PONE-D-19-21374

Aspartate aminotransferase-to-platelet ratio index (APRI): a potential marker for diagnosis in patients at risk of severe malaria caused by Plasmodium vivax

PLOS ONE

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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: No

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

Reviewer #1: Yes

Reviewer #2: No

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

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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: No

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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: The goal of the present study was to describe the clinical and laboratory characteristics of patients with acute P. vivax infection and evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a method of identifying patients with severe disease.

Some points to be clarified:

1. What is "potentially severe disease", used several times across the manuscript. Please change to "severe disease" or "severe malaria".

2. In Introduction: "In contrast, monocyte and neutrophil counts are significantly higher in infected individuals compared to those not infected with Plasmodium [13, 14]." If I understood correctly, this sentence is related to malaria infection rather than severe malaria. Delete it.

3. What do the authors refer to as noninvasive? Techniques involving biological samples from venous puncture are not invasive? I do no agree. Change across the manuscript.

4. Methods:

"Patients with other concomitant infections, such as hepatitis B, hepatitis C, dengue, HIV, or bacterial infection, were excluded from this analysis." Were they systematically tested? Clarify.

5. "Treatment for all patients was provided in compliance with the recommendations of the Ministry of Health for the treatment of P. vivax infections [24]." Were all blood samples collected before treatment began? Clarify.

6. What is "microscopy optics"?

7. Discussion:

"Drug resistance, genomic alterations in the parasite, and changes in the host inflammatory response may have contributed to this clinical phenomenon [40]."

Genomic alterations? Change to parasite genotype selection or similar.

Reviewer #2: Aspartate aminotransferase-to-platelet ratio index (APRI): a potential marker for diagnosis in patients at risk of severe malaria caused by Plasmodium vivax

Thank you for giving me an opportunity to review this paper. I have read this manuscript with keen interest. The authors have attempted a study with two objectives; i) to describe the clinical and laboratory characteristics of patients with P. vivax infection, and ii) to evaluate the APRI as a method of identifying patients with potentially severe disease.

This is an interesting research area in the light of malaria pre-/elimination context. However, I feel that the manuscript needs substantial improvement on an array of areas.

The followings are not exhaustive, only some examples to improve the quality of presentation.

Abstract

Please, update the abstract based on the comments given below.

Line# 29…It should be better to describe as ‘the objectives’, rather than the goal.

Line #32…. I feel, this is a retrospective cohort analysis of the clinical-epidemiological data. The study data were obtained from the medical records.

Line # 38.. Please, clarify whether these are 130 patients or 130 patient’s records.

Line # 40….. It should read as ‘severe vivax malaria’.

Line # 44,45,47….. I feel, there is some exaggerations in interpretations.

The ROC value was 0.645 (0.494; 0.795), specificity was 56.0% and accuracy was 65.0%.

Line # 47…….The authors have concluded that “This simple index can serve as a diagnostic biomarker………”……….The authors need to revise the interpretation and conclusion.

TEXT

A substantial improvement in English language/grammar/ punctuation are required throughout the manuscript.

Overall, the current version of manuscript is not well written.

Background

This section is not well written. Also, it is not in sequential order. There is redundant information.

The study objectives were not well described. I feel, there are two objectives. Please, explicitly describe the objectives.

Methods

Overall, this section is not well presented.

I feel, this is a retrospective cohort analysis of the patient’s records. (Plese, see my comments to the abstract).

The authors need to improve this section. It will be better to follow the STROBE checklist.

Line# 159.. The authors assessed whether there is normal distribution of the continuous data. This is an appreciable effort.

Line # 160-61 The authors stated that they used a non-parametric Mann-Whitney test.

In Table 1 (Foot note)……. The results came out from the Fisher’s exact test/Chi-squared test for linear trend. Please, clarify.

Results

Overall, this section is not well presented.

Table 1… Title is too long.

Table 1.. Only two parameters (Platelets and APRI ) are significantly different between the two groups.

Severe TCP ( n=1), APRI > 1,5 (n = 9)

I feel, the authors can provide a correlation between these two parameters.

Line # 200……… The average APRI value was 1.24. In Table 1, it was 1.2.

Two decimal or 1 decimal?

The authors stated, “An APRI cut-off of 0.74 was reasonably sensitive and specific for identification of patients with a higher potential for severe disease”.

Please, consider that a chance of getting false positive is considerable (specificity 56%, accuracy 65%).

Line # 268-269. For this reason, it is hypothesized that the APRI is …..;; by Plasmodium [23]. This supporting information is valuable, and it will be much better to describe under “Background”.

Line # 318.. A cut-off point of 0.74 for the APRI value has good sensitivity and specificity to identify …………. I feel, an exaggeration in interpretation as 74% is not representing the specificity. please, rephrase this sentence. [Also, see my comments to the Abstract].

Thank you

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Reviewer #1: No

Reviewer #2: No

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Aspartate aminotransferase-to-platelet ratio index (APRI): a potential marker for diagnosis in patients at risk of severe malaria caused by Plasmodium vivax

PONE-D-19-21374R1

Dear Dr. Fontes,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Leonardo Jose de Moura Carvalho

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

Reviewer #2: 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

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

Reviewer #2: Yes

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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

Reviewer #2: 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: I accept as it is in this version of the manuscript "Aspartate aminotransferase-to-platelet ratio index (APRI): a potential marker for diagnosis in patients at risk of severe malaria caused by Plasmodium vivax" (PONE-D-19-21374R1). All the queries were properly responded.

Reviewer #2: The authors have fully addressed almost all comments.

For a better flow, it still need to polish English language throughout the text.

Thank you

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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

Reviewer #2: Yes: Professor Cho Naing