Rhizopus homothallicus, an uncommon causative agent of Rhino-orbital mucormycosis: A Case report

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Abstract

Introduction: Rhizopus oryzae is the most common Mucorales to cause angio-invasive infections though other species may also be found to be associated with different type of invasive infections. This case is about an uncommon species of Mucorales found to cause fungal sinusitis. Case presentation: A male patient in his late 60s with known history of uncontrolled type 2 diabetes for about last 10 years presented with headache, nasal congestion and with history of fever in recent past. As condition did not improve with initial symptomatic treatment given, further workup was advised. Magnetic resonance imaging (MRI) was carried out which was suggestive of sinusitis. Biopsy was taken from affected sinus for further testing and work up. Microscopic examination from material taken out by biopsy showed few broad aseptate hyaline hyphae with right angle branching (Figure 1).  Fungal culture in Sabouraud Dextrose Agar media incubated at 37o C and 25o C showed white cottony growth within 3 days. Lactophenol Cotton Blue mount showed broad, aseptate hyphae with not-well-developed sporangiophores bearing few globose sporangia and many large numbers of golden brown zygospores with stellate walls and with suspensor cells, which was identified as Rhizopus homothallicus. Liposomal amphotericin B was given for treatment along with resection of local infected area. Subsequently patient improved with treatment. Conclusion: Our purpose of reporting this case was to highlight the fact that though uncommon this species may emerge sporadically. More cases like this may be reported in future from different parts of the world as well.

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  1. Comments to Author

    This manuscript by Saha et al, Manuscript ID; ACMI-D-22-00116R1, entitled "Rhizopus homothallicus, an uncommon causative agent of Rhino-orbital mucormycosis: A case report" presents a case of Rhino-orbital mucormycosis causes by Rhizopus homothallicus. The addressed subject is interesting and within the journal's scope, but this manuscript contains some minor points. The manuscript has been revised based on reviewer comments and suggestions, but some points need to be revised. Firstly, As mentioned earlier in the first revision, the English language is probably the main problem of this manuscript. This paper would benefit from being reviewed by a native English speaker to assist with sentence construction and spelling. 2. Abstract * Line 34: please delete "(Figure 1)" in the abstract section. 5. Case Presentation * Line 58: Please add treatment for typhoid. * Line 58: magnetic resonance imaging (MRI) * Line 76: please correct ". (Figure 2)" to "(Figure 2).". * Line 84 and 85: Please correct "Canter" to "Center". Discussion * The discussion part is weak and it has to be rewritten. It has not been discussed the other studies that reported Rhizopus homothelicus in the Discussion part.  It is recommended to add a review of the literature about mucormycosis caused by Rhizopus homothallicus. 1. Chakrabarti A, Marak RS, Shivaprakash MR, Gupta S, Garg R, Sakhuja V, Singhal S, Baghela A, Dixit A, Garg MK, Padhye AA. Cavitary pulmonary zygomycosis caused by Rhizopus homothallicus. Journal of Clinical Microbiology. 2010 May;48(5):1965-9. 2. Kokkayil P, Pandey M, Agarwal R, Kale P, Singh G, Xess I. Rhizopus homothallicus causing invasive infections: Series of three cases from a single centre in north India. Mycopathologia. 2017 Oct;182(9):921-6. 3. Compain F, Aït-Ammar N, Botterel F, Gibault L, Le Pimpec Barthes F, Dannaoui E. Fatal pulmonary mucormycosis due to Rhizopus homothallicus. Mycopathologia. 2017 Oct;182(9):907-13. 4. Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, Pamidimukkala U, Jillwin J, Varma S, Das A, Panda NK. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Medical mycology. 2019 Jun 1;57(4):395-402. 5. Kaur H, Kanaujia R, Rudramurthy SM. Rhizopus homothallicus: An emerging pathogen in era of COVID-19 associated mucormycosis. Indian Journal of Medical Microbiology. 2021 Oct;39(4):473. 6. Vithiya G. Rising Rhizopus homothallicus. Indian journal of medical microbiology. 2022;40(1):175. 7. Taneja J, Chatterjee K, Sachdeva RA, Abbas SZ, Sen MK. Rhizopus homothallicus, an emerging pathogen causing cavitary lung lesions. Access Microbiology. 2022 Nov 29:000526-v1. * Line 96: Please delete : (earlier known as Absedia)" in the discussion section. * Line 98: Please add "dot" after "[2-5]". * Line 100: Please correct "Cavitary" to "cavitary". * Line 101: Please change "Rhizopus homothelicus" to "R. homothallicus". * Line 102: Please change "Rhizopus homothelicus" to "this species". Figure 1 and Figure 2 * Please combine Figure 1 and Figure 2 as Figure 1 (A and B). * Line 93: Please correct "LCB" to "Lactophenol Cotton Blue". Conclusion: * There is no clear conclusion, please make a paragraph concluding your findings.

