Peer Review History

Original SubmissionOctober 15, 2025
Decision Letter - Joshua Nosanchuk, Editor

In VitroResponse to ReviewersRevised Manuscript with Track ChangesManuscript

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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Reviewers' comments:

Key Review Criteria Required for Acceptance?

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Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

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Reviewer #1: (No Response)

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Results

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Reviewer #1: (No Response)

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Conclusions

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Reviewer #1: (No Response)

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Editorial and Data Presentation Modifications?

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Reviewer #1: (No Response)

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Summary and General Comments

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Reviewer #1: 1.The text states: "Conversely, AmB is a large molecule that has variable penetration in the lungs, liver, kidneys, and a poor penetration in the brain and CSF (30,31). The disruption of pyrimidine biosynthesis by 5FC leads to structural defects in the fungal cell wall, facilitating membrane and tissue penetration of AmB and potentiating the fungicidal effect of AmB (29)."(Line 323-327)

The current phrasing, particularly the use of "Conversely... facilitating... tissue penetration of AmB", could be misinterpreted. The reason is:

The "tissue penetration of AmB" (e.g., in lungs, brain) is a pharmacokinetic concept, describing the drug's distribution in human organs and across barriers like the blood-brain barrier.

The "disruption of the fungal cell wall by 5FC" is a pharmacodynamic concept, describing the drug's effect on the pathogen's microstructure.

Linking them in this way might incorrectly suggest that the damage to the fungal cell wallby 5FC enhances the penetration of AmB through human tissues.

2.The paper notes that all four isolates showing full synergy were from northern Vietnam, raising the question of clade-specific treatment effects. Could the authors please discuss or speculate on the potential molecular mechanisms that might underlie this interesting observation? Furthermore, have similar geographically or phylogenetically clade-specific synergistic effects of antimicrobial combinations been reported in other important fungi, such as Candidaor Cryptococcusspecies?

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Reviewer #1: No

Figure resubmission:

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Revision 1

Attachments
Attachment
Submitted filename: Response to Reviewers_AmB-5FC_talaromycosis.docx
Decision Letter - Joshua Nosanchuk, Editor

Dear Dr Natesan Sambath,

We are pleased to inform you that your manuscript 'In Vitro Evidence to Support Amphotericin B and Flucytosine Combination Therapy for Talaromycosis' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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Formally Accepted
Acceptance Letter - Joshua Nosanchuk, Editor

Dear Dr Natesan Sambath,

We are delighted to inform you that your manuscript, "In Vitro Evidence to Support Amphotericin B and Flucytosine Combination Therapy for Talaromycosis," has been formally accepted for publication in PLOS Neglected Tropical Diseases.

We have now passed your article onto the PLOS Production Department who will complete the rest of the publication process. All authors will receive a confirmation email upon publication.

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Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

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