First Case Report of Salmonella enterica Serovar Haifa in a Patient from Mysore, Karnataka, India

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is an interesting case reported in India. Given that the case arose due to a visit to the rural area with potential exposure to livestock/birds. Since the case could not identify a potential source, it is better to recommend collecting more information on exposure during clinical history-taking. Also, it is best to test family members who travel with him to see whether they are colonized with this bacterium. Although rare, if this is the first case, retrospective tracking would help study further. Any bacterial isolation pictures would help to readers on how it looks like.

Author Response

Dear Reviewer,
 "Please see the attachment."

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript describes a 70-year-old diabetic male presenting with acute gastroenteritis, from whom Salmonella enterica serovar Haifa was isolated and confirmed through reference laboratory testing. The authors state that this represents the first human clinical case of S. Haifa reported in India. The isolate demonstrated resistance to ampicillin, ceftriaxone, and ciprofloxacin, and the patient responded clinically to azithromycin therapy.

The case is clinically relevant due to:

 The rarity of S. Haifa in human infections

 The multidrug-resistant (MDR) profile

 The potential zoonotic link

 Regional epidemiological importance

However, several issues require clarification and refinement before the manuscript is suitable for publication.

 

Major Comments

1. Claim of “First Human Case in India” Requires Stronger Evidence

The authors claim this is the first human case of S. Haifa in India. While this may be true, the manuscript does not clearly describe:

 A structured literature search strategy

 National surveillance data review

 Confirmation that no prior clinical reports exist

Recommendation:

 Clarify how the authors confirmed this is the first documented human case.

 Include a brief statement on literature search strategy (databases searched, time frame).

 Use cautious phrasing such as:

To the best of our knowledge, this appears to be the first documented human case…”

2. Multidrug Resistance (MDR) Statement Needs Clarification

The isolate was resistant to ampicillin, ceftriaxone, and ciprofloxacin. However:

 MDR is usually defined as resistance to ≥3 antimicrobial classes.

 The manuscript should clearly specify the antimicrobial classes involved.

 MIC values are not provided.

Recommendation:

 Provide MIC values if available.

 Clarify the definition used for MDR.

 Avoid overstating resistance unless classification is standardized.

3. Microbiological Characterization Could Be Strengthened

The identification relied on:

 VITEK 2

 Agglutination

 Confirmation at a national reference center

However:

 No molecular typing (e.g., PCR, WGS) is described.

 No mention of resistance gene analysis.

Given the rarity of this serovar, deeper characterization would strengthen the report.

Recommendation:

If available, include:

 Molecular confirmation methods used by the reference center

 Any genetic resistance markers identified

 Serotyping methodology details

4. Elevated Procalcitonin With Leukopenia Requires Discussion

The patient had:

 Leukopenia (TLC 2,600)

 Elevated procalcitonin (3.73 ng/mL)

These findings may suggest systemic involvement. However:

 Blood cultures were not reported.

 The possibility of invasive NTS was not discussed.

 

Recommendation:

 Clarify whether blood cultures were performed.

 Discuss the significance of leukopenia and elevated procalcitonin in NTS.

 Explain whether invasive disease was considered.

5. Antibiotic Management Needs Justification

The patient received IV azithromycin for 3 days.

Points needing clarification:

 Was this empirical or guided by AST?

 Why was azithromycin chosen over other options?

 Was oral step-down therapy given?

 Was follow-up stool culture performed?

Recommendation:

Provide rationale for antibiotic selection and duration.

6. Zoonotic Link Is Hypothetical

The manuscript suggests zoonotic spillover due to cattle/poultry exposure. However:

 No environmental or animal sampling was performed.

 The epidemiological link remains speculative.

The limitation section mentions this appropriately, but the Discussion sometimes implies stronger linkage than supported.

Recommendation:

Tone down direct zoonotic attribution and clearly state that the source remains unconfirmed.

 Minor Comments

1. Several grammatical issues throughout the manuscript require professional editing.
2. Formatting inconsistencies:

    Extra spacing (e.g., “Mandya , Karnataka”).

    Inconsistent capitalization of antimicrobial names.

3. “Livestock” unnecessarily capitalized in one section.
4. Table formatting can be improved for clarity.
5. Some references appear repetitive or not optimally cited.
6. Reference formatting requires journal-style uniformity.

 

 

Author Response

Dear Reviewer,
 "Please see the attachment."

