A Cautionary Tale of False Positive Histoplasma Urine Antigen in an HIV Patient: A Case Report
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Introduction. Coccidioidomycosis, or Valley fever, is a fungal disease caused by Coccidioides species, prevalent in parts of the southwestern United States. It usually results from inhaling spores from soil and is a common cause of pneumonia in these regions. Case Presentation. We present a unique case of coccidioidomycosis in an immunodeficient male patient secondary to HIV infection with poor adherence to ART. After presenting with non-specific symptoms and pre-syncope, he was initially diagnosed with pneumonia based on chest X-ray findings, but his symptoms failed to improve with antibiotics. He was treated for presumed pulmonary histoplasmosis following a positive histoplasma urine antigen test. However, the patient worsened clinically. Following a CT scan demonstrating a large necrotic lung consolidation, fungal stain and culture of tissue biopsied through EBUS confirmed coccidioidomycosis. The patient received two weeks of liposomal amphotericin with clinical improvement before discharge with itraconazole. Conclusion. The histoplasma antigen test can be falsely positive due to cross-reaction with other fungal infections like blastomycosis, paracoccidioidomycosis, or talaromycosis, and less frequently, coccidioidomycosis or aspergillosis. Diagnosis of coccidioidomycosis requires a high index of suspicion outside the expected geographic distribution in the appropriate clinical setting. Our case highlights the risk of false positive antigen test results and the importance of invasive diagnostics, including bronchoscopy to obtain fungal cultures, if the diagnosis remains uncertain.
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The work presented is clear and the arguments well formed. This study would be a valuable contribution to the existing literature. The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
1. On line 69: why the author did not mention the right aerial bronchogram seat 2.On Line 85: It would be more interesting if you can provide more details about the tissue cultures, such as which medium was used for the culture 3. On line 86-87: can you please precise which fungal stain was used? was it the Grocott's methanamine stain? 4. on line 89: Figure 2: Not important to mention the pleural effusion blade? 5. On line 105: Figure 3 : if you want to compare both figures 2 and 3, normally you should also performed a CT scan with IV contrast and keep the same area than you present on figure 2 6. Why the authors did not put the fungal staining images?
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions …
Comments to Author
1. On line 69: why the author did not mention the right aerial bronchogram seat 2.On Line 85: It would be more interesting if you can provide more details about the tissue cultures, such as which medium was used for the culture 3. On line 86-87: can you please precise which fungal stain was used? was it the Grocott's methanamine stain? 4. on line 89: Figure 2: Not important to mention the pleural effusion blade? 5. On line 105: Figure 3 : if you want to compare both figures 2 and 3, normally you should also performed a CT scan with IV contrast and keep the same area than you present on figure 2 6. Why the authors did not put the fungal staining images?
Please rate the quality of the presentation and structure of the manuscript
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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Comments to Author
The article contains very basic and concise information, providing a simple explanation of the clinical findings in the patient presented. The information about the case is very important for the scientific community since the case can be classified as unusual, as presented by the authors as a case of cocci that occurs outside the area considered endemic for that microorganism. Publication is recommended. In the article there is a comment about coccidioidomycosis and histoplasma cross reaction in test, a small review or input about the mechanisms for this is valued if included. Detection of coccidioidomycosis (mycosis) is usually done by culture or visualization. Classical detection methods are not as accurate as desired but they still prove to be useful. Culture of some mycosis (cocci) is high …
Comments to Author
The article contains very basic and concise information, providing a simple explanation of the clinical findings in the patient presented. The information about the case is very important for the scientific community since the case can be classified as unusual, as presented by the authors as a case of cocci that occurs outside the area considered endemic for that microorganism. Publication is recommended. In the article there is a comment about coccidioidomycosis and histoplasma cross reaction in test, a small review or input about the mechanisms for this is valued if included. Detection of coccidioidomycosis (mycosis) is usually done by culture or visualization. Classical detection methods are not as accurate as desired but they still prove to be useful. Culture of some mycosis (cocci) is high risk. Silver Stain is frequently used to detect cocci spherules in body fluids or biopsy tissue by direct observation. Microbe detection can be performed in steps regarding complexity of tests, price, availability, etc. Direct observation such as KOH or special staining such as Silver Staining can be performed as a first step due to easiness and low cost, especially in low income settings where resources are scarce. Autors can consider this to input on introduction and or discussion. Coccidioides antigen detection tests exist, but their sensitivity is lower than histoplasma antigen tests to detect Coccidioides. (In addition to this) Ag detection using urine sample is non- invasive and sensitivity seems to be higher than that of Ag detection using serum or bronchoalveolar lavage. Ag and Ab tests still play an important role in clinical settings, but they may be of little help on their own. The combination of Ab and Ag EIA tests improves the detection accuracy for coccidioidomycosis. (cite: Advances in diagnosis of progressive pulmonary and disseminated coccidioidomycosis) While research paves the way for PCR assays employing novel histoplasma primers, these tests are not yet commercially available…. ?? Is this test pcr based and available, FDA approved, GeneSTAT Coccidioides assay in the USA
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
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