been informed that my participation is voluntary and that the data I provide will remain confidential. I hereby consent to take part in this study.

Name of participant

Signature of participant____________________________ Date: ______________

OR

Obtained verbal consent of participant_________________ Date: ______________

Please note that by consenting to participating in this study, you have not waived any rights to legal recourse in the event of research-related harm.

STATEMENT BY PERSON PROVIDING INFORMATION ON STUDY

I have explained to the above participant the nature, requirements and the purpose of the study, potential benefits, and possible risks associated with participation in this study. I have answered any questions that have been raised. I believe that the participant understands the implications and the voluntary nature of the study.

Researcher Signature: ____________________________ Date: ______________

Research Team:

Dr. Duncan Webster, Division of Infectious Diseases, Department of Medicine, Saint John Regional Hospital, duncan.webster@horizonnb.ca

Dr. Isdore Chola Shamputa, Department of Nursing & Health Sciences, University of New Brunswick Saint John, chola.shamputa@unb.ca

Dr. Kimberly Barker, Medical Officer of Health, South Region, New Brunswick Department of Health, Kimberley.Barker@gnb.ca

Dr. Duyen Nguyen, Regional Senior Program Advisor, Government of New Brunswick, duyen.nguyen@gnb.ca

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Reviewer #2:

Thank you for the opportunity to review this manuscript. This study protocol describes a plan to for a pilot study to systematically screen newcomers from TB endemic countries for latent tuberculosis infection, using IGRA tests. My comments are provided to help strengthen the protocol and this manuscript.

Abstract – the abstract includes only the Introduction, objectives and methods sections, but would be better to summarize all sections of the manuscript, including the analysis plan, discussion, etc.

Authors’ Response: The following information has been added to the Abstract to address this concern:

”For the quantitative portion of the study, descriptive statistics will be used to summarize participant characteristics and feedback. Simultaneous logistic regression will be performed to identify variables associated with the IGRA test outcome and evidence of increased CD8 T-cell immune response among those found to be LTBI-positive. Qualitative results will be analyzed using inductive thematic analysis.

Discussion: The findings from this study will allow us to understand the role of the IGRA LTBI screening assay and its feasibility and acceptability by immigrants and HCPs in New Brunswick (NB). The findings will additionally provide information on the enhancers and barriers of LTBI screening and management useful in determining how best to expand the latent TB screening program if deemed appropriate.” [see lines 43-52].

Recruitment – over 19 years of age – please explain why recruitment does not include adults aged 18 years

Authors’ response: Individuals below 19 years are considered minors in Canadian Province of New Brunswick and thus cannot legally provide consent to participate in the study; that is why we are including individuals who are at least 19 years old (see definition of majority age: https://www.canada.ca/en/immigration-refugees-citizenship/corporate/publications-manuals/operational-bulletins-manuals/refugee-protection/canada/processing-provincial-definitions-minor.html).

Delighted to see the intent to apply a SGBA approach. When referring to gender, in the participant recruitment (line 113), for example, will this be a demographic question about self-identity?

Authors’ response: Yes. Gender is included as a demographic question [see enclosed LTBI Form below (S3 Appendix)].

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

LTBI Indicator Form

Patient ID (assigned by researcher):____________________________

Patient Demographic Information:

1. Date of birth________________________

2. Sex: 1. Male 2. Female

3. Gender: 1. Male 2. Female 3. Other: ________________

4. Country/Region of birth: ________________

5. Countries where you lived for more than 6 months (before coming to Canada):_________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________

6. Date of immigration/arrival to Canada: _____________________

7. Immigration stream:

1. Economic 2. Family Reunification 3. Study Permit

4. Work Permit 5. Refugee/Refugee Claimant 6. Temporary Visitors

Pre-Visit Data: (to be completed by Public Health)

8. New LTBI case? 1. Yes 2. No

9. Known prior contact with active TB? 1.Yes 2. No 3. Unknown; If yes, when?________

10. Client enrolled in IGRA study? 1. Yes 2. No

11. Medical Surveillance client?. 1. Yes 2. No

12. TST…………………………………….__________________(mm of induration)

13. IGRA……………………………………1. Positive 2. Negative 3. Not performed

14. IGRA result data…………….. TB1:________; TB2:_________; NIL:__________

15. Date of referral for LTBI treatment assessment:______________________________

Visit Data: (to be completed by assessing healthcare provider)