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Reviewer’s Comments to the Authors:

Title

• The authors are requested to correct the mistake in the title. The title Salmonella enterica, can be italicised.
• In “Enterica”, ‘E’ should be small ‘e’.

Abstract

• Abstract can be short and more precise.
• Line no. 28, 138: Salmonella enterica has to be kept with italicised uniformity throughout the manuscript.
• Line no. 24: Add space after full stop.
• Line no. 24: “S. Haifa” is not scientific way to write. It should be written as “ enterica serovar Haifa”

Keywords

• Keywords are appropriate

Introduction

• Line no. 41: Check the brackets [ ] and parentheses ( ) for reference and use uniformly. In ‘Introduction’, ‘Case presentation’ parts, ‘[ ]’ is used and in ‘Discussion’ part, ‘( )’ is used.
• Lines nos. 51 & 62: the hyphen ‘-’ is unnecessary

Case Presentation

• The methodology describing the enrichment step requires clarification. An incubation period of only two hours may be insufficient to allow selective enrichment of Salmonella while suppressing competing intestinal flora and the raises concerns about the reliability of the isolation procedure as standard microbiological protocols recommend incubating for at least 6–8 hours before subculture. The authors should verify whether this represents a reporting error and revise the methodology accordingly.
• Nutrient agar is not a recommended medium for primary isolation of Salmonella from stool samples, as it lacks selectivity and allows overgrowth of intestinal flora. The authors should clarify the rationale for using nutrient agar.
• Even though the manuscript reports that the isolate was confirmed as Salmonella enterica serovar Haifa by a reference laboratory, it is important to specify the method employed for confirmation for methodological transparency.
• Laboratory procedures are insufficiently described like colony morphology, biochemical identification, serological testing.
• Important biochemical tests are missing like lysine decarboxylase, motility, ornithine decarboxylase.
• Urine microscopy revealed 8–10 pus cells/HPF despite a negative urine culture. The authors should clarify whether this represents asymptomatic pyuria, contamination, or a possible secondary urinary tract infection and the clinical relevance of this finding in the context of Salmonella enterica infection should be discussed.
• In the event of bacterial gastroenteritis, microscopy reportedly showed no inflammatory cells or RBCs in the stool samples, which is to be justified and discussed.
• To have clear picture of the patient condition a detailed leucogram and erythrogram data can be added.
• The detailed recovery schedule along with the protocol followed to improve the gut health as well as managemnet of dehydration in the patient will be helpful for the readers.
• Tables should include units and reference ranges where appropriate.
• The finding of markedly elevated procalcitonin (3.73 ng/mL) not associated with systemic bacterial infection or sepsis rather than localized gastroenteritis should be discussed and the manuscript does not indicate whether blood cultures were performed to rule out bacteremia.
• Line nos. 84-85- not clear, Rewrite for better clarity
• Line no. 110- capitalization errors for the biochemical tests
• Line no. 100: Please mention the stool sample collection media/ condition
• Lines nos. 102-104: Please mention the make of the agar and broth media
• Line no. 107: Check punctuation at the end
• Line no. 116: Why an updated CLSI guideline of 2025 was not referred?
• The authors are requested to provide the information regarding the Catalogue number, brand of the materials, Manufacturer name, city, state, country used throughout the study and particularly in the Case Presentation section. Specific details on the brands of reagents, diagnostic kits, and other materials would help to ensure reproducibility of the methods.

Discussion

• The manuscript suggests that the infection resulted from direct spillover from cattle or poultry based solely on patient history and not by evaluating the route of transmission or establishing the source of infection. Since no animal or environmental samples were analyzed, the conclusion can at best be considered as surmise. The discussion should acknowledge this limitation more clearly.
• The manuscript describes the isolate as multidrug resistant (MDR), however, the antimicrobial susceptibility results indicate resistance only to ampicillin, ceftriaxone, and ciprofloxacin. Even though the tested antibiotics belong to different antimicrobial classes, the manuscript does not clearly demonstrate that resistance to justify classification as MDR. As MDR refers to resistance to at least one agent in three or more antimicrobial classes, authors should clarify the range of antibiotics tested and the criteria used for defining MDR.
• To get into more on Epidemeology, though the patient had clean habits, whether he used public toilets during transit and the place can be note down. Since, the patient travelled to rural set up to attend a family function any family member from abroad has arrived or from other distant places, to think of the human-human transmission routes.
• Also the authors, if possible can enquire from the patient is their any other family member or the village people had diarrhoea in the same week to confirm for sporadic case.
• Line nos. 164-167: Long sentence, can be rephrased
• Line no. 231: ….is critical ‘in’ reducing…is better instead of ‘to
• The authors are discussing about primary transmission route of non-typhoidal Salmonella (NTS). Hence, authors are requested to cite following most relevant references in a suitable places like Line Nos. 48-61, 153-159, etc.: Milton, A.A.P., Agarwal, R.K., Priya, G.B., Athira, C.K., Saminathan, M., Reddy, A., Aravind, M. and Kumar, A. (2018). Occurrence, antimicrobial susceptibility patterns and genotypic relatedness of Salmonella isolates from captive wildlife, their caretakers, feed and water in India. Epidemiology and Infection, 146(12):1543-1549.

