Review Reports - Point-of-Care Testing for Sexually Transmitted Infections: Is the Future Here Yet?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript entitled “Point of care testing for Sexually Transmitted Infections....is the future here yet?” is a clear and well-written opinion article addressing an important topic in the field of sexually transmitted infections. The article provides a useful overview of the current landscape of point-of-care and near-point-of-care testing for STIs, with appropriate attention to diagnostic performance, regulatory status, implementation barriers, at-home testing and future needs.

Comments

The authors should clarify the article type and methodology. Although the manuscript is submitted as a review/opinion article, it reads largely as a narrative review and includes a Methods section with database and literature searches. The authors should clarify whether the article is intended as an opinion piece, narrative review, or hybrid article, and adjust the wording accordingly.

The authors describe searches in regulatory databases and published literature, it would be useful to add a little more detail on the search period, date of last search, and criteria used to select tests included in the tables. A formal systematic review is not required, but some additional transparency would strengthen the manuscript.

The manuscript refers to searching the EMA database for CE-marked tests. This should be revised or clarified, because CE marking in vitro diagnostic devices is not regulated through the EMA in the same way as medicines. The authors should refer more generally to CE marking under the EU IVDR framework or appropriate European regulatory sources.

The section on at-home STI testing is useful, but the authors should carefully verify the dates and regulatory status of recently authorized products. For example, the Teal Health HPV self-collection device appears to have received FDA authorization in 2025 rather than 2024. Ensuring that all dates and approvals are accurate is important for the rapidly evolving nature of the field.

Tables 1 and 2 are helpful for readers. However, some entries use broad or approximate performance ranges. The authors should ensure that these ranges are consistently referenced.

The manuscript appropriately notes that many current POC platforms are mainly validated for vaginal swabs, which limits their usefulness for MSM and for comprehensive STI screening. This is a point that could be emphasized slightly more, especially in relation to rectal and pharyngeal CT/NG testing.

The manuscript is generally well written, but some minor editing would improve readability. For example, the title could be made more formal by removing the ellipsis, and some table headings appear split or awkwardly formatted.

Author Response

Reply: Thanks for helping us with clarity. We clarified the article type in the Methods section by describing the manuscript as “a narrative review with perspective elements” and by stating that the goal was to summarize representative tests, regulatory status, implementation barriers, and diagnostic gaps rather than to conduct a formal systematic review or meta-analysis. We felt it was important to retain a Methods section because the review discusses specific diagnostic products, regulatory status, and performance characteristics, and readers should understand how those products and sources were identified.

Reply: Thank you for this suggestion. We expanded the Methods section to provide additional transparency regarding source selection and table inclusion. The revised Methods now specifies the regulatory and literature sources searched, including FDA databases, European regulatory and manufacturer sources for CE-marked in vitro diagnostic devices under the EU IVDR framework, TGA, NMPA, WHO prequalification sources, PubMed, Google Scholar, manufacturer specifications, package inserts, and published validation studies. We also clarified that no formal publication-date restriction was applied, that searches were updated during revision, and that recent systematic reviews, meta-analyses, and large validation studies were prioritized while older seminal studies were retained when they established current testing paradigms. These changes are reflected in the Methods section, lines 106–138.

Reply: Thank you for pointing this out. We agree that the original EMA wording was imprecise. We revised the Methods section to remove the implication that CE marking for in vitro diagnostic devices is regulated through the EMA. The revised text now refers to “publicly available European regulatory and manufacturer sources for CE-marked in vitro diagnostic devices under the European Union In Vitro Diagnostic Regulation framework.” We also revised the inclusion criteria to refer to regulatory approval or documented commercial availability through CE marking, TGA, or NMPA rather than EMA approval.

Reply: Thank you for this important correction. We reviewed and revised the at-home testing section to clarify the distinction between fully at-home testing and home-collection models. We corrected the Teal Health wording to state that the Teal Health Wand received FDA De Novo classification in 2025 as a prescription home-collection device that allows users to self-collect and transport vaginal specimens for laboratory-based HPV molecular testing, rather than performing HPV analysis at home. We also retained the March 2025 FDA authorization language for the Visby Medical Women’s Sexual Health Test as a fully at-home CT/NG/TV test.

Tables 1 and 2 are helpful for readers. However, some entries use broad or approximate performance ranges. The authors should ensure that these ranges are consistently referenced.