    Please rate the quality of the presentation and structure of the manuscript

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    To what extent are the conclusions supported by the data?

    Partially 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

  2. Comments to Author

    Line 40 : 'More cases like this may be reported in future from different parts of the world as well.' this is not a conclusion drawn with the case report and its discussion. line 102 Spelling errors : Rhizopus homothelicus line 112: long should be started with capital letter ( beginning of a sentence) The grammar , spelling and language should be improved further.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

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    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

  3. Comments to Author

    * The authors have reported a case of rhinocerebral mucormycosis with typical clinical features and comorbidity. They highlight the importance of reporting the case considering Rhizopus homothallicus as an uncommon species isolated from mucormycosis patients. However, during the COVID 19 pandemic, cases of mucormycosis due to Rhizopus homothallicus have been reported. * it is said that the confirmation of the etiological agent was done by sequencing. The details of sequencing method is not given. (NGS, Sanger of nano pro? etc) .The DNA sequence they have obtained could have been submitted to a data base (NCBI or UNITE etc) and the phylogenetic relationships of the said species could have been given in the paper as well. * The authors have used abbreviations for which the description is not given (Eg. SDA,WHO) * The literature evaluation in the discussion seems inadequate and does not include some of the recent articles describing Rhizopus homothallicus as an emerging cause of mucormycosis specially during COVID19 pandemic. Please refer the citations below. 1. Kaur, H., Kanaujia, R., & Rudramurthy, S. M. (2021). Rhizopus homothallicus: An emerging pathogen in era of COVID-19 associated mucormycosis. Indian journal of medical microbiology, 39(4), 473-474. https://doi.org/10.1016/j.ijmmb.2021.06.013 2. Deganta Ghosh, Sagardeep Dey, Himanko Chakraborty, Sneha Mukherjee, Ankita Halder, Akash Sarkar, Pallab Chakraborty, Rajdeep Ghosh, Joy Sarkar, Mucormycosis: A new threat to Coronavirus disease 2019 with special emphasis on India, Clinical Epidemiology and Global Health,15,2022, https://doi.org/10.1016/j.cegh.2022.101013.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

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    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

