Uncovering a Rarely Diagnosed Disease: Severe Leptospirosis with Multiorgan Failure in Slovakia
Round 1
Reviewer 1 Report
I don't really have any major comments. The only minor issue is to add a little more information on the updated classification of Leptospira spirochaetes based on the recent work by Vincent et al. (2019).
I regret that the authors could not do the MAT test. Certainly, the results of this test would add more value to this report.
Author Response
Dear reviewer, thank you for your feedback and comments. We added the classification of leptospira according to Vincent et al. to our article.
Authors
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Please make the corrections at the attachment
Comments for author File: Comments.pdf
Minor editing of English
Author Response
Dear reviewer, thank you for your feedback and comments. We have added recommended information to the article. The patient agreed to publish the case, and we also have the approval of the hospital's ethics committee. Unfortunately, at the time of the patient hospitalization it was not possible to make statistics from the table, as it is only about the results of monitored laboratory parameters during hospitalization.
Authors
Author Response File: Author Response.pdf
Reviewer 3 Report
Dear Authors
The Case Report shows the potential to raise awareness about the re-emergence of neglected infections and challenges that can appear in their clinical management. Therefore, it shows the relevance and merits publication. However, the evaluation yielded concerns that necessitate thorough corrections. Please find below the detailed comments and suggestions.
Title, abstract, and keywords
The case report should link the two parts of the title.
- Line 15: The aforementioned is not necessary.
- Line 16: Male sex is also relevant information.
- Line 17: How long did the symptoms last before the hospitalization?
- Line 22: Describing the medical history features as indicative of leptospirosis needs additional caution because the suspicion appeared after the comprehensive microbiology screening reported the specific IgM. The lab results seem rather general, not suspective for the leptospirosis.
- Lines 23‒5: There is an ambiguity. The part „a 3rd generation of cephalosporin and“ was not necessary. How long did it take to achieve the clinical remission? After which time was the patient discharged?
- Slovakia is also relevant as a keyword.
Introduction
- Lines 50‒1: What is the percentage of the pathogenic variants?
- Line 54: Urine of rats or form additional vectors?
- Lines 54‒5: What are the most prominent regional differences in the leptospirosis epidemiology?
- Lines 65‒7: Please consider the efforts to avoid repetition.
- Lines 97‒102: What were the leptospirosis epidemiology features before 2020?
- The aim of the case report should be included.
Case report
- Did the patient sign the approval for the case presentation?
- Line 105: Please indicate the year.
- Lines 122‒6: Please rewrite the text to avoid the impression of being copied from the medical report.
- In Table 1, the term monitored is unnecessary before the Lab result. The reference range for every parameter would reinforce the interpretation. Besides the presented data, the comprehensive presentation of the lab workup should include the other routinely assessed hematological parameters. To enhance the follow-up, please split the table into one with the biochemistry and inflammation markers and one with the hematology and hemostasis tests. Units for enzymes should be U/L. The abbreviation GGT is more common than GMT and total instead of overall bilirubin. Please check the units for myoglobin and INR.
- Line 131: The term mineral breakdown is ambiguous.
- Line 145: The term danger of missing needs explanation.
- Line 148: Please include the details about symptomatic treatment.
- Line 150: There is no clinical significance between the platelet number on the 1st and the second day. The significant drop occurred on day 3.
- Line 152: Please include the details about the dosage regimen for the platelet concentrate. Additional information is also necessary for the hemostyptics.
- Figure 1: Using the arrows to highlight the most prominent radiological findings would be appreciated. For comparative purposes, please merge the figures and mark them as 1A at admission and 1B two weeks later.
- In Table 2, please indicate all methods used in the microbiology workup. The suggestion also refers to the autoantibody testing.
- Lines 182‒3: Please include the details about the symptomatic treatment.
- Lines 184‒6: Please rephrase to indicate that the differential workup included testing the serum sample for the presence of the mentioned autoantibodies pannel.
Discussion
- The first paragraph repeats the introductory info. Instead, it should summarize the main features of the presented case and their relevance. Additionally, the sine qua non for the acceptance is the comparison with the previous cases in Slovakia, mentioned in the Introduction. A comparison with the case reports in the surrounding European countries would be appreciated.
- Line 235: Please check the year.
- Line 238: Please provide additional details about lipoprotein-mediated activation of the toll-like receptors and support them with the relevant references.
- Lines 257‒9: Did you consider the iatrogenic causes of the worsening thrombocytopenia?
- Lines 265‒77: It is relevant to emphasize that the mentioned limitations did not negatively challenge the clinical management, notwithstanding their relevance for epidemiological purposes. In that context, please provide additional details about the specific information related to the type of PCR method. Are there referral institutions in Slovakia that offer that kind of confirmatory assay? Is there a possibility to send the samples?
Technical suggestions
- A thorough language editing would contribute to the overall quality of the Manuscript.
- The attention is necessary to use the italic font for the names in Latin.
- Line 78: The abbreviation MAT lacks explanation.
Comments are among the above text.