Conclusion

• Line no. 248: Add ‘following intravenous azithromycin administration’ after ‘….rapid clinical recovery’

References

• It is recommended to thoroughly check all references and ensure that their formatting strictly adheres to the journal guidelines, as several references were found to be inconsistent with the required style.
• Please write the references in a uniform manner/ as per journal standard such as ‘et al’ is used in a few references not in all wherever applicable
• Please check the relevance of old references such as of 2005 and 2009 (reference number 5, 14, 16, 23, 25, 36)

Minor comments to the Authors:

• Few words/ sentences require rephrasing to increase the manuscript's overall impact.
• Please mention the scientific name of the organism as per the standard of binomial nomenclature for scientific names such as italicized word, upper and lower case of letters etc. Further, check in the entire text where the scientific name is written in different formats (such as lines 13, 34 etc.). Please check for spacing and punctuation marks.

Grammatical mistakes need to be avoided throughout the manuscript.

Comments on the Quality of English Language

The manuscript should be modified for scientific soundness

Author Response

Dear Reviewer,
 "Please see the attachment."

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The revised manuscript shows notable improvements; however, I would like to draw attention to the genus names used in the manuscript. They should be revised to adhere to the journal’s guidelines for taxonomic accuracy and consistency. I recommend carefully reviewing the manuscript to ensure that all genus names are properly formatted and in accordance with the journal's requirements. Once these adjustments are made, I believe the manuscript will be suitable for publication in Infectious Disease Reports."

Author Response

Comment 1:We have carefully reviewed the entire manuscript and revised all genus names to ensure they adhere to the journal’s guidelines for taxonomic accuracy and consistency. Specifically, all scientific names have been standardized according to binomial nomenclature conventions, including appropriate italicization and correct use of uppercase and lowercase lettering.

We appreciate the reviewer’s attention to this important detail, which has helped improve the overall clarity and scientific rigor of the manuscript.

 

Response 1: We have carefully reviewed the entire manuscript and revised all genus names to ensure they adhere to the journal’s guidelines for taxonomic accuracy and consistency. Specifically, all scientific names have been standardized according to binomial nomenclature conventions, including appropriate italicization and correct use of uppercase and lowercase lettering.

We appreciate the reviewer’s attention to this important detail, which has helped improve the overall clarity and scientific rigor of the manuscript.

Reviewer 3 Report

Comments and Suggestions for Authors

I have carefully reviewed the revised manuscript and the authors’ responses. All the Reviewer comments have been addressed adequately and comprehensively, and the authors have made thoughtful and meticulous revisions to enhance the manuscript.

I would like to congratulate the team of authors on their efforts and the way they resolved the suggestions made by the Reviewer. It is an important scientific article that highlights the potential zoonotic risk of rare non-typhoidal Salmonella enterica serovar Haifa and the importance of surveillance, routine serotyping, and antimicrobial resistance monitoring.

I wish them continued success in their future work!

Author Response

Comment 1: I have carefully reviewed the revised manuscript and the authors’ responses. All the Reviewer comments have been addressed adequately and comprehensively, and the authors have made thoughtful and meticulous revisions to enhance the manuscript.

I would like to congratulate the team of authors on their efforts and the way they resolved the suggestions made by the Reviewer. It is an important scientific article that highlights the potential zoonotic risk of rare non-typhoidal Salmonella enterica serovar Haifa and the importance of surveillance, routine serotyping, and antimicrobial resistance monitoring.

I wish them continued success in their future work!

Response 1: We sincerely thank the Reviewer for the highly positive and encouraging feedback on our manuscript.

We are deeply grateful for your thoughtful appreciation of our work and for recognising its significance in highlighting the zoonotic potential of rare non-typhoidal Salmonella enterica serovar Haifa.

We truly appreciate your support and valuable insights throughout the review process.