Reply: Thank you for this suggestion. We revised Table 1 so that citations are listed directly next to the test names, allowing the reader to identify the primary sources supporting each row’s performance and regulatory information. We also revised the Table 1 legend to state that performance ranges are approximate, vary by specimen type and study, and were extracted from manufacturer package inserts, regulatory summaries, and/or published validation studies when available. These changes appear in Table 1 and its legend. In Table 2, we expanded the legend to clarify that REASSURED ratings were qualitative author assessments based on published validation studies, manufacturer package inserts or instructions for use, regulatory summaries, WHO prequalification information where applicable, and reported implementation characteristics.

Reply: Thank you for this comment. We expanded the discussion of specimen-type limitations, particularly for MSM and other patients requiring extragenital CT/NG screening. The revised Discussion now emphasizes that many POC platforms remain limited to vaginal swabs or urine and lack approval for rectal and pharyngeal specimens, while noting GeneXpert’s broader specimen validation as an important advantage. We also clarify that self-collection does not fully solve the need for POC platforms validated across rectal and pharyngeal specimens.

Reply: Thank you. We revised the title to remove the ellipsis and make it more formal. The revised title is: “Point-of-Care Testing for Sexually Transmitted Infections: Is the Future Here Yet?” We also reviewed the tables for formatting and readability.

Reviewer 2 Report

Comments and Suggestions for Authors

Peer Review: Venereology 2026

Title: Point of care testing for Sexually Transmitted Infections....is the future here yet?

Journal: Venereology (MDPI)

Review type: Full manuscript review

Overall Impression

This is a well-structured and clinically relevant narrative review addressing an important and timely topic. The authors have done a commendable job synthesizing a broad landscape of POC diagnostics across multiple pathogens into a readable, practical framework. The inclusion of Table 1 (performance characteristics) and Table 2 (REASSURED criteria ratings) adds real value and will be useful for clinicians and policymakers alike. That said, several areas require attention before the manuscript is ready for publication.

Major Comments

1. Scope and Inclusion Criteria: Needs Clarification

The Methods section states that tests were included if they met at least one of four criteria (FDA approval, CE/TGA/NMPA marking, WHO PQ, or peer-reviewed validation). However, several tests discussed in the text, particularly EasyNAT, appear to meet only the last criterion, and their commercial availability is not clearly established. The authors should explicitly state whether commercial availability was a mandatory criterion or merely desirable, and apply this consistently across all platforms discussed.

2. Mycoplasma genitalium: Conspicuous Absence

Mycoplasma genitalium is mentioned once in the Future Directions section as a candidate for multiplex panels, but receives no dedicated discussion despite being an increasingly recognized STI pathogen with rising antimicrobial resistance. Given that several POC-adjacent platforms (e.g., Aptima MG) exist, even a brief critical assessment of the current diagnostic gap would strengthen the review considerably.

3. REASSURED Table (Table 2): Methodological Transparency

The authors acknowledge that ratings in Table 2 are "qualitative author assessments." While this is honest, the table would benefit from a brief supplementary note or legend column indicating which specific published sources or package insert data informed each rating. Without this, readers cannot distinguish evidence-based assessments from author opinion, a distinction that matters for a regulatory-adjacent discussion.

4. At-Home Testing Section: Equity Framing is Underdeveloped

The discussion appropriately flags the $150 per-test cost of the Visby at-home device as a barrier, but the equity analysis stops there. The authors do not discuss insurance reimbursement pathways, Medicaid/Medicare coverage status, or whether any manufacturer assistance programs exist. For a journal with an international readership, a brief comparison with at-home testing costs in LMICs would also be valuable.

5. Loss to Follow-Up Data: Citation Gap

The claim that "20-40% of patients with positive STI results never return for treatment" is central to the paper's argument for POC testing, yet it rests on just two references (refs 7 and 8), both from 2011-2013. More recent data, particularly post-COVID, when telehealth and digital notification systems have changed follow-up dynamics, should be cited or at minimum acknowledged as a potential confounder.

Minor Comments

6. Title Punctuation

The title contains "....is" (four dots). This should be either an em dash or an ellipsis (three dots: "...is"). As written, it appears as a typographic error.