16. Referred LTBI patient seen within 30 days for treatment assessment. 1. Yes 2. No

17. Referred LTBI Patient seen within 90 days for treatment assessment.

1. Yes 2. No 3. N/A

18. Referral source____________________Public Health / ID / Other: ________________

19. BCG vaccine 1. Yes 2. No 3. Unknown

20. Presence of comorbidities increasing risk for activation. 1. Yes 2. No

21. TST in 3D score……….% risk for active TB within next 2 years / % risk for active TB before age 80 years

22. Treatment 1. Yes 2. Prior adequate treatment 3. Refused

23. Planned treatment start date: ______________________________________________

24. Drug regimen chosen or previously administered: _____________________________

Post-Visit Data: (to be completed by assessing healthcare provider)

25. Completed treatment: 1. Yes 2. No

26. # missed doses: ________________________________________________________

27. Adverse effects reported: 1. Yes 2. No

Clinically significant ALT rise (>2-3x upper limit normal?). 1. Yes 2. No

28. 80% or greater compliance with risk adjusted follow up schedule: 1. Yes 2. No

29. Agrees to annual follow up CXR x 2 years. 1. Yes 2. No 3. N/A

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

In the demographics questionnaire, how will “culture” be defined, in comparison to ethnicity for example or country of origin?

Authors response: We thank the reviewer for bringing this point to our attention. Culture, was not explicitly defined and there are no direct questions on it in the demographic questionnaire. For this reason, culture has been removed from that statement.

Similarly, in the participant survey (Likert scales) how will “cultural issues” be presented to respondents as something to comment on?

Authors response: As stated above we do not have specific questions on culture, rather, there are questions such as questions 12, 13, 15 and 16 with open ended questions where participants can elaborate on their response to respective questions. This is where we hope to gain some insights into plausible cultural stigma. Below is the English version of the participant survey depicting the questions alluded to above [see also S2 Appendix]:

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Participant Survey

Instructions: Please circle the response that best describes your agreement with the statement.

1. I received information on why the latent tuberculosis test was being done.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

2. The blood collection site was easy to access.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

3. The blood collection site was easy to commute to.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

4. The blood collection process was simple (e.g. registration, blood collection).

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

5. How long did the blood collection process take (in minutes)___________________________

6. The waiting time for blood collection was reasonable.

Too long Somewhat long Neutral Somewhat short Very short

1 2 3 4 5

7. I received adequate information regarding my latent tuberculosis test results.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

8. I was satisfied with the way my latent tuberculosis test result was communicated to me.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

9. The healthcare provider (i.e., doctor, nurse) clearly explained the test results.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

10. The healthcare provider answered all my questions well.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

11. I was treated with respect by the healthcare provider.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

12. I was satisfied with the overall experience with the latent tuberculosis screening process and/or care I received.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

13. I did not experience any barriers when participating in this study.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

14. I would recommend latent tuberculosis screening services to other newcomers.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

15. I did not feel stigmatized when participating in the study.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

16. I had concerns about participating in the study.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

17. My knowledge, attitudes, beliefs, and/or fear regarding tuberculosis improved by participating in the study.

Strongly Disagree Disagree Neutral Agree Strongly Agree

1 2 3 4 5

18. Do you have any suggestions on how the latent tuberculosis screening process can be improved?

1. Yes 2. No

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

HCP survey – Please spell out what is meant by HCP when it is first used.

Authors’ response: Health Care Provider (HCP) has been spelt out on its first use [see line 36].

What demographic information will be collected from providers?

Authors’ response: Sex and gender.

It will be important to consider gender and sex among this study population as well as the newcomer population.

Authors’ response: We can confirm that both sex and gender were considered for both study populations.

How many HCPs will be recruited to the study?

Authors’ response: There are two health care providers on the research team that will care for all study participants; an infectious diseases physician and a Nurse Practitioner. We have an option of adding another Nurse Practitioner if the need arises.

Was the survey piloted for HCP also written at a grade 3 level?

Authors’ response: Yes it was.

Section 4 LTBI screening – some confounding of screening out participants for their eligibility in the study and screening for LTBI. This should be revised for clarity

Authors’ response: The inclusion criteria targets participants with a high risk for latent TB infection. These are individuals who can benefit most from the study and from whom we can gather most useful information regarding how best the latent TB screening can be utilized, if used widely in New Brunswick. For the type of population and location we are dealing with, we feel that our current criteria is robust enough to identify the most relevant participants. The potential for confusion is limited and can easily be addressed if in doubt because only a few members of the research staff dealing with recruitment are very abreast with the criteria. It is possible that the target population in other settings may be slightly different.

LTBI follow- up – this portion will benefit from additional details about how stigma and treatment-related concerns will be addressed. Is this to be accomplished by this study team?

