Fatal disseminated Cryptococcosis with diverse risk factors: A Case series from a tertiary care hospital in eastern India

  1. Isra Halim
  2. Sweta Jha
  3. Prathyusha Kokkayil
  4. Ravi Kirti
  5. Divendu Bhushan
  6. Asim Sarfraz
  7. Binod Kumar Pati
  8. Bhaskar Thakuria

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Abstract

Background: Cryptococcos noeformans is a ubiquitous fungal infection that can cause life threatening meningitis and fungemia in both immunocompromised and immunocompetent host. Disseminated cryptococcosis is often a retrospective diagnosis when blood cultures are found positive for Cryptococcus species. Case presentation: We report two cases of Disseminated cryptococcosis with different risk factors emphasizing on early clinical suspicion, diagnosis and treatment. First case was of non- alcoholic steatohepatitis patient who presented with complain of abdominal swelling and hemiparesis. Other case was of retro positive male presenting with complains of headache and fever. These patients underwent empirical antibacterial and anti-tubercular therapy which was ineffective. Finally, diagnosis was made on the basis of India ink stain, Gram stain and fungal culture which were confirmed by polymerase chain reaction and gene sequencing of both the isolates. But the patients could not be saved due to delay in diagnosis. Conclusion: Disseminated cryptococcosis is an advanced potentially fatal disease. Cryptococcosis should be suspected not only in cases of HIV or transplant patients but also in cases of chronic liver diseases.  An early clinical suspicion would help recognize these cases sooner. The microbiologist should always have a keen eye and an equally high index of suspicion especially in the presence of capsulated round yeast cells in any sample of sick patients. Early diagnosis and treatment are imperative to prevent mortality.

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  1. Access Microbiology

    The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments. The language used is poor, which can cause ambiguity at times. Please carefully rewrite it. We offer a discounted translation service, Editage (https://www.editage.com/; see https://www.microbiologyresearch.org/prepare-an-article#13 for more information). The paper is poorly structured and written, which has prevented a proper assessment of the research done.

  2. Access Microbiology

    Comments to Author

    1. Description of the case(s) : they need to add more information regarding the case 2. Presentation of results: very casual approach, india ink picture quality can be improved, one grams 'stain picture needs to be deleted , phylogenetic tree needn't give any added informations. Radiological Picture needs to be added 3. How the style and organization of the paper communicates and represents key findings: one case is interesting as from end stage of live diseases 4. Literature analysis or discussion: they should add one reference; Donnelly JP CID 2019 definition of cryptococcosis 5. Any other relevant comments: grammar needs to be improved

    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

    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

  3. Access Microbiology

    Comments to Author

    Reviewer comments Major There are significant number of grammatical errors in this manuscript. I would suggest rewriting portions including but not limited to both case descriptions to improve the quality of the paper. The cases presented in this paper do not appear to add to the current literature regarding risk factors for, nor presentation of cryptococcal infections. The learning points mentioned are not specifically helpful to clinical microbiologists. A combination of clinician education and consideration of cryptococcal immunochromatographic testing would be more helpful. Minor Abstract: Multiple grammar issues, please review and rewrite "retro positive" should be retrovirus or more specifically HIV Introduction: Line 51: grammar and reference Line 57: "Most cases show no specific clinical manifestations…" More than 50% present with meningoencephalitis, therefore most cases do present with specific clinical manifestations Case 1: Multiple grammar issues Overall I think this case can be better summarised Did the patient have any bird or guano exposure? Did he have a relevant occupation? Was a lumbar puncture performed and if not, why? Line 74: Please include reference intervals Line 80: how was TB confirmed? Culture/AFB staining/Molecular? Line 83: injection or intravenous? Line 84-86: blood culture bottles are routinely incubated for 5 days. Please clarify how these were positive on day 10. Similarly, does your lab routinely perform fungal culture on ascetic fluid or was this specifically requested? Also, was microscopy performed on the ascetic fluid at time of collection or only from the positive culture plate? Line 88: "…following cryptococcal peritonitis…" suggests that the ascetic fluid was the primary focus of infection. This is unlikely to be the case. Table 1: On what media did growth occur? Were budding yeast seen in urine on day 1 for case 2? If so, there was no delay in diagnosis, only a delay in presentation. Was a cryptococcal antigen performed for either case? If not, why? Figure 1: poor quality. Suggest using a clearer image or remove. Figure 3 & 4 add very little to the case descriptions and can be removed. Case 2: This case could be better summarised. Was the HIV diagnosis confirmed or just made via serology? What was the patient's CD4 count? Did either patient have brain imaging? It would be very useful to know if cerebral cryptococcomas were present. Discussion: The information provided in the discussion demonstrates that neither cases is novel nor adds significantly to the literature. Line 161: there is no evidence mentioned that this case was indeed co-infected. Line 194: this is not a learning pearl for microbiologists, but rather for the treating clinicians. Could the authors elaborate as to why microbiological samples for the first case were not taken earlier? Line 216: Please elaborate on the role of immunochromatographic testing. This could be a reasonable alternative to MALDI and molecular methods due to cost and ease of use. Please discuss why molecular testing was performed for these to patients. Did the laboratory consider the use of CGB media for Cryptococcus species identification? Again, this may have been cheaper than molecular testing.

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

    Poor

    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

  4. Version published to 10.1099/acmi.0.000687.v1 on Access Microbiology