7. Abstract: Passive Voice Overuse

Several sentences in the abstract read as overly passive and could be tightened. For example: "Several nucleic acid amplification test (NAAT)-based platforms demonstrate excellent sensitivity and specificity" is fine, but the following two sentences lose energy quickly. A light revision would improve readability.

8. Specimen Type Limitations: Repetition

The limitation regarding vaginal-swab-only approval for most POC platforms is mentioned in at least three separate locations (NAAT section, Discussion paragraph 1, At-Home Testing section). This could be consolidated without losing impact.

9. Reference 41: Numbering Gap

In the text, references are cited as [38,41] with no [39] or [40] cited in between in that sentence. Please verify the in-text citation sequence is correct and no reference has been omitted or misassigned.

10. GeneXpert HIV-1 Viral Load: Classification

The GeneXpert HIV-1 Viral Load assay is described as a "near-POC option" in the text but does not appear in Table 1. Either include it in the table for completeness or add a parenthetical note explaining its exclusion.

Strengths Worth Highlighting

The REASSURED framework is applied thoughtfully and not just invoked superficially. The distinction between "rapid," "near-POC," and "true POC" is clearly drawn and maintained throughout, which is one of the manuscript's strongest features. The regulatory section on WHO prequalification vs. FDA approval is unusually informative for a review of this type. The mathematical modeling reference (ref 10) is well-placed and adds quantitative grounding to an otherwise descriptive narrative.

Recommendation

Minor-to-moderate revision required.

The manuscript addresses a relevant clinical question with appropriate breadth and good writing quality. With targeted revisions, particularly around Mycoplasma genitalium, REASSURED table transparency, and updated loss-to-follow-up data, this will be a strong contribution to the field.

Author Response

Scope and Inclusion Criteria: Needs Clarification

Reply: Thank you for this important clarification. We revised the Methods section to state more explicitly how tests were selected for inclusion in the main tables. The revised inclusion criteria now specify that peer-reviewed validation was used for inclusion only when accompanied by clear commercial or regional availability. We also added exclusion criteria stating that tests were excluded from the main tables if they were investigational only, lacked clinical validation in human specimens, were designed exclusively for centralized laboratory workflows without plausible point-of-care or near-patient use, or lacked verifiable regulatory status or commercial availability. For platforms such as EasyNAT, we retained discussion because of its regional availability and relevance to portability in resource-limited settings, while clearly noting that it is not FDA-approved.

Mycoplasma genitalium: Conspicuous Absence

Reply: Thank you for raising this important point. We agree that Mycoplasma genitalium can be an important STI pathogen and that antimicrobial resistance creates a diagnostic and therapeutic challenge. We revised the Future Directions section to explicitly identify M. genitalium as a target that future multiplex STI panels should include, particularly in the context of antimicrobial resistance detection and clinically actionable testing. We also emphasize in that section that future platforms should preserve clinical actionability and affordability rather than simply expanding the number of detectable pathogens.

REASSURED Table (Table 2): Methodological Transparency

Reply: Thank you for pointing this out. We revised the Table 2 legend to make the basis for the REASSURED ratings more transparent. The revised legend now states that the ratings are qualitative author assessments based on published validation studies, manufacturer package inserts or instructions for use, regulatory summaries, WHO prequalification information where applicable, and reported implementation characteristics. We also clarify that the ratings are intended as a heuristic comparison rather than a formal scoring system.

At-Home Testing Section: Equity Framing is Underdeveloped

Reply: Thank you for this important comment. We expanded the at-home testing section to include a broader equity discussion. The revised text now discusses high out-of-pocket costs, variable insurance reimbursement, digital literacy requirements, smartphone access, mailing logistics, uncertain linkage to treatment, and the possibility that at-home testing could widen disparities if it remains primarily self-pay. We also added international context by noting that, in low- and middle-income settings, affordability, supply chains, and linkage to treatment may be even more important determinants of public health impact than analytic performance alone.

Loss to Follow-Up Data: Citation Gap

Reply: Thank you for this helpful point. We revised the Introduction to replace the older 2011–2013 references and the previously cited 20%-40% estimate with more recent U.S. data. The revised text now states that approximately 25%-30% of patients with positive STI results have no documented treatment within 30 days. These updated references include contemporary data collected through 2022, thereby better accounting for changes in follow-up practices associated with telehealth, electronic results portals, and digital notification systems. We also clarified that delayed results may create missed opportunities for same-visit treatment, targeted counseling, partner notification, and interruption of transmission.