Author Response
Dear reviewer, thank you for your feedback and comments. We corrected and implemented everything suggested. As far as we know, at the time of the patient's hospitalization, a PCR test for leptospira DNA evidence was not available in Slovakia. We consider the underlying disease and its severe course rather than an iatrogenic cause to lead to thrombocytopenia.
Authors
Author Response File: Author Response.pdf
Reviewer 4 Report
Review of the paper entitled “Uncovering rarely diagnosed disease: Severe leptospirosis with multiorgan failure in Slovakia by Ondrej Zahornacky, Štefan Porubčin, Alena Rovňáková, Ján Fedačko and Pavol Jarčuška
In the present study the Authors describe the case of a 53-year-old patient without comorbidities who was admitted to an infectious disease center in the east of Slovakia for jaundice, general fatigue and weakness. Based on result of serological tests, epidemiological history and the clinical symptoms the patient was diagnosed with acute leptospirosis with acute renal failure and lung involvement. Antibiotic treatment was administered for 14 days. After 18 days of hospitalization, the patient was discharged in stable condition to outpatient care. This case report is interesting.
My comments
There is a sentence in the Abstract “The aforementioned case report describes the case of a 53-year-old patient without comorbidities who was admitted to an infectious disease center in the east of Slovakia for jaundice, general fatigue, weakness, and subfertility in home conditions” (lines 15,16,17). I think that the phrase “and subfertility in home conditions” needs to be improved because that's probably not what the Authors wanted.
The phrase “…with a 3rd generation of cephalosporin and ceftriaxone in monotherapy…” (line 24) needs also to be improved because ceftriaxone is a third-generation cephalosporin antibiotic.
“However, due to the negative result of the other serological tests (especially Mycoplasma pneumoniae and Chlamydia pneumoniae), we did not continue the treatment with clarithromycin” (lines 172,173,174). On which day of hospitalization clarithromycin was discontinued?
Table 1. In this Table there is a column of days of hospitalization (n): 1,2,3,4,5,6,7,8,18. There is no ninth, tenth, eleventh …. (and so on) day. Authors should state that they deliberately do not include all days and explain why. Authors could place such information under the Table (for example). .
There is a sentence in the Discussion “In the case of the patient from the case report, we already administered two transfusion units of platelets at the beginning of hospitalization (on the second day). We recorded the lowest platelet count on the third day of hospitalization (18x109/l)”. In my opinion this information should be in the section Case report.
Author Response
Dear reviewer, thank you for your feedback and comments. We have added recommended information to the article. Authors
Author Response File: Author Response.pdf
Round 2
Reviewer 3 Report
Dear Authors,
Your efforts to improve the Manuscript's overall quality and implement the suggestions from the previous reviews are evident and appreciated. Please consider the additional efforts to resolve the minor issues that are still present. The detailed comments and suggestions are as follows.
-Line 111: Overlooked seems more suitable than forgotten.
-Lines 134–7: Contact with infectious hepatitis is unnecessary because the syntagm is confusing per se, and the other anamnestic data provide the analogous info.
-Tables 1 & 2: Please reformat the data using one decimal (urea, total & direct bilirubin, CRP, HGB, and WBC) or round number (creatinine, enzymes, myoglobin).
-Line 152: Data showing the disbalance in the mineral homeostasis are missing.
-Line 184: Did the symptomatic therapy include antipyretics and analgetics?
-Table 3: what does the asterisk mark?
-Line 221: Analgetics are more suitable than painkillers.
-Lines 222–6: The proper description would be that the sample was collected to test the presence of autoantibodies.
-Lines 249–52: Are these patients linked with the data described in lines 111–4?
Technical suggestions
- Please consider the additional efforts to check for typos throughout the Manuscript.
- Additional caution is necessary to ensure the uniform usage of the abbreviations.
Suggestions are part of the Comments for Authors.
Author Response
Dear reviewer,
many thank´s you for your feedback and comments. We have added recommended information to the article and corrected english.
Best regards, authors
-Line 111: Overlooked seems more suitable than forgotten. - corrected
-Lines 134–7: Contact with infectious hepatitis is unnecessary because the syntagm is confusing per se, and the other anamnestic data provide the analogous info - corrected
-Tables 1 & 2: Please reformat the data using one decimal (urea, total & direct bilirubin, CRP, HGB, and WBC) or round number (creatinine, enzymes, myoglobin) - reformated
-Line 152: Data showing the disbalance in the mineral homeostasis are missing - added data
-Line 184: Did the symptomatic therapy include antipyretics and analgetics? - yes, corrected
-Table 3: what does the asterisk mark? - it mean repeated examination, added
-Line 221: Analgetics are more suitable than painkillers - corrected
-Lines 222–6: The proper description would be that the sample was collected to test the presence of autoantibodies - corrected
-Lines 249–52: Are these patients linked with the data described in lines 111–4? -yes
Technical suggestions
- Please consider the additional efforts to check for typos throughout the Manuscript - corrected typos
- Additional caution is necessary to ensure the uniform usage of the abbreviations - corrected
Author Response File: Author Response.pdf
