When an underestimated zoonosis and antimicrobial resistance collide: Corynebacterium ulcerans
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In the European region, diphtheria is now rarely suspected in patients presenting with upper respiratory tract symptoms. Corynebacterium ulcerans is the underestimated zoonosis that is replacing C. diphtheria infections in industrialized countries, but extensive human and animal prevalence studies are lacking. The range of hosts that can act as reservoirs for C. ulcerans is very broad, companion pets currently being the main source of human infection. We report a case of macrolide-resistant C. ulcerans infection with no apparent zoonotic transmission and outline the efforts required for the public and zooprophylactic management of these cases. We describe the main critical issues to be addressed to comprehensively tackle this zoonosis in the future.
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I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed and this study would be a valuable contribution to the existing literature.
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Dear Dr Mori, Thank you for submitting your manuscript, titled (Macrolide Resistant Corynebacterium ulcerans Infection in a Patient with No Evidence of Zoonotic Transmission) to Access Microbiology Journal. I appreciate the work you have put into this manuscript and the significance of presenting a macrolide-resistant C. ulcerans. However, based on the detailed feedback from the reviewers, I am requesting a major revision to address several important concerns before we can move forward with your submission. Reviewer Feedback Summary Both reviewers found the case report to have potential but suggested that additional detail and clarity are needed to highlight its significance. Specifically: • Clarify the potential role of zoonotic transmission even in the absence of isolates from companion animals. • Expand on testing methods for …
Dear Dr Mori, Thank you for submitting your manuscript, titled (Macrolide Resistant Corynebacterium ulcerans Infection in a Patient with No Evidence of Zoonotic Transmission) to Access Microbiology Journal. I appreciate the work you have put into this manuscript and the significance of presenting a macrolide-resistant C. ulcerans. However, based on the detailed feedback from the reviewers, I am requesting a major revision to address several important concerns before we can move forward with your submission. Reviewer Feedback Summary Both reviewers found the case report to have potential but suggested that additional detail and clarity are needed to highlight its significance. Specifically: • Clarify the potential role of zoonotic transmission even in the absence of isolates from companion animals. • Expand on testing methods for close contacts to address potential missed transmissions. • Provide more background on C. ulcerans, its relation to C. diphtheria and any potential vaccine cross-protection. • Add technical details on pathogen identification methods and breakpoints for resistance. By addressing these points, your manuscript will better demonstrate the clinical and public health importance of this case. Decision and Next Steps Please address the reviewers’ revisions to improve the manuscript further. I encourage you to carefully consider the reviewers' comments and make the necessary improvements to your manuscript. Should you decide to resubmit, please include a detailed point-by-point response to the reviewers' comments, outlining how each concern has been addressed. We appreciate your interest in publishing with Access Microbiology and we look forward to your response. Best regards, Dr Zina Alfahl
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Comments to Author
In the article, "When an underestimated zoonosis and antimicrobial resistance collide: Corynebacterium ulcerans" Mori et al describe a perplexing case of C. ulcerans infection in an adult woman. This is preceded by an introduction on the topic of C. ulcerans. Overall, it is unclear as to what makes this particular case unique and compelling as a case report. In addition, there are several points that the authors should consider addressing (below). Abstract - The abstract could use a little more detail. For example, the unfamiliar reader might wonder, what is the animal reservoir of this organism? Modes of transmission? Current estimated disease burden? Introduction Line 16 - describe "pseudomembrane" in greater detail Line 19 - "sensibility"... perhaps "sensitivity" would be better The introduction …
Comments to Author
In the article, "When an underestimated zoonosis and antimicrobial resistance collide: Corynebacterium ulcerans" Mori et al describe a perplexing case of C. ulcerans infection in an adult woman. This is preceded by an introduction on the topic of C. ulcerans. Overall, it is unclear as to what makes this particular case unique and compelling as a case report. In addition, there are several points that the authors should consider addressing (below). Abstract - The abstract could use a little more detail. For example, the unfamiliar reader might wonder, what is the animal reservoir of this organism? Modes of transmission? Current estimated disease burden? Introduction Line 16 - describe "pseudomembrane" in greater detail Line 19 - "sensibility"... perhaps "sensitivity" would be better The introduction is lacking with regards to two major questions: 1. What is the relationship between ulcerans and diptheriae? How divergent are they? Are their toxins similar? How are these toxins encoded, and can they be shared on a plasmid? 2. Does the TDAP vaccine (or other vaccines) provide cross-protection to ulcerans? Is there data on this? What are the correlates of immunity? If these are unknowns, they need to be stated as unknowns. Case description Line 59 - what was the method used to speciate C. ulcerans? MALDI-ToF-MS? What instrument? Which library and version? Table - it would be useful to provide the breakpoints used to establish susceptibility vs resistance… this can help readers understand how potent the resistance is.
Please rate the quality of the presentation and structure of the manuscript
Poor
To what extent are the conclusions supported by the data?
Not at all
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Please ONLY put comments for the Author(s) in here This case report describes the detection of macrolide resistant Corynebacterium ulcerans infection in a patient with no evidence of zoonotic transmission. Whilst reports of C. ulcerans infection with unknown source and separately the identification of a macrolide resistant isolate are not necessarily novel, the identification of a macrolide resistant isolate from a patient in this case report highlights the importance for increased awareness of the infection along with the need for antimicrobial susceptibility testing and research to understand the colonisation, transmission and pathogenicity of the infection and how this can be used to inform and develop public health actions and guidance. Overall, I am satisfied that this is a well-presented case …
Comments to Author
Please ONLY put comments for the Author(s) in here This case report describes the detection of macrolide resistant Corynebacterium ulcerans infection in a patient with no evidence of zoonotic transmission. Whilst reports of C. ulcerans infection with unknown source and separately the identification of a macrolide resistant isolate are not necessarily novel, the identification of a macrolide resistant isolate from a patient in this case report highlights the importance for increased awareness of the infection along with the need for antimicrobial susceptibility testing and research to understand the colonisation, transmission and pathogenicity of the infection and how this can be used to inform and develop public health actions and guidance. Overall, I am satisfied that this is a well-presented case report however I have a couple of suggestions that the authors may choose to consider when presenting their conclusions. 1. Whilst C. ulcerans is considered to be a zoonotic pathogen due to it's wide host range of which includes domestic, wild and captive animals and the fact that most reported cases have contact with domestic and companion animals, in many of these cases the organism was not isolated from the animal contact. For this reason, it may be reasonable for the authors to note that the absence of an isolate from the patient's three companion cats is not unusual in C. ulcerans cases and therefore does not necessarily rule out the cats as a potential source of the infection. 2. In lines 73-74, the authors state nasopharyngeal swabs were collected from the six close contacts to test for carriage. The WHO Surveillance Standards for Diphtheria recommends collection of nasopharyngeal/nose and oropharyngeal/throat swabs when screening suspected cases, which includes recent contact with a diphtheria case in the absence of travel. Consideration should also be given to the fact that contacts may have asymptomatic infection or be incubating the organism in the early stages of infection. Furthermore, a case of suspected person-to-person transmission has been reported by detection of C. ulcerans from a throat swab of a close contact (Possible human-to-human transmission of toxigenic Corynebacterium ulcerans. Konrad, R. et al. Clinical Microbiology and Infection, Volume 21, Issue 8, 768 - 771). Therefore, it may be possible that transmission to or from one of the six close contacts in this case report was missed.
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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