Minor Comments

Title Punctuation

The title contains "....is" (four dots). This should be either an em dash or an ellipsis (three dots: "...is"). As written, it appears as a typographic error.

Reply: Thank you. We revised the title to remove the four-dot ellipsis and improve formality. The revised title is: “Point-of-Care Testing for Sexually Transmitted Infections: Is the Future Here Yet?”

Abstract: Passive Voice Overuse

Reply: Thank you. We revised the abstract to improve readability and make the language more direct. For example, we changed the NAAT sentence to state that “Several nucleic acid amplification test (NAAT)-based platforms now provide rapid, excellent sensitivity and specificity for common bacterial and protozoal STIs.” We also reviewed the remaining abstract for flow and readability.

Specimen Type Limitations: Repetition

Reply: Thank you for identifying this repetition. We revised the manuscript to consolidate the discussion of specimen-type limitations primarily within the Discussion section, where we address the issue in relation to test performance, MSM screening, and rectal/pharyngeal CT/NG testing. The revised discussion emphasizes the clinical importance of extragenital specimen validation while reducing repeated mentions across multiple sections.

Reference 41: Numbering Gap

Reply: Thank you for catching this. We reviewed and corrected the citation sequence in the viral STI section. The revised text now cites HIV POC testing sources sequentially as [38,39] and then cites GeneXpert HIV-1 Viral Load sources as [40,41].

GeneXpert HIV-1 Viral Load: Classification

Reply: Thank you for this helpful clarification. We added a note to the Table 1 legend explaining why GeneXpert HIV-1 Viral Load was not included in Table 1. Although the assay shows promise as a near-POC option, Table 1 focuses on diagnostic testing for STI pathogen detection rather than HIV disease monitoring.

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for your submission and contribution to the literature. This is a very important topic.

The manuscript is clearly written, and you have adequately made the case for why this review is necessary. Please see my comments below.

Could you elaborate on the inclusion and exclusion criteria for the publications in your study?

Does your subheading "Point-of-Care Tests: Current Landscape" indicate the beginning of your results? Also, maybe include how many studies were ultimately included and how many additional sources were included.

You have done a great job at identifying the critical gaps. Could you elaborate more on future directions, and maybe comment on some of the steps necessary or that could be taken to bring us closer to the reality of POC testing?

Author Response

Could you elaborate on the inclusion and exclusion criteria for the publications in your study?

Reply: Thank you for this suggestion. We expanded the Methods section to clarify both inclusion and exclusion criteria. The revised text now states that tests were included if they met at least one of the following criteria: FDA clearance, approval, authorization, or CLIA waiver; regulatory approval or documented commercial availability through CE marking, TGA, or NMPA; WHO prequalification; or peer-reviewed clinical validation with clear commercial or regional availability. We also added exclusion criteria for tests that were investigational only, lacked clinical validation in human specimens, were designed exclusively for centralized laboratory workflows without plausible point-of-care or near-patient use, or lacked verifiable regulatory status or commercial availability.

Reply: Thank you for this comment. We revised the manuscript structure to clarify that the “Current Landscape” section functions as the narrative synthesis/results portion of the review rather than a formal systematic-review results section. The heading was revised to “Current Landscape of Point-of-Care and Near-Point-of-Care STI Testing,” and the opening paragraph now states that we highlight representative and topical tests rather than cataloging every available assay or presenting formal systematic-review results. Because this is a narrative review rather than a systematic review, we did not report a formal count of included studies or perform a PRISMA-style source accounting.

Reply: Thank you for this encouraging comment. We expanded the Critical Gaps and Future Directions section to more clearly identify practical steps needed to move the field closer to true POC STI testing. The revised section now emphasizes antimicrobial resistance detection for Neisseria gonorrhoeae, broader multiplex testing, expanded rectal and pharyngeal specimen validation, real-time connectivity with electronic health records and public health reporting, development of instrument-free NAAT approaches, and the need for implementation science addressing clinician adoption, reimbursement pathways, treatment access, and workflow integration.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have responded constructively to the first round of review, and the manuscript is improved. The Methods now state inclusion and exclusion criteria explicitly, the loss-to-follow-up estimate has been updated with contemporary data, the Table 2 legend is more transparent, the equity discussion of at-home testing is substantially broader, and the title has been corrected. The new subsection on WHO prequalification versus national regulatory approval is a genuine addition that distinguishes this review from earlier surveys of the field. My remaining comments are largely matters of citation accuracy and text cleanup rather than requests for new analysis.