  4. Comments to Author

    This manuscript by Saha et al, entitled "Rhizopus homothallicus, an uncommon causative agent of Rhino-orbital mucormycosis: Case report" presents a case of Rhino-orbital mucormycosis causes by Rhizopus homothallicus.The addressed subject is interesting and within the journal's scope, but this manuscript contains some major points. Firstly, this paper would benefit from review by a native English speaker to assist with sentence construction and spelling. * You declared that sequencing was used for species-level confirmation. Please add the gene name for sequencing to the manuscript. * It is recommended to add a review of literature about mucormycosis caused by Rhizopus homothallicus. 1. Chakrabarti A, Marak RS, Shivaprakash MR, Gupta S, Garg R, Sakhuja V, Singhal S, Baghela A, Dixit A, Garg MK, Padhye AA. Cavitary pulmonary zygomycosis caused by Rhizopus homothallicus. Journal of Clinical Microbiology. 2010 May;48(5):1965-9. 2. Kokkayil P, Pandey M, Agarwal R, Kale P, Singh G, Xess I. Rhizopus homothallicus causing invasive infections: Series of three cases from a single centre in north India. Mycopathologia. 2017 Oct;182(9):921-6. 3. Compain F, Aït-Ammar N, Botterel F, Gibault L, Le Pimpec Barthes F, Dannaoui E. Fatal pulmonary mucormycosis due to Rhizopus homothallicus. Mycopathologia. 2017 Oct;182(9):907-13. 4. Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, Pamidimukkala U, Jillwin J, Varma S, Das A, Panda NK. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Medical mycology. 2019 Jun 1;57(4):395-402. 5. Kaur H, Kanaujia R, Rudramurthy SM. Rhizopus homothallicus: An emerging pathogen in era of COVID-19 associated mucormycosis. Indian Journal of Medical Microbiology. 2021 Oct;39(4):473. 6. Vithiya G. Rising Rhizopus homothallicus. Indian journal of medical microbiology. 2022;40(1):175. 7. Taneja J, Chatterjee K, Sachdeva RA, Abbas SZ, Sen MK. Rhizopus homothallicus, an emerging pathogen causing cavitary lung lesions. Access Microbiology. 2022 Nov 29:000526-v1. * It is recommended to add a Phylogenetic tree for this manuscript. * It is recommended to add a timeline using a figure to improve comprehension of the manuscript. * Did the patient give informed consent for publication? * Please add a photo of broad aseptate hyphae in surgical debridement in direct smear with KOH. * It is recommended to add MRI photo to determine the involved sinus area. Herein are some comments to improve the manuscript: Manuscript title * Please italicize "Rhizopus homothallicus" in the Manuscript title. * Please correct "Case report" to "A case report". 1.2 Affiliation * The affiliations are incomplete. Please correct them. 1.4 Keywords * Please delete "post COVID mucormycosis" in the Keywords, Because this patient's covid disease has not been confirmed. 2. Abstract * Line 24: Please italicize "Rhizopus oryzae". * Line 25: This sentence, "though other species may also be found. This case is about a rare species of Mucorales", does not need to be italic. Please correct it. * Line 26: What type of diabetes does the patient have? * Line 27-28: Please delete "patient had history of close contact with spouse who was diagnosed as COVID-19 positive.". * Line 30: Please delete "(KOH Mount)" in thee abstract. * Line 33: Please correct "LCB" to "Lactophenol Cotton Blue". * Please add therapeutic interventions (surgery and antifungal thrapy) and outcome to the abstract. 4. Introduction * Line 43: Please italicize "Rhizopus". * Line 44: Please italicize "Rhizopus oryzae". * Line 48: Please italicize "Rhizopus". 5. Case Presentation * Please add the gender of this patient. * Line 51: What type of diabetes does the patient have? * How was the patient's condition in terms of diabetes? uncontrolled or controlled diabetes? * Was it evaluated according to the diabetes sufferer? * Line 57: Please correct "POSITIVE" to "positive". * Line 58: Please add a full-length word of "ENT". * Line 59: Please add a full-length word of "MRI". * Line 60: Please add a full-length word of "OT". * Line 64: Please correct "SDA" to " Sabouraud dextrose agar (SDA)". * Line 68: Please correct "LCB" to "Lactophenol Cotton Blue". * Line 68: Please correct "Culture" to "culture". * Line 70: Please correct "(picture1)" to "Figure 1". * Line 71-72: Please italicize "Rhizopus homothallicus". * Line 73: Please add dosage and duration of Liposomal amphotericin B for this patient. * Line 81: The authors reconfirmed by use of molecular tools; therefore, we need GenBank accession number; Please add the obtained accession number to the manuscript. 6. Figures and tables * Line 70: Please correct "Figures and tables" to "Figure legend". 7. Discussion: * It is recommended to add and discusses relevant literature review to the Discussion section. * Line 86: Please italicize "Rhizopus". * Line 87: Please italicize "Rhizopus". * Line 87: Please italicize "R. oryzae". * Line 89: Please italicize "R. homothallicus". * Line 103: Please change "Rhizopus homothalicus" to "R. homothallicus" and then italicize it. * Line 108: Please correct "Amphotericin B" to "amphotericin B".

    Please rate the quality of the presentation and structure of the manuscript

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    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

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    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