Authors’ response: TB stigma and treatment concerns are being partially addressed in this study but are also being considered as a separate undertaking by the research team. In this study, discussions regarding TB-related stigma and treatment concerns commence during recruitment. In addition, when delivering the participants' latent TB test results, the team's infectious diseases physician addresses these concerns. The infectious diseases physician also assesses, counsels, and may offer treatment to those with positive test results, if indicated. This channel of communication will remain open to the participants during treatment follow up. A Nurse Practitioner is also available an as extra resource. In addition, there are separate ongoing efforts by the research team focused on addressing TB- stigma-related concerns and providing education on TB, particularly the differences between active and latent tuberculosis and the associated risks. For example, the study team speaks to different ethnocultural groupings about TB, answering questions and dispelling misinformation in the community. The team has also developed various leaflets regarding TB as a follow up to similar findings from our previous study with a similar population (Shamputa et al., 2022).

Participant and HCP surveys will be administered after LTBI follow-up – what is that timeframe? Does that refer to completion of treatment? Needs clarification.

Authors’ response: Participant questionnaires administration will be done as the last step of participating in the study. For participants with a negative latent TB result, the survey will be administered soon after the physician informs them of their test results. Typically, this is within 2 weeks of providing a sample for testing. For participants with a positive latent TB result, the survey is administered after the participant completes treatment about 4-months later (if they accepted treatment) or soon after they’ve had a discussion with the physician about their test results, if they decline treatment. The following statement has been added to the manuscript

“ i i) the participant has received a negative IGRA result, ii) after the completion of treatment for those with a positive IGRA result, were assessed by a HCP, offered and agreed to be treated, or iii) after receiving a positive IGRA result, were assessed by a HCP, offered but declined treatment.” [see lines 218-221]. HCP surveys will be administered at the end of the study [see lines 222-223].

Statistical Analyses – “predictors of the logistic regression” will be age, gender, country of origin, etc. I recommend using sex as one of the predictors. The progression of TB and other diseases is entwined with sex – anatomy and physiology, whereas gender – which refers to social norms, roles and identities, will also be important in terms of ability to participate in the study or in follow-up, but for different (social) reason.

Authors’ response: As per Reviewer 2’s recommendation, sex has been added as one of the predictors [see line 236] (six in total now). Note that this has resulted in the increase in the sample size to 288 (and updated throughout the manuscript).

Description of qualitative analyses is too brief. Will a constant comparison method be used for the analyses, for example? And how many research team members will be looking for and validating codes and themes?

Authors’ response: This section has been expanded in response to this observation and a reference regarding the “constant” method that will be used to conduct thematic analysis added. That section now reads as follows

“...as described elsewhere [25]. Briefly, two research team members will independently familiarize themselves with all of the data. Next, initial codes will be generated independently and collaboratively with a third-team member. Subsequently, codes will be integrated into emerging themes; these will be reviewed by the entire team and modified if necessary” [see lines 249-252 and 410-411].

Three research members with expertise in qualitative data analyses will perform the primary analysis, which will be shared and discussed with the entire research team.

Discussion: I recommend some mention of the benefit of reducing the burden of TB disease and suffering, not just as a health care cost saving.

Authors’ response: As recommended by reviewer 2, the following information has been added to the manuscript:

“Further, the detection and treatment of individuals with latent TB have several other advantages; first, given that an estimated one-quarter of the world's human population is infected with TB [1], detecting and treating latent TB is one of the critical strategies for the elimination of TB as a global public health threat [26]. Second, mathematical modeling studies have demonstrated that through screening and control strategies targeting latent TB, the development of active TB can be reduced between 20.6 [27] and 40% on a population level [28]. Third, the prevention of active TB by detecting and treating latent TB can also help prevent numerous health problems and post-TB sequelae that may be experienced by individuals despite adequate and successful treatment of active TB [29].” [see lines 280-288] and the respective citations have been added to the reference list [see lines 412-422].

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (53.1KB, docx)

Decision Letter 1

Jinsoo Min

13 Oct 2022

PONE-D-22-13477R1Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study ProtocolPLOS ONE

Dear Dr. Shamputa,

Thank you for submitting your manuscript to PLOS ONE. 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. Please submit your revised manuscript by Nov 27 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Jinsoo Min

Academic Editor

PLOS ONE

Journal Requirements:

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 (if provided):

(1) Please, define the abbreviations if it used first in the manuscript body. (HCP, NB, PC)

For example, full name of 'HCP' is missing in both abstract and manuscript body.

(2) Please, minimize the use of the abbreviation.

For exmaple, I think that it is unecessary to use "NB" in the abstract, because it is used only one time in the abstract. Another example is "PC".

(3) I think you need to insert branckets before and after "SGBA+".

(4) Please, check any minor erros. PLOS ONE does not copyedit accepted manuscripts.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I am satisfied that the authors have made the necessary revisions to this manuscript and it is ready for publication. I note that the authors comment that data will be presented in their final form in aggregated form, however I encourage the authors to continue with plans to analyze AND present the data by sub-tabulations as possible (e.g., by sex) so that the results can be most useful to other researchers and LTBI program managers.