Points from the first round that are now resolved

Title punctuation, the Table 1 note explaining exclusion of the GeneXpert HIV-1 Viral Load assay, and the citation sequence around references 38 to 41 are all addressed.
The inclusion and exclusion criteria are now stated clearly, and the treatment of EasyNAT as a regionally available but non-FDA-approved platform is consistent with those criteria.
Replacing the 2011 and 2013 sources with the American Family Cohort analysis and the Virginia clinic data is an improvement, and rephrasing the endpoint as no documented treatment within 30 days is more defensible than the previous wording. One caveat is worth a clause in the text: the newer source draws on a primary care electronic health record registry, so treatment delivered in STI clinics, emergency departments, or through expedited partner therapy may not be captured, which could inflate the apparent untreated proportion. Note also that only one of the two cited sources extends past 2019, so the response letter's claim that both reflect the post-telehealth period is stronger than the references support.

Points requiring attention before acceptance

Abstract and Methods now contradict each other. The Methods no longer claim that a European Medicines Agency database was searched, and correctly refer instead to CE marking under the In Vitro Diagnostic Regulation framework (lines 109 to 113). The Abstract still states that tests were identified through governmental databases including the EMA (lines 16 to 18). The EMA does not regulate in vitro diagnostics, so the Abstract as written is inaccurate. Please align the Abstract with the revised Methods, and consider mentioning the TGA and NMPA searches there as well.
Performance data for the at-home Visby device are attributed to the wrong sources. The sensitivity figures reported for the Visby Medical Women's Sexual Health Test (lines 266 to 271) are supported by references 19 and 51. Reference 19 is the 2021 Lancet Infectious Diseases evaluation of the professional-use point-of-care device, not the over-the-counter device, and reference 51 is the manufacturer's website. Since the FDA published performance data at the time of the De Novo authorization, the appropriate citation is the FDA decision summary or classification order for the over-the-counter device. Please cite that instead, and state explicitly that the figures derive from the regulatory submission rather than from an independently published clinical trial. This single change would resolve most of my concern about industry-sourced evidence.
Reference 54 is misdated and the sentence contains a residual edit. The Teal Wand received FDA De Novo authorization on 9 May 2025, not in 2024. The reference is dated May 2024 and the sentence at lines 274 to 277 still carries a parenthetical "(2024)" alongside the corrected year. Please correct both. The revised description of the device as a home collection kit for vaginal self-sampling with laboratory-based HPV testing is otherwise accurate.
The stated search date conflicts with the reference list. The Methods state that searches were updated through May 2025 (lines 135 to 136), yet the reference list includes items dated November 2025, January 2026, and a website accessed in February 2026. Please update the search date to reflect when the literature was last examined.
Table 1 cites the wrong reference for the HSV-2 UniGold row. Reference 42 is a national prevalence data brief, not an evaluation of the UniGold assay. Reference 43 is the point-of-care serologic assay evaluation and appears to be the intended source.
The WHO prequalification claim should be phrased more precisely. WHO prequalified the Determine Antenatal Care Panel on 10 July 2025 as a bundled set of three rapid diagnostic tests performed on a single finger-stick sample, rather than as a single multiplexed device. Rewording to reflect the bundled format would be more accurate and would also clarify why it is described as a panel.
Mycoplasma genitalium remains thinly covered. The addition to Future Directions and reference 74 partially address the first-round comment, but the manuscript still offers no assessment of the current diagnostic landscape for this organism. Given that the review already discusses ResistancePlus GC for ciprofloxacin resistance, two or three sentences on the parallel macrolide resistance assay for M. genitalium and on why resistance-guided therapy makes this a distinctive point-of-care use case would close the gap with minimal added length.
Table 2 transparency. The revised legend is an improvement and the framing as a heuristic rather than a formal score is appropriate. If the journal permits, a supplementary table mapping each rating to its supporting source would still add value, though I do not regard this as a condition of acceptance.
Consider adding the first authorized at-home syphilis test. The at-home testing section covers CT, NG, TV, and HPV self-collection but does not mention that a lateral flow syphilis test received FDA De Novo authorization for over-the-counter use in 2024. Given the review's emphasis on syphilis and antenatal screening, this is a notable omission. Please verify the regulatory details before citing.
Residual editing artifacts. Several sentences did not survive the revision cleanly and should be checked in the clean copy:

