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PONE-D-21-40474Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of CongoPLOS ONE

Dear Dr. ZONO,

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Although well conducted, the study requires further experiments; in particular the Authors should evaluate the susceptibility of strains to antifungal agents. Furthermore, the manuscript requires a strong revisions concerning English Language and an update of the bibliography.

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PLOS ONE

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4. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. 

( It is noteworthy that comparative data between PLHIV with Cryptococcus neoformans versus Cryptococcus curvatus/ C. laurentii meningitis are presented in another published paper (https://doi.org/10.1186/s12879-021-06849-3). Although carried out in the same study population by the same research team, the data are presented separately without any interference)

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 #1: Yes

Reviewer #2: Yes

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4. 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 #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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

Reviewer #1: This is a well written manuscript that addresses a pathogen that continues to cause high morbidity and mortality among PLHIV with advanced disease. What i see missing are implication of this work programmatically. Nonetheless, this is a well written review

Reviewer #2: The manuscript by Zono Bive et al. deals with the genetic diversity of Cryptococcus strains isolated in the Democratic Republic of Congo. They use ITS sequencing, MALDI-TOF and MLST. The article is well conducted despite a limited number of strains. The structure of the article is logical and well built. However, the English language could be proofread. An evaluation of the susceptibility of the tested strains is also missing.

Concerning the remarks, they are essentially general:

- The new nomenclature of Cryptococcus laurentii and Cryptococcus curvatus (i.e. Cutaneotrichospora and Papiliotrema) should be used (Liu 2015, Sujita 2017)

- The epidemiological data used (Park 2009) are obsolete. Those published by Rajasingham in 2017 (ref. 1) should be cited

- p 6. The 194 correct 55.8

- Tables should be reformatted according to journal standards

- Regarding Table 2, the MALDI-TOF scores should be specified to know the reliability of the identifications. This could explain the wrong identification of Papiliotrema.Percentages are not really useful in this table.

- Figure 1 is not appropriate. It is necessary to generate a Minimum Spanning Tree and to place the STs in a global environment allowing to determine CCs.

- There is a serious lack of data on the susceptibility of strains to major antifungal drugs. This would strengthen this study and strongly support the Discussion.

- In the Discussion section (p10. L 266-268): the references are too old (ref. 18) and the choice of countries is not relevant. There are very good studies on cryptococcosis in Africa and they deserve to be added to your Discussion.For example, there are studies in Cameroon, Côte d'Ivoire or Kenya (Loyse 2019, Kassi 2019, Gitonga 2019).

- P10. L 268-272: ST can also explain your hypothesis.

- p11. L 300-302: C. laurentii has long been known to cause infections in humans (Kamalam 1976, Lynch 1981).

- P 11. L 313-314: Here again, it is imperative to compare the data with those published in other African countries (e.g. ST 5 and 93 are present in Ivory Coast).

-P 11. L317-322: please cite references

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-2140474 Reviewer comments.docx

Attachment

Submitted filename: PONE-D-21-40474.pdf

Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of Congo

PONE-D-21-40474R1

Dear Dr. ZONO,

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.

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Kind regards,

Adriana Calderaro

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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

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

Reviewer #1: Yes

**********

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

Reviewer #1: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 #1: 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 #1: Yes

**********

6. Review Comments to the Author

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

Reviewer #1: Excellent responses to the review comments. The paper reads well with a good description of the context, the impact of cryptococcosis and implications for clinical care clearly laid out.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No