**********

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Reviewer #2: No

**********

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PLoS One. 2022 Nov 4;17(11):e0277255. doi: 10.1371/journal.pone.0277255.r004

Author response to Decision Letter 1

13 Oct 2022

Responses to Reviewers’ comments:

Below are our responses to the reviewers’ comments:

(1) Please, define the abbreviations if it used first in the manuscript body. (HCP, NB, PC)

For example, full name of 'HCP' is missing in both abstract and manuscript body.

Response: i) “HCP” has been defined in line 36; ii) NB and PC are addressed below:

(2) Please, minimize the use of the abbreviation.

For example, I think that it is unnecessary to use "NB" in the abstract, because it is used only one time in the abstract. Another example is "PC".

Response: i) “NB” abbreviation has been deleted from the abstract and introduced in the manuscript body (see line 81) and ii)“PC”, this abbreviation has been deleted and replaced by “Personal Computers.” (see lines 257 and 258).

(3) I think you need to insert brackets before and after "SGBA+".

Response: brackets have been inserted (see line 233).

(4) Please, check any minor errors. PLOS ONE does not copyedit accepted manuscripts.

Response: This has been done.

Reviewer #2, “...I note that the authors comment that data will be presented in their final form in aggregated form, however I encourage the authors to continue with plans to analyze AND present the data by sub-tabulations as possible (e.g., by sex) so that the results can be most useful to other researchers and LTBI program managers.”

Response: This will be done.

Attachment

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Decision Letter 2

Jinsoo Min

17 Oct 2022

PONE-D-22-13477R2Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study ProtocolPLOS ONE

Dear Dr. Shamputa,

Thank you for submitting your manuscript to PLOS ONE. 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.

Please submit your revised manuscript by Dec 01 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Jinsoo Min

Academic Editor

PLOS ONE

Journal Requirements:

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:

(1) Define abbreviations upon first appearance in the text.

: IGRA is not defined in the manuscript body.

(2) Keep abbreviations to a minimum.

: 'COVID-19' is only used once. Please, change the "COVID-19" to "coronavirus disease 2019".

(3) The author states that "This sutdy uses the fourth-generaion IGRA". I thick this assays is the QuantiFERON-TB Gold Plus. Please, mention the name of the assay and its manufacturer in an appropirate place.

(4) Please, check any minor erros. PLOS ONE does not copyedit accepted manuscripts.

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Nov 4;17(11):e0277255. doi: 10.1371/journal.pone.0277255.r006

Author response to Decision Letter 2

18 Oct 2022

Editor’s comment:

(1) Define abbreviations upon first appearance in the text.

IGRA is not defined in the manuscript body.

Authors’ Response:

IGRA has been defined in the manuscript (see line 94).

Editor’s comment:

(2) Keep abbreviations to a minimum.

'COVID-19' is only used once. Please, change the "COVID-19" to "coronavirus disease 2019".

Authors’ Response:

As suggested, COVID-19" has now been changed to "coronavirus disease 2019" (see line 194).

Editor’s comment:

(3) The author states that "This study uses the fourth-generaion IGRA". I thick this assays is the QuantiFERON-TB Gold Plus. Please, mention the name of the assay and its manufacturer in an appropriate place.

Authors’ Response:

That is correct. The statement in question has been updated and now reads as follows,

“This study is using the QuantiFERON-TB Gold Plus (QFT-Plus) interferon-gamma release assay (IGRA) (QIAGEN),....” (see lines 93-94).

Editor’s comment:

(4) Please, check any minor errors. PLOS ONE does not copyedit accepted manuscripts.

Authors’ Response:

This has been done.

Attachment

Submitted filename: Responses to Reviewers.docx

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Decision Letter 3

Jinsoo Min

24 Oct 2022

Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study Protocol

PONE-D-22-13477R3

Dear Dr. Shamputa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Jinsoo Min

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix. Informed consent form in multiple languages.

    (PDF)

    Click here for additional data file. (6.3MB, pdf)
    S2 Appendix. Participant surveys multiple languages.

    (PDF)

    Click here for additional data file. (338.6KB, pdf)
    S3 Appendix. LTBI indicator form.

    (PDF)

    Click here for additional data file. (69.4KB, pdf)
    S4 Appendix. Health care practitioner survey.

    (PDF)

    Click here for additional data file. (98KB, pdf)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (53.1KB, docx)
    Attachment

    Submitted filename: Response to Reviewers comments.docx

    Click here for additional data file. (13.6KB, docx)
    Attachment

    Submitted filename: Responses to Reviewers.docx

    Click here for additional data file. (13.7KB, docx)

    Data Availability Statement

    No datasets were generated or analyzed during the current study. All relevant deidentified data will be made publicly available when the study is completed and published.

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