Abstract, lines 19 to 21: platforms that "now provide rapid, excellent sensitivity and specificity" does not parse. Suggest wording such as: now deliver results rapidly with excellent sensitivity and specificity.
Discussion, lines 319 to 321: the sentence about vaginal swabs contains overlapping fragments of the old and new text.
Discussion, lines 326 to 329: the self-collection sentence contains a doubled comma, a duplicated citation to reference 62, and two competing clause endings.
Table 2 legend, lines 255 to 258: ends with a stray conjunction before the following sentence.
Critical Gaps, lines 367 to 389: the enumeration should be verified in the clean copy, since the tracked version shows duplicated ordinals.
Keywords use "Point of Care testing" while the revised title uses the hyphenated form.

Specimen-type repetition. Consolidation has helped, but the vaginal-swab-only limitation still appears in the NAAT section, the Discussion, and the at-home testing section. One further trim in the NAAT section would suffice.
Reference list check. Please confirm in the clean copy that the Minichiello scoping review appears only once and that all in-text citations map to the renumbered list, since the tracked version shows this entry in two positions.

Author Response

Abstract and Methods now contradict each other. The Methods no longer claim that a European Medicines Agency database was searched, and correctly refer instead to CE marking under the In Vitro Diagnostic Regulation framework (lines 109 to 113). The Abstract still states that tests were identified through governmental databases including the EMA (lines 16 to 18). The EMA does not regulate in vitro diagnostics, so the Abstract as written is inaccurate. Please align the Abstract with the revised Methods, and consider mentioning the TGA and NMPA searches there as well.

Reply: We thank the editor for identifying this inconsistency. We revised the Abstract to remove the reference to an EMA database and aligned the wording with the revised Methods. The Abstract now refers to FDA, WHO prequalification, TGA, NMPA, publicly available European regulatory/manufacturer sources for CE-marked IVDs under the EU IVDR framework, and published literature.

Performance data for the at-home Visby device are attributed to the wrong sources. The sensitivity figures reported for the Visby Medical Women's Sexual Health Test (lines 266 to 271) are supported by references 19 and 51. Reference 19 is the 2021 Lancet Infectious Diseases evaluation of the professional-use point-of-care device, not the over-the-counter device, and reference 51 is the manufacturer's website. Since the FDA published performance data at the time of the De Novo authorization, the appropriate citation is the FDA decision summary or classification order for the over-the-counter device. Please cite that instead, and state explicitly that the figures derive from the regulatory submission rather than from an independently published clinical trial. This single change would resolve most of my concern about industry-sourced evidence.

Reply: We revised the at-home Visby section so that performance values for the over-the-counter Visby Medical Women’s Sexual Health Test are attributed to the FDA De Novo decision summary rather than to the 2021 professional-use device study or manufacturer website. We also clarified in the text that these values derive from the FDA regulatory submission rather than from an independently published clinical trial.

Reference 54 is misdated and the sentence contains a residual edit. The Teal Wand received FDA De Novo authorization on 9 May 2025, not in 2024. The reference is dated May 2024 and the sentence at lines 274 to 277 still carries a parenthetical "(2024)" alongside the corrected year. Please correct both. The revised description of the device as a home collection kit for vaginal self-sampling with laboratory-based HPV testing is otherwise accurate.

Reply: We corrected the Teal Wand reference to a decision date of May 9, 2025, and confirmed that the manuscript describes the device as a prescription home-collection/self-sampling device for laboratory-based HPV molecular testing rather than an at-home HPV analysis test.

The stated search date conflicts with the reference list. The Methods state that searches were updated through May 2025 (lines 135 to 136), yet the reference list includes items dated November 2025, January 2026, and a website accessed in February 2026. Please update the search date to reflect when the literature was last examined.

Reply: We updated the Methods search date to reflect the final literature and regulatory source review.

Table 1 cites the wrong reference for the HSV-2 UniGold row. Reference 42 is a national prevalence data brief, not an evaluation of the UniGold assay. Reference 43 is the point-of-care serologic assay evaluation and appears to be the intended source.

Reply: We corrected the HSV-2 UniGold Table 1 citation from reference 42 to reference 43.

The WHO prequalification claim should be phrased more precisely. WHO prequalified the Determine Antenatal Care Panel on 10 July 2025 as a bundled set of three rapid diagnostic tests performed on a single finger-stick sample, rather than as a single multiplexed device. Rewording to reflect the bundled format would be more accurate and would also clarify why it is described as a panel.

Reply: We revised the WHO prequalification statement to clarify that the Determine Antenatal Care Panel is a bundled set of three rapid diagnostic tests performed from a single finger-stick sample, rather than a single multiplexed device.

Mycoplasma genitalium remains thinly covered. The addition to Future Directions and reference 74 partially address the first-round comment, but the manuscript still offers no assessment of the current diagnostic landscape for this organism. Given that the review already discusses ResistancePlus GC for ciprofloxacin resistance, two or three sentences on the parallel macrolide resistance assay for M. genitalium and on why resistance-guided therapy makes this a distinctive point-of-care use case would close the gap with minimal added length.

Reply: We expanded the Future Directions section with several sentences on M. genitalium as a distinctive POC use case. The revised text now notes that organism detection alone may be insufficient because resistance-guided therapy is increasingly important, that laboratory NAATs and macrolide-resistance assays such as ResistancePlus MG are available in some regions, and that future POC approaches should prioritize resistance-guided testing rather than simply adding organism detection to broad multiplex panels.

Table 2 transparency. The revised legend is an improvement and the framing as a heuristic rather than a formal score is appropriate. If the journal permits, a supplementary table mapping each rating to its supporting source would still add value, though I do not regard this as a condition of acceptance.

Reply: We appreciate this suggestion. Because the reviewer indicated that a supplementary source-mapping table is not required for acceptance, we retained the expanded Table 2 legend, which clarifies that ratings are heuristic qualitative assessments based on published validation studies, package inserts or instructions for use, regulatory summaries, WHO prequalification information where applicable, and reported implementation characteristics.

Consider adding the first authorized at-home syphilis test. The at-home testing section covers CT, NG, TV, and HPV self-collection but does not mention that a lateral flow syphilis test received FDA De Novo authorization for over-the-counter use in 2024. Given the review's emphasis on syphilis and antenatal screening, this is a notable omission. Please verify the regulatory details before citing.

Reply: We added the FDA-authorized First To Know Syphilis Test to the at-home testing section. The revised text identifies it as the first at-home, over-the-counter rapid antibody test for Treponema pallidum in finger-stick whole blood and clarifies that positive results require confirmatory laboratory testing.

Residual editing artifacts. Several sentences did not survive the revision cleanly and should be checked in the clean copy:

Abstract, lines 19 to 21: platforms that "now provide rapid, excellent sensitivity and specificity" does not parse. Suggest wording such as: now deliver results rapidly with excellent sensitivity and specificity.
Discussion, lines 319 to 321: the sentence about vaginal swabs contains overlapping fragments of the old and new text.
Discussion, lines 326 to 329: the self-collection sentence contains a doubled comma, a duplicated citation to reference 62, and two competing clause endings.
Table 2 legend, lines 255 to 258: ends with a stray conjunction before the following sentence.
Critical Gaps, lines 367 to 389: the enumeration should be verified in the clean copy, since the tracked version shows duplicated ordinals.
Keywords use "Point of Care testing" while the revised title uses the hyphenated form.

Reply: We reviewed the clean copy for residual editing artifacts and corrected the Abstract wording, specimen-type discussion, self-collection sentence, Table 2 legend, Critical Gaps enumeration, and keyword hyphenation.

Specimen-type repetition. Consolidation has helped, but the vaginal-swab-only limitation still appears in the NAAT section, the Discussion, and the at-home testing section. One further trim in the NAAT section would suffice.

Reply: We further reduced repetition by trimming the vaginal-swab-only limitation from the NAAT section and retaining the fuller discussion of specimen-type limitations in the Discussion, where it is addressed in relation to rectal and pharyngeal CT/NG testing.

Reference list check. Please confirm in the clean copy that the Minichiello scoping review appears only once and that all in-text citations map to the renumbered list, since the tracked version shows this entry in two positions.

Reply: We reviewed the reference list in the clean copy, confirmed that the Minichiello scoping review appears only once, and checked that in-text citations map to the renumbered reference list.